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Abstract Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of β-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

Pulverized fuel ash (PFA) is a by-product from coal-fired power plants. The generation of PFA is huge and increases yearly. A large amount of untreated PFA is harmful to the environment, and it is also a waste of resources. Recycling PFA as construction materials would improve resource utilization efficiency, reduce environmental risks, conform to the demand for high-efficient and low-carbon utilization of solid waste and help to achieve the national strategy goals of carbon peak and carbon neutrality. The utilization efficiency of PFA as construction materials could be improved by optimizing production processes and developing new technologies, which would promote its large-scale and high-value utilization. In this paper, the general situation and physical and chemical properties of PFA are summarized. Various value-added utilization technologies of PFA as construction materials, including raw materials for cement production, supplementary cementitious materials, bricks and blocks, artificial aggregates, glass-ceramic materials, fire-resistant insulation materials, and new intelligent construction materials are comprehensively reviewed. This paper also introduces the research status of the utilization of PFA in construction materials, analyzes the applicability of different technologies, summarizes the latest technologies for preparing the PFA-based green construction materials and challenges faced in future research, provides detailed introductions to the mechanism of PFA application, and proposes thoughts on the problems existing in the utilization of PFA as construction materials. Finally, the further perspectives of the development of the PFA-derived low-carbon construction materials are highlighted. The study suggests that the “traditional large-scale consumption of PFA” and “high-value utilization of PFA” should be researched in parallel, and theoretical research and engineering practice should support each other, which would provide some scientific references for the sustainable management of PFA.

Summary: The building sector is integral to climate change mitigation in China as well as the globe. By considering the impact of green innovation, we explore the long-term trend of carbon emissions in China’s building sector until 2060, encompassing its entire life cycle. Results show that CO2 emissions of China’s building sector will peak at 6.98–7.69 Bt in 2035 and maintain at 1.11 Bt in 2060 under the business-as-usual (BAU) scenario. The “3060 dual carbon goal” will only be achieved under the technological breakthrough (TB) scenario. These findings show that existing or relatively lax policies are insufficient to achieve the “3060” goal for the building sector. China should actively pursue green technological innovation throughout the building sector’s life cycle, with a focus on accelerating the green and low-carbon production of key products, such as steel and cement, at the building material production stage.

In this paper, a spiral motion computation method based on transformation optics for computing the microwave heating processes with irregular food is presented. Firstly, the theoretical derivations of the rotating, lifting, and overlapping regions caused by rotating and lifting are conducted. Secondly, the electric field distribution computed by the proposed method is verified, and the computation accuracy and time are compared with implicit function and level set methods (IFLSM). It was found that the root-mean-square-errors (RMSEs) of the port reflection coefficients for rotating motion, lifting motion, and spiral motion are 0.021, 0.164, and 0.151, respectively, demonstrating the effectiveness of the proposed method in computing the spiral motion of irregular food shapes. Finally, the computation of spiral microwave heating of irregular-shaped bears with different materials under different motion states is studied, and the industrial application of cookies in secondary processing is analyzed.

Abstract Over the past 30 years, the Arctic Dipole Anomaly (DA) has repeatedly led to record lows in summer sea ice extent, with cloud radiative effects (CRE) playing a crucial regulatory role. Here, we reveal the CRE variations between positive and negative DA events and elucidate the slowing impacts of CRE on sea ice thickness (SIT) changes. The DA triggers robust meridional winds and transpolar drift, markedly reducing SIT in the Beaufort Sea (BeS), Chukchi Sea (CS), and East Siberian Sea (ESS), while increasing it in the Greenland Sea (GS). CRE significantly slow SIT changes, contributing +14.4, +4.4, +16.4, and −26.7 cm to changes from June to August, against total changes of −55.9, −29.4, −39.8, and +42.8 cm in September over BeS, CS, ESS, and GS, respectively. This study underscores the key impacts of CRE on sea ice variation, emphasizing their significance in the polar climate system.

BackgroundSepsis is a life-threatening condition that requires rapid assessment to reduce mortality. This study investigates the relationship between the Neutrophil-to-Monocyte/Lymphocyte Ratio (NMLR) upon ICU admission and 28-day mortality in sepsis patients.MethodsA retrospective analysis was performed using clinical data from sepsis patients in the Medical Information Mart for Intensive Care IV (MIMIC-IV). Multivariate logistic regression, sensitivity analyses, and Restricted Cubic Spline (RCS) models were employed to explore the relationship between ICU admission NMLR and 28-day mortality. Kaplan–Meier method and inverse probability weighting (IPW) were used to adjust for confounders and estimate survival outcomes. Receiver operating characteristic (ROC) curve evaluating the predictive value of NLMR for 28-day mortality in ICU sepsis patients. Subgroup analyses considered factors like age, sex, race, comorbidities, and disease severity.ResultsIn total, 8,710 patients were included. Increased NMLR was associated with higher 28-day all-cause mortality, confirmed by multiple logistic regression models. In Model 3, after adjusting for confounders, each standard deviation increase in NMLR was associated with a 1.5% increase in 28-day mortality risk. Kaplan–Meier and IPW survival analyses showed higher 28-day all-cause mortality in patients with elevated NMLR levels at ICU admission compared to those with lower levels (p

Soft adhesive systems (SASs), which consist of a soft adhesive layer and/or soft adherends, have been extensively applied in advanced fields such as biomedicine, flexible electronics, and soft robotics. Understanding the fatigue failure of SASs is crucial for ensuring their structural safety and functional stability, as they are often subjected to fatigue loading. This paper systematically reviews the fatigue failure of SASs, aiming to provide a comprehensive understanding and contribute to the study of fatigue failure mechanisms and lifetime prediction of SASs. The review starts by introducing classical research methods for fatigue failure of adhesive systems, with a focus on total fatigue lifetime and fatigue crack growth (FCG). After summarizing the complexity of fatigue failure in SASs, it provides an overview of fatigue research for the three types of SASs: “soft interface”, “soft adherend”, and “soft-soft” adhesive systems. Then, the relations between the fatigue failure and energy dissipation of various SASs are specifically discussed noting that significant energy dissipation accompanying the cyclic deformation of SASs during fatigue loading can substantially affect the final fatigue failure of SASs. Finally, the current unresolved issues and challenges in this field are presented.

Abstract Background Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. Methods Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. Results A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P

Abstract The challenges posed by delayed atrophic healing and nonunion stand as formidable obstacles in osteoporotic fracture treatment. The processes of type H angiogenesis and osteogenesis emerge as pivotal mechanisms during bone regeneration. Notably, the preconditioning of adipose-derived stem cell (ADSC) exosomes under hypoxic conditions has garnered attention for its potential to augment the secretion and functionality of these exosomes. In the present investigation, we embarked upon a comprehensive elucidation of the underlying mechanisms of hypo-ADSC-Exos within the milieu of osteoporotic bone regeneration. Our findings revealed that hypo-ADSC-Exos harboured a preeminent miRNA, namely, miR-21-5p, which emerged as the principal orchestrator of angiogenic effects. Through in vitro experiments, we demonstrated the capacity of hypo-ADSC-Exos to stimulate the proliferation, migration, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) via the mediation of miR-21-5p. The inhibition of miR-21-5p effectively attenuated the proangiogenic effects mediated by hypo-ADSC-Exos. Mechanistically, our investigation revealed that exosomal miR-21-5p emanating from hypo-ADSCs exerts its regulatory influence by targeting sprouly1 (SPRY1) within HUVECs, thereby facilitating the activation of the PI3K/AKT signalling pathway. Notably, knockdown of SPRY1 in HUVECs was found to potentiate PI3K/AKT activation and, concomitantly, HUVEC proliferation, migration, and angiogenesis. The culminating stage of our study involved a compelling in vivo demonstration wherein GelMA loaded with hypo-ADSC-Exos was validated to substantially enhance local type H angiogenesis and concomitant bone regeneration. This enhancement was unequivocally attributed to the exosomal modulation of SPRY1. In summary, our investigation offers a pioneering perspective on the potential utility of hypo-ADSC-Exos as readily available for osteoporotic fracture treatment. Graphical Abstract

ObjectiveThis study aims to assess the early clinical outcomes of bipolar hemiarthroplasty for treating femoral neck fractures in elderly patients aged 75 and above using the Orthopädische Chirurgie München (OCM) approach.MethodsA retrospective analysis was conducted on a cohort of 95 elderly patients who underwent bipolar hemiarthroplasty for Garden Type III and IV femoral neck fractures between January 2020 and December 2022. The participants were categorized into two groups according to the surgical approach used: the OCM approach and the posterior-lateral approach (PLA). The average follow-up duration was 11.20 ± 2.80 months for the OCM group and 11.12 ± 2.95 months for the PLA group, with both groups ranging from 6 to 18 months. Clinical outcomes assessed included surgical duration, incision length, postoperative hospital stay, time to ambulation, hemoglobin levels, serum creatine kinase (CK) levels, C-reactive protein (CRP) levels, pain (assessed using the Visual Analogue Scale, VAS), and functional recovery (evaluated through Harris hip scores). Additionally, complications such as intraoperative and postoperative fractures, deep vein thrombosis, wound infection, nerve injury, postoperative dislocation, leg length discrepancy, and Trendelenburg gait were monitored.ResultsThere was no significant difference in the surgical duration between the OCM and PLA groups. However, the OCM group exhibited shorter incision lengths, reduced postoperative hospital stays, and earlier ambulation times compared to the PLA group. Significantly lower intraoperative blood loss, smaller decreases in hemoglobin levels on postoperative days 1 and 3, lesser hidden blood loss, and decreased levels of CK and CRP were observed in the OCM group. Pain levels, measured by VAS scores, were lower, and Harris hip scores, indicating functional recovery, were higher at 2 and 6 weeks postoperatively in the OCM group than in the PLA group. The incidence of complications, such as periprosthetic fractures, intramuscular venous thrombosis, hip dislocations, Trendelenburg gait, and leg length discrepancies, showed no significant differences between the groups.ConclusionThe OCM approach for bipolar hemiarthroplasty in patients aged 75 and above with femoral neck fractures offers significant early clinical benefits over the traditional PLA, including faster recovery, reduced postoperative pain, and enhanced early functional recovery.

IntroductionImmunotherapy is critical for treating many cancers, and its therapeutic success is linked to the tumor microenvironment. Although anti-angiogenic drugs are used to treat gastric cancer (GC), their efficacy remains limited. Cancer-associated fibroblast (CAF)-targeted therapies complement immunotherapy; however, the lack of CAF-specific markers poses a challenge. Therefore, we developed a CAF angiogenesis prognostic score (CAPS) system to evaluate prognosis and immunotherapy response in patients with GC, aiming to improve patient stratification and treatment efficacy.MethodsWe assessed patient-derived GC CAFs for promoting angiogenesis using EdU, cell cycle, apoptosis, wound healing, and angiogenesis analysis.ResultsWe then identified CAF-angiogenesis-associated differentially-expressed genes, leading to the development of CAPS, which included THBS1, SPARC, EDNRA, and VCAN. We used RT-qPCR to conduct gene-level validation, and eight GEO datasets and the HPA database to validate the CAPS system at the gene and protein levels. Six independent GEO datasets were utilized for validation. Overall survival time was shorter in the high- than the low-CAPS group. Immune microenvironment and immunotherapy response analysis showed that the high-CAPS group had a greater tendency toward immune escape and reduced immunotherapy efficacy than the low-CAPS group.DiscussionCAPS is closely associated with GC prognosis and immunotherapy outcomes. It is therefore an independent predictor of GC prognosis and immunotherapy efficacy.

High salinity inhibits microbial activity in the bioremediation of saline wastewater. To alleviate osmotic stress, glycine betaine (GB), an osmoprotectant, is added to enhance the secretion of extracellular polymeric substances (EPS). These EPS are pivotal in withstanding environmental stressors, yet the intricate interplay between GB supplementation and microbial responses through EPS modifications—encompassing composition, molecular architecture, and electrochemical features—remains elusive in hypersaline conditions. Here we show microbial strategies for salinity endurance by investigating the impact of GB on the dynamic alterations of EPS properties. Our findings reveal that GB supplementation at 3.5% salinity elevates the total EPS (T-EPS) content from 12.50 ± 0.05 to 24.58 ± 0.96 mg per g dry cell weight. The observed shift in zeta potential from −28.95 to −6.25 mV at 0% and 3.5% salinity, respectively, with GB treatment, indicates a reduction in electrostatic repulsion and compaction. Notably, the EPS protein secondary structure transition from β-sheet to α-helix, with GB addition, signifies a more compact protein configuration, less susceptible to salinity fluctuations. Electrochemical analyses, including cyclic voltammetry (CV) and differential pulse voltammetry (DPV), reveal GB's role in promoting the release of exogenous electron shuttles, such as flavins and c-type cytochromes (c-Cyts). The enhancement in DPV peak areas (QDPV) with GB addition implies an increase in available extracellular electron transfer sites. This investigation advances our comprehension of microbial adaptation mechanisms to salinity through EPS modifications facilitated by GB in saline habitats.

This study aims to explore the impact of metabolites from three vaginal bacteria on the expression of Syndecan 1 (SDC-1). Human cervical epithelial cells (HcerEpic) were separately incubated with the cell-free supernatants of Lactobacillus crispatus (LCS group), Gardnerella vaginalis (GVS group), and Atopobium vaginalis (AVS group). LCS showed a proliferative effect on HcerEpic, with the most significant effect observed at a concentration of 30 % (P 0.05). LCS promotes HcerEpic proliferation, without significant impact on SDC-1 expression and shedding. This provides molecular evidence for LCS as a protective factor against human papillomavirus infection in the cervix. Metabolites of GV and AV inhibit HcerEpic proliferation, induce cytokine secretion, suppress SDC-1 transcription and expression, and promote SDC-1 shedding.

Summary: Coexpressing multiple identical single guide RNAs (sgRNAs) in CRISPR-dependent engineering triggers genetic instability and phenotype loss. To provide sgRNA derivatives for efficient DNA digestion, we design a high-throughput digestion-activity-dependent positive screening strategy and astonishingly obtain functional nonrepetitive sgRNA mutants with up to 48 out of the 61 nucleotides mutated, and these nonrepetitive mutants completely lose canonical secondary sgRNA structure in simulation. Cas9-sgRNA complexes containing these noncanonical sgRNAs maintain wild-type level of digestion activities in vivo, indicating that the Cas9 protein is compatible with or is able to adjust the secondary structure of sgRNAs. Using these noncanonical sgRNAs, we achieve multiplex genetic engineering for gene knockout and base editing in microbial cell factories. Libraries of strains with rewired metabolism are constructed, and overproducers of isobutanol or 1,3-propanediol are identified by biosensor-based fluorescence-activated cell sorting (FACS). This work sheds light on the remarkable flexibility of the secondary structure of functional sgRNA.

BackgroundFrailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. Previous observational studies have reported a strong relationship of frailty with the gut microbiota; however, further studies are warranted to establish a causal link. Accordingly, we aimed to conduct a bidirectional Mendelian randomization study to assess the causal relationship between frailty, as measured by the frailty index, and gut microbiota composition.MethodsInstrumental variables for the frailty index (N = 175, 226) and 211 gut bacteria (N = 18,340) were obtained through a genome-wide association study. A two-sample Mendelian randomization analysis was performed to assess the causal relationship of gut microbiota with frailty. Additionally, we performed inverse Mendelian randomization analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, which was supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results.ResultsBacteroidia (b = −0.041, SE = 0.017, p = 0.014) and Eubacterium ruminantium (b = −0.027, SE = 0.012, p = 0.028) were protective against frailty amelioration. Additionally, the following five bacteria types were associated with high frailty: Betaproteobacteria (b = 0.049, SE = 0.024, p = 0.042), Bifidobacterium (b = 0.042, SE = 0.016, p = 0.013), Clostridium innocuum (b = 0.023, SE = 0.011, p = 0.036), E. coprostanoligenes (b = 0.054, SE = 0.018, p = 0.003), and Allisonella (b = 0.032, SE = 0.013, p = 0.012). Contrastingly, frailty affected Butyrivibrio in the gut microbiota (b = 1.225, SE = 0.570, p = 0.031). The results remained stable within sensitivity and validation analyses.ConclusionOur findings strengthen the evidence of a bidirectional causal link between the gut microbiota and frailty. It is important to elucidate this relationship to optimally enhance the care of older adults and improve their quality of life.

Abstract It is often thought that an external threat increases the internal cohesion of a nation, and thus decreases polarization. We examine this proposition by analyzing NATO discussion dynamics on Finnish social media following the Russian invasion of Ukraine in February 2022. In Finland, public opinion on joining the North Atlantic Treaty Organization (NATO) had long been polarized along the left-right partisan axis, but the invasion led to a rapid convergence of opinion toward joining NATO. We investigate whether and how this depolarization took place among polarized actors on Finnish Twitter. By analyzing retweet patterns, we find three separate user groups before the invasion: a pro-NATO, a left-wing anti-NATO, and a conspiracy-charged anti-NATO group. After the invasion, the left-wing anti-NATO group members broke out of their retweeting bubble and connected with the pro-NATO group despite their difference in partisanship, while the conspiracy-charged anti-NATO group mostly remained a separate cluster. Our content analysis reveals that the left-wing anti-NATO group and the pro-NATO group were bridged by a shared condemnation of Russia’s actions and shared democratic norms, while the other anti-NATO group, mainly built around conspiracy theories and disinformation, consistently demonstrated a clear anti-NATO attitude. We show that an external threat can bridge partisan divides in issues linked to the threat, but bubbles upheld by conspiracy theories and disinformation may persist even under dramatic external threats.

Abstract The experimental observation of quantum phase transitions predicted by the quantum Rabi model in quantum critical systems is usually challenging due to the lack of signature experimental observables associated with them. Here, we describe a method to identify the dynamical critical phenomenon in the quantum Rabi model consisting of a three-level atom and a cavity at the quantum phase transition. Such a critical phenomenon manifests itself as a sudden change of steady-state output photons in the system driven by two classical fields, when both the atom and the cavity are initially unexcited. The process occurs as the high-frequency pump field is converted into the low-frequency Stokes field and multiple cavity photons in the normal phase, while this conversion cannot occur in the superradiant phase. The sudden change of steady-state output photons is an experimentally accessible measure to probe quantum phase transitions, as it does not require preparing the equilibrium state.

Abstract Endometrial cancer (EC) stands as one of the most prevalent malignancies affecting the female genital tract, witnessing a rapid surge in incidence globally. Despite the well-established association of histone methyltransferase SMYD3 with the development and progression of various cancers, its specific oncogenic role in endometrial cancer remains unexplored. In the present study, we report that the expression level of SMYD3 is significantly upregulated in EC samples and associated with EC progression. Through meticulous in vivo and in vitro experiments, we reveal that depletion of SMYD3 curtails cell proliferation, migration, and invasion capabilities, leading to compromised non-homologous end joining repair (NHEJ) and heightened sensitivity of EC cells to radiation. Furthermore, our pathway enrichment analysis underscores the pivotal involvement of the DNA damage repair pathway in regulating EC progression. Mechanistically, in response to DNA damage, SMYD3 is recruited to these sites in a PARP1-dependent manner, specifically methylating LIG4. This methylation sets off a sequential assembly of the LIG4/XRCC4/XLF complex, actively participating in the NHEJ pathway and thereby fostering EC progression. Notably, our findings highlight the promise of SMYD3 as a crucial player in NHEJ repair and its direct correlation with EC progression. Intriguingly, pharmacological intervention targeting SMYD3 with its specific inhibitor, BCI-121, emerges as a potent strategy, markedly suppressing the tumorigenicity of EC cells and significantly enhancing the efficacy of radiotherapy. Collectively, our comprehensive data position SMYD3 as a central factor in NHEJ repair and underscore its potential as a promising pharmacological target for endometrial cancer therapy, validated through both in vitro and in vivo systems.

Due to the large-scale changes of different forms of traffic signs and the rapid speed of vehicles, the detection accuracy and real-time performance of general object detectors are greatly challenged, especially the detection accuracy of small objects. In order to solve this problem, a multi-scale traffic sign detection model CR-YOLOv8 is proposed based on the latest YOLOv8. In the feature extraction stage, the attention module is introduced to enhance the channel and spatial features, so that the network can learn the key information of the small objects more easily. The RFB module is introduced in the feature fusion stage, which improves the feature diversity with less computational overhead and improves the network’s ability to detect multi-scale objects. By improving the loss function to enable the model to effectively balance multi-scale objectives during training, the model generalization ability is improved.The experimental results on TT100k dataset show that compared with the baseline network, the average detection accuracy of the improved method is increased by 2.3 %, and the detection accuracy of small objects is increased by 1.6 %, which effectively reduces the detection accuracy gap among different scales.

Excessive N-acetyl-p-benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP) overdose caused acute liver failure (ALF). S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity. Glutaredoxin-1 (Glrx1), a glutathione-specific thioltransferase, is a primary enzyme to catalyze deglutathionylation. The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP. The Glrx1 knockout mice (Glrx1−/−) and liver-specific overexpression of Glrx1 (AAV8-Glrx1) mice were produced and underwent APAP-induced ALF. Pirfenidone (PFD), a potential inducer of Glrx1, was administrated preceding APAP to assess its protective effects. Our results revealed that the hepatic total protein S-glutathionylation (PSSG) increased and the Glrx1 level reduced in mice after APAP toxicity. Glrx1−/− mice were more sensitive to APAP overdose, with higher oxidative stress and more toxic metabolites of APAP. This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a11 (Cyp3a11), which likely increased the activity of Cyp3a11. Conversely, AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11, which reduced the toxic metabolites of APAP and oxidative stress. PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress. We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose. Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

The given power and grid frequency disturbances can cause transient oscillations and steady-state deviations in the output power of a virtual synchronous generator (VSG), which can be effectively addressed by adding transient damping. However, this approach may result in significant power overshoot. This article proposes an improved VSG control strategy based on transient electromagnetic power feedback compensation and a small-signal model reduction scheme. Firstly, the grid-connected active closed-loop small-signal models of typical VSG control and transient damping VSG control are established, respectively. The transient oscillation suppression mechanism of active power is revealed through root locus and frequency response analyses, and the power overshoot characteristics of the two control strategies are analysed by combining them with the system of zero points. Secondly, the active transient feedback compensation method and the small-signal model reduction design method are introduced in detail. Finally, comparative analysis experiments are conducted using the Matlab/Simulink and hardware-in-the-loop experimental platform. It is verified that the proposed control strategy can suppress transient oscillations in active power, prevent steady-state deviations, and effectively mitigate the power overshoot problem of the system.

The spatial characteristics, pollution sources, and risks of soil heavy metals were analyzed on Hainan Island. The results showed that the heavily polluted points accounted for 0.56%, and the number of mildly and above polluted points accounted for 15.27%, respectively, which were mainly distributed in the northern part of the study area. The principal component analysis–absolute principal component score–multiple linear regression (APCS-MLR) and the positive matrix factorization (PMF) revealed four sources of heavy metals: agricultural pollution sources for cadmium, (Cd), industrial and mining pollution sources for arsenic, (As), transportation pollution sources for zinc and lead (Zn and Pb), and natural pollution sources for chromium, nickel, and copper (Cr, Ni, and Cu). The human health risk assessment indicated that the average non-carcinogenic risk (HI) for both adults and children was within the safe threshold (1, indicating a potential health risk above the safe threshold. Meanwhile, nearly 100% and 99.94% of the TCR values exceeded 1 × 10−4 for children and adults, indicating that Cr and Ni are priority heavy metals for control. The research results provide the necessary scientific basis for the prevention and control of heavy metals in agricultural soils.

BackgroundPreeclampsia (PE) is one of the most severe pregnancy-related diseases; however, there is still a lack of reliable biomarkers. In this study, we aimed to develop models for predicting early-onset PE, severe PE, and the gestation duration of patients with PE.MethodsEligible patients with PE were enrolled and divided into a training (n = 253) and a validation (n = 108) cohort. Multivariate logistic and Cox models were used to identify factors associated with early-onset PE, severe PE, and the gestation duration of patients with PE. Based on significant factors, nomograms were developed and evaluated using the area under the curve (AUC) and a calibration curve.ResultsIn the training cohort, multiple gravidity experience (p = 0.005), lower albumin (ALB; p < 0.001), and higher lactate dehydrogenase (LDH; p < 0.001) were significantly associated with early-onset PE. Abortion history (p = 0.017), prolonged thrombin time (TT; p < 0.001), and higher aspartate aminotransferase (p = 0.002) and LDH (p = 0.003) were significantly associated with severe PE. Abortion history (p < 0.001), gemellary pregnancy (p < 0.001), prolonged TT (p < 0.001), higher mean platelet volume (p = 0.014) and LDH (p < 0.001), and lower ALB (p < 0.001) were significantly associated with shorter gestation duration. Three nomograms were developed and validated to predict the probability of early-onset PE, severe PE, and delivery time for each patient with PE. The AUC showed good predictive performance, and the calibration curve and decision curve analysis demonstrated clinical practicability.ConclusionBased on the clinical features and peripheral blood laboratory indicators, we identified significant factors and developed models to predict early-onset PE, severe PE, and the gestation duration of pregnant women with PE, which could help clinicians assess the clinical outcomes early and design appropriate strategies for patients.

Traditionally, waste plastics have been recycled using crude recycling processes, which pose serious environmental pollution and low recycling efficiency. The best option for managing waste plastics is to upgrade them into high‐value‐added chemicals by breaking down specific chemical bonds in plastic polymers. Herein, this article reviews recent representative research advancements in photo‐ and electrodegradation of plastics for obtaining small‐molecule, high‐value‐added chemicals. The focus is on the application and analysis of emerging technological processes and catalytic materials concepts in these upcycling pathways, with particular emphasis on the diverse functions exhibited by various catalysts. Through the optimization of plastic degradation processes with the rational design of degradation technical processes and catalysts, efficient and selective access to the target products, with the assistance of light and electrical energy with similar action principles, can be achieved. These efforts have yielded promising results, paving the way for resourceful plastic recycling. Particularly, the challenges that arise in upcycling of waste plastics are seriously discussed, and reasonable recommendations have been made to understand future developments and prospects in this research area. It is believed that photocatalysis and electrocatalysis, two emerging degradation methods, play an increasingly important role in the field of plastic upcycling.

Mitochondria-associated ferroptosis exacerbates cardiac microvascular dysfunction in diabetic cardiomyopathy (DCM). Nicorandil, an ATP-sensitive K+ channel opener, protects against endothelial dysfunction, mitochondrial dysfunction, and DCM; however, its effects on ferroptosis and mitophagy remain unexplored. The present study aimed to assess the beneficial effects of nicorandil against endothelial ferroptosis in DCM and the underlying mechanisms. Cardiac microvascular perfusion was assessed using a lectin perfusion assay, while mitophagy was assessed via mt-Keima transfection and transmission electron microscopy. Ferroptosis was examined using mRNA sequencing, fluorescence staining, and western blotting. The mitochondrial localization of Parkin, ACSL4, and AMPK was determined via immunofluorescence staining. Following long-term diabetes, nicorandil treatment improved cardiac function and remodeling by alleviating cardiac microvascular injuries, as evidenced by the improved microvascular perfusion and structural integrity. mRNA-sequencing and biochemical analyses showed that ferroptosis occurred and Pink1/Parkin-dependent mitophagy was suppressed in cardiac microvascular endothelial cells after diabetes. Nicorandil treatment suppressed mitochondria-associated ferroptosis by promoting the Pink1/Parkin-dependent mitophagy. Moreover, nicorandil treatment increased the phosphorylation level of AMPKα1 and promoted its mitochondrial translocation, which further inhibited the mitochondrial translocation of ACSL4 via mitophagy and ultimately suppressed mitochondria-associated ferroptosis. Importantly, overexpression of mitochondria-localized AMPKα1 (mitoAα1) shared similar benefits with nicorandil on mitophagy, ferroptosis and cardiovascular protection against diabetic injury. In conclusion, the present study demonstrated the therapeutic effects of nicorandil against cardiac microvascular ferroptosis in DCM and revealed that the mitochondria-localized AMPK-Parkin-ACSL4 signaling pathway mediates mitochondria-associated ferroptosis and the development of cardiac microvascular dysfunction.

Abstract Background Follicular microenvironment has been proposed as an important factor for oocyte grown and maturation. We sought to evaluate the oxidative stress and inflammatory levels in follicular fluid (FF) and association with embryo quality in patients with diminished ovarian reserve (DOR). Methods The current research included 46 DOR cases and 56 normal ovarian reserve (NOR) cases. Twelve representative oxidative stress markers and eight representative inflammatory factors were measured in the FF. Results Oxidative stress markers total GSH (T-GSH) was decreased in the FF from women with DOR compared with that in NOR group (P = 0.041). More modest differences were observed for reduced GSH (rGSH) and rGSH/GSSG. Women with DOR compared to controls had higher level of TNF-α (P = 0.000) and lower level of IL-18 (P = 0.013). Correlation analysis revealed that GSSG was negatively correlated with normal fertilization rate in NOR group (r = -0.358, P = 0.008), and reduced GSH was negatively correlated with normal fertilization rate in DOR group (r = -0.299, P = 0.049). Moreover, as the regression analysis data showed, the GSSG level was significantly associated with embryo quality indicator. Conclusions The FF in DOR patients was accompanied by increased oxidative stress and inflammatory levels. Follicular development of women with DOR might be influenced by unusual IL-18 and TNF-α levels in FF. And oxidative stress marker GSSG in NOR group was a negative predictor for embryo quality.

Abstract Although originally predicted in relativistic quantum mechanics, Zitterbewegung can also appear in some classical systems, which leads to the important question of whether Zitterbewegung of Dirac particles is underlain by a more fundamental and universal interference behavior without classical analogs. We here reveal such an interference pattern in phase space, which underlies but goes beyond Zitterbewegung, and whose nonclassicality is manifested by the negativity of the phase space quasiprobability distribution, and the associated pseudospin-momentum entanglement. We confirm this discovery by numerical simulation and an on-chip experiment, where a superconducting qubit and a quantized microwave field respectively emulate the internal and external degrees of freedom of a Dirac particle. The measured quasiprobability negativities agree well with the numerical simulation. Besides being of fundamental importance, the demonstrated nonclassical effects are useful in quantum technology.

Abstract Background Allyl isothiocyanate (AITC) is a natural product with high volatility that is used as a biofumigant to alleviate soil-borne plant diseases, and problems such as root knot nematodes (RKNs) that necessitate continuous cropping. However, little research has assessed the effects of AITC fumigation on medicinal plants. Results AITC significantly reduced the population of RKNs in soil (p

AIM: To evaluate the potential of two trabecular meshwork (TM)-specific promoters, Chitinase 3-like 1 (Ch3L1) and matrix gla protein (MGP), for improving specificity and safety in glaucoma gene therapy based on self-complementary AAV2 (scAAV2) vector technologies. METHODS: An scAAV2 vector with C3 transferase (C3) as the reporter gene (scAAV2-C3) was selected. The scAAV2-C3 vectors were driven by Ch3L1 (scAAV2-Ch3L1-C3), MGP (scAAV2-MGP-C3), enhanced MGP (scAAV2-eMGP-C3) and cytomegalovirus (scAAV2-CMV-C3), respectively. The cultured primary human TM cells were treated with each vector at different multiplicities of infections. Changes in cell morphology were observed by phase contrast microscopy. Actin stress fibers and Rho GTPases/Rho-associated protein kinase pathway-related molecules were assessed by immunofluorescence staining, real-time quantitative polymerase chain reaction and Western blot. Each vector was injected intracamerally into the one eye of each rat at low and high doses respectively. In vivo green fluorescence was visualized by a Micron III Retinal Imaging Microscope. Intraocular pressure (IOP) was monitored using a rebound tonometer. Ocular responses were evaluated by slit-lamp microscopy. Ocular histopathology analysis was examined by hematoxylin and eosin staining. RESULTS: In TM cell culture studies, the vector-mediated C3 expression induced morphologic changes, disruption of actin cytoskeleton and reduction of fibronectin expression in TM cells by inhibiting the Rho GTPases/Rho-associated protein kinase signaling pathway. At the same dose, these changes were significant in TM cells treated with scAAV2-CMV-C3 or scAAV2-Ch3L1-C3, but not in cells treated with scAAV2-eMGP-C3 or scAAV2-MGP-C3. At low-injected dose, the IOP was significantly decreased in the scAAV2-Ch3L1-C3-injected eyes but not in scAAV2-MGP-C3-injected and scAAV2-eMGP-C3-injected eyes. At high-injected dose, significant IOP reduction was observed in the scAAV2-eMGP-C3-injected eyes but not in scAAV2-MGP-C3-injected eyes. Similar to scAAV2-CMV-C3, scAAV2-Ch3L1-C3 vector showed efficient transduction both in the TM and corneal endothelium. In anterior segment tissues of scAAV2-eMGP-C3-injected eyes, no obvious morphological changes were found except for the TM. Inflammation was absent. CONCLUSION: In scAAV2-transduced TM cells, the promoter-driven efficiency of Ch3L1 is close to that of cytomegalovirus, but obviously higher than that of MGP. In the anterior chamber of rat eye, the transgene expression pattern of scAAV2 vector is presumably affected by MGP promoter, but not by Ch3L1 promoter. These findings would provide a useful reference for improvement of specificity and safety in glaucoma gene therapy using scAAV2 vector.

HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation was carried out among 473 newly diagnosed ART-naive HIV-1-infected individuals between January and December 2022. The protease–reverse transcriptase (PR-RT) region and integrase (IN) region of HIV-1 were amplified by two separately nested PCRs, followed by sequencing. Drug resistance mutations (DRMs) and drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were analyzed. The PDR prevalence was 6.5% [95% CI: 4.4–9.1] for any anti-retroviral drug, 0.9% [95% CI: 0.3–2.3] for NRTIs, 4.1% [95% CI: 2.5–6.5] for NNRTIs, 1.8% [95% CI: 0.8–3.6] for PIs and 0.5% [95% CI: 0.1–1.8] for INSTIs. According to the subtyping results of the PR-RT region, 11 different subtypes and 31 unique recombinant forms (URFs) were found. CRF07_BC was the dominant subtype (53.7%, 233/434), followed by CRF01_AE (25.3%, 110/434). V179D (1.6%) and K103N (1.4%) were the most predominant types of NNRTI DRMs. Q58E (1.2%) and M184V (0.7%) were the most frequent PI DRMs and NRTI DRMs, respectively. The INSTI-related DRMs Y143S (causes high-level resistance to RAL) and G163K (causes low-level resistance to EVG and RAL) were found in one patient each. Given the relatively high PDR prevalence of NNRTI (4.1%), non-NNRTI-based ART may be preferred in the future. It is recommended to include genotypic resistance testing before starting ART in regions where feasible.

In the field of human health research, the homeostasis of copper (Cu) is receiving increased attention due to its connection to pathological conditions, including diabetes mellitus (DM). Recent studies have demonstrated that proteins associated with Cu homeostasis, such as ATOX1, FDX1, ATP7A, ATPB, SLC31A1, p53, and UPS, also contribute to DM. Cuproptosis, characterized by Cu homeostasis dysregulation and Cu overload, has been found to cause the oligomerization of lipoylated proteins in mitochondria, loss of iron–sulfur protein, depletion of glutathione, production of reactive oxygen species, and cell death. Further research into how cuproptosis affects DM is essential to uncover its mechanism of action and identify effective interventions. In this article, we review the molecular mechanism of Cu homeostasis and the role of cuproptosis in the pathogenesis of DM. The study of small-molecule drugs that affect these proteins offers the possibility of moving from symptomatic treatment to treating the underlying causes of DM.

In recent years, artificial intelligence (AI) has made incredible progress. Advanced foundation models such as ChatGPT can offer powerful conversation, in-context learning, and code generation abilities for a broad range of open-domain tasks. They can also generate high-level solution outlines for domain-specific tasks based on their acquired common-sense knowledge. Nonetheless, they still face difficulties in specialized tasks because they lack sufficient domain-specific data during pretraining and can make errors in neural network computations requiring accurate execution. However, many existing models and systems can perform domain-specific tasks very well, although they are not easily accessible or compatible with foundation models because of the different implementations or working mechanisms. Therefore, there is a clear and pressing need for a mechanism that can leverage foundation models to propose task solution outlines and then automatically match the subtasks in the outlines to off-the-shelf models and systems with special functionalities to complete these subtasks. Inspired by this, we introduce TaskMatrix.AI as a new AI ecosystem that connects foundation models to millions of application programming interfaces (APIs) for task completion. Unlike most previous studies, which aimed to improve a single AI model, TaskMatrix.AI focuses on using an existing foundation model (as a brain-like central system) and APIs of other AI models and systems (as subtask solvers) to realize diversified tasks in both the digital and physical domains.

Air pollution poses a significant threat to human health and the environment globally. Precise analysis and prediction of pollutant concentrations are essential for monitoring and managing air quality. However, reliable analysis and prediction require comprehensive and high-quality data, which is often compromised due to missing data during collection. Unfortunately, conventional methods for addressing missing data fall short of providing adequate solutions. The missing data for air quality indicators are commonly systematic, with all data points missing for extended periods. This makes it difficult to establish correlations and populate the missing data accurately. To address this problem, we propose a Densely Connected Causal Convolutional Network Separating Past and Future Data (DCCN-SPF), a deep learning-based model that fills in continuous missing PM2.5 concentration data in the original dataset. It extracts features from past and future data separately using densely connected causal convolutional networks and incorporates linear interpolation and deep learning structures to improve prediction accuracy. Using air quality monitoring data from the China Environmental Monitoring Station between 2017 and 2021 in Beijing, we compare our proposed model with baseline models and find that our model outperforms others in predicting PM2.5 concentrations. The evaluation metrics MAE and RMSE are used, revealing significant reductions of 8.7–21.6 % for MAE and 7.1–23.5 % for RMSE in favor of our proposed DCCN-SPF model.

An innovative layout of a recompression supercritical carbon dioxide (S–CO2) cycle for nuclear spacecraft was proposed in this work. Thermodynamic and exergoeconomic analysis of the innovative cycle have been performed to study the effect of essential operating parameters on the split ratio, maximum operating pressure ratio, minimum operating temperature, maximum operating temperature, and compressor C4 inlet pressure based on the first and second laws of exergoeconomics and efficiency. Finally, the innovative power cycle is optimized with high efficiencies, low cost and lightweight. The results show that the optimization progress is based on the thermodynamic and exergoeconomics method; the minimum operating temperature can significantly improve efficiencies and reduce circular investment cost; then after the multi-objective optimization progress, the thermal efficiency (ηth), exergy efficiency (ηex) and mass of Brayton turbomachinery unit (MBTU) improved by 2.71 %, 3.69 %, and 2.8 %; total capital cost rate (total) and levelized cost of electricity (LCOE) reduced by 0.88 % and 4.55 %, respectively.

Background: Emerging data have supported the immunostimulatory role of radiotherapy, which could exert a synergistic effect with immune checkpoint inhibitors (ICIs). With proven effective but suboptimal effect of ICI and chemotherapy in triple-negative breast cancer (TNBC), we designed a pilot study to explore the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) plus adebrelimab and chemotherapy in TNBC patients. Methods: Treatment-naïve TNBC patients received two cycles of intravenous adebrelimab (20 mg/kg, every 3 weeks), and SBRT (24 Gy/3 f, every other day) started at the second cycle, then followed by six cycles of adebrelimab plus nab-paclitaxel (125 mg/m² on days 1 and 8) and carboplatin (area under the curve 6 mg/mL per min on day 1) every 3 weeks. The surgery was performed within 3–5 weeks after the end of neoadjuvant therapy. Primary endpoint was pathological complete response (pCR, ypT0/is ypN0). Secondary endpoints included objective response rate (ORR), residual cancer burden (RCB) 0-I, and safety. Results: 13 patients were enrolled and received at least one dose of therapy. 10 (76.9%) patients completed SBRT and were included in efficacy analysis. 90% (9/10) of patients achieved pCR, both RCB 0-I and ORR reached 100% with three patients achieved complete remission. Adverse events (AEs) of all-grade and grade 3–4 occurred in 92.3% and 53.8%, respectively. One (7.7%) patient had treatment-related serious AEs. No radiation-related dermatitis or death occurred. Conclusions: Adding SBRT to adebrelimab and neoadjuvant chemotherapy led to a substantial proportion of pCR with acceptable toxicities, supporting further exploration of this combination in TNBC patients. Funding: None. Clinical trial number: NCT05132790.

Titanium has been widely used in orthopedics and dental implants due to its excellent biocompatibility and mechanical properties. However, the surface of titanium is biologically inert and lacks biological activity, resulting in poor integration between titanium-based implants and surrounding natural bone tissue, which is a common challenge in its clinical application. Surface modification is currently an effective means to improve the biocompatibility and bioactivity of titanium implants. The natural tissues of the human body are assembled from nanomodules, so from a biomimetic perspective, nanostructures should have better biological activity. TiO2 nanotubes have unique physical and chemical properties due to their elastic modulus, large specific surface area, and regular hollow structure similar to those of bone tissue. This study used anodic oxidation technology to prepare TiO2 nanotubes on the surface of titanium. The surface properties of the nanotubes were evaluated using field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), atomic force microscopy profilometry, contact angle measurements, etc. The corrosion resistance was tested using an electrochemical workstation. The results indicate that anodic oxidation can be used to successfully prepare titanium dioxide nanotube arrays on the surface of titanium. The nanotubes not only exhibit a good structure but also improve the surface hydrophilicity and corrosion resistance of titanium, thereby demonstrating potential for clinical application.

A decision analytic model was constructed to assess the cost–effectiveness of obinutuzumab plus bendamustine followed by obinutuzumabmaintenance therapy (O-B-O) in Chinese patients with relapsed and refractory follicular lymphoma (rrFL). O-B-O was associated with a dominant or more favorable cost–effectiveness than the conventional therapies. Survival outcomes, quality of life of progression free survival, and subsequent treatment costs for progressive disease were the main drivers of the cost– effectiveness of O-B-O. The cost–effectiveness proportions of O-B-O relative to conventional therapies under the recommended cost–effectiveness threshold ranged from 61.0% to 99.9%. Thus, O-B-O was highly cost-effective for treating patients with rrFL in China compared with conventional therapies.

The demand for efficient and compact heating for dynamic dielectric liquid has grown significantly. Compared with traditional heating, microwave heating has the advantages of being fast and efficient. Moreover, the demand for outdoor portable heating and industrial compact heating is increasing. To address this limitation, this study proposes a compact heating system based on a metamaterial-based circular waveguide. First, asymmetric propagation theory is introduced, and an asymmetric propagation circular waveguide is designed in detail according to the discretisation of the relative permittivity. Then, a multi-physics model using a circular waveguide and a mug for high heating efficiency is developed by coupling Maxwell's equations and the heat transfer equation. Furthermore, heating experiments are performed for liquids with different relative permittivity and the experimental results consistently validated an efficiency rate of over 88 %, which agrees with the simulation results. Finally, the effects of the dielectric properties of the material and mug on the heating efficiency are discussed to highlight the robustness of the proposed heating system, with heating efficiency consistently maintained at 75 % or higher. In summary, the proposed design features a compact structure that is suitable for practical microwave heating applications.

Abstract Statins have been proven to be effective in minimizing the risk of cardiovascular adverse events, however, their effect on BP variability is debatable with respect to their significance and their use as a potential anti‐hypertensive. Using a meta‐analysis approach, the aim of this study was to explore whether certain statins have the potential to lower blood pressure (BP). For the period 2002–2022, Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched for the studies that examined the effect of statins on blood pressure in normotensive or hypertensive individuals. Randomized controlled clinical trials that investigated this effect were included based on our inclusion criteria. Our primary outcomes were changes in systolic and diastolic blood pressure (DBP). The final analysis of the study included 49 RCTs involving 45 173 participants randomized to receive either statins or placebo. Among the two groups, the total weighted mean difference (WMD) for systolic blood pressure (ΔSBP) was –1.42 (95% CI: –2.38, –0.46; p = .004) and diastolic blood pressure (ΔDBP) was 0.82 (95% CI: –1.28, –0.36; p = .0005). Despite various studies suggesting the efficacy of statins in blood pressure lowering to be significant and non‐significant both, we observed a decrease in SBP and DBP both, although the change was not as large and could be considered significant. A large multicenter, multi‐ethnic, large sample pool size, and a long period follow‐up study is still required to assert these claims.

Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and continues to have a significant impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, which is primarily responsible for the host immune response upon infection. Here we present the preclinical studies of a broadly protective SARS-CoV-2 subunit vaccine developed from our trimer domain platform using the Delta spike protein, from antigen design through purification, vaccine evaluation and manufacturability. The pre-fusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. Immunogenicity studies have shown that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous viral challenge. Neutralizing antibodies induced by this vaccine show cross-reactivity against the ancestral WA1, Delta and several Omicrons, including BA.5.2. The formulated PF-D Trimer is stable for up to six months without refrigeration. The Trimer Domain platform was proven to be a key technology in the rapid production of PF-D-Trimer vaccine and may be crucial to accelerate the development and accessibility of updated versions of SARS-CoV-2 vaccines.

A fine-grained WC-15wt%Al0.5CoCrFeNi cemented carbide was prepared through a vacuum and gas pressure sintering. For achieving high surface integrity, diamond wheel grinding serves as the primary molding process for the machining of WC cemented carbide. To reveal the influence of grinding on the surface integrity of fine-grained WC-HEA cemented carbide, studies were conducted on grinding force, surface microstructure, surface roughness, residual stress, microhardness, and bending strength. The morphological analysis of the ground surface indicated a transition in the material removal mechanism of WC-HEA cemented carbide from ductile removal to brittle removal, with brittle removal becoming predominant as the depth of grinding increases. With the increasing depth of grinding, the grinding force increases, and the grinding force increases while the surface roughness decreases. Correspondingly, there is an improvement in both hardness and bending strength. Additionally, grinding induces high residual compressive stress on the surface, with a maximum compressive stress of 1795 MPa. The bending strength of the material is found to be dependent on the residual stress.

How prevalent is spontaneous thrombosis in a population containing all sizes of intracranial aneurysms? How can we calibrate computational models of thrombosis based on published data? How does spontaneous thrombosis differ in normo- and hypertensive subjects? We address the first question through a thorough analysis of published datasets that provide spontaneous thrombosis rates across different aneurysm characteristics. This analysis provides data for a subgroup of the general population of aneurysms, namely, those of large and giant size (>10 mm). Based on these observed spontaneous thrombosis rates, our computational modeling platform enables the first in silico observational study of spontaneous thrombosis prevalence across a broader set of aneurysm phenotypes. We generate 109 virtual patients and use a novel approach to calibrate two trigger thresholds: residence time and shear rate, thus addressing the second question. We then address the third question by utilizing this calibrated model to provide new insight into the effects of hypertension on spontaneous thrombosis. We demonstrate how a mechanistic thrombosis model calibrated on an intracranial aneurysm cohort can help estimate spontaneous thrombosis prevalence in a broader aneurysm population. This study is enabled through a fully automatic multi-scale modeling pipeline. We use the clinical spontaneous thrombosis data as an indirect population-level validation of a complex computational modeling framework. Furthermore, our framework allows exploration of the influence of hypertension in spontaneous thrombosis. This lays the foundation for in silico clinical trials of cerebrovascular devices in high-risk populations, e.g., assessing the performance of flow diverters in aneurysms for hypertensive patients.

Abstract Heavy summer precipitation over the southern slope of the Tibetan Plateau has dramatic influences on water resources and hydrological disasters in South Asia. It experienced increasing trends over 1979–1996 and decreasing trends over 1996–2022, which are not yet well understood. Here we show observational and numerical evidence that stratospheric ozone has significant impacts on long‐term trends of summer precipitation in this strong convection area. It is found that stratospheric ozone depletion, by modulating the lower stratospheric temperature and upper‐tropospheric static stability, enhances deep convection and precipitation over the southern slope of the Tibetan Plateau. The results suggest that the ozone recovery in the future may reduce the summer precipitation over the southern slope of the Tibetan Plateau in the first half of the 21st century, which would be imperative for future water resource management in South Asia.

Background: Periprocedural myocardial injury (PMI) is a common complication of percutaneous coronary intervention (PCI) associated with poor prognosis. Inflammation has been demonstrated to exert a crucial role in PMI. However, how the inflammation is initiated or sustained in PMI remains elusive. Methods: RNA-seq in peripheral blood mononuclear cells (PBMCs) from 3 Non-PMI and 6 PMI patients was performed with subsequent bioinformatics analysis. RNA-seq results were verified in a patient cohort. We also established the coronary microembolization (CME) mice model to mimic PMI. The activity of caspase-1 in PBMCs was detected by flow cytometry. The levels of interleukin (IL)-1β, IL-18 and cardiac troponin in plasma were measured by enzyme-linked immunosorbent assay. Results: We identified a total of 901 differentially expressed genes (DEGs) between Non-PMI and PMI patients. These DEGs participated in several inflammation-related processes. NOD-like receptor signaling pathway was significantly enriched in pathway analysis. All the key genes composed in the NLRP3 inflammasome, including NLRP3, PYCARD, CASP1 and IL1B, were upregulated in PMI patients. The activation of NLRP3 inflammasome was then verified by increased activity of caspase-1 in PBMCs, and elevated levels of IL-1β and IL-18 in plasma in PMI patients. Spearman analysis confirmed tight correlations between caspase-1 activity, IL-1β, IL-18 levels and troponin T level. In addition, caspase-1 activity, IL-1β and IL-18 levels were also enhanced in CME mice. Conclusions: We discovered that NLRP3 inflammasome was involved in PMI, thus providing evidence supporting the therapeutic value of NLRP3 inflammasome-targeted strategies in PMI.

Ensuring the promptly removal of foreign objects from transmission lines is crucial for electricity safety. However, the existing object detection algorithms exhibit low precision and recall due to factors such as uncertainty in the type of foreign objects, imbalance of positive and negative samples, and the complexity of aerial photography backgrounds. Therefore, in this paper, an algorithm called DF-YOLO (Deformable Faster-You Only Look Once) for transmission line foreign object detection is proposed to resolve these problems. The algorithm is based on YOLOv7-Tiny and tailored to the dataset’s characteristics to achieve high precision along with excellent recall. The Focal-DIoU loss function is utilized to balance positive and negative sample proportions during training. Additionally, the algorithm incorporates the deformable convolution (DCN) module and the SimAM attention mechanism to enhance model performance, particularly in terms of foreign object recall and detection accuracy. Moreover, we optimized the network inference speed with the improved SPPCSPC_S-F module. Experimental results demonstrate that the improved DF-YOLO network achieves a 2.04% increase in mAP@.5 compared to the original YOLOv7-Tiny network. The recall rate also improves from 89% to 91.51%. Additionally, the inference speed of the network rises from 130 to 140 FPS, which enhances detection effectiveness and reduces the frequency of transmission line leaks triggered by foreign object incursion.

Highlights 1. RNF31 restrains cancer cell progression in TNBC. 2. RNF31 regulates YAP protein stability via promoting YAP K48-linked poly-ubiquitination. 3. RNF31 represses immune evasion via suppressing YAP/PD-L1 axis in TNBC.

In this study, we conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in various sexual risk behaviour groups in a developed area in eastern China based on phylogenetic inference, molecular transmission networks, and Bayesian analyses. A total of 1083 pol sequences (91.23%, 1083/1187) from newly diagnosed HIV-1-positive patients from 2017 to 2020 were successfully obtained and involved thirteen HIV-1 subtypes, in which the major HIV-1 subtypes were CRF07_BC (36.10%, 391/1083) and CRF01_AE (34.63%, 375/1083). 485 individuals (44.78%,485/1083) formed 146 clusters in the network. Of which CRF07_BC showed extensive clustering driven by men who have sex with men (MSM) within larger networks, CRF01_AE and other subtypes were generally driven by small clusters (SCs) and medium clusters (MCs) among various risk groups. Through Sankey diagrams, the MSM group infected with CRF07_BC had a greater impact on the non-commercial heterosexual group among all cross-risk groups. In addition, a higher number of key individuals infected with CRF07_BC (40.22%, 74/127), suggests the crucial role of CRF07_BC-infected individuals as a local epidemic driver in the context of a mixed HIV-1 epidemic. Further Bayesian analysis confirmed that CRF07_BC was introduced into Jiaxing city from other provinces multiple times and spread rapidly among MSM and heterosexual individuals. Overall, our study provided some insights and information to explore the local transmission dynamics of HIV-1 epidemic strains involving various sexual risk groups, and emphasize that it is necessary to conduct in-depth research and precise intervention targeting key clusters/ individuals to effectively block the continued transmission of AIDS.

Future space exploration is now focused on new field-deep space planets. Deep space exploration and the development and utilization of resources are inestimable strategic significance for the country to seize the initiative and command heights of deep space exploration. Nuclear electric propulsion (NEP) systems convert heat from the fission reactor to electrical power and then use the electrical power to produce thrust. Compared with traditional propulsion technology, the NEP system with variable Ispcan be used for several applications. The NEP spacecraft is more suitable for deep space exploration missions due to the advantages of high specific impulse, high power, and long life. This paper analyzes the relationship between the transfer travel time, specific mass, power, and payload ratio of the NEP spacecraft through simple performance models. Use the mass optimization and specific mass optimization models based on the NEP system composition and small thrust orbit theory to maximize the payload ratio for a given transfer time and technological characteristics. Finally, applied this NEP model to discuss the feasibility of Mars, Jupiter, and Saturn transfer missions and compared it with the Tianwen-1, Juno, and Cassini–Huygens spacecraft, respectively. Results show that when the NEP spacecraft specific mass reaches 4.77 kg/kW, the Earth–Mars transfer time can be changed to 331.31 days, the payload increases to 1650 kg, the transfer time for Jupiter and Saturn mission would be shorted to 661.31 days and 1131.31 days, the corresponding payload significantly increases which achieved to 1270 kg and 2981 kg. The nuclear electric propulsion spacecraft dramatically improves the detection capability of the spacecraft and provides a reference for the feasibility demonstration and subsequent design of the deep space and the extrasolar planet exploration.