Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.

ROS Balance Autoregulating Core-Shell CeO_(2)@ZIF-8/Au Nanoplatform for Wound Repair

Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

适用于低渗透高盐油藏的醇醚磺酸盐与甜菜碱表面活性剂复配增注体系

低渗油藏具有孔喉半径小、渗透能力低、吸水能力差等特点,导致化学驱油效果不理想。针对该问题,在十二醇中引入环氧丙烷和环氧乙烷,并经磺化得到醇醚磺酸盐(DP6E6S),构建了DP6E6S与C16羧基甜菜碱(PNC)表面活性剂的复配体系,评价了该体系的表/界面性能、老化性、吸附性、润湿性和乳化性能,并通过岩心流动实验研究了复配体系的增注性能。结果表明,PNC与DP6E6S具有较强的协同作用,与单一表面活性剂相比,可以有效降低临界胶束浓度和表面张力,提高乳液的稳定性和抗吸附性能。PNC与DP6E6S复配物质的量比为1∶1和2∶3的表面活性剂体系具备较强的抗老化性能,能在较宽的盐度范围(5%~10%)内将油水界面张力维持至10-3mN/m,在60℃下老化30 d后的油水界面张力无明显变化。随着盐度增加,由复配表面活性剂制得的乳液会经历从Winsor I到WinsorⅢ再到WinsorⅡ的相转变过程,中相乳液体积较大,乳液稳定性好。Na Cl加量为8%时,配比为1∶1和2∶3的复配表面活性剂乳液的平均粒径均达到最小值,分别为7.52、10.01μm。此外,该配比下的复配表面活性剂溶液还具有良好的增溶效果,油增溶量分别高达68、64 mL/g。具有低界面张力和高润湿角的PNC/DP6E6S复配体系有利于低渗透储层的降压增注。与水驱相比,配比为1∶1和2∶3的表面活性剂体系的降压率分别可达到28.9%和23.9%,采收率提高21.85百分点和18.92百分点。PNC、DP6E6S配比为1∶1的复配表面活性剂体系降低毛细管力的能力强于配比为2∶3的体系,降压增注效果更好。

深度学习加速器在不同剪枝策略下的运行优化

卷积神经网络在图像分析领域已经取得了巨大的成功。随着深度学习的发展,深度学习模型越来越复杂,深度学习的计算量迅速增加。稀疏化算法能在不降低准确率的前提下有效地减少深度学习的计算量。在ResNet18模型和GoogleNet模型下使用3种不同的剪枝策略减少深度学习模型的计算量。研究表明,在不减少准确率的前提下,全局非结构化剪枝策略使得ResNet18和GoogleNet模型稀疏度分别达到了94%和90%;在基本不减少准确率的情况下,层级非结构化剪枝策略使得ResNet18和GoogleNet模型稀疏度分别达到了83%和56%;在轻微降低准确率的情况下,层级结构化剪枝策略使得ResNet18和GoogleNet模型稀疏度分别达到了34%和22%。3种剪枝策略下,在Eyeriss深度学习加速器结构中运行深度学习剪枝模型。研究结果表明,相较于未剪枝策略,在ResNet模型下,使用全局非结构化剪枝策略的延迟降低了66.0%,功耗降低了60.7%;使用层级非结构化剪枝策略的延迟降低了88.1%,功耗降低了80.6%;使用层级结构化剪枝策略的延迟降低了65.6%,功耗降低了33.5%。相较于未剪枝策略,在GoogleNet模型下,使用全局非结构化剪枝策略的延迟降低了74.5%,功耗降低了63.2%;使用层级非结构化剪枝策略的延迟降低了73.6%,功耗降低了55.0%;使用层级结构化剪枝策略的延迟降低了26.8%,功耗降低了5.8%。因此,可以得出:在不降低准确率的前提下,使用全局非结构化剪枝策略能大幅度地减少模型运算的延迟和能耗;在轻微降低准确率的前提下,使用层次非结构化剪枝策略能大幅度地降低模型运算的延迟和能耗。

激光熔覆Ti-Al-N复合涂层高温氧化及摩擦磨损性能

采用激光熔覆于TC4合金表面原位合成Ti-Al-N复合涂层,对比研究复合涂层及TC4基体的高温氧化行为及宽温域下的摩擦磨损性能。结果表明:复合涂层在800℃以下生成以TiO_(2)为主的多层膜,在900和1000℃下涂层氧化产物为TiO_(2)和Al_(2)O_(3)的混合氧化层,涂层表现出较好的抗高温氧化性能;由于氧化膜增厚及涂层中分布的Ti_2AlN自润滑相的作用,800℃时涂层摩擦因数降至0.2091,磨损率降至0.025×10^(-4)mm^3·N^(-1)·m^(-1)是TC4钛合金基体的1.43%。复合涂层在测试温度区间以磨粒磨损为主,高温条件下氧化物具有明显的润滑作用。

Intelligent Vascularized 3D/4D/5D/6D‑Printed Tissue Scaffolds

Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.

基于改进模糊置信规则的意图识别方法

针对传统意图识别方法只能处理某种类型不确定性信息的不足,该文结合模糊集和DS证据理论优势提出一种模糊置信规则库(BRB)信息处理方法。首先在置信规则前提部分改进了前提属性的连接关系,根据数据集统计分布特点设计了模糊集分割,选取Cauchy型分布作为隶属度函数,较好地避免置信规则无法被有效激活进而导致系统无有效输出问题;其次融合处理辨识框架内不同类别的置信分布,建立规则权重和特征权重优化模型,构建了特征空间与类别空间之间的输入输出关系;在此基础上,计算未知意图数据在相应规则模糊域的匹配度和激活度,采用置信度最大原则进行识别决策。通过实验验证、参数敏感性及结果分析、时间复杂度分析,表明该文方法可以获得比其他识别方法更高的正确率,尤其是在小样本条件下更能体现出该方法的有效性和可靠性。

Conceptualizing the complexity of ferroptosis to treat triple-negative breast cancer:theory-to-practice

Ferroptosis,a type of regulated cell death named one decade ago,is a unique type driven by lipid peroxidation in an iron-dependent manner.Ferroptosis differs radically from apoptosis and other regulated forms of cell death in both morphology and molecular underpinning.Ferroptosis can be triggered by a variety of physiologic conditions and pathologic stresses.There has been growing interest in ferroptosis in recent years,and research on ferroptosis is productive.

Advantages and prospects of traditional Chinese medicine in treating COVID-19

Towards the end of 2019,a novel coronavirus pneumonia(coronavirus disease 19,COVID-19)caused by SARS-CoV-2 infection emerged in Wuhan.The SARS-CoV-2 virus quickly spread across the globe,seriously affecting public health and economic development of countries worldwide.Currently,antiviral drugs developed for COVID-19 lack strong clinical trial support and the high mutation rate of the virus causes difficulties in vaccine development,thus a complex and delayed large scale role out of an efficacious vaccine.Traditional Chinese medicine(TCM)has been used for treating various conditions for thousands of years and has a unique systems theory.It can be individualized into specific therapeutic regimens according to the patients’physical condition,clinical symptoms,and other distinguishing factors.In addition,TCM often has different effects at different disease stages,thus contributing to disease prevention,treatment,and rehabilitation.Existing evidence shows that TCM has efficacy in the treatment of COVID-19.The active ingredients of TCM have various pharmacological properties,including antiviral,anti-inflammatory,and immunomodulatory activity,with clinical trials showing that these prescriptions reduce symptoms of COVID-19,promote viral clearance,and ultimately improve survival in infected patients.This article discusses the advantages and mechanisms of TCM in the treatment of COVID-19,hoping to provide a reference platform in the fight against the disease.

Conversion immunotherapy for deficient mismatch repair locally unresectable colon cancer:A case report

BACKGROUND Owing to the special features of biologics,deficient mismatch repair(dMMR)in patients with colon cancer has achieved little treatment efficacy from chemoradiotherapy.Immunotherapy has shown promising results for the treatment of colon cancer.The high response rate observed suggests a great option for patients presenting with unresectable tumors,as it allows for better oncological resection.Here,we aimed to highlight the significant effects of immunotherapy on dMMR in colon cancer.CASE SUMMARY A 54-year-old man diagnosed with locally unresectable dMMR colon cancer received preoperative immunotherapy(three cycles of pembrolizumab)and achieved a pathological complete response after surgery.CONCLUSION Immunotherapy can be used as a conversion treatment for locally unresectable colon cancer with dMMR.

艾司西酞普兰联合舍曲林治疗心内科门诊焦虑/抑郁患者的疗效分析

目的探讨艾司西酞普兰与舍曲林治疗心内科门诊焦虑/抑郁患者的临床疗效及安全性。方法选取2018年8月—2019年4月中南大学湘雅医院心内科门诊中100例心理障碍并躯体化症状患者。根据不同治疗方法将患者分为艾司西酞普兰组与舍曲林组,分别采用艾司西酞普兰与舍曲林治疗,疗程8周。治疗前与治疗后第4周、第8周采用患者健康问卷躯体症状群量表(PHQ-15)、广泛性焦虑量表(GAD-7)和患者健康问卷抑郁症状群量表(PHQ-9)评定临床症状,治疗第8周采用临床疗效总评量表(CGI-GI)、副反应量表(TESS)进行疗效和副反应评定。结果两组患者治疗前、治疗后第4周、治疗后第8周PHQ-15评分比较,经重复测量设计的方差分析,结果:(1)不同时间点的PHQ-15评分有差异(F=242.604,P<0.05);(2)两组患者PHQ-15评分有差异(F=1.207,P<0.05);(3)两组患者PHQ-15评分的变化趋势无差异(F=2.400,P<0.05)。两组患者治疗前、治疗后第4周、治疗后第8周PHQ-9评分的比较,经重复测量设计的方差分析,结果如下:(1)不同时间点的PHQ-9评分有差异(F=136.784,P<0.05);(2)两组患者PHQ-9评分无差异(F=2.016,P<0.05);(3)两组患者PHQ-9评分的变化趋势有差异(F=4.013,P<0.05)。两组患者治疗前、治疗后第4周、治疗后第8周GAD-7评分比较,经重复测量设计的方差分析,结果如下:(1)不同时间点的GAD-7评分有差异(F=198.537,P<0.05);(2)两组患者GAD-7评分有差异(F=6.606,P<0.05);(3)两组患者GAD-7评分的变化趋势有差异(F=9.774,P<0.05)。艾司西酞普兰组治疗后第8周的CGI-GI较舍曲林组低(P<0.05)。两组患者治疗后第8周的TESS各指标比较,差异无统计学意义(P>0.05)。两组间因副反应的退出试验率比较,差异无统计学意义(P>0.05)。结论艾司西酞普兰与舍曲林治疗心内科门诊焦虑/抑郁患者并躯体化症状均有显著疗效及良好的安全性,但与舍曲林相比较,艾司西酞普兰疗效更加显著,且安全性相同。

基于反馈证据冲突度的概率转换

概率转换是不确定推理中的有效决策方法之一。首先,对现有概率转换公式进行分析,给出两类统一的概率转换公式。针对现有概率转换公式的给出过程较为主观,概率转换方法缺乏严密性的缺陷,提出基于反馈证据冲突度的概率转换方法。再利用遗传算法,求解最小反馈证据冲突度的转换概率。最后,将本文概率转换方法与现有的概率转换方法进行比较,结合仿真分析表明所提方法的有效性。

橡胶粒径及掺量对混凝土断裂韧性的影响

为研究橡胶粒径及掺量对混凝土断裂韧性的影响规律,对不同粒径(30、50目),不同掺量(0、5%、10%、15%、20%)的橡胶混凝土试件进行了楔入劈拉试验,计算得到橡胶混凝土试件起裂韧度、失稳断裂韧度随橡胶粒径及掺量的变化规律。结果表明,掺入橡胶后,混凝土的起裂韧度随橡胶掺量增加呈线性降低,橡胶掺量低于15%的混凝土,失稳断裂韧度高于基准混凝土,20%掺量的橡胶混凝土失稳断裂韧度小于基准混凝土,失稳断裂韧度与橡胶掺量呈高阶函数关系。掺50目橡胶的混凝土试件失稳断裂韧度高于30目橡胶混凝土,表现出更好的断裂韧性。

建立培养创新型实用型人才师范美术教学模式

本文基于项目研究的成果就教学改革和培养人才的实际需要,结合对师范美术教育的特殊性提出的建立综合实验室、教与学、社会实践活动三个方面的科学关系,分析建立多专业方向综合性实验室对教学改革的重要意义。总结培养人才与社会实际需要相结合的重要性,体现培养创新实用型人才师范美术教学模式研究对教育教学的实际意义。

地质钻探复杂地层固壁堵漏新工艺

基于现有地质钻探护壁堵漏技术手段的局限性和约束性,本文提出一种新的复杂地层固壁堵漏工艺。在钻遇松散破碎地层的孔段时,将一个喷嘴下入孔内,到达松散破碎段附近,然后把浆液高速、均匀地喷射在其周围,达到加固孔壁、堵塞漏失通道的效果。通过三维建模软件SolidWorks建立此喷嘴的4种模型,并使用CFD软件Flowsimulation对4种模型进行了模拟和分析;通过改变喷嘴出口角度,对喷嘴内流体流场速度、压力等物理量进行仿真分析。结果表明:进口体积流量为50 L/min时,除了出口角度为60°的模型出口端泄压较为严重外,其余3种模型喷嘴内部压力分布基本无变化;出口角度不同的喷嘴其喷射速度差异明显,出口角度为30°时,喷嘴的喷射速度最大,达到1.25 m/s,使浆液能够喷射渗入地层进行有效地固壁堵漏。

用于异质信息的信任区间交互式多属性识别方法

为了解决混合类型数据与专家知识等异质信息的融合决策问题,该文提出了基于信任区间的交互式多属性识别(BI-TODIM)方法。完善了混合类型数据的距离测度,根据信任区间的构建定理和灰关联方法构建了未知目标混合类型数据的信任区间,阐明了信任区间与直觉模糊数之间的等价关系,创建了混合类型数据和专家知识的识别决策模型,实现了特征层信息和决策层信息的统一表达;分析了基于信度函数的逼近理想解(BFTOPSIS)方法的反转现象及算法的复杂度,定义了区间数的序关系,提出了BI-TODIM识别决策方法,及基于直觉模糊熵的未知权重计算方法。结合算例和目标识别案例,验证了该文方法在解决排序反转和异质信息融合方面的有效性,突出了该方法时间复杂度低、稳定性好、识别准确度高的优点。

热等静压扩散连接CuAgZn/GH909接头组织及力学性能

通过热等静压−扩散连接工艺直接连接CuAgZn和GH909,利用扫描电镜(SEM)、能谱仪(EDS)和X射线衍射仪(XRD)观察接头的显微组织和成分,并通过测试显微硬度和剪切强度研究接头的力学性能。结果表明,CuAgZn/GH909结合界面紧密完整,接头密实、均匀,无未连接的缺陷。接头的最大显微硬度为HV 443,高于两种基体合金,平均剪切强度高达172 MPa。由此得出,CuAgZn和GH909两种合金通过热等静压−扩散连接工艺在700℃、150 MPa和3 h的参数下可以实现良好的冶金结合。

Secreted Frizzled-Related Protein 5 (SFRP5) in Patients with Obstructive Sleep Apnea

Objective Obstructive sleep apnea (OSA) is closely related to obesity, insulin resistance and inflammation. Secreted frizzled-related protein 5 (SFRP5) is a recently discovered adipokine. It is involved in insulin resistance and inflammation in obesity. This study aimed at evaluating the association between SFRP5and sleeping characteristics as well as biochemical parameters of OSA patients.Methods This was a prospective case control study. Nondiabetic OSA patients and controls were consecutively recruited and divided into three groups: OSA group, apnea–hypopnea Index (AHI)≥5/h; healthy controls with normal body mass index (BMI); obese controls without OSA, and BMI > 24.0 kg/m2. All participants underwent polysomnography (PSG). Plasma SFRP5 was examined using enzyme-linked immunosorbent assay (ELISA). Blood biochemical examinations, including fasting blood glucose (FBG), lipid profile, hypersensitive Creactive protein (hsCRP), were performed early in the morning after PSG. Patients with severe OSA were treated with nasal continuous positive airway pressure (nCPAP), and plasma SFRP5 was repeatedly measured for comparison.Results Sixty-eight subjects were enrolled in the study, including 38 patients of OSA, whose medium AHI was 58.70 /h (36.63, 71.15), 20 obese controls, and 10 healthy controls. The plasma SFRP5 level of OSA patients was not significantly different from that of healthy controls or obese controls. In OSA patients, SFRP5 level correlated positively with triglyceride level (r=0.447, P=0.005) and negatively with LDL-cholesterol level and HDLcholesterol level (r=?0.472 and P=0.003; r=?0.478 and P=0.002; respectively). SFRP5 level was not found correlating with FBG, AHI, or any of nocturnal hypoxia parameters. After overnight nCPAP treatment, plasma SFRP5 levels of OSA patients did not change significantly (t=1.557, P = 0.148) compared to that of pretreatment.Conclusions In nondiabetic OSA patients, plasma SFRP5 is associated with the lipid profile. However,no correlation was observed between SFRP5 and FBG or sleep parameters. The SFRP5 level of OSA patients did not differ from that of non-OSA individuals in our study.

基于犹豫模糊集统计相关系数的多源异类数据融合识别

为解决由犹豫模糊数、直觉模糊数、区间数和实数4类基本数据组成的多源异类数据的融合识别问题,在犹豫模糊框架内,提出犹豫模糊集相关系数计算方法进行识别判定。首先,将多源异类数据用犹豫模糊数统一描述;其次,分析现有的犹豫模糊集相关系数的局限性,提出了既满足统计学直觉,又不需要各犹豫模糊数中隶属度个数相同,并具有更强数学概念的犹豫模糊集统计相关系数;最后,应用到多源异类数据的融合识别中,利用最大相关系数准则进行识别判定。仿真算例对比分析验证了犹豫模糊集统计相关系数的有效性,并具有精度高、区分度好的优点。