The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to b...The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.展开更多
Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and hom...Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and homologous recombination(HR)being the two most prominent.Although two major pathways have been extensively studied in Arabidopsis,rice and other mammals,the exact functions and differences between the two DSB repair pathways in maize still remain less well understood.Here,we characterized mre11a and rad50,mutants of HR pathway patterns,which showed drastic degradation of the typically persistent embryo and endosperm during kernel development.Loss of MRE11 or RAD50 function led to chromosomal fragments and chromosomal bridges in anaphase.While we also reported that the NHEJ pathway patterns,KU70 and KU80 are associated with developmental growth and genome stability.ku70 and ku80 both displayed an obvious dwarf phenotype.Cytological analysis of the mutants revealed extensive chromosome fragmentation in metaphase and subsequent stages.Loss of KU70/80 function upregulated the expression of genes involved in cell cycle progression and nuclear division.These results provide insights into how NHEJ and HR are mechanistically executed during different plant developmental periods and highlight a competitive and complementary relationship between the NHEJ and HR pathways for DNA double-strand break repair in maize.展开更多
Several tritylodontid taxa have been reported from the Upper Jurassic of the Wucaiwan area in the Junggar Basin of Xinjiang,northwestern China,including Yuanotherium minor.The original study described the partially pr...Several tritylodontid taxa have been reported from the Upper Jurassic of the Wucaiwan area in the Junggar Basin of Xinjiang,northwestern China,including Yuanotherium minor.The original study described the partially preserved postcanine teeth in the middle of the left upper maxilla.After detailed re-examination of the specimen and by CT scanning,3D reconstruction,and scanning electron microscopy observations,we provided a more detailed description of the osteology,neurosensory,and tooth wear pattern for all the bones preserved in this specimen and clarified some characters.Based on new information about the cusp wear pattern,the chewing movement pattern of the dentition and detailed cusp morphology,we discussed the cuspal homology of upper cheek teeth of tritylodontids and postulate a standardized method for cusp identification.We hypothesize that the unique maxilla characteristics furnish the evidence for transitional stages about the evolution of the upper jaw-palate structure in tritylodontids.展开更多
The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis acro...The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.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
Zinc ion batteries(ZIBs)are promising for large-scale energy storage applications,but the technology lacks high-capacity and high-stability cathode materials.Herein,oxygen vacancy-VN/V_(2)O_(3)/C(Ov-VN/V_(2)O_(3)/C)he...Zinc ion batteries(ZIBs)are promising for large-scale energy storage applications,but the technology lacks high-capacity and high-stability cathode materials.Herein,oxygen vacancy-VN/V_(2)O_(3)/C(Ov-VN/V_(2)O_(3)/C)heterostructural composite was successfully designed and synthesized as high-stability cathode to promote reversible ZIBs.Thanks to the oxygen-vacancy heterojunction features and the transformed amorphous new phase V_(10)O_(24)·12H_(2)O,Ov-VN/V_(2)O_(3)/C provides abundant channels and active sites for Zn^(2+)diffusion and adsorption.Thus,Ov-VN/V_(2)O_(3)/C as a cathode material for aqueous ZIBs exhibits excellent a high reversible capacity of 531mAh g^(-1)at 0.3 A g^(-1),good rate performance(446 mAh g^(-1)at a high current density of 10 A g^(-1)),and good stability(115 mAh g^(-1)at 20 A g^(-1)after 5000 cycles).More importantly,Ov-VN/V_(2)O_(3)/C//Zn assembled quasi-solidstate batteries also have excellent long-term cycling performance.This work not only obtains high-performance cathode materials,but also provides a new idea for the development of the synthesis of transformational new materials with the synergistic effect of vacancies(defects)and heterojunctions.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
Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,poly...Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,polyphenols,and flavonoids that contribute to its antimicrobial,antioxidant,and immuno-modulatory properties.Additionally,honey is effective in managing some conditions,such as antibiotic-resistant infections,inflammation,and oxidative stress-related diseases.This review explores the extensive health benefits of honey,emphasizing the homology between food and medicine,as proposed by TCM philosophy.Further,this review explores the traditional applications of honey in respiratory health,wound healing,and gastrointestinal support,along with modern scientific validation of these uses.Moreover,the role of honey as a dietary supplement,functional food,and preservative in culinary practices is examined.Overall,this review highlights the synergy between ancient wisdom and contemporary science,advocating for the continued exploration of the role of honey in health,nutrition,and medicine.展开更多
Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expres...Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expressed in both healthy and malignant prostate cells.This study aimed to demonstrate the relationship between pathological characteristics,survival,recurrence,and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.Methods:PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019.Inclusion criteria comprised pathological tumor stage(pT)3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm.After case selection,tissue slides were stained for EZH2 and FOXM1 antibodies,and Allred scores were calculated.Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.Results:The pT3b,ductal carcinoma component,and moderate EZH2 expression were associated with relapse(odds ratio[OR]6.21,95%confidence interval[CI]1.41-27.27,p=0.016;OR 7.29,95%CI 1.03-51.43,p=0.046;OR 5.96,95%CI 1.09-32.48,p=0.039;respectively).The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times,and the risk of death by around 9.78 times and 10.79 times,respectively.The pT3b was linked to higher death likelihood(OR 7.16,95%CI 1.38-37.23,p=0.019),while moderate EZH2 expression did not show statistical significance(OR 4.54,95%CI 0.87-23.60,p=0.072,marginally).Pathological regional lymph node stage(pN)1 had significantly higher probability of mortality than pN unknown(3.9%vs.27%,p<0.001).PCa in the neck and apex of the prostate gland increased death risk tenfold.Conclusion:Sufficient immunoexpression of EZH2,ductal carcinoma component,and neoplastic proliferation in the seminal vesicles,apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality.Clinicians should use these criteria for appropriate patient referrals,and a multicenter trial could provide accurate classifications.展开更多
Chronic heart failure(CHF)is a pathological state in which the cardiac ejection fraction is insufficient to meet an individual's metabolic needs owing to changes in the cardiac structure or function.Various etiolo...Chronic heart failure(CHF)is a pathological state in which the cardiac ejection fraction is insufficient to meet an individual's metabolic needs owing to changes in the cardiac structure or function.Various etiologies such as myocardial infarction and inflammation are implicated,and the main symptoms are dyspnea,lower limb edema,fatigue,and discomfort during rest or exercise.CHF is the primary outcome of cardiovascular disease,and the increasing morbidity and mortality rates highlight the significant risks of this condition.According to traditional Chinese medicine,the pathogenesis of CHF is deficiency of heart qi and heart yang,which predominantly affects the heart,but may also impede the function of other zang-organs such as the spleen and kidney,and aggravate the symptoms of heart failure.With technological advancements and enhanced awareness of health conditions and disease prevention,China has promoted traditional medicine practices such as medicine and food homology(MFH),which has received increasing attention in recent years.This concept stipulates that certain medicines and foods have the same origin;ergo,these foods have medicinal properties,with many being used in the pre-vention and treatment of CHF.However,the efficacy and safety of MHF substances have yet to be determined,and there is no consensus regarding the development of disease prevention and treatment strategies.This article therefore reviews the current evidence for MFH in the prevention and treatment of CHF by summarizing the therapeutic potential of this practice and discussing treatment strategies and aims to improve the understanding of Chinese medicine and food homologous substances in the treatment of this condition,as well as highlight the current literature and avenues for future research.展开更多
Pharmaceutical-Food Homologous Plant-Derived Carbon Dots (P-CDs) have emerged as revolutionary nanomaterials in environmental pollutant management, demonstrating transformative potential for green chemistry and sustai...Pharmaceutical-Food Homologous Plant-Derived Carbon Dots (P-CDs) have emerged as revolutionary nanomaterials in environmental pollutant management, demonstrating transformative potential for green chemistry and sustainable material applications. These carbon dots establish an innovative technical framework by integrating dual "detection-remediation" functionalities through eco-friendly synthesis and high-value conversion of medicinal-edible plants and agroforestry waste. Their core advantages originate from structural templating effects induced by natural functional groups (polyphenols, amino acids) in plant precursors combined with heteroatom self-doping, which synergistically optimizes optical properties. This combination achieves quantum yields ranging from 3.06% to 84.9% and detection sensitivities spanning nanomolar to micromolar concentrations. In pollutant detection applications, P-CDs enable ultrasensitive identification of heavy metals (Hg^(2+) , Cu^(2+) , Fe^(3+) ) and organic contaminants (pesticides, antibiotics) through multi-mechanistic interactions including static quenching (SQ), dynamic quenching (DQ), and F rster resonance energy transfer (FRET). However, technological translation faces critical challenges including quantum yield heterogeneity (>40-fold variation), matrix interference in complex environmental samples (signal drift exceeding 12%), and scalability-related process inconsistencies. Future research priorities should focus on three key areas: standardization of synthesis protocols, development of surface passivation strategies ( e.g. , SiO_(2) encapsulation), and optimization of heterojunction designs to enhance interference resistance. The integration of in situ characterization techniques (particularly X-ray absorption spectroscopy) with machine learning-driven parameter optimization could significantly refine detection-remediation synergies. Concurrently, establishing a comprehensive lifecycle assessment framework becomes imperative for evaluating environmental impacts and scalability potential. This technology pioneers a sustainable paradigm for pollution control by bridging the gap between nanomaterial innovation and industrial deployment, thereby accelerating progress toward global ecological security objectives.展开更多
This editorial highlighted the central role of pancreatic β-cell dysfunction in the pathogenesis of diabetes mellitus and discussed the emerging significance of Ras homolog enriched in brain 1(Rheb1)as a key regulato...This editorial highlighted the central role of pancreatic β-cell dysfunction in the pathogenesis of diabetes mellitus and discussed the emerging significance of Ras homolog enriched in brain 1(Rheb1)as a key regulator of β-cell mass and insulinsecretory capacity.While molecular mechanisms governing β-cell homeostasis remain incompletely defined,Yang et al have recently demonstrated that Rheb1 could promote β-cell proliferation through dual activation of mechanistic target of rapamycin complex 1 and AMP-activated protein kinase signaling pathways,rather than relying solely on mechanistic target of rapamycin complex 1.Notably,Rheb1 expression is higher in pancreatic islets from younger individuals and upregulates hepatocyte nuclear factor 4 alpha,which is recognized as a transcription factor essential for β-cell identity and insulin production.These insights position Rheb1 as a pivotal regulator of β-cell growth and metabolic function,with potential therapeutic implications for diabetes.Targeting Rheb1 may shift treatment paradigms from conventional glucose-lowering strategies towardβ-cell restoration,providing a novel approach to preserve or enhance functionalβ-cell mass in diabetic patients.Further investigation into Rheb1’s upstream regulators and downstream effectors may provide innovative therapeutic directions.展开更多
Conserved domains e.g. nucleotide binding site (NBS) were found in several cloned plant disease resistance genes. Based on the NBS domain, resistance gene analogs (RGAs) have been isolated previously and were used as ...Conserved domains e.g. nucleotide binding site (NBS) were found in several cloned plant disease resistance genes. Based on the NBS domain, resistance gene analogs (RGAs) have been isolated previously and were used as probes to screen a soybean (Glycine max L. Merr.) cDNA library. A full-length cDNA, KR3, was obtained by screening the library and rapid amplification of cDNA ends (RACE) method. Sequence analysis revealed that the cDNA is 2 353 bp in length and the open reading frame (ORF) codes for a polypeptide of 636 amino acids with a Toll-Interleukin-1 receptor (TIR) and a NBS domain. Sequence alignment showed that it was similar to N gene of tobacco. The phylogenetic tree analysis of R proteins with NBS from higher plants was performed. The KR3 gene has low copies in soybean genome and its expression was induced by exogenous salicylic acid (SA).展开更多
pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical p...pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical properties, hydrophilicity/hydrophobicity, signal peptide, secondary structure, coiled coil, transmembrane domains, O-glycogylation site, active site, subcellular localization, functional structural domains and three-dimensional structure were analyzed by a series of bioinformatics software. The results showed that mPDI was a hydrophobic and stable protein with 3 coiled coils, 30-glycogylation sites, 2 structural domains of thioredoxin, 2 active sites of thioredoxin, and located in rough endoplasmic reticulum. It has 512 amino acids, the theoretical pl is 4.98, and signal peptide located in 1-24AA. In the secondary structure, a-helix, random coil, extended chain is 26.37%, 53.32%, 20.31% respectively. The validation of modeling accords with the stereochemistry.展开更多
In the study, the methods of applied histology and histochemistry were used to determine intestinal villus length, crypt depth, the ratio of intestinal villus length to crypt depth, mucous membrane thickness and intes...In the study, the methods of applied histology and histochemistry were used to determine intestinal villus length, crypt depth, the ratio of intestinal villus length to crypt depth, mucous membrane thickness and intestinal wall thickness of duodenum, jejunum and ileum of 42-day-old broilers, so as to study the effects of different conncentrations of homologous probiottcs on small intestinal mucosa struc- ture of the broilers. The results showed that the effect of 0.3% probiotics on small intestine mucosal structures was the best, such as the length of intestinal villus was the longest, the ratio of villus length to crypt depth was the largest, the thins of mucous membrane and intestinal wall was the thickest. These showed that 0,3% probiotics had best effect on improving and enhancing the digestion-absorption func- tion of the small intestine of the broilers.展开更多
<abstract>Aim: Identification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the ra...<abstract>Aim: Identification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the rat. Methods: 'Electronic screening' of Expressed Sequence Tag (EST) and genomic databases, followed by RT-PCR and Northern blot analysis. Results: Rodent ESTs and genomic sequences homologous to HE3, HE4 and Ce8/Ly6G5C were identified in the public databases and the 'full-length' rat cDNAs cloned. To emphasise their homology to the human and canine genes, they were named Me3/Re3, Me4/Re4 and Re8 for mouse and rat counterparts, respectively. mRNA expression patterns were analysed in rats, including rat HEl and HE5/CD52 counterparts as controls. Re3 and Re8 mRNAs were only found in the rat epididymis, while Re4 showed a broader tissue distribution. Within the epididymis, Re3 and Re4 mRNAs were detected in all regions; Re8, on the other hand, was restricted to the caput. During postnatal development, Re3 and control mRNAs were found from the earliest stages investigated, while Re8 mRNA was observed only from day 24 postnatum, corresponding to the onset of spermatogenesis in the prepubertal testis. Castration and testosterone supplementation of adult male rats suggested that none of the cloned mRNAs was directly androgen-regulated. Efferent duct ligation, however, showed that Re8 mRNA levels depended on testicular factors other than androgens. Conclusion: The novel rodent cDNAs can now be used to monitor epididymal gene expression more closely and to set up various regulatory and functional studies.展开更多
Non-homologous end-joining(NHEJ) is a predominant pathway for the repair of DNA double-strand breaks(DSB). It inhibits the efficiency of homologous recombination(HR) by competing for DSB targets. To improve the effici...Non-homologous end-joining(NHEJ) is a predominant pathway for the repair of DNA double-strand breaks(DSB). It inhibits the efficiency of homologous recombination(HR) by competing for DSB targets. To improve the efficiency of HR, multiple CRISPR interference(CRISPRi) and Natronobacterium gregoryi Argonaute(NgAgo) interference(NgAgoi) systems have been designed for the knockdown of NHEJ key molecules, KU70, KU80, polynucleotide kinase/phosphatase(PNKP), DNA ligase IV(LIG4), and NHEJ1. Suppression of KU70 and KU80 by CRISPRi dramatically promoted(P<0.05) the efficiency of HR to 1.85-and 1.58-fold, respectively, whereas knockdown of PNKP, LIG4, and NHEJ1 repair factors did not significantly increase(P>0.05) HR efficiency. Interestingly, although the NgAgoi system significantly suppressed(P<0.05) KU70, KU80, PNKP, LIG4, and NHEJ1 expression, it did not improve(P>0.05) HR efficiency in primary fetal fibroblasts. Our result showed that both NgAgo and catalytically inactive Cas9(dCas9) could interfere with the expression of target genes, but the downstream factors appear to be more active following CRISPR-mediated interference than that of NgAgo.展开更多
基金supported by the TARCC,Welch Foundation Award(I-1724)the Decherd Foundationthe Pape Adams Foundation,NIH grants NS092616,NS127375,NS117065,NS111776。
文摘The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.
基金supported by the National Natural Science Foundation of China(32372116)to Yan He.
文摘Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and homologous recombination(HR)being the two most prominent.Although two major pathways have been extensively studied in Arabidopsis,rice and other mammals,the exact functions and differences between the two DSB repair pathways in maize still remain less well understood.Here,we characterized mre11a and rad50,mutants of HR pathway patterns,which showed drastic degradation of the typically persistent embryo and endosperm during kernel development.Loss of MRE11 or RAD50 function led to chromosomal fragments and chromosomal bridges in anaphase.While we also reported that the NHEJ pathway patterns,KU70 and KU80 are associated with developmental growth and genome stability.ku70 and ku80 both displayed an obvious dwarf phenotype.Cytological analysis of the mutants revealed extensive chromosome fragmentation in metaphase and subsequent stages.Loss of KU70/80 function upregulated the expression of genes involved in cell cycle progression and nuclear division.These results provide insights into how NHEJ and HR are mechanistically executed during different plant developmental periods and highlight a competitive and complementary relationship between the NHEJ and HR pathways for DNA double-strand break repair in maize.
文摘Several tritylodontid taxa have been reported from the Upper Jurassic of the Wucaiwan area in the Junggar Basin of Xinjiang,northwestern China,including Yuanotherium minor.The original study described the partially preserved postcanine teeth in the middle of the left upper maxilla.After detailed re-examination of the specimen and by CT scanning,3D reconstruction,and scanning electron microscopy observations,we provided a more detailed description of the osteology,neurosensory,and tooth wear pattern for all the bones preserved in this specimen and clarified some characters.Based on new information about the cusp wear pattern,the chewing movement pattern of the dentition and detailed cusp morphology,we discussed the cuspal homology of upper cheek teeth of tritylodontids and postulate a standardized method for cusp identification.We hypothesize that the unique maxilla characteristics furnish the evidence for transitional stages about the evolution of the upper jaw-palate structure in tritylodontids.
基金Supported by the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2023A1515012762 and No.2021A1515010846+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.
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financially supported by the National Natural Science Foundation of China(Nos.22269020 and 42167068)the Central Guidance for Local Science and Technology Development Funds Project(No.YDZX20216200001007)+1 种基金the Project of Key Laboratory of Characteristic Resources Utilization in Hexi Corridor(No.XZ2007)the Industry Support Plan Project from Gansu Provincial Department of Education(No.2023CYZC-68)
文摘Zinc ion batteries(ZIBs)are promising for large-scale energy storage applications,but the technology lacks high-capacity and high-stability cathode materials.Herein,oxygen vacancy-VN/V_(2)O_(3)/C(Ov-VN/V_(2)O_(3)/C)heterostructural composite was successfully designed and synthesized as high-stability cathode to promote reversible ZIBs.Thanks to the oxygen-vacancy heterojunction features and the transformed amorphous new phase V_(10)O_(24)·12H_(2)O,Ov-VN/V_(2)O_(3)/C provides abundant channels and active sites for Zn^(2+)diffusion and adsorption.Thus,Ov-VN/V_(2)O_(3)/C as a cathode material for aqueous ZIBs exhibits excellent a high reversible capacity of 531mAh g^(-1)at 0.3 A g^(-1),good rate performance(446 mAh g^(-1)at a high current density of 10 A g^(-1)),and good stability(115 mAh g^(-1)at 20 A g^(-1)after 5000 cycles).More importantly,Ov-VN/V_(2)O_(3)/C//Zn assembled quasi-solidstate batteries also have excellent long-term cycling performance.This work not only obtains high-performance cathode materials,but also provides a new idea for the development of the synthesis of transformational new materials with the synergistic effect of vacancies(defects)and heterojunctions.
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.
基金supported by the National Natural Science Foundation of China(32322079)Beijing Nova Program(20220484101)Talented Young Scientist Program,Ministry of Science and Technology of the People's Republic of China,and China Postdoctoral Science Foundation(2024M753576).
文摘Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,polyphenols,and flavonoids that contribute to its antimicrobial,antioxidant,and immuno-modulatory properties.Additionally,honey is effective in managing some conditions,such as antibiotic-resistant infections,inflammation,and oxidative stress-related diseases.This review explores the extensive health benefits of honey,emphasizing the homology between food and medicine,as proposed by TCM philosophy.Further,this review explores the traditional applications of honey in respiratory health,wound healing,and gastrointestinal support,along with modern scientific validation of these uses.Moreover,the role of honey as a dietary supplement,functional food,and preservative in culinary practices is examined.Overall,this review highlights the synergy between ancient wisdom and contemporary science,advocating for the continued exploration of the role of honey in health,nutrition,and medicine.
文摘Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expressed in both healthy and malignant prostate cells.This study aimed to demonstrate the relationship between pathological characteristics,survival,recurrence,and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.Methods:PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019.Inclusion criteria comprised pathological tumor stage(pT)3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm.After case selection,tissue slides were stained for EZH2 and FOXM1 antibodies,and Allred scores were calculated.Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.Results:The pT3b,ductal carcinoma component,and moderate EZH2 expression were associated with relapse(odds ratio[OR]6.21,95%confidence interval[CI]1.41-27.27,p=0.016;OR 7.29,95%CI 1.03-51.43,p=0.046;OR 5.96,95%CI 1.09-32.48,p=0.039;respectively).The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times,and the risk of death by around 9.78 times and 10.79 times,respectively.The pT3b was linked to higher death likelihood(OR 7.16,95%CI 1.38-37.23,p=0.019),while moderate EZH2 expression did not show statistical significance(OR 4.54,95%CI 0.87-23.60,p=0.072,marginally).Pathological regional lymph node stage(pN)1 had significantly higher probability of mortality than pN unknown(3.9%vs.27%,p<0.001).PCa in the neck and apex of the prostate gland increased death risk tenfold.Conclusion:Sufficient immunoexpression of EZH2,ductal carcinoma component,and neoplastic proliferation in the seminal vesicles,apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality.Clinicians should use these criteria for appropriate patient referrals,and a multicenter trial could provide accurate classifications.
基金supported by National Natural Science Foundation of China(82274082 and 82204943),Beijing“high-grade,precision and advanced”Project,Beijing Key Laboratory for Basic and Development Research on Chinese Medicine.
文摘Chronic heart failure(CHF)is a pathological state in which the cardiac ejection fraction is insufficient to meet an individual's metabolic needs owing to changes in the cardiac structure or function.Various etiologies such as myocardial infarction and inflammation are implicated,and the main symptoms are dyspnea,lower limb edema,fatigue,and discomfort during rest or exercise.CHF is the primary outcome of cardiovascular disease,and the increasing morbidity and mortality rates highlight the significant risks of this condition.According to traditional Chinese medicine,the pathogenesis of CHF is deficiency of heart qi and heart yang,which predominantly affects the heart,but may also impede the function of other zang-organs such as the spleen and kidney,and aggravate the symptoms of heart failure.With technological advancements and enhanced awareness of health conditions and disease prevention,China has promoted traditional medicine practices such as medicine and food homology(MFH),which has received increasing attention in recent years.This concept stipulates that certain medicines and foods have the same origin;ergo,these foods have medicinal properties,with many being used in the pre-vention and treatment of CHF.However,the efficacy and safety of MHF substances have yet to be determined,and there is no consensus regarding the development of disease prevention and treatment strategies.This article therefore reviews the current evidence for MFH in the prevention and treatment of CHF by summarizing the therapeutic potential of this practice and discussing treatment strategies and aims to improve the understanding of Chinese medicine and food homologous substances in the treatment of this condition,as well as highlight the current literature and avenues for future research.
文摘Pharmaceutical-Food Homologous Plant-Derived Carbon Dots (P-CDs) have emerged as revolutionary nanomaterials in environmental pollutant management, demonstrating transformative potential for green chemistry and sustainable material applications. These carbon dots establish an innovative technical framework by integrating dual "detection-remediation" functionalities through eco-friendly synthesis and high-value conversion of medicinal-edible plants and agroforestry waste. Their core advantages originate from structural templating effects induced by natural functional groups (polyphenols, amino acids) in plant precursors combined with heteroatom self-doping, which synergistically optimizes optical properties. This combination achieves quantum yields ranging from 3.06% to 84.9% and detection sensitivities spanning nanomolar to micromolar concentrations. In pollutant detection applications, P-CDs enable ultrasensitive identification of heavy metals (Hg^(2+) , Cu^(2+) , Fe^(3+) ) and organic contaminants (pesticides, antibiotics) through multi-mechanistic interactions including static quenching (SQ), dynamic quenching (DQ), and F rster resonance energy transfer (FRET). However, technological translation faces critical challenges including quantum yield heterogeneity (>40-fold variation), matrix interference in complex environmental samples (signal drift exceeding 12%), and scalability-related process inconsistencies. Future research priorities should focus on three key areas: standardization of synthesis protocols, development of surface passivation strategies ( e.g. , SiO_(2) encapsulation), and optimization of heterojunction designs to enhance interference resistance. The integration of in situ characterization techniques (particularly X-ray absorption spectroscopy) with machine learning-driven parameter optimization could significantly refine detection-remediation synergies. Concurrently, establishing a comprehensive lifecycle assessment framework becomes imperative for evaluating environmental impacts and scalability potential. This technology pioneers a sustainable paradigm for pollution control by bridging the gap between nanomaterial innovation and industrial deployment, thereby accelerating progress toward global ecological security objectives.
基金Supported by Hubei Provincial Natural Science Foundation,No.2025AFB845Graduate Innovation and Entrepreneurship Fund of Wuhan University of Science and Technology,No.JCX2024044.
文摘This editorial highlighted the central role of pancreatic β-cell dysfunction in the pathogenesis of diabetes mellitus and discussed the emerging significance of Ras homolog enriched in brain 1(Rheb1)as a key regulator of β-cell mass and insulinsecretory capacity.While molecular mechanisms governing β-cell homeostasis remain incompletely defined,Yang et al have recently demonstrated that Rheb1 could promote β-cell proliferation through dual activation of mechanistic target of rapamycin complex 1 and AMP-activated protein kinase signaling pathways,rather than relying solely on mechanistic target of rapamycin complex 1.Notably,Rheb1 expression is higher in pancreatic islets from younger individuals and upregulates hepatocyte nuclear factor 4 alpha,which is recognized as a transcription factor essential for β-cell identity and insulin production.These insights position Rheb1 as a pivotal regulator of β-cell growth and metabolic function,with potential therapeutic implications for diabetes.Targeting Rheb1 may shift treatment paradigms from conventional glucose-lowering strategies towardβ-cell restoration,providing a novel approach to preserve or enhance functionalβ-cell mass in diabetic patients.Further investigation into Rheb1’s upstream regulators and downstream effectors may provide innovative therapeutic directions.
文摘Conserved domains e.g. nucleotide binding site (NBS) were found in several cloned plant disease resistance genes. Based on the NBS domain, resistance gene analogs (RGAs) have been isolated previously and were used as probes to screen a soybean (Glycine max L. Merr.) cDNA library. A full-length cDNA, KR3, was obtained by screening the library and rapid amplification of cDNA ends (RACE) method. Sequence analysis revealed that the cDNA is 2 353 bp in length and the open reading frame (ORF) codes for a polypeptide of 636 amino acids with a Toll-Interleukin-1 receptor (TIR) and a NBS domain. Sequence alignment showed that it was similar to N gene of tobacco. The phylogenetic tree analysis of R proteins with NBS from higher plants was performed. The KR3 gene has low copies in soybean genome and its expression was induced by exogenous salicylic acid (SA).
文摘pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical properties, hydrophilicity/hydrophobicity, signal peptide, secondary structure, coiled coil, transmembrane domains, O-glycogylation site, active site, subcellular localization, functional structural domains and three-dimensional structure were analyzed by a series of bioinformatics software. The results showed that mPDI was a hydrophobic and stable protein with 3 coiled coils, 30-glycogylation sites, 2 structural domains of thioredoxin, 2 active sites of thioredoxin, and located in rough endoplasmic reticulum. It has 512 amino acids, the theoretical pl is 4.98, and signal peptide located in 1-24AA. In the secondary structure, a-helix, random coil, extended chain is 26.37%, 53.32%, 20.31% respectively. The validation of modeling accords with the stereochemistry.
基金Supported by the Project of Beijing Vocational College of Agriculture(XY-YF-14-18XYYF-14-16)~~
文摘In the study, the methods of applied histology and histochemistry were used to determine intestinal villus length, crypt depth, the ratio of intestinal villus length to crypt depth, mucous membrane thickness and intestinal wall thickness of duodenum, jejunum and ileum of 42-day-old broilers, so as to study the effects of different conncentrations of homologous probiottcs on small intestinal mucosa struc- ture of the broilers. The results showed that the effect of 0.3% probiotics on small intestine mucosal structures was the best, such as the length of intestinal villus was the longest, the ratio of villus length to crypt depth was the largest, the thins of mucous membrane and intestinal wall was the thickest. These showed that 0,3% probiotics had best effect on improving and enhancing the digestion-absorption func- tion of the small intestine of the broilers.
文摘<abstract>Aim: Identification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the rat. Methods: 'Electronic screening' of Expressed Sequence Tag (EST) and genomic databases, followed by RT-PCR and Northern blot analysis. Results: Rodent ESTs and genomic sequences homologous to HE3, HE4 and Ce8/Ly6G5C were identified in the public databases and the 'full-length' rat cDNAs cloned. To emphasise their homology to the human and canine genes, they were named Me3/Re3, Me4/Re4 and Re8 for mouse and rat counterparts, respectively. mRNA expression patterns were analysed in rats, including rat HEl and HE5/CD52 counterparts as controls. Re3 and Re8 mRNAs were only found in the rat epididymis, while Re4 showed a broader tissue distribution. Within the epididymis, Re3 and Re4 mRNAs were detected in all regions; Re8, on the other hand, was restricted to the caput. During postnatal development, Re3 and control mRNAs were found from the earliest stages investigated, while Re8 mRNA was observed only from day 24 postnatum, corresponding to the onset of spermatogenesis in the prepubertal testis. Castration and testosterone supplementation of adult male rats suggested that none of the cloned mRNAs was directly androgen-regulated. Efferent duct ligation, however, showed that Re8 mRNA levels depended on testicular factors other than androgens. Conclusion: The novel rodent cDNAs can now be used to monitor epididymal gene expression more closely and to set up various regulatory and functional studies.
基金supported by the National Science and Technology Major Project for Breeding of New Transgenic Organisms, China (2016ZX08006002)the Guangdong Province "Flying Sail Program" Postdoctoral Foundation, China (2016)
文摘Non-homologous end-joining(NHEJ) is a predominant pathway for the repair of DNA double-strand breaks(DSB). It inhibits the efficiency of homologous recombination(HR) by competing for DSB targets. To improve the efficiency of HR, multiple CRISPR interference(CRISPRi) and Natronobacterium gregoryi Argonaute(NgAgo) interference(NgAgoi) systems have been designed for the knockdown of NHEJ key molecules, KU70, KU80, polynucleotide kinase/phosphatase(PNKP), DNA ligase IV(LIG4), and NHEJ1. Suppression of KU70 and KU80 by CRISPRi dramatically promoted(P<0.05) the efficiency of HR to 1.85-and 1.58-fold, respectively, whereas knockdown of PNKP, LIG4, and NHEJ1 repair factors did not significantly increase(P>0.05) HR efficiency. Interestingly, although the NgAgoi system significantly suppressed(P<0.05) KU70, KU80, PNKP, LIG4, and NHEJ1 expression, it did not improve(P>0.05) HR efficiency in primary fetal fibroblasts. Our result showed that both NgAgo and catalytically inactive Cas9(dCas9) could interfere with the expression of target genes, but the downstream factors appear to be more active following CRISPR-mediated interference than that of NgAgo.
