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Efficient fire response and the coordination of various fire vehicles are paramount for delivering optimal services and conducting effective rescue operations. This study explores the challenges of cooperative station location and vehicle assignment, focusing on the synergistic dispatch of fire vehicles from multiple stations. It highlights that the response time of the last arriving vehicle, crucial for forming a complete and effective response unit, is a critical determinant in the overall success of fire rescue operations. The primary objective of the model is to minimize the total system cost, encompassing both the capital investment in fire stations and the potential losses from fire incidents. By employing a Lagrangian relaxation technique, the model effectively simplifies the optimization challenge into more manageable sub-problems, thereby enhancing solution accuracy. The robustness and flexibility of the model were tested through simulations in a hypothetical network and a real-world scenario, using data from urban fire services. The results demonstrate the model’s scalability and adaptability to different network configurations and operational constraints, showcasing its potential to substantially enhance emergency response efficiency and decision-making in urban fire management. This research makes a significant contribution to emergency response management by providing a validated framework that improves the coordination and effectiveness of fire rescue operations, thereby reducing fire damage and enhancing public safety.

Abstract Recurrent breast cancers often develop resistance to standard-of-care therapies. Identifying targetable factors contributing to cancer recurrence remains the rate-limiting step in improving long-term outcomes. In this study, we identify tumor cell-derived osteopontin as an autocrine and paracrine driver of tumor recurrence. Osteopontin promotes tumor cell proliferation, recruits macrophages, and synergizes with IL-4 to further polarize them into a pro-tumorigenic state. Macrophage depletion and osteopontin inhibition decrease recurrent tumor growth. Furthermore, targeting osteopontin in primary tumor-bearing female mice prevents metastasis, permits T cell infiltration and activation, and improves anti-PD-1 immunotherapy response. Clinically, osteopontin expression is higher in recurrent metastatic tumors versus female patient-matched primary breast tumors. Osteopontin positively correlates with macrophage infiltration, increases with higher tumor grade, and its elevated pathway activity is associated with poor prognosis and long-term recurrence. Our findings suggest clinical implications and an alternative therapeutic strategy based on osteopontin’s multiaxial role in breast cancer progression and recurrence.

Abstract Graphene has been extensively utilized as an electrode material for nonaqueous electrochemical capacitors. However, a comprehensive understanding of the charging mechanism and ion arrangement at the graphene/electrolyte interface remain elusive. Herein, a gap-enhanced Raman spectroscopic strategy is designed to characterize the dynamic interfacial process of graphene with an adjustable number of layers, which is based on synergistic enhancement of localized surface plasmons from shell-isolated nanoparticles and a metal substrate. By employing such a strategy combined with complementary characterization techniques, we study the potential-dependent configuration of adsorbed ions and capacitance curves for graphene based on the number of layers. As the number of layers increases, the properties of graphene transform from a metalloid nature to graphite-like behavior. The charging mechanism shifts from co-ion desorption in single-layer graphene to ion exchange domination in few-layer graphene. The increase in area specific capacitance from 64 to 145 µF cm –2 is attributed to the influence on ion packing, thereby impacting the electrochemical performance. Furthermore, the potential-dependent coordination structure of lithium bis(fluorosulfonyl) imide in tetraglyme ([Li(G4)][FSI]) at graphene/electrolyte interface is revealed. This work adds to the understanding of graphene interfaces with distinct properties, offering insights for optimization of electrochemical capacitors.

Abstract The spatiotemporal regulation of inflammasome activation remains unclear. To examine the mechanism underlying the assembly and regulation of the inflammasome response, here we perform an immunoprecipitation-mass spectrometry analysis of apoptosis-associated speck-like protein containing a CARD (ASC) and identify NCF4/1/2 as ASC-binding proteins. Reduced NCF4 expression is associated with colorectal cancer development and decreased five-year survival rate in patients with colorectal cancer. NCF4 cooperates with NCF1 and NCF2 to promote NLRP3 and AIM2 inflammasome activation. Mechanistically, NCF4 phosphorylation and puncta distribution switches from the NADPH complex to the perinuclear region, mediating ASC oligomerization, speck formation and inflammasome activation. NCF4 functions as a sensor of ROS levels, to establish a balance between ROS production and inflammasome activation. NCF4 deficiency causes severe colorectal cancer in mice, increases transit-amplifying and precancerous cells, reduces the frequency and activation of CD8+ T and NK cells, and impairs the inflammasome-IL-18-IFN-γ axis during the early phase of colorectal tumorigenesis. Our study implicates NCF4 in determining the spatial positioning of inflammasome assembly and contributing to inflammasome-mediated anti-tumor responses.

BackgroundIntestinal fungal composition plays a crucial role in modulating host health, and thus is of great significance in the conservation of endangered bird species. However, research on gut fungal composition in birds is limited. Therefore, in this study, we aimed to examine gut fungal community and potential fecal pathogen composition in wild Arborophila rufipectus.MethodsFecal samples were collected from the habitats of wild A. rufipectus and Lophura nycthemera (a widely distributed species belonging to the same family as A. rufipectus) in summer and autumn. Thereafter, RNA was collected and the internal transcribed spacer rRNA gene was sequenced via high-throughput sequencing to investigate seasonal variations in intestinal core fungi, microbial fungi, and potential pathogenic fungi.ResultsThe gut microbiota of A. rufipectus and L. nycthemera were highly similar and mainly consisted of three phyla, Ascomycota (58.46%), Basidiomycota (28.80%), and Zygomycota (3.56%), which accounted for 90.82% of the fungal community in all the samples. Further, the predominant genera were Ascomycota_unclassified (12.24%), Fungi_unclassified (8.37%), Davidiella (5.18%), Helotiales_unclassified (2.76%), Wickerhamomyces (1.84%), and Pleosporales_unclassified (1.14%), and the potential fecal pathogens identified included Candida, Cryptococcus, Trichosporon, and Malassezia.ConclusionOur results provide evidence that the diversity of intestinal fungi in the endangered species, A. rufipectus, is similar to that in the common species, L. nycthemera, and may serve as a basis for monitoring the status of A. rufipectus and for developing conservation measures.

Objective: Resistin (RETN) is an adipocyte-specific hormone that participates in metabolism and modulates cellular inflammation. Our study aimed to assess the effects of RETN treatment on autophagy and the underlying molecular and biological mechanisms in bovine alveolar macrophages (BAMs). Methods: The optimal concentration of RETN + lipopolysaccharide (LPS) on macrophages was screened and then used to co-culture with alveolar macrophages. Autophagosomes in BAMs were examined using a transmission electron microscope (TEM). Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression of microtubule-associated protein light chain 3 (LC3) and p62. Western blot (WB) was used to detect the protein expressions of LC3 and p62. The distribution of LC3 and p62 proteins in the cells was observed by immunofluorescence (IF). The concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were detected using enzyme-linked immunosorbent assay (ELISA). The protein expression of adenosine-monophosphate-activated protein kinase (AMPK), p-AMPK, mammalian target of rapamycin (mTOR), and p-mTOR was detected using WB. Results: The treatment of BAMs with RETN or LPS increased the number of autophagosomes and the ratio of LC3II/LC3I and decreased the expression level of p62 protein. RETN treatment significantly triggered autophagy compared to LPS treatment. Moreover, the ratios of p-AMPK/AMPK and p-mTOR/mTOR were upregulated and downregulated, respectively, after RETN treatment, suggesting that AMPK/mTOR signaling pathway activation is required for RETN-mediated autophagy in BAMs. Additionally, the ratio of LC3-II/LC3-I was lower, and the concentrations of IL-1β, IL-6, and TNF-α significantly decreased in the LPS and RETN co-treatment groups compared to the single LPS treatment group. However, both autophagy- and LPS-induced inflammation were partially alleviated by RETN treatment. Conclusion: RETN can promote autophagy in BAMs by activating the AMPK/mTOR signaling pathway, it may help prevent LPS-induced inflammation.

BackgroundElectronic medical record (EMR) systems are essential in health care for collecting and storing patient medical data. They provide critical information to doctors and caregivers, facilitating improved decision-making and patient care. Despite their significance, optimizing EMR systems is crucial for enhancing health care quality. Implementing the Observational Medical Outcomes Partnership (OMOP) shared data model represents a promising approach to improve EMR performance and overall health care outcomes. ObjectiveThis study aims to evaluate the effects of implementing the OMOP shared data model in EMR systems and to assess its impact on enhancing health care quality. MethodsIn this study, 3 distinct methodologies are used to explore various aspects of health care information systems. First, factor analysis is utilized to investigate the correlations between EMR systems and attitudes toward OMOP. Second, the best-worst method (BWM) is applied to determine the weights of criteria and subcriteria. Lastly, the decision-making trial and evaluation laboratory technique is used to illustrate the interactions and interdependencies among the identified criteria. ResultsIn this research, we evaluated the AliHealth EMR system by surveying 98 users and practitioners to assess its effectiveness and user satisfaction. The study reveals that among all components, “EMR resolution” holds the highest importance with a weight of 0.31007783, highlighting its significant role in the evaluation. Conversely, “EMR ease of use” has the lowest weight of 0.1860467, indicating that stakeholders prioritize the resolution aspect over ease of use in their assessment of EMR systems. ConclusionsThe findings highlight that stakeholders prioritize certain aspects of EMR systems, with “EMR resolution” being the most valued component.

Abstract Background The triglyceride and glucose (TyG) index, a simple surrogate marker of insulin resistance, is related to cardiovascular disease. However, there is a lack of evidence for the relationship between the TyG index and chest pain. This study aimed to investigate the association of the TyG index with chest pain and to evaluate the relationship between the TyG index and all-cause mortality in participants with or without chest pain. Methods The present study utilized data from the 2001–2012 National Health and Nutrition Examination Survey (NHANES), employing a combination of cross-sectional and cohort study designs. The association between the TyG index and chest pain was investigated using weighted logistic regression models. Weighted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality. Restricted cubic spline analysis was used to explore linear or nonlinear relationships between the TyG index and chest pain or all-cause mortality. Results The findings revealed a positive correlation between the TyG index and chest pain, even after adjusting for potential confounding factors (quartile 4 versus quartile 1, odds ratio [OR] 1.42, 95% confidence interval [CI] 1.14–1.77, P = 0.002). During a mean follow-up time of 139 months, a total of 2286 individuals (27.43%) experienced mortality. Weighted multivariate Cox regression models indicated that for each one-unit increase in the TyG index, the adjusted hazard ratio (HR) for mortality was 1.14 (95% CI = 0.94–1.37) for participants with chest pain and 1.25 (95% CI = 1.09–1.43) for those without chest pain. Furthermore, restricted cubic spline analysis revealed a linear relationship between the TyG index and chest pain (P for nonlinearity = 0.902), whereas a nonlinear relationship was shown between the TyG index and all-cause mortality among populations regardless of chest pain (all P for nonlinearity

T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells. A promising strategy is the use of peptide-major histocompatibility class I bispecific antibodies (pMHC-IgGs), which have emerged as an intriguing modality of TCE, based on their ability to selectively redirect highly reactive viral-specific effector memory cytotoxic CD8+ T cells to eliminate cancer cells. However, the relatively low frequency of these effector memory cells in human peripheral blood mononuclear cells (PBMCs) may hamper their redirection as effector cells for clinical applications. To mitigate this potential limitation, we report here the generation of a pMHC-IgG derivative known as guided-pMHC-staging (GPS) carrying a covalent fusion of a monovalent interleukin-2 (IL-2) mutein (H16A, F42A). Using an anti-epidermal growth factor receptor (EGFR) arm as a proof-of-concept, tumor-associated antigen paired with a single-chain HLA-A *02:01/CMVpp65 pMHC fusion moiety, we demonstrate in vitro that the IL-2-armored GPS modality robustly expands CMVpp65-specific CD8+ effector memory T cells and induces potent cytotoxic activity against target cancer cells. Similar to GPS, IL-2-armored GPS molecules induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted TCE. In vivo we show that IL-2-armored GPS, but not the corresponding GPS, effectively expands grafted CMVpp65 CD8+ T cells from unstimulated human PBMCs in an NSG mouse model. Lastly, we demonstrate that the IL-2-armored GPS modality exhibits a favorable developability profile and monoclonal antibody-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, IL-2-armored GPS represents an attractive approach for treating cancer with the potential for inducing vaccine-like antiviral T cell expansion, immune cell redirection as a TCE, and significantly widened TI due to reduced cytokine release.

In the era of emerging technologies, the transportation system is witnessing the introduction of innovative mobility services, such as autonomous vehicles, which possess unique service features that cannot be seen from conventional travel modes. To facilitate the understanding of the behavioral impacts and the adoption of innovative mobilities, a novel binary weibit model with an oddball alternative (BW-O) is developed for the binary choice between conventional and emerging mobilities. The BW-O model explicitly considers the unprecedented (or unique) service features of emerging travel modes while retaining the closed-form choice probability. This study empirically illustrates the application of the BW-O model in the mode choice context. The desirable properties of the BW-O model compared to the existing binary choice models are discussed both theoretically and empirically. In the binary mode choice problem with an emerging travel mode, the unique service features of the emerging mode can lead to the “oddball” effect and “superstar” effect, which play a critical role in the travel behavior and mode adoption. The BW-O model inherently captures both effects by considering a higher perception variance for the emerging mode and asymmetric choice probabilities between different modes. Thus, as revealed by the empirical results, the BW-O model outperforms the basic binary weibit model in terms of both model fit and predictive power. The developed BW-O model is not only applicable to the mode choice problem in transportation systems, but also opens a door for more general class-imbalanced binary choice contexts where an alternative has additional attractiveness and asymmetric choice probability.

Objectives: We investigated how booster interval affects the risks of SARS-CoV-2 infection and Covid-19-related hospitalization and death in different age groups. Methods: We collected data on booster receipts and Covid-19 outcomes between September 22, 2021 and February 9, 2023 for 5,769,205 North Carolina residents ≥12 years of age who had completed their primary vaccination series. We related Covid-19 outcomes to baseline characteristics and booster doses through Cox regression models. Results: For adults ≥65 years of age, boosting every 9 months was associated with proportionate reductions (compared with no boosting) of 18.9% (95% CI, 18.5-19.4) in the cumulative frequency of infection, 37.8% (95% CI, 35.3-40.3) in the cumulative risk of hospitalization or death, and 40.9% (95% CI, 37.2-44.7) in the cumulative risk of death at 2 years after completion of primary vaccination. The reductions were lower by boosting every 12 months and higher by boosting every 6 months. The reductions were smaller for individuals 12-64 years of age. Conclusion: Boosting at a shorter interval was associated with a greater reduction in Covid-19 outcomes, especially hospitalization and death. Frequent boosting conferred greater benefits for individuals aged ≥65 than for individuals aged 12-64.

Despite the recent proliferation of scholarly investigations on servant leadership, clarity remains elusive regarding the specific mechanisms and conditions underpinning employee cognitive processes and their responses to servant leadership. Drawing upon social cognitive theory, proposes a moderated mediation model tested through a time-lagged field data from 489 employees in Study 1 and an experimental data in Study 2. We found that servant leadership indirectly enhances employee voice behavior through increased employee work reflection. Additionally, we considered employee proactive personality as a boundary condition for the positive effect of servant leadership. Our results show that servant leadership prompts employee work reflection only when the level of employee proactive personality is high, which in turn increases employee voice behavior. This study presents significant theoretical and practical implications through the integration of social cognitive theory with servant leadership research.

Abstract This study identified four patterns of regional extreme precipitation events (REPEs) in Central Asia (CA) and their crucial synoptic systems and multiscale interactions. Four patterns with distinct spatial distributions were identified in: northern Kazakhstan, southern Xinjiang, western CA, and the Tianshan Mountains. Focusing on the three most frequent REPEs, the kinetic energy (KE) cross‐scale transfer from the basic‐to synoptic‐scale windows exhibited a zonal dipole, resulting in the development and enhancement of REPEs in northern Kazakhstan. The available potential energy (APE) cross‐scale transfer exhibited opposing patterns between the upper and lower troposphere, indicating baroclinic instability in the lower troposphere and barotropic instability of the basic flow in the upper troposphere. Both mechanisms enhanced the Central Asian vortices (CAVs) in southern Xinjiang and induced REPEs. Conversely, the energy budgets exhibited baroclinic instability of the basic flow throughout the entire region when the Tianshan Mountains REPEs occurred, providing energy for prevalent CAVs.

Abstract Objectives Calcifying nanoparticles (CNPs), referred to as nanobacteria (NB), are recognized to be associated with ectopic calcification. This study aims to isolate and culture CNPs from the dental plaque of patients with periodontal disease and investigate their possible role in unravelling the aetiology of periodontal disease. Material and Methods Supragingival and subgingival plaques were sampled from 30 periodontitis patients for CNPs isolation and culture. Alkaline phosphatase (ALP) content changes were tracked over time. Positive samples underwent thorough morphological identification via hematoxylin and eosin (HE) staining, Alizarin red S (ARS), and transmission electron microscopy (TEM). The chemical composition of CNPs analysis involved calcium (Ca) and phosphorus (P) content determination, Fourier transform infrared spectroscopy (FTIR), and X‐ray diffraction (XRD). Results The subgingival plaque dental group exhibited a higher CNPs isolation rate at 36.67% (11/30) compared to the supragingival dental plaque group at 66.67% (20/30). ALP activity varied among the positive, negative and control groups. Morphological observation characterized the CNPs as round, oval, and ellipsoid particles with Ca deposits. Chemical analysis revealed the Ca/P ratio was 0.6753. Hydroxyl, methyl, carbonate, phosphate, hydrogen phosphate, and dihydrogen phosphate were detected by FTIR; the main chemical components detected by XRD were hydroxyapatite and tricalcium phosphate. Conclusion CNPs were found in periodontitis‐related dental plaque and exhibited the potential to develop calcified structures resembling dental calculus. However, the potential involvement of ALP in CNPs formation requires deeper exploration, as does the precise nature of its role and the interrelation with periodontitis demand a further comprehensive investigation.

Abstract Background Since the outbreak of the COVID-19 pandemic, telemedicine become more and more popular, patients attempt to use telemedicine to meet personal medical needs. Patient satisfaction is a key indicator of insight into the patient experience. Purpose This systematic review aims to explore the measurement factors of patient satisfaction with telemedicine and develop a more comprehensive and systematic scale of patient satisfaction with telemedicine. Methods In February 2023, a literature search was conducted on the PubMed, EMBASE, and Web of Science, identifying measurement factors and tools of patient satisfaction with telemedicine. For inclusion, the studies had to have or make a questionnaire about patient satisfaction with telemedicine delivered through video/audio visits in English. The quality of the studies was evaluated according to the Critical Appraisal Tool for Analytical Cross-Sectional Studies of the Joanna Briggs Institute (JBI). The dimensions and items in each tool were also analyzed. Results The initial search showed 14,020 studies. After eliminating duplicates and utilizing inclusion and exclusion criteria, 44 studies were included. This systematic review identified and integrated the measurement factors and develops a scale of patient satisfaction with telemedicine, which was divided into 9 dimensions and consists of 37 items. Conclusion Future measurement and evaluation of telemedicine will benefit from scale that was developed in this study, and it will more directly reflecting patient needs when patient satisfaction with telemedicine is evaluated.

Prosthetic hands have significant potential to restore the manipulative capabilities and self-confidence of amputees and enhance their quality of life. However, incompatibility between prosthetic devices and residual limbs can lead to secondary injuries such as skin pressure ulcers and restricted joint motion, contributing to a high prosthesis abandonment rate. To address these challenges, this study introduces a data-driven design framework (D3Frame) utilizing a multi-index optimization method. By incorporating motion/ pressure data, as well as clinical criteria such as pain threshold/ tolerance, from various anatomical sites on the residual limbs of amputees, this framework aims to optimize the structural design of the prosthetic socket, including the Antecubital Channel (AC), Lateral Epicondylar Region Contour (LC), Medial Epicondylar Region Contour (MC), Olecranon Region Contour (OC), Lateral Flexor/ Extensor Region (LR), and Medial Flexor/ Extensor Region (MR). Experiments on five forearm amputees verified the improved adaptability of the optimized socket compared to traditional sockets under three load conditions. The experimental results revealed a modest score enhancement on standard clinical scales and reduced muscle fatigue levels. Specifically, the percent effort of muscles and slope value of mean/ median frequency decreased by 19%, 70%, and 99% on average, respectively, and the average values of mean/ median frequency in the motion cycle both increased by approximately 5%. The proposed D3Frame in this study was applied to optimize the structural aspects of designated regions of the prosthetic socket, offering the potential to aid prosthetists in prosthesis design and, consequently, augmenting the adaptability of prosthetic devices.

Abstract Background The overgrowth of Desulfovibrio, an inflammation promoting flagellated bacteria, has been found in ulcerative colitis (UC) patients. However, the molecular mechanism in promoting colitis remains unestablished. Methods The relative abundance Desulfovibrio vulgaris (D. vulgaris) in stool samples of UC patients was detected. Mice were treated with dextran sulfate sodium to induce colitis with or without administration of D. vulgaris or D. vulgaris flagellin (DVF), and the severity of colitis and the leucine-rich repeat containing 19 (LRRC19) signaling were assessed. The interaction between DVF and LRRC19 was identified by surface plasmon resonance and intestinal organoid culture. Lrrc19 −/− and Tlr5 −/− mice were used to investigate the indispensable role of LRRC19. Finally, the blockade of DVF-LRRC19 interaction was selected through virtual screening and the efficacy in colitis was assessed. Results D. vulgaris was enriched in fecal samples of UC patients and was correlated with the disease severity. D. vulgaris or DVF treatment significantly exacerbated colitis in germ-free mice and conventional mice. Mechanistically, DVF could interact with LRRC19 (rather than TLR5) in colitis mice and organoids, and then induce the production of pro-inflammatory cytokines. Lrrc19 knockdown blunted the severity of colitis. Furthermore, typhaneoside, a blockade of binding interfaces, blocked DVF-LRRC19 interaction and dramatically ameliorated DVF-induced colitis. Conclusions D. vulgaris could promote colitis through DVF-LRRC19 interaction. Targeting DVF-LRRC19 interaction might be a new therapeutic strategy for UC therapy. Video Abstract

Abstract Introduction Gestational trophoblastic neoplasia (GTN) with intracardiac metastasis is rare, and here we reported a patient with intracardiac metastasis of high-risk and refractory gestational choriocarcinoma and reviewed relevant literatures. Case presentation A 37-year-old woman presented with vaginal bleeding and high level of β-human chorionic gonadotropin (β-hCG) at 199,060 (mIU/mL). It was clinically diagnosed with gestational choriocarcinoma. The patient initially received eight cycles of chemotherapy but unsatisfactory response was observed, and the level of β-hCG still ranged between 5000 and 10,000. Then there was found intracardiac masses in the right atrium (2.6*1.7 cm), anterior chordae tendineae of the tricuspid valve (1.4*0.7 cm) and the right ventricle (4.1*2.9 cm) by ultrasonic cardiogram (UCG). PET/CT highly suspected the intracardiac metastasis of choriocarcinoma (SUVmax = 9.3) and no disease was found in the lung and pelvis. The patient undertook complete intracardiac masses resection. The pathology confirmed the intracardiac metastasis of disease. After a week of operation, the UCG found a 5.4*4.2 cm mass in the right atrium again. Considering the poor prognosis, the patient received palliative care and eventually died of disease progression. Conclusion Intracardiac metastasis of GTN is an aggressive sign of disease. Patients can benefit from chemotherapy and surgery. Future investigation of PD-1 immunotherapy combines with chemotherapy are expected to improve the prognosis in this group of patients.

Abstract Osteoarthritis (OA) is a chronic degenerative disease resulting joint disability and pain. Accumulating evidences suggest that chondrocyte extracellular matrix calcification plays an important role in the development of OA. Here, we showed that Krüppel-like factor 10 (Klf10) was involved in the regulation of chondrocyte extracellular matrix calcification by regulating the expression of Frizzled9. Knockdown of Klf10 attenuated TBHP induced calcification and reduced calcium content in chondrocytes. Restoring extracellular matrix calcification of chondrocytes could aggravate chondrocyte senescence. Destabilization of a medial meniscus (DMM) mouse model of OA, in vivo experiments revealed that knockdown Klf10 improved the calcification of articular cartilage and ameliorated articular cartilage degeneration. These findings suggested that knockdown Klf10 inhibited extracellular matrix calcification-related changes in chondrocytes and alleviated chondrocyte senescence.

Complex oxide–carbonitrides (MgO-Ti(CN), Al2O3-Ti(CN), and MgO·Al2O3-Ti(CN)) are the most common non-metallic inclusions presented in cast and wrought superalloys. In this work, a coupled kinetics model was proposed to predict the complex oxide–carbonitride inclusion’s precipitation behavior during the solidification of superalloys. This model takes into account thermodynamics, micro-segregation, heterogeneous nucleation in the inter-dendritic liquid, and growth controlled by the diffusion of solute elements and kinetics of interfacial reaction. The results demonstrated that both the cooling rate and nitrogen content take significant effects on the final size of complex oxide–carbonitride inclusions, as the former controls the total growth time and the latter determines the initial precipitation temperature. In comparison, the particle size of primary oxides shows a negligible impact on the final size of complex inclusions. The practice of an industrial vacuum arc remelting confirmed that the inclusion size variation predicted by the present model is reasonably consistent with the experimental results.

Land use and cover change (LUCC) is directly linked to the sustainability of ecosystems and the long-term well-being of human society. The Helong Region in the Loess Plateau has become one of the areas most severely affected by soil and water erosion in China due to its unique geographical location and ecological environment. The long-term construction of terraces and orchards is one of the important measures for this region to combat soil erosion. Despite the important role that terraces and orchards play in this region, current studies on their extraction and understanding remain limited. For this reason, this study designed a land use classification system, including terraces and orchards, to reveal the patterns of LUCC and the effectiveness of ecological restoration projects in the area. Based on this system, this study utilized the Random Forest classification algorithm to create an annual land use and cover (LUC) dataset for the Helong Region that covers eight periods from 1986 to 2020, with a spatial resolution of 30 m. The validation results showed that the maps achieved an average overall accuracy of 87.54% and an average Kappa coefficient of 76.94%. This demonstrates the feasibility of the proposed design and land coverage mapping method in the study area. This study found that, from 1986 to 2020, there was a continuous increase in forest and grassland areas, a significant reduction in cropland and bare land areas, and a notable rise in impervious surface areas. We emphasized that the continuous growth of terraces and orchards was an important LUCC trend in the region. This growth was primarily attributed to the conversion of grasslands, croplands, and forests. This transformation not only reduced soil erosion but also enhanced economic efficiency. The products and insights provided in this study help us better understand the complexities of ecological recovery and land management.

Sound event localization and detection (SELD) is a crucial component of machine listening that aims to simultaneously identify and localize sound events in multichannel audio recordings. This task demands an integrated analysis of spatial, temporal, and frequency domains to accurately characterize sound events. The spatial domain pertains to the varying acoustic signals captured by multichannel microphones, which are essential for determining the location of sound sources. However, the majority of recent studies have focused on time-frequency correlations and spatio-temporal correlations separately, leading to inadequate performance in real-life scenarios. In this paper, we propose a novel SELD method that utilizes the newly developed Spatio-Temporal-Frequency Fusion Network (STFF-Net) to jointly learn comprehensive features across spatial, temporal, and frequency domains of sound events. The backbone of our STFF-Net is the Enhanced-3D (E3D) residual block, which combines 3D convolutions with a parameter-free attention mechanism to capture and refine the intricate correlations among these domains. Furthermore, our method incorporates the multi-ACCDOA format to effectively handle homogeneous overlaps between sound events. During the evaluation, we conduct extensive experiments on three de facto benchmark datasets, and our results demonstrate that the proposed SELD method significantly outperforms current state-of-the-art approaches.

(1) Background: In recent years, forest fires have become increasingly frequent both domestically and internationally. The pollutants emitted from the burning of fuel have exerted considerable environmental stress. To investigate the influence of forest fires on the atmospheric environment, it is crucial to analyze the variations in PM2.5 emissions from various forest fuels under differing fire conditions. This assessment is essential for evaluating the effects on both the atmospheric environment and human health. (2) Methods: Indoor simulated combustion experiments were conducted on the branches, leaves, and bark of typical tree species in the Liangshui National Natural Reserve, including Pinus koraiensis (PK), Larix gmelinii (LG), Picea koraiensis (PAK), Betula platyphylla (BP), Fraxinus mandshurica (FM), and Populus davidiana (PD). The PM2.5 concentrations emitted by six tree species under various combustion states were measured and analyzed, reflecting the impact of moisture content on the emission of pollutants from fuel combustion, as indicated by the emission factors for pollutants. (3) Results: Under different fuel loading and moisture content conditions, the mass concentration values of PM2.5 emitted from the combustion of different organs of various tree species exhibit variability. (4) Conclusions: Among the various tree species, broad-leaved varieties release a greater quantity of PM2.5 compared to coniferous ones. A positive correlation exists between the moisture content of the fuel and the concentration of PM2.5; changes in moisture content notably influence PM2.5 levels. The emission of PM2.5 from fuel with varying loads increases exponentially. Utilizing the Response Surface Methodology (RSM) model for simulation, it was determined that both moisture content and fuel load exert a significant combined effect on the release of PM2.5 during combustion.

Background: Exercise and dietary interventions are essential for maintaining weight and reducing fat accumulation. With the growing popularity of various dietary strategies, evidence suggests that combining exercise with dietary interventions offers greater benefits than either approach alone. Consequently, this combined strategy has become a preferred method for many individuals aiming to maintain health. Calorie restriction, 5/2 intermittent fasting, time-restricted feeding, and the ketogenic diet are among the most popular dietary interventions today. Aerobic exercise, resistance training, and mixed exercise are the most widely practiced forms of physical activity. Exploring the best combinations of these approaches to determine which yields the most effective results is both meaningful and valuable. Despite this trend, a comparative analysis of the effects of different exercise and diet combinations is lacking. This study uses network meta-analysis to evaluate the impact of various combined interventions on body composition and to compare their efficacy. Methods: We systematically reviewed literature from database inception through May 2024, searching PubMed, Web of Science, Embase, and the Cochrane Library. The study was registered in PROSPERO under the title: “Effects of Exercise Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis” (identifier: CRD42024542184). Studies were meticulously selected based on specific inclusion and exclusion criteria (The included studies must be randomized controlled trials involving healthy adults aged 18 to 65 years. Articles were rigorously screened according to the specified inclusion and exclusion criteria.), and their risk of bias was assessed using the Cochrane risk of bias tool. Data were aggregated and analyzed using network meta-analysis, with intervention efficacy ranked by Surface Under the Cumulative Ranking (SUCRA) curves. Results: The network meta-analysis included 78 randomized controlled trials with 5219 participants, comparing the effects of four combined interventions: exercise with calorie restriction (CR+EX), exercise with time-restricted eating (TRF+EX), exercise with 5/2 intermittent fasting (5/2F+EX), and exercise with a ketogenic diet (KD+EX) on body composition. Intervention efficacy ranking was as follows: (1) Weight Reduction: CR+EX > KD+EX > TRF+EX > 5/2F+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.94 (−3.64, 9.52); 2.37 (−0.40, 5.15); 1.80 (−1.75, 5.34)). (2) BMI: CR+EX > KD+EX > 5/2F+EX > TRF+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 1.95 (−0.49, 4.39); 2.20 (1.08, 3.32); 1.23 (−0.26, 2.71)). (3) Body Fat Percentage: CR+EX > 5/2F+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.66 (−1.56, 6.89); 2.84 (0.56, 5.13); 3.14 (0.52, 5.75).). (4) Lean Body Mass in Male: CR+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of TRF+EX and KD+EX are −1.60 (−6.98, 3.78); −2.76 (−7.93, 2.40)). (5) Lean Body Mass in Female: TRF+EX > CR+EX > 5/2F+EX > KD+EX (Relative to TRF+EX, the effect sizes of CR+EX, 5/2F+EX and KD+EX are −0.52 (−2.58, 1.55); −1.83 (−4.71, 1.04); −2.46 (−5.69,0.76).). Conclusion: Calorie restriction combined with exercise emerged as the most effective strategy for reducing weight and fat percentage while maintaining lean body mass. For women, combining exercise with time-restricted eating proved optimal for preserving muscle mass. While combining exercise with a ketogenic diet effectively reduces weight, it is comparatively less effective at decreasing fat percentage and preserving lean body mass. Hence, the ketogenic diet combined with exercise is considered suboptimal.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) and liver cirrhosis are significant clinical concerns, especially among individuals with type 2 diabetes mellitus (T2DM). However, in China, there is a paucity of reliable evidence detailing the characteristics of NAFLD and liver cirrhosis in T2DM. Furthermore, the relationship between blood glucose levels and NAFLD prevalence remains unclear. Methods Data from the Shanghai Suburban Adult Cohort and Biobank were analyzed, including 6621 participants with T2DM. NAFLD was diagnosed by ultrasonography and liver cirrhosis was performed according to the health information systems. Logistic regression and restricted cubic spline analysis were used to explore the potential risk factors for NAFLD and liver cirrhosis. Results The prevalence of NAFLD was 59.36%, and liver cirrhosis was 1.43% among T2DM patients. In these patients, factors like age, being female, marital status, and obesity significantly increased the risk of NAFLD. Specifically, obesity had a strong positive association with NAFLD (odds ratio [OR] = 4.70, 95% confidence interval [CI]: 4.13–5.34). The higher glycated hemoglobin (HbA1c) quartile was associated with a heightened NAFLD risk compared to the lowest quartile (all p 8.00% (OR = 1.03, 95% CI: 0.92–1.15). Conclusion Systematic screening for NAFLD is essential in T2DM patients, especially with poor glucose control and obesity in female.

Abstract On behalf of the journal, AGU, and the scientific community, the editors of Geophysical Research Letters would like to sincerely thank those who reviewed manuscripts for us in 2023. The hours reading and commenting on manuscripts not only improve the manuscripts, but also increase the scientific rigor of future research in the field. With the advent of AGU's data policy, many reviewers have also helped immensely to evaluate the accessibility and availability of data, and many have provided insightful comments that helped to improve the data presentation and quality. We greatly appreciate the assistance of the reviewers in advancing open science, which is a key objective of AGU's data policy. We particularly appreciate the timely reviews in light of the demands imposed by the rapid review process at Geophysical Research Letters. We received 4,512 submissions in 2023 and 5,112 reviewers contributed to their evaluation by providing 8,587 reviews in total. We deeply appreciate their contributions.

BackgroundPediatric cerebral palsy (CP) is a non-progressive brain injury syndrome characterized by central motor dysfunction and insufficient brain coordination ability. The etiology of CP is complex and often accompanied by diverse complications such as intellectual disability and language disorders, making clinical treatment difficult. Despite the availability of pharmacological interventions, rehabilitation programs, and spasticity relief surgery as treatment options for CP, their effectiveness is still constrained. Electroacupuncture (EA) stimulation has demonstrated great improvements in motor function, but its comprehensive, objective therapeutic effects on pediatric CP remain to be clarified.MethodsWe present a case of a 5-year-old Chinese female child who was diagnosed with CP at the age of 4. The patient exhibited severe impairments in motor, language, social, and cognitive functions. We performed a 3-month period of EA rehabilitation, obtaining resting state functional magnetic resonance imaging (rs-fMRI) of the patient at 0 month, 3 months and 5 months since treatment started, then characterized brain functional connectivity patterns in each phase for comparison.ResultsAfter a 12-month follow-up, notable advancements were observed in the patient’s language and social symptoms. Changes of functional connectivity patterns confirmed this therapeutic effect and showed specific benefits for different recovery phase: starting from language functions then modulating social participation and other developmental behaviors.ConclusionThis is a pioneering report demonstrating the longitudinal effect of EA stimulation on functional brain connectivity in CP patients, suggesting EA an effective intervention for developmental disabilities (especially language and social dysfunctions) associated with pediatric CP.

IntroductionThe composition of the intestinal microbiome correlates significantly with an animal’s health status. Hence, this indicator is highly important and sensitive for protecting endangered animals. However, data regarding the fungal diversity of the wild Budorcas taxicolor (takin) gut remain scarce. Therefore, this study analyzes the fungal diversity, community structure, and pathogen composition in the feces of wild B. taxicolor.MethodsTo ensure comprehensive data analyses, we collected 82 fecal samples from five geographical sites. Amplicon sequencing of the internal transcribed spacer (ITS) rRNA was used to assess fecal core microbiota and potential pathogens to determine whether the microflora composition is related to geographical location or diet. We further validated the ITS rRNA sequencing results via amplicon metagenomic sequencing and culturing of fecal fungi.Results and discussionThe fungal diversity in the feces of wild Budorcas taxicolor primarily comprised three phyla (99.69%): Ascomycota (82.19%), Fungi_unclassified (10.37%), and Basidiomycota (7.13%). At the genus level, the predominant fungi included Thelebolus (30.93%), Functional_unclassified (15.35%), and Ascomycota_unclassified (10.37%). Within these genera, certain strains exhibit pathogenic properties, such as Thelebolus, Cryptococcus, Trichosporon, Candida, Zopfiella, and Podospora. Collectively, this study offers valuable information for evaluating the health status of B. taxicolor and formulating protective strategies.

Abstract Background Thoracic adenoid cystic carcinoma (ACC) is rare, and the differences between tracheal and lung lesions have not been fully understood. Methods Patients were identified from a Chinese cancer center (FUSCC) (2005–2022) and the Surveillance, Epidemiology, and End Results (SEER) database (2000–2019). Incidence was calculated and trends were quantified. Clinicopathological features and overall survival (OS) were analyzed. Nomograms predicting OS were constructed. Results Totally, 55 tracheal adenoid cystic carcinoma (TACC) and 25 lung and bronchus adenoid cystic carcinoma (LACC) were included in a Chinese cohort, 121 TACC and 162 LACC included in the SEER cohort. There were larger tumor sizes, more lymph nodes and distant metastases for LACC than TACC patients. TACC patients are more likely to get local treatments. Patients with LACC had significantly worse median OS than patients with TACC (SEER cohort: 68.0 months vs. 109.0 months, p = 0.001, Chinese cohort: 62.9 months vs. 124.8 months, p = 0.061). Age, lymph node metastasis, distant metastasis and local treatment were identified as independent prognostic factors for OS of TACC. Distant metastasis and local treatment were identified for LACC. Specifically, surgery alone or in combination with radiotherapy is crucial for improving survival in both TACC and LACC. Only TACC benefits from radiotherapy alone, while chemotherapy does not improve survival for either. The nomograms constructed using these factors revealed good prognostic accuracy. Conclusions LACC is more aggressive and has a worse prognosis than TACC. TACC patients have more opportunities for local treatment, which is important for the prognosis of both TACC and LACC. Nomograms were created for TACC and LACC to aid in personalized survival predictions and clinical decisions.

Background: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. Objective: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. Methods: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. Results: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6–14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52–54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. Conclusion: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.

Abstract Background To determine the effects of negative heel shoes on perceived pain and knee biomechanical characteristics of runners with patellofemoral pain (PFP) during running. Methods Sixteen runners with PFP ran in negative (−11 mm drops) and positive (5 mm drops) heel shoes while visual analog scale (VAS) scores, retroreflective markers, and ground reaction force were acquired by applying a 10‐cm VAS, infrared motion capture system, and a three‐dimensional force plate. Knee moment, patellofemoral joint stress (PFJS), and other biomechanical parameters during the stance phase were calculated based on inverse dynamics and a biomechanical model of the patellofemoral joint. Results The foot inclination angle, peak PFJS during the stance phase, patellofemoral joint reaction force, knee extension moment, and quadriceps force at the time of peak PFJS of runners with PFP in negative heel shoes were lower than that in positive heel shoes, no significant difference was found in VAS scores, knee flexion angle, patellofemoral contact area, and quadriceps moment arm at the time of peak PFJS. Conclusions Compared to positive heel shoes, running in negative heel shoes decreases peak PFJS in runners with PFP, which may decrease patellofemoral joint loading, thus reducing the possibility of further development of PFP. Trail Registration Sports Science Experiment Ethics Committee of Beijing Sport University. 2023095H, April 18, 2023 (prospectively registered).

Abstract Background The overexpression of ALOX5AP has been observed in many types of cancer and has been identified as an oncogene. However, its role in acute myeloid leukemia (AML) has not been extensively studied. This study aimed to identify the expression and methylation patterns of ALOX5AP in bone marrow (BM) samples of AML patients, and further explore its clinical significance. Methods Eighty-two de novo AML patients and 20 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the alteration of ALOX5AP. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of ALOX5AP expression to discriminate AML. The prognostic value of ALOX5AP was identified by the Kaplan–Meier method and log-rank test. It was further validated in four independent cohorts (n = 1186). Significantly different genes associated with ALOX5AP expression were subsequently compared by LinkedOmics, and Metascape database. Results The level of ALOX5AP expression was significantly increased in bone marrow cells of AML patients compared with healthy donors (P

Background/purpose: Epigallocatechin-3-gallate (EGCG) is playing an increasingly important role in the treatment of oral diseases. However, its mechanisms remain to be clarified. This study aimed to investigate the effect of EGCG on oxidative and inflammatory stress and bone loss in experimental periodontitis. Materials and methods: Periodontitis was induced in rats, followed by gavage using different concentrations of EGCG for 5 weeks. The levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in rats were measured. The degree of alveolar bone loss and the number of inflammatory cells were detected. The integrated optical density of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), NLR pyrin domain-containing 3 (NLRP3) and nuclear factor-kappaB p65 (NF-κB p65) was measured. Results: EGCG (200 mg/kg) significantly reduced alveolar bone loss in the ligated maxillary molars and the number of inflammatory cells in the EGCG-200 group compared with the periodontitis, EGCG-100 and EGCG-400 groups. 200 mg/kg was the optimal dose of EGCG and was used in subsequent experiments. The expression levels of IL-1β, IL-18, TNF-α and MDA were significantly lower and the expression level of SOD was significantly higher in the EGCG-200 group compared with the periodontitis group. The expression of NLRP3 and NF-κB p65 was significantly decreased, while the expression of Nrf2 and HO-1 was significantly increased in the EGCG-200 group compared with the periodontitis group. Conclusion: These results suggest that EGCG inhibits oxidative stress and inflammatory responses in the periodontitis model by modulating the Nrf2/HO-1/NLRP3/NF-κB p65 signaling pathway, thereby decreasing alveolar bone loss.

Abstract Background Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. Methods Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes. Results Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice. Conclusion Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart. Graphic abstract

Breast cancer is a heterogeneous disease that arises as a multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses and therapeutic responses due to alterations in molecular genetics. As an essential marker for the molecular subtyping of breast cancer, long non-coding RNAs (lncRNAs) play a crucial role in gene expression regulation, cell differentiation, and the maintenance of genomic stability. Here, we developed a modular framework for lncRNA identification and applied it to a breast cancer cohort to identify novel lncRNAs not previously annotated. To investigate the potential biological function, regulatory mechanisms, and clinical relevance of the novel lncRNAs, we elucidated the genomic and chromatin features of these lncRNAs, along with the associated protein-coding genes and putative enhancers involved in the breast cancer regulatory networks. Furthermore, we uncovered that the expression patterns of novel and annotated lncRNAs identified in breast cancer were related to the hormone response in the PAM50 subtyping criterion, as well as the immune response and progression states of breast cancer across different immune cells and immune checkpoint genes. Collectively, the comprehensive identification and functional analysis of lncRNAs revealed that these lncRNAs play an essential role in breast cancer by altering gene expression and participating in the regulatory networks, contributing to a better insight into breast cancer heterogeneity and potential avenues for therapeutic intervention.

The ever-increasing demand for oil & gas exploration from land to subsea necessitates using higher-strength and high-ductility heavy-wall thickness pipes, which may increase the microstructural inhomogeneity along the steel plate sections, ultimately impacting the mechanical properties. In this work, the differences in microstructure and mechanical properties between the through-thickness layers of a heavy-wall ferrite/bainite (F/B) dual-phase (DP) X70 pipeline steel plate were studied. The results showed that the size of the ferrite grain and the volume fraction of bainite increased from the surface layer to the mid-thickness layer of the DP X70 pipeline steel plate. The surface and mid-thickness layers had a lower uniform elongation and higher strength and hardness. In comparison, the quarter layer had higher uniform elongation and lower strength and hardness. The refined grain size and the strong {001} texture were responsible for enhanced in strength and hardness. The higher γ-fiber texture at the quarter layer favored the higher plasticity. The analysis results of strain-hardening behaviors based on the modified C-J model showed that the mid-thickness layer had a higher strain-hardening capacity at the beginning of the plastic strain, leading to deformation instability and reduced material plasticity. The surface layer maintained a high hardening exponent even at high plastic strains, which facilitated the deformation properties of the material. The results provide a basis for evaluating the influence of microstructural factors on the strength and plasticity of heavy-wall X70 pipeline steel and the coordination mechanism of micro deformation in DP steels.

Abstract The solid-electrolyte interphase (SEI) plays crucial roles for the reversible operation of lithium metal batteries. However, fundamental understanding of the mechanisms of SEI formation and evolution is still limited. Herein, we develop a depth-sensitive plasmon-enhanced Raman spectroscopy (DS-PERS) method to enable in-situ and nondestructive characterization of the nanostructure and chemistry of SEI, based on synergistic enhancements of localized surface plasmons from nanostructured Cu, shell-isolated Au nanoparticles and Li deposits at different depths. We monitor the sequential formation of SEI in both ether-based and carbonate-based dual-salt electrolytes on a Cu current collector and then on freshly deposited Li, with dramatic chemical reconstruction. The molecular-level insights from the DS-PERS study unravel the profound influences of Li in modifying SEI formation and in turn the roles of SEI in regulating the Li-ion desolvation and the subsequent Li deposition at SEI-coupled interfaces. Last, we develop a cycling protocol that promotes a favorable direct SEI formation route, which significantly enhances the performance of anode-free Li metal batteries.

IntroductionThis study aimed to investigate the potential of short-term aerobic exercise to mitigate skeletal muscle mitochondrial damage following ambient PM2.5 exposure, and how 12 weeks of endurance training can enhance aerobic fitness to protect against such damage.MethodsTwenty-four male C57BL/6 J mice were split into sedentary (SED, n = 12) and endurance training (ETR, n = 12) groups. The ETR group underwent 12 weeks of training (10–15 m/min, 60 min/day, 4 times/week), confirmed by an Endurance Exercise Capacity (EEC) test. Post-initial training, the SED group was further divided into SSED (SED and sedentary, n = 6) and SPE (SED and PM2.5 + Exercise, n = 6). Similarly, the ETR group was divided into EEX (ETR and Exercise, n = 6) and EPE (ETR and PM2.5 + Exercise, n = 6). These groups underwent 1 week of atmospherically relevant artificial PM2.5 exposure and treadmill running (3 times/week). Following treatments, an EEC test was conducted, and mice were sacrificed for blood and skeletal muscle extraction. Blood samples were analyzed for oxidative stress indicators, while skeletal muscles were assessed for mitochondrial oxidative metabolism, antioxidant capacity, and mitochondrial damage using western blot and transmission electron microscopy (TEM).ResultsAfter 12 weeks of endurance training, the EEC significantly increased (p

Abstract We enhance the Community Land Model (CLM) snow albedo modeling by implementing several new features with more realistic and physical representations of snow‐aerosol‐radiation interactions. Specifically, we incorporate the following model enhancements: (a) updating ice and aerosol optical properties with more realistic and accurate data sets, (b) adding multiple dust types, (c) adding multiple surface downward solar spectra to account for different atmospheric conditions, (d) incorporating a more accurate adding‐doubling radiative transfer solver, (e) adding nonspherical snow grain representations, (f) adding black carbon‐snow and dust‐snow internal mixing representations, and (g) adding a hyperspectral (480‐band vs. the default 5‐band) modeling capability. These model features/enhancements are included as new CLM physics/namelist options, which allows for quantification of model sensitivity to snow albedo processes and for multi‐physics model ensemble analyses for uncertainty assessment. The model updates have been included in the latest released CLM version. Sensitivity analyses reveal strong impacts of using the new adding‐doubling solver, nonspherical snow grains, aerosol‐snow internal mixing, updated aerosol optics, and different dust types. These enhanced snow albedo representations improve the CLM simulated global snowpack evolution and land surface conditions, with reduced biases in simulated snow surface albedo, snow cover, snow water equivalent, snow depth, and surface (2‐m) air temperature over many mid‐latitude mountainous regions and seasonal snowpacks but degraded performance in some northern high‐latitude regions.

Summary: Detecting visual features in the environment is crucial for animals’ survival. The superior colliculus (SC) is implicated in motion detection and processing, whereas how the SC integrates visual inputs from the two eyes remains unclear. Using in vivo electrophysiology, we show that mouse SC contains many binocular neurons that display robust ocular dominance (OD) plasticity in a critical period during early development, which is similar to, but not dependent on, the primary visual cortex. NR2A- and NR2B-containing N-methyl-D-aspartate (NMDA) receptors play an essential role in the regulation of SC plasticity. Blocking NMDA receptors can largely prevent the impairment of predatory hunting caused by monocular deprivation, indicating that maintaining the binocularity of SC neurons is required for efficient hunting behavior. Together, our studies reveal the existence and function of OD plasticity in SC, which broadens our understanding of the development of subcortical visual circuitry relating to motion detection and predatory hunting.

Branchiootic syndrome (BOS) is a rare, autosomal dominant syndrome characterized by malformations of the ear associated with hearing loss, second branchial arch anomalies, and the absence of renal anomalies. Herein, we report the case of an 8-year-old male patient with BOS. The proband also experiences mixed conductive and sensorineural hearing loss in the right ear, and severe-to-profound sensorineural hearing loss in the left ear. Preauricular pits, branchial fistulae, and cochlear hypoplasia were present bilaterally. Type III cup-shaped ear, and external auditory canal stenosis were detected in the right ear. Lateral semicircular canal-vestibule dysplasia was detected in the left ear. Moreover, the patient had unilateral secretory otitis media (SOM) in the right ear and bilateral vestibular hypofunction (VH), which has not been reported in previous studies. The patient’s hearing on the right side was restored to nearly normal after myringotomy. Whole exome sequencing identified a novel frameshift mutation in EYA1 (NM_000503.6): c.1697_1698delinT [p.(Lys566IlefsTer73)] in the proband, which was defined a “pathogenic” mutation according to American College of Medical Genetics and Genomics guidelines. This is the first report of a child presenting with BOS, SOM and VH, which expands the known clinical manifestations of this syndrome. We also observed a novel EYA1 gene mutation in this patient with BOS, which enriches the mutation map and provides a reference for genetic diagnosis of this syndrome.

Camellia oil, recognized as a high-quality edible oil endorsed by the Food and Agriculture Organization, is confronted with authenticity issues arising from fraudulent adulteration practices. These practices not only pose health risks but also lead to economic losses. This study proposes a novel machine learning framework, referred to as a transformer encoder backbone with a support vector machine regressor (TES), coupled with an electronic nose (E-nose), for detecting varying adulteration levels in camellia oil. Experimental results indicate that the proposed TES model exhibits the best performance in identifying the adulterated concentration of camellia oi, compared with five other machine learning models (the support vector machine, random forest, XGBoost, K-nearest neighbors, and backpropagation neural network). The results obtained by E-nose detection are verified by complementary Fourier transform infrared (FTIR) spectroscopy analysis for identifying functional groups, ensuring accuracy and providing a comprehensive assessment of the types of adulterants. The proposed TES model combined with E-nose offers a rapid, effective, and practical tool for detecting camellia oil adulteration. This technique not only safeguards consumer health and economic interests but also promotes the application of E-nose in market supervision.

IntroductionThe giant panda (Ailuropoda melanoleuca) reproduction is of worldwide attention, and the vaginal microbiome is one of the most important factors affecting the reproductive rate of giant pandas. The aim of this study is to investigate the diversity of vaginal mycobiota structure, and potential pathogenic fungi in female giant pandas during estrus and non-estrus.MethodsThis study combined with high-throughput sequencing and laboratory testing to compare the diversity of the vaginal mycobiota in giant pandas during estrus and non-estrus, and to investigate the presence of potentially pathogenic fungi. Potentially pathogenic fungi were studied in mice to explore their pathogenicity.Results and discussionThe results revealed that during estrus, the vaginal secretions of giant pandas play a crucial role in fungal colonization. Moreover, the diversity of the vaginal mycobiota is reduced and specificity is enhanced. The abundance of Trichosporon and Cutaneotrichosporon in the vaginal mycobiota of giant pandas during estrus was significantly higher than that during non-estrus periods. Apiotrichum and Cutaneotrichosporon were considered the most important genera, and they primarily originate from the environment owing to marking behavior exhibited during the estrous period of giant pandas. Trichosporon is considered a resident mycobiota of the vagina and is an important pathogen that causes infection when immune system is suppressed. Potentially pathogenic fungi were further isolated and identified from the vaginal secretions of giant pandas during estrus, and seven strains of Apiotrichum (A. brassicae), one strain of Cutaneotrichosporon (C. moniliiforme), and nine strains of Trichosporon (two strains of T. asteroides, one strain of T. inkin, one strain of T. insectorum, and five strains of T. japonicum) were identified. Pathogenicity results showed that T. asteroides was the most pathogenic strain, as it is associated with extensive connective tissue replacement and inflammatory cell infiltration in both liver and kidney tissues. The results of this study improve our understanding of the diversity of the vaginal fungi present in giant pandas and will significantly contribute to improving the reproductive health of giant pandas in the future.

Virus infection is one of the greatest threats to human life and health. In response to viral infection, the host’s innate immune system triggers an antiviral immune response mostly mediated by inflammatory processes. Among the many pathways involved, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome has received wide attention in the context of viral infection. The NLRP3 inflammasome is an intracellular sensor composed of three components, including the innate immune receptor NLRP3, adaptor apoptosis-associated speck-like protein containing CARD (ASC), and the cysteine protease caspase-1. After being assembled, the NLRP3 inflammasome can trigger caspase-1 to induce gasdermin D (GSDMD)-dependent pyroptosis, promoting the maturation and secretion of proinflammatory cytokines such as interleukin-1 (IL-1β) and interleukin-18 (IL-18). Recent studies have revealed that a variety of viruses activate or inhibit the NLRP3 inflammasome via viral particles, proteins, and nucleic acids. In this review, we present a variety of regulatory mechanisms and functions of the NLRP3 inflammasome upon RNA viral infection and demonstrate multiple therapeutic strategies that target the NLRP3 inflammasome for anti-inflammatory effects in viral infection.

IntroductionThe intestinal tract of animals is a complex and dynamic microecosystem that is inextricably linked to the health of the host organism. Takin (Budorcas taxicolor) is a threatened species, and its gut microbiome is poorly understood. Therefore, this study aimed to analyze the microbial community structure and potential pathogens of takin.MethodsTakin fecal samples were collected from five sites in a nature reserve to ensure the uniformity of sample collection, determine the effects of different geographical locations on gut microbes, and analyze the differences in microbial communities between sites. Subsequently, high-throughput 16S rDNA gene sequencing was performed to analyze the microbial diversity and potential pathogens in the gut; the findings were verified by isolating and culturing bacteria and metagenomic sequencing.Results and discussionThe takin gut microflora consisted mainly of four phyla: Firmicutes (69.72%), Bacteroidota (13.55%), Proteobacteria (9.02%), and Verrucomicrobiota (3.77%), representing 96.07% of all microorganisms. The main genera were UCG-005 (20.25%), UCG-010_unclassified (12.35%), Firmicus_unclassified (4.03%), and Rumino coccsea_unclassified (3.49%), while the main species were assigned to Bacteria_unclassified. Potential pathogens were also detected, which could be used as a reference for the protection of takin. Pseudomonas presented the highest abundance at Shuichiping and may represent the main pathogen responsible for the death of takin at the site. This study provides an important reference for investigating the composition of the bacterial community in the intestine of takin.

Abstract Solar radiation‐topography interaction plays an important role in surface energy balance over the Tibetan Plateau (TP). However, the impacts of such interaction over the TP on climate locally and in the Asian regions remain unclear. This study uses the Energy Exascale Earth System Model (E3SM) to evaluate the regional and teleconnected impacts of solar radiation‐topography interaction over the TP. Land‐atmosphere coupled experiments show that topography regulates the surface energy balance, snow processes, and surface climate over the TP across seasons. Accounting for solar radiation‐topography interaction improves E3SM simulation of surface climate. The winter cold bias in air temperature decreases from −4.57 to −3.79 K, and the wet bias in summer precipitation is mitigated in southern TP. The TP's solar radiation‐topography interaction further reduces the South and East Asian summer precipitation biases. Our results demonstrate the topographic roles in regional climate over the TP and highlight its teleconnected climate impacts.

Cartilage destruction caused by inflammation is a clinical challenge. Many studies have investigated cartilage destruction in adults, but little research was conducted on children. In this study, the protective effect of gold nanoparticles (AuNPs) on the cartilage of children was realized by counteracting chondrocyte apoptosis and extracellular matrix (ECM) degradation in a young mouse model of lipopolysaccharide (LPS)-induced growth plate (GP) cartilage damage. Initially, engineered AuNPs can be efficiently absorbed by chondrocytes, approximately 20 times the amount absorbed by macrophages, resulting in a 29% ± 0.05% increase in chondrocyte viability. Then, AuNPs exposure significantly reduced the release of inflammatory cytokines and secretion of ECM degradation factors induced by LPS. Subsequently, AuNPs were applied to resist LPS-induced cartilage destruction in young mice. AuNPs inhibited the formation of gaps, without chondrocytes and extracellular matrix, between the proliferative and hypertrophy zones of the GP cartilage, and the gaps were noticeable in the LPS group. This finding can be attributed to the capability of AuNPs to reduce the LPS-induced apoptosis rate of mouse chondrocytes by 72.38% and the LPS-induced ECM degradation rate by 70.89%. Further analysis demonstrated that remission is partly due to AuNPs’ role in maintaining the balance of catabolic and anabolic factors in the ECM. Altogether, these findings indicate that AuNPs can partially protect the cartilage of children from inflammatory damage by suppressing chondrocyte apoptosis and ECM degradation.

ABSTRACTBackground Dental caries is a multifactorial disease, and the bacteria such as Streptococcus mutans (S. mutans) is one of the risk factors. The poor effect of existing anti-bacterial is mainly related to drug resistance, the short time of drug action, and biofilm formation.Methods To address this concern, we report here on the cinnamaldehyde (CA) loaded chitosan (CS) nanocapsules (CA@CS NC) sustained release CA for antibacterial treatment. The size, ζ-potential, and morphology were characterized. The antibacterial activities in vitro were studied by growth curve assay, pH drop assay, biofilm assay, and qRT-PCR In addition, cytotoxicity assay, organ index, body weight, and histopathology results were analyzed to evaluate the safety and biocompatibility in a rat model.Results CA@CS NC can adsorb the bacterial membrane due to electronic interaction, releasing CA slowly for a long time. At the same time, it has reliable antibacterial activity against S. mutans and downregulated the expression levels of QS, virulence, biofilm, and adhesion genes. In addition, it greatly reduced the cytotoxicity of CA and significantly inhibited dental caries in rats without obvious toxicity.Conclusion Our results showed that CA@CS NC had antibacterial and antibiofilm effects on S. mutans and inhibit dental caries. Besides, it showed stronger efficacy and less toxicity, and was able to adsorb bacteria releasing CA slowly, providing a new nanomaterial solution for the treatment of dental caries.

Abstract Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526–0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423–0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201–0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029–0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.

Abstract Background Primary pure mucinous adenocarcinoma (PMA) is a rare type of lung cancer with unique clinical and prognostic features. Previous studies have shown that PMA have more early‐stage cancer compared with other adenocarcinoma (ADC) subtypes. The clinicopathological features and optimal treatment strategies of resectable locally advanced mucinous adenocarcinoma lack evidence and require further study. Methods In this study, we collected information from patients with stage III‐N2 PMA who underwent radical surgery between 2004 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. The clinicopathological parameters, treatments, overall survival (OS), and cancer‐specific survival (CSS) were evaluated. Results Of 242,699 eligible lung adenocarcinoma patients, 124 with PMA and 3405 with other ADCs of stage III‐N2 received radical surgery were identified. Compared with other ADCs, PMA tended to appear more in the lower lobes, with higher degree of differentiation, less early T stage, and more positive lymph nodes numbers. Patients with PMA had significantly worse survival than other ADCs (OS = 45.0 vs. 57.1 months, p = 0.005, CSS = 51.8 vs. 65.5 months, p = 0.017). We explored the benefit population of postoperative radiotherapy (PORT) and found that the population with ≤7 positive lymph nodes could benefit from PORT, and OS was significantly improved (41.2 vs. 69.3 months, p = 0.034). For patients with >7 positive lymph nodes, PORT did not provide a survival benefit, while chemotherapy improved OS (10.9 vs. 23.3 months, p = 0.041). Multivariate analysis showed that race, tumor location, number of positive lymph nodes, and PORT were independent prognostic factors in patients with postoperative III‐N2 lung PMA. Conclusion The prognosis of patients with resectable III‐N2 primary lung PMA was significantly worse than that of other ADCs, and PORT was an independent prognostic factor. Patients with ≤7 positive lymph nodes could benefit from PORT and those with >7 positive lymph nodes could benefit from chemotherapy.