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
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
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
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
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
0 INTRODUCTION The carbon buried in marine sediments in the form of organic carbon or carbonate minerals represents the largest pathway for carbon removal from Earth's surface environments(Sun and Turchyn,2014).Mi...0 INTRODUCTION The carbon buried in marine sediments in the form of organic carbon or carbonate minerals represents the largest pathway for carbon removal from Earth's surface environments(Sun and Turchyn,2014).Microbial sulfate reduction(MSR)is a fundamental biogeochemical process occurring in marine sediments,where sulfate-reducing bacteria(SRB)reduce sulfate(SO42-)to sulfide(S2-)using organic matter or methane as electron donors(Jorgensen,2021).展开更多
Objective To investigate the facial spectrum and color characteristics of patients with essen-tial hypertension post administering antihypertensive drugs,establish a classification and evaluation model based on the fa...Objective To investigate the facial spectrum and color characteristics of patients with essen-tial hypertension post administering antihypertensive drugs,establish a classification and evaluation model based on the facial colors of the enrolled patients,and perform in-depth analysis on the important characteristics of their facial spectrum.Methods From September 3,2018,to March 23,2024,participants with essential hyperten-sion(receiving antihypertensive medication treatment,hypertension group)and normal blood pressure(control group)were recruited from the Cardiology Department of Shanghai Hospital of Traditional Chinese Medicine,the Coronary Care Unit of Shanghai Tenth People's Hospital,the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai Uni-versity of Traditional Chinese Medicine,and the Gaohang Community Health Service Center.This study employed the propensity score matching(PSM)method to reduce study partici-pants selection bias.Spectral information in the facial visible light spectrum of the subjects was collected using a flame spectrometer,and the spectral chromaticity values were calculat-ed using the equal-interval wavelength method.The study analyzed the differences in spec-tral reflectance across various facial regions,including the entire face,forehead,glabella,nose,jaw,left and right zygomatic regions,left and right cheek regions as well as differences in parameters within the Lab color space between the two subject groups.Feature selection was conducted using least absolute shrinkage and selection operator(LASSO)regression,fol-lowed by the application of various machine learning algorithms,including logistic regres-sion(LR),support vector machine(SVM),random forest(RF),Naïve Bayes(NB),and eX-treme Gradient Boosting(XGB).The reduced-dimensional dataset was split in a 7:3 ratio to establish a classification and assessment model for facial coloration related to primary hyper-tension.Additionally,model fusion techniques were applied to enhance the predictive power.The performance of the models was evaluated using metrics including the area under the curve(AUC)and accuracy.Shapley Additive exPlanations(SHAP)was used to interpret the outcomes of the models.Results A total of 114 participants were included in both hypertension and control groups.Reflectance analysis across the entire face and eight predefined areas revealed that the hypertensive group exhibited significantly higher reflectance of corresponding color light in the blue-violet region(P<0.05)and a lower reflectance in the red region(P<0.05)compared with control group.Analysis of Lab color space parameters across the entire face and eight predefined areas showed that hypertensive group had significantly lower a and b values than control group(P<0.05).LASSO regression analysis identified a total of 18 facial color features that were highly correlated with hypertension,including the a values of the chin and the right cheek,the reflectance at 380 nm and at 780 nm of the forehead.The results of the multi-mod-el classification showed that the RF classification model was the most effective,with an AUC of 0.74 and an accuracy of 0.77.The combined model of RF+LR+SVM outperformed a single model in their classification performance,achieving an AUC of 0.80 and an accuracy of 0.76.SHAP model visualization results indicated that the top three contributors to ideal prediction results based on the characteristics from the facial spectrum were the reflectance at 380 nm across the entire face and of the nose as well as the a value of the chin.Conclusion Within the same age group,patients with essential hypertension exhibited signif-icant and regular changes in facial color and facial spectral reflectance parameters after the administration of antihypertensive drugs.Furthermore,facial reflectance indicators,such as the overall reflectance at 380 nm and the a value of the chin,could offer valuable references for clinically assessing the drug efficacy and health status of patients with essential hyperten-sion.展开更多
Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over othe...Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over other Omicron variants(Tamura et al.,2023).However,second-generation vaccines,including the BA.2 or BA.5 bivalent vaccine boosters,did not produce robust neutralization against the newly emerged XBB.1 or EG.5(Zou et al.,2023).Compared with variants BA.2 and BA.5,XBB.1 carries more mutations in the receptor binding domain(RBD)and exhibits significant immune evasion(Wang et al.,2023b).XBB.1 and its descendent lineages have rapidly become the dominant SARS-CoV-2 strain and are causing the next global wave of COVID-19.Therefore,it is essential to develop an updated vaccine against the newly emerged SARS-CoV-2 variants.展开更多
The thermochromic mechanism and the structure-property regulation principle of reversible thermochromic polydiacetylene(PDA)materials have always been a challenging issue.In this work,a series of diacetylene monomers(...The thermochromic mechanism and the structure-property regulation principle of reversible thermochromic polydiacetylene(PDA)materials have always been a challenging issue.In this work,a series of diacetylene monomers(m-PCDA)containing phenyl and amide or carboxyl groups were synthesized from 10,12-pentacosadiynoic acid(PCDA)through the esterification or amidation reactions.The effects of the number and the distribution of the functional groups in m-PCDA molecules on their solid-state polymerization capability,and the thermochromic mechanism of their corresponding polymers(m-PDA)were investigated and discussed in detail.The results show that the m-PCDA monomers containing both benzene ring and groups that can form hydrogen bonding interactions have strong intermolecular interaction,and are easy to carry out the solid phase polymerization under 254-nm UV irradiation to obtain the corresponding new thermochromic m-PDA materials.The thermochromic behavior of m-PDA depends on its melting process.The initial color-change temperature(blue to red)is determined by the onset melting tem perature,and the temperature range in which reversible color recovery can be achieved by repeat heating-cooling treatment is determined by its melting range.According to the proposed thermochromic mechanism of PDA,various new PDA materials with precise thermochromic temperatu res and reversible thermochromic temperature ra nges can be designed and synthesized through the appropriate introduction of benzene ring and groups that can form hydrogen bonding interactions into the molecular structure of linear diacetylene monomer.This work provides a perspective to the precise molecular structure design and the property regulation of the reversible thermochromic PDA materials.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
AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by...AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS： In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 rain of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kB was found between control and P-selectin antibody-treated livers. CONCLUSION： In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.展开更多
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.
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 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.
基金supported by the National Key Research and Development Program of China(No.2022YFE0136300)the National Natural Science Foundation of China(Nos.42276060,42076031)+1 种基金the Natural Science Foundation of Shandong Province(No.ZR2021YQ26)the Taishan Scholars Program of Shandong Province(No.tsqn201909057).
文摘0 INTRODUCTION The carbon buried in marine sediments in the form of organic carbon or carbonate minerals represents the largest pathway for carbon removal from Earth's surface environments(Sun and Turchyn,2014).Microbial sulfate reduction(MSR)is a fundamental biogeochemical process occurring in marine sediments,where sulfate-reducing bacteria(SRB)reduce sulfate(SO42-)to sulfide(S2-)using organic matter or methane as electron donors(Jorgensen,2021).
基金National Natural Science Foundation of China(82104738 and 82004255)Key Discipline Construction Project of High-level Traditional Chinese Medicine of the National Administration of Traditional Chinese Medicine-Traditional Chinese Medical Diagnostics(ZYYZDXK-2023069).
文摘Objective To investigate the facial spectrum and color characteristics of patients with essen-tial hypertension post administering antihypertensive drugs,establish a classification and evaluation model based on the facial colors of the enrolled patients,and perform in-depth analysis on the important characteristics of their facial spectrum.Methods From September 3,2018,to March 23,2024,participants with essential hyperten-sion(receiving antihypertensive medication treatment,hypertension group)and normal blood pressure(control group)were recruited from the Cardiology Department of Shanghai Hospital of Traditional Chinese Medicine,the Coronary Care Unit of Shanghai Tenth People's Hospital,the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai Uni-versity of Traditional Chinese Medicine,and the Gaohang Community Health Service Center.This study employed the propensity score matching(PSM)method to reduce study partici-pants selection bias.Spectral information in the facial visible light spectrum of the subjects was collected using a flame spectrometer,and the spectral chromaticity values were calculat-ed using the equal-interval wavelength method.The study analyzed the differences in spec-tral reflectance across various facial regions,including the entire face,forehead,glabella,nose,jaw,left and right zygomatic regions,left and right cheek regions as well as differences in parameters within the Lab color space between the two subject groups.Feature selection was conducted using least absolute shrinkage and selection operator(LASSO)regression,fol-lowed by the application of various machine learning algorithms,including logistic regres-sion(LR),support vector machine(SVM),random forest(RF),Naïve Bayes(NB),and eX-treme Gradient Boosting(XGB).The reduced-dimensional dataset was split in a 7:3 ratio to establish a classification and assessment model for facial coloration related to primary hyper-tension.Additionally,model fusion techniques were applied to enhance the predictive power.The performance of the models was evaluated using metrics including the area under the curve(AUC)and accuracy.Shapley Additive exPlanations(SHAP)was used to interpret the outcomes of the models.Results A total of 114 participants were included in both hypertension and control groups.Reflectance analysis across the entire face and eight predefined areas revealed that the hypertensive group exhibited significantly higher reflectance of corresponding color light in the blue-violet region(P<0.05)and a lower reflectance in the red region(P<0.05)compared with control group.Analysis of Lab color space parameters across the entire face and eight predefined areas showed that hypertensive group had significantly lower a and b values than control group(P<0.05).LASSO regression analysis identified a total of 18 facial color features that were highly correlated with hypertension,including the a values of the chin and the right cheek,the reflectance at 380 nm and at 780 nm of the forehead.The results of the multi-mod-el classification showed that the RF classification model was the most effective,with an AUC of 0.74 and an accuracy of 0.77.The combined model of RF+LR+SVM outperformed a single model in their classification performance,achieving an AUC of 0.80 and an accuracy of 0.76.SHAP model visualization results indicated that the top three contributors to ideal prediction results based on the characteristics from the facial spectrum were the reflectance at 380 nm across the entire face and of the nose as well as the a value of the chin.Conclusion Within the same age group,patients with essential hypertension exhibited signif-icant and regular changes in facial color and facial spectral reflectance parameters after the administration of antihypertensive drugs.Furthermore,facial reflectance indicators,such as the overall reflectance at 380 nm and the a value of the chin,could offer valuable references for clinically assessing the drug efficacy and health status of patients with essential hyperten-sion.
基金supported by a grant from the National Key R&D Program of China(2023YFC3041600 YW,the National Natural Science Foundation of China(82025001 JZ,92369113 YW,82172240 YW)Guangdong Basic and Applied Research Projects(2023B1515020040 YW,2021B1515130005 JZ,2021B1212030016 JD,2021A1111100009 JD)+7 种基金Science and Technology Planning Project of Guangzhou City(2023A04J1279 LZ)ZhongNanShan Medical Foundation of Guangdong Province(ZNSA-2020013 JZ)the Science and Technology Project of General Administration of Customs,P.R.China(2023HK065 LZ)State Key Laboratory of Respiratory Disease(SKLRD-Z-202214,SKLRD-OP-202309 YW,SKLRD-Z-202411 LZ)the Self-supporting Program of Guangzhou Laboratory(GZNL2023A01006,SRPG22-001)Guangzhou Medical University(YP2022005 YW)Korea Institute of Planning and Evaluation for Technology in Food,Agriculture and Forestry(IPET)through Animal Disease Management Technology Advancement Support Program,funded by the Ministry of Agriculture,Food and Rural Affairs(MAFRA)(122012-2,122060-2 JZ)the National Clinical Research Center for Respiratory Disease(BRD-NCRCRD,Guangzhou,Southern China).Patronus Biotech is a company researching virus-like particle display technology and vaccines.Yu Zhou and Jing Jin are named inventors on a patent invention relating to the described novel SARS-CoV-2 virus-like particle vaccine.All BALB/c mouse experiments complied with relevant ethical regulations for animal research and were approved by the LUYE PHARMA Animal Experimentation Ethics Committee.The K18-hACE2 mouse experiment was reviewed and approved by the Institutional Animal Care and Use Committees of Guangzhou Medical University(2023-0451).All authors declare that they have no conflict of interests.
文摘Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over other Omicron variants(Tamura et al.,2023).However,second-generation vaccines,including the BA.2 or BA.5 bivalent vaccine boosters,did not produce robust neutralization against the newly emerged XBB.1 or EG.5(Zou et al.,2023).Compared with variants BA.2 and BA.5,XBB.1 carries more mutations in the receptor binding domain(RBD)and exhibits significant immune evasion(Wang et al.,2023b).XBB.1 and its descendent lineages have rapidly become the dominant SARS-CoV-2 strain and are causing the next global wave of COVID-19.Therefore,it is essential to develop an updated vaccine against the newly emerged SARS-CoV-2 variants.
基金financially supported by the National Natural Science Foundation of China(No.51973205)the Fundamental Research Funds for the Central Universities(Nos.WK9110000066,WK3450000005 and WK3450000006)。
文摘The thermochromic mechanism and the structure-property regulation principle of reversible thermochromic polydiacetylene(PDA)materials have always been a challenging issue.In this work,a series of diacetylene monomers(m-PCDA)containing phenyl and amide or carboxyl groups were synthesized from 10,12-pentacosadiynoic acid(PCDA)through the esterification or amidation reactions.The effects of the number and the distribution of the functional groups in m-PCDA molecules on their solid-state polymerization capability,and the thermochromic mechanism of their corresponding polymers(m-PDA)were investigated and discussed in detail.The results show that the m-PCDA monomers containing both benzene ring and groups that can form hydrogen bonding interactions have strong intermolecular interaction,and are easy to carry out the solid phase polymerization under 254-nm UV irradiation to obtain the corresponding new thermochromic m-PDA materials.The thermochromic behavior of m-PDA depends on its melting process.The initial color-change temperature(blue to red)is determined by the onset melting tem perature,and the temperature range in which reversible color recovery can be achieved by repeat heating-cooling treatment is determined by its melting range.According to the proposed thermochromic mechanism of PDA,various new PDA materials with precise thermochromic temperatu res and reversible thermochromic temperature ra nges can be designed and synthesized through the appropriate introduction of benzene ring and groups that can form hydrogen bonding interactions into the molecular structure of linear diacetylene monomer.This work provides a perspective to the precise molecular structure design and the property regulation of the reversible thermochromic PDA materials.
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.
基金Supported by Grants from the American Liver Foundation, Naomi Judd Liver Scholar Award, The American Surgical Association Career Development Fellowship, and National Ⅰ
文摘AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS： In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 rain of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kB was found between control and P-selectin antibody-treated livers. CONCLUSION： In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.
