Astragali Radix(AR) and Notoginseng Radix et Rhizoma(NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair(AN) in improving cardiac remodeling and its underl...Astragali Radix(AR) and Notoginseng Radix et Rhizoma(NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair(AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction(TAC) in mice and angiotensin II(Ang II)-induced neonatal rat cardiomyocytes(NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide(NT-pro BNP), cardiac troponin T(CTn-T), and interleukin-6(IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes(ANP, BNP, and MYH7) in vivo and in vitro.Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators(COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1(TGF-β1)/mothers against decapentaplegic homolog 3(Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein(Drp1)(Ser616) expression and upregulated mitogen 2(MFN-2) and optic atrophy 1(OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.展开更多
The Song Chay Dome in southeastern Yunnan Province,China,is intruded by the Late Cretaceous Laojunshan granites.New apatite and zircon fission-track data for the Laojunshan granites allow us to reconstruct the exhumat...The Song Chay Dome in southeastern Yunnan Province,China,is intruded by the Late Cretaceous Laojunshan granites.New apatite and zircon fission-track data for the Laojunshan granites allow us to reconstruct the exhumation history of the Song Chay Dome.The fission-track dating indicates that the Laojunshan granites experienced four main stages of rapid cooling and exhumation at 75–63,53–43,31–20,and 12–4 Ma.The first stage was related to the thermal equilibration with surrounding rocks after magma emplacement.The rapid cooling and exhumation at 53–43 Ma were caused by normal faulting in the Late Mesozoic–Early Cenozoic extensional setting of southwestern South China,which resulted in the Laojunshan granites and Song Chay Dome being exhumed in the footwall of faults.The third stage(31–20 Ma) was the result of southeastward extrusion of the Tibetan Plateau and sinistral strike-slip movement on the NW-SE-trending Nanwenhe and Maguan-Dulong faults.The 31 Ma representing the beginning of the interaction between the Tethyan Himalayan tectonic domain and the South China Block.The final stage was mainly due to activity on the Nanwenhe Fault to the north of the Laojunshan granites,caused by lateral extrusion of the southeastern Tibetan Plateau since ca.15 Ma.These cooling and exhumation events since the Late Cretaceous indicate that the Song Chay Dome and southwestern South China Block have been affected by the Himalayan Orogeny since the Oligocene.展开更多
Microwave ablation(MWA)is emerging as a highly effective treatment for colorectal liver metastases(CRLMs).This review explores the advantages of MWA compared to other ablative techniques such as radiofrequency ablatio...Microwave ablation(MWA)is emerging as a highly effective treatment for colorectal liver metastases(CRLMs).This review explores the advantages of MWA compared to other ablative techniques such as radiofrequency ablation and cryoablation and highlights its clinical efficacy,safety,and technical considerations.MWA offers significant benefits,including higher intratumoral temperatures,larger ablation zones,and reduced susceptibility to the heat-sink effect,which make it particularly suitable for tumors near large blood vessels.This review details the patient selection criteria,procedural approaches,and the use of advanced imaging techniques to improve the precision and effectiveness of MWA.Clinical outcomes indicate that MWA achieves high rates of complete tumor ablation and long-term survival with a favorable safety profile.This review is significant because it provides updated insights into the expanding role of MWA in treating unresectable CRLM and its potential as an alternative to surgical resection for resectable tumors.By summarizing recent studies and clinical trials,this review highlights the comparative effectiveness,safety,and integration with systemic therapies of MWA.In conclusion,MWA is a promising treatment option for CRLM and offers outcomes comparable to or better than those of other ablative techniques.Future research should focus on optimizing technical parameters,integrating MWA with systemic therapies,and conducting large-scale randomized controlled trials to establish standardized treatment protocols.Advancing our understanding of MWA will enhance its application and improve long-term survival and quality of life for patients with CRLM.展开更多
Oral cancer,particularly oral squamous cell carcinoma(OSCC),remains a leading cause of cancer-related morbidity and mortality,with delayed diagnosis being a major contributing factor.Although salivary biomarkers have ...Oral cancer,particularly oral squamous cell carcinoma(OSCC),remains a leading cause of cancer-related morbidity and mortality,with delayed diagnosis being a major contributing factor.Although salivary biomarkers have been explored for over three decades,the need for reliable,non-invasive diagnostic methods that enable early detection and continuous monitoring of OSCC remains unmet.This review aims to provide an updated overview of the latest advancements in salivary biomarker research,focusing on emerging biomarkers such as interleukin-6,interleukin-8,microRNAs and DNA methylation patterns,as well as metabolites and microbiota,all of which show significant promise for early OSCC detection.In addition to discussing well-established biomarkers,we explore recent technological developments that increase the sensitivity and specificity of these biomarkers,such as mass spectrometry,multiplex assays,and nanobiosensors.These developments are complemented by the integration of artificial intelligence for data analysis,which enables more accurate,point-of-care diagnostics that could revolutionize oral cancer screening.This review not only consolidates current knowledge but also addresses the challenges that hinder the widespread clinical adoption of salivary diagnostics,such as saliva variability and assay standardization.By overcoming these barriers,salivary biomarker-based diagnostics have the potential to transform OSCC detection,offering a noninvasive,cost-effective solution that can improve early diagnosis and patient outcomes.展开更多
This study explored the connection between childhood psychological maltreatment and online trolling,as well as the influence of moral disengagement and mindfulness in that relationship.A total of 984 college students(...This study explored the connection between childhood psychological maltreatment and online trolling,as well as the influence of moral disengagement and mindfulness in that relationship.A total of 984 college students(54%females,Mean age=20.9 years,SD=1.57 years)took part in the current research.The students responded to standardized measures of childhood psychological maltreatment,online trolling,moral disengagement,mindfulness.Results following the regression and the mediation analyses showed that childhood psychological maltreatment was associated with higher online trolling among college students.Moral disengagement played a mediating role in the link between childhood psychological maltreatment and online trolling,predicting to increased trolling behavior.Furthermore,mindfulness moderated the direct connection between moral disengagement and online trolling.Specifically,compared to those with high mindfulness,individuals with high moral disengagement were more inclined to engage in online trolling when they had low mindfulness.These findings add to our understanding of how and when childhood psychological maltreatment relates to online trolling of which moral engagement and mindfulness would be protective.展开更多
Litchi(Litchi chinensis Sonn.),an important fruit tree in tropical and subtropical regions,possesses substantial economic value.The branchand leaf-related traits of litchi have a significant impact on litchi yield and...Litchi(Litchi chinensis Sonn.),an important fruit tree in tropical and subtropical regions,possesses substantial economic value.The branchand leaf-related traits of litchi have a significant impact on litchi yield and quality.However,due to limitations such as the density of the genetic linkage map,there have been few studies on mapping QTLs of branch-and leaf-related traits.In this study,a high-density genetic map was constructed by next-generation sequencing(NGS)using an F_(1) population of 264 progenies,derived from the cross between the cultivars‘Sanyuehong'and‘Ziniangxi'.A total of 2574 high-quality BINs(binomial intervals)were obtained,and a genetic linkage map was constructed with a total length of 1753.3 cM and an average marker distance of 0.68 cM.With the genetic map and the phenotyping of single leaf length(SLL),single leaf width(SLW),leaf shape index(LSI),weight of specific leaf(WSL),petiole length(PL)and compound leaf length(CLL)measured in three seasons,11,9,9,10,9 and 12 QTLs were detected for SLL,SLW,WSL,LSI,PL and CLL traits,respectively.Among these QTLs,five QTLs were consistently detected in two seasons and 12 pleiotropic QTLs were identified for at least two traits.These findings will provide new insights for the gene cloning for branch-and leaf-related traits as well as marker-assisted selection(MAS).展开更多
To date, the coronavirus disease 2019 (COVID-19) outbreak has become a global pandemic and public health disaster. In addition to acute respiratory manifestations, patients with COVID-19 exhibit other non-respiratory ...To date, the coronavirus disease 2019 (COVID-19) outbreak has become a global pandemic and public health disaster. In addition to acute respiratory manifestations, patients with COVID-19 exhibit other non-respiratory manifestations, particularly in those with severe underlying disease. Few specific therapeutics are effective for COVID-19, and supportive care is the primary remedy. Here, we comprehensively surveyed the most recent reports on extrapulmonary complications of COVID-19 and their corresponding treatments, as well as the comparison of different clinical symptoms and complications of COVID-19, severe acute respiratory syndrome (SARS), and the Middle East respiratory syndrome (MERS) patients. We wish to provide a molecular and cellular understanding of the complications of COVID-19 and provide guidance for future diagnostics, therapeutics, and prognostics of COVID-19.展开更多
Background: Studies conducted previously indicated that gradual vascular changes in diabetic retinopathy (DR) include reduction in retinal vascular density and choroidal thickness. One device that can be used to detec...Background: Studies conducted previously indicated that gradual vascular changes in diabetic retinopathy (DR) include reduction in retinal vascular density and choroidal thickness. One device that can be used to detect these early changes is optical coherence tomographic angiography (OCTA). Objective: To detect the pre and early diabetic retinal and choroidal microvascular changes in patients with type 2 diabetes mellitus using OCTA. Methods: A total of 188 eyes were included in the study that was conducted at Zhongnan Hospital of Wuhan University Ophthalmology Department. Participants were divided into three groups: controls (90 eyes), pre-DR (70 eyes) and early-DR (28 eyes). We evaluated the changes in vascular density of deep capillary plexus (DCP), intermediate capillary plexus (ICP), superficial vascular complex (SVP), choroidal thickness (CT) and choroidal vascular index (CVI). Results: Vessel density (VD) of deep capillary plexus (DCP) and intermediate capillary plexus (ICP) at 3 × 3 mm was not significant. However, superficial vascular plexus (SVP), was significant in superior quadrant, p = 0.033. In DCP layer at 6 × 6 mm, significant difference was noted superiorly, p = 0.023 and ANOVA p = 0.033. However, ICP layer showed significant changes temporaly and inferiorly in 1 - 3 mm and 1 - 6 mm retinal rings, p Conclusion: Our results reveal that although there were no clinical manifestations in the control group and the pre-DR group, changes in retinal and choroidal blood flow density had already occurred in the pre-DR group through OCTA detection, suggesting that early detection of the lesions provides an objective basis to prevent further retinal microvascular damage. Using OCTA parameters at 3 × 3 mm, 6 × 6 mm and 15 × 12 mm scan radius at different layers of the retina and choroid, we are able to detect early retinal microvascular and choroidal changes in patients with pre-DR and early-DR thereby saving the costs of dealing with advanced diabetic eye disease. OCTA therefore becomes a fundamental tool for the non-invasive diagnosis and prognosis of DR.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated...AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated disease model group andGP-treatment groups.The study involved the evaluation of biochemical parameters,including serum aspartate transaminase(AST),alanine transferase(ALT),blood glucose(BG),triglycerides(TG)and total cholesterol(TC).Additionally,the protective effect of the treatments were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using immunohistochemistry.The expression of proliferatoractivated receptor gamma(PPARγ)and cytochrome P450(CYP450)1A1 m RNA was determined by quantitative RTPCR.RESULTS:GP treatments at oral doses of 200,400,and800 mg/kg per day significantly decreased the levels of serum AST and ALT(P<0.05,P<0.01),especially at the dose of 800 mg/kg per day.To a similar extent,GP at800 mg/kg per day reduced the levels of BG(4.19±0.47,P<0.01),TG(80.08±10.05,P<0.01),TC(134.38±16.39,P<0.01)and serum insulin(42.01±5.04,P<0.01).The expression of TNF-αand NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner,and the expression of PPARγand CYP4501A1 m RNA,as measured using quantitative real-time PCR,were significantly down-regulated by GPs.Moreover,GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dosedependent manner.CONCLUSION:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-αand NF-κB proteins,and PPARγand CYP4501A1 m RNAs.展开更多
Global climate change,growing population,and environmental pollution underscore the need for a greater focus on providing advanced water treatment technologies.Although electrochemical basedprocesses are becoming prom...Global climate change,growing population,and environmental pollution underscore the need for a greater focus on providing advanced water treatment technologies.Although electrochemical basedprocesses are becoming promising solutions,they still face challenges owing to mass transport and upscaling which hinder the exploitation of this technology.Electrode design and reactor configuration are key factors for achieving operational improvements.The electroactive membrane has proven to be a breakthrough technology integrating electrochemistry and membrane separation with an enhanced mass transport by convection.In this review article,we discuss recent progress in environmental applications of electroactive membranes with particular focus on those composed of carbon nanotubes(CNT)due to their intriguing physicochemical prope rties.Their applications in degradation of refractory contaminants,detoxification and sequestration of toxic heavy metal ions,and membrane fouling alleviations are systematically reviewed.We then discuss the existing limitations and opportunities for future research.The development of advanced electroactive systems depends on interdisciplinary collaborations in the areas of materials,electrochemistry,membrane development,and environmental sciences.展开更多
BACKGROUND Secondary hyperparathyroidism,renal osteodystrophy,and cardiovascular adverse events can occur if long-term hyperphosphatemia is not corrected,leading to the adverse prognosis of patients with chronic renal...BACKGROUND Secondary hyperparathyroidism,renal osteodystrophy,and cardiovascular adverse events can occur if long-term hyperphosphatemia is not corrected,leading to the adverse prognosis of patients with chronic renal failure.Besides the use of phosphorus binders,clinical control measures for hyperphosphatemia in these patients should also incorporate diet control.AIM To observe doctor-led intensive diet education effects on health-related quality of life in patients with chronic renal failure and hyperphosphatemia.METHODS We assessed 120 patients with hyperphosphatemia and chronic renal failure on hemodialysis admitted to our hospital(July 2018 to March 2020).The control group(n=60)was given routine nursing guidance,and the observation group(n=60)was given doctor-led intensive diet education.The changes in EQ-5D-3L scores,disease-related knowledge,and compliance scores before intervention and 3 and 6 mo after intervention in the two groups were recorded.The levels of serum parathyroid hormone(iPTH),calcium(Ca),phosphorus(P),calciumphosphorus product(Ca×P),serum creatinine(Scr),and blood urea nitrogen(BUN)before intervention and 3 and 6 mo after intervention in the two groups were assessed along with patient satisfaction.RESULTS There was no significant difference in blood iPTH,Ca,P,Ca×P,Scr,or BUN levels between the groups before intervention.After 3 and 6 mo of intervention,the blood iPTH,Ca,P,and Ca×P levels in the two groups decreased gradually(P<0.05),but there were no significant differences in Scr or BUN.The blood iPTH,Ca,P,and Ca×P levels in the observation group were lower than those in the control group(P<0.05).The satisfaction rate in the observation group after 3 mo was 93.33%and after 6,90.00%,which was high compared with the 80.00%and 71.67%,respectively,in the control group(P<0.05).There was no significant difference in EQ-5D-3L score between the two groups before intervention.After 3 and 6 mo of intervention,the visual analogue scale score of the two groups increased gradually(P<0.05);and the scores of action ability,self-care,daily activities,pain and discomfort,and anxiety and depression decreased gradually(P<0.05).The overall EQ-5D-3L score in the observation group was better than that in the control group(P<0.05).There was no significant difference in diseaserelated knowledge or compliance scores between the groups before intervention.After 3 and 6 mo of intervention,the scores of disease,diet,and medication knowledge and compliance in the two groups increased gradually(P<0.05).The scores of disease-related knowledge and compliance were higher in the observation group than in the control group(P<0.05).CONCLUSION Doctor-led intensive diet education can improve patient satisfaction and the quality of life in patients with chronic renal failure and hyperphosphatemia and promote low-phosphorus diet behavior.展开更多
Litchi(Litchi chinensis Sonn.)is a type of commercially prevalent subtropical and tropical fruit.Since litchi has a highly heterozygous genetic background and a long reproductive cycle,conventional breeding methods(su...Litchi(Litchi chinensis Sonn.)is a type of commercially prevalent subtropical and tropical fruit.Since litchi has a highly heterozygous genetic background and a long reproductive cycle,conventional breeding methods(such as hybridization)have limited ability to nurture new litchi cultivars.Here,an efficient and stable Agrobacterium tumefaciens-mediated genetic transformation of embryogenic callus was established in‘Feizixiao’litchi.Transgenic materials were verified using polymerase chain reaction(PCR)analysis,β-glucuronidase(GUS)assay,and green fluorescent protein(GFP)assay.To implement the technology of the Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/associated protein 9(CRISPR/Cas9)technology in‘Feizixiao’litchi and verify the validity of these transformation systems,the litchi polyphenol oxidase gene(LcPPO,JF926153)was knocked out.Various categories of mutations,covering base insertions,deletions,and substitutions,were found in transgenic materials via sequence analysis.The transformation system achieved high feasibility and efficiency,and the system of CRISPR/Cas9 was successfully employed to edit genes in‘Feizixiao’litchi.This work provides an essential foundation for investigating the functions of genes and accelerating litchi genetic improvement.展开更多
Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma.Here,we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension(COH).In COH r...Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma.Here,we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension(COH).In COH retinas,the microglial proliferation that occurred was inhibited by the P2X7 receptor(P2X7R)blocker BBG or P2X7R knockout,but not by the P2X4R blocker 5-BDBD.Treatment of primary cultured microglia with BzATP,a P2X7R agonist,mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway.Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration,which was completely blocked by 5-BDBD.In vivo and in vitro experiments demonstrated that ATP,released from activated Müller cells through connexin43 hemichannels,acted on P2X7R to induce microglial proliferation,and acted on P2X4R/P2X7R(mainly P2X4R)to induce microglial migration.Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.展开更多
The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-m...The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(>60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 82274231 and 81973506)the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, No.CMEMR2023-B12)+2 种基金the Fundamental Research Funds for the Central Universities (No. 2632023TD06)the Young Talent Support Project of Jiangsu Association for Science and Technology(No. TJ-2022-025)the Qinglan Project of Jiangsu Province。
文摘Astragali Radix(AR) and Notoginseng Radix et Rhizoma(NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair(AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction(TAC) in mice and angiotensin II(Ang II)-induced neonatal rat cardiomyocytes(NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide(NT-pro BNP), cardiac troponin T(CTn-T), and interleukin-6(IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes(ANP, BNP, and MYH7) in vivo and in vitro.Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators(COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1(TGF-β1)/mothers against decapentaplegic homolog 3(Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein(Drp1)(Ser616) expression and upregulated mitogen 2(MFN-2) and optic atrophy 1(OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
基金financially supported by the National Science and Technology Major Project on Deep Earth(No.2024ZD1001705)the National Key Research and Development Program of China(No.2016YFC0600509)。
文摘The Song Chay Dome in southeastern Yunnan Province,China,is intruded by the Late Cretaceous Laojunshan granites.New apatite and zircon fission-track data for the Laojunshan granites allow us to reconstruct the exhumation history of the Song Chay Dome.The fission-track dating indicates that the Laojunshan granites experienced four main stages of rapid cooling and exhumation at 75–63,53–43,31–20,and 12–4 Ma.The first stage was related to the thermal equilibration with surrounding rocks after magma emplacement.The rapid cooling and exhumation at 53–43 Ma were caused by normal faulting in the Late Mesozoic–Early Cenozoic extensional setting of southwestern South China,which resulted in the Laojunshan granites and Song Chay Dome being exhumed in the footwall of faults.The third stage(31–20 Ma) was the result of southeastward extrusion of the Tibetan Plateau and sinistral strike-slip movement on the NW-SE-trending Nanwenhe and Maguan-Dulong faults.The 31 Ma representing the beginning of the interaction between the Tethyan Himalayan tectonic domain and the South China Block.The final stage was mainly due to activity on the Nanwenhe Fault to the north of the Laojunshan granites,caused by lateral extrusion of the southeastern Tibetan Plateau since ca.15 Ma.These cooling and exhumation events since the Late Cretaceous indicate that the Song Chay Dome and southwestern South China Block have been affected by the Himalayan Orogeny since the Oligocene.
基金Supported by the Joint Medical Scientific Research Project of Chongqing Science and Technology Committee and Chongqing Health Committee,No.2021MSXM308.
文摘Microwave ablation(MWA)is emerging as a highly effective treatment for colorectal liver metastases(CRLMs).This review explores the advantages of MWA compared to other ablative techniques such as radiofrequency ablation and cryoablation and highlights its clinical efficacy,safety,and technical considerations.MWA offers significant benefits,including higher intratumoral temperatures,larger ablation zones,and reduced susceptibility to the heat-sink effect,which make it particularly suitable for tumors near large blood vessels.This review details the patient selection criteria,procedural approaches,and the use of advanced imaging techniques to improve the precision and effectiveness of MWA.Clinical outcomes indicate that MWA achieves high rates of complete tumor ablation and long-term survival with a favorable safety profile.This review is significant because it provides updated insights into the expanding role of MWA in treating unresectable CRLM and its potential as an alternative to surgical resection for resectable tumors.By summarizing recent studies and clinical trials,this review highlights the comparative effectiveness,safety,and integration with systemic therapies of MWA.In conclusion,MWA is a promising treatment option for CRLM and offers outcomes comparable to or better than those of other ablative techniques.Future research should focus on optimizing technical parameters,integrating MWA with systemic therapies,and conducting large-scale randomized controlled trials to establish standardized treatment protocols.Advancing our understanding of MWA will enhance its application and improve long-term survival and quality of life for patients with CRLM.
文摘Oral cancer,particularly oral squamous cell carcinoma(OSCC),remains a leading cause of cancer-related morbidity and mortality,with delayed diagnosis being a major contributing factor.Although salivary biomarkers have been explored for over three decades,the need for reliable,non-invasive diagnostic methods that enable early detection and continuous monitoring of OSCC remains unmet.This review aims to provide an updated overview of the latest advancements in salivary biomarker research,focusing on emerging biomarkers such as interleukin-6,interleukin-8,microRNAs and DNA methylation patterns,as well as metabolites and microbiota,all of which show significant promise for early OSCC detection.In addition to discussing well-established biomarkers,we explore recent technological developments that increase the sensitivity and specificity of these biomarkers,such as mass spectrometry,multiplex assays,and nanobiosensors.These developments are complemented by the integration of artificial intelligence for data analysis,which enables more accurate,point-of-care diagnostics that could revolutionize oral cancer screening.This review not only consolidates current knowledge but also addresses the challenges that hinder the widespread clinical adoption of salivary diagnostics,such as saliva variability and assay standardization.By overcoming these barriers,salivary biomarker-based diagnostics have the potential to transform OSCC detection,offering a noninvasive,cost-effective solution that can improve early diagnosis and patient outcomes.
基金supported by the National Social Science Funds of China“A Study of the Psychosocial Mechanisms of Youth Online Trolling”(23BSH143).
文摘This study explored the connection between childhood psychological maltreatment and online trolling,as well as the influence of moral disengagement and mindfulness in that relationship.A total of 984 college students(54%females,Mean age=20.9 years,SD=1.57 years)took part in the current research.The students responded to standardized measures of childhood psychological maltreatment,online trolling,moral disengagement,mindfulness.Results following the regression and the mediation analyses showed that childhood psychological maltreatment was associated with higher online trolling among college students.Moral disengagement played a mediating role in the link between childhood psychological maltreatment and online trolling,predicting to increased trolling behavior.Furthermore,mindfulness moderated the direct connection between moral disengagement and online trolling.Specifically,compared to those with high mindfulness,individuals with high moral disengagement were more inclined to engage in online trolling when they had low mindfulness.These findings add to our understanding of how and when childhood psychological maltreatment relates to online trolling of which moral engagement and mindfulness would be protective.
基金supported by the Science and Technology Special Fund of Hainan Province(Grant Nos.ZDYF2021XDNY159 and ZDYF2021XDNY156)the Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Science(Grant No.1630032022007)China Agricultural Research System of MOF and MARA(Grant No.CARS-32-01)。
文摘Litchi(Litchi chinensis Sonn.),an important fruit tree in tropical and subtropical regions,possesses substantial economic value.The branchand leaf-related traits of litchi have a significant impact on litchi yield and quality.However,due to limitations such as the density of the genetic linkage map,there have been few studies on mapping QTLs of branch-and leaf-related traits.In this study,a high-density genetic map was constructed by next-generation sequencing(NGS)using an F_(1) population of 264 progenies,derived from the cross between the cultivars‘Sanyuehong'and‘Ziniangxi'.A total of 2574 high-quality BINs(binomial intervals)were obtained,and a genetic linkage map was constructed with a total length of 1753.3 cM and an average marker distance of 0.68 cM.With the genetic map and the phenotyping of single leaf length(SLL),single leaf width(SLW),leaf shape index(LSI),weight of specific leaf(WSL),petiole length(PL)and compound leaf length(CLL)measured in three seasons,11,9,9,10,9 and 12 QTLs were detected for SLL,SLW,WSL,LSI,PL and CLL traits,respectively.Among these QTLs,five QTLs were consistently detected in two seasons and 12 pleiotropic QTLs were identified for at least two traits.These findings will provide new insights for the gene cloning for branch-and leaf-related traits as well as marker-assisted selection(MAS).
文摘To date, the coronavirus disease 2019 (COVID-19) outbreak has become a global pandemic and public health disaster. In addition to acute respiratory manifestations, patients with COVID-19 exhibit other non-respiratory manifestations, particularly in those with severe underlying disease. Few specific therapeutics are effective for COVID-19, and supportive care is the primary remedy. Here, we comprehensively surveyed the most recent reports on extrapulmonary complications of COVID-19 and their corresponding treatments, as well as the comparison of different clinical symptoms and complications of COVID-19, severe acute respiratory syndrome (SARS), and the Middle East respiratory syndrome (MERS) patients. We wish to provide a molecular and cellular understanding of the complications of COVID-19 and provide guidance for future diagnostics, therapeutics, and prognostics of COVID-19.
文摘Background: Studies conducted previously indicated that gradual vascular changes in diabetic retinopathy (DR) include reduction in retinal vascular density and choroidal thickness. One device that can be used to detect these early changes is optical coherence tomographic angiography (OCTA). Objective: To detect the pre and early diabetic retinal and choroidal microvascular changes in patients with type 2 diabetes mellitus using OCTA. Methods: A total of 188 eyes were included in the study that was conducted at Zhongnan Hospital of Wuhan University Ophthalmology Department. Participants were divided into three groups: controls (90 eyes), pre-DR (70 eyes) and early-DR (28 eyes). We evaluated the changes in vascular density of deep capillary plexus (DCP), intermediate capillary plexus (ICP), superficial vascular complex (SVP), choroidal thickness (CT) and choroidal vascular index (CVI). Results: Vessel density (VD) of deep capillary plexus (DCP) and intermediate capillary plexus (ICP) at 3 × 3 mm was not significant. However, superficial vascular plexus (SVP), was significant in superior quadrant, p = 0.033. In DCP layer at 6 × 6 mm, significant difference was noted superiorly, p = 0.023 and ANOVA p = 0.033. However, ICP layer showed significant changes temporaly and inferiorly in 1 - 3 mm and 1 - 6 mm retinal rings, p Conclusion: Our results reveal that although there were no clinical manifestations in the control group and the pre-DR group, changes in retinal and choroidal blood flow density had already occurred in the pre-DR group through OCTA detection, suggesting that early detection of the lesions provides an objective basis to prevent further retinal microvascular damage. Using OCTA parameters at 3 × 3 mm, 6 × 6 mm and 15 × 12 mm scan radius at different layers of the retina and choroid, we are able to detect early retinal microvascular and choroidal changes in patients with pre-DR and early-DR thereby saving the costs of dealing with advanced diabetic eye disease. OCTA therefore becomes a fundamental tool for the non-invasive diagnosis and prognosis of DR.
基金National Key R&D Program of China(2016YFD0800902-2),the Anhui Province Major Science and Technology Projects(16030801117),and the National High-Tec hnology Research and Development Program of China(2014AA06A513)。
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金Supported by Bureau of Public Health of Hubei Province
文摘AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated disease model group andGP-treatment groups.The study involved the evaluation of biochemical parameters,including serum aspartate transaminase(AST),alanine transferase(ALT),blood glucose(BG),triglycerides(TG)and total cholesterol(TC).Additionally,the protective effect of the treatments were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using immunohistochemistry.The expression of proliferatoractivated receptor gamma(PPARγ)and cytochrome P450(CYP450)1A1 m RNA was determined by quantitative RTPCR.RESULTS:GP treatments at oral doses of 200,400,and800 mg/kg per day significantly decreased the levels of serum AST and ALT(P<0.05,P<0.01),especially at the dose of 800 mg/kg per day.To a similar extent,GP at800 mg/kg per day reduced the levels of BG(4.19±0.47,P<0.01),TG(80.08±10.05,P<0.01),TC(134.38±16.39,P<0.01)and serum insulin(42.01±5.04,P<0.01).The expression of TNF-αand NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner,and the expression of PPARγand CYP4501A1 m RNA,as measured using quantitative real-time PCR,were significantly down-regulated by GPs.Moreover,GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dosedependent manner.CONCLUSION:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-αand NF-κB proteins,and PPARγand CYP4501A1 m RNAs.
基金the Natural Science Foundation of Shanghai,China(No.18ZR1401000)the Shanghai Pujiang Program(No.18PJ1400400)Donghua University for the start-up grant(No.113-07-005710)。
文摘Global climate change,growing population,and environmental pollution underscore the need for a greater focus on providing advanced water treatment technologies.Although electrochemical basedprocesses are becoming promising solutions,they still face challenges owing to mass transport and upscaling which hinder the exploitation of this technology.Electrode design and reactor configuration are key factors for achieving operational improvements.The electroactive membrane has proven to be a breakthrough technology integrating electrochemistry and membrane separation with an enhanced mass transport by convection.In this review article,we discuss recent progress in environmental applications of electroactive membranes with particular focus on those composed of carbon nanotubes(CNT)due to their intriguing physicochemical prope rties.Their applications in degradation of refractory contaminants,detoxification and sequestration of toxic heavy metal ions,and membrane fouling alleviations are systematically reviewed.We then discuss the existing limitations and opportunities for future research.The development of advanced electroactive systems depends on interdisciplinary collaborations in the areas of materials,electrochemistry,membrane development,and environmental sciences.
文摘BACKGROUND Secondary hyperparathyroidism,renal osteodystrophy,and cardiovascular adverse events can occur if long-term hyperphosphatemia is not corrected,leading to the adverse prognosis of patients with chronic renal failure.Besides the use of phosphorus binders,clinical control measures for hyperphosphatemia in these patients should also incorporate diet control.AIM To observe doctor-led intensive diet education effects on health-related quality of life in patients with chronic renal failure and hyperphosphatemia.METHODS We assessed 120 patients with hyperphosphatemia and chronic renal failure on hemodialysis admitted to our hospital(July 2018 to March 2020).The control group(n=60)was given routine nursing guidance,and the observation group(n=60)was given doctor-led intensive diet education.The changes in EQ-5D-3L scores,disease-related knowledge,and compliance scores before intervention and 3 and 6 mo after intervention in the two groups were recorded.The levels of serum parathyroid hormone(iPTH),calcium(Ca),phosphorus(P),calciumphosphorus product(Ca×P),serum creatinine(Scr),and blood urea nitrogen(BUN)before intervention and 3 and 6 mo after intervention in the two groups were assessed along with patient satisfaction.RESULTS There was no significant difference in blood iPTH,Ca,P,Ca×P,Scr,or BUN levels between the groups before intervention.After 3 and 6 mo of intervention,the blood iPTH,Ca,P,and Ca×P levels in the two groups decreased gradually(P<0.05),but there were no significant differences in Scr or BUN.The blood iPTH,Ca,P,and Ca×P levels in the observation group were lower than those in the control group(P<0.05).The satisfaction rate in the observation group after 3 mo was 93.33%and after 6,90.00%,which was high compared with the 80.00%and 71.67%,respectively,in the control group(P<0.05).There was no significant difference in EQ-5D-3L score between the two groups before intervention.After 3 and 6 mo of intervention,the visual analogue scale score of the two groups increased gradually(P<0.05);and the scores of action ability,self-care,daily activities,pain and discomfort,and anxiety and depression decreased gradually(P<0.05).The overall EQ-5D-3L score in the observation group was better than that in the control group(P<0.05).There was no significant difference in diseaserelated knowledge or compliance scores between the groups before intervention.After 3 and 6 mo of intervention,the scores of disease,diet,and medication knowledge and compliance in the two groups increased gradually(P<0.05).The scores of disease-related knowledge and compliance were higher in the observation group than in the control group(P<0.05).CONCLUSION Doctor-led intensive diet education can improve patient satisfaction and the quality of life in patients with chronic renal failure and hyperphosphatemia and promote low-phosphorus diet behavior.
基金supported by grants from the National Key R&D Program of China(Grant No.2019YFD1000900)the Hainan Province Science and Technology Special Fund(Grant No.ZDYF2022XDNY253)the earmarked fund for CARS(Grant No.CARS-32-01)。
文摘Litchi(Litchi chinensis Sonn.)is a type of commercially prevalent subtropical and tropical fruit.Since litchi has a highly heterozygous genetic background and a long reproductive cycle,conventional breeding methods(such as hybridization)have limited ability to nurture new litchi cultivars.Here,an efficient and stable Agrobacterium tumefaciens-mediated genetic transformation of embryogenic callus was established in‘Feizixiao’litchi.Transgenic materials were verified using polymerase chain reaction(PCR)analysis,β-glucuronidase(GUS)assay,and green fluorescent protein(GFP)assay.To implement the technology of the Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/associated protein 9(CRISPR/Cas9)technology in‘Feizixiao’litchi and verify the validity of these transformation systems,the litchi polyphenol oxidase gene(LcPPO,JF926153)was knocked out.Various categories of mutations,covering base insertions,deletions,and substitutions,were found in transgenic materials via sequence analysis.The transformation system achieved high feasibility and efficiency,and the system of CRISPR/Cas9 was successfully employed to edit genes in‘Feizixiao’litchi.This work provides an essential foundation for investigating the functions of genes and accelerating litchi genetic improvement.
基金This work was supported by grants from the National Natural Science Foundation of China(81790642 and 31872765)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and the Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma.Here,we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension(COH).In COH retinas,the microglial proliferation that occurred was inhibited by the P2X7 receptor(P2X7R)blocker BBG or P2X7R knockout,but not by the P2X4R blocker 5-BDBD.Treatment of primary cultured microglia with BzATP,a P2X7R agonist,mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway.Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration,which was completely blocked by 5-BDBD.In vivo and in vitro experiments demonstrated that ATP,released from activated Müller cells through connexin43 hemichannels,acted on P2X7R to induce microglial proliferation,and acted on P2X4R/P2X7R(mainly P2X4R)to induce microglial migration.Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.
基金financial support from the National Basic Research Program of China(973 Program,No.2009CB930300)
文摘The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(>60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.