The aim of the present study was to investigate the effect of lipoxin A4 （LXA4） pretreatment on cognitive function of aged rats after global cerebral ischemia reperfusion, and to explore its possible mechanism. Thir...The aim of the present study was to investigate the effect of lipoxin A4 （LXA4） pretreatment on cognitive function of aged rats after global cerebral ischemia reperfusion, and to explore its possible mechanism. Thirty-six aged male Sprague-Dawley rats were randomly divided into three groups （n=12 each）： sham-operation group （S group）, global cerebral ischemia reperfusion group （I/R group） and LXA4-pretreatment group （L group）. The rat model of global cerebral ischemia reperfusion was established by occlusion of the bilateral common carotid artery with hypotension. The cognitive function of rats was determined by a step-down type passive avoidance test and Morris Water Maze test on the third day after reperfusion. Rats were sacrificed after Water Maze test and the pathological changes ofhippocampal CA1 region were observed and the related inflammatory mediators were determined. As compared with S group, the escape latency in I/R group was prolonged from the first day to the fifth day, while that in L group was prolonged from the first day to the third day. The retention time in I/R group and L group in the first quadrant was shortened. The reaction time, frequency of reaction mistake and frequency of escape mistake in I/R group increased, and the latent period shortened. The frequency of escape mistake in L group increased, and the damage in the hippocampal CAI region of I/R group and L group was obvious. The levels of S-10013, TNF-α, IL-1β, IL-10 and NF-κB in I/R group and L group increased. As compared with I/R group, the escape latency in L group was shortened from the first day to the fifth day, and the retention time in the first quadrant prolonged. The reaction time, frequency of reaction mistake and frequency of escape mistake in L group decreased, and the latent period prolonged. The damage in the hippocampal CA1 region of L group was alleviated as well. The levels of S-10013, TNF-α, IL-1β and NF-κB in L group decreased, and those of IL-10 increased. It can be concluded that LXA4 pretreatment can improve the cognitive function in aged rats after global cerebral ischemia reperfusion probably by inhibiting the inflammatory reaction.展开更多
Physical and chemical properties of ambient aerosols at the single particle level were studied in Shanghai from December 22 to 28, 2009. A Cavity-Ring-Down Aerosol Extinction Spectrometer（CRD-AES） and a nephelometer...Physical and chemical properties of ambient aerosols at the single particle level were studied in Shanghai from December 22 to 28, 2009. A Cavity-Ring-Down Aerosol Extinction Spectrometer（CRD-AES） and a nephelometer were deployed to measure aerosol light extinction and scattering properties, respectively. An Aerosol Time-of-Flight Mass Spectrometer（ATOFMS）was used to detect single particle sizes and chemical composition. Seven particle types were detected. Air parcels arrived at the sampling site from the vicinity of Shanghai until mid-day of December 25, when they started to originate from North China. The aerosol extinction,scattering, and absorption coefficients all dropped sharply when this cold, clean air arrived.Aerosol particles changed from a highly aged type before this meteorological shift to a relatively fresh type afterwards. The aerosol optical properties were dependent on the wind direction.Aerosols with high extinction coefficient and scattering Angstrom exponent（SAE） were observed when the wind blew from the west and northwest, indicating that they were predominantly fine particles. Nitrate and ammonium correlated most strongly with the change in aerosol optical properties. In the elemental carbon/organic carbon（ECOC） particle type, the diurnal trends of single scattering albedo（SSA） and elemental carbon（EC） signal intensity had a negative correlation. We also found a negative correlation（r =-0.87） between high mass-OC particle number fraction and the SSA in a relatively clean period, suggesting that particulate aromatic components might play an important role in light absorption in urban areas.展开更多
Profound understanding on the diversity of local residents’willingness to pay(WTP)for ecosystem services(ESs)may aid evaluation of policy impacts by uncovering trade-offs and synergies for achieving sustainable envir...Profound understanding on the diversity of local residents’willingness to pay(WTP)for ecosystem services(ESs)may aid evaluation of policy impacts by uncovering trade-offs and synergies for achieving sustainable environmental resource management.However,the reasons for the spatial preference heterogeneity of WTP are still unclear.In this study,an extensive survey with 4,580 residents in the Yangtze River Middle Reaches Megalopolis(YRMRM),central China,was carried out to investigate the public’s WTP to maintain and improve ESs.We identified key influencing factors and explored how they shaped the preference heterogeneity in WTP by random forest model and surface fitting method.Our results showed that 81.4% of residents reported WTP for ESs greater than zero.Water supply,waste treatment,food supply and raw material supply were the preferred ESs for residents.Living environment factors(i.e.,extent of farmland,water and forest near the residence)were found as the key drivers of WTP.Proximity to farmland,water and forests resulted in high WTP values for a series of specific ESs.The reasons for the heterogeneity of WTP are(1)the difference in proximity to farmland,water and forest(i.e.,the contributor to ESs),(2)the divergence of local residents’preferences for ESs.This study disclosed the heterogeneity and causes of public preferences in YRMRM,which could help policy and decision makers to develop eco-compensation initiatives towards conservative and sustainable use of the environmental resources.展开更多
Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at...Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.展开更多
目的:探究火麻仁对SW620结肠癌细胞的抑制作用及其化学成分。方法:以RT-qPCR技术为检测手段,考察火麻仁乙醇提取液对结肠癌SW620细胞三磷酸腺苷家族蛋白2(ATPase family AAA domain-containing protein 2,ATAD2)基因表达水平的影响;采...目的:探究火麻仁对SW620结肠癌细胞的抑制作用及其化学成分。方法:以RT-qPCR技术为检测手段,考察火麻仁乙醇提取液对结肠癌SW620细胞三磷酸腺苷家族蛋白2(ATPase family AAA domain-containing protein 2,ATAD2)基因表达水平的影响;采用超高效液相色谱/四级杆-静电场轨道阱质谱,分别对液相色谱流动相种类、柱温、梯度洗脱条件,质谱分辨率、喷雾电压等条件进行优化,对火麻仁乙醇提取液中的化学成分进行定性检测。结果:火麻仁乙醇提取液可抑制结肠癌SW620细胞ATAD2的基因表达;在火麻仁提取液中共定性检测到22个化学成分。结论:火麻仁乙醇提取液具有潜在的抗结肠癌活性,其潜在活性成分包括脂肪酸类、黄酮类及生物碱类。展开更多
Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarte...Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.展开更多
While biochar amendment enhances plant productivity and water-use efficiency(WUE),particularly under waterlimited conditions,the specific mechanisms driving these benefits remain unclear.Thus,the present study aims to...While biochar amendment enhances plant productivity and water-use efficiency(WUE),particularly under waterlimited conditions,the specific mechanisms driving these benefits remain unclear.Thus,the present study aims to elucidate the synergistic effects of biochar and reduced irrigation on maize(Zea mays L.)plants,focusing on xylem composition,root-to-shoot signaling,stomatal behavior,and WUE.Maize plants were cultivated in splitroot pots filled with clay loam soil,amended by either wheat-straw biochar(WSB)or softwood biochar(SWB)at 2%(w/w).Plants received full irrigation(FI),deficit irrigation(DI),or partial root-zone drying rrigation(PRD)from the 4-leaf to the grain-filling stage.Our results revealed that the WSB amendment significantly enhanced plant water status,biomass accumulation,and WUE under reduced irrigation,particularly when combined with PRD.Although reduced irrigation inhibited photosynthesis,it enhanced WUE by modulating stomatal morphology and conductance.Biochar amendment combined with reduced rrigation significantly increased xylem K^(+),Ca^(2+),Mg^(2+),NO_(3)^(-),Cl^(-),PO_(4)^(3-),and SO_(4)^(2-)-but decreased Na+,which in turn lowered xylem pH.Moreover,biochar amendment and especially WSB amendment further increased abscisic acid(ABA)contents in both leaf and xylem sap under reduced irrigation conditions due to changes in xylem ionic constituents and pH.The synergistic interactions between xylem components and ABA led to refined adjustments in stomatal size and density,thereby affecting stomatal conductance and ultimately improving the WUE of maize plants at different scales.The combined application of WSB and PRD can,therefore,emerge as a promising approach for improving the overall plant performance of maize plants with increased stomatal adaptations and WUE,especially under water-limited conditions.展开更多
BACKGROUND The incidence and mortality of colorectal cancer continue to rise.For early-stage colorectal cancer,endoscopic resection has become a preferred or important treatment option due to its significant advantage...BACKGROUND The incidence and mortality of colorectal cancer continue to rise.For early-stage colorectal cancer,endoscopic resection has become a preferred or important treatment option due to its significant advantages in operative time,extent of trauma,and medical costs.However,increasing lesion diameter significantly elevates the technical difficulty of endoscopic resection.Currently,robust evidence-based evidence regarding the upper size limit for safely and effectively resecting lesions endoscopically remains lacking.AIM To evaluate the efficacy and safety of endoscopic resection for colorectal lesions≥30 mm in diameter.METHODS This retrospective study reviewed data from 102 patients who underwent endoscopic resection for colorectal lesions measuring≥30 mm in diameter at General Hospital of Northern Theater Command between January 2023 and July 2024.RESULTS Among 102 patients who underwent endoscopic resection,99 received endoscopic submucosal dissection and 3 underwent endoscopic full-thickness resection.Four patients(3.9%)required conversion to surgical radical resection postoperatively.All patients exhibited favorable wound healing at the resection sites,and no long-term complications were observed during the 3-month postoperative colonoscopy follow-up.The primary perioperative complication was post-endoscopic submucosal dissection electrocoagulation syndrome(PEECS)(24/102,23.5%).Multivariate analysis identified lesion location in the transverse colon as an independent risk factor for PEECS occurrence(odds ratio=6.734,95%confidence interval:1.623-27.945,P=0.009).CONCLUSION Large colorectal lesion diameter does not constitute an absolute contraindication to endoscopic resection.Experienced endoscopic centers can achieve complete resection with a favorable efficacy and safety profile.Notably,lesion location in the transverse colon is identified as an independent risk factor for PEECS.展开更多
Pancreatic cancer is recognized as one of the leading causes of cancer mortality,representing the second most common source of cancer-related deaths within the gastrointestinal domain.Surgical resection is currently t...Pancreatic cancer is recognized as one of the leading causes of cancer mortality,representing the second most common source of cancer-related deaths within the gastrointestinal domain.Surgical resection is currently the only definitive treatment;however,the subtle emergence of symptoms often leads to a diagnosis at an advanced stage,with merely 10%-15%of patients being eligible for surgical intervention.The primary obstacle to achieving a potential radical resection is the presence of distant metastatic disease or invasion of adjacent major vascular structures.This review aims to highlight the critical role of endoscopic ultrasound in the diagnosis and staging of pancreatic tumors.We systematically searched PubMed,MEDLINE and Web of Science by using‘pancreatic cancer’and‘endoscopic ultrasonography’as keywords.Relevant studies were reviewed and analyzed.Endoscopic ultrasonography(EUS)is efficient in the diagnosis and staging of pancreatic cancer,past studies reported the accuracy of EUS is 63%to 94%for T-staging and 44%to 82%for N-staging but there are still limitations that need to be comprehensively applied with other diagnostic methods to evaluation of distant metastasis for surgical resectability.Our review aims to reveal the value for the staging of pancreatic cancer.展开更多
BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their...BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.展开更多
Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-...Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.展开更多
基金This study was supported by grants from the Innovation Foundation of Health and Family Planning Commission of Hubei Province （No. WJ2017M036） and the National Natural Science Foundation of China （No. 81471858）.
文摘The aim of the present study was to investigate the effect of lipoxin A4 （LXA4） pretreatment on cognitive function of aged rats after global cerebral ischemia reperfusion, and to explore its possible mechanism. Thirty-six aged male Sprague-Dawley rats were randomly divided into three groups （n=12 each）： sham-operation group （S group）, global cerebral ischemia reperfusion group （I/R group） and LXA4-pretreatment group （L group）. The rat model of global cerebral ischemia reperfusion was established by occlusion of the bilateral common carotid artery with hypotension. The cognitive function of rats was determined by a step-down type passive avoidance test and Morris Water Maze test on the third day after reperfusion. Rats were sacrificed after Water Maze test and the pathological changes ofhippocampal CA1 region were observed and the related inflammatory mediators were determined. As compared with S group, the escape latency in I/R group was prolonged from the first day to the fifth day, while that in L group was prolonged from the first day to the third day. The retention time in I/R group and L group in the first quadrant was shortened. The reaction time, frequency of reaction mistake and frequency of escape mistake in I/R group increased, and the latent period shortened. The frequency of escape mistake in L group increased, and the damage in the hippocampal CAI region of I/R group and L group was obvious. The levels of S-10013, TNF-α, IL-1β, IL-10 and NF-κB in I/R group and L group increased. As compared with I/R group, the escape latency in L group was shortened from the first day to the fifth day, and the retention time in the first quadrant prolonged. The reaction time, frequency of reaction mistake and frequency of escape mistake in L group decreased, and the latent period prolonged. The damage in the hippocampal CA1 region of L group was alleviated as well. The levels of S-10013, TNF-α, IL-1β and NF-κB in L group decreased, and those of IL-10 increased. It can be concluded that LXA4 pretreatment can improve the cognitive function in aged rats after global cerebral ischemia reperfusion probably by inhibiting the inflammatory reaction.
基金supported by the National Natural Science Foundation of China(Nos.21177027,41275126)the Science&Technology Commission of Shanghai Municipality(Nos.12DJ1400100,14XD1400600)the Jiangsu Provincial Collaborative Innovation Center of Climate Change
文摘Physical and chemical properties of ambient aerosols at the single particle level were studied in Shanghai from December 22 to 28, 2009. A Cavity-Ring-Down Aerosol Extinction Spectrometer（CRD-AES） and a nephelometer were deployed to measure aerosol light extinction and scattering properties, respectively. An Aerosol Time-of-Flight Mass Spectrometer（ATOFMS）was used to detect single particle sizes and chemical composition. Seven particle types were detected. Air parcels arrived at the sampling site from the vicinity of Shanghai until mid-day of December 25, when they started to originate from North China. The aerosol extinction,scattering, and absorption coefficients all dropped sharply when this cold, clean air arrived.Aerosol particles changed from a highly aged type before this meteorological shift to a relatively fresh type afterwards. The aerosol optical properties were dependent on the wind direction.Aerosols with high extinction coefficient and scattering Angstrom exponent（SAE） were observed when the wind blew from the west and northwest, indicating that they were predominantly fine particles. Nitrate and ammonium correlated most strongly with the change in aerosol optical properties. In the elemental carbon/organic carbon（ECOC） particle type, the diurnal trends of single scattering albedo（SSA） and elemental carbon（EC） signal intensity had a negative correlation. We also found a negative correlation（r =-0.87） between high mass-OC particle number fraction and the SSA in a relatively clean period, suggesting that particulate aromatic components might play an important role in light absorption in urban areas.
基金financially supported by the National Key Research and Development Plan,Ministry of Science and Technology of the People’s Republic of China(Grant No.2020YFC1908704)the Innovative Foundation of Huazhong University of Science and Technology(Grant No.2018KFYYXJJ133).
文摘Profound understanding on the diversity of local residents’willingness to pay(WTP)for ecosystem services(ESs)may aid evaluation of policy impacts by uncovering trade-offs and synergies for achieving sustainable environmental resource management.However,the reasons for the spatial preference heterogeneity of WTP are still unclear.In this study,an extensive survey with 4,580 residents in the Yangtze River Middle Reaches Megalopolis(YRMRM),central China,was carried out to investigate the public’s WTP to maintain and improve ESs.We identified key influencing factors and explored how they shaped the preference heterogeneity in WTP by random forest model and surface fitting method.Our results showed that 81.4% of residents reported WTP for ESs greater than zero.Water supply,waste treatment,food supply and raw material supply were the preferred ESs for residents.Living environment factors(i.e.,extent of farmland,water and forest near the residence)were found as the key drivers of WTP.Proximity to farmland,water and forests resulted in high WTP values for a series of specific ESs.The reasons for the heterogeneity of WTP are(1)the difference in proximity to farmland,water and forest(i.e.,the contributor to ESs),(2)the divergence of local residents’preferences for ESs.This study disclosed the heterogeneity and causes of public preferences in YRMRM,which could help policy and decision makers to develop eco-compensation initiatives towards conservative and sustainable use of the environmental resources.
基金supported by Postdoc Fellowship from the Foundation for Angelman Syndrome Therapeutics(FT2022-005 to JM,PD2023-001 to XY,and FT2024-001 to YAH)STTR R41 MH118747(to JM)。
文摘Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.
文摘目的:探究火麻仁对SW620结肠癌细胞的抑制作用及其化学成分。方法:以RT-qPCR技术为检测手段,考察火麻仁乙醇提取液对结肠癌SW620细胞三磷酸腺苷家族蛋白2(ATPase family AAA domain-containing protein 2,ATAD2)基因表达水平的影响;采用超高效液相色谱/四级杆-静电场轨道阱质谱,分别对液相色谱流动相种类、柱温、梯度洗脱条件,质谱分辨率、喷雾电压等条件进行优化,对火麻仁乙醇提取液中的化学成分进行定性检测。结果:火麻仁乙醇提取液可抑制结肠癌SW620细胞ATAD2的基因表达;在火麻仁提取液中共定性检测到22个化学成分。结论:火麻仁乙醇提取液具有潜在的抗结肠癌活性,其潜在活性成分包括脂肪酸类、黄酮类及生物碱类。
基金supported by grants from the National Natural Science Foundation of China(91959203,82272836 and 82373017)。
文摘Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.
基金supported by the Natural Science Basic Research Program of Shaanxi Province,China(2024JCYBQN-0491)Heng Wan would like to thank the Chinese Scholarship Council(CsC)(202206300064)。
文摘While biochar amendment enhances plant productivity and water-use efficiency(WUE),particularly under waterlimited conditions,the specific mechanisms driving these benefits remain unclear.Thus,the present study aims to elucidate the synergistic effects of biochar and reduced irrigation on maize(Zea mays L.)plants,focusing on xylem composition,root-to-shoot signaling,stomatal behavior,and WUE.Maize plants were cultivated in splitroot pots filled with clay loam soil,amended by either wheat-straw biochar(WSB)or softwood biochar(SWB)at 2%(w/w).Plants received full irrigation(FI),deficit irrigation(DI),or partial root-zone drying rrigation(PRD)from the 4-leaf to the grain-filling stage.Our results revealed that the WSB amendment significantly enhanced plant water status,biomass accumulation,and WUE under reduced irrigation,particularly when combined with PRD.Although reduced irrigation inhibited photosynthesis,it enhanced WUE by modulating stomatal morphology and conductance.Biochar amendment combined with reduced rrigation significantly increased xylem K^(+),Ca^(2+),Mg^(2+),NO_(3)^(-),Cl^(-),PO_(4)^(3-),and SO_(4)^(2-)-but decreased Na+,which in turn lowered xylem pH.Moreover,biochar amendment and especially WSB amendment further increased abscisic acid(ABA)contents in both leaf and xylem sap under reduced irrigation conditions due to changes in xylem ionic constituents and pH.The synergistic interactions between xylem components and ABA led to refined adjustments in stomatal size and density,thereby affecting stomatal conductance and ultimately improving the WUE of maize plants at different scales.The combined application of WSB and PRD can,therefore,emerge as a promising approach for improving the overall plant performance of maize plants with increased stomatal adaptations and WUE,especially under water-limited conditions.
基金Supported by the Shenyang Science and Technology of Liaoning Province,No.22-321-32-15.
文摘BACKGROUND The incidence and mortality of colorectal cancer continue to rise.For early-stage colorectal cancer,endoscopic resection has become a preferred or important treatment option due to its significant advantages in operative time,extent of trauma,and medical costs.However,increasing lesion diameter significantly elevates the technical difficulty of endoscopic resection.Currently,robust evidence-based evidence regarding the upper size limit for safely and effectively resecting lesions endoscopically remains lacking.AIM To evaluate the efficacy and safety of endoscopic resection for colorectal lesions≥30 mm in diameter.METHODS This retrospective study reviewed data from 102 patients who underwent endoscopic resection for colorectal lesions measuring≥30 mm in diameter at General Hospital of Northern Theater Command between January 2023 and July 2024.RESULTS Among 102 patients who underwent endoscopic resection,99 received endoscopic submucosal dissection and 3 underwent endoscopic full-thickness resection.Four patients(3.9%)required conversion to surgical radical resection postoperatively.All patients exhibited favorable wound healing at the resection sites,and no long-term complications were observed during the 3-month postoperative colonoscopy follow-up.The primary perioperative complication was post-endoscopic submucosal dissection electrocoagulation syndrome(PEECS)(24/102,23.5%).Multivariate analysis identified lesion location in the transverse colon as an independent risk factor for PEECS occurrence(odds ratio=6.734,95%confidence interval:1.623-27.945,P=0.009).CONCLUSION Large colorectal lesion diameter does not constitute an absolute contraindication to endoscopic resection.Experienced endoscopic centers can achieve complete resection with a favorable efficacy and safety profile.Notably,lesion location in the transverse colon is identified as an independent risk factor for PEECS.
文摘Pancreatic cancer is recognized as one of the leading causes of cancer mortality,representing the second most common source of cancer-related deaths within the gastrointestinal domain.Surgical resection is currently the only definitive treatment;however,the subtle emergence of symptoms often leads to a diagnosis at an advanced stage,with merely 10%-15%of patients being eligible for surgical intervention.The primary obstacle to achieving a potential radical resection is the presence of distant metastatic disease or invasion of adjacent major vascular structures.This review aims to highlight the critical role of endoscopic ultrasound in the diagnosis and staging of pancreatic tumors.We systematically searched PubMed,MEDLINE and Web of Science by using‘pancreatic cancer’and‘endoscopic ultrasonography’as keywords.Relevant studies were reviewed and analyzed.Endoscopic ultrasonography(EUS)is efficient in the diagnosis and staging of pancreatic cancer,past studies reported the accuracy of EUS is 63%to 94%for T-staging and 44%to 82%for N-staging but there are still limitations that need to be comprehensively applied with other diagnostic methods to evaluation of distant metastasis for surgical resectability.Our review aims to reveal the value for the staging of pancreatic cancer.
基金Supported by the Chongqing Medical University Program for Youth Innovation in Future Medicine,No.W0019Chongqing Municipal Education Commission’s 14th Five-Year Key Discipline Support Project,No.20240101 and No.20240102。
文摘BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.
基金funded by the Natural Science Foundation of Guangdong Province(grant number 2022A1515012315)Guangdong Medical Science and Technology Research Fund Project(grant number A2023185)+2 种基金the Discipline Construction Project of Guangdong Medical University(grant number 4SG22005G)the 2023 Provincial Basic and Applied Basic Research Fund Enterprise Joint Fund Project(grant number 2023A1515220149)Southern Medical University Shunde Hospital 2023 Research Initiation Programme Project(SRSP2023016).
文摘Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.
