Jiaohong pills attenuate neuroinflammation and amyloid-βprotein-induced cognitive deficits by modulating the mitogen-activated protein kinase/nuclear factor kappa-B pathway

Background:Jiaohong pills(JHP)consist of Pericarpium Zanthoxyli(PZ)and Radix Rehmanniae,two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment.However,the precise mechanisms underlying the beneficial effects remain elusive.Here,research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease.Methods:BV-2 cell inflammation was induced by lipopolysaccharide.AD mice were administered amyloid-β(Aβ).Behavioral experiments were used to evaluate learning and memory ability.The levels of nitric oxide(NO),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)were detected using enzymelinked immunosorbent assay(ELISA).The protein expressions of inducible nitric oxide synthase(iNOS)and the phosphorylation level of mitogen-activated protein kinase(MAPK)and nuclear factor kappa-B(NF-κB)were detected using Western blot.Nissl staining was used to detect neuronal degeneration.Results:The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO,IL-1β,TNF-α,and iNOS;increased the expression level of IL-10;and significantly decreased the phosphorylation levels of MAPK and NF-κB.These inhibitory effects were further confirmed in the AD mouse model.Meanwhile,JHP improved learning and memory function in AD mice,reduced neuronal damage,and enriched the Nissl bodies in the hippocampus.Moreover,IL-1βand TNF-αin the cortex were significantly downregulated after JHP administration,whereas IL-10showed increased expression.Conclusions:It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF-κB signaling pathway.

Integration of network pharmacology and bone marrow mesenchymal stem cells experimental research to reveal the molecular mechanisms for Hai Honghua medicinal liquor against osteoporosis

Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.

CT引导下经皮肺穿刺活检术并发症发生的影响因素分析

背景与目的 计算机断层扫描引导下经皮肺穿刺活检术(computed tomography guided percutaneous lung biopsy,CT-PLB)是目前临床广泛应用的肺部病变诊断方式,但其为有创检查,最常见的并发症为气胸和肺出血,严重时可危及生命。本研究旨在分析影响CT-PLB不同并发症发生的独立危险因素,以降低并发症发生率。方法回顾性分析2018年5月至2019年12月于我院行CT-PLB且临床资料完整的605例患者的资料。依病变位置分为胸膜下组和非胸膜下组,根据并发症分为气胸组、肺出血组、气胸合并肺出血组及无气胸/肺出血组,计算各并发症的发生率。分析影响不同并发症发生的危险因素及各并发症的独立危险因素。结果气胸发生率为34.1%,肺出血发生率为28.1%,同时发生气胸及肺出血63例,发生率为10.8%。影响胸膜下组气胸发生的独立危险因素为病变大小(P=0.002)。影响非胸膜下组气胸发生的独立危险因素为穿刺针走行区域平扫CT值(P=0.035)、穿刺针经过肺组织长度(P=0.003)、穿刺针经过胸壁厚度(P=0.020);影响非胸膜下组肺出血发生的独立危险因素为穿刺针经过肺组织长度(P<0.001)、穿刺针走行区域△CT值(P=0.001)、病变大小(P=0.034)及患者体位(P=0.014)。影响气胸、肺出血同时发生的独立危险因素为穿刺针经过肺组织长度(P<0.001)、穿刺针走行区域△CT值(P<0.001)。结论 CT-PLB是一种安全、有效的诊断方式,对肺部占位性病变具有较高的诊断价值,选择合适的穿刺方案可减少气胸、肺出血等并发症,提高诊疗效率。

内外双“管”下ESG表现对企业融资成本的影响研究

本文基于沪深A股上市工业企业2015-2020年面板数据,实证检验了ESG表现对企业融资成本的影响,以及内部控制和媒体关注在二者关系中的重要补充机制。研究结果显示,企业ESG表现及其三个维度对企业融资成本具有差异化负向效应,良好的环境责任和公司治理表现更能显著降低企业融资成本;内部控制和媒体关注度会放大ESG表现对企业融资成本的抑制作用,即随着内控水平和媒体关注度的提高,企业ESG表现及其三个维度对融资成本的抑制效果逐渐得到强化。其中,内部控制的强化效果在公司治理方面体现更为明显,媒体关注的强化效果则在环境责任方面更为突出。

Research of the molecular mechanism of Hai Honghua medicinal liquor in the treatment of fracture based on network pharmacology combined with molecular docking

Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.

交叉学科教学实践——可用于低温环境的可穿戴“电子皮肤”

让数字化走进生活一直是人类追求的目标。可穿戴“电子皮肤”横空出世,已被广泛应用于人体运动监测、健康医疗、人工智能等各个领域。为了探索化学化工与生物医学学科的交叉融合人才培养模式,本实验设计并制备了结冷胶/聚丙烯酰胺双网络导电水凝胶,阐明了双网络水凝胶的构建原理,并将其应用于可穿戴式柔性传感器监测人体运动和生理信号。该教学实验将课题组已发表的相关科研成果与本科教学实验有机结合,由浅入深地向学生介绍这种新兴电子产物的制备及应用,激发了学生的学习兴趣和创新意识。

乡村既有建筑改造中的新旧共生——以南京市高岗村民居改造实践为例

近年来,乡村闲置建筑的活化利用逐渐受到关注,对于建筑改造而言,处理“新”与“旧”的关系始终是核心命题。本文阐述了乡村建筑改造中“新”与“旧”的矛盾,提出一种基于“新旧共生”理念的路径,以团队主持的乡村民居改造项目为案例,提出具体的改造策略,试图探索一种有效的乡村既有建筑改造模式,为相关设计实践提供借鉴。

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

传统和机器学习策略在基于结构虚拟筛选中的应用

计算机辅助药物发现和人工智能驱动药物设计在制药行业中是减少时间和经济成本的重要策略.其中具有代表性的方法包括虚拟筛选、蛋白质-配体相互作用评估、药物药代动力学性质预测以及药物设计.通常来说,虚拟筛选是药物发现的第一步,其主要目标是识别和发现潜在的先导化合物的候选物.在过去的几十年里,已经开发了多种传统的和基于机器学习的方法来提高虚拟筛选的准确性和速度.本综述总结了传统和机器学习方法在基于结构的虚拟筛选中的应用,讨赖性较弱,且分布非常冷并在j=1处达到峰值,但(0,1,0)振动态的转论了它们的性能、优势和局限性等方面.

A 16-bit 18-MSPS flash-assisted SAR ADC with hybrid synchronous and asynchronous control logic

This paper presents a 16-bit,18-MSPS(million samples per second)flash-assisted successive-approximation-register(SAR)analog-to-digital converter(ADC)utilizing hybrid synchronous and asynchronous(HYSAS)timing control logic based on an on-chip delay-locked loop(DLL).The HYSAS scheme can provide a longer settling time for the capacitive digital-to-analog converter(CDAC)than the synchronous and asynchronous SAR ADC.Therefore,the issue of incomplete settling or ringing in the DAC voltage for cases of either on-chip or off-chip reference voltage can be solved to a large extent.In addition,the fore-ground calibration of the CDAC’s mismatch is performed with a finite-impulse-response bandpass filter(FIR-BPF)based least-mean-square(LMS)algorithm in an off-chip FPGA(field programmable gate array).Fabricated in 40-nm CMOS process,the proto-type ADC achieves 94.02-dB spurious-free dynamic range(SFDR),and 75.98-dB signal-to-noise-and-distortion ratio(SNDR)for a 2.88-MHz input under 18-MSPS sampling rate.

Glymphatic system:a gateway for neuroinflammation

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

Annexin A1 in the nervous and ocular systems

The therapeutic potential of Annexin A1,an important member of the Annexin superfamily,has become evident in results of experiments with multiple human systems and animal models.The anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous system.In this review,we initially describe the expression sites of Annexin A1,then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches;and,finally,we discuss the neuroregenerative potential qualities of Annexin A1.The eye and the nervous system are anatomically and functionally connected,but the association between visual system pathogenesis,especially in the retina,and Annexin A1 alterations has not been well summarized.Therefore,we explain the beneficial effects of Annexin A1 for ocular diseases,especially for retinal diseases and glaucoma on the basis of published findings,and we explore present and future delivery strategies for Annexin A1 to the retina.

Density functional theory study of B- and Si-doped carbons and their adsorption interactions with sulfur compounds

Understanding the adsorption interactions between carbon materials and sulfur compounds has far-reaching impacts,in addition to their well-known important role in energy storage and conversion,such as lithium-ion batteries.In this paper,properties of intrinsic B or Si single-atom doped,and B-Si codoped graphene(GR)and graphdiyne(GDY)were investigated by using density functional theory-based calculations,in which the optimal doping configurations were explored for potential applications in adsorbing sulfur compounds.Results showed that both B or Si single-atom doping and B-Si codoping could substantially enhance the electron transport properties of GR and GDY,improving their surface activity.Notably,B and Si atoms displayed synergistic effects for the codoped configurations,where B-Si codoped GR/GDY exhibited much better performance in the adsorption of sulfurcontaining chemicals than single-atom doped systems.In addition,results demonstrated that,after B-Si codoping,the adsorption energy and charge transfer amounts of GDY with sulfur compounds were much larger than those of GR,indicating that B-Si codoped GDY might be a favorable material for more effectively interacting with sulfur reagents.

Exploring the Latest Applications of OpenAI and ChatGPT: An In-Depth Survey

OpenAI and ChatGPT, as state-of-the-art languagemodels driven by cutting-edge artificial intelligence technology,have gained widespread adoption across diverse industries. In the realm of computer vision, these models havebeen employed for intricate tasks including object recognition, image generation, and image processing, leveragingtheir advanced capabilities to fuel transformative breakthroughs. Within the gaming industry, they have foundutility in crafting virtual characters and generating plots and dialogues, thereby enabling immersive and interactiveplayer experiences. Furthermore, these models have been harnessed in the realm of medical diagnosis, providinginvaluable insights and support to healthcare professionals in the realmof disease detection. The principal objectiveof this paper is to offer a comprehensive overview of OpenAI, OpenAI Gym, ChatGPT, DALL E, stable diffusion,the pre-trained clip model, and other pertinent models in various domains, encompassing CLIP Text-to-Image,education, medical imaging, computer vision, social influence, natural language processing, software development,coding assistance, and Chatbot, among others. Particular emphasis will be placed on comparative analysis andexamination of popular text-to-image and text-to-video models under diverse stimuli, shedding light on thecurrent research landscape, emerging trends, and existing challenges within the domains of OpenAI and ChatGPT.Through a rigorous literature review, this paper aims to deliver a professional and insightful overview of theadvancements, potentials, and limitations of these pioneering language models.

Karyotype establishment and development of specific molecular markers of Aegilops geniculata Roth based on SLAF-seq

The constant evolution of pathogens poses a threat to wheat resistance against diseases,endangering food security.Developing resistant wheat varieties is the most practical approach for circumventing this problem.As a close relative of wheat,Aegilops geniculata,particularly accession SY159,has evolved numerous beneficial traits that could be applied to improve wheat.In this study,we established the karyotype of SY159 by fluorescence in situ hybridization(FISH)using the oligonucleotide probes Oligo-pTa535 and Oligo-pSc119.2 and a complete set of wheat–Ae.geniculata accession TA2899 addition lines as a reference.Using specific-locus amplified fragment sequencing(SLAF-seq)technology,400 specific markers were established for detecting the SY159 chromosomes with efficiencies reaching 81.5%.The SY159-specific markers were used to classify the different homologous groups of SY159 against the wheat-Ae.geniculata addition lines.We used these specific markers on the 7Mg chromosome after classification,and successfully confirmed their suitability for studying the different chromosomes of SY159.This study provides a foundation for accelerating the application of SY159 in genetic breeding programs designed to improve wheat.

Improving the operational stability of perovskite solar cells with cesium-doped graphene oxide interlayer

Perovskite solar cells(PSCs)have made great advances in terms of power conversion efficiency(PCE),yet their subpar stability continues to hinder their commercialization.The interface between the perovskite layer and the charge-carrier transporting layers plays a crucial role in undermining the stability of PSCs.In this work,we propose a strategy to stabilize high-performance PSCs with PCE over 23%by introducing a cesium-doped graphene oxide(GO-Cs)as an interlayer between the perovskite and hole-transporting material.The GO-Cs treated PSCs exhibit excellent operational stability with a projected T80(the time where the device PCE reduces to 80%of its initial value)of 2143 h of operation at the maximum powering point under one sun illumination.

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway

Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis model.This study aimed to explore the effects of TL1A on human colonic fibroblasts.Methods A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis.The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)supernatant.The proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western blotting.Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group.Transforming growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group.The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 h.TL1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co cells.Treatment of CCD-18Co cells with TL1A increased the expression of TGF-β1 and p-Smad3.Conclusion TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.

Video caching and scheduling with edge cooperation

In this paper,we explore a distributed collaborative caching and computing model to support the distribution of adaptive bit rate video streaming.The aim is to reduce the average initial buffer delay and improve the quality of user experience.Considering the difference between global and local video popularities and the time-varying characteristics of video popularity,a two-stage caching scheme is proposed to push popular videos closer to users and minimize the average initial buffer delay.Based on both long-term content popularity and short-term content popularity,the proposed caching solution is decouple into the proactive cache stage and the cache update stage.In the proactive cache stage,we develop a proactive cache placement algorithm that can be executed in an off-peak period.In the cache update stage,we propose a reactive cache update algorithm to update the existing cache policy to minimize the buffer delay.Simulation results verify that the proposed caching algorithms can reduce the initial buffer delay efficiently.

Self-Assembly of Bacteria in Alternating-Current Electric Fields

Self-assembly of bacteria in electric fields is a promising route to fabricate biomaterials with reversible and specific structures.However,due to relatively less studies,our understanding of the self-assembly of bacteria in electric fields is still incomplete.Particularly,how different bacterial species behave differently in their fieldmediated self-assembly behavior remains to be disclosed.In this study,we choose four bacterial species,including Shewanella oneidensis,Pseudomonas aeruginosa,Bacillus subtilis and Lactococcus lactis as model systems,and investigate their self-assembly behavior in alternating-current(AC)electric fields for both diluted and concentrated suspensions.The phase diagrams in the plane of applied field strength vs frequency are obtained.The results show that in diluted suspensions,a transition sequence of isotropic–paranematic–string–columnar phases is observed in all strains as the field strength increases.Details of the assembled structures are quantitatively differentiated among different strains.In concentrated suspensions,besides the isotropic and paranematic phases,a higher ordered phase with interdigitating rectangular crystal domains(OIR)and an ordered phase with smectic A liquid crystal domains are observed for S.oneidensis and P.aeruginosa,respectively.Our findings shed new light on fabricating potential biomaterials by assembling cells of appropriately chosen bacterial species that have desired surface properties under AC electric fields.

U-Pb dating of monazite in the Bainiuchang silver polymetallic deposit,Yunnan Province,and its limitation on Mesozoic mineralization

1.Objective The Gejiu-Bozhushan-Laojunshan tin-tungsten polymetallic metallogenic belt is located in southeastern Yunnan.It is bounded by the Mile-Shizong Fault and the Yangzi Plate to the north and west,respectively,while the Honghe Fault represents its southwestern boundary.It is adjacent to the Ailaoshan Fault,and extends to Guangxi and Vietnam to the southeast(Fig.1a;Liu JP et al.,2021).