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Abstract Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis. AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.

Abstract The mislocalization of proteins leads to breast cancer, one of the world’s most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.

Abstract Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K+ Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.

Abstract Background This systematic review and meta-analysis aimed to evaluate the efficiency and safety of percutaneous nephrolithotomy (PCNL) between flank position and prone position for the treatment of renal stones. Methods PubMed, Embase, OVID, and Cochrane Library were comprehensively searched from their inception to Jul 2024. Randomized and nonrandomized trials evaluating renal calculi patients who underwent PCNL via flank position or prone position were included. Data extraction and quality assessment were conducted by two independent reviewers. The outcomes and complications of both groups were compared in this meta-analysis. Results This review involved five articles (554 patients). Specifically, four articles were randomized controlled trials, and the remaining publication was prospective cohort study. No significant difference was found in stone-free rate between the flank group and prone group after the PCNL procedure. Similarly, the percutaneous access time, operative time, and hospital stay of flank position had no significant difference compared with the prone group. There was no significant difference in the comparison of complication rates between the flank group and the prone group. Although further analysis indicated that patients in the prone position suffered more hemoglobin drop than the flank group, no significant difference was found in the hemorrhage and blood transfusion rates. Conclusions Both surgical positions were appropriate for most PCNL procedures and had shown similar efficacy and safety. In practice, the optimal choice should be made according to the patients’ conditions and urologists’ acquaintance.

To enhance the scientific rigor of design decisions and develop new rosewood furniture that aligns with user emotions, this study integrates the strengths of the Hesitant Fuzzy Analytic Hierarchy Process (HFAHP) and Hesitant Fuzzy Quality Function Deployment (HFQFD) within the framework of Kansei Engineering (KE). This method accurately translates Consumer Requirements (CRs) into Engineering Characteristics (ECs). First, the KJ Method was used to screen and categorize Kansei words, create product sample images, and deconstruct the form of rosewood furniture using morphological analysis. Second, after collecting valid questionnaires using a 7-point Likert scale, Factor Analysis (FA) was employed to extract three key Kansei factors. Third, HFAHP was utilized to calculate the weights of the Kansei words. Fourth, HFQFD was applied to construct a hesitant fuzzy correlation matrix between CRs and ECs, determining the priority of design elements for rosewood furniture. Finally, using a square table as an example in the design practice, the optimal Scheme No. 9, which highly meets consumer emotional needs and features harmonious form combinations, was selected. This study enhances the emotional value of rosewood furniture, optimizes the design decision-making process, and improves contemporary consumer satisfaction.

Psychological and physiological cognitive measurements were combined with Kansei engineering theory to study the shape of the traditional Chinese official-hat chair, a kind of Ming-style chairs, while investigating people’s perceptual cognitive process. This work employed focus groups to obtain 5 groups of representative words and 22 typical samples for evaluation experiments. After data preprocessing, principal component analysis (PCA) was used to extract three main components: "Concise-Ornate", "Soft-Strong", and "Elegant-Vulgar". In terms of component weight calculation, the analytic hierarchy process (AHP) was initially used to calculate the subjective cognitive weight of different components, and then eye-tracking technology was used to assist in calculating the physiological cognitive weight. Finally, combining the subjective and objective weights, the weights of the components were determined as: backrest (41.02%) > stretcher (18.29%) > handrail (11.64%) > top rail (11.14%) > outside stick (8.64%) > inside stick (5.32%) > foot rail (3.95%). The four main components—backrest, stretcher, handrail, and top rail—along with perceptual image evaluations, were selected to establish a multivariate linear regression equation, thereby constructing a mathematical mapping relationship between perceptual image and main design elements. This provides theoretical support for designers in creating different perceptual images.

Abstract Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/−) mice did not show any significant changes in body weight or composition. However, Fadd+/− mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/− mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

When large-sized oil pipelines are subjected to skin effect heating under the constraint of limited current, the power supply converter must provide a higher current frequency. However, an inappropriate frequency can lead to increased energy losses and consequently reduce heating efficiency. To achieve higher heating efficiency of large-sized pipelines, this paper proposes a temperature control strategy based on optimal frequency forecast. First, a skin effect heating model is established to illustrate the necessity of frequency forecasting. Then, using the small sample data from the oil field, an optimal frequency forecasting method based on Gradient Boosting Decision Tree (GBDT) is proposed. At the forecasted frequency, a dual closed-loop control strategy for current and temperature, based on a designed three-phase converter, is employed to achieve temperature control under limited current conditions. The feasibility and effectiveness of this approach are demonstrated through a case study involving a 159 mm oil pipeline with a heating current of less than 80A. The experiment shows that with the forecasted frequency, the pipeline temperature reached 40 °C within 14 min, and the energy consumption per unit length of the pipeline is 394 W/m, complying with the standard Q/SY 06022-2016.

Abstract The stochastic EXtended finite‐fault ground‐motion SIMulation algorithm (EXSIM) has been widely applied in simulating and predicting broadband strong ground‐motion. However, an increasingly number of researchers have found that EXSIM may overestimate ground‐motions at low frequencies for some large‐magnitude earthquakes and/or thrust earthquakes, for which the far‐field source model has been explained by a double‐corner‐frequency model. Despite controversy, the double‐corner‐frequency model is now being accepted as one of the main categories of the far‐field source model. This study demonstrated the limited applicability of EXSIM to earthquakes explained by the double‐corner‐frequency source model, by presenting the equivalence between motions generated by EXSIM and those generated by EXSIM's point‐source version, SMSIM, which adopts the ω‐square single‐corner‐frequency model. Furthermore, two improvements to EXSIM have been proposed: (a) the incorporation of the asperity‐distributed stress‐drop compound faults model and (b) the hybrid application of EXSIM with the proposed model. The effects of the two improvements have been verified by comparing EXSIM‐generating motions with recorded ground‐motions for the 2013 Mw 6.7 Lushan thrust earthquake. Significantly, consistent simulation accuracy has been achieved across high‐ and low‐frequency bands as well as in far‐ and near‐fields. The consistent accuracy of the improved EXSIM in simulating high‐ and low‐frequency ground motions enables its direct and independent application to broadband ground motion simulations. Moreover, the first validation of this consistent accuracy in both near‐ and far‐field scenarios further enhances its application in earthquake engineering practices.

Abstract The generation of pressure perturbations in matter stimulated by pulsed light is a method widely recognized as the photoacoustic or light‐induced thermoelastic effect. In a series of psychophysical experiments, the robustness of the tactile perception generated with a variety of light sources is examined: a diverging pulsed laser used for photoacoustic tomography optical parameter oscillation (OPO), a miniature diode laser (MDL), and a commercial digital light processing (DLP) projector. It is demonstrated that participants can accurately detect, categorically describe the sensations, and discern the direction of pulsed light travel. High detection accuracy is reported as follows: (d′ = 4.95 (OPO); d′ = 2.78 (modulated MDL); d′ = 2.99 (DLP)) of the stimulus on glabrous skin coated with a thin layer of dye absorber. For all light sources, the predominant sensation is felt as vibration at the distal phalanx (i.e., fingertip, 55.21–57.29%) and the proximal phalanx (41.67–44.79%). At the fingertip, thermal sensations are perceived less frequently than mechanical ones. Moreover, these haptic effects are preserved under a wide range of pulse widths, spot sizes, optical energies, and wavelengths of the light sources. This form of sensory stimulation demonstrates a generalizable non‐contact, non‐optogenetic, in situ activation of the mechanosensory system.

Abstract Olverembatinib (HQP1351) is a BCR‐ABL1 tyrosine kinase inhibitor with promising clinical activity. It is approved in China for the treatment of patients with chronic myeloid leukemia harboring drug‐resistant mutations, such as T315I. In vitro studies suggested that metabolism of olverembatinib is primarily mediated by cytochrome P450 (CYP3A4). The effects of CYP3A4 inhibition and induction on the pharmacokinetics of olverembatinib were evaluated in an open‐label, 2‐part, fixed‐sequence study in healthy volunteers. In Part 1 of this study, 16 participants received a single oral dose of olverembatinib (20 mg) and the oral CYP3A4 inhibitor itraconazole (200 mg). In Part 2, 16 participants received a single oral dose of olverembatinib (40 mg) and the oral CYP3A4 inducer rifampin (600 mg). To measure pharmacokinetic parameters, serial blood samples were collected after administration of olverembatinib alone and combined with itraconazole or rifampin. Coadministration of olverembatinib with itraconazole increased the peak plasma concentration of olverembatinib, its area under the time‐concentration curve (AUC)0‐last, and AUC0‐inf by 75.63%, 147.06%, and 158.66%, respectively. Coadministration with rifampin decreased these same variables by 61.27%, 74.21%, and 75.19%, respectively. These results confirm that olverembatinib is primarily metabolized by CYP3A4 in humans, suggesting that caution should be exercised with concurrent use of olverembatinib and strong CYP3A4 inhibitors or inducers.

Abstract Carbon reduction is an important issue of global concern today, and with the construction industry accounting for a significant portion of global carbon emissions, carbon reduction research for the civil engineering industry is becoming increasingly important. The current research on carbon emission of buildings mainly focus on energy consumption, choice of building materials, and energy‐saving technologies. While different construction programs can affect the construction sequence and have a significant impact on carbon emissions, especially for ultra‐high‐rise steel structures. In this paper, carbon emission is introduced as the optimization objective, and a nodal optimization procedure based on carbon emission is given to explore the optimization scheme of ultra‐high‐rise steel structure construction based on carbon emission. Calculations using the carbon emission factor method were carried out to analyze the differences in carbon emissions between different construction schemes and to explore the impact of the method of carbon emission optimization. Results show that the combined lifting scheme can save 463.4 kg carbon emissions and reduce the number of lifts by 780 times.

Abstract Background This study aimed to investigate the knowledge, attitudes, and practices (KAP) toward cardiovascular complications among end-stage renal disease patients undergoing maintenance hemodialysis. Methods This web-based cross-sectional study was conducted at Guangdong Provincial People’s Hospital between December 2022, and May 2023. Results A total of 545 valid questionnaires were collected, with an average age of 57.72 ± 13.47 years. The mean knowledge, attitudes and practices scores were 8.17 ± 2.9 (possible range: 0–24), 37.63 ± 3.80 (possible range: 10–50), 33.07 ± 6.10 (possible range: 10–50) respectively. Multivariate logistic regression analysis showed that patients from non-urban area had lower knowledge compared to those from urban area (odds ratio (OR) = 0.411, 95% CI: 0.262–0.644, P

ABSTRACT: Objectives: Pyogenic liver abscess (PLA) is a severe and potentially fatal infectious disease. Klebsiella pneumoniae (K. pneumoniae) is the predominant pathogen responsible for PLA. This study aims to investigate the clinical characteristics and prognostic factors of K. pneumoniae–induced pyogenic liver abscess (KP-PLA), particularly those caused by carbapenem-resistant K. pneumoniae (CRKP). Methods: Analyses were performed on PLA patients from January 2010 to December 2021, to investigate the differences of K. pneumoniae from other etiologically infected PLA patients. Univariate and multivariate logistic regression analyses were used to compare prognostic factors between patients with carbapenem-resistant K. pneumoniae PLA (CRKP-PLA) and patients with carbapenem-sensitive K. pneumoniae PLA. Results: Univariate analysis demonstrated a significant association between KP-PLA and factors including diabetes mellitus (P < 0.001), cholecystitis and cholelithiasis (P = 0.032), single abscess (P = 0.016), and abscesses with a diameter over 50 mm (P = 0.004). The CRKP group exhibited a higher prevalence of therapeutic interventions before K. pneumoniae infection, including abdominal surgery, mechanical ventilation, sputum suction, tracheal cannula, routine drainage of the abdominal cavity, and peripherally inserted central venous catheters (P < 0.05). Multivariate logistic regression analysis revealed that admission to the intensive care unit was an independent risk factor associated with CRKP-PLA (odds ratio 36; 95% confidence interval 1.77–731.56; P = 0.020). Conclusion: The KP-PLA patients were significantly associated with diabetes and were more likely to have single abscesses larger than 50 mm. PLA patients with a history of admission to intensive care unit or invasive therapeutic procedures should be given special consideration if combined with CRKP infection.

WiFi sensing is critical to many applications, such as localization, human activity recognition, and contact-less health monitoring. With metaverse and ubiquitous sensing advances, WiFi sensing becomes increasingly imperative. However, as shown in this paper, WiFi sensing data leaks users’ private attributes (e.g., height, weight, and gender), violating increasingly stricter privacy protection laws and regulations. To demonstrate the leakage of private attributes in WiFi sensing, we investigate two public WiFi sensing datasets and apply a deep learning model to recognize users’ private attributes. Our experimental results clearly show that our model can identify users’ private attributes in WiFi sensing data collected by general WiFi applications, with almost 100% accuracy for gender inference, less than 4 cm error for height inference, and about 4 kg error for weight inference, respectively. Our finding calls for research efforts to preserve data privacy while enabling WiFi sensing-based applications.

Background Secondary hyperparathyroidism (SHPT) is a prevalent chronic complication in patients undergoing hemodialysis. Parathyroidectomy (PTX) is crucial for reducing mortality and improving the prognosis in the treatment of refractory hyperparathyroidism. However, it is often associated with a number of postoperative complications such as postoperative hypotension, hyperkalemia, and hungry bone syndrome. A previous study demonstrated that low blood pressure influences the patency of autogenous arteriovenous fistulas (AVF). Few studies have examined AVF dysfunction following PTX. This study aimed to identify and describe the risk variables associated with AVF dysfunction after PTX.Methods Cases of AVF dysfunction after PTX between 2015 and 2021 were studied. Four controls were identified for each patient and were matched for sex and age. Biochemical parameters and blood pressure of the patients before and after PTX were recorded. Risk factors for AVF dysfunction after PTX were identified using conditional logistic regression analysis.Results Sixteen patients and 64 controls were included in this study. Baseline demographic and laboratory data were compared. Patients in the AVF dysfunction group had lower levels of postoperative calcium than the controls. After surgery, calcium levels decreased more in patients with AVF dysfunction than in the control group. The decrease in systolic blood pressure (ΔSBP) after PTX was greater in the AVF dysfunction group than that in the control group. For each 1 mmHg increment in ΔSBP, the risk of AVF dysfunction after surgery increased by 11.6% (OR = 1.116, 95% CI, 1.005–1.239, p = .040). The likelihood of developing AVF dysfunction after surgery was twelvefold higher in diabetic patients than in non-diabetic patients (OR = 12.506, 95% CI, 1.113–140.492, p = .041). Among patients with ΔSBP > 5.8 mmHg after PTX, the AVF failure rate was significantly greater in patients with diabetes than in those without diabetes. Patients with a history of AVF failure had a nine-fold higher risk of developing AVF dysfunction (OR = 9.143, 95% CI, 1.151–72.627, p = .036). Serum albumin, hemoglobin, ΔiPTH, and age were not independent predictors of AVF dysfunction. The cutoff value for SBP was 5.8 mmHg, as determined by the Youden index of the receiver operating characteristic curve.Conclusion Decreased systolic blood pressure (ΔSBP) after PTX, diabetes, and AVF failure history were risk factors for AVF dysfunction following PTX in patients with SHPT. Diabetes patients with ΔSBP > 5.8 mmHg were more prone to AVF dysfunction after PTX.

Brucellosis, caused by the intracellular pathogen Brucella, is a major zoonotic infection that promotes reproductive disease in domestic animals and chronic debilitating conditions in humans. The ArsR family of transcriptional regulators plays key roles in diverse cellular processes, including metal ion homeostasis, responding to adverse conditions, and virulence. However, little is known about the function of ArsR family members in Brucella. Here, we identified ArsR2 as a nonclassical member of the family that lacks autoregulatory function, but which nevertheless plays a vital role in maintaining copper homeostasis in B. abortus. ArsR2 is a global regulator of 241 genes, including those involved in the VirB type IV secretion system (T4SS). Significantly, ArsR2 regulates T4SS production in B. abortus by targeting VjbR which encodes a LuxR-type family transcriptional regulator. Moreover, copper modulates transcriptional activity of ArsR2, but not of VjbR. Furthermore, deletion of arsR2 attenuated virulence in a mouse model. Collectively, these findings enhance understanding of the mechanism by which ArsR proteins regulate virulence gene expression in pathogenic Brucella species.

ABSTRACT Tuberculosis (TB) remains one of the infectious diseases with high incidence and high mortality. About a quarter of the population has been latently infected with Mycobacterium tuberculosis. At present, the available TB treatment strategies have the disadvantages of too long treatment duration and serious adverse reactions. The sustained inflammatory response leads to permanent tissue damage. Unfortunately, the current selection of treatment regimens does not consider the immunomodulatory effects of various drugs. In this study, we preliminarily evaluated the effects of commonly used anti-tuberculosis drugs on innate immunity at the cellular level. The results showed that clofazimine (CFZ) has a significant innate immunosuppressive effect. CFZ significantly inhibited cytokines and type I interferons (IFNα and IFNβ) expression under both lipopolysaccharide stimulation and CFZ-resistant strain infection. In further mechanistic studies, CFZ strongly inhibited the phosphorylation of nuclear factor kappa B (NF-κB) p65 and had no significant effect on the phosphorylation of p38. In conclusion, our study found that CFZ suppresses innate immunity against Mycobacterium tuberculosis by NF-κB, which should be considered in future regimen development.IMPORTANCEThe complete elimination of Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, from TB patients is a complicated process that takes a long time. The excessive immune inflammatory response of the host for a long time causes irreversible organic damage to the lungs and liver. Current antibiotic-based treatment options involve multiple complex drug combinations, often targeting different physiological processes of Mtb. Given the high incidence of post-tuberculosis lung disease, we should also consider the immunomodulatory properties of other drugs when selecting drug combinations.

Summary: Because of their unique layer structure, 2D materials have demonstrated to be promising electrode materials for rechargeable batteries. However, individual 2D materials cannot meet all the performance requirements of energy density, power density, and cycle life. Constructing 2D materials-based heterostructures offers an opportunity to synergistically handle the deficiencies of individual 2D materials and modulate the physical and electrochemical properties. The enlarged interlayer distance and increased binding energy with ions of heterostructures can facilitate charge transfer, boost electrochemical reactivities, resulting in an enhanced performance in rechargeable batteries. Here we summarize the latest development of heterostructures consisted of 2D materials and their applications in rechargeable batteries. Firstly, different preparation strategies and optimized structure engineering strategies of 2D materials-based heterostructures are systematically introduced. Secondly, the unique functions of 2D materials-based heterostructures in rechargeable batteries are discussed respectively. Finally, challenges and perspectives are presented to inspire the future study of 2D materials-based heterostructures.

Abstract Lung adenocarcinoma (LUAD) is a malignant tumor with high lethality, and the aim of this study was to identify promising biomarkers for LUAD. Using the TCGA-LUAD dataset as a discovery cohort, a novel joint framework VAEjMLP based on variational autoencoder (VAE) and multilayer perceptron (MLP) was proposed. And the Shapley Additive Explanations (SHAP) method was introduced to evaluate the contribution of feature genes to the classification decision, which helped us to develop a biologically meaningful biomarker potential scoring algorithm. Nineteen potential biomarkers for LUAD were identified, which were involved in the regulation of immune and metabolic functions in LUAD. A prognostic risk model for LUAD was constructed by the biomarkers HLA-DRB1, SCGB1A1, and HLA-DRB5 screened by Cox regression analysis, dividing the patients into high-risk and low-risk groups. The prognostic risk model was validated with external datasets. The low-risk group was characterized by enrichment of immune pathways and higher immune infiltration compared to the high-risk group. While, the high-risk group was accompanied by an increase in metabolic pathway activity. There were significant differences between the high- and low-risk groups in metabolic reprogramming of aerobic glycolysis, amino acids, and lipids, as well as in angiogenic activity, epithelial-mesenchymal transition, tumorigenic cytokines, and inflammatory response. Furthermore, high-risk patients were more sensitive to Afatinib, Gefitinib, and Gemcitabine as predicted by the pRRophetic algorithm. This study provides prognostic signatures capable of revealing the immune and metabolic landscapes for LUAD, and may shed light on the identification of other cancer biomarkers.

The aim of this article is to investigate the optimization of electric vehicle charging and swapping for green logistics, as well as path planning considering urban impedance. We improved a road impedance function model suitable for urban road traffic in China to calculate the actual traffic time based on real-time traffic data and the intricate urban road environment. This model is then applied to address the delivery optimization problem. Furthermore, a robust computational approach is introduced to estimate battery degradation costs, accounting for environmental temperature and depth of discharge. The logistics delivery model is effectively tackled using genetic algorithms, and simulation results demonstrate the considerable advantages of electric vehicle swapping, effectively mitigating energy wastage and environmental pollution. Additionally, the integration of road impedance modeling for path optimization proves to significantly reduce logistics costs, time expenditures, and enhance logistics efficiency. A comprehensive sensitivity analysis is also conducted to elucidate the factors influencing electric vehicle battery degradation, revealing a direct correlation between higher temperatures, deeper discharge depth, and increased battery loss. The study underscores the paramount significance of this research for the development and optimization of urban green logistics systems.

ABSTRACT Introduction and aims Sarcopenia is a complication of diabetes mellitus, which can increase hospitalization and lead to poor outcomes. The present study investigated the relationship between the serum musclin concentration and the sarcopenia morbidity in Chinese middle–elderly patients with type 2 diabetes mellitus. Methods We recruited 220 patients with type 2 diabetes mellitus, all of whom completed gait speed, handgrip strength tests, and whole‐body dual‐energy x‐ray measurements to calculate the appendicular skeletal muscle mass index (ASMI). The patients were divided into sarcopenia (n = 110) and non‐sarcopenia groups (n = 110). The serum musclin concentration was measured using an enzyme‐linked immunosorbent assay. Results The serum musclin concentration was significantly lower in the sarcopenia group (712.82 pg/mL) than in the non‐sarcopenia group (922.53 pg/mL). The serum musclin concentration positively correlated with the whole‐body skeletal mass (r = 0.230; P = 0.001). Sarcopenia morbidity declined as the quartile of serum musclin concentration increased (P = 0.001), and a negative correlation was observed between the serum musclin concentration and the prevalence of sarcopenia (odds ratio = 0.998, P = 0.001). The correlation remained when quartiles were considered. Conclusions The serum musclin concentration is an independent protective factor for sarcopenia in Chinese middle‐elderly patients with type 2 diabetes mellitus.

Abstract Objective This study aimed to identify the molecular defects and clinical manifestations in a Chinese family with brachydactyly (BD) type A1 (BDA1) and multiple‐synostoses syndrome 2 (SYNS2). Methods A Chinese family with BDA1 and SYNS2 was enrolled in this study. Whole‐exome sequencing was used to analyze the gene variants in the proband. The sequences of the candidate pathogenic variant in GDF5 was validated via Sanger sequencing. I‐TASSER and PyMOL were used to analyze the functional domains of the corresponding mutant proteins. Results The family was found to have an autosomal‐dominantly inherited combination of BDA1 and SYNS2 caused by the S475N variant in the GDF5 gene. The variant was located within the functional region, and the mutated residue was found to be highly conserved among species. Via bioinformatic analyses, we predicted this variant to be deleterious, which perturb the protein function. The substitution of the negatively charged amino acid S475 with the neutral N475 was predicted to disrupt the formation of salt bridges with Y487 and impair the structure, stability, and function of the protein, consequently, the abnormalities in cartilage and bone development ensue. Conclusions A single genetic variant (S475N) which disrupt the formation of salt bridges with Y487, in the interface of the antagonist‐ and receptor‐binding sites of GDF5 concurrently causes two pathological mechanisms. This is the first report of this variant, identified in a Chinese family with BDA1 and SYNS2.

The control-structure interaction (CSI) between shaking table and eccentric load is one of the most important reasons causing the accuracy degradation of shaking table test. At present, the eccentric ratio (ER) of load and the coupling between actuators pose challenges to study the CSI. Thus, this paper establishes an analytical transfer function matrix of a shaking table and eccentric load. Based on the transfer function matrix, a comprehensive study is conducted to analyse the CSI effect under different eccentric ratio conditions. The analysis proves the influence of the CSI, and the CSI amplifies the actuator coupling more than 22 times at 20.00 Hz. Furthermore, a real-time CSI compensation strategy considering the actuator coupling is proposed. With the adopting of the proposed strategy, the coupling between two actuators is fully eliminated, and the correlation coefficients of ground motion records of two actuators are improved by 14.75% and 5.48%, respectively.

Abstract Interlayer coupling strength dichotomizes two-dimensional (2D) materials into layered and non-layered types. Traditionally, they can be regarded as atomic layers intrinsically linked via van der Waals (vdW) forces or covalent bonds, oriented orthogonally to their growth plane. In our work, we report a material system that differentiates from layered and non-layered materials, termed quasi-layered domino-structured (QLDS) materials, effectively bridging the gap between these two typical categories. Considering the skewed structure, the force orthogonal to the 2D QLDS-GaTe growth plane constitutes a synergistic blend of vdW forces and covalent bonds, with neither of them being perpendicular to the 2D growth plane. This unique amalgamation results in a force that surpasses that in layered materials, yet is weaker than that in non-layered materials. Therefore, the lattice constant contraction along this unique orientation can be as much as 7.7%, tantalizingly close to the theoretical prediction of 10.8%. Meanwhile, this feature endows remarkable anisotropy, second harmonic generation enhancement with a staggering susceptibility of 394.3 pm V−1. These findings endow further applications arranged in nonlinear optics, sensors, and catalysis.

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, with unclear pathogenesis. Although immune disorders, especially T cell infiltration, are thought to play a vital role in PSC, the specific pathogenesis mechanisms remain incompletely understood. This study evaluated the potential key gene associated with the PSC pathogenesis and analyzed the associations of the key gene with prognosis and immune cell infiltration by combining bioinformatics analysis and experimental verification. Methods Transcriptome data of PSC and normal human liver tissues (GSE159676) were obtained from the gene expression omnibus database. Differentially expressed genes (DEGs) were identified, and differences in biological states were analyzed. A protein–protein interaction (PPI) network was constructed. Hub genes were identified, and their expression was verified using transcriptome data of mice fed 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and Mdr2 −/− mice (GSE179993, GSE80776), as well as by immunohistochemistry staining on clinical samples. The correlations between the key gene and other factors were evaluated by Pearson’s correlation coefficient. Immune cell infiltration into human liver (GSE159676) was analyzed by xCell and verified by immunofluorescence staining on PSC liver samples. Results Of the 185 DEGs identified, 113 were upregulated and 72 were downregulated genes in PSC. Genes associated with immune cell infiltration and fibrosis were significantly enriched in PSC. PPI network showed close interactions among DEGs. A module strongly associated with immune infiltration was identified, with annexin A1 (ANXA1) being the core gene. High expression of ANXA1 in PSC was confirmed in two public datasets and by immunohistochemistry staining on clinical samples. High ANXA1 expression was strongly associated with high-risk score for PSC. Also, ANXA1 expression was positively associated with chemokines and chemokine receptors and with the infiltration of immune cells, especially T cells, into liver with PSC. Immune infiltration, fibrosis, and cancer-related processes were markedly enriched in PSC with high expression of ANXA1. Conclusion ANXA1 is a key gene associated with high risk and infiltration of immune cells, especially T cells, in PSC. These findings provide new insight into the key biomarker of PSC and suggest that targeting ANXA1 may be a valuable strategy for the treatment of PSC.

Abstract The tumor vasculature was different from the normal vasculature in both function and morphology, which caused hypoxia in the tumor microenvironment (TME). Previous anti-angiogenesis therapy had led to a modest improvement in cancer immunotherapy. However, antiangiogenic therapy only benefitted a few patients and caused many side effects. Therefore, there was still a need to develop a new approach to affect tumor vasculature formation. The CD93 receptor expressed on the surface of vascular endothelial cells (ECs) and its natural ligands, MMRN2 and IGFBP7, were now considered potential targets in the antiangiogenic treatment because recent studies had reported that anti-CD93 could normalize the tumor vasculature without impacting normal blood vessels. Here, we reviewed recent studies on the role of CD93, IGFBP7, and MMRN2 in angiogenesis. We focused on revealing the interaction between IGFBP7-CD93 and MMRN2-CD93 and the signaling cascaded impacted by CD93, IGFBP7, and MMRN2 during the angiogenesis process. We also reviewed retrospective studies on CD93, IGFBP7, and MMRN2 expression and their relationship with clinical factors. In conclusion, CD93 was a promising target for normalizing the tumor vasculature.

Multifactorial diseases demand therapeutics that can modulate multiple targets for enhanced safety and efficacy, yet the clinical approval of multitarget drugs remains rare. The integration of machine learning (ML) and deep learning (DL) in drug discovery has revolutionized virtual screening. This study investigates the synergy between ML/DL methodologies, molecular representations, and data augmentation strategies. Notably, we found that SVM can match or even surpass the performance of state-of-the-art DL methods. However, conventional data augmentation often involves a trade-off between the true positive rate and false positive rate. To address this, we introduce Negative-Augmented PU-bagging (NAPU-bagging) SVM, a novel semi-supervised learning framework. By leveraging ensemble SVM classifiers trained on resampled bags containing positive, negative, and unlabeled data, our approach is capable of managing false positive rates while maintaining high recall rates. We applied this method to the identification of multitarget-directed ligands (MTDLs), where high recall rates are critical for compiling a list of interaction candidate compounds. Case studies demonstrate that NAPU-bagging SVM can identify structurally novel MTDL hits for ALK-EGFR with favorable docking scores and binding modes, as well as pan-agonists for dopamine receptors. The NAPU-bagging SVM methodology should serve as a promising avenue to virtual screening, especially for the discovery of MTDLs.

This article systematically reviews the extraction and purification methods, structural characteristics, structure–activity relationship, and health benefits of C. speciosa polysaccharides, and their potential application in food, medicine, functional products, and feed, in order to provide a useful reference for future research. Chaenomeles speciosa (Sweet) Nakai. has attracted the attention of health consumers and medical researchers as a traditional Chinese medicine with edible, medicinal, and nutritional benefits. According to this study, C. speciosa polysaccharides have significant health benefits, such as anti-diaetic, anti-inflammatory and analgesic, anti-tumor, and immunomodulatory effects. Researchers determined the molecular weight, structural characteristics, and monosaccharide composition and ratio of C. speciosa polysaccharides by water extraction and alcohol precipitation. This study will lay a solid foundation for further optimization of the extraction process of C. speciosa polysaccharides and the development of their products. As an active ingredient with high value, C. speciosa polysaccharides are worthy of further study and full development. C. speciosa polysaccharides should be further explored in the future, to innovate their extraction methods, enrich their types and biological activities, and lay a solid foundation for further research and development of products containing polysaccharides that are beneficial to the human body.

In this work, within finite liquid spaces confined by elastic walls and the free surface, we investigated the influence of wall and liquid on laser bubble-excited vibrational rarefaction waves, via the dynamics of the laser-induced plasma-mediated bubble and its accompanying small secondary bubble clouds. We observed the modulation of the rebound maximum radius (Rmax2) relative to the first oscillation period (Tosc1) for the laser bubble and the periodic appearance of secondary bubble clouds, which were caused by extra rarefaction waves. We found an approximate constant modulation period of Rmax2 (Tosc1) and increased time intervals between the adjacent secondary bubble clouds with increasing liquid height in the same cuvette, while both of them were remarkably increased with increasing inner size of cuvettes within the same liquid height. This indicated that the cuvette geometry and liquid volume alter the key characteristics of the vibrational rarefaction waves. It was further confirmed that extra rarefaction waves within the liquid are excited by wall vibrations linked to laser bubble expansion and its induced liquid-mass oscillations. Our study provides a better understanding of the interactions of laser-induced cavitation with liquid and elastic walls in confined geometry, which is essential for intraluminal laser surgery.

ABSTRACT Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did not prolong QT interval in animal model studies. This study evaluated the antibacterial activity of this novel compound against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo. The minimum inhibitory concentration (MIC) of WX-081 against three kinds of non-tuberculous mycobacteria (NTM) clinical strains was determined using microplate-based alamarBlue assay (MABA), and the antibacterial activity of WX-081 against NTM in J774A.1 cells and mice was evaluated. MIC ranges of WX-081 against clinical strains of M. avium and M. abscessus were 0.05–0.94 μg/mL, 0.88–7.22 μg/mL (M. abscessus subsp. abscessus), and 0.22–8.67 μg/mL (M. abscessus subsp. massiliense), respectively, which were slightly higher than those of BDQ. For M. avium, M. abscessus, and M. chelonae, WX-081 can reduce the intracellular bacterial load by 0.13–1.18, 0.18–1.50, and 0.17–1.03 log10 colony forming units (CFU)/mL, respectively, in a concentration-dependent manner. WX-081 has bactericidal activity against three NTM species in mice. WX-081 exhibited anti-NTM activity to the same extent as BDQ both in vivo and in vitro. WX-081 is a promising clinical candidate and should be studied further in clinical trials.IMPORTANCEDue to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium chelonae during 2000–2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively.

High catalytic performances of metal-semiconductor heterostructures have gained significant attention in recent years. However, developing fast and low-cost synthesis of multiphase heterojunction catalysts has long been a challenge. Herein, three phases of Cu-CeO2-SrTiO3-δ heterojunction catalyst are successfully synthesized by combining with sol-gel and rapid plasma exsolution method. Using dielectric barrier discharge plasma (DBD), Cu nanoparticles are exsolved and uniformly distributed on the surface of CeO2-SrTiO3-δ. This unique multiphase heterojunction catalyst exhibits superior performance in photothermal reverse water gas shift (RWGS) reactions. The yield of CO from this catalyst is impressive at 11.32 mmol g−1 h−1, 9 times greater than pure SrTiO3, and the selectivity for CO is high (99.95%). The enhanced activity is primarily attributed to the synergistic effect resulting from the incorporation of three phases of Cu nanoparticles, CeO2, and SrTiO3-δ, as well as their interfaces. The increase in oxygen vacancy sites in CeO2 enhances the adsorption of CO2, whereas the doping and exsolution of Cu help to broaden the light absorption range. A significant role is played by the localized surface plasmon resonance (LSPR) effect of Cu nanoparticles in promoting the catalytic performance of RWGS. This study demonstrates a simple and efficient method for fabricating multiphase heterojunction catalysts, providing new strategies for photothermal CO2 reduction.

Abstract The location and origin of Neoproterozoic‐Cambrian sutures provide keys to understand the formation and evolution of the supercontinent Gondwana. The Larsemann Hills is located near a major Neoproterozoic‐Cambrian suture zone in the Prydz Belt, but has not been examined locally by comprehensive geophysical studies. In this study, we analyzed data collected from a one‐dimensional (1D) joint seismic‐MT array deployed during the 36th Chinese National Antarctic Research Expedition. We found that a sharp Moho discontinuity offset of 6–8 km shows up in the stacked image of teleseismic P‐wave receiver function analysis; coinciding with the abrupt Moho offset, a near‐vertical channel with (a) low resistivity extending to the uppermost mantle depths, and (b) high crustal Poisson's ratio in the crust is identified. These findings provide evidence for the determination of the location and collisional nature of the Prydz belt or a portion of it.

Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action.

We investigated laser-induced cavitation dynamics in a small container with elastic thin walls and free or partially confined surface both experimentally and by numerical investigations. The cuvette was only 8–25 times larger than the bubble in its center. The liquid surface was either free, or two thirds were confined by a piston-shaped pressure transducer. Different degrees of confinement were realized by filling the liquid up to the transducer surface or to the top of the cuvette. For reference, some experiments were performed in free liquid. We recorded the bubble dynamics simultaneously by high-speed photography, acoustic measurements, and detection of probe beam scattering. Simultaneous single-shot recording of radius-time curves and oscillation times enabled to perform detailed investigations of the bubble dynamics as a function of bubble size, acoustic feedback from the elastic walls, and degree of surface confinement. The bubble dynamics was numerically simulated using a Rayleigh-Plesset model extended by terms describing the acoustically mediated feedback from the bubble’s environment.Bubble oscillations were approximately spherical as long as no secondary cavitation by tensile stress occurred. Bubble expansion was always similar to the dynamics in free liquid, and the environment influenced mainly the collapse phase and subsequent oscillations. For large bubbles, strong confinement led to a slight reduction of maximum bubble size and to a pronounced reduction of the oscillation time, and both effects increased with bubble size. The joint action of breakdown-induced shock wave and bubble expansion excites cuvette wall vibrations, which produce alternating pressure waves that are focused onto the bubble. This results in a prolongation of the collapse phase and an enlargement of the second oscillation, or in time-delayed re-oscillations. The details of the bubble dynamics depend in a complex manner on the degree of surface confinement and on bubble size. Numerical simulations of the first bubble oscillation agreed well with experimental data. They suggest that the alternating rarefaction/compression waves from breakdown-induced wall vibrations cause a prolongation of the first oscillation. By contrast, liquid mass movement in the cuvette corners result in wall vibrations causing late re-oscillations. The strong and rich interaction between the bubble and its surroundings may be relevant for a variety of applications such as intraluminal laser surgery and laser-induced cavitation in microfluidics.

ATP13A2 is a lysosomal polyamine transporter, mutated in several diseases including juvenile-onset Parkinson’s disease. Here, the authors report structures of human ATP13A2 in six distinct intermediate states, illustrating most of its conformational cycle.

Halo-alkali soil threatens agriculture, reducing growth and crop yield worldwide. In this study, physicochemical and molecular techniques were employed to explore the potential of halo-alkali-tolerant endophytic bacteria strains Sphingomonas sp. pp01, Bacillus sp. pp02, Pantoea sp. pp04, and Enterobacter sp. pp06 to enhance the growth of hybrid Pennisetum under varying saline conditions. The strains exhibited tolerance to high salt concentrations, alkaline pH, and high temperatures. Under controlled conditions, all four strains showed significant growth-promoting effects on hybrid Pennisetum inoculated individually or in combination. However, the effects were significantly reduced in coastal saline soil. The best growth-promoting effect was achieved under greenhouse conditions, increasing shoot fresh and dry weights of hybrid Pennisetum by up to 457.7% and 374.7%, respectively, using irrigating trials. Metagenomic sequencing analysis revealed that the diversity and composition of rhizosphere microbiota underwent significant changes after inoculation with endophytic bacteria. Specifically, pp02 and co-inoculation significantly increased the Dyella and Pseudomonas population. Firmicutes, Mycobacteria, and Proteobacteria phyla were enriched in Bacillus PP02 samples. These may explain the best growth-promoting effects of pp02 and co-inoculation on hybrid Pennisetum under greenhouse conditions. Our findings reveal the performance of endophytic bacterial inoculants in enhancing beneficial microbiota, salt stress tolerance, and hybrid Pennisetum growth.

Drought is one of the most frequent types of natural disasters in the world, and it has been classified into several different categories. Generally, meteorological drought is considered to be the beginning of a drought disaster, while socio-economic drought is the possible ultimate result. However, controversy remains around the main impact factors in the propagation from meteorological drought to socio-economic drought over the past decades. In this study, a comprehensive investigation of the 2022 drought event in the city of Lishui, China was conducted to build a model for analyzing the main impact factors in the propagation from meteorological drought to socio-economic drought. The results showed that the 2022 drought event had a great impact on the city’s socio-economic activities. According to governmental reports on socio-economic drought and basic information on water sources, a random forest attribution analysis model was built. The model demonstrated a great performance in distinguishing whether a socio-economic drought had occurred, with an accuracy of 0.9935, a true positive rate of 0.9489 and a false positive rate of 0.0021. Additionally, the variables related to water sources—including drainage area, covered population and daily water supply volume—were found to be more important than the other variables related to meteorological conditions in the model, meaning that the capacity of water sources is the main impact factor in the propagation between meteorological drought and socio-economic drought. In other words, it is feasible to prevent the propagation of meteorological drought to socio-economic drought through water conservancy engineering construction.

The existence of defects in the enclosure structure is the primary cause of water and sand leakage in foundation pits, as well as being a significant source of danger in pit construction, but current research lacks an in-depth investigation of the generation mechanism and gestation process. In this paper, which comprehensively considers the microscopic particles and macroscopic level, the development mechanism of a water and sand leakage disaster in a foundation pit with a water-rich sand layer was studied using the principle of computational fluid dynamics and discrete element method coupled analysis (CFD–DEM); moreover, based on the anisotropy of the particle force and fluid energy analysis, the deformation of the stratum and ground stress field were analyzed. The results show that the stress field will produce a plugging effect at a certain distance from the defect, and the strata exhibit a dominant displacement tendency in the vertical direction, resulting in the emergence of a gradually concave stress relaxation zone and an elliptical contour in the strata displacement map near the defect. The fluid energy describes the displacement of the sand layer very well, and it is separated into the sand layer’s centralized loss region and the major loss area based on the high and low levels of the fluid energy class. The impact of fluid at the defect reaches the maximum kinetic energy, which penetrates the structural weakness and causes the loss of sand particles, and the cross-section of the water influx near the defect gradually expands with the loss of particles, indicating that there is a danger of further expansion of the defect under the impact of water flow. These results have technical implications for the management of water and sand leakage disasters in foundation pit engineering.

IntroductionLung cancer is a major cause of illness and death worldwide. Lung adenocarcinoma (LUAD) is its most common subtype. Metabolite-mRNA interactions play a crucial role in cancer metabolism. Thus, metabolism-related mRNAs are potential targets for cancer therapy.MethodsThis study constructed a network of metabolite-mRNA interactions (MMIs) using four databases. We retrieved mRNAs from the Tumor Genome Atlas (TCGA)-LUAD cohort showing significant expressional changes between tumor and non-tumor tissues and identified metabolism-related differential expression (DE) mRNAs among the MMIs. Candidate mRNAs showing significant contributions to the deep neural network (DNN) model were mined. Using MMIs and the results of function analysis, we created a subnetwork comprising candidate mRNAs and metabolites.ResultsFinally, 10 biomarkers were obtained after survival analysis and validation. Their good prognostic value in LUAD was validated in independent datasets. Their effectiveness was confirmed in the TCGA and an independent Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset by comparison with traditional machine-learning models.ConclusionTo summarize, 10 metabolism-related biomarkers were identified, and their prognostic value was confirmed successfully through the MMI network and the DNN model. Our strategy bears implications to pave the way for investigating metabolic biomarkers in other cancers.

ABSTRACT Clofazimine (CFZ) has been repurposed for treating tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB). However, the mechanisms of resistance to clofazimine are poorly understood. We previously reported a mutation located in the intergenic region of Rv1453 that was linked to resistance to CFZ and demonstrated that an Rv1453 knockout resulted in an increased minimum inhibitory concentration (MIC) of CFZ. The current study aims to go back and describe in detail how the mutation was identified and further explore its association with CFZ resistance by testing additional 30 isolates. We investigated MICs of clofazimine against 100 clinical strains isolated from MDR-TB patients by microplate alamarBlue assay. Whole-genome sequencing (WGS) was performed on 11 clofazimine-resistant and 7 clofazimine-susceptible strains, including H37Rv. Among the 11 clofazimine-resistant mutants subjected to WGS, the rate of mutation in the intergenic region of the Rv1453 gene was 55% (6/11) in clofazimine-resistant strains. Among another 30 clofazimine-resistant clinical isolates, 27 had mutations in the intergenic region of the Rv1453 gene. A mutation in the Rv1453 gene associated with clofazimine resistance was identified, which shed light on the mechanisms of action and resistance of clofazimine. IMPORTANCE Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, especially the emergence of multidrug-resistant tuberculosis (MDR-TB) brings great distress to humans. Clofazimine (CFZ) plays an important role in the treatment of MDR-TB. To understand the underlying mechanism of clofazimine resistance better, in this study, we review and detail the findings of the mutation of intergenic region of Rv1453 and find additional evidence that this mutation is related to clofazimine resistance in 30 additional isolates. The significance of our research is to contribute to a comprehensive understanding of clofazimine-resistant mechanisms, which is critical for reducing the emergence of resistance and for anti-TB drug discovery.

Background: A new, effective anti-tuberculosis (TB) regimen containing bedaquiline (BDQ) and pyrifazimine (TBI-166) has been recommended for a phase IIb clinical trial. Preclinical drug–drug interaction (DDI) studies of the combination of BDQ and TBI-166 have been designed to support future clinical trials. In this study, we investigated whether a DDI between BDQ and TBI-166 affects the pharmacokinetics of BDQ.Methods: We performed in vitro quantification of the fractional contributions of the fraction of drug metabolism by individual CYP enzymes (fm) of BDQ and the inhibition potency of key metabolic pathways of TBI-166. Furthermore, we conducted an in vivo steady-state pharmacokinetics study in a murine TB model and healthy BALB/c mice.Results: The in vitro fm value indicated that the CYP3A4 pathway contributed more than 75% to BDQ metabolism to N-desmethyl-bedaquiline (M2), and TBI-166 was a moderate (IC50 2.65 µM) potential CYP3A4 inhibitor. Coadministration of BDQ and TBI-166 greatly reduced exposure to metabolite M2 (AUC0-t 76310 vs 115704 h ng/mL, 66% of BDQ alone), whereas the exposure to BDQ and TBI-166 did not changed. The same trend was observed both in healthy and TB model mice. The plasma concentration of M2 decreased significantly after coadministration of BDQ and TBI-166 and decreased further during treatment in the TB model.Conclusions: In conclusion, our results showed that the combination of BDQ and TBI-166 significantly reduced exposure to the toxic metabolite M2 by inhibiting the activity of the CYP3A4 pathway. The potential safety and efficacy benefits demonstrated by the TB treatment highly suggest that coadministration of BDQ and TBI-166 should be studied further.

In this paper, the passive event-triggered control problem for networked control systems with actuator faults is of concern. A sufficient condition is proposed by a Lyapunov-Krasovskii functional, under which such type continuous-time Networked control systems with actuator faults are asymptotically stable and passive. The designing method of controller is developed by using Wirtinger inequality and linear matrix inequalities (LMIs). The given strategy can reduce the number of transmissions, thus saving the communication resources. Finally, two numerical examples are provided to demonstrate the effectiveness of the proposed method.

Machine learning provides a powerful alternative data-driven approach to accomplish many petrophysical tasks from subsurface data. It can assimilate information from large and rich data bases and infer relations, rules, and knowledge hidden in the data. When the physics behind data becomes extremely complex, inexplicit, or even unclear/unknown, machine learning approaches have the advantage of being more flexible with wider applicability over conventional physics-based interpretation models. Moreover, machine learning can be utilized to assist many labor-intensive human interpretation tasks such as bad data identification, facies classification, and geo-features segmentation out of imagery data.However, the validity of the outcome from machine learning largely depends on the quantity, quality, representativeness, and relevance of the feeding data including accurate labels. To achieve the best performance, it requires significant effort in data preparation, feature engineering, algorithm selection, architecture design hyperparameter tuning, and regularization. In addition, it needs to overcome technical issues such as imbalanced population, overfitting, and underfitting.In this paper, advantages, limitations, and conditions of using machine learning to solve petrophysics challenges are discussed. The capability of machine learning algorithms in accomplishing different challenging tasks can only be achieved by overcoming its own limitations. Machine learning, if properly utilized, can become a powerful disruptive tool for assisting a series of critical petrophysics tasks.

Abstract Objective To evaluate the value of the ACEF II score in predicting postoperative hospital death and acute kidney injury requiring dialysis (AKI-D) in Chinese patients. Methods This retrospective study included adult patients who underwent cardiopulmonary bypass open heart surgery between January 2010 and December 2015 at Guangdong Provincial People’s Hospital. ACEF II was evaluated to predict in-hospital death and AKI-D using the Hosmer–Lemeshow goodness of fit test for calibration and area under the receiver operating characteristic (ROC) curve for discrimination in non-elective and elective cardiac surgery. Results A total of 9748 patients were included. Among them, 1080 underwent non-elective surgery, and 8615 underwent elective surgery. Mortality was 1.8% (177/9748). In elective surgery, the area under the ROC (AUC) of the ACEF II score was 0.704 (95% CI: 0.648–0.759), similar to the ACEF score of 0.709 (95% CI: 0.654–0.763). In non-elective surgery, the AUC of the ACEF II score was 0.725 (95% CI: 0.663–0.787), higher than the ACEF score (AUC = 0.625, 95% CI: 0.553–0.697). The incidence of AKI-D was 3.5% (345/9748). The AUC of the ACEF II score was 0.718 (95% CI: 0.687–0.749), higher than the ACEF score (AUC = 0.626, 95% CI: 0.594–0.658). Conclusion ACEF and ACEF II have poor discrimination ability in predicting AKI-D in non-elective surgery. The ACEF II and ACEF scores have the same ability to predict in-hospital death in elective cardiac surgery, and the ACEF II score is better in non-elective surgery. The ACEF II score can be used to assess the risk of AKI-D in elective surgery in Chinese adults.

BackgroundThe dynamics of education and student life have changed since the COVID-19 pandemic. Our society, especially the education system, has become largely dependent on the Internet. This paradigm shifts largely took place in the last few decades. As such, there are various ways in which we cannot comprehend the impact that the Internet can have on student psychology, and how multiple other factors could influence that. Internet addiction and its relationship with academic burnout, along with the impact of loneliness, are all essential factors that must be discussed candidly in the post-COVID-19 era. Hence, the objective of this study was, therefore, to explore the relationship between Internet addiction, loneliness, and academic burnout among Chinese college students as well as the mediating role of loneliness.MethodsWe conducted a cross-sectional questionnaire survey at a Chinese university from October to November 2022. In total, 810 valid respondents were selected via random cluster sampling using the well-established Internet Addiction, Loneliness, and Academic Burnout Scale. The primary approach of mediation analysis and structural equation modeling testing examined the relationships among the three components.ResultsInternet addiction could be responsible for academic burnout among college students. Loneliness partially mediates the relationship between Internet addiction and academic burnout. In a mediated way, different types of loneliness contribute to different types of academic burnout.ConclusionPsychological interventions for loneliness, especially emotional loneliness prevention, are the critical aspects of the problem of Internet addiction accompanied with academic burnout. The causal relationship between Internet addiction and academic burnout, possibly of a two-way nature, needs to be further explored in the next future.

The field of two dimensional (2D) materials experienced a surge of discoveries after the isolation of graphene. Among these, the transition metal compounds of Molybdenum and tungsten have been the most extensively studied materials after graphene. More recently, their group member chromium has only recently come to the limelight after the discovery of its exciting magnetic properties. As such the body of work surrounding 2D chromium-based materials is growing. Here, we present an up-to-date summary of the chromium 2D materials showing the latest advances in their experimental synthesis, characterization and the applications of 2D Chromium-based compounds. Finally, we conclude with a perspective on the future of 2D chromium-based materials. We believe that this study will be helpful to understand the field of chromium-based 2D compounds.

Hypertrophic cardiomyopathy (HCM) is the most prominent cause of sudden cardiac death in young people. Due to heterogeneity in clinical manifestations, conventional HCM drugs have limitations for mitochondrial hypertrophic cardiomyopathy. Discovering more effective compounds would be of substantial benefit for further elucidating the pathogenic mechanisms of HCM and treating patients with this condition. We previously reported the MT-RNR2 variant associated with HCM that results in mitochondrial dysfunction. Here, we screened a mitochondria-associated compound library by quantifying the mitochondrial membrane potential of HCM cybrids and the survival rate of HCM-induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) in galactose media. 1-Deoxynojirimycin (DNJ) was identified to rescue mitochondrial function by targeting optic atrophy protein 1 (OPA1) to promote its oligomerization, leading to reconstruction of the mitochondrial cristae. DNJ treatment further recovered the physiological properties of HCM iPSC-CMs by improving Ca2+ homeostasis and electrophysiological properties. An angiotensin II-induced cardiac hypertrophy mouse model further verified the efficacy of DNJ in promoting cardiac mitochondrial function and alleviating cardiac hypertrophy in vivo. These results demonstrated that DNJ could be a potential mitochondrial rescue agent for mitochondrial hypertrophic cardiomyopathy. Our findings will help elucidate the mechanism of HCM and provide a potential therapeutic strategy.

Objectives This retrospective cohort study investigated the association of socioeconomic status with survival outcomes among patients with nasopharyngeal carcinoma in an endemic area of China. Methods The primary endpoint was overall survival. Survival outcomes were estimated by the Kaplan-Meier method and compared by the log-rank test, and the multivariate Cox proportional hazards model was used to estimate hazard ratios, 95% CIs, and independent prognostic factors. Results A total of 11 069 adult patients with NPC were enrolled and included in the analysis. Kaplan-Meier survival analysis revealed that overall survival was significantly different among socioeconomic status. Compared with high socioeconomic status patients, low socioeconomic status patients (HR, 1.190; 95% CI, 1.063-1.333) and medium socioeconomic status patients (HR, 1.111; 95% CI, 1.006-1.226) were associated with increased hazard ratio (HR) of overall survival. Conclusion This analysis highlights patients with nasopharyngeal carcinoma who had high socioeconomic status had better overall survival compared with those who had low and medium socioeconomic status.

The liver is the central metabolic organ and produces 85–90% of the proteins found in plasma. Accordingly, the plasma proteome is an attractive source of liver disease biomarkers that reflects the different cell types present in this organ, as well as the processes such as responses to acute and chronic injury or the formation of an extracellular matrix. In the first part, we summarize the biomarkers routinely used in clinical evaluations and their biological relevance in the different stages of non-malignant liver disease. Later, we describe the current proteomic approaches, including mass spectrometry and affinity-based techniques, that allow a more comprehensive assessment of the liver function but also require complex data processing. The many approaches of analysis and interpretation and their potential caveats are delineated. While these advances hold the promise to transform our understanding of liver diseases and support the development and validation of new liver-related drugs, an interdisciplinary collaboration is needed.