Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,...Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P<0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P<0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P<0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.展开更多
We establish a slow manifold for a fast-slow dynamical system with anomalous diffusion,where both fast and slow components are influenced by white noise.Furthermore,we verify the exponential tracking property for the ...We establish a slow manifold for a fast-slow dynamical system with anomalous diffusion,where both fast and slow components are influenced by white noise.Furthermore,we verify the exponential tracking property for the established random slow manifold,which leads to a lower dimensional reduced system.Alongside this we consider a parameter estimation method for a nonlocal fast-slow stochastic dynamical system,where only the slow component is observable.In terms of quantifying parameters in stochastic evolutionary systems,the provided method offers the advantage of dimension reduction.展开更多
Objective: Angelicae Sinensis Radix(ASR, Danggui in Chinese), Cistanches Herba(CH, Roucongrong in Chinese), Ginseng Radix et Rhizoma(PG, Renshen in Chinese), and Panacis Quinquefolii Radix(PQ,Xiyangshen in Chinese), w...Objective: Angelicae Sinensis Radix(ASR, Danggui in Chinese), Cistanches Herba(CH, Roucongrong in Chinese), Ginseng Radix et Rhizoma(PG, Renshen in Chinese), and Panacis Quinquefolii Radix(PQ,Xiyangshen in Chinese), widely used as medicine and dietary supplement around the world, are susceptible to fungal and mycotoxin contamination. In this study, we aim to analyze their fungal community by DNA metabarcoding.Methods: A total of 12 root samples were collected from three main production areas in China. The samples were divided into four groups based on herb species, including ASR, CH, PG, and PQ groups. The fungal community on the surface of four root groups was investigated through DNA metabarcoding via targeting the internal transcribed spacer 2 region(ITS2).Results: All the 12 samples were detected with fungal contamination. Rhizopus(13.04%-74.03%),Aspergillus(1.76%-23.92%), and Fusarium(0.26%-15.27%) were the predominant genera. Ten important fungi were identified at the species level, including two potential toxigenic fungi(Penicillium citrinum and P. oxalicum) and eight human pathogenic fungi(Alternaria infectoria, Candida sake, Hyphopichia burtonii, Malassezia globosa, M. restricta, Rhizopus arrhizus, Rhodotorula mucilaginosa, and Ochroconis tshawytschae). Fungal community in ASR and CH groups was significantly different from other groups,while fungal community in PG and PQ groups was relatively similar.Conclusion: DNA metabarcoding revealed the fungal community in four important root herbs. This study provided an important reference for preventing root herbs against fungal and mycotoxin contamination.展开更多
Background and Aims:Hepatic fibrosis(HF)is a critical step in the progression of hepatocellular carcinoma(HCC).Gene associated with retinoid-IFN-induced mortality 19(GRIM19),an essential component of mitochondrial res...Background and Aims:Hepatic fibrosis(HF)is a critical step in the progression of hepatocellular carcinoma(HCC).Gene associated with retinoid-IFN-induced mortality 19(GRIM19),an essential component of mitochondrial respiratory chain complex I,is frequently attenuated in various human cancers,including HCC.Here,we aimed to investigate the potential relationship and underlying mechanism between GRIM19 loss and HF pathogenesis.Methods:GRIM19 expression was evaluated in normal liver tissues,hepatitis,hepatic cirrhosis,and HCC using human liver disease spectrum tissue microarrays.We studied hepatocyte-specific GRIM19 knockout mice and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein-9(Cas9)lentivirus-mediated GRIM19 gene-editing in murine hepatocyte AML12 cells in vitro and in vivo.We performed flow cytometry,immunofluorescence,immunohistochemistry,western blotting,and pharmacological intervention to uncover the potential mechanisms underlying GRIM19 loss-induced HF.Results:Mitochondrial GRIM19 was progressively downregulated in chronic liver disease tissues,including hepatitis,cirrhosis,and HCC tissues.Hepatocyte-specific GRIM19 heterozygous deletion induced spontaneous hepatitis and subsequent liver fibrogenesis in mice.In addition,GRIM19 loss caused chronic liver injury through reactive oxygen species(ROS)-mediated oxidative stress,resulting in aberrant NF-κB activation via an IKK/IKB partner in hepatocytes.Further-more,GRIM19 loss activated NLRP3-mediated IL33 signaling administration of the NLRP3 inhibitor MCC950 dramatically via the ROS/NF-κB pathway in hepatocytes.Intraperitoneal alleviated GRIM19 loss-driven HF in vivo.Conclusions:The mitochondrial GRIM19 loss facilitates liver fibrosis through NLRP3/IL33 activation via ROS/NF-κB signaling,providing potential therapeutic approaches for earlier HF prevention.展开更多
Background In the new International League Against Epilepsy(ILAE)classification of seizure types,generalized seizures such as absence seizures(ASs)may originate from a focal point and rapidly spread to the bilaterally...Background In the new International League Against Epilepsy(ILAE)classification of seizure types,generalized seizures such as absence seizures(ASs)may originate from a focal point and rapidly spread to the bilaterally distributed brain network.Increasing evidence from animal and clinical studies has indicated that focal changes may occur prior to ASs;however,the relationship of ASs with epileptogenic lesions remains unclear.Methods We retrospectively collected and analyzed the clinical,imaging,and electrophysiological data of 16 patients who had ASs and structural lesions with seizure-free outcomes after lesion resection.Results In semiology analysis,nine patients displayed focal onset;only two patients showed simple ASs,and seizure types other than ASs were observed in the remaining patients.On ictal electroencephalography(EEG),four patients showed bilateral synchronous symmetric 3 Hz generalized spike-wave discharges(GSWDs),and the remaining patients showed bilateral 1.5–2.5 Hz GSWDs.Moreover,most patients(13/16,81.3%)exhibited focal features in addition to ASs,while interictal EEG was the same in 12 patients.Furthermore,on stereoelectroencephalogram(SEEG),2/5 patients showed focal discharges before bilateral burst GSWDs.Additionally,all patients had structural lesions on imaging.In four typical AS patients,the lesions were located in deep brain regions.Notably,in 9 patients(9/16,56%),the lesions were located in the posterior cortex.All patients underwent lesion resection and had seizure-free outcomes during follow-up,and intelligence quotient(IQ)also improved by 10.71±3.90 one year after surgery.Conclusions Patients with lesion-related epilepsy may present with ASs that have a focal onset and are associated with good surgical outcomes.展开更多
Background:Programmed cell death-1/ligand 1 inhibitors are a new treatment strategy for advanced urothelial carcinoma.Therefore,a comparative evaluation of their efficacy and toxicity compared with chemotherapy is nec...Background:Programmed cell death-1/ligand 1 inhibitors are a new treatment strategy for advanced urothelial carcinoma.Therefore,a comparative evaluation of their efficacy and toxicity compared with chemotherapy is necessary.Methods:We comprehensively searched PubMed,Web of Science,Embase,and Cochrane Library databases and performed a meta-analysis of randomized controlled trials up to July 2021.We considered overall survival as the primary outcome,and progression-free survival,objective response rate,and treatment-related adverse events as secondary outcomes.Results:Overall,3584 patients from five studies were evaluated.Compared with first-line chemotherapy,programmed cell death-1/ligand 1 inhibitors were significantly associated with worse progression-free survival(p<0.001)and adverse objective response rates(p<0.001).However,the treatments were not significantly different in terms of overall survival(p=0.33).Compared with second-line chemotherapy,programmed cell death-1/ligand 1 inhibitors significantly improved overall survival(p<0.001),and there was no statistically significant difference in progression-free survival(p=0.89)or objective response rate(p=0.34).Compared with chemotherapy,programmed cell death-1/ligand 1 inhibitors were well tolerated(first-line chemotherapy:p<0.001;second-line chemotherapy:p<0.001).Conclusions:The efficacy of programmed cell death-1/ligand 1 inhibitors in patients with advanced urothelial carcinoma is not superior to that of first-line platinum-based chemotherapy but is better than second-line chemotherapy;however,programmed cell death-1/ligand 1 inhibitors are safer than first-and second-line chemotherapy and have a broader prospect for use in combination therapy.展开更多
The safety of traditional Chinese medicine(TCM) is a major strategic issue that involves human health. With the continuous improvement in disease prevention and treatment, the export of TCM and its related products ha...The safety of traditional Chinese medicine(TCM) is a major strategic issue that involves human health. With the continuous improvement in disease prevention and treatment, the export of TCM and its related products has increased dramatically in China. However, the frequent safety issues of Chinese medicine have become the ‘bottleneck' impeding the modernization of TCM. It was proved that mycotoxins seriously affect TCM safety; the pesticide residues of TCM are a key problem in TCM international trade; adulterants have also been detected, which is related to market circulation. These three factors have greatly affected TCM safety. In this study, fast, highly effective, economically-feasible and accurate detection methods concerning TCM safety issues were reviewed, especially on the authenticity, mycotoxins and pesticide residues of medicinal materials.展开更多
The high prevalence and spread of arthropod-borne viruses(arboviruses)make them an important cause of viral encephalitis in humans.Most epidemic viral encephalitides have an etiology associated with arboviruses.Among ...The high prevalence and spread of arthropod-borne viruses(arboviruses)make them an important cause of viral encephalitis in humans.Most epidemic viral encephalitides have an etiology associated with arboviruses.Among various arboviruses,the Japanese encephalitis virus,West Nile virus,Zika virus,Dengue virus and Chikungunya virus can induce seizures.Arboviruses of the genus Flavivirus are usually transmitted by mosquitoes and other host animals.These vector-borne pathogens can cause epidemic viral encephalitis.Seizures may not be the major manifestation in these viral encephalitides,but may predict a poor prognosis.In this article,we discuss the relationships between these viruses and seizures from perspectives of clinical characteristics,pathogenesis,prognosis and treatments of each.展开更多
After publication of this article[1],it is noticed the article contains an error:the section below should be placed between the section headings of‘Pathogenesis’and‘Activated glia’on page 2.Tropism with the brain ...After publication of this article[1],it is noticed the article contains an error:the section below should be placed between the section headings of‘Pathogenesis’and‘Activated glia’on page 2.Tropism with the brain JEV’s neurotropism is a relevant factor of its pathogenesis.Neurotropism is not synonymous with neurovirulence,but they can be associated with each other in some cases.The JEV typically replicates before it spreads to local lymph nodes.Then the liver,heart,kidney and other organs the blood-brain barrier(Fig.2).To cross the barrier,JEV replicates in endothelial cells inflammatory cells that carry the virus(Fig.3).展开更多
基金the Fundamental Research Funds for the Central Universities,China(Grant No.:3332022147)the CAMS Innovation Fund for Medical Sciences,China(Grant Nos.:2021-I2M-1-071 and 2021-I2M-1-031)the National Natural Science Foundation of China(Grant No.:81872999).
文摘Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P<0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P<0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P<0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.
基金supported by NSF (1620449)NSFC (11531006 and 11771449)
文摘We establish a slow manifold for a fast-slow dynamical system with anomalous diffusion,where both fast and slow components are influenced by white noise.Furthermore,we verify the exponential tracking property for the established random slow manifold,which leads to a lower dimensional reduced system.Alongside this we consider a parameter estimation method for a nonlocal fast-slow stochastic dynamical system,where only the slow component is observable.In terms of quantifying parameters in stochastic evolutionary systems,the provided method offers the advantage of dimension reduction.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-071).
文摘Objective: Angelicae Sinensis Radix(ASR, Danggui in Chinese), Cistanches Herba(CH, Roucongrong in Chinese), Ginseng Radix et Rhizoma(PG, Renshen in Chinese), and Panacis Quinquefolii Radix(PQ,Xiyangshen in Chinese), widely used as medicine and dietary supplement around the world, are susceptible to fungal and mycotoxin contamination. In this study, we aim to analyze their fungal community by DNA metabarcoding.Methods: A total of 12 root samples were collected from three main production areas in China. The samples were divided into four groups based on herb species, including ASR, CH, PG, and PQ groups. The fungal community on the surface of four root groups was investigated through DNA metabarcoding via targeting the internal transcribed spacer 2 region(ITS2).Results: All the 12 samples were detected with fungal contamination. Rhizopus(13.04%-74.03%),Aspergillus(1.76%-23.92%), and Fusarium(0.26%-15.27%) were the predominant genera. Ten important fungi were identified at the species level, including two potential toxigenic fungi(Penicillium citrinum and P. oxalicum) and eight human pathogenic fungi(Alternaria infectoria, Candida sake, Hyphopichia burtonii, Malassezia globosa, M. restricta, Rhizopus arrhizus, Rhodotorula mucilaginosa, and Ochroconis tshawytschae). Fungal community in ASR and CH groups was significantly different from other groups,while fungal community in PG and PQ groups was relatively similar.Conclusion: DNA metabarcoding revealed the fungal community in four important root herbs. This study provided an important reference for preventing root herbs against fungal and mycotoxin contamination.
基金partially supported by the National Nature Science Foundation of China[No.32171119,No.32371173]the general basic research project from the Ministry of Education Key Laboratory of Child Development and Disorders[GBRP-202116]+2 种基金the Nature Science Foundation of Chongqing Science and Technology Bureau[CSTB2022NSCQ-MSX0838]the Science and Technology Research Program of Chongqing Municipal Education Commission[KJZD-K202100401]the Future Medical Youth Innovation Team Support Project of Chongqing Medical University[W0175].
文摘Background and Aims:Hepatic fibrosis(HF)is a critical step in the progression of hepatocellular carcinoma(HCC).Gene associated with retinoid-IFN-induced mortality 19(GRIM19),an essential component of mitochondrial respiratory chain complex I,is frequently attenuated in various human cancers,including HCC.Here,we aimed to investigate the potential relationship and underlying mechanism between GRIM19 loss and HF pathogenesis.Methods:GRIM19 expression was evaluated in normal liver tissues,hepatitis,hepatic cirrhosis,and HCC using human liver disease spectrum tissue microarrays.We studied hepatocyte-specific GRIM19 knockout mice and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein-9(Cas9)lentivirus-mediated GRIM19 gene-editing in murine hepatocyte AML12 cells in vitro and in vivo.We performed flow cytometry,immunofluorescence,immunohistochemistry,western blotting,and pharmacological intervention to uncover the potential mechanisms underlying GRIM19 loss-induced HF.Results:Mitochondrial GRIM19 was progressively downregulated in chronic liver disease tissues,including hepatitis,cirrhosis,and HCC tissues.Hepatocyte-specific GRIM19 heterozygous deletion induced spontaneous hepatitis and subsequent liver fibrogenesis in mice.In addition,GRIM19 loss caused chronic liver injury through reactive oxygen species(ROS)-mediated oxidative stress,resulting in aberrant NF-κB activation via an IKK/IKB partner in hepatocytes.Further-more,GRIM19 loss activated NLRP3-mediated IL33 signaling administration of the NLRP3 inhibitor MCC950 dramatically via the ROS/NF-κB pathway in hepatocytes.Intraperitoneal alleviated GRIM19 loss-driven HF in vivo.Conclusions:The mitochondrial GRIM19 loss facilitates liver fibrosis through NLRP3/IL33 activation via ROS/NF-κB signaling,providing potential therapeutic approaches for earlier HF prevention.
基金The National Natural Science Foundation of China supported this work(82171448,82201613).
文摘Background In the new International League Against Epilepsy(ILAE)classification of seizure types,generalized seizures such as absence seizures(ASs)may originate from a focal point and rapidly spread to the bilaterally distributed brain network.Increasing evidence from animal and clinical studies has indicated that focal changes may occur prior to ASs;however,the relationship of ASs with epileptogenic lesions remains unclear.Methods We retrospectively collected and analyzed the clinical,imaging,and electrophysiological data of 16 patients who had ASs and structural lesions with seizure-free outcomes after lesion resection.Results In semiology analysis,nine patients displayed focal onset;only two patients showed simple ASs,and seizure types other than ASs were observed in the remaining patients.On ictal electroencephalography(EEG),four patients showed bilateral synchronous symmetric 3 Hz generalized spike-wave discharges(GSWDs),and the remaining patients showed bilateral 1.5–2.5 Hz GSWDs.Moreover,most patients(13/16,81.3%)exhibited focal features in addition to ASs,while interictal EEG was the same in 12 patients.Furthermore,on stereoelectroencephalogram(SEEG),2/5 patients showed focal discharges before bilateral burst GSWDs.Additionally,all patients had structural lesions on imaging.In four typical AS patients,the lesions were located in deep brain regions.Notably,in 9 patients(9/16,56%),the lesions were located in the posterior cortex.All patients underwent lesion resection and had seizure-free outcomes during follow-up,and intelligence quotient(IQ)also improved by 10.71±3.90 one year after surgery.Conclusions Patients with lesion-related epilepsy may present with ASs that have a focal onset and are associated with good surgical outcomes.
基金Guangdong Province Higher Vocational Colleges&Schools Pearl River Scholar Funded SchemeScience and Technology Planning Project of Guangdong Province,Grant/Award Number:2017B020227007+4 种基金Guangdong Provincial Clinical Research Center for Urological Diseases,Grant/Award Number:2020B1111170006National Natural Science Foundation of China,Grant/Award Numbers:81825016,81772719,8217326,81772728,819723856,81961128027,82002679National Key Research and Development Program of China,Grant/Award Number:2018YFA0902803Key Areas Research and Development Program of Guangdong,Grant/Award Number:2018B010109006Key Laboratory of Malignant Tumor。
文摘Background:Programmed cell death-1/ligand 1 inhibitors are a new treatment strategy for advanced urothelial carcinoma.Therefore,a comparative evaluation of their efficacy and toxicity compared with chemotherapy is necessary.Methods:We comprehensively searched PubMed,Web of Science,Embase,and Cochrane Library databases and performed a meta-analysis of randomized controlled trials up to July 2021.We considered overall survival as the primary outcome,and progression-free survival,objective response rate,and treatment-related adverse events as secondary outcomes.Results:Overall,3584 patients from five studies were evaluated.Compared with first-line chemotherapy,programmed cell death-1/ligand 1 inhibitors were significantly associated with worse progression-free survival(p<0.001)and adverse objective response rates(p<0.001).However,the treatments were not significantly different in terms of overall survival(p=0.33).Compared with second-line chemotherapy,programmed cell death-1/ligand 1 inhibitors significantly improved overall survival(p<0.001),and there was no statistically significant difference in progression-free survival(p=0.89)or objective response rate(p=0.34).Compared with chemotherapy,programmed cell death-1/ligand 1 inhibitors were well tolerated(first-line chemotherapy:p<0.001;second-line chemotherapy:p<0.001).Conclusions:The efficacy of programmed cell death-1/ligand 1 inhibitors in patients with advanced urothelial carcinoma is not superior to that of first-line platinum-based chemotherapy but is better than second-line chemotherapy;however,programmed cell death-1/ligand 1 inhibitors are safer than first-and second-line chemotherapy and have a broader prospect for use in combination therapy.
基金supported by National Natural Science Foundation of China (No. 81473303)the Major Scientific and Technological Special Project for ‘Significant New Drugs Creation’ (No. 2014ZX09304307001)
文摘The safety of traditional Chinese medicine(TCM) is a major strategic issue that involves human health. With the continuous improvement in disease prevention and treatment, the export of TCM and its related products has increased dramatically in China. However, the frequent safety issues of Chinese medicine have become the ‘bottleneck' impeding the modernization of TCM. It was proved that mycotoxins seriously affect TCM safety; the pesticide residues of TCM are a key problem in TCM international trade; adulterants have also been detected, which is related to market circulation. These three factors have greatly affected TCM safety. In this study, fast, highly effective, economically-feasible and accurate detection methods concerning TCM safety issues were reviewed, especially on the authenticity, mycotoxins and pesticide residues of medicinal materials.
基金the National Natural ScienceFoundation of China(No 81971219).
文摘The high prevalence and spread of arthropod-borne viruses(arboviruses)make them an important cause of viral encephalitis in humans.Most epidemic viral encephalitides have an etiology associated with arboviruses.Among various arboviruses,the Japanese encephalitis virus,West Nile virus,Zika virus,Dengue virus and Chikungunya virus can induce seizures.Arboviruses of the genus Flavivirus are usually transmitted by mosquitoes and other host animals.These vector-borne pathogens can cause epidemic viral encephalitis.Seizures may not be the major manifestation in these viral encephalitides,but may predict a poor prognosis.In this article,we discuss the relationships between these viruses and seizures from perspectives of clinical characteristics,pathogenesis,prognosis and treatments of each.
文摘After publication of this article[1],it is noticed the article contains an error:the section below should be placed between the section headings of‘Pathogenesis’and‘Activated glia’on page 2.Tropism with the brain JEV’s neurotropism is a relevant factor of its pathogenesis.Neurotropism is not synonymous with neurovirulence,but they can be associated with each other in some cases.The JEV typically replicates before it spreads to local lymph nodes.Then the liver,heart,kidney and other organs the blood-brain barrier(Fig.2).To cross the barrier,JEV replicates in endothelial cells inflammatory cells that carry the virus(Fig.3).
