Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.

Flat multifunctional liquid crystal elements through multi-dimensional information multiplexing

Flat optical elements have attracted enormous attentions and act as promising candidates for the next generation of optical components.As one of the most outstanding representatives,liquid crystal(LC)has been widely applied in flat panel display industries and inspires the wavefront modulation with the development of LC alignment techniques.However,most LC elements perform only one type of optical manipulation and are difficult to realize the multifunctionality and light integration.Here,flat multifunctional liquid crystal elements(FMLCEs),merely composed of anisotropic LC molecules with space-variant orientations,are presented for multichannel information manipulation by means of polarization,space and wavelength multiplexing.Specifically,benefiting from the unique light response with the change of the incident polarization,observation plane,and working wavelength,a series of FMLCEs are demonstrated to achieve distinct near-and far-field display functions.The proposed strategy takes full advantage of basic optical parameters as the decrypted keys to improve the information capacity and security,and we expect it to find potential applications in information encryption,optical anti-counterfeiting,virtual/augmented reality,etc.

Effectiveness and economic outcomes in patients undergoing laparoscopic radical prostatectomy with a new surgical shear with an integrated energy system:A retrospective study based on a tertiary hospital database in China

Objective:This study aimed to demonstrate a new surgical shear with an integrated energy system(Harmonic ACE^(®)+7)value by determining its effectiveness and economic outcomes compared with conventional ultrasonic shears(CUSs)in a real-world setting.Methods:This was a retrospective study of adults with prostate cancer undergoing laparoscopic radical prostatectomy with the ACE^(®)+7 shear or CUSs between August 2019 and April 2021 at Shanghai Ruijin Hospital(the headquarters and Luwan Center in China).Demographic and diagnosis information,intraoperative and postoperative clinical outcomes,and total and categorical costs were collected.Propensity score matching was performed to form the study population for each clinical group.Data were compared between the two groups using t-test and Chi-squared test.Results:The ACE^(®)+7 was associated with a lower mean number of hemostatic clips used per surgery compared with CUSs(12.8 vs.19.8,p<0.001),a moderate but not significant difference in mean postoperative drainage duration(6.6[standard deviation,SD 2.2]days vs.7.9[SD 4.1]days,p=0.082),a reduction on mean total drainage volume(275.5[SD 374.3] mL vs.492.9[SD 1495.0]mL,p=0.321),and a lower mean rate of postoperative hemostatic drug usage(16.0%vs.52.0%,p<0.001).There was no significant difference in total costs between the ACE^(®)+7 and CUS groups.Conclusion:This study provides real-world data demonstrating that the ACE^(®)+7 shear with an integrated energy system improves clinical outcomes compared with CUSs and can offer cost savings for hospitals and health systems.Using the ACE^(®)+7 during laparoscopic radical prostatectomy allows physicians to help their patients achieve better outcomes and not spend additional money.

Navigating interdisciplinary research:Historical progression and contemporary challenges

Interdisciplinary research plays a crucial role in addressing complex problems by integrating knowledge from multiple disciplines.This integration fosters innovative solutions and enhances understanding across various fields.This study explores the historical and sociological development of interdisciplinary research and maps its evolution through three distinct phases:pre-disciplinary,disciplinary,and post-disciplinary.It identifies key internal dynamics,such as disciplinary diversification,reorganization,and innovation,as primary drivers of this evolution.Additionally,this study highlights how external factors,particularly the urgency of World War II and the subsequent political and economic changes,have accelerated its advancement.The rise of interdisciplinary research has significantly reshaped traditional educational paradigms,promoting its integration across different educational levels.However,the inherent contradictions within interdisciplinary research present cognitive,emotional,and institutional challenges for researchers.Meanwhile,finding a balance between the breadth and depth of knowledge remains a critical challenge in interdisciplinary education.

LQTTrack:Multi-Object Tracking by Focusing on Low-Quality Targets Association

Multi-object tracking(MOT)has seen rapid improvements in recent years.However,frequent occlusion remains a significant challenge in MOT,as it can cause targets to become smaller or disappear entirely,resulting in lowquality targets,leading to trajectory interruptions and reduced tracking performance.Different from some existing methods,which discarded the low-quality targets or ignored low-quality target attributes.LQTTrack,with a lowquality association strategy(LQA),is proposed to pay more attention to low-quality targets.In the association scheme of LQTTrack,firstly,multi-scale feature fusion of FPN(MSFF-FPN)is utilized to enrich the feature information and assist in subsequent data association.Secondly,the normalized Wasserstein distance(NWD)is integrated to replace the original Inter over Union(IoU),thus overcoming the limitations of the traditional IoUbased methods that are sensitive to low-quality targets with small sizes and enhancing the robustness of low-quality target tracking.Moreover,the third association stage is proposed to improve the matching between the current frame’s low-quality targets and previously interrupted trajectories from earlier frames to reduce the problem of track fragmentation or error tracking,thereby increasing the association success rate and improving overall multi-object tracking performance.Extensive experimental results demonstrate the competitive performance of LQTTrack on benchmark datasets(MOT17,MOT20,and DanceTrack).

A Data-Oriented Method to Optimize Hydraulic Fracturing Parameters of Tight Sandstone Reservoirs

Based on the actual data collected from the tight sandstone development zone, correlation analysis using theSpearman method was conducted to determine the main factors influencing the gas production rate of tightsandstone fracturing. An integrated model combining geological engineering and numerical simulation of fracturepropagation and production was completed. Based on data analysis, the hydraulic fracture parameters wereoptimized to develop a differentiated fracturing treatment adjustment plan. The results indicate that the influenceof geological and engineering factors in the X1 and X2 development zones in the study area differs significantly.Therefore, it is challenging to adopt a uniform development strategy to achieve rapid production increase. Thedata analysis reveals that the variation in gas production rate is primarily affected by the reservoir thickness andpermeability parameters as geological factors. On the other hand, the amount of treatment fluid and proppantaddition significantly impact the gas production rate as engineering factors. Among these factors, the influence ofgeological factors is more pronounced in block X1. Therefore, the main focus should be on further optimizing thefracturing interval and adjusting the geological development well location. Given the existing well location, thereis limited potential for further optimizing fracture parameters to increase production. For block X2, the fracturingparameters should be optimized. Data screening was conducted to identify outliers in the entire dataset, and adata-driven fracturing parameter optimization method was employed to determine the basic adjustment directionfor reservoir stimulation in the target block. This approach provides insights into the influence of geological,stimulation, and completion parameters on gas production rate. Consequently, the subsequent fracturing parameteroptimization design can significantly reduce the modeling and simulation workload and guide field operations toimprove and optimize hydraulic fracturing efficiency.

Screening for Anti-tumor Activity of Fractions from Buddleja officinalis Maxim

[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.

Mechanism of Gegen Qinlian Decoction in Treating Type 2 Diabetes Mellitus Complicated with NAFLD Based on Network Pharmacology

[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.

镇肝熄风汤对自发性高血压大鼠JAK2mRNA和蛋白表达的影响

目的:研究不同剂量的镇肝熄风汤对自发性高血压大鼠(SHR)腹主动脉血管组织JAK2蛋白和JAK2 mRNA表达的影响。方法:方法:将24周龄60只SHR大鼠随机分为:模型组、镇肝熄风汤中药低剂量组、中剂量组、高剂量组和复方罗布麻组,每组12只,正常对照组为:雄性12只,同源魏-凯二氏大鼠(WKY)。连续灌胃给药45天后,Western Blot测定腹主动脉血管组织中JAK2蛋白表达,实时聚合酶链反应(RT-PCR)方法测定大鼠JAK2 mRNA基因表达。结果:与模型组比较,镇肝熄风汤中药中剂量和高剂量组JAK2蛋白表达和JAK2 mRNA表达明显降低(F=74. 745,sig=0. 000,P <0. 05)。结论:镇肝熄风汤可以抑制腹主动脉血管组织中JAK2蛋白和JAK2 mRNA表达,减少血管细胞增生,起到降血压的作用。

镇肝熄风汤对SHR大鼠AngⅡ 2型受体蛋白和mRNA表达的影响

目的：研究不同剂量镇肝熄风汤对自发性高血压大鼠（SHR）腹主动脉血管组织中AT2R蛋白、AT2R mRNA表达的影响。方法：将24周龄60只SHR大鼠随机分为：模型组、镇肝熄风汤中药低剂量组、中剂量组、高剂量组和复方罗布麻组,每组12只,正常对照组为：雄性12只,同源魏-凯二氏大鼠（WKY）。连续灌胃给药45天后,用Western Blot方法检测腹主动脉血管组织中AT2R蛋白表达,实时逆转录聚合酶链反应方法（RT-PCR）检测大鼠腹主动脉血管组织中AT2R mRNA基因表达。结果：镇肝熄风汤中药中剂量和高剂量组与模型组比较,腹主动脉血管组织中AT2R蛋白表达、AT2R mRNA表达明显升高（F=46.329,sig=0.000,P〈0.01）。结论：镇肝熄风汤可以促进腹主动脉血管组织中AT2R蛋白和AT2R mRNA表达,起到扩张血管降血压的作用。

船舶海水管路腐蚀及修复技术研究进展

综述了海水管路防腐技术,包括阴极保护法、电绝缘技术和涂层防护技术;概括了管道修复技术(包括换管修复、焊接技术和复合材料修复技术)的研究现状;并针对海水管路的腐蚀泄露问题,提出了更深入的研究方向。

Alg@TiO_(2)微球稳定的Pickering乳液用做防晒乳成分的研究

为了开发一种兼具防晒功能和乳液稳定性的防晒乳配方,设计了一种负载二氧化钛纳米颗粒的海藻酸钙微球(Alg@TiO_(2)微球)来稳定Pickering乳液,用作防晒乳成分。考察了油水比和微球含量对Pickering乳液的影响,探究了乳液类型,并进行了长期保存稳定性测试。结果表明,Alg@TiO_(2)微球形状为球形,大小为2~6μm;Alg@Ti O_(2)微球中二氧化钛纳米颗粒含量为43%;微球与油水的三相接触角为120°;当油水比为1∶1,微球含量为3%(w/%)时,稳定的白油/水体系Pickering乳液为油包水型(W/O型),经100 d室温保存后乳液状态保持稳定。通过紫外吸收实验,和包括市售防晒乳在内的其他3种防晒乳相比,该Pickering乳液具有优异的防晒性能。通过皮肤表面清洗实验,该Pickering乳液具有易清洗的特性。

Differentiation of neuron-like cells from mouse parthenogenetic embryonic stem cells

Parthenogenetic embryonic stem cells have pluripotent differentiation potentials, akin to fertilized embryo-derived embryonic stem cells. The aim of this study was to compare the neuronal differentiation potential of parthenogenetic and fertilized embryo-derived embryonic stem cells. Before differentiation, karyotype analysis was performed, with normal karyotypes detected in both parthenogenetic and fertilized embryo-derived embryonic stem cells. Sex chromosomes were identified as XX. Immunocytochemistry and quantitative real-time PCR detected high expression of the pluripotent gene, Oct4, at both the mRNA and protein levels, indicating pluripotent differentiation potential of the two embryonic stem cell subtypes. Embryonic stern cells were induced with retinoic acid to form embryoid bodies, and then dispersed into single cells. Single cells were differentiated in N2 differentiation medium for 9 days. Immunocytochemistry showed parthenogenetic and fertilized embryo-derived embryonic stem cells both express the neuronal cell markers nestin, ~lll-tubulin and myelin basic protein. Quantitative real-time PCR found expression of neuregenesis related genes （Sox-1, Nestin, GABA, Pax6, Zic5 and Pitxl） in both types of embryonic stem cells, and Oct4 expression was significantly decreased. Nestin and Pax6 expression in parthenogenetic embryonic stem cells was significantly higher than that in fertilized embryo-derived embryonic stem cells. Thus, our experimental findings indicate that parthenogenetic embryonic stem cells have stronger neuronal differentiation potential than fertilized embryo-derived embryonic stem cells.

Construction of Ru/WO3 with hetero-interface structure for efficient hydrogen evolution reaction

Water electrolysis is considered as one most promising technique for hydrogen production.The high efficiency electrocatalyst is the key to accelerating the sluggish kinetics of the hydrogen evolution reaction(HER) in alkaline media.In this work,an efficient HER electrocatalyst with hetero-interfacial metal-metal oxide structure was constructed through a redox solid phase reaction(SPR) strategy.During the annealing process under Ar atmosphere,RuO_(2) and WS_(2)in RuO_(2)/WS_(2)precursor were converted to Ru nanoparticles(NPs) and WO3in situ,where tiny Ru NPs and oxygen vacancies were uniformly distributed onto the newly formed WO3nanosheets.Different characterization techniques were adopted to confirm the successful formation of Ru/WO_(3)electrocatalyst(RWOC).The optimized RWOC sample annealed at 400℃ exhibited the low overpotential value of 13 mV at a current density of 10 mA cm^(-2)and strong durability under the alkaline condition.Density functional theoretical calculations further revealed that the promoted adsorption/desorption rate of reaction intermediates and the accelerated kinetics of HER process were deduced to the synergistic effect between Ru and WO_(3)in electrocatalyst.This work provides a feasible method to fabricate highly efficient HER electrocatalysts.

基于多声源波速结构成像的岩体异常区域超前辨识方法

异常区域超前辨识对于预防地下岩土工程灾害具有重要作用。为了满足地下工程高精度探测的需求,本文提出一种层析成像方法以辨识复杂岩体结构中的异常区域,结合了走时层析、阻尼最小二乘和高斯滤波等技术。该方法克服了空洞区域辨识中速度差限制,减轻了迭代中孤立速度突变所带来的影响。我们开展了数值和室内实验量化评估最短路径法(Shortest-Path Method,SPM)、动态最短路径法(Dynamic Shortest-Path Method,DSPM)和快速扫描法(Fast Sweeping Method,FSM)等正演模拟的识别精度和计算效率。结果表明,在数值和室内实验中DSPM和FSM均能清晰地辨识出异常区域。陕西震奥矿山现场应用结果证明了该方法可利用矿山开采中爆破、微震等多类声源对矿山内部未知结构进行波速场成像。本研究不仅实现了走时层析成像方法在异常区域识别中的应用,而且为地下岩土工程中潜在风险源的探测提供了新的思路。

英国档案开放审核法规内容及启示

开放审核是决定档案可访问状态的关键环节。鉴于此,本文选取英国有关档案开放审核的法规制度,重点分析情形、流程与权责分配方面的内容并总结其特点,认为我国可借鉴的要点包括健全开放审核法规政策体系、前置开放审核环节、建立相对独立的咨询委员会并将解密与划控分开。

Self-magnetization of pyrite and its application in flotation

Pyrite is a special weakly magnetic mineral containing Fe(II). Its self-magnetization only by adjusting slurry temperatureand pH value was able to enhance its magnetism, producing the so-called the magnetized pyrite, which was further used as magneticseeds in the flotation of pyrite ore to promote flotation recovery. Tests, such as self-magnetization, vibrating sample magnetometer(VSM), XPS, size analysis and flotation were carried out. The optimal conditions of the pyrite self-magnetization were pulp pH of11.81 and temperature of 65 °C. The magnetized pyrite was characteristic of the valence change of elemental iron, resulting instronger magnetism of the magnetized pyrite than that of the original pyrite. Then, this magnetized pyrite was applied to the magneticseeding flotation (MSF) of pyrite ore. It was found that the recovery of pyrite flotation grew with the increase of magneticsusceptibility of the magnetic seeds?the magnetized pyrite; and the proper dosage of the magnetized pyrite was 100 g/t. The reasonbehind the increased recovery lies in that the magnetized pyrite promoted the magnetic agglomeration between fine pyrite particles;and the fact that the stronger the magnetism of the magnetized pyrite, the larger the aggregate size, indicates that the agglomeration issomewhat in line with the flotation, also confirming that the MSF is more suitable for fine particles than traditional flotation.

Off-axis multi-wavelength dispersion controllingmetalens for multi-color imaging

Dispersion control is crucial in optical systems,and chromatic aberration is an important factor affecting imaging quality in imaging systems.Due to the inherent property of materials,dispersion engineering is complex and needs to trade off other aberration in traditional ways.Although metasurface offers an effective method to overcome these limits and results in well-engineered dispersion,off-axis dispersion control is still a challenging topic.In this paper,we design a single-layer metalens which is capable of focusing at three wavelengths(473 nm,532 nm,and 632 nm)with different incident angles(0°,-17°and 17°)into the same point.We also demonstrate that this metalens can provide an alternative for the bulky color synthetic prism in a 3-chips digital micromirror device(DMD)laser projection system.Through this approach,various off-axis dispersion controlling optical devices could be realized.

Carbon Doping Triggered Efficient Electrochemical Hydrogen Evolution of Cross-Linked Porous Ru-MoO_(2) Via Solid-Phase Reaction Strategy

The defect-free structure of Mo-based materials is a“double-edged sword”,which endows the material with excellent stability,but limits its chemical versatility and application in electrochemical hydrogen evolution reaction(HER).Carbon doping engineering is an attractive strategy to effectively improve the performance of Mo-based catalyst and maintain their stability.Herein,we report a cross-linked porous carbon-doped MoO_(2)(C–MoO_(2))-based catalyst Ru/C–MoO_(2) for electrochemical HER,which is prepared by the convenient redox solid-phase reaction(SPR)of porous RuO_(2)/Mo_(2)C composite precursor.Theoretical studies reveal that due to the presence of carbon atoms,the electronic structure of C–MoO_(2) has been properly adjusted,and the loaded small Ru nanoparticles provide a fast water dissociation rate and moderate H adsorption strength.In electrochemical studies under a pH-universal environment,Ru/C–MoO_(2) electrocatalyst exhibits a low overpotential at a current density of 10 mA cm^(-2) and has a low Tafel slope.Meanwhile,Ru/C-MoO_(2) has excellent stability for more than 100 h at an initial current density of 100 mA cm^(-2).

Clinical study on the surgical treatment of atypical Lisfranc joint complex injury

BACKGROUND Lisfranc injuries have not received much attention by orthopedic doctors in the past,and there is little related research on the diagnosis and treatment of these injuries.In recent years with the rise in foot and ankle surgery,doctors are now paying more attention to this type of injury.However,there is still a high rate of missed diagnosis due to insufficient attention causing treatment delays or inadequate treatments,which eventually result in greater sequelae;including long-term pain,arthritis,foot deformity etc.In particular,for cases with a mild Lisfranc joint complex injury,the incidence of sequelae is higher.AIM To select an active surgical treatment for an atypical Lisfranc joint complex injury and to evaluate the clinical efficacy of the surgical treatment.METHODS The clinical data of 18 patients,including 10 males and 8 females aged 20-64 years with Lisfranc injuries treated in our department from January 2017 to September 2019 were retrospectively analyzed.All patients were treated with an open reduction and internal fixation method using locking titanium mini-plates and hollow screws or Kirschner wires.X-ray images were taken and follow-up was performed monthly after the operation;the internal fixation was then removed 4-5 mo after the operation;and the American Orthopedic Foot and Ankle Society(AOFAS)score was used for evaluation on the last follow-up.RESULTS All patients were followed up for 6-12 mo.A good/excellent AOFAS score was observed in 88.9%of patients.CONCLUSION For atypical Lisfranc joint complex injuries,active open reduction and internal fixation can be performed to enable patients to obtain a good prognosis and satisfactory functional recovery.