Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds bas...Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.展开更多
Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,K...Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.展开更多
Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely over...Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely overlooked in the past because it is generally less impaired in the early stages of PD than in Alzheimer's disease.展开更多
In recent years,skeleton-based action recognition has made great achievements in Computer Vision.A graph convolutional network(GCN)is effective for action recognition,modelling the human skeleton as a spatio-temporal ...In recent years,skeleton-based action recognition has made great achievements in Computer Vision.A graph convolutional network(GCN)is effective for action recognition,modelling the human skeleton as a spatio-temporal graph.Most GCNs define the graph topology by physical relations of the human joints.However,this predefined graph ignores the spatial relationship between non-adjacent joint pairs in special actions and the behavior dependence between joint pairs,resulting in a low recognition rate for specific actions with implicit correlation between joint pairs.In addition,existing methods ignore the trend correlation between adjacent frames within an action and context clues,leading to erroneous action recognition with similar poses.Therefore,this study proposes a learnable GCN based on behavior dependence,which considers implicit joint correlation by constructing a dynamic learnable graph with extraction of specific behavior dependence of joint pairs.By using the weight relationship between the joint pairs,an adaptive model is constructed.It also designs a self-attention module to obtain their inter-frame topological relationship for exploring the context of actions.Combining the shared topology and the multi-head self-attention map,the module obtains the context-based clue topology to update the dynamic graph convolution,achieving accurate recognition of different actions with similar poses.Detailed experiments on public datasets demonstrate that the proposed method achieves better results and realizes higher quality representation of actions under various evaluation protocols compared to state-of-the-art methods.展开更多
Radiation damage produced in 4H-SiC by electrons of different doses is presented by using multiple characterization techniques. Raman spectra results indicate that SiC crystal structures are essentially impervious to ...Radiation damage produced in 4H-SiC by electrons of different doses is presented by using multiple characterization techniques. Raman spectra results indicate that SiC crystal structures are essentially impervious to 10 Me V electron irradiation with doses up to 3000 kGy. However, irradiation indeed leads to the generation of various defects, which are evaluated through photoluminescence(PL) and deep level transient spectroscopy(DLTS). The PL spectra feature a prominent broad band centered at 500 nm, accompanied by several smaller peaks ranging from 660 to 808 nm. The intensity of each PL peak demonstrates a linear correlation with the irradiation dose, indicating a proportional increase in defect concentration during irradiation. The DLTS spectra reveal several thermally unstable and stable defects that exhibit similarities at low irradiation doses.Notably, after irradiating at the higher dose of 1000 kGy, a new stable defect labeled as R_(2)(Ec-0.51 eV) appeared after annealing at 800 K. Furthermore, the impact of irradiation-induced defects on SiC junction barrier Schottky diodes is discussed. It is observed that high-dose electron irradiation converts SiC n-epilayers to semi-insulating layers. However, subjecting the samples to a temperature of only 800 K results in a significant reduction in resistance due to the annealing out of unstable defects.展开更多
Long-term time series forecasting stands as a crucial research domain within the realm of automated machine learning(AutoML).At present,forecasting,whether rooted in machine learning or statistical learning,typically ...Long-term time series forecasting stands as a crucial research domain within the realm of automated machine learning(AutoML).At present,forecasting,whether rooted in machine learning or statistical learning,typically relies on expert input and necessitates substantial manual involvement.This manual effort spans model development,feature engineering,hyper-parameter tuning,and the intricate construction of time series models.The complexity of these tasks renders complete automation unfeasible,as they inherently demand human intervention at multiple junctures.To surmount these challenges,this article proposes leveraging Long Short-Term Memory,which is the variant of Recurrent Neural Networks,harnessing memory cells and gating mechanisms to facilitate long-term time series prediction.However,forecasting accuracy by particular neural network and traditional models can degrade significantly,when addressing long-term time-series tasks.Therefore,our research demonstrates that this innovative approach outperforms the traditional Autoregressive Integrated Moving Average(ARIMA)method in forecasting long-term univariate time series.ARIMA is a high-quality and competitive model in time series prediction,and yet it requires significant preprocessing efforts.Using multiple accuracy metrics,we have evaluated both ARIMA and proposed method on the simulated time-series data and real data in both short and long term.Furthermore,our findings indicate its superiority over alternative network architectures,including Fully Connected Neural Networks,Convolutional Neural Networks,and Nonpooling Convolutional Neural Networks.Our AutoML approach enables non-professional to attain highly accurate and effective time series forecasting,and can be widely applied to various domains,particularly in business and finance.展开更多
AIM:To quantitatively assess the changes in mean vascular tortuosity(mVT)and mean vascular width(mVW)around the optic disc and their correlation with gestational age(GA)and birth weight(BW)in premature infants without...AIM:To quantitatively assess the changes in mean vascular tortuosity(mVT)and mean vascular width(mVW)around the optic disc and their correlation with gestational age(GA)and birth weight(BW)in premature infants without retinopathy of prematurity(ROP).METHODS:A single-center retrospective study included a total of 133(133 eyes)premature infants[mean corrected gestational age(CGA)43.6wk]without ROP as the premature group and 130(130 eyes)CGA-matched fullterm infants as the control group.The peripapillary mVT and mVW were quantitatively measured using computerassisted techniques.RESULTS:Premature infants had significantly higher mVT(P=0.0032)and lower mVW(P=0.0086)by 2.68(10^(4) cm^(-3))and 1.85μm,respectively.Subgroup analysis with GA showed significant differences(P=0.0244)in mVT between the early preterm and middle to late preterm groups,but the differences between mVW were not significant(P=0.6652).The results of the multiple linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA(P=0.0211 and P=0.0006,respectively).For each day increase in GA at birth,mVT decreased by 0.1281(10^(4) cm^(-3))and for each 1 g increase in BW,mVT decreased by 0.006(10^(4) cm^(-3)).However,GA(P=0.9402)and BW(P=0.7275)were not significantly correlated with mVW.CONCLUSION:Preterm birth significantly affects the peripapillary vascular parameters that indicate higher mVT and narrower mVW in premature infants without ROP.Alterations in these parameters may provide new insights into the pathogenesis of ocular vascular disease.展开更多
Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectivenes...Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.展开更多
Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of...Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.展开更多
One new Daphniphyllum alkaloid,daphnioldhanol A(1),together with three known ones,were isolated from the stem part of Daphniphyllum angustifolium Hutch.Their structures were elucidated by spectroscopic methods and com...One new Daphniphyllum alkaloid,daphnioldhanol A(1),together with three known ones,were isolated from the stem part of Daphniphyllum angustifolium Hutch.Their structures were elucidated by spectroscopic methods and comparing with the literature data.Compound 2 is a new natural product,but known by synthesis as a racemate.Compound 1 exhibited week cytotoxic activity against Hela cell line with IC50 of 31.9μM.展开更多
Background Cognitive-behavioural therapy for insomnia(CBTi)is the first-line treatment for those with this sleep disorder.However,depressive and anxiety symptoms often co-occur with acute insomnia,which may affect the...Background Cognitive-behavioural therapy for insomnia(CBTi)is the first-line treatment for those with this sleep disorder.However,depressive and anxiety symptoms often co-occur with acute insomnia,which may affect the effectiveness of CBTitreatment.Aims This study aimed to determine the impact of depressive and anxiety symptoms on the efficacy of CBTi in treating acute insomnia.Methods A single-arm clinical trial was conducted among individuals who have acute insomnia.Participants underwent self-guided CBTi for 1-week.Their insomnia,depressive symptoms and anxiety symptoms were evaluated using the Insomnia Severity Index and the Hospital Anxiety and Depression Scale at baseline,post-treatment and 3-month follow-up.Repeated measures analysis of variance was used to assess the effectiveness of CBTi in treating insomnia,depressive symptoms and anxiety symptoms.A multivariate Cox regression model was used to determine the impact of depressive and anxiety symptoms on insomnia.Results The study found significant reductions in insomnia,depressive symptoms and anxiety symptoms at both post-treatment and 3-month follow-up(F=17.45,p<0.001;F=36.37,p=0.001;and F=81.51,p<0.001,respectively).The duration of CBTi treatment had a positive impact on insomnia recovery(hazard ratio(HR)=0.94,p=0.018).However,baseline depressive symptoms(HR=1.83,p=0.004)and baseline anxiety symptoms(HR=1.99,p=0.001)had significant negative effects on insomnia recovery.Conclusions The study showed that a 1-week self-guided CBTi treatment is effective in treating acute insomnia and comorbid depressive and anxiety symptoms.However,baseline depressive and anxiety symptoms negatively impact treatment effectiveness.Therefore,clinicians should assess for depressive and anxiety symptoms before treating acute insomnia with monotherapy CBTi.展开更多
Background Previous investigations into the effect of dietary forage on calf performance have been inconsistent,and there is a paucity of information exploring the effect of age on the growth performance and ruminatio...Background Previous investigations into the effect of dietary forage on calf performance have been inconsistent,and there is a paucity of information exploring the effect of age on the growth performance and rumination of calves.Eighty-four female Holstein calves(41.5±4.2 kg)were enrolled at birth,a subset of the calves were fed calf starter only(CON,n=21)while the rest(n=63)were classified into three treatment groups:the early(EHAY,n=26,5.1±0.8 d),the middle(MHAY,n=21,7.9±0.8 d)and the late(LHAY,n=16,12.1±1.4 d)hay consumers.The short-term effect of the age at first forage consump-tion(AFF)on calves’feed intake was monitored until d 84.In addition,the long-term effects of AFF on body weight,structural growth and rumination behavior were recorded until d 196.Rumen samples were collected on d 1,7,35,84 and 196 to ana-lyze the rumen fermentation,while fecal samples were collected from d 78 to 84 to estimate digestibility parameters.Results Treatment had no effect on feed intake.While,the EHAY calves tended to have lower BW and ADG compared to LHAY and CON calves.Several total-tract apparent digestibility parameters and digestible nutrients intake were significantly lower in EHAY calves compared with CON and LHAY calves.Calves in the EHAY group tended to begin ruminating ealier,while CON calves were the latest(12.3 vs.15.5 days of age).A treatment and time interaction was present for rumination time due to greater rumination in calves consuming hay compared to CON calves in week 10 to 12,the differences in rumination disappeared afterwards,no long-lasting significant differences in the rumina-tion and rumen fermentation parameters were found between treatments.Conclusions In conclusion,this study showed that hay consumption earlier in life(in the first week,around 5 days of life)could negatively affect the growth of the calf in the short and long term.Compared to consuming hay from the second week(around 12 days of life)or feeding concentrate only without hay,starting to consume hay from the first week could compromise nutrient digestibility and digestible nutrient intake independent of developing rumination behaviour and rumen fermentation.展开更多
Liver fibrosis accompanies the progression of chronic liver diseases independent of etiologies,such as hepatitis viral infection,alcohol consumption,and metabolicassociated fatty liver disease.It is commonly associate...Liver fibrosis accompanies the progression of chronic liver diseases independent of etiologies,such as hepatitis viral infection,alcohol consumption,and metabolicassociated fatty liver disease.It is commonly associated with liver injury,inflammation,and cell death.Liver fibrosis is characterized by abnormal accumulation of extracellular matrix components that are expressed by liver myofibroblasts such as collagens and alpha-smooth actin proteins.Activated hepatic stellate cells contribute to the major population of myofibroblasts.Many treatments for liver fibrosis have been investigated in clinical trials,including dietary supplementation(e.g.,vitamin C),biological treatment(e.g.,simtuzumab),drug(e.g.,pegbelfermin and natural herbs),genetic regulation(e.g.,non-coding RNAs),and transplantation of stem cells(e.g.,hematopoietic stem cells).However,none of these treatments has been approved by Food and Drug Administration.The treatment efficacy can be evaluated by histological staining methods,imaging methods,and serum biomarkers,as well as fibrosis scoring systems,such as fibrosis-4 index,aspartate aminotransferase to platelet ratio,and non-alcoholic fatty liver disease fibrosis score.Furthermore,the reverse of liver fibrosis is slowly and frequently impossible for advanced fibrosis or cirrhosis.To avoid the lifethreatening stage of liver fibrosis,anti-fibrotic treatments,especially for combined behavior prevention,biological treatment,drugs or herb medicines,and dietary regulation are needed.This review summarizes the past studies and current and future treatments for liver fibrosis.展开更多
The key to construct high-energy supercapacitors is to maximize the capacitance of electrode and the voltage of the device. Realizing this purpose by utilizing sustainable and low-cost resources is still a big challen...The key to construct high-energy supercapacitors is to maximize the capacitance of electrode and the voltage of the device. Realizing this purpose by utilizing sustainable and low-cost resources is still a big challenge. Herein, N, B co-doped carbon nanosheets are obtained through the proposed dual-template assisted approach by using methyl cellulose as the precursor. Due to the synergistic effects form the high surface area with the hierarchical porous structure, N/B dual doping, and a high degree of graphitization, the resultant carbon electrode exhibits a high capacitance of 572 F g^(-1)at 0.5 A g^(-1)and retains 281 F g^(-1)at 50 A g^(-1)in an acidic electrolyte. Furthermore, the symmetric device assembled using bacterial cellulose-based gel polymer electrolyte can deliver high energy density of 43 W h kg^(-1)and excellent cyclability with 97.8% capacity retention after 20 000 cycles in “water in salt” electrolyte. This work successfully realizes the fabrication of high-performance allcellulose-based quasi-solid-state supercapacitors, which brings a cost-effective insight into jointly designing electrodes and electrolytes for supporting highly efficient energy storage.展开更多
SINCE the 18th century,fossil energy in the form of coal,oil,and natural gas has been used on a large scale.These fossil fuels have provided a vast amount of energy,such as electricity,heat,and gas,for industrial prod...SINCE the 18th century,fossil energy in the form of coal,oil,and natural gas has been used on a large scale.These fossil fuels have provided a vast amount of energy,such as electricity,heat,and gas,for industrial production and have been a major contributor to the development of the world economy[1].展开更多
BACKGROUND Primary seminal vesicle adenocarcinoma is a rare malignancy that is difficult to diagnose.CASE SUMMARY A 54-year-old man with an 18-year history of a seminal vesicle cyst presented with worsening hematosper...BACKGROUND Primary seminal vesicle adenocarcinoma is a rare malignancy that is difficult to diagnose.CASE SUMMARY A 54-year-old man with an 18-year history of a seminal vesicle cyst presented with worsening hematospermia that had persisted for one month.Dynamic contrast-enhanced computed tomography and pelvic magnetic resonance imaging indicated a mass with a cystic-solid component.Robot-assisted seminal vesicle tumor resection was performed,and primary seminal vesicle adenocarcinoma was confirmed pathologically.The patient received pelvic radiotherapy for six weeks,and to date,no evidence of recurrence has been found.CONCLUSION Seminal vesicle cysts should be monitored long-term.Seminal vesicle adenocarcinoma presents with non-specific symptoms and can be diagnosed by immunohistochemistry.展开更多
基金supported by the National Natural Science Foundation of China(52003113,31900950,82102334,82002313,82072444)the National Key Research&Development Program of China(2018YFC2001502,2018YFB1105705)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A1515010745,2020A1515110356,2023A1515011986)the Shenzhen Fundamental Research Program(JCYJ20190808120405672)the Key Program of the National Natural Science Foundation of Zhejiang Province(LZ22C100001)the Natural Science Foundation of Shanghai(20ZR1469800)the Integration Innovation Fund of Shanghai Jiao Tong University(2021JCPT03),the Science and Technology Projects of Guangzhou City(202102020359)the Zigong Key Science and Technology Plan(2022ZCNKY07).SXC thanks the financial support under the Startup Grant of the University of Chinese Academy of Sciences(WIUCASQD2021026).HW thanks the Futian Healthcare Research Project(FTWS2022013)the financial support of China Postdoctoral Science Foundation(2021TQ0118).SL thanks the financial support of China Postdoctoral Science Foundation(2022M721490).
文摘Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.
基金supported by the National Natural Science Foundation of China,No. 81771228Shanghai Association of Science and Technology,Nos. 22WZ2501700 and 23WZ2504500 (all to LY)
文摘Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.
基金supported by the STI 2030-Major Projects,No.2021ZD0200500the Natural Science Foundation of Shanghai,No.21ZR1419700(both to SL)。
文摘Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely overlooked in the past because it is generally less impaired in the early stages of PD than in Alzheimer's disease.
基金supported in part by the 2023 Key Supported Project of the 14th Five Year Plan for Education and Science in Hunan Province with No.ND230795.
文摘In recent years,skeleton-based action recognition has made great achievements in Computer Vision.A graph convolutional network(GCN)is effective for action recognition,modelling the human skeleton as a spatio-temporal graph.Most GCNs define the graph topology by physical relations of the human joints.However,this predefined graph ignores the spatial relationship between non-adjacent joint pairs in special actions and the behavior dependence between joint pairs,resulting in a low recognition rate for specific actions with implicit correlation between joint pairs.In addition,existing methods ignore the trend correlation between adjacent frames within an action and context clues,leading to erroneous action recognition with similar poses.Therefore,this study proposes a learnable GCN based on behavior dependence,which considers implicit joint correlation by constructing a dynamic learnable graph with extraction of specific behavior dependence of joint pairs.By using the weight relationship between the joint pairs,an adaptive model is constructed.It also designs a self-attention module to obtain their inter-frame topological relationship for exploring the context of actions.Combining the shared topology and the multi-head self-attention map,the module obtains the context-based clue topology to update the dynamic graph convolution,achieving accurate recognition of different actions with similar poses.Detailed experiments on public datasets demonstrate that the proposed method achieves better results and realizes higher quality representation of actions under various evaluation protocols compared to state-of-the-art methods.
基金supported by the Open Fund(2022E10015)of the Key Laboratory of Power Semiconductor Materials and Devices of Zhejiang Province&Institute of Advanced Semiconductors,ZJU-Hangzhou Global Scientific and Technological Innovation Center。
文摘Radiation damage produced in 4H-SiC by electrons of different doses is presented by using multiple characterization techniques. Raman spectra results indicate that SiC crystal structures are essentially impervious to 10 Me V electron irradiation with doses up to 3000 kGy. However, irradiation indeed leads to the generation of various defects, which are evaluated through photoluminescence(PL) and deep level transient spectroscopy(DLTS). The PL spectra feature a prominent broad band centered at 500 nm, accompanied by several smaller peaks ranging from 660 to 808 nm. The intensity of each PL peak demonstrates a linear correlation with the irradiation dose, indicating a proportional increase in defect concentration during irradiation. The DLTS spectra reveal several thermally unstable and stable defects that exhibit similarities at low irradiation doses.Notably, after irradiating at the higher dose of 1000 kGy, a new stable defect labeled as R_(2)(Ec-0.51 eV) appeared after annealing at 800 K. Furthermore, the impact of irradiation-induced defects on SiC junction barrier Schottky diodes is discussed. It is observed that high-dose electron irradiation converts SiC n-epilayers to semi-insulating layers. However, subjecting the samples to a temperature of only 800 K results in a significant reduction in resistance due to the annealing out of unstable defects.
文摘Long-term time series forecasting stands as a crucial research domain within the realm of automated machine learning(AutoML).At present,forecasting,whether rooted in machine learning or statistical learning,typically relies on expert input and necessitates substantial manual involvement.This manual effort spans model development,feature engineering,hyper-parameter tuning,and the intricate construction of time series models.The complexity of these tasks renders complete automation unfeasible,as they inherently demand human intervention at multiple junctures.To surmount these challenges,this article proposes leveraging Long Short-Term Memory,which is the variant of Recurrent Neural Networks,harnessing memory cells and gating mechanisms to facilitate long-term time series prediction.However,forecasting accuracy by particular neural network and traditional models can degrade significantly,when addressing long-term time-series tasks.Therefore,our research demonstrates that this innovative approach outperforms the traditional Autoregressive Integrated Moving Average(ARIMA)method in forecasting long-term univariate time series.ARIMA is a high-quality and competitive model in time series prediction,and yet it requires significant preprocessing efforts.Using multiple accuracy metrics,we have evaluated both ARIMA and proposed method on the simulated time-series data and real data in both short and long term.Furthermore,our findings indicate its superiority over alternative network architectures,including Fully Connected Neural Networks,Convolutional Neural Networks,and Nonpooling Convolutional Neural Networks.Our AutoML approach enables non-professional to attain highly accurate and effective time series forecasting,and can be widely applied to various domains,particularly in business and finance.
基金Supported by the Fundamental Research Funds for the Central Universities (No.WK2100000045)the National Natural Science Foundation of China (No.U19B2044)+1 种基金Hefei Health Care Commission 2022 Applied Medical Research Project (No.Hwk2022yb028)Zhejiang Lab Open Research Project (No.K2022QA0AB04).
文摘AIM:To quantitatively assess the changes in mean vascular tortuosity(mVT)and mean vascular width(mVW)around the optic disc and their correlation with gestational age(GA)and birth weight(BW)in premature infants without retinopathy of prematurity(ROP).METHODS:A single-center retrospective study included a total of 133(133 eyes)premature infants[mean corrected gestational age(CGA)43.6wk]without ROP as the premature group and 130(130 eyes)CGA-matched fullterm infants as the control group.The peripapillary mVT and mVW were quantitatively measured using computerassisted techniques.RESULTS:Premature infants had significantly higher mVT(P=0.0032)and lower mVW(P=0.0086)by 2.68(10^(4) cm^(-3))and 1.85μm,respectively.Subgroup analysis with GA showed significant differences(P=0.0244)in mVT between the early preterm and middle to late preterm groups,but the differences between mVW were not significant(P=0.6652).The results of the multiple linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA(P=0.0211 and P=0.0006,respectively).For each day increase in GA at birth,mVT decreased by 0.1281(10^(4) cm^(-3))and for each 1 g increase in BW,mVT decreased by 0.006(10^(4) cm^(-3)).However,GA(P=0.9402)and BW(P=0.7275)were not significantly correlated with mVW.CONCLUSION:Preterm birth significantly affects the peripapillary vascular parameters that indicate higher mVT and narrower mVW in premature infants without ROP.Alterations in these parameters may provide new insights into the pathogenesis of ocular vascular disease.
基金funded by the Science and Technology Plan of Inner Mongolia Autonomous Region(no.2022YFSH0097)the Medical Research Advancement Fund Project(no.TB212014).
文摘Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.
基金Funded by the Health Science and Technology Program of Inner Mongolia Autonomous Region(no.202201061)Supported by the Joint Project of theMillion Science and Technology Initiatives of Inner Mongolia Medical University(no.YKD2020KJBW(LH)057).
文摘Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.
基金the National Natural Science Foundation of China(No.31770392 to YTD)the Science and Technology Program of Yunnan Province(2018ZF013 to YTD)The authors are grateful to the analytical group of the Laboratory of Phytochemistry,Kunming Institute of Botany,Chinese Academy of Sciences,for recorded spectra.
文摘One new Daphniphyllum alkaloid,daphnioldhanol A(1),together with three known ones,were isolated from the stem part of Daphniphyllum angustifolium Hutch.Their structures were elucidated by spectroscopic methods and comparing with the literature data.Compound 2 is a new natural product,but known by synthesis as a racemate.Compound 1 exhibited week cytotoxic activity against Hela cell line with IC50 of 31.9μM.
基金supported by the National Natural Science Foundation of China (12132016, 11972032, 12172349)USTC Research Funds of the Double First-Class Initiative (YD2480002004)+1 种基金the Fundamental Research Funds for the Central Universities (WK2480000007)USTC Center for Micro- and Nanoscale Research and Fabrication。
基金supported by the National Key R&D Program of China(BZ:grant number 2021YFC2501500)the Basic and Applied Basic Research Project of Guangzhou Basic Research Program(CZ:grant number 202201011502)+2 种基金the National Natural Science Foundation of China(BZ:grant number 82271525)Nanfang Hospital Clinical Research Project of Southern Medical University(BZ:grant number 2021CR009)the Education Research Projects of Nanfang Hospital(BZ:grant number 21NJ-ZDPY01).
文摘Background Cognitive-behavioural therapy for insomnia(CBTi)is the first-line treatment for those with this sleep disorder.However,depressive and anxiety symptoms often co-occur with acute insomnia,which may affect the effectiveness of CBTitreatment.Aims This study aimed to determine the impact of depressive and anxiety symptoms on the efficacy of CBTi in treating acute insomnia.Methods A single-arm clinical trial was conducted among individuals who have acute insomnia.Participants underwent self-guided CBTi for 1-week.Their insomnia,depressive symptoms and anxiety symptoms were evaluated using the Insomnia Severity Index and the Hospital Anxiety and Depression Scale at baseline,post-treatment and 3-month follow-up.Repeated measures analysis of variance was used to assess the effectiveness of CBTi in treating insomnia,depressive symptoms and anxiety symptoms.A multivariate Cox regression model was used to determine the impact of depressive and anxiety symptoms on insomnia.Results The study found significant reductions in insomnia,depressive symptoms and anxiety symptoms at both post-treatment and 3-month follow-up(F=17.45,p<0.001;F=36.37,p=0.001;and F=81.51,p<0.001,respectively).The duration of CBTi treatment had a positive impact on insomnia recovery(hazard ratio(HR)=0.94,p=0.018).However,baseline depressive symptoms(HR=1.83,p=0.004)and baseline anxiety symptoms(HR=1.99,p=0.001)had significant negative effects on insomnia recovery.Conclusions The study showed that a 1-week self-guided CBTi treatment is effective in treating acute insomnia and comorbid depressive and anxiety symptoms.However,baseline depressive and anxiety symptoms negatively impact treatment effectiveness.Therefore,clinicians should assess for depressive and anxiety symptoms before treating acute insomnia with monotherapy CBTi.
基金supported by the National Key Research and Development Program(No.2021YFF1000703,NKPs)funded by the Ministry of Science and Technology of the People’s Republic of China.
文摘Background Previous investigations into the effect of dietary forage on calf performance have been inconsistent,and there is a paucity of information exploring the effect of age on the growth performance and rumination of calves.Eighty-four female Holstein calves(41.5±4.2 kg)were enrolled at birth,a subset of the calves were fed calf starter only(CON,n=21)while the rest(n=63)were classified into three treatment groups:the early(EHAY,n=26,5.1±0.8 d),the middle(MHAY,n=21,7.9±0.8 d)and the late(LHAY,n=16,12.1±1.4 d)hay consumers.The short-term effect of the age at first forage consump-tion(AFF)on calves’feed intake was monitored until d 84.In addition,the long-term effects of AFF on body weight,structural growth and rumination behavior were recorded until d 196.Rumen samples were collected on d 1,7,35,84 and 196 to ana-lyze the rumen fermentation,while fecal samples were collected from d 78 to 84 to estimate digestibility parameters.Results Treatment had no effect on feed intake.While,the EHAY calves tended to have lower BW and ADG compared to LHAY and CON calves.Several total-tract apparent digestibility parameters and digestible nutrients intake were significantly lower in EHAY calves compared with CON and LHAY calves.Calves in the EHAY group tended to begin ruminating ealier,while CON calves were the latest(12.3 vs.15.5 days of age).A treatment and time interaction was present for rumination time due to greater rumination in calves consuming hay compared to CON calves in week 10 to 12,the differences in rumination disappeared afterwards,no long-lasting significant differences in the rumina-tion and rumen fermentation parameters were found between treatments.Conclusions In conclusion,this study showed that hay consumption earlier in life(in the first week,around 5 days of life)could negatively affect the growth of the calf in the short and long term.Compared to consuming hay from the second week(around 12 days of life)or feeding concentrate only without hay,starting to consume hay from the first week could compromise nutrient digestibility and digestible nutrient intake independent of developing rumination behaviour and rumen fermentation.
文摘Liver fibrosis accompanies the progression of chronic liver diseases independent of etiologies,such as hepatitis viral infection,alcohol consumption,and metabolicassociated fatty liver disease.It is commonly associated with liver injury,inflammation,and cell death.Liver fibrosis is characterized by abnormal accumulation of extracellular matrix components that are expressed by liver myofibroblasts such as collagens and alpha-smooth actin proteins.Activated hepatic stellate cells contribute to the major population of myofibroblasts.Many treatments for liver fibrosis have been investigated in clinical trials,including dietary supplementation(e.g.,vitamin C),biological treatment(e.g.,simtuzumab),drug(e.g.,pegbelfermin and natural herbs),genetic regulation(e.g.,non-coding RNAs),and transplantation of stem cells(e.g.,hematopoietic stem cells).However,none of these treatments has been approved by Food and Drug Administration.The treatment efficacy can be evaluated by histological staining methods,imaging methods,and serum biomarkers,as well as fibrosis scoring systems,such as fibrosis-4 index,aspartate aminotransferase to platelet ratio,and non-alcoholic fatty liver disease fibrosis score.Furthermore,the reverse of liver fibrosis is slowly and frequently impossible for advanced fibrosis or cirrhosis.To avoid the lifethreatening stage of liver fibrosis,anti-fibrotic treatments,especially for combined behavior prevention,biological treatment,drugs or herb medicines,and dietary regulation are needed.This review summarizes the past studies and current and future treatments for liver fibrosis.
基金supported by the National Natural Science Foundation of China (No.22179123 and 21471139)the Shandong Provincial Natural Science Foundation,China (ZR2020ME038)+2 种基金the Fundamental Research Funds for the Central Universities (No.201941010)the Shandong Provincial Key R&D Plan and the Public Welfare Special Program,China (2019GGX102038)the Qingdao City Programs for Science and Technology Plan Projects (19-6-2-77-cg)。
文摘The key to construct high-energy supercapacitors is to maximize the capacitance of electrode and the voltage of the device. Realizing this purpose by utilizing sustainable and low-cost resources is still a big challenge. Herein, N, B co-doped carbon nanosheets are obtained through the proposed dual-template assisted approach by using methyl cellulose as the precursor. Due to the synergistic effects form the high surface area with the hierarchical porous structure, N/B dual doping, and a high degree of graphitization, the resultant carbon electrode exhibits a high capacitance of 572 F g^(-1)at 0.5 A g^(-1)and retains 281 F g^(-1)at 50 A g^(-1)in an acidic electrolyte. Furthermore, the symmetric device assembled using bacterial cellulose-based gel polymer electrolyte can deliver high energy density of 43 W h kg^(-1)and excellent cyclability with 97.8% capacity retention after 20 000 cycles in “water in salt” electrolyte. This work successfully realizes the fabrication of high-performance allcellulose-based quasi-solid-state supercapacitors, which brings a cost-effective insight into jointly designing electrodes and electrolytes for supporting highly efficient energy storage.
基金supported by the National Natural Science Foundation of China(NSFC)(61821004)。
文摘SINCE the 18th century,fossil energy in the form of coal,oil,and natural gas has been used on a large scale.These fossil fuels have provided a vast amount of energy,such as electricity,heat,and gas,for industrial production and have been a major contributor to the development of the world economy[1].
基金Supported by the Natural Science Foundation of Shandong Province,No.ZR2021MH354。
文摘BACKGROUND Primary seminal vesicle adenocarcinoma is a rare malignancy that is difficult to diagnose.CASE SUMMARY A 54-year-old man with an 18-year history of a seminal vesicle cyst presented with worsening hematospermia that had persisted for one month.Dynamic contrast-enhanced computed tomography and pelvic magnetic resonance imaging indicated a mass with a cystic-solid component.Robot-assisted seminal vesicle tumor resection was performed,and primary seminal vesicle adenocarcinoma was confirmed pathologically.The patient received pelvic radiotherapy for six weeks,and to date,no evidence of recurrence has been found.CONCLUSION Seminal vesicle cysts should be monitored long-term.Seminal vesicle adenocarcinoma presents with non-specific symptoms and can be diagnosed by immunohistochemistry.