Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficie...Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.展开更多
AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcino...AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.展开更多
Background:The universal occurrence of randomly distributed dark holes(i.e.,data pits appearing within the tree crown)in LiDAR-derived canopy height models(CHMs)negatively affects the accuracy of extracted forest inve...Background:The universal occurrence of randomly distributed dark holes(i.e.,data pits appearing within the tree crown)in LiDAR-derived canopy height models(CHMs)negatively affects the accuracy of extracted forest inventory parameters.Methods:We develop an algorithm based on cloth simulation for constructing a pit-free CHM.Results:The proposed algorithm effectively fills data pits of various sizes whilst preserving canopy details.Our pitfree CHMs derived from point clouds at different proportions of data pits are remarkably better than those constructed using other algorithms,as evidenced by the lowest average root mean square error(0.4981 m)between the reference CHMs and the constructed pit-free CHMs.Moreover,our pit-free CHMs show the best performance overall in terms of maximum tree height estimation(average bias=0.9674 m).Conclusion:The proposed algorithm can be adopted when working with different quality LiDAR data and shows high potential in forestry applications.展开更多
The dependence of harmonic emission from a solid on the carrier envelope phase (CEP) is discussed by numerically solving the time-dependent Schr?dinger equation. The harmonic spectra periodically exhibit three distinc...The dependence of harmonic emission from a solid on the carrier envelope phase (CEP) is discussed by numerically solving the time-dependent Schr?dinger equation. The harmonic spectra periodically exhibit three distinct oscillating structures, which indicate the different dependences of the cutoff energies on the CEP. Furthermore,with time-dependent population imaging and the populations of different energy bands, the underlying physical mechanism is explored.展开更多
A new pressure-calibration method for calibrating the reduction of second harmonic(2f)amplitude caused by pressure broadening effect in sealed microbial growth environment is present.The new method combines with linew...A new pressure-calibration method for calibrating the reduction of second harmonic(2f)amplitude caused by pressure broadening effect in sealed microbial growth environment is present.The new method combines with linewidth compensation and modulation depth compensation and makes the 2f amplitude accurately retrieve metabolic CO_(2) in microbial growth.In order to verify the method,a simulation experiment is developed,in which the increasing CO_(2) concentration leads to the increasing pressure.Comparing with the relation between the traditional 2f amplitude and gas concentration,there is a monotonous relation between the calibrated 2f amplitude and CO_(2) concentration,particularly,a linear relation is present when the CO_(2) concentration is replaced with the CO_(2) particle number.In terms of microbial measurement,the growth of Escherichia coli is measured,and the culture bottle is sealed during the microbial growth process.The experimental results show that,comparing to the microbial growth retrieved by traditional 2f amplitude,the calibrated 2f amplitude can accurately retrieve microbial growth in sealed environment.展开更多
Recommender systems are rapidly transforming the digital world into intelligent information hubs.The valuable context information associated with the users’prior transactions has played a vital role in determining th...Recommender systems are rapidly transforming the digital world into intelligent information hubs.The valuable context information associated with the users’prior transactions has played a vital role in determining the user preferences for items or rating prediction.It has been a hot research topic in collaborative filtering-based recommender systems for the last two decades.This paper presents a novel Context Based Rating Prediction(CBRP)model with a unique similarity scoring estimation method.The proposed algorithm computes a context score for each candidate user to construct a similarity pool for the given subject user-item pair and intuitively choose the highly influential users to forecast the item ratings.The context scoring strategy has an inherent capability to incorporate multiple conditional factors to filter down the most relevant recommendations.Compared with traditional similarity estimation methods,CBRP makes it possible for the full use of neighboring collaborators’choice on various conditions.We conduct experiments on three publicly available datasets to evaluate our proposed method with random user-item pairs and got considerable improvement in prediction accuracy over the standard evaluation measures.Also,we evaluate prediction accuracy for every user-item pair in the system and the results show that our proposed framework has outperformed existing methods.展开更多
Human p100 protein consists of four repeated domains of staphylococcal nuclease （SN）-like domain, as well as a tudor （TD） domain thereafter. We have previously shown that the SN-like domain of p100 interacted with...Human p100 protein consists of four repeated domains of staphylococcal nuclease （SN）-like domain, as well as a tudor （TD） domain thereafter. We have previously shown that the SN-like domain of p100 interacted with STAT6 and the large subunit of RNA pol Ⅱ , resulting in the enhancement of STAT6-mediated gene transcriptional activation. Here, we show that SN-like domain also interacted with CREB binding protein （CBP） and directly enhanced the acetyl transferase activity of CBP on histone. On the other hand, overexpression of CBP alone had no ability to significantly increase STAT6- dependent transcriptional activation, however, together with p100 protein, sufficiently enhanced the activation of transcription which was in line with the previous result that p100 protein bridged STAT6 with CBP.展开更多
Adolescent idiopathic scoliosis (AIS) is an agnogenic structural scoliosis occurring in adolescence, and the main diagnostic criteria is coronal Cobb angle >10°in total spine X-ray. Studies have shown that AIS...Adolescent idiopathic scoliosis (AIS) is an agnogenic structural scoliosis occurring in adolescence, and the main diagnostic criteria is coronal Cobb angle >10°in total spine X-ray. Studies have shown that AIS may be associated with abnormal postural reflexes, vestibular system is an important component of postural reflexes and its mechanism in the occurrence and development of scoliosis has received wide attention in recent years. In the study, the research progress on the role of abnormal vestibular reflexes in the pathogenesis of AIS was mainly introduced to help the clinicians better understand the pathogenesis of AIS and provide new ideas for AIS study.展开更多
Background Alanine aminotransferase(ALT)is widely used to screen patients with hepatic diseases.However,the current reference ranges(<50 U/L)were developed by laboratories and have not been validated in populations...Background Alanine aminotransferase(ALT)is widely used to screen patients with hepatic diseases.However,the current reference ranges(<50 U/L)were developed by laboratories and have not been validated in populations with a large number of healthy individuals.Methods This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare.We applied the least mean square algorithm to establish age-and sex-related reference percentiles of serum levels of transaminases.For validation,we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital.Using receiver operating characteristic curves,we determined age-and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases.Results This study revealed a significant correlation between serum transaminase levels and age and sex(P<0.01).These transaminase levels exhibited age-and sex-specific patterns.Among individuals in the non-alcoholic fatty liver disease(NAFLD)cohort,elevated ALT levels displayed a positive association with clinical markers of disease severity,including homeostatic model assessment of insulin resistance,waist-hip ratio,and serum uric acid levels(P<0.01).According to the receiver operating characteristic curves,ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity.Conclusions This study provides age-and sex-specific reference ranges for ALT,aspartate aminotransferase,andγ-glutamyltransferase in Chinese children and adolescents,making it the largest population study to date.Furthermore,the study establishes a precise upper limit for ALT levels,facilitating their use in NAFLD screening.展开更多
Photo-stimuli responsive materials show great potential in the fields of information encryption and storage due to their distinctive spatial or temporal color changes.However,the conventional single or multi-color sta...Photo-stimuli responsive materials show great potential in the fields of information encryption and storage due to their distinctive spatial or temporal color changes.However,the conventional single or multi-color static outputs by light stimulus difficulty meet practical requirements for high-security optical storage technologies.Here,a novel dynamic irradiation-responsive phosphor of Na_(2)Ba_(2)Si_(2)O_(7):Eu is demonstrated,exhibiting high storage stability and convenient readout behaviors.The inherent Eu^(2+)luminescence can be dynamically tuned,instantly read out,and conveniently erased by controlling irradiation duration of a portable diode laser(365 nm).The modulation mechanism is unraveled by optically induced oxidation reactions of Eu^(2+)→Eu^(3+)and defects as killer centers.The excellent luminescence modulation degree(ΔR_(t)=89.5%)and the accompanying larger color contrast enable the creation of invisible optical codes with multi-level encryption in bright or dark field.These results indicate potential applications of Na_(2)Ba_(2)Si_(2)O_(7):-based materials in information encryption and invisible optical storage,and are expected to expand more investigations on optically induced PL modulation behaviors based on mixed valences and defects.展开更多
The ent-kaurenoids(e.g.,oridonin and enmein)from the Isodon genus(Lamiaceae)are one class of diterpenoids with rich structural diversity and intriguing pharmaceutical activity.In contrast to the well-established gibbe...The ent-kaurenoids(e.g.,oridonin and enmein)from the Isodon genus(Lamiaceae)are one class of diterpenoids with rich structural diversity and intriguing pharmaceutical activity.In contrast to the well-established gibberellin pathway,oxidative modifications diversifying the ent-kaurene skeleton in Isodon have remained undetermined for half a century.Here we report a chromosome-level genome assembly of I.rubescens,a well-recognized oridonin producer long favored by Asian people as a traditional herb with antitumor effects.The shoot apex was confirmed to be the actual region actively producing ent-kaurene diterpenoids.Through comparative genomics and phylogenetic analyses,we discovered a cluster of tandem-duplicated CYP706V oxygenase-encoding genes located on an ancient genomic block widely distributed in eudicots,whereas almost exclusively emerged in Isodon plants.In the shoot apex,IrCYP706V2 and IrCYP706V7 oxidized the ent-kaurene core in the initial stage of oridonin biosynthesis.Loss of CYP706Vs in other Lamiaceae plants offered an explanation for the specific kaurenoid production in Isodon plants.Moreover,we found that the Isodon genomes encode multiple diterpenoid synthases that are potentially involved in generating diterpenoid diversity.These findings provided new insights into the evolution of the lineage-specific diterpenoid pathway and laid a foundation for improving production of bioactive ent-kaurene-type diterpenoids by molecular breeding and synthetic biology approaches.展开更多
Focusing on the ball double-screw hydraulic knee joint as the research object,this paper analyzes the load driving performance of the hydraulic knee joint.Taking the posture data of the human body such as walking,squa...Focusing on the ball double-screw hydraulic knee joint as the research object,this paper analyzes the load driving performance of the hydraulic knee joint.Taking the posture data of the human body such as walking,squatting and landing buffer as initial learning objects,motion features are extracted.By simplifying the trajectories of different motion actions into key feature control points and flexible trajectory fitting,the trajectory of joint actions is optimized.This method can realize the adaptability of the hydraulic robot knee joint in different movements,and take the flexible action as the optimization goal under the condition of ensuring the movement performance,so as to reduce the damage to the knee joint caused by the foot impact in motion.The simulation model was built by Adams and Matlab to complete the performance analysis and motion optimization experiment of the knee joint.The simulation results show that the foot impact force of the experimental model decreases gradually through optimization.Finally,the method is applied to the hydraulic joint experimental prototype to prove its load capacity and flexible motion control performance.展开更多
Through bioinformatics predictions,we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma(TC).Further,Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and ...Through bioinformatics predictions,we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma(TC).Further,Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression.Therefore,we selected them for this present study,where the effects of bone marrow mesenchymal stem cell-derived EVs(BMSDs-EVs)enriched with GTF2I were evaluated on the epithelial–to–mesenchymal transition(EMT)and stemness maintenance in TC.The under-expression of GTF2I and FAT1 was validated in TC cell lines.Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells,EMT,and stemness maintenance.Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression.MSC-EVs could shuttle GTF2I into TPC-1 cells,where GTF2I inhibited TC malignant phenotypes,EMT,and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation.In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice.Taken together,our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.展开更多
Background The mechanism of hepatitis B virus(HBV)-induced carcinogenesis remains an area of interest.The accumulation of hepatitis B surface antigen in the endoplasmic reticulum(ER)of hepatocytes stimulates persisten...Background The mechanism of hepatitis B virus(HBV)-induced carcinogenesis remains an area of interest.The accumulation of hepatitis B surface antigen in the endoplasmic reticulum(ER)of hepatocytes stimulates persistent ER stress.Activity of the unfolded protein response(UPR)pathway of ER stress may play an important role in inflammatory cancer transformation.How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV-related hepatocellular carcinoma(HCC)is still unclear.Here,we aimed to define the key molecule hyaluronan-mediated motility receptor(HMMR)in this process and explore its role under ER stress in HCC development.Methods An HBV-transgenic mouse model was used to characterize the pathological changes during the tumor progression.Proteomics and transcriptomics analyses were performed to identify the potential key molecule,screen the E3 ligase,and define the activation pathway.Quantitative real-time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines.Luciferase reporter assay,chromatin immunoprecipitation,coimmunoprecipitation,immunoprecipitation,and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress.Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues.Results We found sustained activation of ER stress in the HBV-transgenic mouse model of hepatitis-fibrosis-HCC.HMMR was transcribed by c/EBP homologous protein(CHOP)and degraded by tripartite motif containing 29(TRIM29)after ubiquitination under ER stress,which caused the inconsistent expression of mRNA and protein.Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR.HMMR could alleviate ER stress by increasing autophagic lysosome activity.The negative correlation between HMMR and ER stress,positive correlation between HMMR and autophagy,and negative correlation between ER stress and autophagy were verified in human tissues.Conclusions This study identified the complicated role of HMMR in autophagy and ER stress,that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression,which could be a novel explanation for HBV-related carcinogenesis.展开更多
Indoor microorganisms impact asthma and allergic rhinitis(AR),but the associated microbial taxa often vary extensively due to climate and geographical variations.To provide more consistent environmental assessments,ne...Indoor microorganisms impact asthma and allergic rhinitis(AR),but the associated microbial taxa often vary extensively due to climate and geographical variations.To provide more consistent environmental assessments,new perspectives on microbial exposure for asthma and AR are needed.Home dust from 97 cases(32 asthma alone,37 AR alone,28 comorbidity)and 52 age-and gender-matched controls in Shanghai,China,were analyzed using high-throughput shotgun metagenomic sequencing and liquid chromatography-mass spectrometry.Homes of healthy children were enriched with environmental microbes,including Paracoccus,Pseudomonas,and Psychrobacter,and metabolites like keto acids,indoles,pyridines,and flavonoids(astragalin,hesperidin)(False Discovery Rate<0.05).A neural network co-occurrence probability analysis revealed that environmental microorganisms were involved in producing these keto acids,indoles,and pyridines.Conversely,homes of diseased children were enriched with mycotoxins and synthetic chemicals,including herbicides,insecticides,and food/cosmetic additives.Using a random forest model,characteristic metabolites and microorganisms in Shanghai homes were used to classify high and low prevalence of asthma/AR in an independent dataset in Malaysian schools(N=1290).Indoor metabolites achieved an average accuracy of 74.9%and 77.1%in differentiating schools with high and low prevalence of asthma and AR,respectively,whereas indoor microorganisms only achieved 51.0%and 59.5%,respectively.These results suggest that indoor metabolites and chemicals rather than indoor microbiome are potentially superior environmental indicators for childhood asthma and AR.This study extends the traditional risk assessment focusing on allergens or air pollutants in childhood asthma and AR,thereby revealing potential novel intervention strategies for these diseases.展开更多
As a critical prerequisite for semantic facade reconstruction,accurately separating wall and protrusion points from facade point clouds is required.The performance of traditional separation methods is severely limited...As a critical prerequisite for semantic facade reconstruction,accurately separating wall and protrusion points from facade point clouds is required.The performance of traditional separation methods is severely limited by facade conditions,including wall shapes(e.g.,nonplanar walls),wall compositions(e.g.,walls composed of multiple noncoplanar point clusters),and protrusion structures(e.g.,protrusions without regularity,repetitive,or self-symmetric features).This study proposes a more widely applicable wall and protrusion separation method.The major principle underlying the proposed method is to transform the wall and protrusion separation problem as a ground filtering problem and to separate walls and protrusions using ground filtering methods,since the 2 problems can be solved using the same prior knowledge,that is,protrusions(nonground objects)protrude from walls(ground).After transformation problem,cloth simulation filter was used as an example to separate walls and protrusions in 8 facade point clouds with various characteristics.The proposed method was robust to the facade conditions,with a mean intersection over union of 90.7%,and had substantially higher accuracy compared with the traditional separation methods,including region growing-,random sample consensus-,multipass random sample consensus-based,and hybrid methods,with mean intersection over union values of 69.53%,49.52%,63.93%,and 47.07%,respectively.Besides,the proposed method was general,since existing ground filtering methods(including the maximum slope,progressive morphology,and progressive triangular irregular network densification filters)can also perform well.展开更多
Early childhood development has been linked with adult health and wellbeing.It is a necessary component of the sustainable development goals (SDGs) [1,2],which are conceptualized from a lifespan perspective.Neuroscien...Early childhood development has been linked with adult health and wellbeing.It is a necessary component of the sustainable development goals (SDGs) [1,2],which are conceptualized from a lifespan perspective.Neuroscience researches in the past two decades have elucidated that the period from conception through early childhood (i.e.,at least the first 3 years) is foundational for brain development [3].Children acquire an orderly progression of skills that form the blueprint for subsequent development.Epigenetic,immunological,physiological,and psychological adaptations to the environment occur during this period,and these adaptations affect development throughout the life course [4].Risks including poverty,stunting,and nutritional deficiencies contribute to inequities in children's development [5],resulting in over 200 million children under 5 years of age in low-and middle-income countries not reaching their developmental potential,leading to an average deficit of 19.8% in adult annual income [3].Quality interventions in the early years of children have long-term beneficial effects with cost efficiency,including reductions in violence [6],depression and social inhibition,improving adult health,competence (e.g.,learning and academic attainment),and subsequently economic productivity [7,8].展开更多
基金supported by grants from the Natural Science Foundation of Huai'an Science and Technology Bureau(Grant No.HAB202312)the Science and Technology Development Fund of the Affiliated Hospital of Xuzhou Medical University(Grant No.XYFY2021018).
文摘Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.
基金Supported by National Natural Science Foundation of China,No.81401969Jiangsu Provincial Medical Youth Talent,No.QNRC2016043the Key Medical Science and Technology Development Project of Nanjing,No.ZKX16032
文摘AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.
基金the National Natural Science Foundation of China(Grant Nos.41671414,41971380 and 41171265)the National Key Research and Development Program of China(No.2016YFB0501404).
文摘Background:The universal occurrence of randomly distributed dark holes(i.e.,data pits appearing within the tree crown)in LiDAR-derived canopy height models(CHMs)negatively affects the accuracy of extracted forest inventory parameters.Methods:We develop an algorithm based on cloth simulation for constructing a pit-free CHM.Results:The proposed algorithm effectively fills data pits of various sizes whilst preserving canopy details.Our pitfree CHMs derived from point clouds at different proportions of data pits are remarkably better than those constructed using other algorithms,as evidenced by the lowest average root mean square error(0.4981 m)between the reference CHMs and the constructed pit-free CHMs.Moreover,our pit-free CHMs show the best performance overall in terms of maximum tree height estimation(average bias=0.9674 m).Conclusion:The proposed algorithm can be adopted when working with different quality LiDAR data and shows high potential in forestry applications.
基金Supported by the National Natural Science Foundation of China under Grant Nos 11404204 and 11504221the Program for the Top Young Academic Leaders of Higher Learning Institutions of Shanxi Province+1 种基金the Natural Science Foundation for Young Scientists of Shanxi Normal University under Grant No ZR1805the Project for Graduate Research Innovation of Shanxi Normal University
文摘The dependence of harmonic emission from a solid on the carrier envelope phase (CEP) is discussed by numerically solving the time-dependent Schr?dinger equation. The harmonic spectra periodically exhibit three distinct oscillating structures, which indicate the different dependences of the cutoff energies on the CEP. Furthermore,with time-dependent population imaging and the populations of different energy bands, the underlying physical mechanism is explored.
基金the National Key Research and Development Program of China(Grant Nos.2017YFC0209700 and 2016YFC0303900)the National Natural Science Foundation of China(Grant No.41730103).
文摘A new pressure-calibration method for calibrating the reduction of second harmonic(2f)amplitude caused by pressure broadening effect in sealed microbial growth environment is present.The new method combines with linewidth compensation and modulation depth compensation and makes the 2f amplitude accurately retrieve metabolic CO_(2) in microbial growth.In order to verify the method,a simulation experiment is developed,in which the increasing CO_(2) concentration leads to the increasing pressure.Comparing with the relation between the traditional 2f amplitude and gas concentration,there is a monotonous relation between the calibrated 2f amplitude and CO_(2) concentration,particularly,a linear relation is present when the CO_(2) concentration is replaced with the CO_(2) particle number.In terms of microbial measurement,the growth of Escherichia coli is measured,and the culture bottle is sealed during the microbial growth process.The experimental results show that,comparing to the microbial growth retrieved by traditional 2f amplitude,the calibrated 2f amplitude can accurately retrieve microbial growth in sealed environment.
基金This work is supported by National Natural Science Foundation of China(No.61672133)Sichuan Science and Technology Program(No.2019YFG0535)the 111 Project(No.B17008).
文摘Recommender systems are rapidly transforming the digital world into intelligent information hubs.The valuable context information associated with the users’prior transactions has played a vital role in determining the user preferences for items or rating prediction.It has been a hot research topic in collaborative filtering-based recommender systems for the last two decades.This paper presents a novel Context Based Rating Prediction(CBRP)model with a unique similarity scoring estimation method.The proposed algorithm computes a context score for each candidate user to construct a similarity pool for the given subject user-item pair and intuitively choose the highly influential users to forecast the item ratings.The context scoring strategy has an inherent capability to incorporate multiple conditional factors to filter down the most relevant recommendations.Compared with traditional similarity estimation methods,CBRP makes it possible for the full use of neighboring collaborators’choice on various conditions.We conduct experiments on three publicly available datasets to evaluate our proposed method with random user-item pairs and got considerable improvement in prediction accuracy over the standard evaluation measures.Also,we evaluate prediction accuracy for every user-item pair in the system and the results show that our proposed framework has outperformed existing methods.
文摘Human p100 protein consists of four repeated domains of staphylococcal nuclease （SN）-like domain, as well as a tudor （TD） domain thereafter. We have previously shown that the SN-like domain of p100 interacted with STAT6 and the large subunit of RNA pol Ⅱ , resulting in the enhancement of STAT6-mediated gene transcriptional activation. Here, we show that SN-like domain also interacted with CREB binding protein （CBP） and directly enhanced the acetyl transferase activity of CBP on histone. On the other hand, overexpression of CBP alone had no ability to significantly increase STAT6- dependent transcriptional activation, however, together with p100 protein, sufficiently enhanced the activation of transcription which was in line with the previous result that p100 protein bridged STAT6 with CBP.
基金Natural Science Youth Foundation of China(81501845)Youth Initial Funding of Changhai Hospital(CH201518).
文摘Adolescent idiopathic scoliosis (AIS) is an agnogenic structural scoliosis occurring in adolescence, and the main diagnostic criteria is coronal Cobb angle >10°in total spine X-ray. Studies have shown that AIS may be associated with abnormal postural reflexes, vestibular system is an important component of postural reflexes and its mechanism in the occurrence and development of scoliosis has received wide attention in recent years. In the study, the research progress on the role of abnormal vestibular reflexes in the pathogenesis of AIS was mainly introduced to help the clinicians better understand the pathogenesis of AIS and provide new ideas for AIS study.
基金supported by grants from the National Key Research and Development Program of China(Nos.2021YFC2701901 and 2016YFC1305301)National Natural Science Foundation of China(Nos.82370863 and 81570759)Zhejiang Provincial Key Disciplines of Medicine(Innovation Discipline,11-CX24).
文摘Background Alanine aminotransferase(ALT)is widely used to screen patients with hepatic diseases.However,the current reference ranges(<50 U/L)were developed by laboratories and have not been validated in populations with a large number of healthy individuals.Methods This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare.We applied the least mean square algorithm to establish age-and sex-related reference percentiles of serum levels of transaminases.For validation,we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital.Using receiver operating characteristic curves,we determined age-and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases.Results This study revealed a significant correlation between serum transaminase levels and age and sex(P<0.01).These transaminase levels exhibited age-and sex-specific patterns.Among individuals in the non-alcoholic fatty liver disease(NAFLD)cohort,elevated ALT levels displayed a positive association with clinical markers of disease severity,including homeostatic model assessment of insulin resistance,waist-hip ratio,and serum uric acid levels(P<0.01).According to the receiver operating characteristic curves,ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity.Conclusions This study provides age-and sex-specific reference ranges for ALT,aspartate aminotransferase,andγ-glutamyltransferase in Chinese children and adolescents,making it the largest population study to date.Furthermore,the study establishes a precise upper limit for ALT levels,facilitating their use in NAFLD screening.
基金the National Natural Science Foundation of China(Nos.52062042 and 12164005)the Central Government Guidance Funds for Local Scientific and Technological Development of China(No.Guike ZY22096024).
文摘Photo-stimuli responsive materials show great potential in the fields of information encryption and storage due to their distinctive spatial or temporal color changes.However,the conventional single or multi-color static outputs by light stimulus difficulty meet practical requirements for high-security optical storage technologies.Here,a novel dynamic irradiation-responsive phosphor of Na_(2)Ba_(2)Si_(2)O_(7):Eu is demonstrated,exhibiting high storage stability and convenient readout behaviors.The inherent Eu^(2+)luminescence can be dynamically tuned,instantly read out,and conveniently erased by controlling irradiation duration of a portable diode laser(365 nm).The modulation mechanism is unraveled by optically induced oxidation reactions of Eu^(2+)→Eu^(3+)and defects as killer centers.The excellent luminescence modulation degree(ΔR_(t)=89.5%)and the accompanying larger color contrast enable the creation of invisible optical codes with multi-level encryption in bright or dark field.These results indicate potential applications of Na_(2)Ba_(2)Si_(2)O_(7):-based materials in information encryption and invisible optical storage,and are expected to expand more investigations on optically induced PL modulation behaviors based on mixed valences and defects.
基金funded by the National Key R&D Program of China(2018YFA0900600)the National Natural Science Foundation of China(32070328,22077129,and 41876084),the Program of Shanghai Academic Research Leader(20XD1404400)+2 种基金the Strategic Priority Research Program“Molecular Mechanism of Plant Growth and Development”of CAS(XDB27020202)the Construction of the Registry and Database of Bioparts for Synthetic Biology of the Chinese Academy of Sciences(ZSYS-016),the International Partnership Program of the Chinese Academy of Sciences(153D31KYSB20170121),Derivative Bank of Chinese Biological Resources(KFJ-BRP-009-002)the National Key Laboratory of Plant Molecular Genetics,SIPPE,CAS.Y.S.is supported by the Foundation of Youth Innovation Promotion Association of the Chinese Academy of Sciences.
文摘The ent-kaurenoids(e.g.,oridonin and enmein)from the Isodon genus(Lamiaceae)are one class of diterpenoids with rich structural diversity and intriguing pharmaceutical activity.In contrast to the well-established gibberellin pathway,oxidative modifications diversifying the ent-kaurene skeleton in Isodon have remained undetermined for half a century.Here we report a chromosome-level genome assembly of I.rubescens,a well-recognized oridonin producer long favored by Asian people as a traditional herb with antitumor effects.The shoot apex was confirmed to be the actual region actively producing ent-kaurene diterpenoids.Through comparative genomics and phylogenetic analyses,we discovered a cluster of tandem-duplicated CYP706V oxygenase-encoding genes located on an ancient genomic block widely distributed in eudicots,whereas almost exclusively emerged in Isodon plants.In the shoot apex,IrCYP706V2 and IrCYP706V7 oxidized the ent-kaurene core in the initial stage of oridonin biosynthesis.Loss of CYP706Vs in other Lamiaceae plants offered an explanation for the specific kaurenoid production in Isodon plants.Moreover,we found that the Isodon genomes encode multiple diterpenoid synthases that are potentially involved in generating diterpenoid diversity.These findings provided new insights into the evolution of the lineage-specific diterpenoid pathway and laid a foundation for improving production of bioactive ent-kaurene-type diterpenoids by molecular breeding and synthetic biology approaches.
基金supported by the Top Discipline Plan of Shanghai Universities-Class I,the National Natural Science Foundation of China(52205279)the China National Postdoctoral Program for Innovative Talents(BX20190242)+1 种基金the Open Foundation of the State Key Laboratory of Fluid Power and Mechatronic Systems(GZKF-202017)the Open Foundation of the National Engineering Technology Research Center for Prefabrication Construction in Civil Engineering(2021CPCCE-K02).
文摘Focusing on the ball double-screw hydraulic knee joint as the research object,this paper analyzes the load driving performance of the hydraulic knee joint.Taking the posture data of the human body such as walking,squatting and landing buffer as initial learning objects,motion features are extracted.By simplifying the trajectories of different motion actions into key feature control points and flexible trajectory fitting,the trajectory of joint actions is optimized.This method can realize the adaptability of the hydraulic robot knee joint in different movements,and take the flexible action as the optimization goal under the condition of ensuring the movement performance,so as to reduce the damage to the knee joint caused by the foot impact in motion.The simulation model was built by Adams and Matlab to complete the performance analysis and motion optimization experiment of the knee joint.The simulation results show that the foot impact force of the experimental model decreases gradually through optimization.Finally,the method is applied to the hydraulic joint experimental prototype to prove its load capacity and flexible motion control performance.
基金supported by Shanghai Shenkang Hospital Development Center(No.SHDC12019X38).
文摘Through bioinformatics predictions,we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma(TC).Further,Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression.Therefore,we selected them for this present study,where the effects of bone marrow mesenchymal stem cell-derived EVs(BMSDs-EVs)enriched with GTF2I were evaluated on the epithelial–to–mesenchymal transition(EMT)and stemness maintenance in TC.The under-expression of GTF2I and FAT1 was validated in TC cell lines.Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells,EMT,and stemness maintenance.Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression.MSC-EVs could shuttle GTF2I into TPC-1 cells,where GTF2I inhibited TC malignant phenotypes,EMT,and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation.In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice.Taken together,our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.
基金National Natural Science Foundation of China,Grant/Award Number:82130084Shaanxi Provincial Key R&D Program,Grant/Award Number:2021SF-110。
文摘Background The mechanism of hepatitis B virus(HBV)-induced carcinogenesis remains an area of interest.The accumulation of hepatitis B surface antigen in the endoplasmic reticulum(ER)of hepatocytes stimulates persistent ER stress.Activity of the unfolded protein response(UPR)pathway of ER stress may play an important role in inflammatory cancer transformation.How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV-related hepatocellular carcinoma(HCC)is still unclear.Here,we aimed to define the key molecule hyaluronan-mediated motility receptor(HMMR)in this process and explore its role under ER stress in HCC development.Methods An HBV-transgenic mouse model was used to characterize the pathological changes during the tumor progression.Proteomics and transcriptomics analyses were performed to identify the potential key molecule,screen the E3 ligase,and define the activation pathway.Quantitative real-time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines.Luciferase reporter assay,chromatin immunoprecipitation,coimmunoprecipitation,immunoprecipitation,and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress.Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues.Results We found sustained activation of ER stress in the HBV-transgenic mouse model of hepatitis-fibrosis-HCC.HMMR was transcribed by c/EBP homologous protein(CHOP)and degraded by tripartite motif containing 29(TRIM29)after ubiquitination under ER stress,which caused the inconsistent expression of mRNA and protein.Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR.HMMR could alleviate ER stress by increasing autophagic lysosome activity.The negative correlation between HMMR and ER stress,positive correlation between HMMR and autophagy,and negative correlation between ER stress and autophagy were verified in human tissues.Conclusions This study identified the complicated role of HMMR in autophagy and ER stress,that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression,which could be a novel explanation for HBV-related carcinogenesis.
基金The study was funded by the National Natural Science Foundation of China(No.81861138005)the Natural Science Foundation of Guangdong Province(Nos.2020A1515010845 and 2021A1515010492)+1 种基金the Science and Technology Program of Guangzhou(No.202102080362)Shanghai B&R Joint Laboratory(No.22230750300)and the Swedish Research Council(Vetenskapsrådet)project(No.2017-05845).
文摘Indoor microorganisms impact asthma and allergic rhinitis(AR),but the associated microbial taxa often vary extensively due to climate and geographical variations.To provide more consistent environmental assessments,new perspectives on microbial exposure for asthma and AR are needed.Home dust from 97 cases(32 asthma alone,37 AR alone,28 comorbidity)and 52 age-and gender-matched controls in Shanghai,China,were analyzed using high-throughput shotgun metagenomic sequencing and liquid chromatography-mass spectrometry.Homes of healthy children were enriched with environmental microbes,including Paracoccus,Pseudomonas,and Psychrobacter,and metabolites like keto acids,indoles,pyridines,and flavonoids(astragalin,hesperidin)(False Discovery Rate<0.05).A neural network co-occurrence probability analysis revealed that environmental microorganisms were involved in producing these keto acids,indoles,and pyridines.Conversely,homes of diseased children were enriched with mycotoxins and synthetic chemicals,including herbicides,insecticides,and food/cosmetic additives.Using a random forest model,characteristic metabolites and microorganisms in Shanghai homes were used to classify high and low prevalence of asthma/AR in an independent dataset in Malaysian schools(N=1290).Indoor metabolites achieved an average accuracy of 74.9%and 77.1%in differentiating schools with high and low prevalence of asthma and AR,respectively,whereas indoor microorganisms only achieved 51.0%and 59.5%,respectively.These results suggest that indoor metabolites and chemicals rather than indoor microbiome are potentially superior environmental indicators for childhood asthma and AR.This study extends the traditional risk assessment focusing on allergens or air pollutants in childhood asthma and AR,thereby revealing potential novel intervention strategies for these diseases.
基金supported by the National Natural Science Foundation of China,grant nos.41971380 and 41671414supported by Guangxi Natural Science Fund for Innovation Research Team(grant no.2019JJF50001)+1 种基金the Open Fund of State Key Laboratory of Remote Sensing Science(grant no.OFSLRSS201920)leading talents of Guangdong Pearl River Talent Program(grant no.2021CX02S024).
文摘As a critical prerequisite for semantic facade reconstruction,accurately separating wall and protrusion points from facade point clouds is required.The performance of traditional separation methods is severely limited by facade conditions,including wall shapes(e.g.,nonplanar walls),wall compositions(e.g.,walls composed of multiple noncoplanar point clusters),and protrusion structures(e.g.,protrusions without regularity,repetitive,or self-symmetric features).This study proposes a more widely applicable wall and protrusion separation method.The major principle underlying the proposed method is to transform the wall and protrusion separation problem as a ground filtering problem and to separate walls and protrusions using ground filtering methods,since the 2 problems can be solved using the same prior knowledge,that is,protrusions(nonground objects)protrude from walls(ground).After transformation problem,cloth simulation filter was used as an example to separate walls and protrusions in 8 facade point clouds with various characteristics.The proposed method was robust to the facade conditions,with a mean intersection over union of 90.7%,and had substantially higher accuracy compared with the traditional separation methods,including region growing-,random sample consensus-,multipass random sample consensus-based,and hybrid methods,with mean intersection over union values of 69.53%,49.52%,63.93%,and 47.07%,respectively.Besides,the proposed method was general,since existing ground filtering methods(including the maximum slope,progressive morphology,and progressive triangular irregular network densification filters)can also perform well.
基金the Natural Science Foundation of China(81773440).
文摘Early childhood development has been linked with adult health and wellbeing.It is a necessary component of the sustainable development goals (SDGs) [1,2],which are conceptualized from a lifespan perspective.Neuroscience researches in the past two decades have elucidated that the period from conception through early childhood (i.e.,at least the first 3 years) is foundational for brain development [3].Children acquire an orderly progression of skills that form the blueprint for subsequent development.Epigenetic,immunological,physiological,and psychological adaptations to the environment occur during this period,and these adaptations affect development throughout the life course [4].Risks including poverty,stunting,and nutritional deficiencies contribute to inequities in children's development [5],resulting in over 200 million children under 5 years of age in low-and middle-income countries not reaching their developmental potential,leading to an average deficit of 19.8% in adult annual income [3].Quality interventions in the early years of children have long-term beneficial effects with cost efficiency,including reductions in violence [6],depression and social inhibition,improving adult health,competence (e.g.,learning and academic attainment),and subsequently economic productivity [7,8].
