CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Althou...CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.展开更多
Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usu...Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usually involves complex procedures and extremely depends on unidirectional freezing technique.Herein,we propose a groundbreaking approach that leverages the assemblies of salting-out protein induced by ammonium metatungstate(AM)as the precursor,and then acquire directional three-dimensional carbon-based foams through simple pyrolysis.The electrostatic interaction between AM and protein ensures well dispersion of WC_(1−x)nanoparticles on carbon frameworks.The content of WC_(1−x)nanoparticles can be rationally regulated by AM dosage,and it also affects the electromagnetic(EM)properties of final carbon-based foams.The optimized foam exhibits exceptional EM absorption performance,achieving a remarkable minimum reflection loss of−72.0 dB and an effective absorption bandwidth of 6.3 GHz when EM wave propagates parallel to the directional pores.Such performance benefits from the synergistic effects of macroporous architecture and compositional design.Although there is a directional dependence of EM absorption,radar stealth simulation demonstrates that these foams can still promise considerable reduction in radar cross section with the change of incident angle.Moreover,COMSOL simulation further identifies their good performance in preventing EM interference among different electronic components.展开更多
Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One ...Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One thousand nine hundred and twenty Ross 308 male broilers were housed in 64 pens in 4 climate-controlled rooms,2 under cyclical HS(d 28–43;32±2℃;60%–70%RH;09:30–15:30)and 2 under thermoneutral(TN)conditions.In the finisher phase,broilers were allocated to 4 dietary treatments,analyzed values are given except for metabolizable energy(ME):low crude protein(CP)and control fat(LowCP-ConF;17.0%CP,5.9%crude fat(CF),2,925 kcal/kg ME),low CP and high fat(LowCP-HighF;17.2%CP,7.9%CF,3,019 kcal/kg ME),control CP and high fat(ConCP-HighF;18.1%CP,8.0%CF,2,992 kcal/kg ME)and a basal control(ConCP-ConF;18.7%CP,6.3%CF,2,913 kcal/kg ME).LowCP diets contained control levels of digestible amino acids.Results During the finisher phase,compared to control CP levels,LowCP increased average daily feed intake(ADFI)(+2.15%;P=0.020)and affected average daily gain(ADG)and feed conversion ratio(FCR)negatively under TN(-3.77%and+6.49%;P=0.003 and P<0.001,respectively),but not during HS.Compared to control CF,HighF decreased ADFI during TN and HS(-3.16%and-3.17%;P<0.001 and P=0.022)and reduced ADG in TN groups(-3.17%;P=0.010),but not during HS.Mortality was higher in broilers receiving HighF during HS(P=0.040).Slaughter weights were unaffected.LowCP decreased plasma uric acid and lactate dehydrogenase levels during TN,but increased plasma glucose during HS.LowCP increased breast meat redness(a*)during TN and HS(P<0.05).HighF decreased fat(-1.68%;P=0.017),but increased protein levels(+1.53%;P<0.001)in breast meat of HS-broilers.Conclusion LowCP and HighF impaired performance under TN but not under HS.HighF increased mortality under HS,yet improved breast meat composition.These findings highlight the challenge of designing an optimal diet for both conditions and underscore the need to better understand amino acid needs and energy-to-protein ratios during HS.展开更多
Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein ...Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.展开更多
BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often dif...BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A(MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of Mx A to distinguish viral from bacterial infections.METHODS: We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic(ROC) curve analysis were used to determine the diagnostic value of Mx A, either alone or in combination with C-reactive protein(CRP) or procalcitonin(PCT), in patients with viral, bacterial, or co-infections.RESULTS: The value of MxA(ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections(82.3 [24.5–182.9] vs. 16.4 [10.8–26.5], P<0.0001)(82.3 [24.5–182.9] vs. 28.5 [10.2–106.8], P=0.0237). The area under the curve(AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799(95% confidence interval [95% CI] 0.696–0.903), with a sensitivity of 68.9%(95% CI 54.3%–80.5%) and specificity of 90.0%(95% CI 74.4%–96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus(15.8 [9.6–47.6] ng/mL) and Epstein-Barr virus(12.9 [8.5–21.0] ng/mL) infections.CONCLUSION: Our study showed the diagnostic efficacy of Mx A in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, EpsteinBarr virus and human cytomegalovirus infections did not elicit elevated Mx A expression.展开更多
BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rec...BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rectal cancer progression.METHODS CENPA protein expression in rectal cancer tissues and cell lines were detected.CENPA was overexpressed and knocked down in SW837 and SW480 cells,and proliferation,invasion,apoptosis and epithelial-mesenchymal transition(EMT)marker protein levels were examined.O6-methylguanine DNA methyltransferase(MGMT)promoter methylation was assessed with methylation-specific poly-merase chain reaction.Co-immunoprecipitation assay verified the interaction between MGMT and protein tyrosine phosphatase nonreceptor type 4(PTPN4).SW837 cells with CENPA knockdown were injected subcutaneously into mice,and tumor growth was examined.RESULTS CENPA was upregulated in rectal cancer tissues and cell lines.CENPA overex-pression promoted proliferation,invasion and EMT,and inhibited apoptosis in rectal cancer cells.Whereas CENPA knockdown showed the opposite results.Moreover,CENPA inhibited MGMT expression by promoting DNA methyltrans-ferase 1-mediated MGMT promoter methylation.MGMT knockdown abolished the CENPA knockdown-mediated inhibition of rectal cancer cell progression.MGMT increased PTPN4 protein stability by inhibiting PTPN4 ubiquitination degradation via competing with ubiquitin-conjugating enzyme E2O for interacting with PTPN4.PTPN4 knockdown abolished the inhibitory effects of MGMT overexpression on rectal cancer cell progression.Moreover,CENPA knockdown inhibited xenograft tumor growth in vivo.CONCLUSION CENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.展开更多
BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the rol...BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.展开更多
BACKGROUND Upper gastrointestinal hemorrhage is a life-threatening manifestation of cow’s milk protein allergy(CMPA).We analyze the clinical characteristics of a case of milk protein allergy manifested as severe uppe...BACKGROUND Upper gastrointestinal hemorrhage is a life-threatening manifestation of cow’s milk protein allergy(CMPA).We analyze the clinical characteristics of a case of milk protein allergy manifested as severe upper gastrointestinal hemorrhage.CASE SUMMARY The hospital admitted a 2-month-old male infant due to“melena for 6 days,he-matemesis twice”.The main symptom was melena,initially occurring once or twice per day,then gradually increasing to five or six times per day at their peak.During the course of the illness,the infant vomited blood,but there were no re-ports of vomiting,fever,pale complexion,dyspnea,wheezing,or difficulty brea-thing.Laboratory tests showed hemoglobin level of 87 g/L,platelet count of 349×109/L,and eosinophil percentage of 0.031.Coagulation studies were normal.After avoiding certain foods and feeding with an amino acid formula for 2 weeks,a repeat gastroscopy revealed less bleeding.After six weeks,a positive oral food challenge test confirmed a severe CMPA.At the 4-month follow-up,there was no gastrointestinal bleeding,and the infant was growing and developing well.CONCLUSION The manifestations of milk protein allergy are diverse and nonspecific,with gas-trointestinal bleeding being less common,especially in infants.When infants present with unexplained massive hematemesis,it’s critical to investigate the possibility of CMPA.展开更多
Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitor...Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitors have emerged as a key strategy in cancer treatment.However,anti-programmed cell death 1/programmed death ligand 1 therapies,one of the main immunotherapeutic approaches,only elicit a response in only approximately 20%of advanced HCC.This suggests that there may be other immune checkpoints playing important roles in HCC immunotherapy.Recent studies have highlighted Signal regulatory protein alpha(SIRPα)is a phagocytic checkpoint in macrophages and other immune cells,as a promising novel therapeutic target in tumor immunotherapy.This review summarizes current progress on SIRPαin HCC and identifies key challenges for future related research.展开更多
BACKGROUND Pancreatic cancer tissues mainly consist of fibrotic and dense stroma,which limits their therapeutic efficacy.The stromal fibroblasts of pancreatic tumors frequently express the secreted protein acidic and ...BACKGROUND Pancreatic cancer tissues mainly consist of fibrotic and dense stroma,which limits their therapeutic efficacy.The stromal fibroblasts of pancreatic tumors frequently express the secreted protein acidic and rich in cysteine(SPARC).AIM To assess the impact of SPARC and its oncological relevance in patients undergoing pancreatic cancer resection.METHODS Ninety-one pancreatic ductal adenocarcinoma specimens were obtained from patients with curative resection between January 2009 and December 2015 as a retrospective study.SPARC expression patterns were analyzed using immunohistochemistry.Oncological outcomes were analyzed based on SPARC expression patterns.Oncological outcomes,based on SPARC expression,were analyzed in The Cancer Genome Atlas-Pancreatic Adenocarcinoma cohort(retrieved from a public database).RESULTS Patients with stromal SPARC expression(sSPARC+)had poorer overall survival than that in those without it(sSPARC-)(P=0.035).However,among patients who received adjuvant treatment,no difference was observed in survival between the sSPARC+and the sSPARC-groups(P=0.14).In The Cancer Genome Atlas-Pancreatic Adenocarcinoma samples,the high SPARC expression group exhibited noticeably lower overall survival than that in the low expression group(cutoff:14.1295,P=0.0222).Furthermore,SPARC expression was strongly correlated with the percentage the CD10+stromal component(R2=0.804,P<0.001).CONCLUSION Adjuvant chemotherapy improves survivals in sSPARC+pancreatic cancer patients,indicating suggesting sSPARC expression as a prognostic biomarker and potential indicator for neoadjuvant treatment planning.展开更多
Cow milk protein allergy(CMPA)is a prevalent food allergy in infancy.It often presents with symptoms that overlap with other conditions,such as gastroeso-phageal reflux disease,lactose intolerance,food protein-induced...Cow milk protein allergy(CMPA)is a prevalent food allergy in infancy.It often presents with symptoms that overlap with other conditions,such as gastroeso-phageal reflux disease,lactose intolerance,food protein-induced enterocolitis syndrome,and eosinophilic esophagitis.This diagnostic overlap makes distin-guishing CMPA from its mimics difficult,resulting in potential misdiagnoses and unnecessary dietary restrictions.This review aims to comprehensively analyze CMPA and its mimicking conditions,highlighting their clinical presentations,diagnostic approaches,and management strategies to enhance diagnostic accu-racy and optimize patient care.A systematic literature search was conducted using PubMed,Scopus,Web of Science,and Google Scholar,focusing on studies published within the last 20 years.Articles addressing CMPA and its mimicking conditions were selected,with data synthesized into comparative analyses of diagnostic methods and management strategies.Accurate differentiation between CMPA and its mimics requires a thorough clinical evaluation supported by diagnostic tests such as skin prick tests,serum-specific IgE,and oral food challenges.Misdiagnosis can lead to nutritional deficiencies,psychological stress,and increased healthcare costs.Emerging diagnostic technologies,including component-resolved diagnostics and cytokine profiling,offer promising avenues for improving accuracy.A multidisciplinary approach involving pediatricians,allergists,and dietitians is essential for precise diagnosis and effective management.Ongoing research and education are crucial to enhancing clinical outcomes and reducing the burden on families.展开更多
Arsenic-related oxidative stress and resultant diseases have attracted global concern,while longitudinal studies are scarce.To assess the relationship between arsenic exposure and systemic oxidative damage,we performe...Arsenic-related oxidative stress and resultant diseases have attracted global concern,while longitudinal studies are scarce.To assess the relationship between arsenic exposure and systemic oxidative damage,we performed two repeatedmeasures among 5236 observations(4067 participants)in theWuhan-Zhuhai cohort at the baseline and follow-up after 3 years.Urinary total arsenic,biomarkers of DNA oxidative damage(8-hydroxy-2-deoxyguanosine(8-OHdG)),lipid peroxidation(8-isoprostaglandin F2alpha(8-isoPGF2α)),and protein oxidative damage(protein carbonyls(PCO))were detected for all observations.Here we used linearmixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage.Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions.After adjusting for potential confounders,arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners.In cross-sectional analyses,each 1%increase in arsenic levelwas associated with a 0.406%(95%confidence interval(CI):0.379%to 0.433%),0.360%(0.301%to 0.420%),and 0.079%(0.055%to 0.103%)increase in 8-isoPGF2α,8-OHdG,and PCO,respectively.More importantly,arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α(β:0.147;95%CI:0.130 to 0.164),8-OHdG(0.155;0.118 to 0.192),and PCO(0.050;0.035 to 0.064)in the longitudinal analyses.Our study suggested that arsenic exposurewas not only positively related with global oxidative damage to lipid,DNA,and protein in cross-sectional analyses,but also associated with annual increased rates of these biomarkers in dose-dependent manners.展开更多
Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods...Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10- min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions. Results Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region （P 〈 0.01 vs 10-min ischemia group）. Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates（P〈0.01 vs 10-min ischemia group）.Conelusion Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.展开更多
Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and p...Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and peripheral neuropathy.This review aims to overview the roles of high sensitivity C-reactive protein(hs-CRP),C-reactive protein(CRP),CRP-to-lymphocyte count ratio(CLR),and the CRP-to-albumin ratio(CAR)as biomarkers for assessing systemic inflammation and predicting the development and severity of diabetic chronic microvascular complications.Elevated levels of CRP and hs-CRP have been consistently associated with increased risk of these complications,reflecting ongoing inflammatory processes that contribute to endothelial dysfunction and tissue damage.Furthermore,CAR and CLR,which combine CRP with albumin and lymphocyte counts respectively,offer a more nuanced understanding of the inflammatory and immune response in T2DM patients.While individual studies have demonstrated the clinical relevance of these biomarkers in predicting disease onset and progression,further investigation is needed to establish their utility in clinical practice.This review highlights the potential of these biomarkers for enhancing early detection,risk stratification,and personalized management of diabetic patients,ultimately aiming to improve outcomes and reduce the burden of diabetic chronic microvascular complications.展开更多
Sesame(Sesamum indicum L.)is an ancient diploid oilseed crop valued for its high oil content,quality protein,unsaturated fatty acids,and antioxidants.The emerging research focuses on the utilization of vegetable prote...Sesame(Sesamum indicum L.)is an ancient diploid oilseed crop valued for its high oil content,quality protein,unsaturated fatty acids,and antioxidants.The emerging research focuses on the utilization of vegetable proteins in the development of novel products and the formulation of functional foods.Developing sesame genotypes with higher protein and oil content is a current focus for improving sesame quality traits,as preferred by the sesame seed oil industry and consumers.Despite previous genome-wide association studies(GWAS)on various agronomic and biochemical traits in sesame,the genetic basis of protein content and oil content remains limited.Therefore,this study was designed to identify candidate genes and quantitative trait loci(QTLs)regulating the target traits using 401 sesame accessions grown in three environments(2018WH,2018LQ,and 2022WH).The protein and oil content in the sesame population varied significantly.The protein content ranged from 15.06%to 26.45%,while the oil content was between 41.68%and 60.15%.Furthermore,the white seeds had a higher oil content,while the black seeds had a higher protein content,indicating an association between seed colour and oil and protein content.GWAS results revealed that 632 and 269 QTLs were selected as significant genetic regions for protein and oil content,respectively.Of these significant QTLs,we identified 10 and 22 stable QTLs for protein and oil content,respectively.A total of 17 candidate genes related to protein and oil content were identified within 32 stable quantitative trait loci(QTLs).Interestingly,two variant sites,SNP13:10093594 and In Del13:10935497,related to protein content,were identified in the gene sequences of SINPZ1300586 and SINPZ1300694.Four SNPs,SNP1:22608987,SNP4:13355820,SNP8:21686488,and SNP11:142842,for oil content were found correspond to the genes SINPZ0102106,SINPZ0401222,SINPZ0801731,and SINPZ1100015,respectively.The findings provide light on the genetic basis of protein and oil characteristics.These genes and QTLs can aid the molecular breeding and genetic engineering of innovative sesame germplasm,with improved potential for protein and oil content,as well as desired quality attributes.展开更多
Background With the global expansion of aquaculture and the increasing demand for fish meal,identifying appropriate and sustainable alternative protein sources for aquafeeds has become essential.Single-cell protein(SC...Background With the global expansion of aquaculture and the increasing demand for fish meal,identifying appropriate and sustainable alternative protein sources for aquafeeds has become essential.Single-cell protein(SCP),derived from methanotrophic bacteria,presents a promising alternative by converting methane into protein,potentially addressing both the need for alternative protein sources and reducing industrial greenhouse gas emissions.This study aimed to evaluate the effects of different levels of SCP inclusion(0%,25%,50%,and 75%fish meal replacement)on the health,gene expression,and gut microbiome of yellowtail kingfish(YTK,Seriola lalandi)following a 35-day growth trial.Results The study found that SCP inclusion at the highest level of fishmeal replacement(75%)induced a mild inflammatory response in the hindgut of the fish.However,micromorphological assessments of the hindgut,serum biochemistry,and gene expression analyses revealed no significant detrimental effects from SCP replacement.Notably,there were indications of improved lipid digestibility with SCP.Furthermore,SCP inclusion significantly enhanced microbial richness and altered the composition of the gut microbiome,introducing beneficial bacterial taxa that may contribute to improved gut health and resilience.Conclusions This study highlights SCP as a viable and sustainable alternative to fish meal in YTK diets.The findings suggest that SCP can be included in YTK diets without adverse health effects at moderate levels and may even offer benefits in terms of lipid digestibility and gut microbiome diversity.These results contribute to the advancement of more sustainable aquaculture practices.展开更多
Background Transgenic research in crops involves using genetic engineering techniques to introduce specific genes of interest from other organisms,or even entirely new genes into plant genomes to create crops with des...Background Transgenic research in crops involves using genetic engineering techniques to introduce specific genes of interest from other organisms,or even entirely new genes into plant genomes to create crops with desirable traits that wouldn’t be possible through conventional breeding methods.Transgenic crops have been developed for various traits globally.Whitefly,Bemisia tabaci(Gennadius)is one of the major sucking pests of cotton that cause significant damage to the cotton production.To combat whitefly infestations,researchers have developed four transgenic cotton lines expressing the fern protein.And those transgenic lines need to be evaluated for their performance against the target pest—whitefly.The evaluation was designed as controlled trials in polyhouse or muslin cloth cages under open-choice and no-choice conditions by comparing four transgenic cotton lines(A,B,C,and D)with three control groups,including untransformed cotton plants with a same genetic background of the transgenic line,conventionally bred whitefly-resistant cotton,and whitefly-susceptible cotton.In order to study the generational effect,the evaluation also involved studies on whitefly development in laboratory,muslin cloth cage,and polyhouse conditions.Results Both open-choice and no-choice experiments had shown that all the four transgenic cotton lines(A,B,C,and D)expressing the fern protein reduced adult whitefly numbers significantly compared with the control lines,except for the no-choice conditions in 2021,where the transgenic line C was non-significant different from the resistant control line.Notably,the nymphal population on the resistant control line was relatively low and nonsignificant different from the transgenic line C in 2021;and the transgenic lines A and C in 2022 under open-choice conditions.Under no-choice condition,the nymphal counts in the resistant control line was non-significant different from transgenic lines C and D in 2021;and transgenic line D in 2022.All transgenic lines showed significant decrease in egg hatching in 2021 and nymphal development in 2022,except for the transgenic line C which had no significant different in the nymphal development comparing with non-transgenic control lines in 2022.Adult emergence rates in both years of evaluation showed significant decrease in transgenic lines A and B comparing with the control lines.Additionally,the results showed a significant reduction in cotton leaf curl disease and sooty mold development in all the four transgenic lines compared with susceptible control under open-choice conditions,indicating potential benefits of transgenic lines beyond direct effect on whitefly control.Furthermore,the research explored the generational effects of the fern protein on whitefly which revealed the lowest fecundity in the transgenic line C across F0,F1 and F3 generations,lower egg hatching in F1 and F2 generations in transgenic lines A and B,shorter nymphal duration in F1 and F2 generations in transgenic line B,and the least total adult emergence in the transgenic line C in F0 and F3 generations.Conclusions These findings suggest that the transgenic cotton lines expressing fern protein disrupts whitefly populations and the life cycle to a certain extent.However,results are not consistent over generations and years of study,indicating these transgenic lines were not superior over control lines and need to be improved in future breeding.展开更多
The aging of biomolecular condensates has been implicated in the pathogenesis of various neurodegenerative diseases,characterized by a transition from a physiologically liquid-like state to a pathologically ordered st...The aging of biomolecular condensates has been implicated in the pathogenesis of various neurodegenerative diseases,characterized by a transition from a physiologically liquid-like state to a pathologically ordered structure.However,the mechanisms governing the formation of these pathological aggregates remain poorly understood.To address this,the present study utilizes coarse-grained molecular dynamics simulations based on Langevin dynamics to explore the structural,dynamical,and material property changes of protein condensates during the aging process.Here,we further develop a nonequilibrium simulation algorithm that not only captures the characteristics of time-dependent amount of aging beads but also reflects the structural information of chain-like connections between aging beads.Our findings reveal that aging induces compaction of the condensates,accompanied by a decrease in diffusion rates and an increase in viscosity.Further analysis suggests that the heterogeneous diffusivity within the condensates may drive the aging process to initiate preferentially at the condensate surface.Our simulation results align with the experimental phenomena and provide a clear physical picture of the aging dynamics.展开更多
Objective:To investigate the potential of hydro-alcoholic extract of Gentiana lutea roots(GLE)in scopolamine-induced amnesia model in mice.Methods:The active chemical constituents were determined by GC-MS analysis.In ...Objective:To investigate the potential of hydro-alcoholic extract of Gentiana lutea roots(GLE)in scopolamine-induced amnesia model in mice.Methods:The active chemical constituents were determined by GC-MS analysis.In vitro antioxidant activity was performed by the DPPH free radical scavenging method.Ex vivo anti-acetylcholinesterase assay was conducted to investigate the effect on the cholinergic system.A scopolamine-induced memory impairment model was used.The levels of beta-amyloid(Aβ)and tau protein were measured.The behavioral studies were performed through Morris water maze and passive avoidance learning tests,followed by estimation of biochemical markers(GSH and MDA),immunohistochemistry,and histopathological studies on isolated brain tissues.Results:GLE exhibited DPPH free radical scavenging activity with an IC50 value of(76.68±2.28)μg/mL.GLE also manifested inhibitory effect on acetylcholinesterase[IC50(36.58±0.73)μg/mL]to upregulate the cholinergic system.GLE at 200 mg/kg and 400 mg/kg significantly restored the memory impairment induced by scopolamine.GLE at 200 mg/kg and 400 mg/kg significantly reduced brain oxidative stress(P<0.001).Immunohistochemistry investigation showed a significant reduction in Aβdeposition and p-tau protein expression in the GLE treatment groups(P<0.001).Administration of GLE effectively reduced scopolamine-induced neuronal damage in a dose-dependent manner.Conclusions:The study demonstrates that GLE ameliorates scopolamine-induced memory impairment by alleviating Aβ/p-tau protein accumulation and upregulation in the cholinergic system to improve cognitive dysfunction and behavioral problems.展开更多
Background In intensive aquaculture systems,the frequent incidence of enteritis reduces production efficiency and results in significant economic losses.Protein feeds account for 40%–60%of aquafeed expenses,and with ...Background In intensive aquaculture systems,the frequent incidence of enteritis reduces production efficiency and results in significant economic losses.Protein feeds account for 40%–60%of aquafeed expenses,and with the growth of intensive aquaculture,demand for fishmeal as a key protein source outstrips supply,driving up prices.This study investigated the therapeutic potential of reducing dietary protein levels by 3%and adding enzymatic cottonseed protein(ECP)in juvenile yellow catfish with dextran sulfate sodium(DSS)-induced enteritis.Methods A total of 1,260 healthy juvenile yellow catfish(Pelteobagrus fulvidraco),with an average body weight of 5.90±0.05 g,were randomly allocated into 7 experimental groups,each with 3 replicates.The fish were fed one of seven diets for 10 weeks:a normal-protein diet(42%;NP)and 6 low-protein diets(39%;LP)supplemented with graded levels of ECP at 0%(ECP0),1%(ECP1),2%(ECP2),3%(ECP3),4%(ECP4),and 5%(ECP5),respectively.Subsequently,48 fish from each group were selected to receive 1 mL of 6%DSS solution.Results Our findings demonstrated that:(1)The DSS+ECP0 group aggravated DSS-induced enteritis in juvenile yellow catfish compared to the DSS+NP group.(2)Dietary supplementation of ECP in LP diets significantly enhanced the enzymatic activity and levels of immunoreactive substances,including LZM,C3,C4,and ACP(P<0.05).Mechanistically,first,ECP supplementation modulated macrophage polarization by inhibiting the M1 phenotype while promoting the M2 phenotype,potentially through the JAK-STAT signaling pathway;second,dietary ECP suppressed the phosphorylation cascade of key necroptosis-related proteins,including RIP1,RIP3,and MLKL,potentially via the NF-κB and MAPK signaling pathways.(3)The DSS+ECP2 group demonstrated comparable or superior efficacy to the DSS+NP group in mitigating DSS-induced intestinal enteritis.Conclusions Our results demonstrated that ECP can alleviate DSS-induced enteritis by regulating macrophage polarization and reducing necroptosis.Furthermore,ECP supplementation effectively counteracted the exacerbation of enteritis caused by dietary protein reduction.These findings highlighted the effectiveness and feasibility of ECP in alleviating enteritis and saving protein.展开更多
基金supported by the director of Indian Council of Agricultural Research and International Rice Research Institute (ICAR-CRRI), Cuttack, Indiathe coordinator of the ICAR-sponsored project ‘C-reactive protein (CRP) in Biofortification in Selected Crops’, India
文摘CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.
基金financially supported by the National Natural Science Foundation of China(Nos.22475057 and No.52373262).
文摘Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usually involves complex procedures and extremely depends on unidirectional freezing technique.Herein,we propose a groundbreaking approach that leverages the assemblies of salting-out protein induced by ammonium metatungstate(AM)as the precursor,and then acquire directional three-dimensional carbon-based foams through simple pyrolysis.The electrostatic interaction between AM and protein ensures well dispersion of WC_(1−x)nanoparticles on carbon frameworks.The content of WC_(1−x)nanoparticles can be rationally regulated by AM dosage,and it also affects the electromagnetic(EM)properties of final carbon-based foams.The optimized foam exhibits exceptional EM absorption performance,achieving a remarkable minimum reflection loss of−72.0 dB and an effective absorption bandwidth of 6.3 GHz when EM wave propagates parallel to the directional pores.Such performance benefits from the synergistic effects of macroporous architecture and compositional design.Although there is a directional dependence of EM absorption,radar stealth simulation demonstrates that these foams can still promise considerable reduction in radar cross section with the change of incident angle.Moreover,COMSOL simulation further identifies their good performance in preventing EM interference among different electronic components.
基金funded by VLAIO(Flemish Innovation&Entrepreneurship),grant number HBC.2020.3165。
文摘Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One thousand nine hundred and twenty Ross 308 male broilers were housed in 64 pens in 4 climate-controlled rooms,2 under cyclical HS(d 28–43;32±2℃;60%–70%RH;09:30–15:30)and 2 under thermoneutral(TN)conditions.In the finisher phase,broilers were allocated to 4 dietary treatments,analyzed values are given except for metabolizable energy(ME):low crude protein(CP)and control fat(LowCP-ConF;17.0%CP,5.9%crude fat(CF),2,925 kcal/kg ME),low CP and high fat(LowCP-HighF;17.2%CP,7.9%CF,3,019 kcal/kg ME),control CP and high fat(ConCP-HighF;18.1%CP,8.0%CF,2,992 kcal/kg ME)and a basal control(ConCP-ConF;18.7%CP,6.3%CF,2,913 kcal/kg ME).LowCP diets contained control levels of digestible amino acids.Results During the finisher phase,compared to control CP levels,LowCP increased average daily feed intake(ADFI)(+2.15%;P=0.020)and affected average daily gain(ADG)and feed conversion ratio(FCR)negatively under TN(-3.77%and+6.49%;P=0.003 and P<0.001,respectively),but not during HS.Compared to control CF,HighF decreased ADFI during TN and HS(-3.16%and-3.17%;P<0.001 and P=0.022)and reduced ADG in TN groups(-3.17%;P=0.010),but not during HS.Mortality was higher in broilers receiving HighF during HS(P=0.040).Slaughter weights were unaffected.LowCP decreased plasma uric acid and lactate dehydrogenase levels during TN,but increased plasma glucose during HS.LowCP increased breast meat redness(a*)during TN and HS(P<0.05).HighF decreased fat(-1.68%;P=0.017),but increased protein levels(+1.53%;P<0.001)in breast meat of HS-broilers.Conclusion LowCP and HighF impaired performance under TN but not under HS.HighF increased mortality under HS,yet improved breast meat composition.These findings highlight the challenge of designing an optimal diet for both conditions and underscore the need to better understand amino acid needs and energy-to-protein ratios during HS.
基金supported by the National Natural Science Foundation of China,Nos.82001178(to LW),81901129(to LH),82001175(to FX)Shanghai Sailing Program,No.20YF1439200(to LW)+1 种基金the Natural Science Foundation of Shanghai,China,No.23ZR1450800(to LH)and the Fundamental Research Funds for the Central Universities,No.YG2023LC15(to ZX)。
文摘Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.
基金supported by the National Natural Science Foundation of China (82272196 and 82272220)。
文摘BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A(MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of Mx A to distinguish viral from bacterial infections.METHODS: We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic(ROC) curve analysis were used to determine the diagnostic value of Mx A, either alone or in combination with C-reactive protein(CRP) or procalcitonin(PCT), in patients with viral, bacterial, or co-infections.RESULTS: The value of MxA(ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections(82.3 [24.5–182.9] vs. 16.4 [10.8–26.5], P<0.0001)(82.3 [24.5–182.9] vs. 28.5 [10.2–106.8], P=0.0237). The area under the curve(AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799(95% confidence interval [95% CI] 0.696–0.903), with a sensitivity of 68.9%(95% CI 54.3%–80.5%) and specificity of 90.0%(95% CI 74.4%–96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus(15.8 [9.6–47.6] ng/mL) and Epstein-Barr virus(12.9 [8.5–21.0] ng/mL) infections.CONCLUSION: Our study showed the diagnostic efficacy of Mx A in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, EpsteinBarr virus and human cytomegalovirus infections did not elicit elevated Mx A expression.
基金This study was reviewed and approved by the Ethic Committee of Medical College of Henan Vocational University of Science and Technology(Approval No.HVUYL414101416920231017001)all participants signed a written informed consent.
文摘BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rectal cancer progression.METHODS CENPA protein expression in rectal cancer tissues and cell lines were detected.CENPA was overexpressed and knocked down in SW837 and SW480 cells,and proliferation,invasion,apoptosis and epithelial-mesenchymal transition(EMT)marker protein levels were examined.O6-methylguanine DNA methyltransferase(MGMT)promoter methylation was assessed with methylation-specific poly-merase chain reaction.Co-immunoprecipitation assay verified the interaction between MGMT and protein tyrosine phosphatase nonreceptor type 4(PTPN4).SW837 cells with CENPA knockdown were injected subcutaneously into mice,and tumor growth was examined.RESULTS CENPA was upregulated in rectal cancer tissues and cell lines.CENPA overex-pression promoted proliferation,invasion and EMT,and inhibited apoptosis in rectal cancer cells.Whereas CENPA knockdown showed the opposite results.Moreover,CENPA inhibited MGMT expression by promoting DNA methyltrans-ferase 1-mediated MGMT promoter methylation.MGMT knockdown abolished the CENPA knockdown-mediated inhibition of rectal cancer cell progression.MGMT increased PTPN4 protein stability by inhibiting PTPN4 ubiquitination degradation via competing with ubiquitin-conjugating enzyme E2O for interacting with PTPN4.PTPN4 knockdown abolished the inhibitory effects of MGMT overexpression on rectal cancer cell progression.Moreover,CENPA knockdown inhibited xenograft tumor growth in vivo.CONCLUSION CENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.
基金Supported by the National Research Foundation of Korea Grant Funded by the Korea Government,No.RS-2024-00440477the Korea Institute of Science and Technology Institutional Program,No.2E33111-24-042.
文摘BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.
基金Supported by the Excellent Medical Talents Training Program of the First Affiliated Hospital of Guangxi Medical University,Difficult and Critical illness Center,Pediatric Clinical Medical Research Center of Guangxi,No.Gui Ke AD22035219the Key Laboratory of Children’s Disease Research in Guangxi’s Colleges and Universities,Education Department of Guangxi Zhuang Autonomous Region.
文摘BACKGROUND Upper gastrointestinal hemorrhage is a life-threatening manifestation of cow’s milk protein allergy(CMPA).We analyze the clinical characteristics of a case of milk protein allergy manifested as severe upper gastrointestinal hemorrhage.CASE SUMMARY The hospital admitted a 2-month-old male infant due to“melena for 6 days,he-matemesis twice”.The main symptom was melena,initially occurring once or twice per day,then gradually increasing to five or six times per day at their peak.During the course of the illness,the infant vomited blood,but there were no re-ports of vomiting,fever,pale complexion,dyspnea,wheezing,or difficulty brea-thing.Laboratory tests showed hemoglobin level of 87 g/L,platelet count of 349×109/L,and eosinophil percentage of 0.031.Coagulation studies were normal.After avoiding certain foods and feeding with an amino acid formula for 2 weeks,a repeat gastroscopy revealed less bleeding.After six weeks,a positive oral food challenge test confirmed a severe CMPA.At the 4-month follow-up,there was no gastrointestinal bleeding,and the infant was growing and developing well.CONCLUSION The manifestations of milk protein allergy are diverse and nonspecific,with gas-trointestinal bleeding being less common,especially in infants.When infants present with unexplained massive hematemesis,it’s critical to investigate the possibility of CMPA.
基金Supported by the National Key Sci-Tech Special Project of China,No.2018ZX10302207the Beijing Natural Science Foundation,No.7222191+3 种基金the Beijing Natural Science Foundation,No.7244426the Fundamental Research Funds for the Central Universities,Peking University,No.PKU2024XGK005the Peking University Medicine Seed Fund for Interdisciplinary Research,No.BMU2021MX007 and No.BMU2022MX001Fundamental Research Funds for the Central Universities,Peking University People’s Hospital Scientific Research Development Funds,No.RDY2020-06 and No.RDJ2022-14.
文摘Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitors have emerged as a key strategy in cancer treatment.However,anti-programmed cell death 1/programmed death ligand 1 therapies,one of the main immunotherapeutic approaches,only elicit a response in only approximately 20%of advanced HCC.This suggests that there may be other immune checkpoints playing important roles in HCC immunotherapy.Recent studies have highlighted Signal regulatory protein alpha(SIRPα)is a phagocytic checkpoint in macrophages and other immune cells,as a promising novel therapeutic target in tumor immunotherapy.This review summarizes current progress on SIRPαin HCC and identifies key challenges for future related research.
基金Supported by Faculty Research Grant from Yonsei University College of Medicine,No.6-2017-0155.
文摘BACKGROUND Pancreatic cancer tissues mainly consist of fibrotic and dense stroma,which limits their therapeutic efficacy.The stromal fibroblasts of pancreatic tumors frequently express the secreted protein acidic and rich in cysteine(SPARC).AIM To assess the impact of SPARC and its oncological relevance in patients undergoing pancreatic cancer resection.METHODS Ninety-one pancreatic ductal adenocarcinoma specimens were obtained from patients with curative resection between January 2009 and December 2015 as a retrospective study.SPARC expression patterns were analyzed using immunohistochemistry.Oncological outcomes were analyzed based on SPARC expression patterns.Oncological outcomes,based on SPARC expression,were analyzed in The Cancer Genome Atlas-Pancreatic Adenocarcinoma cohort(retrieved from a public database).RESULTS Patients with stromal SPARC expression(sSPARC+)had poorer overall survival than that in those without it(sSPARC-)(P=0.035).However,among patients who received adjuvant treatment,no difference was observed in survival between the sSPARC+and the sSPARC-groups(P=0.14).In The Cancer Genome Atlas-Pancreatic Adenocarcinoma samples,the high SPARC expression group exhibited noticeably lower overall survival than that in the low expression group(cutoff:14.1295,P=0.0222).Furthermore,SPARC expression was strongly correlated with the percentage the CD10+stromal component(R2=0.804,P<0.001).CONCLUSION Adjuvant chemotherapy improves survivals in sSPARC+pancreatic cancer patients,indicating suggesting sSPARC expression as a prognostic biomarker and potential indicator for neoadjuvant treatment planning.
文摘Cow milk protein allergy(CMPA)is a prevalent food allergy in infancy.It often presents with symptoms that overlap with other conditions,such as gastroeso-phageal reflux disease,lactose intolerance,food protein-induced enterocolitis syndrome,and eosinophilic esophagitis.This diagnostic overlap makes distin-guishing CMPA from its mimics difficult,resulting in potential misdiagnoses and unnecessary dietary restrictions.This review aims to comprehensively analyze CMPA and its mimicking conditions,highlighting their clinical presentations,diagnostic approaches,and management strategies to enhance diagnostic accu-racy and optimize patient care.A systematic literature search was conducted using PubMed,Scopus,Web of Science,and Google Scholar,focusing on studies published within the last 20 years.Articles addressing CMPA and its mimicking conditions were selected,with data synthesized into comparative analyses of diagnostic methods and management strategies.Accurate differentiation between CMPA and its mimics requires a thorough clinical evaluation supported by diagnostic tests such as skin prick tests,serum-specific IgE,and oral food challenges.Misdiagnosis can lead to nutritional deficiencies,psychological stress,and increased healthcare costs.Emerging diagnostic technologies,including component-resolved diagnostics and cytokine profiling,offer promising avenues for improving accuracy.A multidisciplinary approach involving pediatricians,allergists,and dietitians is essential for precise diagnosis and effective management.Ongoing research and education are crucial to enhancing clinical outcomes and reducing the burden on families.
基金supported by the National Natural Science Foundation of China(Nos.82241088 and 82203996)the China Postdoctoral Science Foundation(Nos.2022T150230 and 2021M691131).
文摘Arsenic-related oxidative stress and resultant diseases have attracted global concern,while longitudinal studies are scarce.To assess the relationship between arsenic exposure and systemic oxidative damage,we performed two repeatedmeasures among 5236 observations(4067 participants)in theWuhan-Zhuhai cohort at the baseline and follow-up after 3 years.Urinary total arsenic,biomarkers of DNA oxidative damage(8-hydroxy-2-deoxyguanosine(8-OHdG)),lipid peroxidation(8-isoprostaglandin F2alpha(8-isoPGF2α)),and protein oxidative damage(protein carbonyls(PCO))were detected for all observations.Here we used linearmixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage.Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions.After adjusting for potential confounders,arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners.In cross-sectional analyses,each 1%increase in arsenic levelwas associated with a 0.406%(95%confidence interval(CI):0.379%to 0.433%),0.360%(0.301%to 0.420%),and 0.079%(0.055%to 0.103%)increase in 8-isoPGF2α,8-OHdG,and PCO,respectively.More importantly,arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α(β:0.147;95%CI:0.130 to 0.164),8-OHdG(0.155;0.118 to 0.192),and PCO(0.050;0.035 to 0.064)in the longitudinal analyses.Our study suggested that arsenic exposurewas not only positively related with global oxidative damage to lipid,DNA,and protein in cross-sectional analyses,but also associated with annual increased rates of these biomarkers in dose-dependent manners.
基金the grants from the Department of Science and Technology of Jilin Province, China (No. 20070721)the Bureau of Science and Technology of Changchun, Jilin Province, China (No. 2007129).
文摘Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10- min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions. Results Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region （P 〈 0.01 vs 10-min ischemia group）. Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates（P〈0.01 vs 10-min ischemia group）.Conelusion Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.
文摘Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and peripheral neuropathy.This review aims to overview the roles of high sensitivity C-reactive protein(hs-CRP),C-reactive protein(CRP),CRP-to-lymphocyte count ratio(CLR),and the CRP-to-albumin ratio(CAR)as biomarkers for assessing systemic inflammation and predicting the development and severity of diabetic chronic microvascular complications.Elevated levels of CRP and hs-CRP have been consistently associated with increased risk of these complications,reflecting ongoing inflammatory processes that contribute to endothelial dysfunction and tissue damage.Furthermore,CAR and CLR,which combine CRP with albumin and lymphocyte counts respectively,offer a more nuanced understanding of the inflammatory and immune response in T2DM patients.While individual studies have demonstrated the clinical relevance of these biomarkers in predicting disease onset and progression,further investigation is needed to establish their utility in clinical practice.This review highlights the potential of these biomarkers for enhancing early detection,risk stratification,and personalized management of diabetic patients,ultimately aiming to improve outcomes and reduce the burden of diabetic chronic microvascular complications.
基金funded by the National Key Research and Development Program of China(2024YFD1600100)the Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2021-OCRI)+3 种基金China Agriculture Research System(CARS-14)Hubei International Science and Technology Cooperation Project(2024EHA055)Science and Technology Innovation Project of Hubei province(2024-620-000-001-031)Fundamental Research Funds for Central Non-profit Scientific Institution(1610172023003)。
文摘Sesame(Sesamum indicum L.)is an ancient diploid oilseed crop valued for its high oil content,quality protein,unsaturated fatty acids,and antioxidants.The emerging research focuses on the utilization of vegetable proteins in the development of novel products and the formulation of functional foods.Developing sesame genotypes with higher protein and oil content is a current focus for improving sesame quality traits,as preferred by the sesame seed oil industry and consumers.Despite previous genome-wide association studies(GWAS)on various agronomic and biochemical traits in sesame,the genetic basis of protein content and oil content remains limited.Therefore,this study was designed to identify candidate genes and quantitative trait loci(QTLs)regulating the target traits using 401 sesame accessions grown in three environments(2018WH,2018LQ,and 2022WH).The protein and oil content in the sesame population varied significantly.The protein content ranged from 15.06%to 26.45%,while the oil content was between 41.68%and 60.15%.Furthermore,the white seeds had a higher oil content,while the black seeds had a higher protein content,indicating an association between seed colour and oil and protein content.GWAS results revealed that 632 and 269 QTLs were selected as significant genetic regions for protein and oil content,respectively.Of these significant QTLs,we identified 10 and 22 stable QTLs for protein and oil content,respectively.A total of 17 candidate genes related to protein and oil content were identified within 32 stable quantitative trait loci(QTLs).Interestingly,two variant sites,SNP13:10093594 and In Del13:10935497,related to protein content,were identified in the gene sequences of SINPZ1300586 and SINPZ1300694.Four SNPs,SNP1:22608987,SNP4:13355820,SNP8:21686488,and SNP11:142842,for oil content were found correspond to the genes SINPZ0102106,SINPZ0401222,SINPZ0801731,and SINPZ1100015,respectively.The findings provide light on the genetic basis of protein and oil characteristics.These genes and QTLs can aid the molecular breeding and genetic engineering of innovative sesame germplasm,with improved potential for protein and oil content,as well as desired quality attributes.
基金Fisheries Research Development Corporation,Grant/Award Number:2017-030.
文摘Background With the global expansion of aquaculture and the increasing demand for fish meal,identifying appropriate and sustainable alternative protein sources for aquafeeds has become essential.Single-cell protein(SCP),derived from methanotrophic bacteria,presents a promising alternative by converting methane into protein,potentially addressing both the need for alternative protein sources and reducing industrial greenhouse gas emissions.This study aimed to evaluate the effects of different levels of SCP inclusion(0%,25%,50%,and 75%fish meal replacement)on the health,gene expression,and gut microbiome of yellowtail kingfish(YTK,Seriola lalandi)following a 35-day growth trial.Results The study found that SCP inclusion at the highest level of fishmeal replacement(75%)induced a mild inflammatory response in the hindgut of the fish.However,micromorphological assessments of the hindgut,serum biochemistry,and gene expression analyses revealed no significant detrimental effects from SCP replacement.Notably,there were indications of improved lipid digestibility with SCP.Furthermore,SCP inclusion significantly enhanced microbial richness and altered the composition of the gut microbiome,introducing beneficial bacterial taxa that may contribute to improved gut health and resilience.Conclusions This study highlights SCP as a viable and sustainable alternative to fish meal in YTK diets.The findings suggest that SCP can be included in YTK diets without adverse health effects at moderate levels and may even offer benefits in terms of lipid digestibility and gut microbiome diversity.These results contribute to the advancement of more sustainable aquaculture practices.
文摘Background Transgenic research in crops involves using genetic engineering techniques to introduce specific genes of interest from other organisms,or even entirely new genes into plant genomes to create crops with desirable traits that wouldn’t be possible through conventional breeding methods.Transgenic crops have been developed for various traits globally.Whitefly,Bemisia tabaci(Gennadius)is one of the major sucking pests of cotton that cause significant damage to the cotton production.To combat whitefly infestations,researchers have developed four transgenic cotton lines expressing the fern protein.And those transgenic lines need to be evaluated for their performance against the target pest—whitefly.The evaluation was designed as controlled trials in polyhouse or muslin cloth cages under open-choice and no-choice conditions by comparing four transgenic cotton lines(A,B,C,and D)with three control groups,including untransformed cotton plants with a same genetic background of the transgenic line,conventionally bred whitefly-resistant cotton,and whitefly-susceptible cotton.In order to study the generational effect,the evaluation also involved studies on whitefly development in laboratory,muslin cloth cage,and polyhouse conditions.Results Both open-choice and no-choice experiments had shown that all the four transgenic cotton lines(A,B,C,and D)expressing the fern protein reduced adult whitefly numbers significantly compared with the control lines,except for the no-choice conditions in 2021,where the transgenic line C was non-significant different from the resistant control line.Notably,the nymphal population on the resistant control line was relatively low and nonsignificant different from the transgenic line C in 2021;and the transgenic lines A and C in 2022 under open-choice conditions.Under no-choice condition,the nymphal counts in the resistant control line was non-significant different from transgenic lines C and D in 2021;and transgenic line D in 2022.All transgenic lines showed significant decrease in egg hatching in 2021 and nymphal development in 2022,except for the transgenic line C which had no significant different in the nymphal development comparing with non-transgenic control lines in 2022.Adult emergence rates in both years of evaluation showed significant decrease in transgenic lines A and B comparing with the control lines.Additionally,the results showed a significant reduction in cotton leaf curl disease and sooty mold development in all the four transgenic lines compared with susceptible control under open-choice conditions,indicating potential benefits of transgenic lines beyond direct effect on whitefly control.Furthermore,the research explored the generational effects of the fern protein on whitefly which revealed the lowest fecundity in the transgenic line C across F0,F1 and F3 generations,lower egg hatching in F1 and F2 generations in transgenic lines A and B,shorter nymphal duration in F1 and F2 generations in transgenic line B,and the least total adult emergence in the transgenic line C in F0 and F3 generations.Conclusions These findings suggest that the transgenic cotton lines expressing fern protein disrupts whitefly populations and the life cycle to a certain extent.However,results are not consistent over generations and years of study,indicating these transgenic lines were not superior over control lines and need to be improved in future breeding.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFA1405000)the National Natural Science Foundation of China(Grant Nos.12274212,12347102,and 12174184)Innovation Program for Quantum Science and Technology(Grant No.2024ZD0300101).
文摘The aging of biomolecular condensates has been implicated in the pathogenesis of various neurodegenerative diseases,characterized by a transition from a physiologically liquid-like state to a pathologically ordered structure.However,the mechanisms governing the formation of these pathological aggregates remain poorly understood.To address this,the present study utilizes coarse-grained molecular dynamics simulations based on Langevin dynamics to explore the structural,dynamical,and material property changes of protein condensates during the aging process.Here,we further develop a nonequilibrium simulation algorithm that not only captures the characteristics of time-dependent amount of aging beads but also reflects the structural information of chain-like connections between aging beads.Our findings reveal that aging induces compaction of the condensates,accompanied by a decrease in diffusion rates and an increase in viscosity.Further analysis suggests that the heterogeneous diffusivity within the condensates may drive the aging process to initiate preferentially at the condensate surface.Our simulation results align with the experimental phenomena and provide a clear physical picture of the aging dynamics.
文摘Objective:To investigate the potential of hydro-alcoholic extract of Gentiana lutea roots(GLE)in scopolamine-induced amnesia model in mice.Methods:The active chemical constituents were determined by GC-MS analysis.In vitro antioxidant activity was performed by the DPPH free radical scavenging method.Ex vivo anti-acetylcholinesterase assay was conducted to investigate the effect on the cholinergic system.A scopolamine-induced memory impairment model was used.The levels of beta-amyloid(Aβ)and tau protein were measured.The behavioral studies were performed through Morris water maze and passive avoidance learning tests,followed by estimation of biochemical markers(GSH and MDA),immunohistochemistry,and histopathological studies on isolated brain tissues.Results:GLE exhibited DPPH free radical scavenging activity with an IC50 value of(76.68±2.28)μg/mL.GLE also manifested inhibitory effect on acetylcholinesterase[IC50(36.58±0.73)μg/mL]to upregulate the cholinergic system.GLE at 200 mg/kg and 400 mg/kg significantly restored the memory impairment induced by scopolamine.GLE at 200 mg/kg and 400 mg/kg significantly reduced brain oxidative stress(P<0.001).Immunohistochemistry investigation showed a significant reduction in Aβdeposition and p-tau protein expression in the GLE treatment groups(P<0.001).Administration of GLE effectively reduced scopolamine-induced neuronal damage in a dose-dependent manner.Conclusions:The study demonstrates that GLE ameliorates scopolamine-induced memory impairment by alleviating Aβ/p-tau protein accumulation and upregulation in the cholinergic system to improve cognitive dysfunction and behavioral problems.
基金National Science Fund for Distinguished Young Scholars of China(32425056)National Natural Science Foundation of China(U23A20250)+2 种基金the earmarked fund for CARS(CARS-45)the National Key R&D Program of China(2023YFD2400600)Sichuan Innovation Team of National Modern Agricultural Industry Technology System(SCCXTD-2024-15).
文摘Background In intensive aquaculture systems,the frequent incidence of enteritis reduces production efficiency and results in significant economic losses.Protein feeds account for 40%–60%of aquafeed expenses,and with the growth of intensive aquaculture,demand for fishmeal as a key protein source outstrips supply,driving up prices.This study investigated the therapeutic potential of reducing dietary protein levels by 3%and adding enzymatic cottonseed protein(ECP)in juvenile yellow catfish with dextran sulfate sodium(DSS)-induced enteritis.Methods A total of 1,260 healthy juvenile yellow catfish(Pelteobagrus fulvidraco),with an average body weight of 5.90±0.05 g,were randomly allocated into 7 experimental groups,each with 3 replicates.The fish were fed one of seven diets for 10 weeks:a normal-protein diet(42%;NP)and 6 low-protein diets(39%;LP)supplemented with graded levels of ECP at 0%(ECP0),1%(ECP1),2%(ECP2),3%(ECP3),4%(ECP4),and 5%(ECP5),respectively.Subsequently,48 fish from each group were selected to receive 1 mL of 6%DSS solution.Results Our findings demonstrated that:(1)The DSS+ECP0 group aggravated DSS-induced enteritis in juvenile yellow catfish compared to the DSS+NP group.(2)Dietary supplementation of ECP in LP diets significantly enhanced the enzymatic activity and levels of immunoreactive substances,including LZM,C3,C4,and ACP(P<0.05).Mechanistically,first,ECP supplementation modulated macrophage polarization by inhibiting the M1 phenotype while promoting the M2 phenotype,potentially through the JAK-STAT signaling pathway;second,dietary ECP suppressed the phosphorylation cascade of key necroptosis-related proteins,including RIP1,RIP3,and MLKL,potentially via the NF-κB and MAPK signaling pathways.(3)The DSS+ECP2 group demonstrated comparable or superior efficacy to the DSS+NP group in mitigating DSS-induced intestinal enteritis.Conclusions Our results demonstrated that ECP can alleviate DSS-induced enteritis by regulating macrophage polarization and reducing necroptosis.Furthermore,ECP supplementation effectively counteracted the exacerbation of enteritis caused by dietary protein reduction.These findings highlighted the effectiveness and feasibility of ECP in alleviating enteritis and saving protein.
