Birds exhibit a high degree of migratory diversity,which is influenced by various ecological factors and life history strategies.Conducting studies on tropical bird migration,of which research is scarce,and comparing ...Birds exhibit a high degree of migratory diversity,which is influenced by various ecological factors and life history strategies.Conducting studies on tropical bird migration,of which research is scarce,and comparing it with temperate birds can enhance our understanding of bird migration behaviour and its underlying mecha-nisms.In this study,we explored the migration behaviour of a breeding population of the Barn Swallow(Hirundo rustica)in Zhanjiang,southern China,a region located in the northern tropics,using light-level geolocators.From 2021 to 2023,we deployed geolocators on 92 breeding swallows and retrieved geolocators successfully from 23 individuals.These swallows all exhibited migratory behaviour,and wintering on various islands in Southeast Asia.They displayed sex differences in their wintering locations.All males concentrated in Borneo,while females primarily chose Borneo but also dispersed to the Philippines,South China Sea,and Vietnam for wintering.The studied swallow population adopted a seasonal migration pattern of“indirect in autumn,direct in spring”,bypassing the ecological barrier of the South China Sea in autumn and tending to directly cross it in spring migration.Moreover,the distance and duration of autumn migration was significantly longer than those of the spring migration.Compared to temperate Barn Swallows,the Barn Swallow population breeding in Zhanjiang adopts a pattern of“intra-tropical migration”and initiates autumn migration earlier.The formation of their migration pattern may be limited by ecological and physiological factors.展开更多
Single-molecule magnetic tweezers(MTs) have revealed multiple transition barriers along the unfolding pathway of several two-state proteins, such as GB1 and Csp. In this study, we utilized MTs to measure the force-dep...Single-molecule magnetic tweezers(MTs) have revealed multiple transition barriers along the unfolding pathway of several two-state proteins, such as GB1 and Csp. In this study, we utilized MTs to measure the force-dependent folding and unfolding rates of both protein L(PLWT) and its Y47W mutant(PLY47W) where the mutation point is not at the force-bearing β-strands. The measurements were conducted within a force range of 3–120 pN. Notably, the unfolding rates of both PLWT and PWY47W exhibit distinct force sensitivities below 50 pN and above 60 pN, implying a two-barrier free energy landscape. Both PLWT and PLY47W share the same force-dependent folding rate and the same transition barriers,but the unfolding rate of PLY47W is faster than that of PLWT. Our finding demonstrates that the residue outside of the force-bearing region will also affect the force-induced unfolding dynamics.展开更多
Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to iden...Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.展开更多
BACKGROUND Colorectal cancer(CRC)is a commonly diagnosed cancer of the digestive system worldwide.Although chemotherapeutic agents and targeted therapeutic drugs are currently available for CRC treatment,drug resistan...BACKGROUND Colorectal cancer(CRC)is a commonly diagnosed cancer of the digestive system worldwide.Although chemotherapeutic agents and targeted therapeutic drugs are currently available for CRC treatment,drug resistance is a problem that cannot be ignored and needs to be solved.AIM To explore the relationship between circular RNA(circRNA)and CRC drug resistance.circRNA plays a key role in the occurrence and development of cancers,but its function in the process of drug resistance has not been widely revealed.METHODS To explore the role of circRNA in 5-fluorouracil(5-Fu)resistance,we performed the circRNA expression profile in two CRC cell lines and their homologous 5-Fu resistant cells by high-throughput sequencing.RESULTS We validated the differentially expressed circRNAs in other two paired CRC cells,confirmed that circ_0002813 and circ_0000236 could have a potential competitive endogenous RNA mechanism and be involved in the formation of 5-Fu resistance.And we combined the sequencing results of mRNA to construct the regulatory network of circRNA-miRNA-mRNA.CONCLUSION Our study revealed that circ_0002813 and circ_0000236 may as the biomarkers to predict the occurrence of 5-Fu resistance in CRC.展开更多
The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neuro...The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.展开更多
Cancer is one of the leading causes of death in most countries and regions,accounting for about ten million deaths each year worldwide.Despite the endeavors and achievements made in treating cancer during the past dec...Cancer is one of the leading causes of death in most countries and regions,accounting for about ten million deaths each year worldwide.Despite the endeavors and achievements made in treating cancer during the past decades,rapid resistance to the current clinically used targeted drugs or targeted chemotherapeutic agents continues to be a major problem in cancer therapies.Moreover,many cancer patients are suffering from tumor complications or cancer-related symptoms.Traditional medicine has been practiced for thousands of years and is also currently diffusely used worldwide as an alternative therapy for cancer.Areas of investigation of traditional medicine in cancer treatment,such as traditional formulas,chemical components derived from herbal medicines,and acupuncture,have received increasing attention,especially in recent years.Here,we included selected studies reported last year regarding traditional medicine for cancer treatment in an attempt to summarize the most relevant findings,providing a valuable reference for the future investigation of traditional medicine in the cancer field.展开更多
Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may a...Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may affect APOD expression.Therefore,this paper aims to investigate the significance of APOD expression and APOD DNA methylation in breast cancer.Methods:This study utilized comprehensive bioinformatics analysis of APOD using Gene Expression database of Normal and Tumor tissues 2,UCSC Xena,etc.Clinical and survival information obtained from the The Cancer Genome Atlas and Gene Expression Omnibus datasets were extracted for data mining.Results:The correlation between APOD and breast cancer was examined,along with the connection between APOD DNA methylation and APOD expression.In the The Cancer Genome Atlas cohort,as well as GSE31448 and GSE65194 datasets,APOD expression decreased in breast cancer(P<0.0001).Clinical feature analysis results showed that APOD expression was correlated with the PAM50 subtype,with the lowest expression in the Basal subtype(P<0.0001).High APOD expression is a good prognostic marker for breast cancer(HR=0.71,P=0.037).APOD methylation level was significantly negatively correlated with expression level(R=−0.4770,P<0.001),and cg15231202,cg23720929,and cg05624196 were important regulatory targets.High APOD expression was associated with higher metabolism and extracellular matrix scores.Conclusion:APOD is an independent prognostic marker for breast cancer and is regulated by DNA methylation to modulate mRNA expression.展开更多
We compare the ability of coupled global climate models from the phases 5 and 6 of the Coupled Model Intercomparison Project(CMIP5 and CMIP6,respectively)in simulating the temperature and precipitation climatology and...We compare the ability of coupled global climate models from the phases 5 and 6 of the Coupled Model Intercomparison Project(CMIP5 and CMIP6,respectively)in simulating the temperature and precipitation climatology and interannual variability over China for the period 1961–2005 and the climatological East Asian monsoon for the period 1979–2005.All 92 models are able to simulate the geographical distribution of the above variables reasonably well.Compared with earlier CMIP5 models,current CMIP6 models have nationally weaker cold biases,a similar nationwide overestimation of precipitation and a weaker underestimation of the southeast–northwest precipitation gradient,a comparable overestimation of the spatial variability of the interannual variability,and a similar underestimation of the strength of winter monsoon over northern Asia.Pairwise comparison indicates that models have improved from CMIP5 to CMIP6 for climatological temperature and precipitation and winter monsoon but display little improvement for the interannual temperature and precipitation variability and summer monsoon.The ability of models relates to their horizontal resolutions in certain aspects.Both the multi-model arithmetic mean and median display similar skills and outperform most of the individual models in all considered aspects.展开更多
Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors.Transforming growth factor-betas(TGF-βs)and their most specific signal transducti...Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors.Transforming growth factor-betas(TGF-βs)and their most specific signal transduction factors,Smads,are expressed in the endometrium during the window of implantation.Recent researches indicated that Smad dependent TGF-β signaling may play an important role in the process of embryo implantation.In this study,we measured the expression of TGF-β1,TGF-β receptor type I(TpRI),Smad3 and p-Smad3 in the endometrium of mice and observed their elevation on day 4,5 and 6 of pseudopregnancy.Then we administrated a specific Smad3 inhibitor(Sis3)into the uterine cavity of mice on day 3 of pregnancy.The results showed a reduction in insulin-like growth factor-1(IGFBP-1)expression and the decreased number of implanted embryo after the administration.In addition,Sis3 was found to reduce the IGFBP-1 secretion in decidualized endometrial stromal cells.Taken all together,our findings demonstrated that TGF-β/Smad3 signaling is involved in the process of embryo implantation.展开更多
1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that...1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that the door-to-balloon(D2B)time,as a quality metric of primary percutaneous coronary intervention(PCI)in patients with STEMI,should be≤90 min and preferably less than 60 min.[3,4]However,significant variations from guidelines exist in the real world practices at hospitals.展开更多
The virulent factors of Escherichia coil （E.cofi） play an important role in the process of pathopoiesis. The study aimed to compare drug-resistant genes and virulence genes between extended spectrum β-1actamases （...The virulent factors of Escherichia coil （E.cofi） play an important role in the process of pathopoiesis. The study aimed to compare drug-resistant genes and virulence genes between extended spectrum β-1actamases （ESBLs）-producing E.coli and non-ESBLs-producing E.cofi to provide a reference for physicians in management of hospital infection. From October 2010 to August 2011,96 drug-resistant strains of E. coli isolated were collected from the specimens in Qingdao Municipal Hospital, Qingdao, China. These bacteria strains were divided into a ESBLs-producing group and a non-ESBLs-producing group. Drug sensitivity tests were performed using the Kirby-Bauer （K-B） method. Disinfectant gene, qacEAl-sull and 8 virulence genes （CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1） were tested by polymerase chain reaction （PCR）. Among the 96 E.coli isolates, the ESBLs-producing E.coli comprised 46 （47.9%） strains and the non-ESBLs-producing E.cofi consisted of 50 （52.1%） strains. The detection rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA,VT1, est, bfpA, elt, and CNF1 in 46 ESBLs-producing E.coli isolates were 89.1%, 76.1%, 6.5%, 69.6%, 69.6%, 89.1%, 10.9%, 26.1%, 8.7%, and 19.6%, respectively. In the non-ESBLs-producing E.cofi strains, the positive rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1 were 62.0%, 80.0%, 16.0%, 28.0%, 64.0%, 38.0%, 6.0%, 34.0%, 10.0%, and 24.0%, respectively. The difference in the detection rates of multiple drug-resistant strain, hlyA and VT1 between the ESBLs-producing E.cofi strains and the non-ESBLs-producing E.cofi strains was statistically significant （P〈0.05）. The positive rate of multiple drug-resistant strains is higher in the ESBLs-producing strains than in the non-ESBLs-producing strains. The expression of some virulence genes hlyA and VT1 varies between the ESBLs-producing strains and the non-ESBLs-producing strains. Increased awareness of clinicians and enhanced testing by laboratories are required to reduce treatment failures and prevent the spread of multiple drug-resistant strains.展开更多
A high flocculation performance composite flocculant was prepared with sodium alginate, polyaluminium ferric chloride and cationic polyacrylamide. And the composite flocculant was used in papermaking wastewater treatm...A high flocculation performance composite flocculant was prepared with sodium alginate, polyaluminium ferric chloride and cationic polyacrylamide. And the composite flocculant was used in papermaking wastewater treatment. Results indicated that it achieve the best flocculation performance when the raw material mass ratio was 2:1:1, the dosage of the composite flocculant was 20 mg/L, and the removal efficiency of COD and turbidity with this composite flocculant reached 89.6% and 99.2%, respectively.展开更多
The G2019S mutation of the leucine-rich repeat kinase 2(LRRK2)is the most common genetic cause of Parkinson's disease (PD).However,the molecular mechanisms of LRRK2 mutation contributing to the onset and progressi...The G2019S mutation of the leucine-rich repeat kinase 2(LRRK2)is the most common genetic cause of Parkinson's disease (PD).However,the molecular mechanisms of LRRK2 mutation contributing to the onset and progression of PD have not been fully illustrated.We generated HEK293 cells stably transfected with α-synuclein and investigated the effect of LRRK2 G2019S mutation on the degradation of α-synuclein.The lysosomal activity was assessed by the protein degradation of glyceraldehyde-3-phosphate dehydrogenase and ribonuclease A.It was found that α-synuclein was mainly degraded in lysosomes.LRRK2G2019S inhibited the degradation of α-synuclein,and promoted its aggregation.LRRK2G 2019S also decreased the activities of lysosomal enzymes including cathepsin B and cathepsin L.Furthermore,the inhibitory effect of LRRK2 G2019S on lysosomal functions did not depend on its kinase activity.These findings indicated that the inhibitory effect of LRRK2 G2019S on α-synuclein degradation could underlie the pathogenesis of aberrant α-synuclein aggregation in PD with LRRK2 mutation.展开更多
Heat shock protein 70（HSP70） maintains Ca^2＋ homeostasis in PC12 cells,which may protect against apoptosis;however,the mechanisms of neuroprotection are unclear.Therefore,in this study,we examined Ca^2＋ levels in ...Heat shock protein 70（HSP70） maintains Ca^2＋ homeostasis in PC12 cells,which may protect against apoptosis;however,the mechanisms of neuroprotection are unclear.Therefore,in this study,we examined Ca^2＋ levels in PC12 cells transfected with an exogenous lentiviral HSP70 gene expression construct,and we subsequently subjected the cells to ischemia-hypoxia/reoxygenation injury.HSP70 overexpression increased neuronal viability and ATPase activity,and it decreased cellular reactive oxygen species levels and intracellular Ca^2＋ concentration after hypoxia/reoxygenation.HSP70 overexpression enhanced the protein and m RNA expression levels of sarcoplasmic/endoplasmic reticulum Ca^2＋-ATPase（SERCA）,but it decreased the protein and m RNA levels of inositol 1,4,5-trisphosphate receptor（IP3R）,thereby leading to decreased intracellular Ca^2＋concentration after ischemia-hypoxia/reoxygenation.These results suggest that exogenous HSP70 protects against ischemia-hypoxia/reoxygenation injury,at least in part,by maintaining cellular Ca^2＋ homeostasis,by upregulating SERCA expression and by downregulating IP_3 R expression.展开更多
Dear Editor,I am Dr. Chang-Mei Guo, from the Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China. We write to present a case of unilateral orbital cellulit...Dear Editor,I am Dr. Chang-Mei Guo, from the Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China. We write to present a case of unilateral orbital cellulitis after bilateral strabismus surgery. This study has been performed in accordance with the Declaration of Helsinki and written informed consent for publication of photographs was obtained from the patient.展开更多
基金supported by the National Natural Science Foundation of China(32101236,32270518)National Key R&D Program of China(2022YFF0802400).
文摘Birds exhibit a high degree of migratory diversity,which is influenced by various ecological factors and life history strategies.Conducting studies on tropical bird migration,of which research is scarce,and comparing it with temperate birds can enhance our understanding of bird migration behaviour and its underlying mecha-nisms.In this study,we explored the migration behaviour of a breeding population of the Barn Swallow(Hirundo rustica)in Zhanjiang,southern China,a region located in the northern tropics,using light-level geolocators.From 2021 to 2023,we deployed geolocators on 92 breeding swallows and retrieved geolocators successfully from 23 individuals.These swallows all exhibited migratory behaviour,and wintering on various islands in Southeast Asia.They displayed sex differences in their wintering locations.All males concentrated in Borneo,while females primarily chose Borneo but also dispersed to the Philippines,South China Sea,and Vietnam for wintering.The studied swallow population adopted a seasonal migration pattern of“indirect in autumn,direct in spring”,bypassing the ecological barrier of the South China Sea in autumn and tending to directly cross it in spring migration.Moreover,the distance and duration of autumn migration was significantly longer than those of the spring migration.Compared to temperate Barn Swallows,the Barn Swallow population breeding in Zhanjiang adopts a pattern of“intra-tropical migration”and initiates autumn migration earlier.The formation of their migration pattern may be limited by ecological and physiological factors.
基金supported by the National Natural Science Foundation of China(Grant Nos.12174322 to HC and 12204124 to ZG)111 Project(Grant No.B16029)+1 种基金the Graduate Scientific Research Foundation of Wenzhou University(Grant No.3162023003034 to JH)research grant from Wenzhou Institute。
文摘Single-molecule magnetic tweezers(MTs) have revealed multiple transition barriers along the unfolding pathway of several two-state proteins, such as GB1 and Csp. In this study, we utilized MTs to measure the force-dependent folding and unfolding rates of both protein L(PLWT) and its Y47W mutant(PLY47W) where the mutation point is not at the force-bearing β-strands. The measurements were conducted within a force range of 3–120 pN. Notably, the unfolding rates of both PLWT and PWY47W exhibit distinct force sensitivities below 50 pN and above 60 pN, implying a two-barrier free energy landscape. Both PLWT and PLY47W share the same force-dependent folding rate and the same transition barriers,but the unfolding rate of PLY47W is faster than that of PLWT. Our finding demonstrates that the residue outside of the force-bearing region will also affect the force-induced unfolding dynamics.
文摘Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.
基金Supported by National Natural Science Foundation of China,No.81874206Shanghai Rising-Star Program,No.20QA1409300the Program for Young Eastern Scholar at Shanghai Institutions of Higher Learning,No.QD2019034
文摘BACKGROUND Colorectal cancer(CRC)is a commonly diagnosed cancer of the digestive system worldwide.Although chemotherapeutic agents and targeted therapeutic drugs are currently available for CRC treatment,drug resistance is a problem that cannot be ignored and needs to be solved.AIM To explore the relationship between circular RNA(circRNA)and CRC drug resistance.circRNA plays a key role in the occurrence and development of cancers,but its function in the process of drug resistance has not been widely revealed.METHODS To explore the role of circRNA in 5-fluorouracil(5-Fu)resistance,we performed the circRNA expression profile in two CRC cell lines and their homologous 5-Fu resistant cells by high-throughput sequencing.RESULTS We validated the differentially expressed circRNAs in other two paired CRC cells,confirmed that circ_0002813 and circ_0000236 could have a potential competitive endogenous RNA mechanism and be involved in the formation of 5-Fu resistance.And we combined the sequencing results of mRNA to construct the regulatory network of circRNA-miRNA-mRNA.CONCLUSION Our study revealed that circ_0002813 and circ_0000236 may as the biomarkers to predict the occurrence of 5-Fu resistance in CRC.
基金supported by the National Natural Science Foundation of China,Nos.30772368(to DH),81371034(to XH)the Key Project of Natural Science Foundation of Shaanxi Province,No.2017JZ025(to DH).
文摘The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.
基金supported by the National Key Research and Development Program of China(2019YFA0904400)the National Natural Science Foundation of China(81822027,81630090,and 81902108)。
文摘延长基于蛋白质治疗药物的半衰期可以提高药物疗效。然而,基因治疗本质上是长期表达所需的治疗性药物,药物半衰期对基因治疗疗效的影响尚不清楚。在这项腺相关病毒(adeno-associated virus,AAV)基因治疗研究中,通过与免疫球蛋白G1(immunoglobulin G 1,IgG1)可溶性单体Fc区(soluble monomeric IgG1 fragment crystallizable,sFc)或Fc区融合,设计了几种能够延长半衰期的蛋白质。研究表明,延长AAV递送的小分子双功能蛋白和成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)的半衰期显著增加了它们在血液循环中的浓度。此外,AAV递送FGF21延长其半衰期使2型糖尿病动物模型中肝损伤和血糖显著降低,并改善了葡萄糖耐量和胰岛素敏感性。这些结果证明了延长药物半衰期的基因治疗在应对人类疾病中的治疗潜力。
基金We extend a sincere apology to those whose work was not discussed or cited in this review due to space limitations.Fu-Wen Yuan was supported by the National Natural Science Foundation of China(No.82202922)the Topnotch Personnel Program from Shanghai University of Traditional Chinese Medicine。
文摘Cancer is one of the leading causes of death in most countries and regions,accounting for about ten million deaths each year worldwide.Despite the endeavors and achievements made in treating cancer during the past decades,rapid resistance to the current clinically used targeted drugs or targeted chemotherapeutic agents continues to be a major problem in cancer therapies.Moreover,many cancer patients are suffering from tumor complications or cancer-related symptoms.Traditional medicine has been practiced for thousands of years and is also currently diffusely used worldwide as an alternative therapy for cancer.Areas of investigation of traditional medicine in cancer treatment,such as traditional formulas,chemical components derived from herbal medicines,and acupuncture,have received increasing attention,especially in recent years.Here,we included selected studies reported last year regarding traditional medicine for cancer treatment in an attempt to summarize the most relevant findings,providing a valuable reference for the future investigation of traditional medicine in the cancer field.
基金The study design,data collection,data analysis,manuscript preparation,and publication decisions of this work were supported by the Science and Technology Program of Zhejiang Province Traditional Chinese Medicine(2023ZL056,2023ZL409)the Foundation Project of Zhejiang Chinese Medical University(2022JKZKTS26,2022JKJNTZ16,2022JKJNTZ23).
文摘Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may affect APOD expression.Therefore,this paper aims to investigate the significance of APOD expression and APOD DNA methylation in breast cancer.Methods:This study utilized comprehensive bioinformatics analysis of APOD using Gene Expression database of Normal and Tumor tissues 2,UCSC Xena,etc.Clinical and survival information obtained from the The Cancer Genome Atlas and Gene Expression Omnibus datasets were extracted for data mining.Results:The correlation between APOD and breast cancer was examined,along with the connection between APOD DNA methylation and APOD expression.In the The Cancer Genome Atlas cohort,as well as GSE31448 and GSE65194 datasets,APOD expression decreased in breast cancer(P<0.0001).Clinical feature analysis results showed that APOD expression was correlated with the PAM50 subtype,with the lowest expression in the Basal subtype(P<0.0001).High APOD expression is a good prognostic marker for breast cancer(HR=0.71,P=0.037).APOD methylation level was significantly negatively correlated with expression level(R=−0.4770,P<0.001),and cg15231202,cg23720929,and cg05624196 were important regulatory targets.High APOD expression was associated with higher metabolism and extracellular matrix scores.Conclusion:APOD is an independent prognostic marker for breast cancer and is regulated by DNA methylation to modulate mRNA expression.
文摘We compare the ability of coupled global climate models from the phases 5 and 6 of the Coupled Model Intercomparison Project(CMIP5 and CMIP6,respectively)in simulating the temperature and precipitation climatology and interannual variability over China for the period 1961–2005 and the climatological East Asian monsoon for the period 1979–2005.All 92 models are able to simulate the geographical distribution of the above variables reasonably well.Compared with earlier CMIP5 models,current CMIP6 models have nationally weaker cold biases,a similar nationwide overestimation of precipitation and a weaker underestimation of the southeast–northwest precipitation gradient,a comparable overestimation of the spatial variability of the interannual variability,and a similar underestimation of the strength of winter monsoon over northern Asia.Pairwise comparison indicates that models have improved from CMIP5 to CMIP6 for climatological temperature and precipitation and winter monsoon but display little improvement for the interannual temperature and precipitation variability and summer monsoon.The ability of models relates to their horizontal resolutions in certain aspects.Both the multi-model arithmetic mean and median display similar skills and outperform most of the individual models in all considered aspects.
基金the National Natural Science Foundation of China(No.81701450).
文摘Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors.Transforming growth factor-betas(TGF-βs)and their most specific signal transduction factors,Smads,are expressed in the endometrium during the window of implantation.Recent researches indicated that Smad dependent TGF-β signaling may play an important role in the process of embryo implantation.In this study,we measured the expression of TGF-β1,TGF-β receptor type I(TpRI),Smad3 and p-Smad3 in the endometrium of mice and observed their elevation on day 4,5 and 6 of pseudopregnancy.Then we administrated a specific Smad3 inhibitor(Sis3)into the uterine cavity of mice on day 3 of pregnancy.The results showed a reduction in insulin-like growth factor-1(IGFBP-1)expression and the decreased number of implanted embryo after the administration.In addition,Sis3 was found to reduce the IGFBP-1 secretion in decidualized endometrial stromal cells.Taken all together,our findings demonstrated that TGF-β/Smad3 signaling is involved in the process of embryo implantation.
基金the National Natural Science Foundation of China(No.81770356&No.81470473)the Capital Health Research and Development of Special(No.2016-2-4083).
文摘1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that the door-to-balloon(D2B)time,as a quality metric of primary percutaneous coronary intervention(PCI)in patients with STEMI,should be≤90 min and preferably less than 60 min.[3,4]However,significant variations from guidelines exist in the real world practices at hospitals.
文摘The virulent factors of Escherichia coil （E.cofi） play an important role in the process of pathopoiesis. The study aimed to compare drug-resistant genes and virulence genes between extended spectrum β-1actamases （ESBLs）-producing E.coli and non-ESBLs-producing E.cofi to provide a reference for physicians in management of hospital infection. From October 2010 to August 2011,96 drug-resistant strains of E. coli isolated were collected from the specimens in Qingdao Municipal Hospital, Qingdao, China. These bacteria strains were divided into a ESBLs-producing group and a non-ESBLs-producing group. Drug sensitivity tests were performed using the Kirby-Bauer （K-B） method. Disinfectant gene, qacEAl-sull and 8 virulence genes （CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1） were tested by polymerase chain reaction （PCR）. Among the 96 E.coli isolates, the ESBLs-producing E.coli comprised 46 （47.9%） strains and the non-ESBLs-producing E.cofi consisted of 50 （52.1%） strains. The detection rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA,VT1, est, bfpA, elt, and CNF1 in 46 ESBLs-producing E.coli isolates were 89.1%, 76.1%, 6.5%, 69.6%, 69.6%, 89.1%, 10.9%, 26.1%, 8.7%, and 19.6%, respectively. In the non-ESBLs-producing E.cofi strains, the positive rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1 were 62.0%, 80.0%, 16.0%, 28.0%, 64.0%, 38.0%, 6.0%, 34.0%, 10.0%, and 24.0%, respectively. The difference in the detection rates of multiple drug-resistant strain, hlyA and VT1 between the ESBLs-producing E.cofi strains and the non-ESBLs-producing E.cofi strains was statistically significant （P〈0.05）. The positive rate of multiple drug-resistant strains is higher in the ESBLs-producing strains than in the non-ESBLs-producing strains. The expression of some virulence genes hlyA and VT1 varies between the ESBLs-producing strains and the non-ESBLs-producing strains. Increased awareness of clinicians and enhanced testing by laboratories are required to reduce treatment failures and prevent the spread of multiple drug-resistant strains.
文摘A high flocculation performance composite flocculant was prepared with sodium alginate, polyaluminium ferric chloride and cationic polyacrylamide. And the composite flocculant was used in papermaking wastewater treatment. Results indicated that it achieve the best flocculation performance when the raw material mass ratio was 2:1:1, the dosage of the composite flocculant was 20 mg/L, and the removal efficiency of COD and turbidity with this composite flocculant reached 89.6% and 99.2%, respectively.
基金the National Natura Science Foundation of China(NSFC)(No.81401051,No 81671051,and No.81501107).
文摘The G2019S mutation of the leucine-rich repeat kinase 2(LRRK2)is the most common genetic cause of Parkinson's disease (PD).However,the molecular mechanisms of LRRK2 mutation contributing to the onset and progression of PD have not been fully illustrated.We generated HEK293 cells stably transfected with α-synuclein and investigated the effect of LRRK2 G2019S mutation on the degradation of α-synuclein.The lysosomal activity was assessed by the protein degradation of glyceraldehyde-3-phosphate dehydrogenase and ribonuclease A.It was found that α-synuclein was mainly degraded in lysosomes.LRRK2G2019S inhibited the degradation of α-synuclein,and promoted its aggregation.LRRK2G 2019S also decreased the activities of lysosomal enzymes including cathepsin B and cathepsin L.Furthermore,the inhibitory effect of LRRK2 G2019S on lysosomal functions did not depend on its kinase activity.These findings indicated that the inhibitory effect of LRRK2 G2019S on α-synuclein degradation could underlie the pathogenesis of aberrant α-synuclein aggregation in PD with LRRK2 mutation.
基金supported by the National Natural Science Foundation of China,No.81571938 and 81501706the Natural Science Foundation of Shandong Province of China,No.Y2007C133
文摘Heat shock protein 70（HSP70） maintains Ca^2＋ homeostasis in PC12 cells,which may protect against apoptosis;however,the mechanisms of neuroprotection are unclear.Therefore,in this study,we examined Ca^2＋ levels in PC12 cells transfected with an exogenous lentiviral HSP70 gene expression construct,and we subsequently subjected the cells to ischemia-hypoxia/reoxygenation injury.HSP70 overexpression increased neuronal viability and ATPase activity,and it decreased cellular reactive oxygen species levels and intracellular Ca^2＋ concentration after hypoxia/reoxygenation.HSP70 overexpression enhanced the protein and m RNA expression levels of sarcoplasmic/endoplasmic reticulum Ca^2＋-ATPase（SERCA）,but it decreased the protein and m RNA levels of inositol 1,4,5-trisphosphate receptor（IP3R）,thereby leading to decreased intracellular Ca^2＋concentration after ischemia-hypoxia/reoxygenation.These results suggest that exogenous HSP70 protects against ischemia-hypoxia/reoxygenation injury,at least in part,by maintaining cellular Ca^2＋ homeostasis,by upregulating SERCA expression and by downregulating IP_3 R expression.
基金the National Natural Science Foundation of China (No.81470655)Multidisciplinary Projects of the Subject Boosting Program of Xijing Hospital (No.XJZT19MDT12)。
文摘Dear Editor,I am Dr. Chang-Mei Guo, from the Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China. We write to present a case of unilateral orbital cellulitis after bilateral strabismus surgery. This study has been performed in accordance with the Declaration of Helsinki and written informed consent for publication of photographs was obtained from the patient.
