Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

2023-08-23辽宁普兰店M 4.6地震震源参数测定及发震构造初判

2023-08-2318:19辽宁省大连市普兰店区发生M 4.6地震,为准确描述本次地震的震源特征,探讨其孕育和发震机理,本文通过测定地震的震源深度,反演震源机制、矩张量及质心深度,给出震源机制中心解;同时分析震源机制与构造应力场的关系,根据小震重定位结果对发震断层面进行拟合,初步确定了本次地震的发震断层。结果表明,普兰店M 4.6地震初始破裂深度为12.0 km,震源机制解参数为节面Ⅰ走向50°,倾伏角75°,滑动角-169°;节面Ⅱ走向317°,倾伏角80°,滑动角-15°,矩震级M W4.8,最优质心深度12 km;地震矩M_(0)为1.796×10^(16)Nm,矩张量解M_(rr)、M_(tt)、M_(pp)、M_(rt)、M_(rp)、M_(tp)分别为-0.004、0.946、-0.942、0.017、-0.305、-0.125;中心解参数为节面Ⅰ走向47.03°,倾伏角79.04°,滑动角-168.15°;节面Ⅱ走向314.75°,倾伏角78.37°,滑动角-11.19°。构造应力场作用在中心解节面Ⅰ上的相对剪应力为0.877,相对正应力为-0.544;投影于节面Ⅱ上的相对剪应力为0.911,相对正应力为0.161。拟合的断层面走向148.91°,倾伏角89.85°,其在构造应力体系下的滑动角为26.47°。综合分析认为,普兰店M 4.6地震发生在NW向普兰店-长海构造带,是沿应力场最优节面以左旋走滑为错动方式的天然地震。

罗汉果苷V调控高糖状态巨噬细胞M1极化促进骨髓间充质干细胞的成骨分化

背景:糖尿病微环境会造成巨噬细胞过度M1极化,这种高糖炎症状态会抑制骨髓间充质干细胞的成骨分化,从而影响糖尿病骨缺损的愈合。研究表明罗汉果苷Ⅴ具有抗炎、抗氧化、降血糖的作用,但其能否调节高糖炎症状态下巨噬细胞M1极化及骨髓间充质干细胞的成骨分化尚不清楚。目的:探讨罗汉果苷Ⅴ在高糖炎症状态下调节巨噬细胞M1型极化对骨髓间充质干细胞成骨分化的影响。方法:构建糖尿病C57BL/6小鼠模型,从正常和糖尿病小鼠分离骨髓来源巨噬细胞,分别培养于低糖和高糖培养基。使用脂多糖和干扰素γ作为炎症刺激诱导骨髓来源巨噬细胞的M1型极化,同时以160,320,640μmol/L罗汉果苷Ⅴ干预,用流式细胞术检测F4/80^(+)CD86^(+)细胞比例,qRT-PCR检测诱导型一氧化氮合酶、白细胞介素1β、白细胞介素6的mRNA表达水平,ELISA检测骨髓来源巨噬细胞上清液中肿瘤坏死因子α水平。分离C57BL/6小鼠骨髓间充质干细胞,分别使用低糖或高糖成骨诱导液诱导成骨分化,添加M1型巨噬细胞条件培养基作为炎症刺激,以及320μmol/L罗汉果苷Ⅴ干预,成骨诱导14 d后采用qRT-PCR检测碱性磷酸酶、Runt相关因子2、骨钙素、骨桥蛋白的mRNA表达水平,成骨诱导21 d后进行茜素红染色及定量分析。结果与结论:①流式细胞术结果显示320,640μmol/L罗汉果苷Ⅴ组的F4/80^(+)CD86^(+)细胞比例明显低于高糖炎症对照组(P<0.05);②qRT-PCR结果显示160,320,640μmol/L罗汉果苷Ⅴ组的诱导型一氧化氮合酶、白细胞介素6的mRNA相对表达量较高糖炎症对照组显著降低(P<0.05),320,640μmol/L罗汉果苷Ⅴ组白细胞介素1β的mRNA相对表达量较高糖炎症对照组显著降低(P<0.05);③ELISA结果显示160,320,640μmol/L罗汉果苷Ⅴ组的肿瘤坏死因子α分泌水平较高糖炎症对照组显著降低(P<0.05);④320μmol/L罗汉果苷Ⅴ干预后,高糖炎症状态下骨髓间充质干细胞的钙盐沉积增加(P<0.05),且碱性磷酸酶、Runt相关因子2和骨桥蛋白的mRNA相对表达量增加(P<0.05)。结果表明,罗汉果苷Ⅴ可通过抑制高糖炎症状态下骨髓来源巨噬细胞的M1型极化及炎症因子表达,促进骨髓间充质干细胞的成骨分化。

M2型巨噬细胞衍生外泌体促进小胶质细胞M2型极化

背景:目前对于M2型巨噬细胞衍生外泌体的研究多集中于促进伤口愈合及成骨细胞的增殖和分化,而很少有研究关注其对小胶质细胞表型的调控作用。目的:探讨M2型巨噬细胞衍生外泌体对于小胶质细胞的表型调控作用及分子机制。方法:①提取骨髓原代巨噬细胞,用50 ng/m L白细胞介素4刺激巨噬细胞24 h促进巨噬细胞M2型极化,流式细胞术和细胞免疫荧光鉴定M2型巨噬细胞标志物CD206;②提取和鉴定M2型巨噬细胞衍生外泌体;③将小胶质细胞BV2随机分为3组:对照组、脂多糖组、治疗组,对照组不做处理,脂多糖组加入500 ng/m L脂多糖干预24 h,治疗组同时加入500 ng/m L脂多糖和25μg/m L M2型巨噬细胞衍生外泌体干预24 h,ELISA检测培养上清中肿瘤坏死因子α和白细胞介素10的分泌量,q RT-PCR检测细胞中诱导型一氧化氮合酶、精氨酸酶1、白细胞介素1β和白细胞介素10的m RNA表达,Western blot检测诱导型一氧化氮合酶、精氨酸酶1的蛋白表达以及核因子κB信号通路相关蛋白表达。结果与结论:①ELISA结果显示,与对照组相比,脂多糖组肿瘤坏死因子α分泌明显增多;与脂多糖组相比,治疗组肿瘤坏死因子α的分泌减少而白细胞介素10的分泌增多;②q RT-PCR结果显示,与对照组相比,脂多糖组白细胞介素1β、诱导型一氧化氮合酶m RNA表达升高;与脂多糖组相比,治疗组白细胞介素1β、诱导型一氧化氮合酶m RNA表达降低,白细胞介素10、精氨酸酶1 m RNA表达升高;③Western blot结果显示,与对照组相比,脂多糖组诱导型一氧化氮合酶蛋白表达升高;与脂多糖组相比,治疗组诱导型一氧化氮合酶蛋白表达降低,而精氨酸酶1蛋白表达升高;(4)与对照组相比,脂多糖组核因子κB信号通路中P65、p-IκB-α蛋白表达降低;与脂多糖组相比,治疗组P65、p-IκB-α蛋白表达升高。结果表明:M2型巨噬细胞衍生外泌体可以显著抑制脂多糖诱导小胶质细胞的炎症反应,促进抗炎因子白细胞介素10的表达,抑制促炎因子肿瘤坏死因子α、白细胞介素1β的表达,促进小胶质细胞表型由M1型向M2型极化,其机制可能与M2型巨噬细胞衍生外泌体抑制核因子κB信号通路激活有关。

特发性间质性肺炎病人血清STAT3和FOXM1水平与病情程度及预后的关系研究

目的探讨特发性间质性肺炎(IIP)病人血清信号转导及转录激活因子3(STAT3)、叉头框转录因子M1(FOXM1)表达水平与其病情程度和预后的关系。方法选取2017年1月至2022年10月四川省建筑医院收治的298例IIP病人为IIP组,选取同时期该院收治的298例普通型间质性肺炎(UIP)病人为UIP组,另选取同时期在该院体检的280例健康人员为对照组。采用酶联免疫吸附测定(ELISA)检测血清STAT3与FOXM1表达水平,并采用全肺纤维化高分辨率CT(HRCT)评分评价IIP病情严重程度。分析三组受试者血清STAT3与FOXM1表达水平差异。对IIP组病人随访3个月,根据其生存情况分为预后良好组与预后不良组,分析预后不良与预后良好组IIP病人血清STAT3与FOXM1表达水平差异,并采用Spearman法分析IIP病人血清STAT3与FOXM1表达水平与全肺纤维化HRCT评分之间的关系。采用logistic回归分析IIP病人预后不良的影响因素,绘制受试者操作特征曲线(ROC曲线)评估血清STAT3与FOXM1表达水平对IIP病人预后不良的预测效能。结果IIP组、UIP组、对照组血清STAT3[(1.50±0.39)ng/L、(1.32±0.31)ng/L、(1.01±0.27)ng/L]、FOXM1[(34.56±5.64)ng/L、(22.69±4.11)ng/L、(15.51±3.94)ng/L]水平均依次降低(P<0.05)。IIP病人随访3个月共有41例病人死亡,预后不良发生率为13.76%(41/298);预后不良组IIP病人血清STAT3、FOXM1水平均高于预后良好组(P<0.05)。Spearman相关性分析表明,IIP病人血清STAT3、FOXM1水平均与全肺纤维化HRCT评分正相关(rs=0.65,rs=0.57;P<0.001)。另预后不良组年龄、Ⅱ型肺泡细胞表面抗原(KL-6)、白细胞计数、红细胞沉降率(ESR)、C反应蛋白(CRP)水平、全肺纤维化HRCT评分均高于预后良好组(P<0.05);第一秒用力呼气量(FEV1)、最大自主通气量(MVV)均低于预后良好组(P<0.05)。多因素logistic回归分析显示,年龄、KL-6、白细胞、ESR、CRP、STAT3、FOXM1水平、全肺纤维化HRCT评分均是导致IIP病人预后不良的危险因素(P<0.05),FEV1、MVV为保护因素(P<0.05)。ROC分析结果表明,血清STAT3、FOXM1水平联合预测IIP病人预后的灵敏度高于STAT3、FOXM1单独预测的灵敏度(χ^(2)=8.10、6.12,P=0.002、0.008);联合预测的曲线下面积(AUC)高于STAT3、FOXM1单独预测的AUC(Z=3.15、2.54,P=0.002、0.011)。结论IIP病人血清STAT3、FOXM1表达水平均上升,二者与IIP病情程度正相关,均对IIP病人预后具有良好的预测价值,且联合预测效能更高。

Microglia:a promising therapeutic target in spinal cord injury

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.

Unraveling the therapeutic potential of Calculus Bovis in liver cancer:A novel step for targeted cancer treatment

Hepatocellular carcinoma is one of the leading causes of cancer-related deaths globally,and effective treatments are urgently needed.The present study aimed to investigate the inhibitory effect of Calculus Bovis(CB)on liver cancer and the underlying mechanisms.CB inhibited M2 tumor-associated macrophage polarization and modulated the Wnt/β-catenin signaling pathway,thereby suppressing the proliferation of liver cancer cells.The inhibitory effect on liver cancer growth was confirmed by both in vivo and in vitro experiments(detailed by Huang et al).The present study provides a theoretical basis for the application of CB for the treatment of liver cancer,providing new avenues for liver cancer treatment.

Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions

A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

血清PKM2、Gal-3、CitH3水平升高可预测机械通气并发肺部感染

目的探讨血清丙酮酸激酶M2(PKM2)、乳糖凝集素-3(Gal-3)、瓜氨酸化组蛋白H3(CitH3)水平与机械通气(MV)患者并发肺部感染的关系及预后评估价值。方法将2022年10月至2024年3月于金华市中心医院收治的120例行MV的患者纳入研究,根据是否并发肺部感染分为肺部感染组(n=50)和非肺部感染组(n=70),ELISA检测血清PKM2、Gal-3、CitH3水平;收集临床资料;预后随访并分为预后良好组(n=79)和预后不良组(n=41);多因素Logistic回归分析影响MV患者发生预后不良的因素;受试者工作特征(ROC)曲线分析血清PKM2、Gal-3、CitH3对MV患者发生预后不良的预测价值。结果与非肺部感染组相比,肺部感染组血清PKM2、Gal-3、CitH3水平均升高(P<0.05);与预后良好组相比,预后不良组血清PKM2、Gal-3、CitH3水平均升高(P<0.05);预后不良组较预后良好组临床肺部感染评分(CPIS)升高(P<0.05);PKM2、Gal-3、CitH3皆为MV患者发生预后不良的危险因素(P<0.05);PKM2、Gal-3、CitH3及联合预测患者发生预后不良的曲线下面积(AUC)分别为0.712、0.839、0.779、0.925,3者联合诊断的AUC优于各自单独检测(Z=4.261、2.521、3.676,P<0.001、0.05、0.001)。结论MV并发肺部感染患者血清PKM2、Gal-3、CitH3水平均较未发生肺部感染患者升高,三者对MV患者发生预后不良有一定的预测价值。

Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

A Real-Time Small Target Vehicle Detection Algorithm with an Improved YOLOv5m Network Model

To address the challenges of high complexity,poor real-time performance,and low detection rates for small target vehicles in existing vehicle object detection algorithms,this paper proposes a real-time lightweight architecture based on You Only Look Once(YOLO)v5m.Firstly,a lightweight upsampling operator called Content-Aware Reassembly of Features(CARAFE)is introduced in the feature fusion layer of the network to maximize the extraction of deep-level features for small target vehicles,reducing the missed detection rate and false detection rate.Secondly,a new prediction layer for tiny targets is added,and the feature fusion network is redesigned to enhance the detection capability for small targets.Finally,this paper applies L1 regularization to train the improved network,followed by pruning and fine-tuning operations to remove redundant channels,reducing computational and parameter complexity and enhancing the detection efficiency of the network.Training is conducted on the VisDrone2019-DET dataset.The experimental results show that the proposed algorithmreduces parameters and computation by 63.8% and 65.8%,respectively.The average detection accuracy improves by 5.15%,and the detection speed reaches 47 images per second,satisfying real-time requirements.Compared with existing approaches,including YOLOv5m and classical vehicle detection algorithms,our method achieves higher accuracy and faster speed for real-time detection of small target vehicles in edge computing.

Multi-Model Approach for Assessing the Influence of Calibration Criteria on the Water Balance in Ouémé Basin

Hydrological models are very useful tools for evaluating water resources, and the hydroclimatic hazards associated with the water cycle. However, their calibration and validation require the use of performance criteria which choice is not straightforward. This paper aims to evaluate the influence of the performance criteria on water balance components and water extremes using two global rainfall-runoff models (HBV and GR4J) over the Ouémé watershed at the Bonou and Savè outlets. Three (3) Efficacy criteria (Nash, coefficient of determination, and KGE) were considered for calibration and validation. The results show that the Nash criterion provides a good assessment of the simulation of the different parts of the hydrograph. KGE is better for simulating peak flows and water balance elements than other efficiency criteria. This study could serve as a basis for the choice of performance criteria in hydrological modelling.

Impaired pericyte-Müller glia interaction via PDGFRβ suppression aggravates photoreceptor loss in a rodent model of light-induced retinal injury

AIM:To investigate the involvement of pericyte-Müller glia interaction in retinal damage repair and assess the influence of suppressing the platelet-derived growth factor receptorβ(PDGFRβ)signaling pathway in retinal pericytes on photoreceptor loss and Müller glial response.METHODS:Sprague-Dawley rats were exposed to intense light to induce retinal injury.Neutralizing antibody against PDGFRβwere deployed to block the signaling pathway in retinal pericytes through intravitreal injection.Retinal histology and Müller glial reaction were assessed following light injury.In vitro,normal and PDGFRβ-blocked retinal pericytes were cocultured with Müller cell line(rMC-1)to examine morphological and protein expression changes upon supplementation with light-injured supernatants of homogenized retinas(SHRs).RESULTS:PDGFRβblockage 24h prior to intense light exposure resulted in a significant exacerbation of photoreceptor loss.The upregulation of GFAP and p-STAT3,observed after intense light exposure,was significantly inhibited in the PDGFRβblockage group.Fur ther upregulation of cytokines monocyte chemoattractant protein 1(MCP-1)and interleukin-1β(IL-1β)was also observed following PDGFRβinhibition.In the in vitro coculture system,the addition of light-injured SHRs induced pericyte deformation and upregulation of proliferating cell nuclear antigen(PCNA)expression,while Müller cells exhibited neuron-like morphology and expressed Nestin.However,PDGFRβblockage in retinal pericytes abolished these cellular responses to light-induced damage,consistent with the in vivo PDGFRβblockage findings.CONCLUSION:Pericyte-Müller glia interaction plays a potential role in the endogenous repair process of retinal injury.Impairment of this interaction exacerbates photoreceptor degeneration in light-induced retinal injury.

Hydrological Modelling of the Casamance River in Its Upstream Section (Basin at Kolda Level) to Predict Its Future States as a Function of Different Stresses

Flow records for stations in the Casamance basin are incomplete. Several gaps were noted over the 1980-2021 study period, making this study tedious. The aim of this study is to assess the potential impact of climate change on the flow of the Casamance watershed at Kolda. To this end, hydrological series are simulated and then extended using the GR2M rainfall-runoff model, with a monthly time step. Projected climate data are derived from a multi-model ensemble under scenarios SSP2-4.5 (scenario with additional radiative forcing of 4.5 W/m2 by 2099) and SSP5-8.5 (scenario with additional radiative forcing of 8.5 W/m2 by 2099). An analysis of the homogeneity of the rainfall data series from the Kolda station was carried out using KhronoStat software. The Casamance watershed was then delimited using ArcGIS to determine the morphometric parameters of the basin, which will be decisive for the rest of the work. Next, monthly evapotranspiration was calculated using the formula proposed by Oudin et al. This, together with rainfall and runoff, forms the input data for the model. The GR2M model was then calibrated and cross-validated using various simulations to assess its performance and robustness in the Casamance watershed. The version of the model with the calibrated parameters will make it possible to extend Casamance river flows to 2099. This simulation of future flows with GR2M shows a decrease in the flow of the Casamance at Kolda with the two scenarios SSP2-4.5 and SSP5-8.5 during the rainy period, and almost zero flows during the dry season from the period 2040-2059.

Identification of M2 macrophage-related genes for establishing a prognostic model in pancreatic cancer: FCGR3A as key gene

Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the growth and migration of cancers.However,the mechanisms and targets mediating M2 macrophage infiltration in pancreatic cancer remain elusive.Methods:The M2 macrophage infiltration score of patients was assessed using the xCell algorithm.Using weighted gene co-expression network analysis(WGCNA),module genes associated with M2 macrophages were identified,and a predictive model was designed.The variations in immunological cell patterns,cancer mutations,and enrichment pathways between the cohorts with the high-and low-risk were examined.Additionally,the expression of FCGR3A and RNASE2,as well as their association with M2 macrophages were evaluated using the HPA,TNMplot,and GEPIA2 databases and verified by tissue immunofluorescence staining.Moreover,in vitro cell experiments were conducted,where FCGR3A was knocked down in pancreatic cancer cells using siRNA to analyze its effects on M2 macrophage infiltration,tumor proliferation,and metastasis.Results:The prognosis of patients in high-risk and low-risk groups was successfully distinguished using a prognostic risk score model of M2 macrophage-related genes(p=0.024).Between the high-and low-risk cohorts,there have been notable variations in immune cell infiltration patterns,tumor mutations,and biological functions.The risk score was linked to the manifestation of prevalent immunological checkpoints,immunological scores,and stroma values(all p<0.05).In vitro experiments and tissue immunofluorescence staining revealed that FCGR3A can promote the infiltration or polarization of M2 macrophages and enhance tumor proliferation and migration.Conclusions:In this study,an M2 macrophage-related pancreatic cancer risk score model was established,and found that FCGR3A was correlated with tumor formation,metastasis,and M2 macrophage infiltration.

高速铁路主跨320 m钢-混部分斜拉桥无砟轨道适应性研究

南玉高铁六景郁江特大桥设计将钢-混部分斜拉桥结构引入时速350 km高速铁路领域,而300 m级以上大跨度桥上无砟轨道的竖向变形极易超限,影响列车通过的安全性和舒适性,因此,系统研究在此大跨桥梁结构上铺设无砟轨道的适应性十分必要。通过建立有限元及动力学模型,分析不同组合工况下无砟轨道结构的变形特点及动力特性,运用60 m弦测法探究各工况下无砟轨道的线形变化规律,从而确定大跨度钢-混部分斜拉桥铺设无砟轨道的适应性,并对设计和施工提出合理化建议。主要结论如下:在各种不利组合荷载作用下,桥上无砟轨道结构强度满足规范要求,列车通过大桥的各项安全性与舒适性指标均满足规范要求;混凝土收缩徐变和斜拉索升降温是影响无砟轨道线形标准的两大主因,应在无砟轨道施工前确保足够的沉降观测期和收缩徐变释放期,并充分考虑拉索的保温设计;在温度组合荷载作用下,桥上无砟轨道的60 m弦测不平顺幅值为6.79 mm,满足高速铁路静态验收标准;但在叠加列车荷载和收缩徐变后,变形弦测值均出现Ⅱ级及以上超限,通过合理设置预拱度后可有效改善轨道平顺性标准。

过表达lncRNAHEM2M改善非酒精性脂肪肝病小鼠的肝脏损伤

目的探讨过表达长链非编码RNA(lncRNA)HEM2M对非酒精性脂肪肝病(NAFLD)小鼠肝损伤的影响。方法野生型C57BL/6(WT)和条件性髓系细胞lncRNAHEM2M过表达(MYKI)小鼠分别喂饲普通饮食(ND)和高脂饮食(HFD),即为WT+ND、MYKI+ND、WT+HFD和MYKI+HFD组。12周后行腹腔糖耐量及胰岛素耐量试验后处死小鼠,检测小鼠血清和肝脏组织的肝功能指标,制备肝脏组织切片后行HE染色和F4/80免疫组化染色,ELISA法检测肝脏组织中IL-6、IL-1β和TNF-α水平,qRT-PCR检测M1型(TNF-α、iNOS和IL-6)和M2型(Arg-1、YM-1和IL-10)巨噬细胞标志物mRNA表达,免疫印迹检测肝脏组织中P-AKT、T-AKT、NLRC4、caspase-1和GSDMD蛋白表达,比色法和免疫荧光测定肝脏组织caspase-1活性。结果与HFD喂饲的WT小鼠相比,MYKI+HFD小鼠肝功能损伤减轻(P<0.01),肝脏脂肪变缓解,肝脏巨噬细胞浸润减少,糖耐量损伤及胰岛素抵抗改善(P<0.01);MYKI+HFD小鼠肝脏组织IL-6、IL-1β和TNF-α水平降低(P<0.01),M1型巨噬细胞标志物mRNA表达减少(P<0.01),M2型mRNA表达增加(P<0.01);MYKI+HFD小鼠肝脏组织NLRC4炎症小体活性降低(P<0.01),活性caspase-1减少,GSDMD-N蛋白表达降低(P<0.05)。结论过表达lncRNAHEM2M降低NAFLD小鼠肝脏炎症因子水平,进而改善胰岛素抵抗并抑制肝脏NLRC4炎症小体激活,减少肝细胞焦亡,最终改善NAFLD小鼠肝脏损伤。