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Abstract GeTe is a promising p-type material with increasingly enhanced thermoelectric properties reported in recent years, demonstrating its superiority for mid-temperature applications. In this work, the thermoelectric performance of GeTe is improved by a facile composite approach. We find that incorporating a small amount of boron particles into the Bi-doped GeTe leads to significant enhancement in power factor and simultaneous reduction in thermal conductivity, through which the synergistic modulation of electrical and thermal transport properties is realized. The thermal mismatch between the boron particles and the matrix induces high-density dislocations that effectively scatter the mid-frequency phonons, accounting for a minimum lattice thermal conductivity of 0.43 Wm−1K−1 at 613 K. Furthermore, the presence of boron/GeTe interfaces modifies the interfacial potential barriers, resulting in increased Seebeck coefficient and hence enhanced power factor (25.4 μWcm−1K−2 at 300 K). Consequently, we obtain a maximum figure of merit Z max of 4.0 × 10−3 K−1 at 613 K in the GeTe-based composites, which is the record-high value in GeTe-based thermoelectric materials and also superior to most of thermoelectric systems for mid-temperature applications. This work provides an effective way to further enhance the performance of GeTe-based thermoelectrics.

Abstract Background This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker. Methods Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon β (IFN-β) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package. Results The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P 0.05), and the serum IFN-β concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-β in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively. Conclusions The expression level of TBK1 and IRF3 in PBMCs, and IFN-β in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-β in serum has higher sensitivity when used to differentiate between patients with active and stable lesions.

Working temperatures, thermal insulation performance, and life span of thermal barrier coatings (TBCs) are primarily influenced by their high-temperature stability, thermal expansion coefficients (TECs), thermal conductivity, and fracture toughness. To address the limitations of current zirconate- and tantalate-based oxides, dual-phase zirconate/tantalate high-entropy ceramics (HECs) are designed and synthesized to improve their thermal and mechanical properties. The combined effects of high entropy, high concentrations of oxygen vacancies, and relatively low phonon velocity result in glass-like thermal conductivity, with a minimum value of 1.55 W m−1 K−1 at 1200 °C. The high TECs (10.6–10.9 × 10−6 K−1 at 1400 °C) and exceptional high-temperature stability demonstrate that these materials can withstand 1300 °C for more than 300 h, significantly surpassing the performance of traditional yttria-stabilized zirconia (YSZ). Compared with YSZ (3.6 MPa m1/2) and YTaO4 (2.5 MPa m1/2), the increments in fracture toughness (4.4 MPa m1/2) of dual-phase zirconate/tantalate HECs are as high as 22.2% and 76.0%, respectively. It is evident that the designed dual-phase zirconate/tantalate HECs can effectively promote thermal properties and fracture toughness, positioning them as the next-generation TBCs with high operating temperatures and outstanding thermal insulation performance.

Nowadays, a good corrosion resistance of lightweight steel is demanded for its application. However, due to the high contents of Mn and C, which are always corrosion-susceptible elements in steels, the conventional lightweight steel is not desirable for this mission. Although Cr is widely believed to be a common alloying element to improve the corrosion resistance of most steels, it is considered to be ineligible using in the lightweight steel due to the relatively high content of C. This is because the trade-off between corrosion resistance and mechanical properties by alloying Cr. In recent years, the rapid developments of additive and coating manufacturing have provided new possibilities for both the Cr alloying and microstructural modulation to improve corrosion resistance of lightweight steel. In this case, to design a certain chemical composition using in additive and coating manufacturing, it is interesting to clarify the effects of Cr alloying on the corrosion resistance of lightweight steel. To reveal it, in the present work, the Fe–Mn–Al–Cr–Si–Mo–C lightweight steel alloyed with Cr contents of 4 wt%, 8 wt% and 12 wt% are prepared. The corrosion resistances and mechanisms of Cr-alloyed lightweight steels in 3.5 wt% NaCl solution are investigated by electrochemical and immersion tests. The present work may provide new insights for the composition design of lightweight steel, especially for the directions of additive and coating manufacturing.

Abstract Background Acute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD. Methods We conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission. Results Patients with a variety of ILD classification were included. Connective–tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p

Abstract Background The purpose of this in vitro study was to compare and evaluate the stress distribution of maxillary first premolar residual crowns restored with post-core crowns, endocrowns and inlay crowns after deep margin elevation, to explore the fitting restoration for residual crowns using finite element analysis. Methods A healthy complete right maxillary first premolar from a male adult was scanned by cone beam computed tomography (CBCT). The finite element model of the tooth was established by reverse engineering software such as Mimics, Geomagic and Hypermesh. On this basis, the residual crown model after deep margin elevation was made, and the experimental group models were divided into three groups, those restored with post core crowns, endocrowns and inlay crowns. Vertical and oblique static loads were applied to the experimental models to simulate the force on the tooth during mastication (the loading position was located in the central fossa of the occipital surface, and the load was 100 N) using Abaqus software. Results The peak value and distribution of von Mises stress in each part of the experimental model were observed. After deep margin elevation, the peak dentin von Mises stresses were lower than the tensile strength of normal dentin in the post-core crown, endocrown, and inlay crown groups; the lowest stress results were found in the post-core crown group for the dentin, restoration, enamel, and deep margin elevation (DME) layers under vertical and oblique loading. In terms of stress distribution clouds, the peak stresses in the dentin tissue were located in the apical 1/3 of the root after postcore crown restorations for both loads, while stress concentrations were evident in the cervical and root areas after endocrown and inlay crown restorations; regardless of the load and restoration method, the corresponding stress concentration areas appeared at the junction of the DME and dentin tissue at the loading site of the restorations; Conclusions Post-core crowns, endocrowns and inlay crowns can be used to restore residual crowns after deep margin elevation, and post-core crowns can better protect the residual tooth tissue.

Abstract Globally, breast cancer continues to be the leading cause of cancer-related incidence and mortality among females. Research has shown that sleep patterns significantly influence tumor onset and progression. In this research, the association was examined through the application of a two-sample Mendelian randomization (MR) approach. For the analysis of seven sleep patterns, genetic tools were sourced from both the UK Biobank and 23andMe, including morning/evening person (chronotype) n = 177,604, morning person (chronotype) n = 248,094, daytime dozing/sleepiness n = 193,472, getting up in the morning n = 193,717, and sleeplessness n = 193,987; sleep duration n = 192,810; and nap during the day n = 166,853. The Breast Cancer Association Consortium (BCAC) supplied genome-wide association studies (GWAS) data, including 133,384 breast cancer cases and 113,789 controls, alongside subtype-specific data with 106,278 cases and 91,477 controls. We discovered that chronotype encompasses both morning and evening types contributes to the risk of overall breast cancer. While daytime dozing and morning person (chronotype) are linked to a lower risk of breast cancer in general, In subtype-specific analyses, morning person (chronotype) was negatively associated with luminal B, HER2-negative-like, and daytime dozing was negatively correlated with luminal A-like, luminal B-like, and HER2-enriched-like. The study corroborates that chronotype is a danger element for breast cancer, aligning with previous observational findings. The association between being a morning person (chronotype) or having daytime dozing and a decreased risk of breast cancer underscores the significance of sleep patterns in formulating strategies for cancer prevention.

Abstract This paper provides a study for crystallographic orientation-dependent corrosion rate of aluminum employing an ab initio model with inputs from first-principles calculations. Results showed that the sequence of corrosion rate is in the order of (111)

Introduction Vaccination against SARS-CoV-2 is an integral pillar of the public health approach to COVID-19. With the emergence of variants of concern that increase transmissibility and escape from vaccine- or infection-induced protection, vaccines have been developed to more closely match the newly circulating SARS-CoV-2 strains to improve protection. The safety and immunogenicity of multiple authorized messenger RNA (mRNA)-based COVID-19 vaccines targeting the omicron sublineage (BA.1, BA.4/BA.5, and XBB.1.5) have been demonstrated in several clinical trials among adults and children.Areas covered This review will comprehensively detail the available evidence (published through July 2024) from ongoing clinical trials on omicron variant-containing mRNA-1273 vaccines administered as additional doses in previously vaccinated target demographics.Expert opinion Across three clinical trials, omicron variant-containing mRNA-1273 vaccines induced immune responses to vaccine-matched omicron strains as well as ancestral SARS-CoV-2, with a safety and reactogenicity profile comparable to the original mRNA-1273 vaccine. Combined with pivotal data demonstrating the safety, efficacy, and effectiveness of the original mRNA-1273 vaccine, these findings support the use of variant-containing mRNA-1273 vaccines and provide confidence that expeditious development of updated vaccines using this established mRNA platform can maintain protection against COVID-19.

Altered cell-cell communication is a hallmark of aging, but its impact on bone marrow aging remains poorly understood. Based on a common and effective pipeline and single-cell transcriptome sequencing, we detected 384,124 interactions including 2575 ligand-receptor pairs and 16 non-adherent bone marrow cell types in old and young mouse and identified a total of 5560 significantly different interactions, which were then verified by flow cytometry and quantitative real-time PCR. These differential ligand-receptor interactions exhibited enrichment for the senescence-associated secretory phenotypes. Further validation demonstrated supplementing specific extracellular ligands could modify the senescent signs of hematopoietic stem cells derived from old mouse. Our work provides an effective procedure to detect the ligand-receptor interactions based on single-cell sequencing, which contributes to understand mechanisms and provides a potential strategy for intervention of bone marrow aging.

Recent years have witnessed significant advancements in methodologies and techniques for the synthesis of energetic materials, which are expected to shape future manufacturing and applications. Techniques including continuous flow chemistry, electrochemical synthesis, microwave-assisted synthesis, and biosynthesis have been extensively employed in the pharmaceutical and fine chemical industries and, gratifyingly, have found broader applications. This review comprehensively introduces recent advancements in the utilization of these emerging techniques, aiming to provide a catalyst for the development of novel green methods and techniques for synthesizing energetic materials.

Abstract In acidic soils, aluminum (Al) toxicity inhibits the growth and development of plant roots and affects nutrient and water absorption, leading to reduced yield and quality. Therefore, it is crucial to investigate and identify candidate genes for Al tolerance and elucidate their physiological and molecular mechanisms under Al stress. In this study, we identified a new gene OsAlR3 regulating Al tolerance, and analyzed its mechanism from physiological, transcriptional and metabolic levels. Compared with the WT, malondialdehyde (MDA) and hydrogen peroxide (H2O2) content were significantly increased, superoxide dismutase (SOD) activity and citric acid (CA) content were significantly decreased in the osalr3 mutant lines when exposed to Al stress. Under Al stress, the osalr3 exhibited decreased expression of antioxidant-related genes and lower organic acid content compared with WT. Integrated transcriptome and metabolome analysis showed the phenylpropanoid biosynthetic pathway plays an important role in OsAlR3-mediated Al tolerance. Exogenous CA and oxalic acid (OA) could increase total root length and enhance the antioxidant capacity in the mutant lines under Al stress. Conclusively, we found a new gene OsAlR3 that positively regulates Al tolerance by promoting the chelation of Al ions through the secretion of organic acids, and increasing the expression of antioxidant genes.

Abstract Commutation failure (CF) is one of the most common issues in line‐commuted converter‐based high voltage direct current systems (LCC‐HVDC), leading to critical power system security and stability problems. Accurate and rapid identification of CF is crucial to prevent subsequent CF in HVDC systems. However, the existing CF identification methods are lack of the required accuracy and speed. The relationship between bridge arm current, commutation voltage, and trigger pulse based on the commutation progress mechanism after the AC fault is analysed in this paper. A novel CF identification method is presented, which utilises the CF identification factor, enabling fast and high‐accurate identification without relying on the value of the extinction angle. The proposed method offers a simpler and more efficient implementation in engineering practice. Finally, the effectiveness of the proposed method is verified in both the standard International Council on Large Electric systems HVDC model and the Hardware in Loop test using practical project parameters. The results demonstrate that the proposed method can accurately and fast identify CF.

Abstract Efficient charge-carrier injection and transport in organic light-emitting devices (OLEDs) are essential to simultaneously achieving their high efficiency and long-term stability. However, the charge-transporting layers (CTLs) deposited by various vapor or solution processes are usually in amorphous forms, and their low charge-carrier mobilities, defect-induced high trap densities and inhomogeneous thickness with rough surface morphologies have been obstacles towards high-performance devices. Here, organic single-crystalline (SC) films were employed as the hole-transporting layers (HTLs) instead of the conventional amorphous films to fabricate highly efficient and stable OLEDs. The high-mobility and ultrasmooth morphology of the SC-HTLs facilitate superior interfacial characteristics of both HTL/electrode and HTL/emissive layer interfaces, resulting in a high Haacke’s figure of merit (FoM) of the ultrathin top electrode and low series-resistance joule-heat loss ratio of the SC-OLEDs. Moreover, the thick and compact SC-HTL can function as a barrier layer against moisture and oxygen permeation. As a result, the SC-OLEDs show much improved efficiency and stability compared to the OLEDs based on amorphous or polycrystalline HTLs, suggesting a new strategy to developing advanced OLEDs with high efficiency and high stability.

In situ phase separation precipitates play an important role in enhancing the thermoelectric properties of copper sulfides by suppressing phonon transmission. In this study, Cu1.8S composites were fabricated by melting reactions and spark plasma sintering. The complex structures, namely, micron-PbS, Sb2S3, nano-FeS, and multiscale pores, originate from the introduction of FePb4Sb6S14 into the Cu1.8S matrix. Using effective element (Fe) doping and multiscale precipitates, the Cu1.8S+0.5 wt% FePb4Sb6S14 bulk composite reached a high dimensionless figure of merit (ZT) value of 1.1 at 773 K. Furthermore, the modulus obtained for this sample was approximately 40.27 GPa, which was higher than that of the pristine sample. This study provides a novel strategy for realizing heterovalent doping while forming various precipitates via in situ phase separation by natural minerals, which has been proven to be effective in improving the thermoelectric and mechanical performance of copper sulfides and is worth promoting in other thermoelectric systems.

Retinoblastoma (RB) is the most common intraocular malignant tumor in children, primarily attributed to the bi-allelic loss of the RB1 gene in the developing retina. Despite significant progress in understanding the basic pathogenesis of RB, comprehensively unravelling the intricate network of genetics and epigenetics underlying RB tumorigenesis remains a major challenge. Conventional clinical treatment options are limited, and despite the continuous identification of genetic loci associated with cancer pathogenesis, the development of targeted therapies lags behind. This review focuses on the reported genomic and epigenomic alterations in retinoblastoma, summarizing potential therapeutic targets for RB and providing insights for research into targeted therapies.

Abstract Objective To identify critical satisfaction gaps in a home nursing mobile application (APP) using a systematic decision-making model. Methods Initially, the decision-making trial and evaluation laboratory method was used to analyze the relationship structure and corresponding weights among the indicators. The Importance-Performance Analysis (IPA) method was used to identify the categories of all indicators and their corresponding strategic directions. Twenty-six home nursing specialists currently providing home nursing services were recruited for this study. Results The IPA results revealed that “Assurance,” “Reliability,” and “Personal security protection” are critical satisfaction gaps. From the influence network and weight results, “information quality” and “system quality” were the critical quality factors in the home nursing mobile APP. The influence of the network relationship structure and weight demonstrated a 98.12% significance level, indicating good stability. Conclusion Continuous improvement in information and system quality is recommended to optimize the overall quality of the home nursing mobile APP. Additionally, user demands should be considered, and personal safety guarantee functions should be developed and integrated into the system to ensure the safety of home nursing workers.

Abstract The high mobility group nucleosome binding (HMGN) family, constitutes a large family of non-histone protein family known to bind the acidic patch of the nucleosomes with various key cellular functions. Several studies have highlighted the pivotal roles of HMGNs in the pathogenic process of various cancer types. However, the roles of HMGN family in lung adenocarcinoma (LUAD) have not been fully elucidated. Herein, integrative analyses of multiple-omics data revealed that HMGNs frequently exhibit dysregulation in LUAD. Subsequent analysis of the clinical relevance of HMGN1 demonstrated its association with poor prognosis in LUAD and its potential as a diagnostic marker to differentiate LUAD from healthy controls. Additionally, functional enrichment analysis suggested that HMGN1 was mainly involved in DNA repair. To corroborate these findings, cellular experiments were conducted, confirming HMGN1’s crucial involvement in homologous recombination repair and its potential to enhance the sensitivity of LUAD cells to standard chemotherapeutic drugs. This study proposes HMGN1 as a novel prognostic biomarker and a promising target for chemotherapy in lung adenocarcinoma.

Designing compositions for novel alloys requires a fundamental grasp of the role of each alloying element in its properties. This study delves into the influence of alloying elements in Ultra-High Strength Steels on essential high-temperature properties, including thermoelasticity, thermal stress, and strength, utilizing first-principles phonon calculations. These properties are pivotal for steels used in high-temperature applications. Our investigation quantitatively forecasts the impact of alloying elements on elastic properties, providing valuable insights for advanced alloy design in high-temperature environments. The introduction of alloying elements markedly amplifies the elastic modulus of Fe-based alloys. The Ni, Mo, Cr, and C elements significantly enhance the anisotropy of the alloy. While refining elastic modulus and mechanical properties, alloying elements induce thermal stress, posing a potential risk of high-temperature cracking. The quantitative analysis underscores the robust strengthening potential for C, Ni, Mo, and W elements, with interstitial C emerging as pivotal in enhancing mechanical properties. The findings of this study illuminate the diverse roles played by different alloying elements and offer theoretical guidance for the design of advanced Ultra-High Strength Steels.

The generation and evaluation of severely high thermal stress (σ) is known to be responsible for failure of thermal barrier coatings (TBCs) during thermal cycling. It is crucial and challenging to capture fluctuations in σ caused by the phase transition, which has motivated us to develop a high-throughput multiscale evaluation method for σ in TBCs that considers the phase transition of the top ceramic materials by coupling first-principles calculations with finite element simulations. The method quantitatively evaluates and visualizes σ of the real TBC structure under thermal cycling by multifield coupling. Additionally, the thermophysical properties calculated by the first-principles calculations consider the effects of temperature and phase transition, which not only reduces the cost of obtaining data but also has a more physical connotation. In this work, rare earth tantalites (RETaO4) are introduced as ceramic layers, and the results demonstrate that σ undergoes a rapid escalation near the phase transition temperature (Tt), particularly in the TBCs_GdTaO4 system, where it rises from 224 to 435 MPa. This discontinuity in σ may originate from the significant alterations in Young’s modulus (increase by 27%–78%) and thermal conductivity (increase by 53%–146%) near Tt. The TBCs_NdTaO4 and TBCs_SmTaO4 systems exhibit noteworthy temperature drop gradients and minimal σ fluctuations, which are beneficial for extending service lifetime of TBCs. This approach facilitates the prediction of failure mechanisms and provides theoretical guidance for the reverse design of TBC materials to obtain low thermal stress systems.

ObjectivesThis study aimed to investigate the level of acceptance of family doctors (FDs) exhibited by residents in China.MethodsA cross-sectional study based on a structured self-administered questionnaire was conducted to investigate residents in eastern, central, and western China between September and December 2021. A multivariable stepwise logistic regression model was employed to identify the factors associated with health-seeking behavior after the signing of agreements concerning family doctor contract services (FDCS) as well as residents’ willingness to change FDs.ResultsAmong the 2,394 respondents included in this research, 55.8% sought primary care from their FDs when they became ill, whereas 9.7% expressed a willingness to change FDs. Residents who reported high levels of satisfaction with FDCS [odds ratio (OR) = 2.162] and trust in FDs (OR = 1.430) were more likely to seek initial help from FDs. In addition, residents from central China (OR = 0.546) and western China (OR = 0.704) and those who exhibited a high level of trust in FDs (OR = 0.238) were less likely to change FDs.ConclusionThe level of FD acceptance among Chinese residents was relatively high. Satisfaction with FDCS and trust in FDs were associated with the acceptance of FDs among residents. FDs should make efforts to enhance the quality of health services as well as the overall health experience of residents.

Summary: Spatial transcriptomics enables a single-cell resolution view of gene expression patterns in tissues, providing insight into their biological functions. However, applying this approach to the skin presents inherent challenges. Here, we present a protocol for preparing mammalian skin samples encompassing hair follicles for spatial transcriptomics. We describe steps for sample preparation, embedding, acquisition of frozen slices, RNA quality control, tissue mounting, fixation, staining, and imaging. We then detail procedures for permeabilization, reverse transcription, and cDNA collection.For complete details on the use and execution of this protocol, please refer to Chen et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Objective: The cause of syncope is generally determined based on clinical manifestations. There has been little discussion about the value of electrocardiograms for diagnosing neurally mediated syncope. The aim of this study was to test the predictive value of the isolated very low QRS voltage in tilt-table testing for suspected neurally mediated syncope in a Chinese population. Methods: This retrospective study enrolled patients with suspected neurally mediated syncope. Tilt-table testing was a part of the diagnostic examination. Each patient underwent echocardiography and electrocardiogram. isolated very low QRS voltage referred to a voltage of ⩽0.3 mV for the QRS complex in an isolated frontal lead or ⩽0.7 mV for the QRS complex in an isolated precordial lead. Results: In total, 157 patients were included in the tilt-table testing positive group, and 242 patients were included in the tilt-table testing negative group. Compared with the testing negative group, the testing positive group had more patients with isolated very low QRS voltage in the frontal leads ( p

Objective This study aims to investigate the effects of semaglutide on gut microbiota, cognitive function, and inflammation in obese mice. Method Twenty-four C57BL/6J male mice were randomly assigned to three groups: a normal-chow diet group (NCD, n = 8), high-fat diet group (HFD, n = 8), and HFD+semaglutide group (Sema, n = 8). The mice were fed a HFD to establish an animal model of obesity and then administered with semaglutide or saline for 12 weeks. Cognitive function was assessed using the Morris water maze test. Serum pro-inflammatory cytokines were measured. 16S rRNA gene sequencing technology was used to explore gut microbiota characteristics in obese mice. Result Obese mice showed significant cognitive impairment and inflammation. Semaglutide improved cognitive function and attenuated inflammation induced by a HFD diet. The abundance of gut microbiota was significantly changed in the HFD group, including decreased Akkermansia, Muribaculaceae, Coriobacteriaceae_UCG_002, Clostridia_UCG_014 and increased Romboutsia, Dubosiella, Enterorhabdus. Whereas semaglutide could dramatically reverse the relative abundance of these gut microbiota. Correlation analysis suggested that cognitive function was positively correlated with Muribaculaceae and Clostridia_UCG_014, and negatively associated with Romboutsia and Dubosiella. Romboutsia was positively correlated with TNFα, IL-6 and IL-1β. While Clostridia_UCG_014 was negatively related to TNFα, IL-6 and IL-1β. Conclusions For the first time semaglutide displayed different regulatory effects on HFD-induced gut microbiota dysbiosis. Semaglutide could regulate the structure and composition of gut microbiota associated with cognitive function and inflammation. Thus, affecting gut microbiota might be a potential mechanism of semaglutide in attenuating cognitive function and inflammation.

Background High levels of catecholamines are cardiotoxic and associated with stress‐induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. Methods and Results Purpose‐bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine‐stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High‐dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular‐aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800‐fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular‐aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. Conclusions Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion‐induced ischemia. However, epinephrine itself has potentially harmful long‐lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Background Septic shock is associated with increases in end‐diastolic volume (EDV) and decreases in ejection fraction that reverse within 10 days. Nonsurvivors do not develop EDV increases. The mechanism is unknown. Methods and Results Purpose‐bred beagles (n=33) were randomized to receive intrabronchial Staphylococcus aureus or saline. Over 96 hours, cardiac magnetic resonance imaging and echocardiograms were performed. Tissue was obtained at 66 hours. From 0 to 96 hours after bacterial challenge, septic animals versus controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%). On histology, the major finding was nonocclusive microvascular injury with edema in myocytes, the interstitium, and endothelial cells. Edema was associated with significant worsening of biventricular ejection fractions, ventricular‐arterial coupling, and circumferential strain. Early during sepsis, (0–24 hours), the EDV decreased; significantly more in nonsurvivors (ie, greater diastolic dysfunction). From 24 to 48 hours, septic animals' biventricular chamber sizes increased; in survivors significantly greater than baseline and nonsurvivors, whose EDVs were not different from baseline. Preload, afterload, or heart rate differences did not explain these differential changes. Conclusions The cardiac dysfunction of sepsis is associated with wall edema. In nonsurvivors, at 0 to 24 hours, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part, explain the EDV increases from 24 to 48 hours because of a potentially reparative process removing damaged wall tissue. Septic cardiomyopathy is most consistent with a nonocclusive microvascular injury resulting in edema causing reversible systolic and diastolic dysfunction with more severe diastolic dysfunction being associated with a decreased EDV and death.

The discovery of an inhibitor for acyl-CoA synthetase long-chain family member 4 (ACSL4), a protein involved in the process of cell injury through ferroptosis, has the potential to ameliorate cell damage. In this study, we aimed to investigate the potential of berberine (BBR) as an inhibitor of ACSL4 in order to suppress endothelial ferroptosis and provide protection against atherosclerosis. An atherosclerosis model was created in ApoE-/- mice by feeding a high fat diet for 16 weeks. Additionally, a mouse model with endothelium-specific overexpression of ACSL4 was established. BBR was administered orally to assess its potential therapeutic effects on atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were exposed to oxidized low density lipoprotein (ox-LDL) to simulate atherosclerotic endothelial damage in vitro. The interaction between ACSL4 and BBR has been confirmed, with BBR playing a role in inhibiting erastin-induced ferroptosis by regulating ACSL4. Additionally, BBR has been found to inhibit lipid deposition, plaque formation, and collagen deposition in the aorta, thereby delaying the progression of atherosclerosis. It also restored the abnormal expression of ferroptosis-related proteins in atherosclerotic vascular endothelial cells both in vivo and in vitro. In conclusion, BBR, acting as an ACSL4 inhibitor, can improve atherosclerosis by inhibiting ferroptosis in endothelial cells. This highlights the potential of targeted inhibition of vascular endothelial ACSL4 as a strategy for treating atherosclerosis, with BBR being a candidate for this purpose.

Ultrasound imaging has a history of several decades. With its non-invasive, low-cost advantages, this technology has been widely used in medicine and there have been many significant breakthroughs in ultrasound imaging. Even so, there are still some drawbacks. Therefore, some novel image reconstruction and image analysis algorithms have been proposed to solve these problems. Although these new solutions have some effects, many of them introduce some other side effects, such as high computational complexity in beamforming. At the same time, the usage requirements of medical ultrasound equipment are relatively high, and it is not very user-friendly for inexperienced beginners. As artificial intelligence technology advances, some researchers have initiated efforts to deploy deep learning to address challenges in ultrasound imaging, such as reducing computational complexity in adaptive beamforming and aiding novices in image acquisition. In this survey, we are about to explore the application of deep learning in medical ultrasound imaging, spanning from image reconstruction to clinical diagnosis.

Constructing heat-resistant fused heterocyclic compounds is increasingly fascinating in the field of energetic materials due to their excellent energy, high thermal stability, and low sensitivity, as well as high density in general. This study synthesized a novel heat-resistant explosive based on the imidazo [1,2-b]pyridazine fused ring，3,7-dinitroimidazo [1,2-b]pyridazine-6,8-diamine (5)，using a three-step facile method. This compound exhibited a high density (1.856 g cm−3) and low mechanical sensitivities (IS = 40 J, FS = 350 N). Meanwhile, it displayed a higher thermal decomposition temperature of 324 °C compared to conventional heat-resistant explosive HNS (Td = 318 °C). In addition, it demonstrated significantly higher detonation performance (D = 8336 m s−1, p = 27.25 GPa) than both TNT (D = 6881 m s−1, p = 19.5 GPa) and HNS (D = 7612 m s−1, p = 24.3 GPa). Theoretical analysis shows that the intramolecular hydrogen bonding interactions of NH2–NO2–NH2 might be the main reason for the heat resistance of energetic materials based on the imidazo [1,2-b]pyridazine fused ring. The results of this study suggest that compound 5 is a promising building block and a candidate for heat-resistant energetic materials.

Abstract Optimizing thermoelectric conversion efficiency requires the compromise of electrical and thermal properties of materials, which are hard to simultaneously improve due to the strong coupling of carrier and phonon transport. Herein, a one-pot approach realizing simultaneous second phase and Cu vacancies modulation is proposed, which is effective in synergistically optimizing thermoelectric performance in copper sulfides. Multiple lattice defects, including nanoprecipitates, dislocations, and nanopores are produced by adding a refined ratio of Sn and Se. Phonon transport is significantly suppressed by multiple mechanisms. An ultralow lattice thermal conductivity is therefore obtained. Furthermore, extra Se is added in the copper sulfide for optimizing electrical transport properties by inducing generating Cu vacancies. Ultimately, an excellent figure of merit of ~1.6 at 873 K is realized in the Cu1.992SSe0.016(Cu2SnSe4)0.004 bulk sample. The simple strategy of inducing compositional and structural modulation for improving thermoelectric parameters promotes low-cost high-performance copper sulfides as alternatives in thermoelectric applications.

Abstract Objectives Predicting secondary loss of response (SLR) to infliximab (IFX) is paramount for tailoring personalized management regimens. Concurrent pancreatic manifestations in patients with Crohn’s disease (CD) may correlate with SLR to anti-tumor necrosis factor treatment. This work aimed to evaluate the potential of pancreatic radiomics to predict SLR to IFX in biologic-naive individuals with CD. Methods Three models were developed by logistic regression analyses to identify high-risk subgroup prone to SLR. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and integrated discrimination improvement (IDI) were applied for the verification of model performance. A quantitative nomogram was proposed based on the optimal prediction model, and its reliability was substantiated by 10-fold cross-validation. Results In total, 184 CD patients were enrolled in the period January 2016 to February 2022. The clinical model incorporated age of onset, disease duration, disease location, and disease behavior, whereas the radiomics model consisted of five texture features. These clinical parameters and the radiomics score calculated by selected texture features were applied to build the combined model. Compared to other two models, combined model achieved favorable, significantly improved discrimination power (AUCcombined vs clinical 0.851 vs 0.694, p = 0.02; AUCcombined vs radiomics 0.851 vs 0.740, p = 0.04) and superior clinical usefulness, which was further converted into reliable nomogram with an accuracy of 0.860 and AUC of 0.872. Conclusions The first proposed pancreatic-related nomogram represents a credible, noninvasive predictive instrument to assist clinicians in accurately identifying SLR and non-SLR in CD patients. Critical relevance statement This study first built a visual nomogram incorporating pancreatic texture features and clinical factors, which could facilitate clinicians to make personalized treatment decisions and optimize cost-effectiveness ratio for patients with CD. Key points • The first proposed pancreatic-related model predicts secondary loss of response for infliximab in Crohn’s disease. • The model achieved satisfactory predictive accuracy, calibration ability, and clinical value. • The model-based nomogram has the potential to identify long-term failure in advance and tailor personalized management regimens. Graphical Abstract

Abstract Background Home phototherapy (HPT) remains a contentious alternative to inpatient phototherapy (IPT) for neonatal hyperbilirubinemia. To guide evidence-based clinical decision-making, we conducted a meta-analysis of randomized clinical trials (RCTs) and cohort studies and assessed the comparative risks and benefits of HPT and IPT. Methods PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technique Journals Database, ClinicalTrials.gov, and International Clinical Trial Registry Platform trial were searched from inception until June 2, 2023. We included RCTs and cohort studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Cochrane Collaboration Risk of Bias tool and the Newcastle–Ottawa scale. The outcome measures were phototherapy duration, daily bilirubin level reduction, exchange transfusion, hospital readmission, parental stress scale, and complications. We used fixed- or random-effects meta-analysis models, assessed heterogeneity (I 2 ), conducted subgroup analyses, evaluated publication bias, and graded evidence quality. Results Nine studies (998 patients) were included (four RCTs, five cohort studies). HPT was associated with longer phototherapy duration (SMD = 0.55, 95% CI: 0.06–1.04, P = 0.03). Cohort study subgroup analysis yielded consistent results (SMD = 0.90; 95% CI: 0.69 to 1.11, P

SETDB2 is a H3K9 histone methyltransferase required for accurate chromosome segregation. Its H3K9 histone methyltransferase activity was reported to be associated with chromosomes during metaphase. Here, we confirm that SETDB2 is required for mitosis and accurate chromosome segregation. However, these functions are independent of its histone methyltransferase activity. Further analysis showed that SETDB2 can interact with BUBR1, and is required for CDC20 binding to BUBR1 and APC/C complex and CYCLIN B1 degradation. The ability of SETDB2 to regulate the binding of CDC20 to BUBR1 or APC/C complex, and stabilization of CYCLIN B1 are also independent of its histone methyltransferase activity. These results suggest that SETDB2 interacts with BUBR1 to promote binding of CDC20 to BUBR1 and APC3, then degrades CYCLIN B1 to ensure accurate chromosome segregation and mitosis, independently of its histone methyltransferase activity.

Abstract Background The autophagy adapter SQSTM1/p62 is crucial for maintaining homeostasis in various organs and cells due to its protein–protein interaction domains and involvement in diverse physiological and pathological processes. Vascular endothelium cells play a unique role in vascular biology and contribute to vascular health. Methods Using the Cre-loxP system, we generated mice with endothelium cell-specific knockout of p62 mediated by Tek (Tek receptor tyrosine kinase)-cre to investigate the essential role of p62 in the endothelium. In vitro, we employed protein mass spectrometry and IPA to identify differentially expressed proteins upon knockdown of p62. Immunoprecipitation assays were conducted to demonstrate the interaction between p62 and FN1 or LAMC2 in human umbilical vein endothelium cells (HUVECs). Additionally, we identified the degradation pathway of FN1 and LAMC2 using the autophagy inhibitor 3-methyladenine (3-MA) or proteasome inhibitor MG132. Finally, the results of immunoprecipitation demonstrated that the interaction between p62 and LAMC2 was abolished in the PB1 truncation group of p62, while the interaction between p62 and FN1 was abolished in the UBA truncation group of p62. Results Our findings revealed that p62 Endo mice exhibited heart, lung, and kidney fibrosis compared to littermate controls, accompanied by severe cardiac dysfunction. Immunoprecipitation assays provided evidence of p62 acting as an autophagy adapter in the autophagy-lysosome pathway for FN1 and LAMC2 degradation respectively through PB1 and UBA domain with these proteins rather than proteasome system. Conclusions Our study demonstrates that defects in p62 within endothelium cells induce multi-organ fibrosis and cardiac dysfunction in mice. Our findings indicate that FN1 and LAMC2, as markers of (EndoMT), have detrimental effects on HUVECs and elucidate the autophagy-lysosome degradation mechanism of FN1 and LAMC2.

Jasmine (Jasminum sambac Aiton) is a well-known cultivated plant species for its fragrant flowers used in the perfume industry and cosmetics. However, the genetic basis of its floral scent is largely unknown. In this study, using PacBio, Illumina, 10× Genomics and high-throughput chromosome conformation capture (Hi-C) sequencing technologies, a high-quality chromosome-level reference genome for J. sambac was obtained, exploiting a double-petal phenotype cultivar ‘Shuangbanmoli’ (JSSB). The results showed that the final assembled genome of JSSB is 580.33 Mb in size (contig N50 = 1.05 Mb; scaffold N50 = 45.07 Mb) with a total of 39 618 predicted protein-coding genes. Our analyses revealed that the JSSB genome has undergone an ancient whole-genome duplication (WGD) event at 91.68 million years ago (Mya). It was estimated that J. sambac diverged from the lineage leading to Olea europaea and Osmanthus fragrans about 28.8 Mya. On the basis of a combination of genomic, transcriptomic and metabolomic analyses, a range of floral scent volatiles and genes were identified involved in the benzenoid/phenylpropanoid and terpenoid biosynthesis pathways. The results provide new insights into the molecular mechanism of its fragrance biosynthesis in jasmine.

Crop diseases, as one of the major problems in global agricultural production, lead to crop yield reduction, death, and even total extinction, with serious impacts on farmers and the food supply. Traditionally, crop diseases are identified by visual inspection and based on the experience of farmers and agricultural experts, a method that not only consumes human resources but also has a certain degree of subjectivity and inaccuracy. The development of artificial intelligence technology successfully achieves real-time monitoring, automatic identification, and intelligent decision by combining the Internet of Things (IoT) technology and cloud computing technology. Herein, we proposed an EfficientNet Convolutional Group-Wise Transformer (EGWT) architecture. The local features of crop leaf images are extracted by EfficientNet convolution and then input into a group-wise transformer architecture. In the group-wise transformer process, the input features are divided into multiple groups. An attention mechanism is used within each group to calculate correlations between features. After calculating the intra-group attention, the output features of each group are stitched together to form the final output features. Our proposed model achieves 99.8% accuracy on the PlantVillage dataset, 86.9% accuracy on the cassava dataset, and 99.4% accuracy on the Tomato leaves dataset, with the least number of parameters 23.04M in the state-of-the-art convolutional combinatorial transformer hybrid model. The experimental results indicate that the proposed model has the best accuracy and optimal model complexity so far compared to other neural networks based on CNN, transformer, and the hybrid structure of CNN and transformer.

Objective: To investigate the interrelationship between cardiovascular health awareness, risk perception, behavioural intention, and INTERHEART risk stratification in a middle-aged adult population in Malaysia. Methods: A cross-sectional survey with convenience sampling was conducted during November 2022 and January 2023. Participants completed validated questionnaires assessing cardiovascular health awareness, risk perception of cardiovascular diseases, behavioural intention towards adopting healthy habits, and INTERHEART risk stratification score (IHRS) based on established risk factors. A total of 602 respondents were included in the final analysis. Data were analysed with independent t-test/one-way ANOVA or Mann- Whitney/Kruskai-Wailis to test the differences, Pearson correlation or linear regression test to analyze the association of independent and dependent variables. Results: There was a significant positive correlation between medical knowledge related to cardiovascular disease (CVD) and knowledge related to CVD risk prevention, risk perception, behavioural intention and IHRS (P

Abstract Based on investment data from 214 sustainable universities in the United States, a study on the characteristics and affordability of universities with a willingness to invest in sustainability was conducted. First, according to the concept of ESG, the related factors of sustainability are classified. Then, the important variables are selected by the Cp method. Finally, the main characteristics and maximum affordability of universities with investment willingness for sustainability are quantitatively studied through the logit regression model. The findings are as follows: (1) Most universities take sustainable industries as their investment objective, promoting investment through a series of sustainable policies. (2) The characteristics of universities are as follows: (a) the size of the campus within a certain range; (b) sustainability instruction training for new employees; (c) the encouragement of employees for community service; and (d) the establishment of CIR (Committees on Investor Responsibility). (3) The maximum affordability is 30.3% of the total investment, and approximately 94% of universities do not actually invest as much in sustainability as in willingness. The study defines the identification factors of universities to provide an important basis for the formulation and implementation of guiding policies related to investment in the sustainability of universities in the future.

Abstract Background Cervical cancer is strongly associated with human papillomavirus (HPV) infection. In this retrospective study, we analyzed the data of postmenopausal women who were tested for HPV in Nanjing First Hospital from 2019 to 2021. Methods We retrospectively analyzed the data of 14,608 postmenopausal women aged 45–90 years, who underwent HPV examination in Nanjing First Hospital between January 2019 and December 2021. All participants were tested for 23 HPV genotypes. We subsequently analyzed the infection rate and evaluated the distribution of HPV using the chi-square test. Results Our results showed that the HPV infection rate in postmenopausal women in Nanjing, China was 22.36%. In terms of age group, the infection rate was 19.54%, 24.30%, 26.58%, and 14.99% in those aged ≤ 50, 51–60, 61–70, and ≥ 71 years, respectively. The most common HPV subtypes were HPV52 (22.1 3%), HPV58 (15.86%), HPV53 (14.17%), HPV16 (12.61%), and HPV81 (11.66%), in that order. The single-HPV infection rate was 14.23%, and the multiple-genotype infection rate was 8.14% (1189/14,608). Conclusions This study showed that in Nanjing, China, the different age groups of post-menopausal women could have different rates of HPV infection, and the most common types were HPV52, HPV58, HPV53, HPV16 and HPV81. These findings highlighted the importance of understanding the epidemiology of HPV infection in specific populations, such as postmenopausal women in Nanjing, China. The results could provide valuable information for healthcare professionals and policymakers to develop targeted prevention and screening strategies for reducing the burden of HPV-related diseases in this population.

Abstract Background The peritoneal cancer index (PCI) has been used to predict surgical outcomes for pseudomyxoma peritonei (PMP). The present study aimed to establish the optimal cutoff point for PCI to predict surgical resectability of PMP. Methods A total of 366 PMP patients were included. The patients were divided into low-grade and high-grade groups. Based on the completeness of the cytoreduction (CC) score, both low-grade and high-grade PMP patients were further divided into complete cytoreductive surgery (CRS) and maximal tumor debulking (MTD) subgroups. The ability to predict surgical resectability of total and selected PCI (regions 2 + 9 to 12) was analyzed through receiver operating characteristic (ROC) curves. Results Both total and selected PCI demonstrated excellent discriminative ability in predicting surgical resectability for low-grade PMP patients (n = 266), with the ROC-AUC of 0.940 (95% CI: 0.904–0.965) and 0.927 (95% CI: 0.889–0.955). The corresponding optimal cutoff point was 21 and 5, respectively. For high-grade PMP patients (n = 100), both total and selected PCI exhibited good performance in predicting surgical resectability, with the ROC-AUC of 0.894 (95% CI: 0.816–0.946) and 0.888 (95% CI: 0.810–0.943); correspondingly, the optimal cutoff point was 25 and 8, respectively. The discriminative ability between total and selected PCI in predicting surgical resectability did not show a statistical difference. Conclusions Both total and selected PCI exhibited good performance and similarity in predicting complete surgical resection for both low-grade and high-grade PMP patients. However, the selected PCI was simpler and time-saving in clinical practice. In the future, new imaging techniques or predictive models may be developed to better predict PCI preoperatively, which might assist in confirming whether complete surgical resection can be achieved.

ABSTRACTChronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.

AimsPrimary pigmented nodular adrenocortical disease (PPNAD), as a rare kind of Cushing’s syndrome, is frequently misdiagnosed. To get a better understanding of the disease, we analyzed the clinical characteristics and pathogenic variants of PPNAD.MethodsDatabases were searched, and the pathogenic variants and clinical manifestations of patients were summarized from the relevant articles.ResultsA total of 210 patients in 86 articles were enrolled with a median age of 22 and a female-to-male ratio of 2:1. Sixty-six (31.43%) patients were combined with Carney complex (CNC) and 94.29% were combined with osteoporosis/osteopenia. Among 151 patients who underwent genetic testing, 87.42% (132/151) had pathogenic variants. Six gene mutations (PRKAR1A, PDE11A, PRKACA, CTNNB1, PDE8B, and ARMC5) were detected in the patients. The most common mutation was PKAR1A, accounting for 79.47% (120/151). There was a significant correlation between PRKAR1A pathogenic variant and spotty skin pigmentation in CNC concurrent with PPNAD (p < 0.05). Among pregnant patients with PPNAD, those without surgical treatment and with bilateral adrenalectomy suffered from a high-risk perinatal period. However, patients with unilateral adrenalectomy presented a safe perinatal period.ConclusionsFor young patients with Cushing’s syndrome, especially female patients with spotty skin pigmentation and osteoporosis/osteopenia, PPNAD should be considered. Unilateral adrenal resection may be considered as an option for women with fertility needs. In view of the difficulty of PPNAD diagnosis, genetic testing before surgery might be a reasonable option. Patients with PPNAD with spotty skin pigmentation should consider the PRKAR1A pathogenic variant and pay attention to CNC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023416988.

Abstract Background Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non‐Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown. Methods The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP‐5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes. Results Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non‐Asians: (weighted mean difference [WMD], −0.59, 95% CI, −0.73 to −0.45, p .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, −5.12, 95% CI, −5.84 to −4.41, p

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p

There are various types of land use in the agricultural and pastoral areas of northern China, including natural grassland and artificial grassland, scrub land, forest land and farmland, may change the soil microbial community However, the soil microbial communities in these different land use types remain poorly understood. In this study, we compared soil microbial communities in these five land use types within the agro-pastoral ecotone of northern China. Our results showed that land use has had a considerable impact on soil bacterial and fungal community structures. Bacterial diversity was highest in shrubland and lowest in natural grassland; fungal diversity was highest in woodland. Microbial network structural complexity also differed significantly among land use types. The lower complexity of artificial grassland and farmland may be a result of the high intensity of anthropogenic activities in these two land-use types, while the higher structural complexity of the shrubland and woodland networks characterised by low-intensity management may be a result of low anthropogenic disturbance. Correlation analysis of soil properties (e.g., soil physicochemical properties, soil nutrients, and microbiomass carbon and nitrogen levels) and soil microbial communities demonstrated that although microbial taxa were correlated to some extent with soil environmental factors, these factors did not sufficiently explain the microbial community differences among land use types. Understanding variability among soil microbial communities within agro-pastoral areas of northern China is critical for determining the most effective land management strategies and conserving microbial diversity at the regional level.

Abstract Peritoneal cancer index (PCI) is the surgical variable most commonly used to quantify the extent of peritoneal metastases for pseudomyxoma peritonei (PMP) patients. The present study aimed to investigate the agreement between CT predicted and surgical PCI by the Bland–Altman method for PMP of appendiceal origin. A total of 167 PMP patients of appendiceal origin were included between 2016 and 2021. Bland–Altman analysis was performed for both total PCI and selected PCI (regions 2 + 9–12). After the Bland–Altman plot was drawn, the mean bias and its 95% limit of agreements (LoAs) was quantified. Besides, the correlation coefficients between CT-PCI and surgical PCI were also been calculated. The Bland–Altman plot showed the mean bias ± SD between total CT-PCI and surgical PCI as 0.431 ± 3.005, with the LoAs from − 5.459 to 6.321. There were nine points of difference in total PCI exceeded the 95% LoAs, with the rate of 5.39% (9/167). As for selected CT-PCI, Bland–Altman plot showed the mean bias ± SD between selected CT-PCI and surgical PCI as − 0.287 ± 1.955, with the LoAs from − 4.118 to 3.544. There were ten points of difference in selected PCI exceeded the 95% LoAs, with the rate of 5.99% (10/167). The Spearman's rank correlation coefficient between total CT-PCI and surgical PCI was 0.911, P

Abstract Cushing's syndrome is a rare cause of myocardial infarction and heart failure. Herein, we report a female patient who presented acute myocardial infarction and heart failure with reduced ejection fraction. The patient was found to have hypercortisolism secondary to adrenocortical adenoma and responded well to therapy. This case underlines the effects of hypercortisolism on the cardiovascular system. The clinical presentation of this patient is unique because non‐atherosclerotic myocardial infarction is rarely reported in Cushing's syndrome patients.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 (5) and AZD5099 (6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 (6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure–activity relationships of the compounds were also studied.

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine characterized by a compromised intestinal epithelial barrier. Mucin glycans are crucial in preserving barrier function during bacterial infections, although the underlying mechanisms remain largely unexplored. Methods A cohort comprising 15 patients diagnosed with UC and 15 healthy individuals was recruited. Stool samples were collected to perform 16S rRNA gene sequencing, while biopsy samples were subjected to nanocapillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to assess O-glycosylation. Gene expression was evaluated through qPCR analysis and Western blotting. Furthermore, animal experiments were conducted to investigate the effects of Escherichia coli and/or O-glycan inhibitor benzyl-α-GalNAc on the development of colitis in mice. Results Our findings revealed that the mucus barrier was disrupted during the early stages of UC, while the MUC2 protein content remained unaltered. Additionally, a noteworthy reduction in the o-glycosylation of MUC2 was observed, along with significant changes in the intestinal microbiota during the early stages of UC. These changes included a decrease in intestinal species richness and an increase in the abundance of Escherichia coli (E. coli). Moreover, subsequent to the administration of galactose or o-glycan inhibitor to intestinal epithelial cells, it was observed that the cell culture supernatant had the ability to modify the proliferation and adhesive capacity of E. coli. Furthermore, when pathogenic E. coli or commensal E. coli were cocultured with intestinal epithelium, both strains elicited activation of the NF-KB signaling pathway in epithelial cells and facilitated the expression of serine protease in comparison to the untreated control. Consistently, the inhibition of o-glycans has been observed to enhance the pathogenicity of E. coli in vivo. Furthermore, a correlation has been established between the level of o-glycans and the development of ulcerative colitis. Specifically, a reduction in the O-glycan content of MUC2 cells has been found to increase the virulence of E. coli, thereby compromising the integrity of the intestinal epithelial barrier. Conclusions Together, there exist complex interactions between the intestinal epithelium, o-glycans, and the intestinal microbiota, which may inform the development of novel therapeutic strategies for the treatment of ulcerative colitis.