Sporadic or late-onset Alzheimer’s disease(LOAD)occurs in 1 of 10 people over 65 years of age and comprises 95%of all AD patients.Unlike early-onset AD,which is caused by defined single gene mutations,the mechanisms ...Sporadic or late-onset Alzheimer’s disease(LOAD)occurs in 1 of 10 people over 65 years of age and comprises 95%of all AD patients.Unlike early-onset AD,which is caused by defined single gene mutations,the mechanisms and events underlying risk for LOAD are not fully understood and no substantial disease-modifying interventions are currently available.Age is the most prominent risk factor for LOAD,and interacting age-related and LOAD-associated factors contribute to its pathogenesis.Among these factors are changes in bioenergetic cell functions,which metabolize substrates and produce energy stored in adenosine triphosphate.展开更多
This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmon...This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmony,and to provide a treatment plan.Professor Li Tingquan believes that the occurrence and development of chronic atrophic gastritis(CAG)is fundamentally a process of harmony imbalance of the spleen and stomach.Its specific manifestation lies in the interaction between qi deficiency and stagnation,namely,spleen deficiency as the root cause,and qi stagnation,phlegm-dampness,and blood stasis obstructing the middle energizer as the secondary manifestations.These factors are mutually causal and interact with one another.Based on this,he proposed a four-step method to treat the disease:eliminating pathogenic factors,harmonizing the spleen and stomach,activating blood circulation to resolve stasis,and tonifying the kidney to generate blood(metaphorically described as"closing the mountains to cultivate forests and thicken the soil,breeding seeds and irrigating for stomach recovery").This approach aims to restore the harmonious state of the middle energizer,providing a complete clinical framework of theory,principle,formula,and herbs for the prevention and treatment of CAG.展开更多
Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various phy...Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.展开更多
Zinc(Zn)is an essential micronutrient for both plants and humans.Zn deficiency is common in many paddy fields and reduces yield and grain Zn content(GZC).To accelerate breeding for improved GZC and Zn deficiency toler...Zinc(Zn)is an essential micronutrient for both plants and humans.Zn deficiency is common in many paddy fields and reduces yield and grain Zn content(GZC).To accelerate breeding for improved GZC and Zn deficiency tolerance(ZDT)rice varieties,it is important to identify genes regulating Zn homeostasis.In this study,a member of the Ser/Thr protein phosphatase family,LOC_Os07g48840(named as OsGZ7),was found to contributed to ZDT and GZC in rice.The expression of OsGZ7 in roots and shoots was inhibited by Zn deficiency and toxicity,but induced by iron(Fe),manganese(Mn),and copper(Cu)deficiency,as well as chromium toxicity.OsGZ7 localized to the cytoplasm and was expressed in all tissues during the tillering,flowering,and grain-filling stages,particularly in the leaf blade and leaf sheath.At the seedling stage,knockout of OsGZ7 enhanced ZDT and increased Zn accumulation in both roots and shoots.At the maturity stage,knockout of OsGZ7 enhanced GZC,while overexpression of OsGZ7 reduced GZC.RNA-seq analysis suggested that OsGZ7 might regulate Zn homeostasis by affecting metal binding,hormone signal transduction,and oxidoreductase activity.Taken together,our findings indicate that OsGZ7 contributes to ZDT and Zn accumulation in rice.展开更多
OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which...OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which serve as key references for disease prevention and management.METHODS:The dataset containing the data of Yin and Yang deficiency constitution was identified through the Gene Expression Omnibus database.This database was used for differential expression genes(DEGs)analysis and weighted gene co-expression network analysis(WGCNA),and the characteristic genes were then obtained in the dataset using a machine learning method.The hub genes of Yin and Yang deficiency constitution were obtained after analysis using the above three methods,and the hub genes were enriched and analyzed.Subsequently,the hub genes of Yin and Yang deficiency constitution were validated using external datasets.Receiver operating characteristic(ROC)analysis was used on each hub genes of the two groups to further understand their diagnostic performance.The mi RNA–lnc RNA-gene network was used to further analyze the hub genes.Immunoinfiltration and gene set enrichment analysis were performed on the shared hub genes.RESULTS:The GSE87474 dataset was used for DEGs analysis and WGCNA.Using machine learning analyses,we identified 15 and 14 hub genes for Yin and Yang deficiency constitutions,respectively.The results of enrichment analyses showed that Yin deficiency constitution was associated with interleukin-17 signaling pathway,whereas Yang deficiency constitution was associated with glycosaminoglycan biosynthesis–keratan sulfate.The validation dataset GSE56116 showed statistically significant data for s-adenosylmethionine sensor upstream of MTORC1(SAMTOR,also named C7orf60),cofilin 2(CFL2),cytohesin 1 interacting protein(CYTIP),G protein-coupled receptor 183(GPR183),hippocampus abundant transcript 1(HIAT1),kelch like family member 15(KLHL15),mitogen-activated protein kinase 6(MAPK6),and prostaglandin-endoperoxide synthase 2(PTGS2)in Yin deficiency and fucosyltransferase 8(FUT8),TATA-box binding protein associated factor,RNA polymerase I subunit D(TAF1D),zinc finger protein 24(ZNF24),MAPK6,and leptin receptor overlapping transcript like 1(LEPROTL1)in Yang deficiency.The ROC results indicated that these genes have diagnostic value.MAPK6 is a shared hub gene for Yin and Yang deficiencies.CONCLUSIONS:This study identified C7orf60,CFL2,CYTIP,GPR183,HIAT1,KLHL15,MAPK6,and PTGS2 in Yin deficiency and FUT8,TAF1D,ZNF24,MAPK6,and LEPROTL1 in Yang deficiency as potential biomarkers,providing insights into their pathogenesis.This theory not only guides the diagnostic approach in TCM but also extends its influence to various scientific research fields.展开更多
Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first t...Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.展开更多
BACKGROUND Functional bowel disorder(FBD)may be caused by a decrease in disaccharidase activity.Thus,the timely diagnosis of disaccharidase deficiency could lead to a better prognosis in patients with this condition.A...BACKGROUND Functional bowel disorder(FBD)may be caused by a decrease in disaccharidase activity.Thus,the timely diagnosis of disaccharidase deficiency could lead to a better prognosis in patients with this condition.AIM To determine the potential value of intestinal disaccharidases glucoamylase,maltase,sucrase,and lactase in understanding the etiology and pathogenesis of FBD.METHODS A total of 82 FBD patients were examined.According to the Rome IV criteria(2016),23 patients had diarrhea-predominant irritable bowel syndrome(IBS),33 had functional diarrhea,10 had constipation-predominant IBS,4 had functional constipation,and 12 had mixed IBS.The Dahlqvist method was used to measure disaccharidase activity in the brush-border membrane of mature enterocytes of the small intestine,in duodenal biopsies obtained during esophagogastroduodenoscopy.RESULTS Lactase deficiency was detected in 86.5%of patients,maltase deficiency in 48.7%,sucrase deficiency in 50%,and glucoamylase deficiency in 84.1%.The activities of all enzymes were reduced in 31.7%of patients,and carbohydrase deficiency was detected in 63.5%of patients.The low activity of enzymes involved in membrane digestion in the small intestine was found in 95.2%of patients.CONCLUSION In 78 of the 82 patients with FBD,gastrointestinal symptoms were associated with disaccharidase deficiency.展开更多
Deficiency or restriction of Zn absorption in soils is one of the most common micronutrients deficient in cereal plants. To investigate critical micronutrient interaction in zinc deficiency and zinc sufficient in soil...Deficiency or restriction of Zn absorption in soils is one of the most common micronutrients deficient in cereal plants. To investigate critical micronutrient interaction in zinc deficiency and zinc sufficient in soil, a factorial experiment based on completely randomized design (CRD) with three replications was conducted in 2023. Six wheat cultivars with different Zn efficiency were used. The cultivars were grown under Zn deficiency and adequate conditions. Results showed that in Zn deficiency conditions, with increasing Zn concentration in the roots, Fe concentrations were increased too, while the Cu and Mn concentrations decreased. In the same condition and with increasing Zn concentration in shoots, the concentrations of Fe and Mn decreased, while Cu were increased. However, by increasing Zn concentration, Fe, Cu, and Mn concentrations were increased in Zn deficiency condition in grains, as well as Zn sufficient conditions. RST (root to shoot micronutrient translocation) comparison of cultivars showed that in lack of Zn, the ability of translocation of Zn, Fe, and Mn in Zn-inefficient cultivar from root to shoot was higher than inefficient cultivar. In the same conditions, the capability of Zn-inefficient cultivar in Cu translocation from root to shoot was lower than other cultivars. In general, it seems that in Zn deficiency conditions, there are antagonistic effects among Zn, Cu and Mn and synergistic effects between Zn and Fe in the root. Also, in Zn sufficient conditions, there were synergistic effects among all studies micronutrients which include Zn, Fe, Cu, and Mn.展开更多
Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically t...Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically tailored for non-small cell lung cancer(NSCLC)have yet to be established.Further research is needed to clarify the precise role and clinical implications of HRD in NSCLC.Methods:A cohort of 580 treatment-naive NSCLC patients was retrospectively enrolled.Comprehensive genomic profiling(CGP)was performed for all patients,and HRD status was evaluated using two genomic scar score(GSS)-based algorithms:a machine learning-based GSS(ML-GSS)and a continuous linear regression-based GSS(CLR-GSS).To assess the diagnostic performance(sensitivity and specificity)of the ML-GSS and CLR-GSS algorithms for HRD detection,immunohistochemical(IHC)staining was conducted for two HRD-related biomarkers:Schlafen 11(SLFN11)and RAD51.Survival analysis,including progression-free survival(PFS),along with multivariable Cox proportional hazards models,was performed to compare the prognostic value of the two HRD algorithms.Results:Among all patients,146(25.2%)and 46(7.9%)were classified as HRD-positive(HRD+)by ML-GSS and CLR-GSS,respectively.Using SLFN11 IHC expression as the reference standard,comparative analysis demonstrated that ML-GSS exhibited significantly higher sensitivity but lower specificity than CLR-GSS.This trend was consistently observed in RAD51 staining analysis.Compared to HRD-negative(HRD-)patients,MLGSS-defined HRD+cases displayed distinct clinicopathological and genomic features,including a higher prevalence of homologous recombination(HR)-related genes mutations,BRCA1/2 mutations,TP53 mutations,elevated tumor mutation burden(TMB),and increased copy number variations(CNVs).In contrast,CLR-GSSdefined HRD+patients were only enriched for BRCA1/2 mutations,TP53 mutations,and elevated TMB.Furthermore,ML-GSS-defined HRD+status was associated with significantly worse prognosis following first-line therapy compared to HRD-patients.Univariate and multivariable Cox analyses identified ML-GSS-defined HRD+and TP53 mutations as significant predictors and independent risk factors,respectively.No such associations were observed in the CLR-GSS-defined HRD+cohort.Conclusions:ML-GSS demonstrated superior performance to CLR-GSS in assessing chromosomal instability(CIN)and showed greater clinical utility.We recommend the ML-GSS algorithm as a robust and clinically validated tool for HRD/CIN evaluation in NSCLC.Furthermore,ML-GSS-defined HRD+status was identified as both a significant predictor and an independent risk factor.展开更多
Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying...Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying etiology remains complex.Recent studies suggest a close link between the gut microbiota and the synthesis,absorption,and metabolism of these vitamins.However,the specific causal relationships between the gut microbiota composition and vitamin deficiencies remain poorly understood.Identifying key bacterial species and understanding their role in vitamin metabolism could provide critical insights for targeted interventions.Methods We conducted a two-sample Mendelian randomization(MR)study to assess the causal relationship between the gut microbiota and vitamin deficiencies(A,B12,D).The genome-wide association study data for vitamin deficiencies were sourced from the FinnGen biobank,and the gut microbiota data were from the MiBioGen consortium.MR analyses included inverse variance-weighted(IVW),MR‒Egger,weighted median,and weighted mode approaches.Sensitivity analyses and reverse causality assessments were performed to ensure robustness and validate the findings.Results After FDR adjustment,vitamin B12 deficiency was associated with the class Verrucomicrobiae,order Verrucomicrobiales,family Verrucomicrobiaceae,and genus Akkermansia.Vitamin A deficiency was associated with the phylum Firmicutes and the genera Fusicatenibacter and Ruminiclostridium 6.Additional associations for vitamin B12 deficiency included the Enterobacteriaceae and Rhodospirillaceae and the genera Coprococcus 2,Lactococcus,and Ruminococcaceae UCG002.Vitamin D deficiency was associated with the genera Allisonella,Eubacterium,and Tyzzerella 3.Lachnospiraceae and Lactococcus were common risk factors for both B12 and D deficiency.Sensitivity analyses confirmed the robustness of the findings against heterogeneity and horizontal pleiotropy,and reverse MR tests indicated no evidence of reverse causality.Conclusions Our findings reveal a possible causal relationship between specific gut microbiota characteristics and vitamin A,B12 and D deficiencies,providing a theoretical basis for addressing these nutritional deficiencies through the modulation of the gut microbiota in the future and laying the groundwork for related interventions.展开更多
Objective To explore the clinical characteristics and methods for syndrome differentiation prediction,as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ische...Objective To explore the clinical characteristics and methods for syndrome differentiation prediction,as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ischemic stroke(AIS).Methods This study employed a retrospective case-control design to analyze patients with AIS who received inpatient treatment at the Neurology Department of The First Hospital of Hunan University of Chinese Medicine from January 1,2013 to December 31,2022.AIS patients meeting the diagnostic criteria for Qi deficiency and blood stasis syndrome were stratified into case group,while those without Qi deficiency and blood stasis syndrome were stratified into control group.The demographic characteristics(age and gender),clinical parameters[time from onset to admission,National Institutes of Health Stroke Scale(NIHSS)score,and blood pressure],past medical history,traditional Chinese medicine(TCM)diagnostic characteristics(tongue and pulse),neurological symptoms and signs,imaging findings[magnetic resonance imaging-diffusion weighted imaging(MRI-DWI)],and biochemical indicators of the two groups were collected and compared.The indicators with statistical difference(P<0.05)in univariate analysis were included in multivariate logistic regression analysis to evaluate their predictive value for the diagnosis of Qi deficiency and blood stasis syndrome,and the predictive model was constructed by receiver operating characteristic(ROC)curve analysis.Results The study included 1035 AIS patients,with 404 cases in case group and 631 cases in control group.Compared with control group,patients in case group were significantly older,had extended onset-to-admission time,lower diastolic blood pressure,and lower NIHSS scores(P<0.05).Case group showed lower incidence of hypertension history(P<0.05).Regarding tongue and pulse characteristics,pale and dark tongue colors,white tongue coating,fine pulse,astringent pulse,and sinking pulse were more common in case group.Imaging examinations demonstrated higher proportions of centrum semiovale infarction,cerebral atrophy,and vertebral artery stenosis in case group(P<0.05).Among biochemical indicators,case group showed higher proportions of elevated fasting blood glucose and glycated hemoglobin(HbA1c),while lower proportions of elevated white blood cell count,reduced hemoglobin,and reduced high-density lipoprotein cholesterol(HDL-C)(P<0.05).Multivariate logistic regression analysis identified significant predictors for Qi deficiency and blood stasis syndrome including:fine pulse[odds ratio(OR)=4.38],astringent pulse(OR=3.67),superficial sensory abnormalities(OR=1.86),centrum semiovale infarction(OR=1.57),cerebral atrophy(OR=1.55),vertebral artery stenosis(OR=1.62),and elevated HbA1c(OR=3.52).The ROC curve analysis of the comprehensive prediction model yielded an area under the curve(AUC)of 0.878[95%confidence interval(CI)=0.855-0.900].Conclusion This study finds out that Qi deficiency and blood stasis syndrome represents one of the primary types of AIS.Fine pulse,astringent pulse,superficial sensory abnormalities,centrum semiovale infarction,cerebral atrophy,vertebral artery stenosis,elevated blood glucose,elevated HbA1c,pale and dark tongue colors,and white tongue coating are key objective diagnostic indicators for the syndrome differentiation of AIS with Qi deficiency and blood stasis syndrome.Based on these indicators,a syndrome differentiation prediction model has been developed,offering a more objective basis for clinical diagnosis,and help to rapidly identify this syndrome in clinical practice and reduce misdiagnosis and missed diagnosis.展开更多
This study presents a detailed investigation of the microstructure of the oxygen-deficient perovskite material Ca2FeGaO6-δ using Scanning Electron Microscopy (SEM). The material exhibits significant porosity and irre...This study presents a detailed investigation of the microstructure of the oxygen-deficient perovskite material Ca2FeGaO6-δ using Scanning Electron Microscopy (SEM). The material exhibits significant porosity and irregular grain morphology, with variations in grain size and growth. Unlike conventional perovskite structures, Ca2FeGaO6-δ shows non-uniform grain development, which can be attributed to the presence of oxygen vacancies (δ). SEM analysis reveals that the irregularities in grain size and shape, coupled with the porous nature of the material, are likely to influence its functional properties. These findings provide valuable insights into the structural features of Ca2FeGaO6-δ, offering a foundation for understanding its potential applications in catalysis, sensors, and other technologies. The study highlights the critical role of microstructural characteristics in determining the material’s performance.展开更多
Background:Iron facilitates key biological functions underpinning sports performance,and up to 60%of female athletes experience iron deficiency.However,the effects of iron deficiency on sports performance in female at...Background:Iron facilitates key biological functions underpinning sports performance,and up to 60%of female athletes experience iron deficiency.However,the effects of iron deficiency on sports performance in female athletes is unclear,as are the degree of benefits of iron supplementation(FeSup).This study characterizes the effects of iron deficiency and FeSup on sports performance in high-level female athletes.Methods:Searches of the electronic databases MEDLINE,SPORTDiscus,Web of Science,Scopus,and CINAHL were performed in July 2023.Studies were included that evaluated the effects of iron deficiency or FeSup on sports performance in high-level(maximal oxygen uptake(VO2max)>45 mL/kg/min,or trained>5 h/week)iron deficient(ID)(serum ferritin(sFer)<40 mg/L)female athletes.Studies were assessed using a modified Downs and Black Quality Assessment Checklist.Results:A total of 23 studies comprising 669 athletes(age range:13-47 years)across 16 sports were included in the review.Iron deficiency negatively affects endurance performance by 3%-4%.However,endurance performance improved by 2%-20%when ID athletes were treated with 100 mg/day of elemental iron for up to 56 days via oral supplementation,or bi-daily via parenteral administration over 8-10 days.ID nonanemic athletes with low sFer stores may be predisposed to reduced maximal aerobic capacity.However,maximal aerobic capacity improved by 6%-15%following 16 mg/day-100 mg/day of elemental iron for 36-126 days.Isokinetic strength and anaerobic power performance may be impeded(-23%to+4%)among ID athletes,but the effect of FeSup on anaerobic power varied markedly(-5%to+9%)following 100 mg/day of elemental iron over 42-56 days,or 100 mg of elemental iron bi-daily over 8-10 days.The quality of studies was moderate(77%),ranging from low(57%)to high(100%).Moststudies(n=18)contained group sizes-20 athletes,thus limiting the likelihood of detecting significant effects(statistical power>0.80).Conclusion:High-level ID female athletes experience a negative impact on endurance performance,which can be improved by supplementing with»100 mg of elemental iron per day or bi-daily.The decrements in other performance parameters characterizing a range of sports coincide with the severity of iron deficiency.展开更多
BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-st...BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-stable(MSS)CRC patients is considerably restricted.This study sought to evaluate the effectiveness of immu-notherapy in MSS patients characterized by homologous recombination defi-ciency(HRD)as opposed to those with homologous recombination proficiency(HRP).AIM To investigate and compare the clinicopathological characteristics,treatment modalities,and outcomes between the HRD and HRP groups in CRC.METHODS Next-generation sequencing was performed on 268 CRC patients to identify tumor-associated genetic alterations and assess their HRD scores and MSI status.Patients with HRD-related gene alterations or an HRD score≥30 were classified into the HRD group,while the remaining patients were assigned to the HRP group.Clinical data,including staging and treatment regimens,were collected for analysis.Cox regression and Kaplan-Meier survival curves were employed to evaluate whether the HRD group demonstrated improved survival outcomes following immunotherapy treatment.RESULTS Among the 268 patients,64 were classified into the HRD group,which had a higher proportion of early-stage CRC diagnoses compared to the HRP group.Kaplan-Meier survival curves indicated significantly better survival rates in the HRD group compared to the HRP group across all cohorts,as well as among MSS patients treated with immunotherapy(P<0.05).CONCLUSION This study demonstrates that CRC patients with HRD have a more favorable prognosis and suggests that HRD status could serve as a predictive marker for immunotherapy response in MSS patients.展开更多
Brassica napus(oilseed rape)is sensitive to boron(B)deficiency and exhibits young leaf curling in response to low-B stress at the seedling stage,which leads to reduced photosynthesis and plant growth.So far,no gene ha...Brassica napus(oilseed rape)is sensitive to boron(B)deficiency and exhibits young leaf curling in response to low-B stress at the seedling stage,which leads to reduced photosynthesis and plant growth.So far,no gene has been identified to be involved in B deficiency induced leaf curling.Our previous results showed the transcription factor BnaA1.WRKY53 might be involved in B-deficiency tolerance.However,altered BnaA1.WRKY53 expression does not influence B concentration in shoot,root and leaf cell walls,which suggests Bna A1.WRKY53 might be involved in other biological processes.Indeed,phenotypic and anatomical analyses revealed that BnaA1.WRKY53 negatively regulated the leaf curling induced by leaf epinasty by suppressing the overexpansion of palisade cells under B deficiency.Further transcriptome enrichment analysis of differentially expressed genes(DEGs)between wild-type and BnaA1.WRKY53overexpression line showed auxin response pathway was enriched.In addition,Arabidopsis DR5::GFP auxin reporter line showed B deficiency caused predominant auxin signal accumulation in the adaxial side and concomitant adaxial cell expansion,which indicated that B deficiency may induce leaf curling by altering auxin distribution.Phytohormone quantification and gene expression analysis demonstrated that BnaA1.WRKY53 prevent auxin overaccumulation in leaves by suppressing auxin biosynthetic genes under B deficiency.Furthermore,exogenous 1-naphthlcetic acid(NAA)treatment experiments revealed that high auxin could induce leaf curling and BnaA1.WRKY53 expression.Overall,these findings demonstrate that auxin and the transcription factor BnaA1.WRKY53 synergistically regulate leaf curling to maintain an optimal leaf area under B deficiency,and provide novel insights into the resistance mechanisms against B-deficiency-induced leaf curling in oilseed rape.展开更多
Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachrono...Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.展开更多
AIM:To compare the Ishihara test errors scores of colour vision deficiency(CVD)subjects when wearing four different types of red-tinted contact lenses(RCL)that differ in their transmittance as determined using a spect...AIM:To compare the Ishihara test errors scores of colour vision deficiency(CVD)subjects when wearing four different types of red-tinted contact lenses(RCL)that differ in their transmittance as determined using a spectrophotometer.METHODS:Six congenital CVD subjects volunteered to participate in this study.Ishihara plates were used to determine the colour vision errors made,whereas Farnsworth-Munsell 100 Hue test was conducted to determine the total error scores(TES)and type of CVD.Four types of RCL(Types A,B,C and D)were inserted in the non-dominant eye and tested in a randomised manner by a masked operator.Errors scores in Ishihara test were determined at baseline without any contact lens and after wearing the four different RCL.The subjects were then divided into two groups based on the mean TES.RESULTS:Repeated measures ANOVA with Greenhouse-Geisser corrections showed that there was a highly significant effect of RCL type on Ishihara error score[F(2.056,10.282)=30.214,P<0.001].Error scores with RCL Type B were significantly lower than errors made when no lens was worn,and with RCL Type C and Type D(all P<0.001).Error scores with RCL Type B were also lower than those made with RCL Type A,however,they were not significantly different.For subjects with TES values less than 180,RCL type B showed the largest improvement in Ishihara error score(50%)compared to the other three RCLs.RCL type A showed the best performance in TES value of more than 180,with an improvement of 80%in Ishihara score.RCL Type A has the lowest transmittance at the confusion wavelength(450-568 nm),followed by RCL Types B,D and C.CONCLUSION:This study shows that RCL can improve Ishihara error scores.RCL with lower transmission at 450-568 nm and 90%transmittance beyond 637 nm are the most effective.Lenses which could block more light between 550-580 nm are more effective for colour defectives with more severe colour defects.展开更多
The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se ...The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se deficiency accusers more frequently in low-Se regions.Therefore,to investigate the Se status and inflammatory response of the mammary gland under marginal dietary Se levels,an lipopolysaccharide(LPS)induced mouse mastitis model was established.Mice were fed with moderate Se diet(0.087 mg•kg^(-1) Se),adequate Se diet(0.15 mg•kg^(-1) Se)or excessive Se diet(1.5 mg•kg^(-1) Se)for 60 days.Se status and inflammatory factors were investigated.Results showed that the Se status of mammary gland correlated with dietary Se levels.Marginal Se deficiency exacerbated mammary tissue histopathology;increased the mRNA level of inflammatory genes tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and cyclooxygenase-2(COX-2);and enhanced the phosphorylation of NF-κB p65 in mammary gland tissues.Supplementation of Se in diet higher than recommended levels reduced the inflammatory reaction of mammary glands in LPS-induced mastitis model and provided a protective effect.展开更多
Objective:To investigate whether differences exist in DNA fragmentation levels and protamine deficiency in the sperm of obese men compared to those of overweight and proven fertile,normal weight men and evaluate the a...Objective:To investigate whether differences exist in DNA fragmentation levels and protamine deficiency in the sperm of obese men compared to those of overweight and proven fertile,normal weight men and evaluate the alterations related to reproductive hormones,semen parameters and their association with body mass index(BMI).Methods:Participants in this observational study were divided into three groups based on their BMI:proven fertile,normal weight men(n=200);overweight men(n=200);and obese men(n=200).After 3 days of abstinence,seminal fluid was collected from all participants and analyzed.Blood samples were also collected on the same day for hormonal analysis.Sperm DNA fragmentation and protamine deficiency were also assessed.Results:A total of 600 men with a mean age of(34.3±7.9)2 years were included in the study.Obese males(BMI 30 kg/m or higher)exhibited significant reductions in semen volume,sperm concentration,total sperm motility percentage,progressive motility,non-progressive motility,and levels of total testosterone,follicle-stimulating hormone(FSH)and luteinizing hormone(LH)compared to overweight(BMI 25 to 29.9 kg/m2)and normal weight males(BMI 18.5 to 24.9 kg/m2)(P<0.001).Conversely,obese males showed a significant increase in prolactin level,sperm DNA fragmentation,and protamine deficiency compared to overweight and normal weight males(P<0.001).Significant negative correlations were demonstrated between BMI and sperm concentration,motility,total testosterone,FSH and LH(P<0.001),whereas prolactin,sperm DNA fragmentation and protamine deficiency were positively correlated with BMI(P<0.001).Conclusions:This study provides clear evidence that obesity contributes potentially to male infertility by inducing sperm DNA fragmentation and protamine deficiency,as well as negatively impacting reproductive hormones and semen quality.展开更多
BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)...BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.展开更多
文摘Sporadic or late-onset Alzheimer’s disease(LOAD)occurs in 1 of 10 people over 65 years of age and comprises 95%of all AD patients.Unlike early-onset AD,which is caused by defined single gene mutations,the mechanisms and events underlying risk for LOAD are not fully understood and no substantial disease-modifying interventions are currently available.Age is the most prominent risk factor for LOAD,and interacting age-related and LOAD-associated factors contribute to its pathogenesis.Among these factors are changes in bioenergetic cell functions,which metabolize substrates and produce energy stored in adenosine triphosphate.
基金Supported by General Project of Shanxi Administration of Traditional Chinese Medicine(2023ZYYA007&2024ZYY2D009)Young Scientists Project of Shanxi Provincial Department of Science and Technology(202203021212026)Scientific and Technological Innovation Capacity Cultivation Program for Basic and Clinical Cooperative Research Project of Shanxi University of Chinese Medicine(2024PY-JL-23-01).
文摘This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmony,and to provide a treatment plan.Professor Li Tingquan believes that the occurrence and development of chronic atrophic gastritis(CAG)is fundamentally a process of harmony imbalance of the spleen and stomach.Its specific manifestation lies in the interaction between qi deficiency and stagnation,namely,spleen deficiency as the root cause,and qi stagnation,phlegm-dampness,and blood stasis obstructing the middle energizer as the secondary manifestations.These factors are mutually causal and interact with one another.Based on this,he proposed a four-step method to treat the disease:eliminating pathogenic factors,harmonizing the spleen and stomach,activating blood circulation to resolve stasis,and tonifying the kidney to generate blood(metaphorically described as"closing the mountains to cultivate forests and thicken the soil,breeding seeds and irrigating for stomach recovery").This approach aims to restore the harmonious state of the middle energizer,providing a complete clinical framework of theory,principle,formula,and herbs for the prevention and treatment of CAG.
基金funded by the Entrusted service project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23001)2023 Sanqin Talent Special Support Program Innovation and Entrepreneurship Team Project,and Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine(2023).
文摘Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.
基金supported by the National Key R&D Program of China(Grant No.2022YFE0139400)the National Natural Science Foundation of China(Grant No.31961143016)the Shenzhen Science and Technology Program,China(Grant No.JCYJ20200109150650397).
文摘Zinc(Zn)is an essential micronutrient for both plants and humans.Zn deficiency is common in many paddy fields and reduces yield and grain Zn content(GZC).To accelerate breeding for improved GZC and Zn deficiency tolerance(ZDT)rice varieties,it is important to identify genes regulating Zn homeostasis.In this study,a member of the Ser/Thr protein phosphatase family,LOC_Os07g48840(named as OsGZ7),was found to contributed to ZDT and GZC in rice.The expression of OsGZ7 in roots and shoots was inhibited by Zn deficiency and toxicity,but induced by iron(Fe),manganese(Mn),and copper(Cu)deficiency,as well as chromium toxicity.OsGZ7 localized to the cytoplasm and was expressed in all tissues during the tillering,flowering,and grain-filling stages,particularly in the leaf blade and leaf sheath.At the seedling stage,knockout of OsGZ7 enhanced ZDT and increased Zn accumulation in both roots and shoots.At the maturity stage,knockout of OsGZ7 enhanced GZC,while overexpression of OsGZ7 reduced GZC.RNA-seq analysis suggested that OsGZ7 might regulate Zn homeostasis by affecting metal binding,hormone signal transduction,and oxidoreductase activity.Taken together,our findings indicate that OsGZ7 contributes to ZDT and Zn accumulation in rice.
基金Supported by National Natural Science Foundation of China:Establishment and Validation of a High-throughput Screening System for Traditional Chinese Medicine Against Dry Eye Disease based on transforming growth factor-βand B-cell lymphoma-2(No.81574031)2023 Hunan Provincial Department of Education Scientific Research Project:Yiguanjian Decoction Regulates Th17/Treg Cell Balance and Its Intervention Mechanism in Dry Eye with Liver Yin Deficiency Syndrome(No.23A0300)。
文摘OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which serve as key references for disease prevention and management.METHODS:The dataset containing the data of Yin and Yang deficiency constitution was identified through the Gene Expression Omnibus database.This database was used for differential expression genes(DEGs)analysis and weighted gene co-expression network analysis(WGCNA),and the characteristic genes were then obtained in the dataset using a machine learning method.The hub genes of Yin and Yang deficiency constitution were obtained after analysis using the above three methods,and the hub genes were enriched and analyzed.Subsequently,the hub genes of Yin and Yang deficiency constitution were validated using external datasets.Receiver operating characteristic(ROC)analysis was used on each hub genes of the two groups to further understand their diagnostic performance.The mi RNA–lnc RNA-gene network was used to further analyze the hub genes.Immunoinfiltration and gene set enrichment analysis were performed on the shared hub genes.RESULTS:The GSE87474 dataset was used for DEGs analysis and WGCNA.Using machine learning analyses,we identified 15 and 14 hub genes for Yin and Yang deficiency constitutions,respectively.The results of enrichment analyses showed that Yin deficiency constitution was associated with interleukin-17 signaling pathway,whereas Yang deficiency constitution was associated with glycosaminoglycan biosynthesis–keratan sulfate.The validation dataset GSE56116 showed statistically significant data for s-adenosylmethionine sensor upstream of MTORC1(SAMTOR,also named C7orf60),cofilin 2(CFL2),cytohesin 1 interacting protein(CYTIP),G protein-coupled receptor 183(GPR183),hippocampus abundant transcript 1(HIAT1),kelch like family member 15(KLHL15),mitogen-activated protein kinase 6(MAPK6),and prostaglandin-endoperoxide synthase 2(PTGS2)in Yin deficiency and fucosyltransferase 8(FUT8),TATA-box binding protein associated factor,RNA polymerase I subunit D(TAF1D),zinc finger protein 24(ZNF24),MAPK6,and leptin receptor overlapping transcript like 1(LEPROTL1)in Yang deficiency.The ROC results indicated that these genes have diagnostic value.MAPK6 is a shared hub gene for Yin and Yang deficiencies.CONCLUSIONS:This study identified C7orf60,CFL2,CYTIP,GPR183,HIAT1,KLHL15,MAPK6,and PTGS2 in Yin deficiency and FUT8,TAF1D,ZNF24,MAPK6,and LEPROTL1 in Yang deficiency as potential biomarkers,providing insights into their pathogenesis.This theory not only guides the diagnostic approach in TCM but also extends its influence to various scientific research fields.
基金supported by the National Natural Science Foundation of China Regional Joint Innovation Fund (No.U22A20524)the Heilongjiang Province Natural Science Foundation Key projects (No.ZD2023C002).
文摘Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.
文摘BACKGROUND Functional bowel disorder(FBD)may be caused by a decrease in disaccharidase activity.Thus,the timely diagnosis of disaccharidase deficiency could lead to a better prognosis in patients with this condition.AIM To determine the potential value of intestinal disaccharidases glucoamylase,maltase,sucrase,and lactase in understanding the etiology and pathogenesis of FBD.METHODS A total of 82 FBD patients were examined.According to the Rome IV criteria(2016),23 patients had diarrhea-predominant irritable bowel syndrome(IBS),33 had functional diarrhea,10 had constipation-predominant IBS,4 had functional constipation,and 12 had mixed IBS.The Dahlqvist method was used to measure disaccharidase activity in the brush-border membrane of mature enterocytes of the small intestine,in duodenal biopsies obtained during esophagogastroduodenoscopy.RESULTS Lactase deficiency was detected in 86.5%of patients,maltase deficiency in 48.7%,sucrase deficiency in 50%,and glucoamylase deficiency in 84.1%.The activities of all enzymes were reduced in 31.7%of patients,and carbohydrase deficiency was detected in 63.5%of patients.The low activity of enzymes involved in membrane digestion in the small intestine was found in 95.2%of patients.CONCLUSION In 78 of the 82 patients with FBD,gastrointestinal symptoms were associated with disaccharidase deficiency.
文摘Deficiency or restriction of Zn absorption in soils is one of the most common micronutrients deficient in cereal plants. To investigate critical micronutrient interaction in zinc deficiency and zinc sufficient in soil, a factorial experiment based on completely randomized design (CRD) with three replications was conducted in 2023. Six wheat cultivars with different Zn efficiency were used. The cultivars were grown under Zn deficiency and adequate conditions. Results showed that in Zn deficiency conditions, with increasing Zn concentration in the roots, Fe concentrations were increased too, while the Cu and Mn concentrations decreased. In the same condition and with increasing Zn concentration in shoots, the concentrations of Fe and Mn decreased, while Cu were increased. However, by increasing Zn concentration, Fe, Cu, and Mn concentrations were increased in Zn deficiency condition in grains, as well as Zn sufficient conditions. RST (root to shoot micronutrient translocation) comparison of cultivars showed that in lack of Zn, the ability of translocation of Zn, Fe, and Mn in Zn-inefficient cultivar from root to shoot was higher than inefficient cultivar. In the same conditions, the capability of Zn-inefficient cultivar in Cu translocation from root to shoot was lower than other cultivars. In general, it seems that in Zn deficiency conditions, there are antagonistic effects among Zn, Cu and Mn and synergistic effects between Zn and Fe in the root. Also, in Zn sufficient conditions, there were synergistic effects among all studies micronutrients which include Zn, Fe, Cu, and Mn.
基金supported by the National High Level Hospital Clinical Research Funding(No.BJ-2019-195)the National High Level Hospital Clinical Research Funding(No.BJ-2023-090)。
文摘Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically tailored for non-small cell lung cancer(NSCLC)have yet to be established.Further research is needed to clarify the precise role and clinical implications of HRD in NSCLC.Methods:A cohort of 580 treatment-naive NSCLC patients was retrospectively enrolled.Comprehensive genomic profiling(CGP)was performed for all patients,and HRD status was evaluated using two genomic scar score(GSS)-based algorithms:a machine learning-based GSS(ML-GSS)and a continuous linear regression-based GSS(CLR-GSS).To assess the diagnostic performance(sensitivity and specificity)of the ML-GSS and CLR-GSS algorithms for HRD detection,immunohistochemical(IHC)staining was conducted for two HRD-related biomarkers:Schlafen 11(SLFN11)and RAD51.Survival analysis,including progression-free survival(PFS),along with multivariable Cox proportional hazards models,was performed to compare the prognostic value of the two HRD algorithms.Results:Among all patients,146(25.2%)and 46(7.9%)were classified as HRD-positive(HRD+)by ML-GSS and CLR-GSS,respectively.Using SLFN11 IHC expression as the reference standard,comparative analysis demonstrated that ML-GSS exhibited significantly higher sensitivity but lower specificity than CLR-GSS.This trend was consistently observed in RAD51 staining analysis.Compared to HRD-negative(HRD-)patients,MLGSS-defined HRD+cases displayed distinct clinicopathological and genomic features,including a higher prevalence of homologous recombination(HR)-related genes mutations,BRCA1/2 mutations,TP53 mutations,elevated tumor mutation burden(TMB),and increased copy number variations(CNVs).In contrast,CLR-GSSdefined HRD+patients were only enriched for BRCA1/2 mutations,TP53 mutations,and elevated TMB.Furthermore,ML-GSS-defined HRD+status was associated with significantly worse prognosis following first-line therapy compared to HRD-patients.Univariate and multivariable Cox analyses identified ML-GSS-defined HRD+and TP53 mutations as significant predictors and independent risk factors,respectively.No such associations were observed in the CLR-GSS-defined HRD+cohort.Conclusions:ML-GSS demonstrated superior performance to CLR-GSS in assessing chromosomal instability(CIN)and showed greater clinical utility.We recommend the ML-GSS algorithm as a robust and clinically validated tool for HRD/CIN evaluation in NSCLC.Furthermore,ML-GSS-defined HRD+status was identified as both a significant predictor and an independent risk factor.
文摘Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying etiology remains complex.Recent studies suggest a close link between the gut microbiota and the synthesis,absorption,and metabolism of these vitamins.However,the specific causal relationships between the gut microbiota composition and vitamin deficiencies remain poorly understood.Identifying key bacterial species and understanding their role in vitamin metabolism could provide critical insights for targeted interventions.Methods We conducted a two-sample Mendelian randomization(MR)study to assess the causal relationship between the gut microbiota and vitamin deficiencies(A,B12,D).The genome-wide association study data for vitamin deficiencies were sourced from the FinnGen biobank,and the gut microbiota data were from the MiBioGen consortium.MR analyses included inverse variance-weighted(IVW),MR‒Egger,weighted median,and weighted mode approaches.Sensitivity analyses and reverse causality assessments were performed to ensure robustness and validate the findings.Results After FDR adjustment,vitamin B12 deficiency was associated with the class Verrucomicrobiae,order Verrucomicrobiales,family Verrucomicrobiaceae,and genus Akkermansia.Vitamin A deficiency was associated with the phylum Firmicutes and the genera Fusicatenibacter and Ruminiclostridium 6.Additional associations for vitamin B12 deficiency included the Enterobacteriaceae and Rhodospirillaceae and the genera Coprococcus 2,Lactococcus,and Ruminococcaceae UCG002.Vitamin D deficiency was associated with the genera Allisonella,Eubacterium,and Tyzzerella 3.Lachnospiraceae and Lactococcus were common risk factors for both B12 and D deficiency.Sensitivity analyses confirmed the robustness of the findings against heterogeneity and horizontal pleiotropy,and reverse MR tests indicated no evidence of reverse causality.Conclusions Our findings reveal a possible causal relationship between specific gut microbiota characteristics and vitamin A,B12 and D deficiencies,providing a theoretical basis for addressing these nutritional deficiencies through the modulation of the gut microbiota in the future and laying the groundwork for related interventions.
基金National Natural Science Foundation of China(U22A20377)Natural Science Foundation of Hunan Province of China(23C0168).
文摘Objective To explore the clinical characteristics and methods for syndrome differentiation prediction,as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ischemic stroke(AIS).Methods This study employed a retrospective case-control design to analyze patients with AIS who received inpatient treatment at the Neurology Department of The First Hospital of Hunan University of Chinese Medicine from January 1,2013 to December 31,2022.AIS patients meeting the diagnostic criteria for Qi deficiency and blood stasis syndrome were stratified into case group,while those without Qi deficiency and blood stasis syndrome were stratified into control group.The demographic characteristics(age and gender),clinical parameters[time from onset to admission,National Institutes of Health Stroke Scale(NIHSS)score,and blood pressure],past medical history,traditional Chinese medicine(TCM)diagnostic characteristics(tongue and pulse),neurological symptoms and signs,imaging findings[magnetic resonance imaging-diffusion weighted imaging(MRI-DWI)],and biochemical indicators of the two groups were collected and compared.The indicators with statistical difference(P<0.05)in univariate analysis were included in multivariate logistic regression analysis to evaluate their predictive value for the diagnosis of Qi deficiency and blood stasis syndrome,and the predictive model was constructed by receiver operating characteristic(ROC)curve analysis.Results The study included 1035 AIS patients,with 404 cases in case group and 631 cases in control group.Compared with control group,patients in case group were significantly older,had extended onset-to-admission time,lower diastolic blood pressure,and lower NIHSS scores(P<0.05).Case group showed lower incidence of hypertension history(P<0.05).Regarding tongue and pulse characteristics,pale and dark tongue colors,white tongue coating,fine pulse,astringent pulse,and sinking pulse were more common in case group.Imaging examinations demonstrated higher proportions of centrum semiovale infarction,cerebral atrophy,and vertebral artery stenosis in case group(P<0.05).Among biochemical indicators,case group showed higher proportions of elevated fasting blood glucose and glycated hemoglobin(HbA1c),while lower proportions of elevated white blood cell count,reduced hemoglobin,and reduced high-density lipoprotein cholesterol(HDL-C)(P<0.05).Multivariate logistic regression analysis identified significant predictors for Qi deficiency and blood stasis syndrome including:fine pulse[odds ratio(OR)=4.38],astringent pulse(OR=3.67),superficial sensory abnormalities(OR=1.86),centrum semiovale infarction(OR=1.57),cerebral atrophy(OR=1.55),vertebral artery stenosis(OR=1.62),and elevated HbA1c(OR=3.52).The ROC curve analysis of the comprehensive prediction model yielded an area under the curve(AUC)of 0.878[95%confidence interval(CI)=0.855-0.900].Conclusion This study finds out that Qi deficiency and blood stasis syndrome represents one of the primary types of AIS.Fine pulse,astringent pulse,superficial sensory abnormalities,centrum semiovale infarction,cerebral atrophy,vertebral artery stenosis,elevated blood glucose,elevated HbA1c,pale and dark tongue colors,and white tongue coating are key objective diagnostic indicators for the syndrome differentiation of AIS with Qi deficiency and blood stasis syndrome.Based on these indicators,a syndrome differentiation prediction model has been developed,offering a more objective basis for clinical diagnosis,and help to rapidly identify this syndrome in clinical practice and reduce misdiagnosis and missed diagnosis.
文摘This study presents a detailed investigation of the microstructure of the oxygen-deficient perovskite material Ca2FeGaO6-δ using Scanning Electron Microscopy (SEM). The material exhibits significant porosity and irregular grain morphology, with variations in grain size and growth. Unlike conventional perovskite structures, Ca2FeGaO6-δ shows non-uniform grain development, which can be attributed to the presence of oxygen vacancies (δ). SEM analysis reveals that the irregularities in grain size and shape, coupled with the porous nature of the material, are likely to influence its functional properties. These findings provide valuable insights into the structural features of Ca2FeGaO6-δ, offering a foundation for understanding its potential applications in catalysis, sensors, and other technologies. The study highlights the critical role of microstructural characteristics in determining the material’s performance.
文摘Background:Iron facilitates key biological functions underpinning sports performance,and up to 60%of female athletes experience iron deficiency.However,the effects of iron deficiency on sports performance in female athletes is unclear,as are the degree of benefits of iron supplementation(FeSup).This study characterizes the effects of iron deficiency and FeSup on sports performance in high-level female athletes.Methods:Searches of the electronic databases MEDLINE,SPORTDiscus,Web of Science,Scopus,and CINAHL were performed in July 2023.Studies were included that evaluated the effects of iron deficiency or FeSup on sports performance in high-level(maximal oxygen uptake(VO2max)>45 mL/kg/min,or trained>5 h/week)iron deficient(ID)(serum ferritin(sFer)<40 mg/L)female athletes.Studies were assessed using a modified Downs and Black Quality Assessment Checklist.Results:A total of 23 studies comprising 669 athletes(age range:13-47 years)across 16 sports were included in the review.Iron deficiency negatively affects endurance performance by 3%-4%.However,endurance performance improved by 2%-20%when ID athletes were treated with 100 mg/day of elemental iron for up to 56 days via oral supplementation,or bi-daily via parenteral administration over 8-10 days.ID nonanemic athletes with low sFer stores may be predisposed to reduced maximal aerobic capacity.However,maximal aerobic capacity improved by 6%-15%following 16 mg/day-100 mg/day of elemental iron for 36-126 days.Isokinetic strength and anaerobic power performance may be impeded(-23%to+4%)among ID athletes,but the effect of FeSup on anaerobic power varied markedly(-5%to+9%)following 100 mg/day of elemental iron over 42-56 days,or 100 mg of elemental iron bi-daily over 8-10 days.The quality of studies was moderate(77%),ranging from low(57%)to high(100%).Moststudies(n=18)contained group sizes-20 athletes,thus limiting the likelihood of detecting significant effects(statistical power>0.80).Conclusion:High-level ID female athletes experience a negative impact on endurance performance,which can be improved by supplementing with»100 mg of elemental iron per day or bi-daily.The decrements in other performance parameters characterizing a range of sports coincide with the severity of iron deficiency.
基金Supported by Natural Science Foundation of Guangdong Province,No.2021A1515011146 and No.2023A1515010785Key Areas Research and Development Programs of Guangdong Province,No.2023B1111050009.
文摘BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-stable(MSS)CRC patients is considerably restricted.This study sought to evaluate the effectiveness of immu-notherapy in MSS patients characterized by homologous recombination defi-ciency(HRD)as opposed to those with homologous recombination proficiency(HRP).AIM To investigate and compare the clinicopathological characteristics,treatment modalities,and outcomes between the HRD and HRP groups in CRC.METHODS Next-generation sequencing was performed on 268 CRC patients to identify tumor-associated genetic alterations and assess their HRD scores and MSI status.Patients with HRD-related gene alterations or an HRD score≥30 were classified into the HRD group,while the remaining patients were assigned to the HRP group.Clinical data,including staging and treatment regimens,were collected for analysis.Cox regression and Kaplan-Meier survival curves were employed to evaluate whether the HRD group demonstrated improved survival outcomes following immunotherapy treatment.RESULTS Among the 268 patients,64 were classified into the HRD group,which had a higher proportion of early-stage CRC diagnoses compared to the HRP group.Kaplan-Meier survival curves indicated significantly better survival rates in the HRD group compared to the HRP group across all cohorts,as well as among MSS patients treated with immunotherapy(P<0.05).CONCLUSION This study demonstrates that CRC patients with HRD have a more favorable prognosis and suggests that HRD status could serve as a predictive marker for immunotherapy response in MSS patients.
基金supported by the National Natural Science Foundation of China(32002122,32372805)。
文摘Brassica napus(oilseed rape)is sensitive to boron(B)deficiency and exhibits young leaf curling in response to low-B stress at the seedling stage,which leads to reduced photosynthesis and plant growth.So far,no gene has been identified to be involved in B deficiency induced leaf curling.Our previous results showed the transcription factor BnaA1.WRKY53 might be involved in B-deficiency tolerance.However,altered BnaA1.WRKY53 expression does not influence B concentration in shoot,root and leaf cell walls,which suggests Bna A1.WRKY53 might be involved in other biological processes.Indeed,phenotypic and anatomical analyses revealed that BnaA1.WRKY53 negatively regulated the leaf curling induced by leaf epinasty by suppressing the overexpansion of palisade cells under B deficiency.Further transcriptome enrichment analysis of differentially expressed genes(DEGs)between wild-type and BnaA1.WRKY53overexpression line showed auxin response pathway was enriched.In addition,Arabidopsis DR5::GFP auxin reporter line showed B deficiency caused predominant auxin signal accumulation in the adaxial side and concomitant adaxial cell expansion,which indicated that B deficiency may induce leaf curling by altering auxin distribution.Phytohormone quantification and gene expression analysis demonstrated that BnaA1.WRKY53 prevent auxin overaccumulation in leaves by suppressing auxin biosynthetic genes under B deficiency.Furthermore,exogenous 1-naphthlcetic acid(NAA)treatment experiments revealed that high auxin could induce leaf curling and BnaA1.WRKY53 expression.Overall,these findings demonstrate that auxin and the transcription factor BnaA1.WRKY53 synergistically regulate leaf curling to maintain an optimal leaf area under B deficiency,and provide novel insights into the resistance mechanisms against B-deficiency-induced leaf curling in oilseed rape.
基金Brazilian National Program of Genomics and Precision Health-Genomas Brasil,Grant/Award Number:MS-SECTICS-Decit/CNPq 16/2023São Paulo Research Foundation,Grant/Award Number:FAPESP-2021/07957-5+5 种基金Barretos Cancer Hospital,Grant/Award Number:13/2021National Oncology Care Support Program (PRONON),CNPq,Grant/Award Number:444217/2023-1Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer)Brazilian Ministry of Health (MoH)National Council for Scientific and Technological DevelopmentCNPq Productivity
文摘Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.
文摘AIM:To compare the Ishihara test errors scores of colour vision deficiency(CVD)subjects when wearing four different types of red-tinted contact lenses(RCL)that differ in their transmittance as determined using a spectrophotometer.METHODS:Six congenital CVD subjects volunteered to participate in this study.Ishihara plates were used to determine the colour vision errors made,whereas Farnsworth-Munsell 100 Hue test was conducted to determine the total error scores(TES)and type of CVD.Four types of RCL(Types A,B,C and D)were inserted in the non-dominant eye and tested in a randomised manner by a masked operator.Errors scores in Ishihara test were determined at baseline without any contact lens and after wearing the four different RCL.The subjects were then divided into two groups based on the mean TES.RESULTS:Repeated measures ANOVA with Greenhouse-Geisser corrections showed that there was a highly significant effect of RCL type on Ishihara error score[F(2.056,10.282)=30.214,P<0.001].Error scores with RCL Type B were significantly lower than errors made when no lens was worn,and with RCL Type C and Type D(all P<0.001).Error scores with RCL Type B were also lower than those made with RCL Type A,however,they were not significantly different.For subjects with TES values less than 180,RCL type B showed the largest improvement in Ishihara error score(50%)compared to the other three RCLs.RCL type A showed the best performance in TES value of more than 180,with an improvement of 80%in Ishihara score.RCL Type A has the lowest transmittance at the confusion wavelength(450-568 nm),followed by RCL Types B,D and C.CONCLUSION:This study shows that RCL can improve Ishihara error scores.RCL with lower transmission at 450-568 nm and 90%transmittance beyond 637 nm are the most effective.Lenses which could block more light between 550-580 nm are more effective for colour defectives with more severe colour defects.
基金Supported by the Natural Science Foundation of the Heilongjiang Province of China(C2016003)China Postdoctoral Science Foundation(2015M581415)Heilongjiang Postdoctoral Fund(LBH-Z15005)。
文摘The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se deficiency accusers more frequently in low-Se regions.Therefore,to investigate the Se status and inflammatory response of the mammary gland under marginal dietary Se levels,an lipopolysaccharide(LPS)induced mouse mastitis model was established.Mice were fed with moderate Se diet(0.087 mg•kg^(-1) Se),adequate Se diet(0.15 mg•kg^(-1) Se)or excessive Se diet(1.5 mg•kg^(-1) Se)for 60 days.Se status and inflammatory factors were investigated.Results showed that the Se status of mammary gland correlated with dietary Se levels.Marginal Se deficiency exacerbated mammary tissue histopathology;increased the mRNA level of inflammatory genes tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and cyclooxygenase-2(COX-2);and enhanced the phosphorylation of NF-κB p65 in mammary gland tissues.Supplementation of Se in diet higher than recommended levels reduced the inflammatory reaction of mammary glands in LPS-induced mastitis model and provided a protective effect.
文摘Objective:To investigate whether differences exist in DNA fragmentation levels and protamine deficiency in the sperm of obese men compared to those of overweight and proven fertile,normal weight men and evaluate the alterations related to reproductive hormones,semen parameters and their association with body mass index(BMI).Methods:Participants in this observational study were divided into three groups based on their BMI:proven fertile,normal weight men(n=200);overweight men(n=200);and obese men(n=200).After 3 days of abstinence,seminal fluid was collected from all participants and analyzed.Blood samples were also collected on the same day for hormonal analysis.Sperm DNA fragmentation and protamine deficiency were also assessed.Results:A total of 600 men with a mean age of(34.3±7.9)2 years were included in the study.Obese males(BMI 30 kg/m or higher)exhibited significant reductions in semen volume,sperm concentration,total sperm motility percentage,progressive motility,non-progressive motility,and levels of total testosterone,follicle-stimulating hormone(FSH)and luteinizing hormone(LH)compared to overweight(BMI 25 to 29.9 kg/m2)and normal weight males(BMI 18.5 to 24.9 kg/m2)(P<0.001).Conversely,obese males showed a significant increase in prolactin level,sperm DNA fragmentation,and protamine deficiency compared to overweight and normal weight males(P<0.001).Significant negative correlations were demonstrated between BMI and sperm concentration,motility,total testosterone,FSH and LH(P<0.001),whereas prolactin,sperm DNA fragmentation and protamine deficiency were positively correlated with BMI(P<0.001).Conclusions:This study provides clear evidence that obesity contributes potentially to male infertility by inducing sperm DNA fragmentation and protamine deficiency,as well as negatively impacting reproductive hormones and semen quality.
文摘BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.
