The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we develope...The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we developed in vivo second near-infrared(NIR-II)window fluorescence(FL)and ratiometric photoacoustic(RPA)dual-modality imaging of GSH using a GSH-activatable probe(LET-14).LET-14 was synthesized based on a rhodamine hybrid xanthene skeleton with a FL shielding 2,4-dinitrobenzene sulfonyl group that can be specifically cleaved by GSH,thus resulting in a markedly bathochromic-shift absorption,a 6.5-fold increase in NIR-II FL intensity(FL920)and a 13-fold increase in RPA signal(PA880/PA705)in vitro.Intriguingly,LET-14 exhibits good selectivity and sensitivity for NIR-II FL and RPA dual-modality imaging of GSH in 4T1 tumor-bearing mouse model.Our findings develop an in vivo detection tool of GSH,which has great potential in the field of cancer diagnosis.展开更多
Ganoderma lingzhi is a new species of the prize medicinal mushroom Ganoderma(Agaricomycetes).Using angiotensin I-converting enzyme(ACE)as a target,a tripeptide Ser-Tyr-Pro(SYP)was discovered with preponderant ACE inhi...Ganoderma lingzhi is a new species of the prize medicinal mushroom Ganoderma(Agaricomycetes).Using angiotensin I-converting enzyme(ACE)as a target,a tripeptide Ser-Tyr-Pro(SYP)was discovered with preponderant ACE inhibitory activity with an 50%inhibiting concentration(IC_(50))value of 62.50μg/mL attribute to the formed salt bridge and hydrogen bonds between SYP and ACE.SYP even maintained superior bioactivity after intestinal digestion,and exerted no cytotoxicity,but presented incomplete bioavailability in blood of spontaneous hypertensive rats(SHRs).Furthermore,it performed antihypertensive effect in vivo by inhibiting the influx of Ca^(2+)through activating endothelial NO synthase(e NOS)/NO/guanosine 3',5'-cyclic monophosphate(c GMP)pathway,accompanied by attenuating angiotensin II(Ang II)/NADPH oxidase(NOX)/reactive oxygen species(ROS)pathway.This work not only discoverers a novel pharmacological ingredient from medicinal mushroom G.lingzhi for hypertension therapy,but also provides an insight into molecular mechanism of the ACE inhibitory peptide(ACEIP)on lowering blood pressure.展开更多
Objective To identify the key features of facial and tongue images associated with anemia in female populations,establish anemia risk-screening models,and evaluate their performance.Methods A total of 533 female parti...Objective To identify the key features of facial and tongue images associated with anemia in female populations,establish anemia risk-screening models,and evaluate their performance.Methods A total of 533 female participants(anemic and healthy)were recruited from Shuguang Hospital.Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument.Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System(FDAS)and Tongue Diagnosis Analysis System version 2.0(TDAS v2.0).Least Absolute Shrinkage and Selection Operator(LASSO)regression was used for feature selection.Ten machine learning models and one deep learning model(ResNet50V2+Conv1D)were developed and evaluated.Results Anemic women showed lower a-values,higher L-and b-values across all age groups.Texture features analysis showed that women aged 30–39 with anemia had higher angular second moment(ASM)and lower entropy(ENT)values in facial images,while those aged 40–49 had lower contrast(CON),ENT,and MEAN values in tongue images but higher ASM.Anemic women exhibited age-related trends similar to healthy women,with decreasing L-values and increasing a-,b-,and ASM-values.LASSO identified 19 key features from 62.Among classifiers,the Artificial Neural Network(ANN)model achieved the best performance[area under the curve(AUC):0.849,accuracy:0.781].The ResNet50V2 model achieved comparable results[AUC:0.846,accuracy:0.818].Conclusion Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.展开更多
Antarctic krill(Euphausia superba),widely distributes around Antarctica,is a key species supporting the biodiversity of the Southern Ocean ecosystem.The Commission for the Conservation of Antarctic Marine Living Resou...Antarctic krill(Euphausia superba),widely distributes around Antarctica,is a key species supporting the biodiversity of the Southern Ocean ecosystem.The Commission for the Conservation of Antarctic Marine Living Resources(CCAMLR)has thus managed the krill fishery according to a precautionary way.Currently,CCAMLR is making effort to develop a refined krill fishery management approach based on more solid science,which requires accurate predictions of krill distribution.To address this need,this study investigated the effects of algorithm and spatial resolution on the performance of Antarctic krill distribution modelling.We integrated acoustic data from 4 surveys conducted in the waters adjacent to the Antarctic Peninsula with 11 environmental variables characterizing krill prey conditions,water mass properties,and seafloor topography.These data were processed at 4 spatial resolutions(5,10,15,and 20 km)to fit distribution models using 4 algorithms:Random Forests(RF),Generalized Additive Models(GAM),Extreme Gradient Boosting(XGBoost),and Artificial Neural Networks(ANN).Model performance was assessed and compared in terms of goodness-of-fit and predictive accuracy.The results showed that RF achieved the highest predictive performance at most resolutions,whereas GAM performed best at the coarsest resolution(20 km).XGBoost closely following RF in accuracy and demonstrated robustness as evidenced by the highly consistent partial dependence curves across resolutions.In contrast,ANN exhibited limitations with smaller sample sizes,resulting in comparatively poorer predictive performance.The analysis revealed a trade-off whereby reducing spatial resolution improved model fit and mitigated zero-inflation at the expense of fine-scale information and overall predictive accuracy.Ensemble models,integrating RF,GAM,and XGBoost,are proposed as potential balanced solutions to improve predictive stability,offering a more robust scientific basis for the refinement of krill management.展开更多
The rapid intensification(RI)magnitude of tropical cyclones(TCs)over the western North Pacific(WNP)exhibits significant interannual variability and is influenced by multiple factors across various scales.These factors...The rapid intensification(RI)magnitude of tropical cyclones(TCs)over the western North Pacific(WNP)exhibits significant interannual variability and is influenced by multiple factors across various scales.These factors primarily include:interannual factors—sea surface temperature(SST)in key regions of the WNP,eastern Indian Ocean SST,El Niño-Southern Oscillation(ENSO),South Pacific Subtropical Dipole(SPSD),and western Pacific teleconnection;decadal factors—Atlantic Multidecadal Oscillation(AMO)and Pacific Decadal Oscillation(PDO);and longer-term factor—global warming.This study systematically analyzes these factors and their potential impacts,quantitatively assessing their relative importance.A statistical prediction model for the WNP TC-RI magnitude is developed based on ridge regression methods.The results indicate that the influence of these factors on the RI magnitude is closely related to the large-scale thermodynamic and dynamic conditions.Among them,the SPSD plays the most critical role in the interannual variability of the RI magnitude,followed by global warming and the AMO.Further analysis reveals that the statistical prediction model based on multiple factors demonstrates good predictive skill for the interannual variability of the TC RI magnitude.展开更多
Background: Plexiform neurofibromas(PNF) are highly vascular tumors with the potential for significant growth.Surgical removal of giant PNF is often challenging because of intraoperative hemorrhage.This study proposed...Background: Plexiform neurofibromas(PNF) are highly vascular tumors with the potential for significant growth.Surgical removal of giant PNF is often challenging because of intraoperative hemorrhage.This study proposed and evaluated an innovative surgical approach involving FENCY ligation and the role of preoperative embolization in the resection of giant PNF.Methods: This was a retrospective,interventional,and sequential case series conducted in a plastic and reconstructive surgery unit.We summarized all patients with PNF who underwent resection at our center between2019 and 2024.Surgical case notes from 11 patients with giant PNF who underwent FENCY ligation were reviewed,including three patients who received preoperative embolization.All patients participated in structured telephone interviews.Patient demographics,surgical safety,postoperative recovery,and patient satisfaction were evaluated.Results: Among 456 patients with 494 PNF who underwent surgical resection,we categorized the procedures into median,large,and giant PNF subgroups.To illustrate comprehensive perioperative and surgical approaches,we analyzed seven female and four male patients with giant PNF.The median maximum tumor diameter at the time of surgery was 30.4 cm(range,11.5–55.6 cm).Most PNF were located on the face(63.6%),followed by the back(18.2%),buttocks(18.2%),upper limbs(9.1%),and neck(9.1%).The median intraoperative hemorrhage volume was 366 m L(range,10–2 034 m L),And the median hospital stay was 17 days(range,14–33 days).The mean follow-up duration was 2.5 years(range,0.4–5.5 years).No severe complications were observed,except for one case of infection.Conclusion: PNF resection,particularly giant PNF resection,is a high-risk treatment option.Comprehensive evaluation,perioperative preparation,and surgical techniques are required to ensure efficacy and safety.FENCY ligation and preoperative embolization can be used to resect giant PNF in multiple complex regions with satisfactory outcomes.展开更多
Epigenetic regulation in the rumen,a unique ruminant organ,remains largely unexplored compared with other tissues studied in model species.In this study,we perform an in-depth analysis of the epigenetic and transcript...Epigenetic regulation in the rumen,a unique ruminant organ,remains largely unexplored compared with other tissues studied in model species.In this study,we perform an in-depth analysis of the epigenetic and transcriptional landscapes across fetal and adult bovine tissues as well as pluripotent stem cells.Among the extensive methylation differences across various stages and tissues,we identify tissue-specific differentially methylated regions(tsDMRs)unique to the rumen,which are crucial for regulating epithelial development and energy metabolism.These tsDMRs cluster within super-enhancer regions that overlap with transcription factor(TF)binding sites.Regression models indicate that DNA methylation,along with H3K27me3 and H3K27ac,can be used to predict enhancer activity.Key upstream TFs,including SOX2,FOSL1/2,and SMAD2/3,primarily maintain an inhibitory state through bivalent modifications during fetal development.Downstream functional genes are maintained mainly in a stable repressive state via DNA methylation until differentiation is complete.Our study underscores the critical role of tsDMRs in regulating distal components of rumen morphology and function,providing key insights into the epigenetic regulatory mechanisms that may influence bovine production traits.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)requires accurate liver fibrosis assessment for management.While liver biopsy remains the gold standard,its invasiveness drives demand for non-invasive bi...Metabolic dysfunction-associated steatotic liver disease(MASLD)requires accurate liver fibrosis assessment for management.While liver biopsy remains the gold standard,its invasiveness drives demand for non-invasive biomarkers.This review evaluates blood biomarkers for MASLD fibrosis staging.Established scores(fibrosis-4,non-alcoholic fatty liver disease fibrosis score)offer accessible screening but exhibit variable performance influenced by age,obesity,and comorbidities.Patented panels(e.g.,enhanced liver fibrosis test,FibroMeter)improve accuracy by integrating extracellular matrix or metabolic markers,though context-specific thresholds are essential.Emerging biomarkers like propeptide of type 3 collagen,Mac-2 binding protein glycosylation isomer,epigenetic markers(proliferator-activated receptor-γmethylation),and angiopoietin-like proteins a family of eight glycoproteins show promise but require large-scale validation.Genetic risk scores and multi-omics approaches face generalizability challenges.Integration strategies,such as combining serum biomarkers with liver stiffness measurement via Agile scores,enhance diagnostic precision and reduce indeterminate classifications.Current tools aid risk stratification,but no single biomarker replicates biopsy-level precision.Future efforts must prioritize MASLD-specific diagnostic frameworks,standardized protocols,and multi-modal integration to enhance clinical utility and address MASLD’s growing burden.展开更多
The production of hydrogen peroxide(H_(2)O_(2))via artificial photosynthesis using single-atom semiconductor photocatalysts represents a promising green and sustainable technology.However,its efficiency is still limit...The production of hydrogen peroxide(H_(2)O_(2))via artificial photosynthesis using single-atom semiconductor photocatalysts represents a promising green and sustainable technology.However,its efficiency is still limited by sluggish water oxidation kinetics,poor photogenerated charge separation,and insufficient O_(2)adsorption and activation capabilities.Herein,uniformly dispersed single-atom catalysts(SACs)with a Co-N_(4)coordination structure have been synthesized by thermally transforming cobalt phthalocyanine(CoPc)assemblies pre-anchored on phosphate functionalized reduced graphene oxide(Co@rGO-P),and then used to construct heterojunctions with perylenetetracarboxylic acid(PTA)nanosheets for photocatalytic H_(2)O_(2)production by an in-situ growth method.The optimized Co@rGO-P/PTA achieved an H_(2)O_(2)production rate of 1.4 mmol g^(-1)h^(-1)in pure water,with a 12.9-fold enhancement compared to pristine PTA nanosheets exhibiting competitive photoactivity among reported perylene-based materials.Femtosecond transient absorption spectra,in-situ diffuse reflectance infrared Fourier transform spectra and theoretical calculations reveal that the exceptional performance is attributed to the enhanced electron transfer from PTA to rGO via the phosphate bridge and then to the Co-N_(4),and to the promoted O_(2)adsorption and activation at Co-N_(4)active sites.This work provides a feasible and effective strategy for designing highly efficient single-atom semiconductor heterojunction photocatalysts for H_(2)O_(2)production.展开更多
Up to now,“Turn-on”fluorescence sensor exhibits promising potential toward the detection of heavy metal ions,anions,drugs,organic dyes,DNA,pesticides,and other amino acids due to their simple,quick detection,and hig...Up to now,“Turn-on”fluorescence sensor exhibits promising potential toward the detection of heavy metal ions,anions,drugs,organic dyes,DNA,pesticides,and other amino acids due to their simple,quick detection,and high sensitivity and selectivity.Herein,a novel fluorescence method of detecting Cr^(3+)in an aqueous solution was described based on the fluorescence resonance energy transfer between rhodamine B(Rh B)and gold nanoparticles(Au NPs).The fluorescence of Rh B solution could be obviously quenched(“off”state)with the presence of citrate-stabilized Au NPs.However,upon addition of Cr^(3+)to Au NPs@Rh B system,the fluorescence of Au NPs was recovered owing to the strong interaction between Cr^(3+)and the specific groups on the surface of citrate-stabilized Au NPs,which will lead to the aggregation of Au NPs(“on”state).At this point,the color of the reaction solution turned to black.Under optimal conditions,the limit of detection(LOD)for Cr^(3+)was 0.95 n M(signal-to-noise ratio,S/N=3)with a linear range of 0.164 n M to 3.270μM.Furthermore,the proposed method exhibits excellent performances,such as rapid analysis,high sensitivity,extraordinary selectivity,easy preparation,switch-on fluorescence response,and non-time consuming.展开更多
BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and li...BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.展开更多
Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive ...Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive patients,and those with hematological malignancies.It poses a risk of liver fibrosis and cirrhosis.Data sources:Relevant articles published till September 2024 were located using Pub Med searches.The further search terms utilized were:“immunocompromised”,“solid organ transplant”,“HIV”,“hematological malignancy”,and“hepatitis E virus”.A manual search of references from pivotal articles extended further publications.The search parameters encompass publications in English.Results:The epidemiology,clinical manifestations,diagnostic measures,and therapeutic modalities of chronic hepatitis E were discussed.Immunocompromised individuals who are infected with HEV are at an increased risk of developing chronic infections,which may progress to liver fibrosis and cirrhosis.Current understanding of HEV is still limited,and there is no medicine that specifically targets hepatitis E.Consequently,the prevention and management of hepatitis E continue to present a significant challenge.Conclusions:Chronic hepatitis E patients need special attention in clinical practice.The relevant risk factors must be identified to facilitate accurate diagnosis and the implementation of more effective preventive measures,thereby enhancing the monitoring,treatment,and prevention of immunocompromised individuals.展开更多
With global industrialization and the excessive use of fossil fuels,greenhouse gas emissions have substantially increased,particularly the concentrations of carbon dioxide(CO_(2)),which have had profound impacts on gl...With global industrialization and the excessive use of fossil fuels,greenhouse gas emissions have substantially increased,particularly the concentrations of carbon dioxide(CO_(2)),which have had profound impacts on global warming and extreme climate events.As a key technology to combat climate change,mineral carbonation has been widely recognized as an effective technique for CO_(2)sequestration and utilization.In recent years,seawater-based solutions(including desalination brine and seawater-based wastewater)have become a research hotspot in mineral carbonation due to their strong alkalinity,high content of Ca^(2+)and Mg^(2+),and lower costs compared to chemical solvents.This article comprehensively reviews the CO_(2)mineral carbonation mechanisms based on seawater-based solutions,highlighting recent research achievements and potential development trends in capturing CO_(2)through the pH swing method,modified Solvay process,chemical precipitation method,and chemical absorption method.By comparing the use of seawater-based solutions for mineral carbonation with traditional techniques,this study evaluates its advantages and the challenges it may face in practical applications,aiming to provide a more accurate assessment of the impact and future development of this technology.展开更多
Liposomal drugs have significantly improved cancer treatment in recent years.However,the clinical application of conventional liposomes is limited by factors such as the complexity of the preparation process and the m...Liposomal drugs have significantly improved cancer treatment in recent years.However,the clinical application of conventional liposomes is limited by factors such as the complexity of the preparation process and the multitude of auxiliary components.By replacing phospholipids and cholesterol with vitamin E succinate(VES),this study addresses these shortcomings by developing a novel modified nanoprodrug,and the new formulation is used to deliver cisplatin.Concurrently,liposomes encapsulating cisplatin were prepared by conventional formulations for comparative experiments.Moreover,VES can inhibit the expression of mitochondrial uncoupling protein 2(UCP2),further enhancing mitochondrial damage in tumor cells within the tumor microenvironment(TME)and suppressing the tricarboxylic acid cycle,thereby reducing ATP production.Additionally,cisplatin damages DNA structure,affecting the binding of Nrf2 to the antioxidant response element(ARE),thereby inhibiting the signaling expression of heme oxygenase1(HO-1).The combined action of cisplatin and VES disrupts the redox balanceleading to a significant accumulation of reactive oxygen species(ROS).The nanoprodrug effectively alters the redox state of the TME and inhibits antioxidant defenses,thereby amplifying oxidative stress damage and enhancing the efficacy of cisplatin.Notably,compared to free cisplatin,the nanoprodrug demonstrates greater efficacy in both cell line-derived xenograft(CDX)and patient-derived tumor xenograft(PDX)liver cancer models.Overall,this study successfully develops a novel mitochondrial-targeted nanoprodrug by modifying the conventional liposome formulation.This provides a new strategy for amplifying oxidative stress in order to disrupt redox balance,and enhance cisplatin efficacy.展开更多
Objectives:Exosomal long noncoding RNAs(lncRNAs)might facilitate epithelial–mesenchymal transition(EMT)in liver cancer after transarterial chemoembolization(TACE),thereby enhancing tumor cell invasiveness and migrati...Objectives:Exosomal long noncoding RNAs(lncRNAs)might facilitate epithelial–mesenchymal transition(EMT)in liver cancer after transarterial chemoembolization(TACE),thereby enhancing tumor cell invasiveness and migration.This study investigated the prognostic role of plasma exosomal long noncoding RNA-plasmacytoma variant translocation 1(lncRNA-PVT1)in TACE treated hepatocellular carcinoma(HCC).Methods:Plasma exosomal lncRNA-PVT1 was evaluated via qPCR before and after TACE.Hepatoma cell behavior was investigated in different HCC cell lines.A lncRNA-PVT1 plasmid was synthesized and overexpressed,and si-lncRNA PVT1 was transfected into poorly invasive cells to reveal its influence on cell characteristics.The lncRNA-PVT1–FoxM1 interaction was elucidated using a double-luciferase reporter gene assay.The effect of miRNA-345-5p on minimally invasive hepatoma cells was assessed.Three experimental groups were established:poorly invasive cells,poorly invasive cells co-cultured with exosomes from hypoxia-induced highly invasive cells,and poorly invasive cells co-cultured with normal hepatocyte exosomes.Liver cancer cells were subcutaneously inoculated into nude mice,with subsequent observations of weight,tumor formation,and tumor size.Results:We identified two lncRNAs(lncRNA-PVT1 and GAPLINC)associated with EMT in the hypoxic microenvironment of liver cancer.Cox multivariate regression analysis was used to establish a prognostic model distinguishing high-and low-risk groups.Hypoxia-induced HepG2 exosomes significantly promoted EMT in poorly invasive HCC cells.LncRNA-PVT1 overexpression and silencing altered E-cadherin,vimentin,and FoxM1 expression,cell proliferation,invasion,migration,and apoptosis.miR-345-5p directly targeted lncRNA-PVT1 and FoxM1,affecting downstream targets.In vivo,co-culturing poorly invasive hepatoma cells with exosomes from highly invasive cells increased tumor volumes,upregulated lncRNA-PVT1,FoxM1,Ki67,and MMP9 expression,and downregulated miR-345-5p expression.Conclusions:Plasma exosomal lncRNA-PVT1 expression is upregulated in highly invasive cells post-hypoxia,potentially serving as a biomarker for evaluating liver cancer prognosis after TACE.Through a miRNA-345-5p-mediated competing endogenous RNA mechanism,it promotes EMT in poorly invasive cells,likely contributing to recurrence and metastasis post-HCC interventional embolization.展开更多
Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular ...Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular microenvironment.However,the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink,making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials.To overcome this limitation,we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel.This medium possesses yield stress and self-healing properties,facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it.By adjusting the printing speed,we controlled the filament diameter,achieving a range from 250μm to 1000μm,and ensuring precise control over ink deposition locations and filament shapes.Using the in situ endothelialization method,we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells.In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue.We also investigated the impact of varying vascular densities on liver tissue function.Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways.In summary,this method is adaptable to various materials,allowing the rheological properties of the supporting bath and the tissue's porosity to be modified using microgels,thus enabling precise regulation of the liver tissue microenvironment.Additionally,it facilitates the rapid construction of three-dimensional vascular structures within liver tissue.The resulting vascularized liver tissue model exhibits enhanced biological functionality,opening new opportunities for biomedical applications.展开更多
Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contri...Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contributors to CP,the carboxypeptidase A1 p.Ser282Pro(CPA1^(S282P))variant has been proposed to promote disease through misfolding-induced endoplasmic reticulum stress(ERS),although the broader pathogenic landscape remains incompletely defined.This study generated a rabbit model mimicking the human CPA1S282P mutation using the SpRY-ABE-8.17 system.Homozygous CPA1^(S282P)rabbits exhibited characteristic human CP phenotypes following alcohol induction,including visceral pain,elevated serum lipase and amylase,inflammatory cell infiltration,and extensive pancreatic fibrosis.Biochemical analyses confirmed that the p.S282P mutation induced CPA1 misfolding and elevated the expression of ERS markers GRP78 and CHOP in both transfected HEK293T cells and homozygous mutant rabbits.Notably,the CPA1^(S282P)mutation markedly disrupted intra-pancreatic lipid homeostasis,contributing to the development of CP in mutant rabbits.This study successfully established the first rabbit model of CP that accurately recapitulates CP caused by a defined human point mutation.Additionally,this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism,offering a foundation for identifying novel therapeutic targets for human CP.展开更多
The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation...The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown.In this study,we first detected and validated the rich club in the structural networks of mouse,monkey,and human brains using neuronal tracing or diffusion magnetic resonance imaging data.Further,we assessed the role of rich clubs in functional integration,segregation,and balance using quantitative metrics.Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species,with the functional networks of higher species exhibiting greater integration.These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.展开更多
AIM:To investigate the value of combined detection of circulating cell-free DNA(cfDNA),a-fetal protein(AFP) and a L-fucosidase(AFU) for diagnosis of hepatocellular carcinoma(HCC).METHODS:Serum samples from 39 HCC pati...AIM:To investigate the value of combined detection of circulating cell-free DNA(cfDNA),a-fetal protein(AFP) and a L-fucosidase(AFU) for diagnosis of hepatocellular carcinoma(HCC).METHODS:Serum samples from 39 HCC patients and 45 normal controls were collected.Branched DNA(bDNA) was used to detect the level of cfDNA,and a receiver operating characteristic curve was employed to evaluate the diagnostic sensitivity,specificity,accuracy,positive predictive value,negative predictive value,positive likelihood ratio,negative likelihood ratio and Youden index,and to assess the diagnostic efficiency and their correlations with the clinicopathological features.AFP and AFU were detected by chemiluminescence and colorimetry,respectively.The significance of combined detection of the three biomarkers was discussed.RESULTS:cfDNA level was increased in 22 of the 39 HCC samples and in 2 of the 45 normal controls.cfDNA level in HCC samples was significantly higher than that in normal controls(P < 0.05).There were significant differences in sex and extra-and intrahepatic metastasis(P < 0.05).There was no significant correlation between cfDNA,AFP and AFU in the detection of HCC.The sensitivity of combined detection of cfDNA with one marker(AFP or AFU) and cfDNA with two markers(AFP and AFU) was 71.8%,87.2% and 89.7% vs 56.4%,53.8% and 66.7% for cfDNA,AFP and AFU used alone,respectively,the difference being statistically significant(P < 0.05).CONCLUSION:Quantitative analysis of cfDNA is sensitive and feasible,and the combined detection of cfDNA with AFP or AFU or both could improve the diagnostic sensitivity for HCC.展开更多
Objective To create transgenic rabbits by microinjecting human apolipoprotein A-Ⅱ (apoA-Ⅱ) gene into one-cell embryos, to study apoA-Ⅱ gene function on plasma lipoprotein metabolism and atherosclerosis. Methods S...Objective To create transgenic rabbits by microinjecting human apolipoprotein A-Ⅱ (apoA-Ⅱ) gene into one-cell embryos, to study apoA-Ⅱ gene function on plasma lipoprotein metabolism and atherosclerosis. Methods Superovulation and synchronization of estrus were induced in female Japanese White Rabbits by injecting hormone, then mating with male. After collected the fertilized eggs, the human apoA-Ⅱ gene was microinjected into the male pronucleus of eggs. The injected eggs were transferred into recipient female rabbits. Last, extract DNA from the new borns ear and determine whether the newborns were transgenic by polymerase chain reaction (PCR) or Southern blot analysis. Results A total of 822 embryos with microinjection of human apoAⅡ gene were implanted into 28 recipient rabbits. The number of surviving newborns was 37. 3 transgenic positive surviving founders were found with human apoA-Ⅱ.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82372116,U23A2097)Guangdong Basic and Applied Basic Research Foundation(No.2022A1515010620)+2 种基金Shenzhen Medical Research Fund(Nos.B2302047,A2302047)Shenzhen Science and Technology Program(No.JCYJ20220818095806014)Research Team Cultivation Program of Shenzhen University(No.2023QNT019).
文摘The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we developed in vivo second near-infrared(NIR-II)window fluorescence(FL)and ratiometric photoacoustic(RPA)dual-modality imaging of GSH using a GSH-activatable probe(LET-14).LET-14 was synthesized based on a rhodamine hybrid xanthene skeleton with a FL shielding 2,4-dinitrobenzene sulfonyl group that can be specifically cleaved by GSH,thus resulting in a markedly bathochromic-shift absorption,a 6.5-fold increase in NIR-II FL intensity(FL920)and a 13-fold increase in RPA signal(PA880/PA705)in vitro.Intriguingly,LET-14 exhibits good selectivity and sensitivity for NIR-II FL and RPA dual-modality imaging of GSH in 4T1 tumor-bearing mouse model.Our findings develop an in vivo detection tool of GSH,which has great potential in the field of cancer diagnosis.
基金supported by the National Natural Science Foundation of China(32071673 and 32202573)the Program of Hunan Science and Technology Innovation Team(2021RC4063)+1 种基金the Natural Science Foundation of Hunan Province(2021JJ31151 and 2022JJ50028)the Key Scientific Research Project of Hunan Education Department(22A0538)。
文摘Ganoderma lingzhi is a new species of the prize medicinal mushroom Ganoderma(Agaricomycetes).Using angiotensin I-converting enzyme(ACE)as a target,a tripeptide Ser-Tyr-Pro(SYP)was discovered with preponderant ACE inhibitory activity with an 50%inhibiting concentration(IC_(50))value of 62.50μg/mL attribute to the formed salt bridge and hydrogen bonds between SYP and ACE.SYP even maintained superior bioactivity after intestinal digestion,and exerted no cytotoxicity,but presented incomplete bioavailability in blood of spontaneous hypertensive rats(SHRs).Furthermore,it performed antihypertensive effect in vivo by inhibiting the influx of Ca^(2+)through activating endothelial NO synthase(e NOS)/NO/guanosine 3',5'-cyclic monophosphate(c GMP)pathway,accompanied by attenuating angiotensin II(Ang II)/NADPH oxidase(NOX)/reactive oxygen species(ROS)pathway.This work not only discoverers a novel pharmacological ingredient from medicinal mushroom G.lingzhi for hypertension therapy,but also provides an insight into molecular mechanism of the ACE inhibitory peptide(ACEIP)on lowering blood pressure.
基金Funding This research was funded by funding from the National Natural Science Foundation of China(No.82305090,No.82104738)Key Discipline Construction Project of High-level Traditional Chinese Medicine of the National Administration of Traditional Chinese Medicine-Traditional Chinese Medical Diagnostics(ZYYZDXK-2023069)+5 种基金Shanghai Municipal Health Commission Project(No.20234Y0168,No.2024QN018)Shanghai Science and Technology Commission Rising Star Cultivation Project(No.22YF1448900)Capacity Building of Local Colleges and Universities under the Shanghai Municipal Science and Technology Commission(21010504400)General Program of China Postdoctoral Science Foundation(2023M732337)Shanghai“Super Postdoctoral”Incentive Plan(2022509)Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine(23KFL005).
文摘Objective To identify the key features of facial and tongue images associated with anemia in female populations,establish anemia risk-screening models,and evaluate their performance.Methods A total of 533 female participants(anemic and healthy)were recruited from Shuguang Hospital.Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument.Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System(FDAS)and Tongue Diagnosis Analysis System version 2.0(TDAS v2.0).Least Absolute Shrinkage and Selection Operator(LASSO)regression was used for feature selection.Ten machine learning models and one deep learning model(ResNet50V2+Conv1D)were developed and evaluated.Results Anemic women showed lower a-values,higher L-and b-values across all age groups.Texture features analysis showed that women aged 30–39 with anemia had higher angular second moment(ASM)and lower entropy(ENT)values in facial images,while those aged 40–49 had lower contrast(CON),ENT,and MEAN values in tongue images but higher ASM.Anemic women exhibited age-related trends similar to healthy women,with decreasing L-values and increasing a-,b-,and ASM-values.LASSO identified 19 key features from 62.Among classifiers,the Artificial Neural Network(ANN)model achieved the best performance[area under the curve(AUC):0.849,accuracy:0.781].The ResNet50V2 model achieved comparable results[AUC:0.846,accuracy:0.818].Conclusion Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
基金funded by the National Key R&D Program of China(Grant no.2022YFC2807504)the Marine S&T Fund of Shandong Province for Qingdao Marine Science and Technology Center(Grant no.2022QNLM030002-1)the Central Public-interest Scientific Institution Basal Research(Grant no.2023TD02).
文摘Antarctic krill(Euphausia superba),widely distributes around Antarctica,is a key species supporting the biodiversity of the Southern Ocean ecosystem.The Commission for the Conservation of Antarctic Marine Living Resources(CCAMLR)has thus managed the krill fishery according to a precautionary way.Currently,CCAMLR is making effort to develop a refined krill fishery management approach based on more solid science,which requires accurate predictions of krill distribution.To address this need,this study investigated the effects of algorithm and spatial resolution on the performance of Antarctic krill distribution modelling.We integrated acoustic data from 4 surveys conducted in the waters adjacent to the Antarctic Peninsula with 11 environmental variables characterizing krill prey conditions,water mass properties,and seafloor topography.These data were processed at 4 spatial resolutions(5,10,15,and 20 km)to fit distribution models using 4 algorithms:Random Forests(RF),Generalized Additive Models(GAM),Extreme Gradient Boosting(XGBoost),and Artificial Neural Networks(ANN).Model performance was assessed and compared in terms of goodness-of-fit and predictive accuracy.The results showed that RF achieved the highest predictive performance at most resolutions,whereas GAM performed best at the coarsest resolution(20 km).XGBoost closely following RF in accuracy and demonstrated robustness as evidenced by the highly consistent partial dependence curves across resolutions.In contrast,ANN exhibited limitations with smaller sample sizes,resulting in comparatively poorer predictive performance.The analysis revealed a trade-off whereby reducing spatial resolution improved model fit and mitigated zero-inflation at the expense of fine-scale information and overall predictive accuracy.Ensemble models,integrating RF,GAM,and XGBoost,are proposed as potential balanced solutions to improve predictive stability,offering a more robust scientific basis for the refinement of krill management.
基金Guangdong Major Project of Basic and Applied Basic Research(2020B0301030004)National Natural Science Foundation of China(41875114)Science and Technology Commission of Shanghai Municipality,China(23DZ1204703)。
文摘The rapid intensification(RI)magnitude of tropical cyclones(TCs)over the western North Pacific(WNP)exhibits significant interannual variability and is influenced by multiple factors across various scales.These factors primarily include:interannual factors—sea surface temperature(SST)in key regions of the WNP,eastern Indian Ocean SST,El Niño-Southern Oscillation(ENSO),South Pacific Subtropical Dipole(SPSD),and western Pacific teleconnection;decadal factors—Atlantic Multidecadal Oscillation(AMO)and Pacific Decadal Oscillation(PDO);and longer-term factor—global warming.This study systematically analyzes these factors and their potential impacts,quantitatively assessing their relative importance.A statistical prediction model for the WNP TC-RI magnitude is developed based on ridge regression methods.The results indicate that the influence of these factors on the RI magnitude is closely related to the large-scale thermodynamic and dynamic conditions.Among them,the SPSD plays the most critical role in the interannual variability of the RI magnitude,followed by global warming and the AMO.Further analysis reveals that the statistical prediction model based on multiple factors demonstrates good predictive skill for the interannual variability of the TC RI magnitude.
基金supported by grants from the National Natural Science Foundation of China (grant nos.82472579,82172228,and 82202470)Shanghai Plastic Surgery Research Center of Shanghai Priority Research Center (grant no.2023ZZ02023)+2 种基金Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by the Science and Technology Commission of Shanghai Municipality (grant no.22MC1940300)Project of Biobank (grant no.YBKA202204) from Shanghai Ninth People’s Hospital of Shanghai Jiao Tong University School of MedicineCross-Disciplinary Research Fund of Shanghai Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine (grant no.JYJC202407)。
文摘Background: Plexiform neurofibromas(PNF) are highly vascular tumors with the potential for significant growth.Surgical removal of giant PNF is often challenging because of intraoperative hemorrhage.This study proposed and evaluated an innovative surgical approach involving FENCY ligation and the role of preoperative embolization in the resection of giant PNF.Methods: This was a retrospective,interventional,and sequential case series conducted in a plastic and reconstructive surgery unit.We summarized all patients with PNF who underwent resection at our center between2019 and 2024.Surgical case notes from 11 patients with giant PNF who underwent FENCY ligation were reviewed,including three patients who received preoperative embolization.All patients participated in structured telephone interviews.Patient demographics,surgical safety,postoperative recovery,and patient satisfaction were evaluated.Results: Among 456 patients with 494 PNF who underwent surgical resection,we categorized the procedures into median,large,and giant PNF subgroups.To illustrate comprehensive perioperative and surgical approaches,we analyzed seven female and four male patients with giant PNF.The median maximum tumor diameter at the time of surgery was 30.4 cm(range,11.5–55.6 cm).Most PNF were located on the face(63.6%),followed by the back(18.2%),buttocks(18.2%),upper limbs(9.1%),and neck(9.1%).The median intraoperative hemorrhage volume was 366 m L(range,10–2 034 m L),And the median hospital stay was 17 days(range,14–33 days).The mean follow-up duration was 2.5 years(range,0.4–5.5 years).No severe complications were observed,except for one case of infection.Conclusion: PNF resection,particularly giant PNF resection,is a high-risk treatment option.Comprehensive evaluation,perioperative preparation,and surgical techniques are required to ensure efficacy and safety.FENCY ligation and preoperative embolization can be used to resect giant PNF in multiple complex regions with satisfactory outcomes.
基金funded by the Science and Technology Major Project of the Inner Mongolia Autonomous Region of China to the State Key Laboratory of Reproductive Regulation(2023KYPT0010 and 2021ZD0048)STI 2030-Major Projects(2023ZD0407504)of China+1 种基金the development plan for young scientific and technological talents in colleges and universities of Inner Mongolia Autonomous Region of China(NMGIRT2204)the National Natural Science Foundation of China(32160172).
文摘Epigenetic regulation in the rumen,a unique ruminant organ,remains largely unexplored compared with other tissues studied in model species.In this study,we perform an in-depth analysis of the epigenetic and transcriptional landscapes across fetal and adult bovine tissues as well as pluripotent stem cells.Among the extensive methylation differences across various stages and tissues,we identify tissue-specific differentially methylated regions(tsDMRs)unique to the rumen,which are crucial for regulating epithelial development and energy metabolism.These tsDMRs cluster within super-enhancer regions that overlap with transcription factor(TF)binding sites.Regression models indicate that DNA methylation,along with H3K27me3 and H3K27ac,can be used to predict enhancer activity.Key upstream TFs,including SOX2,FOSL1/2,and SMAD2/3,primarily maintain an inhibitory state through bivalent modifications during fetal development.Downstream functional genes are maintained mainly in a stable repressive state via DNA methylation until differentiation is complete.Our study underscores the critical role of tsDMRs in regulating distal components of rumen morphology and function,providing key insights into the epigenetic regulatory mechanisms that may influence bovine production traits.
基金Supported by the National Natural Science Foundation of China,No.82402719Sichuan Science and Technology Program,No.2025ZNSFSC1553.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)requires accurate liver fibrosis assessment for management.While liver biopsy remains the gold standard,its invasiveness drives demand for non-invasive biomarkers.This review evaluates blood biomarkers for MASLD fibrosis staging.Established scores(fibrosis-4,non-alcoholic fatty liver disease fibrosis score)offer accessible screening but exhibit variable performance influenced by age,obesity,and comorbidities.Patented panels(e.g.,enhanced liver fibrosis test,FibroMeter)improve accuracy by integrating extracellular matrix or metabolic markers,though context-specific thresholds are essential.Emerging biomarkers like propeptide of type 3 collagen,Mac-2 binding protein glycosylation isomer,epigenetic markers(proliferator-activated receptor-γmethylation),and angiopoietin-like proteins a family of eight glycoproteins show promise but require large-scale validation.Genetic risk scores and multi-omics approaches face generalizability challenges.Integration strategies,such as combining serum biomarkers with liver stiffness measurement via Agile scores,enhance diagnostic precision and reduce indeterminate classifications.Current tools aid risk stratification,but no single biomarker replicates biopsy-level precision.Future efforts must prioritize MASLD-specific diagnostic frameworks,standardized protocols,and multi-modal integration to enhance clinical utility and address MASLD’s growing burden.
文摘The production of hydrogen peroxide(H_(2)O_(2))via artificial photosynthesis using single-atom semiconductor photocatalysts represents a promising green and sustainable technology.However,its efficiency is still limited by sluggish water oxidation kinetics,poor photogenerated charge separation,and insufficient O_(2)adsorption and activation capabilities.Herein,uniformly dispersed single-atom catalysts(SACs)with a Co-N_(4)coordination structure have been synthesized by thermally transforming cobalt phthalocyanine(CoPc)assemblies pre-anchored on phosphate functionalized reduced graphene oxide(Co@rGO-P),and then used to construct heterojunctions with perylenetetracarboxylic acid(PTA)nanosheets for photocatalytic H_(2)O_(2)production by an in-situ growth method.The optimized Co@rGO-P/PTA achieved an H_(2)O_(2)production rate of 1.4 mmol g^(-1)h^(-1)in pure water,with a 12.9-fold enhancement compared to pristine PTA nanosheets exhibiting competitive photoactivity among reported perylene-based materials.Femtosecond transient absorption spectra,in-situ diffuse reflectance infrared Fourier transform spectra and theoretical calculations reveal that the exceptional performance is attributed to the enhanced electron transfer from PTA to rGO via the phosphate bridge and then to the Co-N_(4),and to the promoted O_(2)adsorption and activation at Co-N_(4)active sites.This work provides a feasible and effective strategy for designing highly efficient single-atom semiconductor heterojunction photocatalysts for H_(2)O_(2)production.
基金supported by the Natural Science Foundation of Qinghai Province in China(No.2019-ZJ-944Q)the University-level Planning Project of Qinghai Minzu University of Qinghai Province in China(Nos.2022GH11 and 2022GH13)。
文摘Up to now,“Turn-on”fluorescence sensor exhibits promising potential toward the detection of heavy metal ions,anions,drugs,organic dyes,DNA,pesticides,and other amino acids due to their simple,quick detection,and high sensitivity and selectivity.Herein,a novel fluorescence method of detecting Cr^(3+)in an aqueous solution was described based on the fluorescence resonance energy transfer between rhodamine B(Rh B)and gold nanoparticles(Au NPs).The fluorescence of Rh B solution could be obviously quenched(“off”state)with the presence of citrate-stabilized Au NPs.However,upon addition of Cr^(3+)to Au NPs@Rh B system,the fluorescence of Au NPs was recovered owing to the strong interaction between Cr^(3+)and the specific groups on the surface of citrate-stabilized Au NPs,which will lead to the aggregation of Au NPs(“on”state).At this point,the color of the reaction solution turned to black.Under optimal conditions,the limit of detection(LOD)for Cr^(3+)was 0.95 n M(signal-to-noise ratio,S/N=3)with a linear range of 0.164 n M to 3.270μM.Furthermore,the proposed method exhibits excellent performances,such as rapid analysis,high sensitivity,extraordinary selectivity,easy preparation,switch-on fluorescence response,and non-time consuming.
基金Supported by Special Research Plan 2023 of Chaozhou,No.202303GY05。
文摘BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.
基金supported by grants from the National Natural Science Foundation of China(82272396)Gusu Health Project of Suzhou(GSWS2022076 and GSWS2023004)。
文摘Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive patients,and those with hematological malignancies.It poses a risk of liver fibrosis and cirrhosis.Data sources:Relevant articles published till September 2024 were located using Pub Med searches.The further search terms utilized were:“immunocompromised”,“solid organ transplant”,“HIV”,“hematological malignancy”,and“hepatitis E virus”.A manual search of references from pivotal articles extended further publications.The search parameters encompass publications in English.Results:The epidemiology,clinical manifestations,diagnostic measures,and therapeutic modalities of chronic hepatitis E were discussed.Immunocompromised individuals who are infected with HEV are at an increased risk of developing chronic infections,which may progress to liver fibrosis and cirrhosis.Current understanding of HEV is still limited,and there is no medicine that specifically targets hepatitis E.Consequently,the prevention and management of hepatitis E continue to present a significant challenge.Conclusions:Chronic hepatitis E patients need special attention in clinical practice.The relevant risk factors must be identified to facilitate accurate diagnosis and the implementation of more effective preventive measures,thereby enhancing the monitoring,treatment,and prevention of immunocompromised individuals.
基金The National Natural Science Foundation of China under contract Nos 42406040 and 42476204the Shandong Provincial Postdoctoral Foundation Project(Innovation Project)under contract No.SDCX-ZG-202400181+2 种基金the Postdoctoral Fellowship Program of CPSF under contract No.GZC20232705the Qingdao Postdoctoral Applied Research Project under contract No.QDBSH20240101018the Laoshan Laboratory under contract Nos LSKJ202204001 and LSKJ202205001.
文摘With global industrialization and the excessive use of fossil fuels,greenhouse gas emissions have substantially increased,particularly the concentrations of carbon dioxide(CO_(2)),which have had profound impacts on global warming and extreme climate events.As a key technology to combat climate change,mineral carbonation has been widely recognized as an effective technique for CO_(2)sequestration and utilization.In recent years,seawater-based solutions(including desalination brine and seawater-based wastewater)have become a research hotspot in mineral carbonation due to their strong alkalinity,high content of Ca^(2+)and Mg^(2+),and lower costs compared to chemical solvents.This article comprehensively reviews the CO_(2)mineral carbonation mechanisms based on seawater-based solutions,highlighting recent research achievements and potential development trends in capturing CO_(2)through the pH swing method,modified Solvay process,chemical precipitation method,and chemical absorption method.By comparing the use of seawater-based solutions for mineral carbonation with traditional techniques,this study evaluates its advantages and the challenges it may face in practical applications,aiming to provide a more accurate assessment of the impact and future development of this technology.
基金financed by National Natural Science Foundation of China(Nos.81773642,52073139)Guangdong Provincial Clinical Research Center for Laboratory Medicine(No.2023B110008)the Provincial subsidies for the construction of high-level hospitals(No.K202201)。
文摘Liposomal drugs have significantly improved cancer treatment in recent years.However,the clinical application of conventional liposomes is limited by factors such as the complexity of the preparation process and the multitude of auxiliary components.By replacing phospholipids and cholesterol with vitamin E succinate(VES),this study addresses these shortcomings by developing a novel modified nanoprodrug,and the new formulation is used to deliver cisplatin.Concurrently,liposomes encapsulating cisplatin were prepared by conventional formulations for comparative experiments.Moreover,VES can inhibit the expression of mitochondrial uncoupling protein 2(UCP2),further enhancing mitochondrial damage in tumor cells within the tumor microenvironment(TME)and suppressing the tricarboxylic acid cycle,thereby reducing ATP production.Additionally,cisplatin damages DNA structure,affecting the binding of Nrf2 to the antioxidant response element(ARE),thereby inhibiting the signaling expression of heme oxygenase1(HO-1).The combined action of cisplatin and VES disrupts the redox balanceleading to a significant accumulation of reactive oxygen species(ROS).The nanoprodrug effectively alters the redox state of the TME and inhibits antioxidant defenses,thereby amplifying oxidative stress damage and enhancing the efficacy of cisplatin.Notably,compared to free cisplatin,the nanoprodrug demonstrates greater efficacy in both cell line-derived xenograft(CDX)and patient-derived tumor xenograft(PDX)liver cancer models.Overall,this study successfully develops a novel mitochondrial-targeted nanoprodrug by modifying the conventional liposome formulation.This provides a new strategy for amplifying oxidative stress in order to disrupt redox balance,and enhance cisplatin efficacy.
基金the Ethics Committee of the West China Hospital,Sichuan University(No.2018256)the Animal Ethical and Welfare Committee of Sichuan University in China(No.20211218A).
文摘Objectives:Exosomal long noncoding RNAs(lncRNAs)might facilitate epithelial–mesenchymal transition(EMT)in liver cancer after transarterial chemoembolization(TACE),thereby enhancing tumor cell invasiveness and migration.This study investigated the prognostic role of plasma exosomal long noncoding RNA-plasmacytoma variant translocation 1(lncRNA-PVT1)in TACE treated hepatocellular carcinoma(HCC).Methods:Plasma exosomal lncRNA-PVT1 was evaluated via qPCR before and after TACE.Hepatoma cell behavior was investigated in different HCC cell lines.A lncRNA-PVT1 plasmid was synthesized and overexpressed,and si-lncRNA PVT1 was transfected into poorly invasive cells to reveal its influence on cell characteristics.The lncRNA-PVT1–FoxM1 interaction was elucidated using a double-luciferase reporter gene assay.The effect of miRNA-345-5p on minimally invasive hepatoma cells was assessed.Three experimental groups were established:poorly invasive cells,poorly invasive cells co-cultured with exosomes from hypoxia-induced highly invasive cells,and poorly invasive cells co-cultured with normal hepatocyte exosomes.Liver cancer cells were subcutaneously inoculated into nude mice,with subsequent observations of weight,tumor formation,and tumor size.Results:We identified two lncRNAs(lncRNA-PVT1 and GAPLINC)associated with EMT in the hypoxic microenvironment of liver cancer.Cox multivariate regression analysis was used to establish a prognostic model distinguishing high-and low-risk groups.Hypoxia-induced HepG2 exosomes significantly promoted EMT in poorly invasive HCC cells.LncRNA-PVT1 overexpression and silencing altered E-cadherin,vimentin,and FoxM1 expression,cell proliferation,invasion,migration,and apoptosis.miR-345-5p directly targeted lncRNA-PVT1 and FoxM1,affecting downstream targets.In vivo,co-culturing poorly invasive hepatoma cells with exosomes from highly invasive cells increased tumor volumes,upregulated lncRNA-PVT1,FoxM1,Ki67,and MMP9 expression,and downregulated miR-345-5p expression.Conclusions:Plasma exosomal lncRNA-PVT1 expression is upregulated in highly invasive cells post-hypoxia,potentially serving as a biomarker for evaluating liver cancer prognosis after TACE.Through a miRNA-345-5p-mediated competing endogenous RNA mechanism,it promotes EMT in poorly invasive cells,likely contributing to recurrence and metastasis post-HCC interventional embolization.
基金the funding from the National Natural Science Foundation of China No.52275294the National Key Research and Development Program of China(No.2018YFA0703000)。
文摘Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular microenvironment.However,the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink,making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials.To overcome this limitation,we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel.This medium possesses yield stress and self-healing properties,facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it.By adjusting the printing speed,we controlled the filament diameter,achieving a range from 250μm to 1000μm,and ensuring precise control over ink deposition locations and filament shapes.Using the in situ endothelialization method,we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells.In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue.We also investigated the impact of varying vascular densities on liver tissue function.Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways.In summary,this method is adaptable to various materials,allowing the rheological properties of the supporting bath and the tissue's porosity to be modified using microgels,thus enabling precise regulation of the liver tissue microenvironment.Additionally,it facilitates the rapid construction of three-dimensional vascular structures within liver tissue.The resulting vascularized liver tissue model exhibits enhanced biological functionality,opening new opportunities for biomedical applications.
基金supported by the Jilin Provincial Department of Education Science and Technology Research Project(JJKH20231141K)Natural Science Foundation of Jilin Province of China(20230101154JC)Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)。
文摘Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contributors to CP,the carboxypeptidase A1 p.Ser282Pro(CPA1^(S282P))variant has been proposed to promote disease through misfolding-induced endoplasmic reticulum stress(ERS),although the broader pathogenic landscape remains incompletely defined.This study generated a rabbit model mimicking the human CPA1S282P mutation using the SpRY-ABE-8.17 system.Homozygous CPA1^(S282P)rabbits exhibited characteristic human CP phenotypes following alcohol induction,including visceral pain,elevated serum lipase and amylase,inflammatory cell infiltration,and extensive pancreatic fibrosis.Biochemical analyses confirmed that the p.S282P mutation induced CPA1 misfolding and elevated the expression of ERS markers GRP78 and CHOP in both transfected HEK293T cells and homozygous mutant rabbits.Notably,the CPA1^(S282P)mutation markedly disrupted intra-pancreatic lipid homeostasis,contributing to the development of CP in mutant rabbits.This study successfully established the first rabbit model of CP that accurately recapitulates CP caused by a defined human point mutation.Additionally,this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism,offering a foundation for identifying novel therapeutic targets for human CP.
基金supported by STI2030-Major Projects(2021ZD0200200)the National Natural Science Foundation of China(62327805 and 82151307)+1 种基金the Equipment Development Project of the Chinese Academy of Sciences(YJKYYQ20190040)the Science and Technology Innovation Program of Hunan Province(2024RC4028).
文摘The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown.In this study,we first detected and validated the rich club in the structural networks of mouse,monkey,and human brains using neuronal tracing or diffusion magnetic resonance imaging data.Further,we assessed the role of rich clubs in functional integration,segregation,and balance using quantitative metrics.Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species,with the functional networks of higher species exhibiting greater integration.These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
文摘AIM:To investigate the value of combined detection of circulating cell-free DNA(cfDNA),a-fetal protein(AFP) and a L-fucosidase(AFU) for diagnosis of hepatocellular carcinoma(HCC).METHODS:Serum samples from 39 HCC patients and 45 normal controls were collected.Branched DNA(bDNA) was used to detect the level of cfDNA,and a receiver operating characteristic curve was employed to evaluate the diagnostic sensitivity,specificity,accuracy,positive predictive value,negative predictive value,positive likelihood ratio,negative likelihood ratio and Youden index,and to assess the diagnostic efficiency and their correlations with the clinicopathological features.AFP and AFU were detected by chemiluminescence and colorimetry,respectively.The significance of combined detection of the three biomarkers was discussed.RESULTS:cfDNA level was increased in 22 of the 39 HCC samples and in 2 of the 45 normal controls.cfDNA level in HCC samples was significantly higher than that in normal controls(P < 0.05).There were significant differences in sex and extra-and intrahepatic metastasis(P < 0.05).There was no significant correlation between cfDNA,AFP and AFU in the detection of HCC.The sensitivity of combined detection of cfDNA with one marker(AFP or AFU) and cfDNA with two markers(AFP and AFU) was 71.8%,87.2% and 89.7% vs 56.4%,53.8% and 66.7% for cfDNA,AFP and AFU used alone,respectively,the difference being statistically significant(P < 0.05).CONCLUSION:Quantitative analysis of cfDNA is sensitive and feasible,and the combined detection of cfDNA with AFP or AFU or both could improve the diagnostic sensitivity for HCC.
文摘Objective To create transgenic rabbits by microinjecting human apolipoprotein A-Ⅱ (apoA-Ⅱ) gene into one-cell embryos, to study apoA-Ⅱ gene function on plasma lipoprotein metabolism and atherosclerosis. Methods Superovulation and synchronization of estrus were induced in female Japanese White Rabbits by injecting hormone, then mating with male. After collected the fertilized eggs, the human apoA-Ⅱ gene was microinjected into the male pronucleus of eggs. The injected eggs were transferred into recipient female rabbits. Last, extract DNA from the new borns ear and determine whether the newborns were transgenic by polymerase chain reaction (PCR) or Southern blot analysis. Results A total of 822 embryos with microinjection of human apoAⅡ gene were implanted into 28 recipient rabbits. The number of surviving newborns was 37. 3 transgenic positive surviving founders were found with human apoA-Ⅱ.
