Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual pat...Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testic...To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.展开更多
Species endangerment represents one of the most pressing challenges to global ecological stability.The latest assessments reveal that many plant species face imminent extinction threats due to factors such as climate ...Species endangerment represents one of the most pressing challenges to global ecological stability.The latest assessments reveal that many plant species face imminent extinction threats due to factors such as climate change,habitat loss,invasive species,and overexploitation(Thuiller et al.,2005;Humphreys et al.,2019).Consequently,understanding the mechanisms driving plant endangerment is urgently required to inform effective conservation strategies and mitigate further losses.展开更多
(+)-Strebloside,a significant bioactive compound isolated from the roots of Streblus asper Lour.,demonstrates inhibitory effects against multiple malignancies.However,its specific function and underlying mechanistic p...(+)-Strebloside,a significant bioactive compound isolated from the roots of Streblus asper Lour.,demonstrates inhibitory effects against multiple malignancies.However,its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma(NHL)remain unexplored.This investigation sought to elucidate the role and potential mechanisms of(+)-strebloside-induced NHL cell death.The results demonstrated that(+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells,including those from Raji cell-derived xenograft models.Mechanistic analyses revealed that(+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3(STEAP3)-induced ferroptosis in NHL,and STEAP3 inhibition reduced the proliferation-inhibitory effects of(+)-strebloside.Furthermore,(+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase(MAPK)pathway,and extracellular signal-regulated kinase(ERK)inhibition diminished the proliferation-inhibitory activity induced by(+)-strebloside.These findings indicate that(+)-strebloside presents promising therapeutic potential for NHL treatment.展开更多
With the rapid development of artificial intelligence(AI)technology,its application in special education has demonstrated great potential for enhancing educational effectiveness and promoting inclusivity.This article ...With the rapid development of artificial intelligence(AI)technology,its application in special education has demonstrated great potential for enhancing educational effectiveness and promoting inclusivity.This article explores the current applications and future trends of AI in special education settings from a human-computer interaction perspective,with particular focus on children with autism.The paper first outlines the transition from universal computer-assisted education toward AI-driven specialized interventions that meet the personalized needs of special education students.Through research cases applying affective computing systems,speech recognition technology,and large language model tools for children,it illustrates how AI enables personalized learning and real-time feedback.Finally,the article prospects future directions for AI in special education,emphasizing human-centered approaches to support the comprehensive development of learners with special needs.展开更多
The virus SARS-CoV2,which causes the Coronavirus disease COVID-19 has become a pandemic and has spread to every inhabited continent.Given the increasing caseload,there is an urgent need to augment clinical skills in o...The virus SARS-CoV2,which causes the Coronavirus disease COVID-19 has become a pandemic and has spread to every inhabited continent.Given the increasing caseload,there is an urgent need to augment clinical skills in order to identify from among the many mild cases the few that will progress to critical illness.We present a first step towards building an artificial intelligence(AI)framework,with predictive analytics(PA)capabilities applied to real patient data,to provide rapid clinical decision-making support.COVID-19 has presented a pressing need as a)clinicians are still developing clinical acumen given the disease’s novelty,and b)resource limitations in a rapidly expanding pandemic require difficult decisions relating to resource allocation.The objectives of this research are:(1)to algorithmically identify the combinations of clinical characteristics of COVID-19 that predict outcomes,and(2)to develop a tool with AI capabilities that will predict patients at risk for more severe illness on initial presentation.The predictive models learn from historical data to help predict specifically who will develop acute respiratory distress syndrome(ARDS),a severe outcome in COVID-19.Our experimental results based on two hospitals in Wenzhou,Zhejang,China identify features most predictive of ARDS in COVID-19 initial presentation which would not have stood out to clinicians.A mild increase in elevated alanine aminotransferase(ALT)(a liver enzyme)),a presence of myalgias(body aches),and an increase in hemoglobin,in this order,are the clinical features,on presentation,that are the most predictive.Those two centers’COVID-19 case series symptoms on initial presentation can help predict severe outcomes.Predictive models that learned from historical data of patients from two Chinese hospitals achieved 70%to 80%accuracy in predicting severe cases.展开更多
Wistar rats were intragastrical y perfused with Chinese medicines used for tonifying the kidney. These included 0.180 g/mL of Herba Epimedi （Epimedium）, Semen Cuscutae （Dodder Seed）, or Herba Cistanches （Desertli...Wistar rats were intragastrical y perfused with Chinese medicines used for tonifying the kidney. These included 0.180 g/mL of Herba Epimedi （Epimedium）, Semen Cuscutae （Dodder Seed）, or Herba Cistanches （Desertliving Cistanche）, 0.04 mg/mL monoamine oxidase-B inhibitor selegiline, or distil ed water for 14 consecutive days to prepare drug-containing serum or blank serum. MES23.5 cells in the logarithmic phase were cultured in media supplemented with 15%drug-containing serum for 24 hours, fol owed by incubation in culture solution containing 100μmol/L H2O2 for 3 hours. 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and flow tometry results showed that al drug-containing serums improved the survival rate of H 2 O 2-injured MES23.5 cells, inhibited pro-apoptotic FasL and caspase-3 expression, promoted anti-apoptotic Bcl-2 expression. However, drug-containing serums had little influence on Fas expression in H 2 O 2-injured MES23.5 cells. Enzyme-linked immunosorbent assay results showed that serum containing Herba Cistanches or Herba Epimedi increased the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cellline-derived neurotrophic factor in injured MES23.5 cells;serum containing Semen Cuscutae only increased brain-derived neurotrophic factor expres-sion; while expression of the above neurotrophic factors remained the same in cells treated with serum containing selegiline. These findings indicate that Chinese medicines used to tonify the kid-ney can protect nerve cells by regulating the expression of apoptosis-related factors and neuro-trophic factors in MES23.5 cells.展开更多
基金supported by the Natural Science Foundation of Guangdong Province(No.2021B1515120053)Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515140166).
文摘Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金supported by the Shenzhen Fundamental Research Program(No.JCYJ20210324121807021).
文摘To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.
基金supported by the National Key R&D Program of China(2022YFC3400300).
文摘Species endangerment represents one of the most pressing challenges to global ecological stability.The latest assessments reveal that many plant species face imminent extinction threats due to factors such as climate change,habitat loss,invasive species,and overexploitation(Thuiller et al.,2005;Humphreys et al.,2019).Consequently,understanding the mechanisms driving plant endangerment is urgently required to inform effective conservation strategies and mitigate further losses.
基金supported by the"Double First-Class"University Project(No.CPU2018GY34).
文摘(+)-Strebloside,a significant bioactive compound isolated from the roots of Streblus asper Lour.,demonstrates inhibitory effects against multiple malignancies.However,its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma(NHL)remain unexplored.This investigation sought to elucidate the role and potential mechanisms of(+)-strebloside-induced NHL cell death.The results demonstrated that(+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells,including those from Raji cell-derived xenograft models.Mechanistic analyses revealed that(+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3(STEAP3)-induced ferroptosis in NHL,and STEAP3 inhibition reduced the proliferation-inhibitory effects of(+)-strebloside.Furthermore,(+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase(MAPK)pathway,and extracellular signal-regulated kinase(ERK)inhibition diminished the proliferation-inhibitory activity induced by(+)-strebloside.These findings indicate that(+)-strebloside presents promising therapeutic potential for NHL treatment.
基金supported by the 2025 Lingnan Normal University Quality Basic Education Support Program(No.14).
文摘With the rapid development of artificial intelligence(AI)technology,its application in special education has demonstrated great potential for enhancing educational effectiveness and promoting inclusivity.This article explores the current applications and future trends of AI in special education settings from a human-computer interaction perspective,with particular focus on children with autism.The paper first outlines the transition from universal computer-assisted education toward AI-driven specialized interventions that meet the personalized needs of special education students.Through research cases applying affective computing systems,speech recognition technology,and large language model tools for children,it illustrates how AI enables personalized learning and real-time feedback.Finally,the article prospects future directions for AI in special education,emphasizing human-centered approaches to support the comprehensive development of learners with special needs.
文摘The virus SARS-CoV2,which causes the Coronavirus disease COVID-19 has become a pandemic and has spread to every inhabited continent.Given the increasing caseload,there is an urgent need to augment clinical skills in order to identify from among the many mild cases the few that will progress to critical illness.We present a first step towards building an artificial intelligence(AI)framework,with predictive analytics(PA)capabilities applied to real patient data,to provide rapid clinical decision-making support.COVID-19 has presented a pressing need as a)clinicians are still developing clinical acumen given the disease’s novelty,and b)resource limitations in a rapidly expanding pandemic require difficult decisions relating to resource allocation.The objectives of this research are:(1)to algorithmically identify the combinations of clinical characteristics of COVID-19 that predict outcomes,and(2)to develop a tool with AI capabilities that will predict patients at risk for more severe illness on initial presentation.The predictive models learn from historical data to help predict specifically who will develop acute respiratory distress syndrome(ARDS),a severe outcome in COVID-19.Our experimental results based on two hospitals in Wenzhou,Zhejang,China identify features most predictive of ARDS in COVID-19 initial presentation which would not have stood out to clinicians.A mild increase in elevated alanine aminotransferase(ALT)(a liver enzyme)),a presence of myalgias(body aches),and an increase in hemoglobin,in this order,are the clinical features,on presentation,that are the most predictive.Those two centers’COVID-19 case series symptoms on initial presentation can help predict severe outcomes.Predictive models that learned from historical data of patients from two Chinese hospitals achieved 70%to 80%accuracy in predicting severe cases.
基金supported by the Developmental Fund of Chen Keji Integrative Medicine,No.CKJ2010025the Key Foundation of Society Development in Fujian Province,No.2013Y0059
文摘Wistar rats were intragastrical y perfused with Chinese medicines used for tonifying the kidney. These included 0.180 g/mL of Herba Epimedi （Epimedium）, Semen Cuscutae （Dodder Seed）, or Herba Cistanches （Desertliving Cistanche）, 0.04 mg/mL monoamine oxidase-B inhibitor selegiline, or distil ed water for 14 consecutive days to prepare drug-containing serum or blank serum. MES23.5 cells in the logarithmic phase were cultured in media supplemented with 15%drug-containing serum for 24 hours, fol owed by incubation in culture solution containing 100μmol/L H2O2 for 3 hours. 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and flow tometry results showed that al drug-containing serums improved the survival rate of H 2 O 2-injured MES23.5 cells, inhibited pro-apoptotic FasL and caspase-3 expression, promoted anti-apoptotic Bcl-2 expression. However, drug-containing serums had little influence on Fas expression in H 2 O 2-injured MES23.5 cells. Enzyme-linked immunosorbent assay results showed that serum containing Herba Cistanches or Herba Epimedi increased the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cellline-derived neurotrophic factor in injured MES23.5 cells;serum containing Semen Cuscutae only increased brain-derived neurotrophic factor expres-sion; while expression of the above neurotrophic factors remained the same in cells treated with serum containing selegiline. These findings indicate that Chinese medicines used to tonify the kid-ney can protect nerve cells by regulating the expression of apoptosis-related factors and neuro-trophic factors in MES23.5 cells.
