Charcot-Marie-Tooth disease(CMT) is a heterogeneous group of inherited peripheral neuro pathies;it is characterized by muscle weakness and wasting,as well as sensory dysfunction,that typically begins during adolescenc...Charcot-Marie-Tooth disease(CMT) is a heterogeneous group of inherited peripheral neuro pathies;it is characterized by muscle weakness and wasting,as well as sensory dysfunction,that typically begins during adolescence and ultimately leads to lifelong disability.Occurring in~1 in 2500individuals,CMT is the most common hereditary neuromuscular condition and results from mutations in> 100 different genes.CMT is grouped into type1(CMT1),where demyelination and loss of nerve conduction velocity occur,type 2(CMT2),where motor and sensory axons degenerate without loss of myelination/nerve conduction velocity,and intermediate CMT,where both demyelination and axon loss present alongside intermediate nerve condu ction velocities.展开更多
The sustainable sourcing of novel bioactive compounds from natural sources is crucial to the success of the pharmaceutical,food,and cosmetics industries.Iris bucharica Foster(syn.Juno bucharica(Foster)Vved.)is a promi...The sustainable sourcing of novel bioactive compounds from natural sources is crucial to the success of the pharmaceutical,food,and cosmetics industries.Iris bucharica Foster(syn.Juno bucharica(Foster)Vved.)is a promising source of novel bioactive molecules,particularly phenolic compounds,which are renowned for their antioxidant properties.In this study,we developed a reliable HPLC-UV-DAD method to identify and quantify phenolic compounds in the leaves and bulbs of I.bucharica,establishing the first set of quality control markers for this species.A total of 21 phenolic compounds were identified in the leaves,with flavonoids isoorientin,guaijaverin,hyperoside,and cosmosiin,the isoflavonoid biochanin A,and the simple phenolic ferulic acid being the most prominent.In comparison,14 compounds were identified in the bulbs,primarily isoflavonoids,including tectoridin and germanaism B,and flavonoid apigenin.The leaves extracts exhibited significant antioxidant activity,whereas the anti-allergic and anti-inflammatory effects were mild.These findings highlight I.bucharica as a sustainable source of bioactive compounds with potential industrial applications.However,further studies are needed to evaluate bioavailability and in vivo efficacy,as well as to optimise extraction methods to realize its industrial potential fully.展开更多
Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the cas...Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the case of a 65-year-old man presenting with rectorrhagia and anal pain, initially diagnosed as hemorrhoidal disease. Subsequent proctological examination revealed an ulcerating-bourging tumor, confirmed histologically as an anorectal melanoma. After a normal extension workup, an abdominoperineal amputation was performed. Anorectal melanoma is a pathology with a poor prognosis, requiring early diagnosis to improve chances of survival.展开更多
Against the backdrop of increasingly prominent global energy shortages and environmental issues,the development of efficient energy conversion and storage technologies has become crucial.Zero-dimensional(0D)metal oxid...Against the backdrop of increasingly prominent global energy shortages and environmental issues,the development of efficient energy conversion and storage technologies has become crucial.Zero-dimensional(0D)metal oxide composites exhibit significant application value in the field of energy chemistry due to their unique properties,such as quantum size effect and high specific surface area.From a broad perspective,this paper reviews the main synthesis methods of these composites,including sol-gel method,hydrothermal/solvothermal method,precipitation method,and template method,while analyzing the characteristics of each method.It further discusses their applications in photocatalytic hydrogen production,fuel cells,lithium-ion batteries,and supercapacitors.Additionally,the current challenges,such as material dispersibility and interface bonding,are pointed out,and future development directions are prospected,aiming to provide references for related research.展开更多
Epilepsy affects over 50 million people worldwide.Drug-resistant epilepsy(DRE)accounts for up to a third of these cases,and neuro-inflammation is thought to play a role in such cases.Despite being a long-debated issue...Epilepsy affects over 50 million people worldwide.Drug-resistant epilepsy(DRE)accounts for up to a third of these cases,and neuro-inflammation is thought to play a role in such cases.Despite being a long-debated issue in the field of DRE,the mechanisms underlying neuroinflammation have yet to be fully elucidated.The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics.Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes,such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis.The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems.We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application.We hope to provide an insightful overview to advance the quest for better DRE treatments.展开更多
In the pharmaceutical industry,model-based prediction is a crucial stage in process development that allows pharmaceutical companies to simulate different scenarios toward improving process efficiency,reducing costs,a...In the pharmaceutical industry,model-based prediction is a crucial stage in process development that allows pharmaceutical companies to simulate different scenarios toward improving process efficiency,reducing costs,and enhancing product quality.Nevertheless,ensuring the quality of formulated pharmaceutical products through the management of raw material variations has always been a challenging task.In this work,data-driven chance-constrained recurrent neural networks(CCRNNs)are developed to address the issue arising from raw material uncertainty.Our goal is to explore how,by proactively incorporating uncertainty into the model training process,more accurate predictions and enhanced robustness can be realized.The proposed approach is tested on a fluid bed dryer(FBD)from a continuous pharmaceutical manufacturing pilot plant.The results demonstrate that CCRNN models offer more robust and accurate predictions for the critical quality attribute(CQA)-in this case,moisture content-when material variations occur,compared with conventional recurrent neural network-based models.展开更多
The first liver transplantation(LT)in humans was performed by Thomas Starzl on March 1,1963[1,2](Fig.1).During the period 1963-1983,this challenging procedure was performed in four centers only,one in the USA and thre...The first liver transplantation(LT)in humans was performed by Thomas Starzl on March 1,1963[1,2](Fig.1).During the period 1963-1983,this challenging procedure was performed in four centers only,one in the USA and three in Western Europe:Denver,Cambridge,Hannover and Groningen.Their collected experience including only 540 cases(meaning 27(!)cases yearly)was the basis of the 1983 National Institutes of Health(NIH)development consensus conference leading to the conclusion that LT could become“a promising alternative to the current therapy in the management of the late phase of several forms of serious liver disease…candidates are those who exhausted alternative medical and surgical treatments…and are approaching the terminal phase of their illness”.Patients presenting liver tumors and inherited,liver based,metabolic diseases could also be considered for LT[3].This conference put forward ten absolute and five relative contraindications restricting thereby the access to LT to a minority of very well selected liver diseased patients.展开更多
Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging ther...Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging therapeutic opportunity of Janus kinase inhibitor(JAKi)in the role of systemic inflammation in AMD pathogenesis(2).This study offers a real-world examination of the relationship between JAKi and AMD,comparing the incidence of AMD in patients treated with JAKi and those receiving other immunotherapies for existing autoimmune diseases.展开更多
The Gannan Yellow River source area(YRSA)is a typical ecological fragile region.Assessing the temporal and spatial patterns of resource and environmental carrying capacity(RECC)is crucial for both ecological security ...The Gannan Yellow River source area(YRSA)is a typical ecological fragile region.Assessing the temporal and spatial patterns of resource and environmental carrying capacity(RECC)is crucial for both ecological security and sustainable development of the Yellow River Basin and the YRSA.Based on RECC theory,this study developed a novel index system focused on human-livestock-grassland relationships to accurately capture resource and environmental carrying characteristics in pastoral regions.By establishing region-specific evaluation thresholds and using a comprehensive index approach,we analyzed spatial and temporal patterns of resource carrying capacity(RCC),environmental carrying capacity(ECC),and resource and environmental carrying capacity(RECC)in the Gannan region from 2005 to 2020.The results indicate that:1)The RECC followed an increasing–decreasing–increasing trajectory from 2005 to 2020,with values ranging from 0.30 to 0.69.The RECC in pastoral areas was not only higher but also exhibited greater variability compared to that in agricultural areas.2)The RCC remained at a low level,with values between 0.06 to 0.098.The index of water consumption per ten thousand Yuan of GDP increased significantly,suggesting that improvements in water use efficiency contributed to the enhancement of RCC.3)The ECC increased notably,shifting from the middle to a very high level,with values ranging from 0.233 to 0.611.ECC emerged as a key determinant of RECC,exhibiting a temporal trend closely aligned with that of RECC.Changes in ECC were primarily driven by factors such as overgrazing rates,the extent of grassland rodent control,and the area of grassland for reseeding and improvement.Based on these findings,future priorities should include the adoption of efficient water-saving irrigation technologies,the promotion of rotational grazing practices,and the optimization of land management strategies.展开更多
BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but da...BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but data from cohort studies are scarce.AIM To investigate the association between insulin and pathological LFT,liver disease,and cirrhosis in a populationbased retrospective cohort study.METHODS Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used.LFT were obtained at two time points 8 years to 24 years after baseline.Liver disease diagnoses were obtained from nationwide registries.The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.RESULTS Total follow-up was 54054 person-years for women and 27556 person-years for men.Insulin levels were positively correlated with elevated LFT during follow-up,whereas physical activity and coffee consumption were negatively correlated.Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease,adjusted hazard ratio(aHR)of 4.3(95%CI:1.6-14.6)and cirrhosis(aHR=4.8,95%CI:1.6-14.6).CONCLUSION This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease.The results support the concept of metabolic dysfunction associated liver disease.展开更多
Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained...Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained largely unknown.In this study,we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study(GWAS),including 9674 East Asians and 10,115 Europeans,quantitatively assessing 78 facial traits using 3D facial images.We identify 71 genomic loci associated with facial features,including 21 novel loci.We develop a facial polygenic score(FPS)that enables the prediction of facial features based on genetic information.Interestingly,the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features.Furthermore,we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records.Our results suggest that Neanderthals and Denisovans likely share similar facial features,such as a wider but shorter nose and a wider endocanthion distance.The decreased mouth width is characterized specifically in Denisovans.The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.展开更多
基金funding from the Medical Research Council (MR/S006990/1, MR/Y010949/1)the Rosetrees Trust (M806)the UCL Neurogenetic Therapies Programme funded by The Sigrid Rausing Trust and the UCL Therapeutic Acceleration Support scheme supported by funding from MRC IAA 2021 UCL MR/X502984/1 (to JNS)。
文摘Charcot-Marie-Tooth disease(CMT) is a heterogeneous group of inherited peripheral neuro pathies;it is characterized by muscle weakness and wasting,as well as sensory dysfunction,that typically begins during adolescence and ultimately leads to lifelong disability.Occurring in~1 in 2500individuals,CMT is the most common hereditary neuromuscular condition and results from mutations in> 100 different genes.CMT is grouped into type1(CMT1),where demyelination and loss of nerve conduction velocity occur,type 2(CMT2),where motor and sensory axons degenerate without loss of myelination/nerve conduction velocity,and intermediate CMT,where both demyelination and axon loss present alongside intermediate nerve condu ction velocities.
基金supported by grants from the National Science and Technology Council(NSTC),Taiwan(NSTC 114-2320-B-037-020-MY3,113-2320-B-037-023,and 112-2320-B-037-012 granted to M.K.,113-2321-B-255-001,113-2321-B-182-003,112-2321-B-182-003,112-2321-B-255-001,111-2320-B-255-006-MY3,and 111-2321-B-255-001 granted to T.L.H.)Kaohsiung Medical University Research Foundation[KMU-Q113011 awarded to M.K.and KMU-M114020 awarded to B.H.C.]NSYSU-KMU joint research project(NSYSU-KMU-114-P16)awarded to M.K.
文摘The sustainable sourcing of novel bioactive compounds from natural sources is crucial to the success of the pharmaceutical,food,and cosmetics industries.Iris bucharica Foster(syn.Juno bucharica(Foster)Vved.)is a promising source of novel bioactive molecules,particularly phenolic compounds,which are renowned for their antioxidant properties.In this study,we developed a reliable HPLC-UV-DAD method to identify and quantify phenolic compounds in the leaves and bulbs of I.bucharica,establishing the first set of quality control markers for this species.A total of 21 phenolic compounds were identified in the leaves,with flavonoids isoorientin,guaijaverin,hyperoside,and cosmosiin,the isoflavonoid biochanin A,and the simple phenolic ferulic acid being the most prominent.In comparison,14 compounds were identified in the bulbs,primarily isoflavonoids,including tectoridin and germanaism B,and flavonoid apigenin.The leaves extracts exhibited significant antioxidant activity,whereas the anti-allergic and anti-inflammatory effects were mild.These findings highlight I.bucharica as a sustainable source of bioactive compounds with potential industrial applications.However,further studies are needed to evaluate bioavailability and in vivo efficacy,as well as to optimise extraction methods to realize its industrial potential fully.
文摘Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the case of a 65-year-old man presenting with rectorrhagia and anal pain, initially diagnosed as hemorrhoidal disease. Subsequent proctological examination revealed an ulcerating-bourging tumor, confirmed histologically as an anorectal melanoma. After a normal extension workup, an abdominoperineal amputation was performed. Anorectal melanoma is a pathology with a poor prognosis, requiring early diagnosis to improve chances of survival.
文摘Against the backdrop of increasingly prominent global energy shortages and environmental issues,the development of efficient energy conversion and storage technologies has become crucial.Zero-dimensional(0D)metal oxide composites exhibit significant application value in the field of energy chemistry due to their unique properties,such as quantum size effect and high specific surface area.From a broad perspective,this paper reviews the main synthesis methods of these composites,including sol-gel method,hydrothermal/solvothermal method,precipitation method,and template method,while analyzing the characteristics of each method.It further discusses their applications in photocatalytic hydrogen production,fuel cells,lithium-ion batteries,and supercapacitors.Additionally,the current challenges,such as material dispersibility and interface bonding,are pointed out,and future development directions are prospected,aiming to provide references for related research.
基金supported by the National Natural Science Foundation of China(82030037)the Translational and Application Project of Brain-inspired and Network Neuroscience on Brain Disorders(11000023T000002036286).
文摘Epilepsy affects over 50 million people worldwide.Drug-resistant epilepsy(DRE)accounts for up to a third of these cases,and neuro-inflammation is thought to play a role in such cases.Despite being a long-debated issue in the field of DRE,the mechanisms underlying neuroinflammation have yet to be fully elucidated.The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics.Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes,such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis.The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems.We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application.We hope to provide an insightful overview to advance the quest for better DRE treatments.
基金Financial support from the Engineering and Physical Sciences Research Council grant EP/V034723/1(RiFTMaP)is gratefully acknowledged.
文摘In the pharmaceutical industry,model-based prediction is a crucial stage in process development that allows pharmaceutical companies to simulate different scenarios toward improving process efficiency,reducing costs,and enhancing product quality.Nevertheless,ensuring the quality of formulated pharmaceutical products through the management of raw material variations has always been a challenging task.In this work,data-driven chance-constrained recurrent neural networks(CCRNNs)are developed to address the issue arising from raw material uncertainty.Our goal is to explore how,by proactively incorporating uncertainty into the model training process,more accurate predictions and enhanced robustness can be realized.The proposed approach is tested on a fluid bed dryer(FBD)from a continuous pharmaceutical manufacturing pilot plant.The results demonstrate that CCRNN models offer more robust and accurate predictions for the critical quality attribute(CQA)-in this case,moisture content-when material variations occur,compared with conventional recurrent neural network-based models.
文摘The first liver transplantation(LT)in humans was performed by Thomas Starzl on March 1,1963[1,2](Fig.1).During the period 1963-1983,this challenging procedure was performed in four centers only,one in the USA and three in Western Europe:Denver,Cambridge,Hannover and Groningen.Their collected experience including only 540 cases(meaning 27(!)cases yearly)was the basis of the 1983 National Institutes of Health(NIH)development consensus conference leading to the conclusion that LT could become“a promising alternative to the current therapy in the management of the late phase of several forms of serious liver disease…candidates are those who exhausted alternative medical and surgical treatments…and are approaching the terminal phase of their illness”.Patients presenting liver tumors and inherited,liver based,metabolic diseases could also be considered for LT[3].This conference put forward ten absolute and five relative contraindications restricting thereby the access to LT to a minority of very well selected liver diseased patients.
基金supported by Health Education England/National Institute for Health Research(NIHR)(Clinical Lectureship CL-2020-18-009 for C.H.).
文摘Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging therapeutic opportunity of Janus kinase inhibitor(JAKi)in the role of systemic inflammation in AMD pathogenesis(2).This study offers a real-world examination of the relationship between JAKi and AMD,comparing the incidence of AMD in patients treated with JAKi and those receiving other immunotherapies for existing autoimmune diseases.
基金funded by the Gansu Provincial Science and Technology Program in China(Grant No.22ZD6FA005)。
文摘The Gannan Yellow River source area(YRSA)is a typical ecological fragile region.Assessing the temporal and spatial patterns of resource and environmental carrying capacity(RECC)is crucial for both ecological security and sustainable development of the Yellow River Basin and the YRSA.Based on RECC theory,this study developed a novel index system focused on human-livestock-grassland relationships to accurately capture resource and environmental carrying characteristics in pastoral regions.By establishing region-specific evaluation thresholds and using a comprehensive index approach,we analyzed spatial and temporal patterns of resource carrying capacity(RCC),environmental carrying capacity(ECC),and resource and environmental carrying capacity(RECC)in the Gannan region from 2005 to 2020.The results indicate that:1)The RECC followed an increasing–decreasing–increasing trajectory from 2005 to 2020,with values ranging from 0.30 to 0.69.The RECC in pastoral areas was not only higher but also exhibited greater variability compared to that in agricultural areas.2)The RCC remained at a low level,with values between 0.06 to 0.098.The index of water consumption per ten thousand Yuan of GDP increased significantly,suggesting that improvements in water use efficiency contributed to the enhancement of RCC.3)The ECC increased notably,shifting from the middle to a very high level,with values ranging from 0.233 to 0.611.ECC emerged as a key determinant of RECC,exhibiting a temporal trend closely aligned with that of RECC.Changes in ECC were primarily driven by factors such as overgrazing rates,the extent of grassland rodent control,and the area of grassland for reseeding and improvement.Based on these findings,future priorities should include the adoption of efficient water-saving irrigation technologies,the promotion of rotational grazing practices,and the optimization of land management strategies.
文摘BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but data from cohort studies are scarce.AIM To investigate the association between insulin and pathological LFT,liver disease,and cirrhosis in a populationbased retrospective cohort study.METHODS Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used.LFT were obtained at two time points 8 years to 24 years after baseline.Liver disease diagnoses were obtained from nationwide registries.The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.RESULTS Total follow-up was 54054 person-years for women and 27556 person-years for men.Insulin levels were positively correlated with elevated LFT during follow-up,whereas physical activity and coffee consumption were negatively correlated.Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease,adjusted hazard ratio(aHR)of 4.3(95%CI:1.6-14.6)and cirrhosis(aHR=4.8,95%CI:1.6-14.6).CONCLUSION This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease.The results support the concept of metabolic dysfunction associated liver disease.
基金funded by the following grants and contracts:Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38020400 to S.W.)the National Natural Science Foundation of China(32325013 to S.W.,32271186 to J.T.,31900408 to M.Z.)+5 种基金the CAS Project for Young Scientists in Basic Research(YSBR-077 to S.W.)Shanghai Science and Technology Commission Excellent Academic Leaders Program(22XD1424700 to S.W.)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-066 to L.J.and J.W.)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01 to L.J.and S.W.)the National Science and Technology Basic Research Project(2015FY111700 to L.J.)the 111 Project(B13016 to L.J.).
文摘Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained largely unknown.In this study,we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study(GWAS),including 9674 East Asians and 10,115 Europeans,quantitatively assessing 78 facial traits using 3D facial images.We identify 71 genomic loci associated with facial features,including 21 novel loci.We develop a facial polygenic score(FPS)that enables the prediction of facial features based on genetic information.Interestingly,the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features.Furthermore,we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records.Our results suggest that Neanderthals and Denisovans likely share similar facial features,such as a wider but shorter nose and a wider endocanthion distance.The decreased mouth width is characterized specifically in Denisovans.The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.
