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Due to the fatigue and continuous energy input during high-speed dynamic friction polishing (DFP), the diamond crystal beneath the polished surface (roughness 50 nm) and even preferential crystal cleavage with the non-diamond phase (distributing at the position in micrometers range).

AbstractPatients in the Intensive care unit need remarkable observation. This unit consists of people who are critically ill and may tend to lose their lives anytime. Healthcare professionals in critical care tend to commit prescription errors for many reasons. Since patients in intensive care are severely ill and have complicated health issues, mistakes while prescribing medicines can have serious repercussions. In this study, a federated learning model is simulated to reduce the mistakes while prescribing medicines in the intensive care unit, which provides an opportunity for many hospitals to collaborate, keeping their data local to themselves. Local training is performed with Logistic regression, Simple neural network, and Multilayer perceptron in which simple neural network achieves the highest accuracy of 95%. Model weights transferred to a federated server may be vulnerable to data and model poisoning attacks, eavesdropping, and model inversion attacks. So, model weights are encrypted using Paillier homomorphic encryption (PHE), achieving a model accuracy of 93.26% for a key size of 2048. With key size, the effect of encryption and decryption time is observed. The model is also applied with differential privacy, which achieved an accuracy of 94.24% when c = 0.5 and sigma = 0.05. Thus, this privacy-preserving federated learning model can be used to reduce drug prescription errors in critical care.

Background Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . Methods and Results Cis‐expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3–6 versus 0–2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome‐wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P

Extracellular vesicles (EVs) are nanovesicles containing bioactive molecules including proteins, nucleic acids and lipids that mediate intercellular and inter-organ communications, holding promise as potential therapeutics for multiple diseases. Adipose tissue (AT) serves as a dynamically distributed energy storage organ throughout the body, whose accumulation leads to obesity, a condition characterized by infiltration with abundant immune cells. Emerging evidence has illustrated that EVs secreted by AT are the novel class of adipokines that regulate the homeostasis between AT and peripheral organs. However, most of the studies focused on the investigations of EVs derived from adipocytes or adipose-derived stem cells (ADSCs), the summarization of functions in cellular and inter-organ crosstalk of EVs directly derived from adipose tissue (AT-EVs) are still limited. Here, we provide a systemic summary on the key components and functions of EVs derived from healthy adipose tissue, showing their significance on the tissue recovery and metabolic homeostasis regulation. Also, we discuss the harmful influences of EVs derived from obese adipose tissue on the distal organs. Furthermore, we elucidate the potential applications and constraints of EVs from healthy patients lipoaspirates as therapeutic agents, highlighting the potential of AT-EVs as a valuable biological material with broad prospects for future clinical use.

China’s reform began in the countryside, and rural reform began in Anhui. This study uses Anhui Province, China as an example in analyzing the impact of agricultural science and technology innovation resource allocation on rural revitalization, particularly by constructing an econometric model. Results indicate that the allocation of agricultural science and technology innovation resources has a steady positive impact on rural revitalization. Improvements in the allocation of agricultural science and technology innovation resources can effectively promote the development of rural revitalization and the spatial spillover of rural development, thereby facilitating the promotion of the spillover of neighboring areas to local rural development. A nonlinear relationship exists between allocation of agricultural science and technology innovation resources and rural revitalization. Lastly, rural revitalization can only be promoted substantially when the allocation of agricultural science and technology innovation resources reaches a certain condition.

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory disease in humans. High fatality rates and continued infectiousness remain a pressing concern for global health preparedness. Antibodies targeted at the receptor-binding domain (RBD) are major countermeasures against human viral infection. Here, we report four potent nanobodies against MERS-CoV, which are isolated from alpaca, and especially the potency of Nb14 is highest in the pseudotyped virus assay. Structural studies show that Nb14 framework regions (FRs) are mainly involved in interactions targeting a novel epitope, which is entirely distinct from all previously reported antibodies, and disrupt the protein-carbohydrate interaction between residue W535 of RBD and hDPP4 N229-linked carbohydrate moiety (hDPP4-N229-glycan). Different from Nb14, Nb9 targets the cryptic face of RBD, which is distinctive from the hDPP4 binding site and the Nb14 epitope, and it induces the β5-β6 loop to inflect towards a shallow groove of the RBD and dampens the accommodation of a short helix of hDPP4. The particularly striking epitopes endow the two Nbs administrate synergistically in the pseudotyped MERS-CoV assays. These results not only character unprecedented epitopes for antibody recognition but also provide promising agents for prophylaxis and therapy of MERS-CoV infection.

BackgroundAtherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic’s anti-atherosclerotic effects remain unclear.AimsThis study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis.MethodsThe study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets.ResultsThe integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis.ConclusionGarlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.

Aim: This study aims to investigate the influence of ASAP1 (ADP ribosylation factor guanylate kinase 1) on the malignant behavior of gastric cancer (GC) cells and to elucidate the potential molecular mechanisms involved in cancer development and progression. Methods: We assessed the impact of ASAP1 overexpression and knockdown on GC cell malignancy using CCK8, colony formation, flow cytometry (Annexin V/propidium iodide), Transwell migration, invasion, and scratch assays. Western blot analysis was used to assess the effects of ASAP1 on angiogenesis, matrix metalloproteinases (MMPs), apoptotic proteins, epithelial-mesenchymal transition (EMT)-related proteins, as well as AKT and p-AKT. The influence of ASAP1 knockdown was also evaluated in nude mice bearing BGC823 cell-derived tumors. Results: Our findings revealed that ASAP1 was significantly overexpressed in GC cells, enhancing their proliferation, invasion, and migration, while reducing apoptosis. Conversely, ASAP1 knockdown reversed these effects, markedly increasing the expression of cleaved-caspase 3 (Casp3), PARP, and the epithelial marker E-cadherin, and significantly decreasing MMP2, MMP9, VEGFA, and mesenchymal markers such as N-cadherin and vimentin. Additionally, it reduced AKT, and p-AKT levels (P

BackgroundPrevious research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study.MethodsGenetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test.ResultsWe identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08–2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42–0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25–3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P

The hybrid grouper (Epinephelus lanceolatus♂ × E. fuscoguttatus♀) is a novel and commercially important fish for mariculture in China. Recent years, the outbreak of viral and bacterial diseases have caused huge losses of hybrid grouper culture. However, the immune response of hybrid grouper against viral and bacterial infection remains unexplored. In this study, a total of 9 splenic transcriptomic libraries of hybrid grouper including untreated control, Red-spotted grouper nervous necrosis virus (RGNNV)-challenged, Vibrio alginolyticus-challenged were constructed. A sum of 6024 differentially expressed genes (DEGs) with significant differences were identified, of which the overlapped DEGs between RGNNV and V. alginolyticus challenged were significantly enriched in multiple immune-related pathway including interleukin-17 NOD-like receptor, C-type lectin receptor, chemokine signaling pathway and natural killer cell mediated cytotoxicity, indicating their important roles in immune defense of hybrid grouper against (both) viral and bacterial infection. To the best of our knowledge, this is the first report that investigated the immune response of hybrid grouper following viral and bacterial pathogen stimuli using transcriptomic analysis. These results provide comprehensive understandings of the innate immunity of hybrid grouper and valuable references to develop disease control strategy in grouper aquaculture.

Introduction: Rydberg atoms are ideal for measuring electric fields due to their unique physical properties. However, low-frequency electric fields below MHz can be challenging due to the accumulation of ionized free electrons on the atomic vapor cell’s surface, acting as a shield.Method: This paper proposes a Cavity-enhanced three-photon system (CETPS) measurement scheme, which uses a long-wavelength laser to excite the Rydberg state, reducing atomic ionization and enhancing detection spectrum resolution. A theoretical model is proposed to explain the quantum coherence effect of the light field, measured electric field, and the atomic system.Result: The results show that the proposed scheme significantly increases the electromagnetically induced transparency (EIT) spectral peak and narrows the spectral width, resulting in the maximum slope increasing by more than an order of magnitude.Discussion: The paper also discusses the impact of the Rabi frequency of the two laser fields and the coupling coefficient of the optical cavity on the transmission spectrum amplitude and linewidth, along with the optimal configuration of these parameters in the CEPTS scheme.

The ultimate enrichment level and quantity of gas hydrate resources are influenced by the dynamic process of accumulation and preservation. High-resolution 3-D seismic data, logging while drilling (LWD), pressured coring, and in situ testing were used to characterize the dynamic accumulation and preservation of the trial production high-grade gas hydrate reservoir (HGGHR) in the Shenhu area. Through seismic variance analysis and ant-tracking, we found that newly identified mud diapir-associated faults with three development stages controlled the migration and accumulation of gas hydrate and shifted the base of the gas hydrate stability zone (BGHSZ), resulting in dynamic accumulation and dissociation of gas hydrates. The recognized double bottom simulating reflectors (BSRs) were concluded to have been formed due to the shift of the BGHSZ caused by the variational equilibrium conditions. The interval between the double BSRs was inferred to be a disequilibrium zone where gas recycling occurred, contributing to the coexistence of gas hydrates and free gas and the dynamic formation of the HGGHR. Multiple gliding faults formed within the GHSZ in the late period have altered the HGGHR and control the present thickness and distribution of the gas hydrates and free gas in the hanging wall and footwall. Under the influence of geothermal fluids and the fault system associated with the mud diapir, the HGGHR experienced dynamic accumulation with three stages, including early accumulation, medium-term adjustment, and late alteration and preservation. We conclude that four factors affected the formation, distribution, and occurrence of the HGGHR: the geothermal fluids accompanying the deep mud diapir below the reservoir, the dual supply of thermogenic gas and biogenic gas, the recycling of hydrate gas beneath the BGHSZ, and the post-gas hydrate faults developed within the GHSZ. A geological model illustrating the dynamic formation of the trial production HGGHR was proposed, providing a reference for future exploration of HGGHRs with a great production potential in deepwater settings.

Objective: To explore the potential targets for melatonin in the treatment of periodontitis through network pharmacologic analysis and experimental validation via in vivo animal models and in vitro cellular experiments. Materials and methods: In this study, we first screened melatonin targets from Pharm Mapper for putative targets, Drug Bank, and TCMSP databases for known targets. Then, disease database was searched and screened for differential expressed genes associated with periodontitis. The intersection of disease and melatonin-related genes yielded potential target genes of melatonin treatment for periodontitis. These target genes were further investigated by protein-protein interaction network and GO/KEGG enrichment analysis. In addition, the interactions between melatonin and key target genes were interrogated by molecular docking simulations. Then, we performed animal studies to validate the therapeutic effect of melatonin by injecting melatonin into the peritoneal cavity of ligation-induced periodontitis (LIP) mice. The effects of melatonin on the predicted target proteins were also analyzed using Western blot and immunofluorescence techniques. Finally, we constructed an in vitro cellular model and validated the direct effect of melatonin on the predicted targets by using qPCR. Results: We identified 8 potential target genes by network pharmacology analysis. Enrichment analysis suggests that melatonin may treat periodontitis by inhibiting the expression of three potential targets (MPO, MMP8, and MMP9). Molecular docking results showed that melatonin could effectively bind to MMP8 and MMP9. Subsequently, melatonin was further validated in a mouse LIP model to inhibit the expression of MPO, MMP8, and MMP9 in the periodontal tissue. Finally, we verified the direct effect of melatonin on the mRNA expression of MPO, MMP8, and MMP9 in an in vitro cellular model. Conclusions: Through a combination of network pharmacology and experimental validation, this study provides a more comprehensive understanding of the mechanism of melatonin to treat periodontitis. Our study suggests that MPO, MMP8, and MMP9 as key target genes of melatonin to treat periodontitis. These findings present a more comprehensive basis for further investigation into the mechanisms of pharmacological treatment of periodontitis by melatonin.

Smoking disrupts bone homeostasis and serves as an independent risk factor for the development and progression of osteoporosis. Tobacco toxins inhibit the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), promote BMSCs aging and exhaustion, but the specific mechanisms are not yet fully understood. Herein, we successfully established a smoking-related osteoporosis (SROP) model in rats and mice through intraperitoneal injection of cigarette smoke extract (CSE), which significantly reduced bone density and induced aging and inhibited osteogenic differentiation of BMSCs both in vivo and in vitro. Bioinformatics analysis and in vitro experiments confirmed that CSE disrupts mitochondrial homeostasis through oxidative stress and inhibition of mitophagy. Furthermore, we discovered that CSE induced BMSCs aging by upregulating phosphorylated AKT, which in turn inhibited the expression of FOXO3a and the Pink1/Parkin pathway, leading to the suppression of mitophagy and the accumulation of damaged mitochondria. MitoQ, a mitochondrial-targeted antioxidant and mitophagy agonist, was effective in reducing CSE-induced mitochondrial oxidative stress, promoting mitophagy, significantly downregulating the expression of aging markers in BMSCs, restoring osteogenic differentiation, and alleviating bone loss and autophagy levels in CSE-exposed mice. In summary, our results suggest that BMSCs aging caused by the inhibition of mitophagy through the AKT/FOXO3a/Pink1/Parkin axis is a key mechanism in smoking-related osteoporosis.

The ideal implant surface plays a substantial role in maintaining bone homeostasis by simultaneously promoting osteoblast differentiation and limiting overactive osteoclast activity to a certain extent, which leads to satisfactory dynamic osseointegration. However, the rational search for implant materials with an ideal surface structure is challenging and a hot research topic in the field of tissue engineering. In this study, we constructed titanium dioxide titanium nanotubes (TNTs) by anodic oxidation and found that this structure significantly promoted osteoblast differentiation and inhibited osteoclast formation and function while simultaneously inhibiting the total protein levels of proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK). Knockdown of the PYK2 gene by siRNA significantly suppressed the number and osteoclastic differentiation activity of mouse bone marrow mononuclear cells (BMMs), while overexpression of PYK2 inhibited osteogenesis and increased osteoclastic activity. Surprisingly, we found for the first time that neither knockdown nor overexpression of the FAK gene alone caused changes in osteogenesis or osteoclastic function. More importantly, compared with deletion or overexpression of PYK2/FAK alone, coexpression or cosilencing of the two kinases accelerated the effects of TNTs on osteoclastic and osteogenic differentiation on the surface of cells. Furthermore, in vivo experiments revealed a significant increase in positiveexpression-PYK2 cells on the surface of TNTs, but no significant change in positiveexpression -FAK cells was observed. In summary, PYK2 is a key effector molecule by which osteoblasts sense nanotopological mechanical signals and maintain bone homeostasis around implants. These results provide a referable molecular mechanism for the future development and design of homeostasis-based regulatory implant biomaterials.

Abstract High or medium- entropy alloys (HEAs/MEAs) are multi-principal element alloys with equal atomic elemental composition, some of which have shown record-breaking mechanical performance. However, the link between short-range order (SRO) and the exceptional mechanical properties of these alloys has remained elusive. The local destruction of SRO by dislocation glide has been predicted to lead to a rejuvenated state with increased entropy and free energy, creating softer zones within the matrix and planar fault boundaries that enhance the ductility, but this has not been verified. Here, we integrate in situ nanomechanical testing with energy-filtered four-dimensional scanning transmission electron microscopy (4D-STEM) and directly observe the rejuvenation during cyclic mechanical loading in single crystal CrCoNi at room temperature. Surprisingly, stacking faults (SFs) and twin boundaries (TBs) are reversible in initial cycles but become irreversible after a thousand cycles, indicating SF energy reduction and rejuvenation. Molecular dynamics (MD) simulation further reveals that the local breakdown of SRO in the MEA triggers these SF reversibility changes. As a result, the deformation features in HEAs/MEAs remain planar and highly localized to the rejuvenated planes, leading to the superior damage tolerance characteristic in this class of alloys.

The Yellow River basin (YRB) is a major ecological functional area in China, and its ecological safety development and change have extremely significant impacts on the natural environment and human society. However, existing studies on the YRB lack spatiotemporal characteristics analysis and prediction of ecological safety with vegetation as the core. Therefore, this study proposes to construct an ecological safety index (ESI) of the YRB based on the comprehensive multidimensional ecological safety evaluation system “vigor-pressure-state-response,” using the normalized difference vegetation index, vegetation carbon sink indicator parameters, temperature, precipitation, the digital elevation model, population density, and the per capita gross domestic product from 2000 to 2020. The spatiotemporal characteristics of the ESI were then analyzed for the YRB, and a long-term and short-term memory network model was constructed to predict the ESI trend of the YRB over the next 10 years. According to the results, from 2000 to 2020, the ESI of the YRB showed a fluctuating upward trend, and the annual average of the ESI changed abruptly in 2015 due to drastic changes in hazardous areas. The ESI in most areas of the YRB showed a significant upward trend, the stability of ESI changes was weak in some areas, and the overall spatial distribution showed significant positive spatial agglomeration characteristics. Further, the response of ESI to landscape complexity in different reaches of the YRB varied. Most of the middle reaches were positively correlated with landscape complexity, while most of the upper and lower reaches were not significantly or negatively correlated. Notably, over the next 10 years, YRB's ESI growth will slow down, with areas with degradation increasing, areas with significant growth decreasing, and areas currently showing stability improvement.

To reduce power waste and improve the operational safety of renewable energy grids, this study proposes an auxiliary decision-making method for power dispatching based on flexible super-capacitors and proximal policy optimization algorithms. The results demonstrated that the impedance of Mn&Ni-based composite electrodes was small, about $118~\Omega $ , and when the current density was 1A/g, the constant current charging and discharging time could reach 128 seconds, with a specific capacitance of 39F/g. In addition, when the power density of the capacitor was 8500W/kg, the energy density could reach up to 125Wh/kg. As for the auxiliary decision-making model for power dispatching, the reward value of the proximal policy optimization algorithm began to converge after approximately 50,000 iterations, at which point its reward value was approximately 257. The reward value of the one-step scheduling strategy gradually stabilized at around 1.0 after the number of scheduling steps reached 560,000. When the energy output rate of renewable energy units was high, the consumption rate of renewable energy was 90.1%. The above results indicate that the power scheduling method combining flexible super-capacitors and proximal policy optimization algorithms can effectively achieve the storage of electricity and improve the consumption rate of renewable energy.

Abstract Background Insulin resistance (IR), a hallmark of proceeding diabetes and cardiovascular (CV) disease, has been shown to predict prognosis in patients undergoing percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and metabolic score for insulin resistance (METS-IR) have been shown to be simple and reliable non-insulin-based surrogates for IR. However, limited studies have determined the associations between distinct non-insulin-based IR markers and CV outcomes in patients undergoing complex PCI who are at higher risk of CV events after PCI. Therefore, this study aimed to investigate and compare the prognostic value of these markers in patients undergoing complex PCI. Methods This was a descriptive cohort study. From January 2017 to December 2018, a total of 9514 patients undergoing complex PCI at Fuwai Hospital were consecutively enrolled in this study. The 3 IR indices were estimated from the included patients. The primary study endpoint was CV events, defined as a composite of CV death, nonfatal myocardial infarction and nonfatal stroke. Results During a median follow-up of 3.1 years, 324 (3.5%) CV events occurred. Multivariable Cox regression models showed per-unit increase in the TyG index (hazard ratio [HR], 1.42; 95% confidence interval [CI] 1.13–1.77), rather than per-unit elevation in either Ln(TG/HDL-C ratio) (HR, 1.18; 95%CI 0.96–1.45) or METS-IR (HR, 1.00; 95%CI 0.98–1.02), was associated with increased risk of CV events. Meanwhile, adding the TyG index to the original model led to a significant improvement in C-statistics (0.618 vs. 0.627, P 0.05) to the original model. Conclusions The TyG index, not TG/HDL-C ratio and METS-IR, was positively associated with worse CV outcomes in patients undergoing complex PCI. Our study, for the first time, demonstrated that the TyG index can serve as the suitable non-insulin-based IR marker to help in risk stratification and prognosis in this population.