A Wnt10a-Notch signaling axis controls Hertwig’s epithelial root sheath cell behaviors during root furcation patterning

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig’s epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a^(fl/fl)mice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a^(fl/fl)mice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10a^(fl/fl)molars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

The Energy Sources and the Explosion Mechanism of Ca-rich Supernova PTF 10iuv

In this paper,we perform the detailed modeling for the light curves(LCs)of PTF 10iuv which is a calcium-rich(Ca-rich)supernova(SN)to constrain the physical properties of its ejecta and the energy sources,as well as the explosion mechanism.We find that the^(56)Ni model and the56Ni plus circumstellar interaction model fail to explain the LCs,while the four-element(^(56)Ni,^(48)Cr,^(52)Fe,and^(44)Ti)model can account for the LCs.The ejecta mass of PTF10iuv derived by the model(1.52_(-0.25)^(+0.34)M_(⊙))is consistent with that of the merger of a sub-Chandrasekhar mass white dwarf.The early-time LCs were mainly powered by^(56)Ni whose mass is~0.03 M_(⊙),while the contributions of^(48)Cr and^(52)Fe can be neglected.The derived^(44)Ti mass(~0.25 M_(⊙))is~1.8 times the upper limit of the derived^(44)Ti mass of Ca-rich SN 2005E.We suggest that subtracting the contributions of the host-galaxy,which are unknown,and including the flux from other long-lived elements(e.g.,^(57)Co,^(55)Fe,^(60)Co)can reduce the amount of^(44)Ti,and that this value can be regarded as an upper limit.

miR-10b通过激活KLF4/Notch-1/STAT3信号途径加速腹主动脉瘤的进展

目的:miR-10b促进动脉瘤的进展但其机制未明确,本实验通过检测miR-10b对KLF4/Notch-1/STAT3途径的影响阐明其机理。方法:双荧光素酶实验验证miR-10b的靶基因。取20只apoE-/-小鼠构建腹主动脉瘤模型,其中10只尾静脉注射miR-10b过表达的慢病毒,分别记为模型组和miR-10b组。另取10只apoE-/-小鼠作为假手术组,28 d后解剖小鼠腹主动脉行病理学染色、Western-blot实验。将血管紧张素Ⅱ(AngⅡ)作用后的THP-1巨噬细胞根据是否转染miR-10b mimic及其Nc对照、是否添加抑制剂分组:(1)Nc组;(2)miR-10b mimic组;(3)Nc+KLF4抑制组;(4)miR-10b mimic+KLF4抑制组;(5)Nc+Notch-1抑制组;(6)miR-10b mimic+Notch-1抑制组;(7)Nc+STAT3抑制组;(8)miR-10b mimic+STAT3抑制组,检测细胞内蛋白水平。结果:检测双荧光素酶活性得知miR-10b可靶向作用于基因KLF4。小鼠血管病理实验发现,与正常小鼠相比,动脉瘤模型小鼠的血管明显增粗、组织结构异常,miR-10b可加重血管病变;CD68+巨噬细胞、蛋白Notch-1、p-STAT3、MMP-2、MMP-9在假手术组、模型组与miR-10b逐渐增多,而α-SMA、蛋白KLF4逐渐减少。(1)、(2)两组细胞间,后者KLF4表达较少、而Notch-1、p-STAT3、MMP-2、MMP-9表达显著偏多;KLF4抑制剂抑制KLF4表达,而Notch-1显著增多;Notch-1被抑制而减少表达,p-STAT3也随之减少;p-STAT3被抑制表达,MMP-2与MMP-9表达量也明显降低。结论:miR-10b通过作用于KLF4/Notch-1/STAT3信号途径,引起动脉瘤组织中MMP-2、MMP-9表达增加,从而加速动脉瘤的进程。

复合氨基酸Amino M-10在化妆品中的应用研究

复合氨基酸Amino M-10是由10种氨基酸科学配比复配而成,总氨基酸浓度为7.5~8.5%。通过采用理化分析、细胞模型试验、人体功效评价试验、配方应用实例、消费者调查等多种方法,研究了复合氨基酸Amino M-10的基本性能、护肤功效、护发功效及其在洗护和护肤化妆品中的应用,研究结果显示,复合氨基酸Amino M-10具有很好的保湿、舒缓、抗氧化、抗衰老、祛红血丝、护发等功效。人体斑贴试验和细胞活力检测结果也显示复合氨基酸Amino M-10温和而无刺激,可广泛应用于洗护和护肤化妆品中,具有广阔的市场前景和研究价值。

The CBL-interacting protein kinase OsCIPK1 phosphorylated by SAPK10 positively regulates responses to ABA and osmotic stress in rice

SubclassⅢsucrose nonfermenting1-related protein kinase 2s(SnRK2s)function in ABA and abiotic stress responses by unknown mechanisms.We found that osmotic stress/ABA-activated protein kinase 10(SAPK10),a member of rice SnRK2s,physically interacted with CBL-interacting protein kinase 1(OsCIPK1).OsCIPK1 expression was up-regulated by ABA and PEG treatment,and overexpression increased the ABA sensitivity of seed germination and root growth and plant osmotic stress tolerance.Osmotic stress or ABA-induced activation of OsCIPK1 is dependent on SAPK10.SAPK10 phosphorylates Thr-24 of OsCIPK1 in vitro,and this phosphorylation increases the activity of OsCIPK1 and positively regulates the function of OsCIPK1 in ABA responses and plant osmotic stress tolerance.This study suggests that OsCIPK1 is a direct phosphorylated substrate of SAPK10,and SAPK10-mediated phosphorylation of OsCIPK1 functions in ABA signaling and increases rice osmotic stress tolerance.

A chromosome-level genome assembly for Chinese plum‘Wushancuili'reveals the molecular basis of its fruit color and susceptibility to rain-cracking

Chinese plum(Prunus salicina Lindl.)originates from China and makes a large contribution to the global production of plums.The P.salicina‘Wushancuili'has a green coloration and high fruit quality and is economically important in eliminating poverty and protecting ecology in the Yangtze River Three Gorges Reservoir.However,rain-induced cracking(rain-cracking,literally skin cracking caused by rain)is a limitation to‘Wushancuili'fruit production and causes severe losses.This study reported a high-quality‘Wushancuili'genome assembly consisting of a 302.17-Mb sequence with eight pseudo-chromosomes and a contig N50 of 23.59 Mb through the combination of Illumina sequencing,Pacific Biosciences HiFiⅢsequencing,and high-throughput chromosome conformation capture technology.A total of 25109 protein-coding genes are predicted and 54.17%of the genome is composed of repetitive sequences.‘Wushancuili'underwent a remarkable orthoselection during evolution.Gene identification revealed that loss-of-function in four core MYB10 genes results in the anthocyanin deficiency and absence of red color,revealing the green coloration due to the residual high chlorophyll in fruit skin.Besides,the occurrence of cracking is assumed to be closely associated with cell wall modification and frequently rain-induced pathogen enrichment through transcriptomic analysis.The loss of MYB10 genes might render fruit more susceptible to pathogen-mediated cracking by weakening the epidermal strength and reactive oxygen species(ROS)scavenging.Our findings provided fundamental knowledge regarding fruit coloration and rain-cracking and will facilitate genetic improvement and cultivation management in Chinese plums.

Study of the response of 10B-doped MCP to wide-energy range neutrons from eV to MeV

Neutron-sensitive microchannel plates(nMCPs)have applications in neutron detection,including energy spectrum measurements,neutron-induced cross sections,and neutron imaging.10B-doped MCPs(B-MCPs)have attracted significant attention owing to their potential for exhibiting a high neutron detection efficiency over a large neutron energy range.Good spatial and temporal resolutions are useful for neutron energy-resolved imaging.However,their practical applications still face many technical challenges.In this study,a B-MCP with 10 mol%10B was tested for its response to wide-energy neutrons from eV to MeV at the Back-n white neutron source at the China Spallation Neutron Source.The neutron detection efficiency was calibrated at 1 eV,which is approximately 300 times that of an ordinary MCP and indicates the success of 10 B doping.The factors that caused the reduction in the detection efficiency were simulated and discussed.The neutron energy spectrum obtained using B-MCP was compared with that obtained by other measurement methods,and showed very good consistency for neutron energies below tens of keV.The response is more complicated at higher neutron energy,at which point the elastic and nonelastic reactions of all nuclides of B-MCP gradually become dominant.This is beneficial for the detection of neutrons,as it compensates for the detection efficiency of B-MCP for high-energy neutrons.

In vitro polymerization of the dopamine-borate melanin precursor:A proof-of-concept regarding^(10)boron neutron-capture therapy for melanoma

The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.

Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.

C6H10S2O联合Nano-CaCO3对铅染毒小鼠海马学习记忆功能的影响

评价 C6H10S2O联合Nano-CaCO3对铅染毒小鼠的海马学习记忆功能产生的影响,以指导铅染毒相关问题的处理。方法 选择齐齐哈尔医学院动物实验中心提供的20-30g 健康雌性 KM 小鼠,健康清洁级,分为正常对照组、模型对照组、C6H10S2O 组、Nano-CaCO3组、联合治疗组,其中后四组均为铅染毒模型。五组的饲养条件相同,方法 /剂量建立铅染毒模型,提供对应治疗方法,通过评估体质量与血液中铅元素含量、NO含量和ACHE活力、水迷宫、新物体识别测量的结果,判断治疗效果。结果 与空白对照组比较,模型对照组的体质量显著降低(P<0.05),血铅含量显著增加(P<0.05);与模型对照组比较,C6H10S2O组和联合治疗组小鼠的体质量显著提高(P<0.05),而血铅含量仅在联合治疗组显著减少(P<0.05);其他三组的体质量和血铅含量均无统计学差异(P>0.05)。与模型对照组比较,联合治疗组的跨越隐匿平台次数和平台象限游泳路程显著增加(P<0.05);与Nano-CaCO3组比较,联合治疗组的跨越隐匿平台次数和平台象限游泳路程也显著增加(P<0.05)。五组在NO含量和ACHE活力、认知指数方面的对比,差异均不存在统计学意义(P>0.05)。结论 C6H10S2O联合Nano-CaCO3可以减少铅含量,提高体质量,对空间学习能力有一定影响,但对认知能力、学习记忆能力不存在显著影响。

AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.

Long non-coding RNA DPP10-AS1 represses the proliferation and invasiveness of glioblastoma by regulating miR-24-3p/CHD5 signaling pathway

This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)within both the patient tissue specimens and glioblastoma cell lines.The relationship between lncRNA DPP10-AS1 expression in glioblastoma and patient prognosis was investigated.Cell Counting Kit-8(CCK-8),transwell,and clonogenic experiments were utilized to assess tumor cells’proliferation,invasiveness,and migratory potentials after lncRNA DPP10-AS1 expression was up or down-regulated.Using an online bioinformatics prediction tool,the intracellular localization of lncRNA DPP10-AS1 and its target miRNA were predicted,and RNA-FISH verified results.A dual-luciferase reporter experiment validated the relationship across miR-24-3p together with lncRNA DPP10-AS1.MiR-24-3p expression within glioblastoma was identified through RT-qPCR,and potential link across miR-24-3p and lncRNA DPP10-AS1 was assessed using Pearson correlation analysis.Moreover,influence from lncRNA DPP10-AS1/miR-24-3p axis upon glioblastoma cell progression was assessed in vivo via a subcutaneous xenograft tumor model.Results:The expression of lncRNA DPP10-AS1 was notably reduced in both surgical specimens of glioblastoma and the equivalent cell lines.Low level of lncRNA DPP10-AS1 in glioblastoma is following poor prognosis.The downregulation of lncRNA DPP10-AS1 in glioblastoma cells resulted in enhanced cellular proliferation,migration,and invasion capabilities,accompanied by downregulated E-cadherin and upregulated vimentin and N-cadherin.Additionally,the observed upregulation of lncRNA DPP10-AS1 demonstrated a substantial inhibitory function upon proliferation,invasion,and migratory capabilities of LN229 cells.Subcellular localization disclosed that lncRNA DPP10-AS1 had a binding site that interacted with miR-24-3p.Upregulated miR-24-3p was detected in glioblastomas,displaying an inverse correlation with lncRNA DPP10-AS1 expression.MiR-24-3p downstream target has been determined as chromodomain helicase DNA binding protein 5(CHD5).LncRNA DPP10-AS1 affected the invasion and proliferation of glioblastoma by controlling the miR-24-3p/CHD5 axis.Conclusion:The present study demonstrated that lncRNA DPP10-AS1 can inhibit the invasive,migratory,and proliferative properties of glioblastoma by regulating the miR-24-3p/CHD5 signaling pathway.Consequently,lncRNA DPP10-AS1 has potential as a tumor suppressor and might be utilized for accurate diagnosis and targeted treatments of glioblastomas.

Analysis of the Factors Influencing Urban Size on Air Concentrations of Particulate Matter PM_(2.5)and PM_(10)in China

In the construction of resilient cities,regional air pollution prevention plays a pivotal role.Building on the previous research experience,the relationship between air pollution concentration and urban size exhibits a sublinear allometric growth pattern.To identify effective strategies for mitigating particulate matter air pollution,this study quantitatively explored 6 variables influencing urbanization in China’s cities and established an allometry model.Empirical analysis was conducted using data from 293 prefecturelevel cities and 1,827 county-level cities to examine the relationship between annual concentrations of fine particulate matter PM_(2.5) and PM_(10) in the atmosphere.①The findings of this study provided partial validation for the Kuznets curve and demonstrated a reverse‘U’-shaped association between urbanization and levels of PM_(2.5) and PM_(10) pollution.②By partitioning the Hu Huanyong line,this study identified the spatial distribution pattern of PM_(2.5) and PM_(10).In central and western regions,as urban size expands,inhalable particle concentrations tended to increase further;whereas in the southeast region,inhalable particle concentrations gradually decreased and stabilized after a certain threshold of urban scale expansion was reached.Among the factors influencing urban size,green coverage within built-up areas exerted the most significant impact on both PM_(2.5) and PM_(10) concentrations,followed by the extent of built-up areas and the scale of secondary industries.This study presented an effective strategy for reconciling conflicts between urban expansion and air pollution management,while concurrently promoting resilient cities characterized by high levels of modernization and superior quality.

Higher Plasma Potassium Level Reduces 10-Year Cardiovascular Disease Risk Predicted by the Framingham Risk Score among Taxi-Motorbike Drivers Residing and Working in Cotonou, Benin

Hypertension, obesity, smoking, dyslipidemia, and type 2 diabetes (T2D) are the major risk factors for developing cardiovascular diseases (CVD). Recent studies revealed that taxi-motorbike drivers (TMDs) in Cotonou had higher rates of CVD risk factors, but their impacts on cardiovascular events have rarely been studied. The Framingham risk score (FRS) is an algorithm that considers CVD risk factors and estimates the risk of developing CVD in the next 10 years. Our objectives were to assess the 10-year CVD risk predicted by the FRS, and to examine the relationships of 10-year CVD risk with plasma iron and potassium levels among TMDs. We included 134 TMDs (22 - 59 years old) who had no prior diagnosis of CVD or T2D, and not taking medications affecting iron and potassium homeostasis. Conventional cardiovascular risk factors were used to calculate the 10-year CVD risk, which was categorized as low (20%). FRS > 2%, which corresponded to the 75th percentile of FRS distribution in our study population, was used as a cut-off value to classify participants into two groups. Plasma iron and potassium levels were segregated into tertiles and their associations with 10-year CVD risk were quantified by multivariate-adjusted logistic regression to calculate the odd ratios (ORs) to being above the 75th percentile of 10-year CVD risk with the corresponding 95% confidence intervals (CIs). We found that 62.0% of participants had at least one of cardiovascular risk factors. Approximately 97.8% of TMDs had 10-year CVD risk 4.8 mmol/L led to an 83% risk reduction of having 10-year CVD risk > 2% (OR = 0.17, 95% CI: 0.04 - 0.82, P = 0.027). In conclusion, our findings showed that high plasma potassium levels associate with reduced 10-year CVD risk among TMDs. Interventions focused on monitoring of plasma potassium, particularly in those with existing cardiovascular risk factors, may help prevent CVD.

Yangyin Huowei mixture alleviates chronic atrophic gastritis by inhibiting the IL-10/JAK1/STAT3 pathway

BACKGROUND The Chinese medicine Yangyin Huowei mixture(YYHWM)exhibits good clinical efficacy in the treatment of chronic atrophic gastritis(CAG),but the mechanisms underlying its activity remain unclear.AIM To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model.METHODS Sprague-Dawley rats were allocated into control,model,vitacoenzyme,and low,medium,and high-dose YYHWM groups.CAG was induced in rats using Nmethyl-N′-nitro-N-nitrosoguanidine,ranitidine hydrochloride,hunger and satiety perturbation,and ethanol gavage.Following an 8-wk intervention period,stomach samples were taken,stained,and examined for histopathological changes.ELISA was utilized to quantify serum levels of PG-I,PG-II,G-17,IL-1β,IL-6,and TNF-α.Western blot analysis was performed to evaluate protein expression of IL-10,JAK1,and STAT3.RESULTS The model group showed gastric mucosal layer disruption and inflammatory cell infiltration.Compared with the blank control group,serum levels of PGI,PGII,and G-17 in the model group were significantly reduced(82.41±3.53 vs 38.52±1.71,23.06±0.96 vs 11.06±0.70,and 493.09±12.17 vs 225.52±17.44,P<0.01 for all),whereas those of IL-1β,IL-6,and TNF-αwere significantly increased(30.15±3.07 vs 80.98±4.47,69.05±12.72 vs 110.85±6.68,and 209.24±11.62 vs 313.37±36.77,P<0.01 for all),and the protein levels of IL-10,JAK1,and STAT3 were higher in gastric mucosal tissues(0.47±0.10 vs 1.11±0.09,0.49±0.05 vs 0.99±0.07,and 0.24±0.05 vs 1.04±0.14,P<0.01 for all).Compared with the model group,high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage,increased the levels of PGI,PGII,and G-17(38.52±1.71 vs 50.41±3.53,11.06±0.70 vs 15.33±1.24,and 225.52±17.44 vs 329.22±29.11,P<0.01 for all),decreased the levels of IL-1β,IL-6,and TNF-α(80.98±4.47 vs 61.56±4.02,110.85±6.68 vs 89.20±8.48,and 313.37±36.77 vs 267.30±9.31,P<0.01 for all),and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues(1.11±0.09 vs 0.19±0.07 and 1.04±0.14 vs 0.55±0.09,P<0.01 for both).CONCLUSION YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway,alleviating gastric mucosal damage,and enhancing gastric secretory function,thereby ameliorating CAG development and cancer transformation.

Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome

AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene.METHODS:Ophthalmological examinations,including slit-lamp biomicroscopy and lacrimal duct probing,and computed tomography dacryocystography(CT-DCG)were performed for all participants.The family pedigree was drawn,genetic features were analyzed,and the genomic DNA of the subjects was extracted.Pathogenic genes were screened via whole exome sequencing(WES)and confirmed using Sanger sequencing.RESULTS:Six patients belonged to this three-generation family,and their clinical manifestations included congenital nasolacrimal duct obstruction,congenital absence of lacrimal puncta and canaliculi,lacrimal fistulae,and limb deformities.This pattern indicates autosomal dominant inheritance.Diagnosis was based on the clinical characteristics of LADD syndrome,which presented in all the patients in this family.A novel frameshif t mutation in the FGF10 gene(NM_004465.1),c.234dup C(p.Trp79Leus*15),was identified in all patients via WES.The variant was confirmed by Sanger sequencing and classified as a“pathogenic mutation”according to the American College of Medical Genetics and Genomics(ACMG)variant interpretation guidelines.CONCLUSION:A novel frameshift mutation in the FGF10 gene is found in all patients.This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.

Temporal and Spatial Variation Characteristics of Snow Cover Area in the Pamirs from 2010 to 2020

Scientific and comprehensive monitoring of snow cover changes in the Pamirs is of great significance to the prevention of snow disasters around the Pamirs and the full utilization of water resources. Utilize the 2010-2020 snow cover product MOD10A2, Synthesis by maximum, The temporal and spatial variation characteristics of snow cover area in the Pamirs in the past 11 years have been obtained. Research indicates: In terms of interannual changes, the snow cover area of the Pamir Plateau from 2010 to 2020 generally showed a slight decrease trend. The average snow cover area in 2012 was the largest, reaching 54.167% of the total area. In 2014, the average snow cover area was the smallest, accounting for only 44.863% of the total area. In terms of annual changes, there are obvious changes with the change of seasons. The largest snow area is in March, and the smallest snow area is in August. In the past 11 years, the average snow cover area in spring and summer showed a slow decreasing trend, and there was almost no change in autumn and winter. In terms of space, the snow cover area of the Pamirs is significantly affected by altitude, and the high snow cover areas are mainly distributed in the Karakoram Mountains and other areas with an altitude greater than 5000 meters.

高校仪器设备10S精细化管理的研究与实践

高校仪器设备的投入不断增加,如何管好、管活仪器设备,使其在教学和科研方面发挥更大的作用,是广大高校仪器设备管理工作者努力解决的问题。四川大学经过长期积极探索与不断实践,首次提出10S精细化仪器设备管理体系,以管理促发展,理论与实践相结合,仪器设备日常管理规范化与现代化相结合,大幅提升了仪器设备管理的科学化和精细化水平,有效提高了仪器设备开放共享的效益和受益面。对10S精细化管理在仪器设备管理中的具体内容进行了阐述与分析,可为其他高校仪器设备管理提供一定的借鉴和帮助。

非小细胞肺癌组织中CLDN10和CSPG4水平表达与临床病理特征及预后的关系研究

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中紧密连接蛋白10(claudin 10,CLDN10)和硫酸软骨素蛋白聚糖4(chondroitin sulfate proteoglycan 4,CSPG4)表达与临床病理特征和预后的关系。方法随机选取2017年1月~2018年4月于南京医科大学附属泰州市人民医院进行手术的136例NSCLC患者为研究对象,并根据随访结局(生存或死亡)分为生存组(n=63)和死亡组(n=69)。收集136例患者于手术过程中切除的癌组织及癌旁组织标本;实时荧光定量PCR(real-time fluorescence quantitative PCR,RT-qPCR)检测癌组织及癌旁组织CLDN10和CSPG4表达水平,并分别以NSCLC患者癌组织中CLDN10和CSPG4表达水平的平均数为界限,分为CLDN10高表达组(n=66),CLDN10低表达组(n=70)和CSPG4高表达组(n=71),CSPG4低表达组(n=65);采用多因素COX回归分析确定NSCLC患者预后的影响因素;采用Kaplan-Meier生存曲线分析NSCLC患者CLDN10和CSPG4表达水平与其预后的关系。结果NSCLC组织中CLDN10表达水平(0.96±0.25)低于癌旁组织(1.73±0.42),CSPG4表达水平(1.80±0.46)高于癌旁组织(1.04±0.27),差异有统计学意义(t=18.372,16.617,均P<0.05)。与生存组比较,死亡组低未分化占比、淋巴结转移占比及癌组织中CSPG4表达水平较高,CLDN10表达水平较低,差异具有统计学意义(t/χ^(2)=8.463,7.423,11.696,6.426,均P<0.05)。CLDN10高表达组五年存活率(58.46%)高于低表达组(37.31%),CSPG4低表达组患者五年存活率(55.56%)高于高表达组(40.58%),差异有统计学意义(χ^(2)=7.848,4.018,均P<0.05)。多因素COX分析结果显示,CLDN10低表达、CSPG4高表达、低分化程度、淋巴结转移是NSCLC患者预后的危险因素(HR=1.362,1.368,1.335,1.314,均P<0.05)。结论NSCLC患者癌组织中CLDN10表达水平较低,CSPG4水平较高,且与NSCLC发展和预后密切相关。