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The performance of refractory high-entropy alloys (RHEAs) is closely related to the content of their constituent elements, which makes compositional exploration through traditional trial-and-error methods a challenging and time-consuming endeavour, with the goal of developing an alloy that exhibits both high ductility and high specific yield strength. A dataset of the alloys' performance parameters was established by applying first-principles and molecular dynamics calculations. The combination of the aforementioned dataset with the solid solution strengthening (SSH) model and the D (γs/γusf) parameter enabled the construction of a highly accurate strength-ductility prediction model for the alloys through the use of an XGBoost algorithm. The model was employed to predict the compositions of two novel RHEAs and their mechanical properties were verified by experiments. The predicted results are in general agreement with the trends of the experimental data. The Ti35V35Nb10Mo20 alloy exhibiting excellent comprehensive performance, achieving a specific yield strength of 149.55 kPa m3/kg, which is 10.97% higher than that of traditional equiatomic alloy, and a compressive strain exceeding 50%. In conclusion, this work presents an effective alloy design strategy, offering a new approach for the future design of high-performance RHEAs.

Hard carbon (HC) is widely used in sodium-ion batteries (SIBs), but its performance has always been limited by low initial Coulombic efficiency (ICE) and cycling stability. Cathode compensation agent is a favorable strategy to make up for the loss of active sodium ions consumed by HC anode. Yet it lacks agent that effectively decomposes to increase the active sodium ions as well as regulate carbon defects for decreasing the irreversible sodium ions consumption. Here, we propose 1,2-dihydroxybenzene Na salt (NaDB) as a cathode compensation agent with high specific capacity (347.9 mAh g−1), lower desodiation potential (2.4–2.8 V) and high utilization (99%). Meanwhile, its byproduct could functionalize HC with more CO groups and promote its reversible capacity. Consequently, the presodiation hard carbon (pHC) anode exhibits highly reversible capacity of 204.7 mAh g−1 with 98% retention at 5 C rate over 1000 cycles. Moreover, with 5 wt% NaDB initially coated on the Na3V2(PO4)3 (NVP) cathode, the capacity retention of NVP + NaDB|HC cell could increase from 22% to 89% after 1000 cycles at 1 C rate. This work provides a new avenue to improve reversible capacity and cycling performance of SIBs through designing functional cathode compensation agent.

Abstract Preeclampsia (PE) is a prevalent and severe pregnancy complication that significantly impacts maternal and perinatal health. Epidemiological studies and animal experiments have demonstrated that PE adversely affects the cardiovascular and nervous systems of offspring, increasing their risk of hypertension and renal pathology. However, the mechanisms underlying this increased risk remain unclear. This study utilized an L-NAME-induced preeclampsia mouse model (PELS model) to investigate the effects of PE on offspring blood pressure and renal pathology, focusing on the expression of Angiotensin II Type 1 Receptors (AT1R) and related molecules in renal tissues. Our findings show that L-NAME-induced pre-eclampsia led to reduced birth weights and significantly elevated systolic blood pressure in 6-week-old offspring. Histopathological analysis revealed pronounced glomerular and tubular damage in the kidneys of both 1-week and 6-week-old offspring from the pre-eclampsia group. At 1 week of age, the pre-eclampsia group exhibited elevated mRNA and protein expression levels of AT1R, GRK4, AQP2, ENaC, and NCC in renal tissues compared to controls. However, these differences were no longer significant at 6 weeks of age. No significant gender differences were observed in either blood pressure or renal pathological changes. Preeclampsia induced by L-NAME results in increased blood pressure and renal damage in offspring, potentially mediated by early alterations in the renal RAS system. The observed changes in AT1R and related molecules appear to be transient, suggesting that the early impact of pre-eclampsia on renal structure may trigger, but not sustain, hypertension in offspring. Further studies are needed to elucidate the long-term mechanisms driving hypertension in this population.

Abstract Balanced self-renewal and differentiation of stem cells are crucial for maintaining tissue homeostasis, but the underlying mechanisms of this process remain poorly understood. Here, from an RNA interference (RNAi) screen in adult Drosophila intestinal stem cells (ISCs), we identify a factor, Pax, which is orthologous to mammalian PXN, coordinates the proliferation and differentiation of ISCs during both normal homeostasis and injury-induced midgut regeneration in Drosophila. Loss of Pax promotes ISC proliferation while suppressing its differentiation into absorptive enterocytes (ECs). Mechanistically, our findings demonstrate that Pax is a conserved target gene of the Hippo signaling pathway in both Drosophila and mammals. Subsequent investigations have revealed Pax interacts with Yki and enhances its cytoplasmic localization, thereby establishing a feedback regulatory mechanism that attenuates Yki activity and ultimately inhibits ISCs proliferation. Additionally, Pax induces the differentiation of ISCs into ECs by activating Notch expression, thus facilitating the differentiation process. Overall, our study highlights Pax as a pivotal component of the Hippo and Notch pathways in regulating midgut homeostasis, shedding light on this growth-related pathway in tissue maintenance and intestinal function.

Abstract An ancient and counterintuitive phenomenon known as the Mpemba effect (water can cool faster when initially heated up) showcases the critical role of initial conditions in relaxation processes. How to realize and utilize this effect for speeding up relaxation is an important but challenging task in purely quantum system till now. Here, we experimentally study the strong Mpemba effect in a single trapped ion system in which an exponentially accelerated relaxation in time is observed by preparing an optimal quantum initial state with no excitation of the slowest decaying mode. Also, we demonstrate that the condition of realizing such effect coincides with the Liouvillian exceptional point, featuring the coalescence of both the eigenvalues and the eigenmodes of the systems. Our work provides an efficient strategy to engineer the dynamics of open quantum system, and suggests a link unexplored yet between the Mpemba effect and the non-Hermitian physics.

Abstract Background The relationship between the systemic immune-inflammatory index (SII) and the mortality of adults with depression is uncertain. Methods This study included adults with depression who were surveyed in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for mortality.The restricted cubic spline(RCS), Kaplan-Meier curve analysis, time-dependent ROC analysis, subgroup and sensitivity analyses were also used. Results A total of 2442 adults with depression were included in the final analysis(average age: 46.51 ± 0.44 years). During a median follow-up of 89 months, there were 302 all-cause deaths and 74 cardiovascular deaths. The fully adjusted model showed that an increment of 100 unit in SII corresponded to an increased HR of 1.05(95% CI,1.02,1.08, p = 0.003) for all-cause mortality and 1.06(95% CI,1.02,1.10, p = 0.004) for cardiovascular mortality, respectively. The RCS analysis indicated a J-shape relationship between SII and all-cause mortality and a positive linear association between SII and cardiovascular mortality.The time-dependent ROC analysis exhibited excellent efficacy in SII for predicting all-cause and cardiovascular mortality at 1, 3, 5 and 10 years. Conclusions Higher SII levels were associated with increased risk of all-cause and cardiovascular mortality in adults with depression. Clinical trial number Not applicable.

Abstract Background Enteric infections are among the most common infectious diseases. The aim of this article was to track the global trends in morbidity and mortality from enteric infections in 204 countries or territories from 1990 to 2019. Methods Data were obtained from the Global Burden of Disease 2019 study. Average annual percentage changes (AAPCs) in age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were calculated to quantify trends in enteric infections. Age-period-cohort models were used to estimate the annual percentage changes from 0 to 4 to 80 − 84 years (local drifts), period and cohort effects between 1990 and 2019 in different socio-demographic index (SDI) regions. Results In 2019, there were 6.59 billion incident cases of enteric infections, and caused 1,748,251 deaths worldwide. From 1990 to 2019, the trend in the global ASIR of enteric infections was relatively stable, but that of ASMR declined (AAPC=-3.30, 95% confidence interval [CI]: -3.54 to -3.07), and global mortality decreased in all age groups. Meanwhile, decreasing trends in ASMR were observed in 173 countries/territories (P

Fused silica glass, known for its exceptional physical and chemical properties, is widely used across diverse industries. Cerium oxide (CeO2), a common polishing abrasive, is extensively employed in polishing fused silica surfaces. Studies have revealed that chemical reactions occur on fused silica surfaces during polishing processes with CeO2 abrasives. While these chemical reactions have been studied in the context of chemical-mechanical polishing on fused silica surfaces, the chemical impacts of employing a small, compliant polishing tool on fused silica surfaces remain unclear. In this study, we use CeO2 abrasive and alumina (Al2O3) abrasive as polishing slurries and utilize a bonnet tool to polish fused silica surfaces. Through a comparative analysis of the removal efficiency of the tool influence function, alterations in surface hardness, and the sub-surface damage layer, we found that the primary factor governing material removal is the chemical reactions between CeO2 and fused silica. These reactions effectively soften the fused silica molecule layers and contribute to rapid material removal. This research fills the knowledge gap regarding the chemical effects during bonnet polishing with CeO2 abrasive. It offers valuable insights for efficient material removal control in the context of bonnet polishing fused silica surfaces. These insights will also be applicable to other computer-controlled polishing processes for fused silica glass utilizing CeO2 slurry.

Extracellular vesicles (EVs) have garnered significant attention in biomedical applications. However, the rapid, efficient, and unbiased separation of EVs from complex biological fluids remains a challenge due to their heterogeneity and low abundance in biofluids. Herein, we report a novel approach to reconfigure and modify an artificial insertion peptide for the unbiased and rapid isolation of EVs in 20 min with ∼80% recovery in neutral conditions. Moreover, the approach demonstrates exceptional anti-interference capability and achieves a high purity of EVs comparable to standard ultracentrifugation and other methods. Importantly, the isolated EVs could be directly applied for downstream protein and nucleic acid analyses, including proteomics analysis, exome sequencing analysis, as well as the detection of both epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) gene mutation in clinical plasma samples. Our approach offers great possibilities for utilizing EVs in liquid biopsy, as well as in various other biomedical applications.

The shale of the Cambrian Qiongzhusi Formation in the Sichuan Basin is characterized by large burial depth and high maturity, but the shale gas enrichment pattern is still unclear. Based on the detailed characterization of Deyang-Anyue aulacogen, analysis of its depositional environments, together with reconstruction of shale gas generation and enrichment evolution against the background of the Leshan-Longnüsi paleouplift, the aulacogen-uplift enrichment pattern was elucidated. It is revealed that the Deyang-Anyue aulacogen controls the depositional environment of the Qiongzhusi Formation, where high-quality sedimentary facies and thick strata are observed. Meanwhile, the Leshan-Longnüsi paleouplift controls the maturity evolution of the shale in the Qiongzhusi Formation, with the uplift located in a high position and exhibiting a moderate degree of thermal evolution and a high resistivity. The aulacogen-uplift overlap area is conducive to the enrichment of shale gas during the deposition, oil generation, gas generation, and oil-gas adjustment stage, which also has a joint control on the development of reservoirs, resulting in multiple reservoirs of high quality and large thickness. Based on the aulacogen-uplift enrichment pattern and combination, four types of shale gas play are identified, and the sweet spot evaluation criteria for the Qiongzhusi Formation is established. Accordingly, a sweet spot area of 8 200 km2 in the aulacogen is determined, successfully guiding the deployment of Well Zi 201 with a high-yield industrial gas flow of 73.88×104 m3/d. The new geological insights on the aulacogen-uplift enrichment pattern provide a significant theoretical basis for the exploration and breakthrough of deep to ultra-deep Cambrian shale gas, highlighting the promising exploration prospect in this domain.

Abstract Angioimmunoblastic T-cell lymphoma (AITL) is a kind of aggressive T-cell lymphoma with significant enrichment of non-malignant tumor microenvironment (TME) cells. However, the complexity of TME in AITL progression is poorly understood. We performed single-cell RNA-Seq (scRNA-seq) and imaging mass cytometry (IMC) analysis to compare the cellular composition and spatial architecture between relapsed/refractory AITL (RR-AITL) and newly diagnosed AITL (ND-AITL). Our results showed that the malignant T follicular helper (Tfh) cells showed significantly increased proliferation driven by transcriptional activation of YY1 in RR-AITL, which is markedly associated with the poor prognosis of AITL patients. The CD8+ T cell proportion and cytotoxicity decreased in RR-AITL TME, resulting from elevated expression of the inhibitory checkpoints such as PD-1, TIGIT, and CTLA4. Notably, the transcriptional pattern of B cells in RR-AITL showed an intermediate state of malignant transformation to B-cell-lymphoma, and contributed to immune evasion by highly expressing CD47 and PD-L1. Besides, compared to ND-AITL samples, myeloid-cells-centered spatial communities were more prevalent but showed reduced phagocytic activity and impaired antigen processing and presentation in RR-AITL TME. Furthermore, specific inhibitory ligand-receptor interactions, such as CLEC2D-KLRB1, CTLA4-CD86, and MIF-CD74, were exclusively identified in the RR-AITL TME. Our study provides a high-resolution characterization of the immunosuppression ecosystem and reveals the potential therapeutic targets for RR-AITL patients.

Lead-bismuth coolant in nuclear reactors generates and accumulates 210Po during operation, which has strong toxicity and high volatility. When the coolant leaks or the reactor is opened, some of the 210Po on the surface of the coolant and in the covering gas will diffuse out of the main system if not properly handled and released into the environment, posing a potential serious threat to the ecological environment and human health. The high-temperature distillation capture technology can effectively extract large amounts of 210Po from the lead-bismuth coolant. Since 210Po is an extremely toxic radioactive isotope with no stable isotope, and to facilitate the experimental study of the capture process, this study ultimately chose its isotopic cousin, Te, as a substitute for 210Po for experimental research. Measuring the trace amount of Te in the distillation capture product can provide strong support for the 210Po extraction process. In the experiment, Te was extracted from the distillation capture film using nitric acid, and the 717 strong basic anion resin was used to separate Te from the extraction solution to eliminate the interference of impurity ions. SnCl2 reduced Te4+ to Te in HCl medium, and the absorbance was measured on a spectrophotometer to obtain the content of trace Te in the sample. The influence of interfering ions in the extraction solution on the measurement value of Te was investigated; the effects of the pH of the column liquid, the concentration and amount of the elution agent, and the washing rate on the separation of Te were explored; and a spectrophotometric method for the determination of trace Te in the distillation capture product of lead-bismuth coolant was established. The results show that at room temperature, the HCl concentration of the column liquid is 4 mol/L, the eluent is ultrapure water, the washing rate is 2 mL/min. The 717 strong basic anion resin demonstrates excellent separation performance for Te across a concentration range of 0 to 10 mg/L, where the absorbance shows a strong linear correlation with Te concentration. The correlation coefficient is r2=0.999 9, with a relative standard deviation of measurement ranging from 0.3% to 2.7%(n=6). The recovery rate is between 96.0% and 101.9%. This measurement method satisfies the requirements for researching the 210Po extraction process.

Abstract Background Babesia is a tick-borne protozoan blood parasite that can cause hemolytic anemia, thrombocytopenia, lethargy and splenomegaly in giant pandas. Methods We evaluated the efficacy and safety profile of a therapeutic regimen combining atovaquone and zithromycin in the context of babesiosis in giant pandas that have been naturally infected. The examined pandas underwent clinical and laboratory analyses, including hematology, biochemistry and thyroid hormone profiles. Upon diagnosis, the giant pandas were administered a compounded treatment consisting of atovaquone oral suspension (15 mg/kg, PO, q8 h), azithromycin tablets (10 mg/kg, PO, q24 h) and Enteral Nutritional Suspension (TPF) as a fat-rich supplement (0.5 ml/kg, PO, q8 h) for a 10-day period. Results The combination treatment increased the red blood cell count, hemoglobin levels and hematocrit in the pandas within a short period, while also reducing parasite levels below the PCR detection threshold. Conclusions Our study suggested that atovaquone and azithromycin combination therapy is highly effective for emergency treatment of Babesia sp. infection in giant pandas. Graphical Abstract

Abstract The gut microbiome, recognized as a critical component in the development of chronic diseases and aging processes, constitutes a promising approach for predicting host health status. Previous research has underscored the potential of microbiome-based predictions, and the rapid advancements of machine learning techniques have introduced new opportunities for exploiting microbiome data. To predict various host nonhealthy conditions, this study proposed an integrated machine learning-based estimation pipeline of Gut Age Index (GAI) by establishing a health aging baseline with the gut microbiome data from healthy individuals. We assessed the performance of GAI pipeline on two extensive cohorts - the Guangdong Gut Microbiome Project (GGMP) and the American Gut Project (AGP). In the GGMP cohort, for 20 common chronic diseases such as metabolic syndrome, obesity, and cardiovascular diseases, the proposed GAI achieved a balanced accuracy, ranging from 66 to 75%, with the prediction performance for atherosclerosis being the highest. In the AGP cohort, the balanced accuracy of GAI ranged from 58 to 72% for 10 diseases. Based on the results from these two datasets, we conclude that our proposed approach in this study can be used to predict individual health status, which offers the potential for scalable, cost-effective, and personalized health insights.

Abstract Background The functional aspects of non-suicidal self-injury (NSSI) among adolescents represent a complex phenomenon requiring deeper understanding. While research has identified various NSSI functions, including emotional regulation, attention-seeking, and social avoidance, the field lacks comprehensive analysis of how these functions cluster into distinct profiles. Understanding these functional profiles is crucial for developing targeted interventions. Method A cross-sectional study of 1,783 adolescents (1,464 girls, 318 boys) aged 12–18 years was conducted across 14 psychiatric or general hospitals in nine Chinese provinces. Participants completed the Functional Assessment of Self-Mutilation (FASM), which assesses 22 distinct NSSI functions across three primary dimensions: emotional regulation, attention-seeking, and social avoidance. Additional measures included the Patient Health Questionnaire (PHQ-9) for depression and Generalized Anxiety Disorder Scale (GAD-7) for anxiety symptoms. Latent profile analysis was employed to identify distinct patterns in NSSI functions, with model selection based on fit indices including AIC, BIC, entropy, and LMRT. Results Latent profile analysis revealed four distinct functional profiles: low attention-seeking-high social avoidance (LA-HS, 19.7%), high attention-seeking-high social avoidance (HA-HS, 9.5%), low attention-seeking and social avoidance (LA-LS, 57.8%), and high attention-seeking-low social avoidance (HA-LS, 13.0%). The HA-HS profile demonstrated the most severe clinical presentation, showing significantly elevated scores in NSSI frequency (M = 26.160, SD = 9.771), anxiety (GAD-7: M = 16.265, SD = 4.951), and depression (PHQ-9: M = 20.612, SD = 6.003). The LA-HS profile showed the second-highest severity (NSSI: M = 25.800, SD = 10.058; GAD-7: M = 14.775, SD = 5.376; PHQ-9: M = 19.966, SD = 5.938). Both profiles also demonstrated significantly higher rates of suicidal ideation (HA-HS: 77.6%; LA-HS: 79.2%) compared to other profiles. Conclusions Our findings reveal distinct patterns in how adolescents utilize NSSI functionally, particularly regarding attention-seeking and social avoidance dimensions. These functional profiles show meaningful associations with psychological outcomes, suggesting that understanding NSSI functions, rather than just behaviors, may be crucial for assessment and intervention. The identification of these distinct functional profiles among Chinese adolescents highlights the importance of function-specific approaches in clinical assessment and treatment planning.

Sepsis, a life-threatening medical condition, manifests as new or worsening organ failures due to a dysregulated host response to infection. Many patients with sepsis have manifested a hyperinflammatory phenotype leading to the identification of inflammatory modulation by corticosteroids as a key treatment modality. However, the optimal use of corticosteroids in sepsis treatment remains a contentious subject, necessitating a deeper understanding of their physiological and pharmacological effects. Our study conducts a comprehensive review of randomized controlled trials (RCTs) focusing on traditional corticosteroid treatment in sepsis, alongside an analysis of evolving clinical guidelines. Additionally, we explore the emerging role of artificial intelligence (AI) in medicine, particularly in diagnosing, prognosticating, and treating sepsis. AI's advanced data processing capabilities reveal new avenues for enhancing corticosteroid therapeutic strategies in sepsis. The integration of AI in sepsis treatment has the potential to address existing gaps in knowledge, especially in the application of corticosteroids. Our findings suggest that combining corticosteroid therapy with AI-driven insights could lead to more personalized and effective sepsis treatments. This approach holds promise for improving clinical outcomes and presents a significant advancement in the management of this complex and often fatal condition.

In order to reduce the cost of coal mine filling and mining, and achieve the synergistic utilization of multi-source coal based solid waste, special filling cementitious material is prepared using solid waste such as fly ash, gasification slag, and desulfurization gypsum as the main raw materials. By conducting orthogonal test, the optimal ratio of each component in the cementitious material was determined, and the Tesser five-step method was used to study the occurrence and leaching characteristics of heavy metal elements in the cementitious material. The results show that the optimal ratio of cementitious material, fly ash∶furnace bottom ash∶gasification slag∶cement clinker∶desulfurization gypsum∶quicklime, is 39.1%∶23.4%∶15.6%∶10.9%∶4.7%∶6.3%; after curing for 7 days, the hydration products mainly exist in the form of needles and are connected by flocculent and filamentous products; the curing age reaches 28 days, and the hydration products mainly exist in the form of clumps or blocks. The hydration products bind tightly, and the net slurry strength of the cementitious material reaches 1.83 MPa and 2.44 MPa at 7 and 28 days, respectively. The filling cementitious material prepared from solid waste such as fly ash can effectively solidify heavy metals and has no risk of heavy metal pollution to the underground environment.

Abstract This multicohort phase II trial (ALTER-G-001; NCT05262335) aimed to assess the efficacy of first-line anlotinib plus chemotherapy for gastrointestinal (GI) cancer patients with unresectable liver metastases. Eligible patients with colorectal cancer (Cohort A) or noncolorectal and nonesophageal GI cancer (Cohort C) received six cycles of anlotinib plus standard chemotherapeutic regimens followed by anlotinib plus metronomic capecitabine as a maintenance therapy. Liver metastasectomy can be performed when liver metastases are converted to resectable lesions. The primary outcome was the investigator-confirmed objective response rate (ORR) in the intention-to-treat population. Among the 47 patients in Cohort A, the ORR was 40.4% (95% CI 26.4–55.7), including 1 with a complete response (CR) and 18 who achieved a partial response (PR). The median progression-free survival (PFS) was 8.7 months (95% CI 7.3-NE), and the median overall survival (OS) was not reached. In Cohort C, 14 of 44 patients achieved a PR, with an ORR of 31.8% (95% CI 18.6–47.6). The PFS and OS were 5.8 months (95% CI 4.8–6.5) and 11.4 months (95% CI 5.8–19.3), respectively. The liver metastasectomy rate in patients with liver-limited disease was 22.7% (5/22) in Cohort A and 6.7% (2/30) in Cohort C. For pancreatic cancer patients, the ORR of the efficacy-evaluable population was 36.0% (9/25), and those with liver-limited metastasis had better survival. Moreover, no new safety concerns emerged. In conclusion, an anlotinib-based first-line regimen demonstrated promising antitumor activity among GI cancer patients with unresectable liver metastases and led to liver metastasectomy in selected patients.

The wild raspberry species Rubus sumatranus Miq 1861 is a promising resource for breeding thermotolerant cultivars. Its complete chloroplast genome spans 155,935 base pairs (bp), featuring the classic quadripartite structure: an 18,729 bp small single-copy region, an 85,662 bp large single-copy region, and two 25,772 bp inverted repeats. A total of 130 genes were identified, including 86 protein-coding, 36 tRNA genes, and 8 rRNA genes. A maximum likelihood phylogenetic tree based on chloroplast genomes shows that R. sumatranus, within the subgenus Idaeobatus, is sister to the subgenus Batothamnus. This confirms the polyphyletic nature of the subgenus Idaeobatus. The chloroplast genome assembly of R. sumatranus enhances our understanding of its evolutionary history.

Based on the background of Jiaxing City’s preliminary completion of institutional reform and revision of earthquake emergency plans, this paper deeply analyzes the current situation of earthquake emergency work faced by Jiaxing City. It proposes a strategic path for building and improving the earthquake emergency system in Jiaxing City from eight aspects, including reconstructing and strengthening collaborative emergency systems, improving emergency plans, and guiding social participation. The goal is to enhance the emergency response capacity of Jiaxing City in response to sudden earthquake events, while also hoping to provide valuable reference and inspiration for other cities in the Yangtze River Delta region with similar geographical and socio-economic characteristics in the construction of earthquake emergency systems.

In current genomic research, the widely used methods for predicting antimicrobial resistance (AMR) often rely on prior knowledge of known AMR genes or reference genomes. However, these methods have limitations, potentially resulting in imprecise predictions owing to incomplete coverage of AMR mechanisms and genetic variations. To overcome these limitations, we propose a pan-genome-based machine learning approach to advance our understanding of AMR gene repertoires and uncover possible feature sets for precise AMR classification. By building compacted de Brujin graphs (cDBGs) from thousands of genomes and collecting the presence/absence patterns of unique sequences (unitigs) for Pseudomonas aeruginosa, we determined that using machine learning models on unitig-centered pan-genomes showed significant promise for accurately predicting the antibiotic resistance or susceptibility of microbial strains. Applying a feature-selection-based machine learning algorithm led to satisfactory predictive performance for the training dataset (with an area under the receiver operating characteristic curve (AUC) of > 0.929) and an independent validation dataset (AUC, approximately 0.77). Furthermore, the selected unitigs revealed previously unidentified resistance genes, allowing for the expansion of the resistance gene repertoire to those that have not previously been described in the literature on antibiotic resistance. These results demonstrate that our proposed unitig-based pan-genome feature set was effective in constructing machine learning predictors that could accurately identify AMR pathogens. Gene sets extracted using this approach may offer valuable insights into expanding known AMR genes and forming new hypotheses to uncover the underlying mechanisms of bacterial AMR.

The objective of this study was to investigate the influences of integrated solution and aging treatment (SAT) on the compressive properties of laser powder bed fusion (LPBF) Corrax maraging stainless steel lattices. Cubic and face-centered cubic with Z-axis strut (FCCZ) lattices were produced and used to formulate two types of functionally-graded material (FGM) lattices. The lattices with FGM directions parallel and vertical to the stress were designated as FGM-P and FGM-V lattices, respectively. The compressive performances and fracture mechanisms were identified experimentally by digital image correction and theoretically by finite element analysis.The results show that SAT can significantly increase the specific strengths of these lattices by 34–42 %. The compressive performances and fracture mode of the FGM-V sample principally corresponded to the rule of mixture. However, the FGM-P sample did not follow the rule of mixture because its deformation concentrated only in the cubic-dominated regions. Moreover, the SEAs of the cubic and FGM-P samples were respectively improved by 30 % and 19 % by SAT, given their higher compressive strength and stable stress–strain curve. SAT can be applied to further extend the future application of these materials as cost-effective, high-performance lightweight structural materials.

This study investigates the microstructure and tensile properties of vacuum-brazed joints of Ti–48Al–2Cr–2Nb (Ti4822) and Ti–22Al–25Nb (Ti2AlNb) intermetallic alloys using Ti-based filler metals, with and without the addition of Zr element. Detailed microstructural characterization of the brazed joints was conducted using Electron Backscatter Diffraction and Transmission Electron Microscopy, identifying various phases and their distributions. The tensile properties were tested at room temperature and at 650 °C, revealing the influence of Zr on the mechanical performance of the joints. The results demonstrated that the microstructure of joints brazed with Zr-containing filler metals exhibited a layered structure with brittle Zr-enriched intermetallic compounds, limiting their mechanical properties. Conversely, Zr-free filler metals yielded more homogeneous and ductile microstructures, significantly improving tensile strength and elongation. The Zr-free joints obtained after holding at 980 °C for 60 min exhibits the highest tensile strength, reaching 368.23 MPa at room-temperature and 293.46 MPa at 650 °C, respectively. These findings provide valuable insights for optimizing brazing processes and filler metal compositions to enhance the performance of TiAl-based intermetallic alloy joints.

To improve the tribological properties of polyurethane (PU) based water-lubricated bearings specifically under severe conditions, expanded graphite/paraffin (EG/paraffin) is synthesized as self-lubricating additives and incorporated into the polyurethane matrix. The tribological performance of the PU-EG/paraffin composites at dry and water-lubricated conditions is investigated systemically. Results show that the friction coefficient of PU-EG/paraffin composites can reach a minimum value of 0.18 and 0.08 under dry and water lubricating conditions, respectively, with a reduction of 77% and 62% compared to that of pure PU. Meanwhile, the wear rate of these composites also exhibits a significant decrease under both conditions. The wear surface morphology indicates that a lubricating film can be formed by paraffin or paraffin-water emulsion between the friction pairs, thereby significantly enhancing the lubrication state under dry and water lubricating conditions, respectively. The present work puts forward a practical and effective approach for manufacturing self-lubricating water-lubricated bearing materials.

In this study, nanotwinned Cu (NT-Cu) and SiO2 hybrid joints were fabricated at 200 °C and subjected to thermal cycling tests (TCTs) up to 2000 cycles for the reliability evaluation. It is intriguing that the measured electrical resistance of the Cu–Cu joints decreased as the cycle number increased. Interfacial microstructure analyses were carried out by plan-view and cross-sectional scanning transmission electron microscope (STEM) to analyze the evolution of microstructures at the bonding interfaces and correlate with the increase in the electrical conductivity. Results showed that the bonding quality and conductivity of the NT-Cu/SiO2 hybrid joints were enhanced after the TCTs. The electrical resistance of the joints decreased by 18% after 2000 temperature cycles. Plan-view STEM images indicate the boning interface consisted of numerous discrete nanoscale voids for the as-fabricated Cu–Cu joints, and they merged into larger voids of approximately 100 nm in diameter through Ostwald ripening mechanism during thermal cycling. Furthermore, grain growth also occurred in the interface, resulting in excellent bonding interfaces.

Among substances, opiates and psychostimulants are responsible for the most significant public health problems, yet few studies have characterized their similarities or differences in the cortical plasticity of individuals with these substance related problems. This investigation utilized concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to examine cortical plasticity characteristics of individuals with heroin and methamphetamine related substance use disorder (SUD) relative to healthy controls. TMS-EEG data were collected from healthy control subjects (N = 35), subjects with heroin (N = 72) and methamphetamine (N = 69) use disorder. The data were analyzed using our fully-automated artifact rejection algorithm (ARTIST). Analyses were performed separately for F3, F4 and P3 stimulation sites. Linear mixed effects models were used to examine Group (heroin, methamphetamine, healthy control) x Time (pre, post single-session rTMS) interactions. To evaluate plasticity differences across groups, we observed the changes in single pulse TMS before and after single-session of rTMS. There was no change in alpha power after stimulation of the F3 or F4 sites across groups. The alpha power of the control group was significantly decreased when stimulating the P3 site, while there was no significant change in alpha power for either drug group during the same time window. The beta power of the healthy control group increased significantly when the F3 site was stimulated. In contrast, there was no significant change in either the methamphetamine or heroin group. Following a single-session of rTMS intervention, there was a significant difference in alpha-band power between the healthy control group and the two drug groups. Taking together, the study findings identified differential plasticity effects in the two types of SUD population, and highlighted the network effects of rTMS. The findings point to an exciting future path for using rTMS to test new plasticity-based interventions for treating drug addiction.

Abstract Objective This study aims to explore the appropriate surgical treatment method for acute intestinal obstruction caused by gastrointestinal foreign bodies in children through a comparison of clinical characteristics in patients treated via laparoscopically assisted approach and open surgery. Methods This study retrospectively analyzed 12 children with acute intestinal obstruction caused by gastrointestinal foreign bodies treated at Shanghai Children’s Hospital and Huzhou Maternity and Child Care Hospital from June 2019 to June 2024. Basic information, treatment methods, and prognoses of the patients were collected. General data, operation time, postoperative fasting time, postoperative hospital stay, and intraoperative and postoperative complications were compared between the two groups. Categorical data were compared using Fisher’s exact test. Normally distributed continuous data were expressed as mean ± standard deviation and analyzed using an independent samples t-test; non-normally distributed data were expressed as M (P25, P75) and analyzed using the non-parametric Mann-Whitney U test. Results Six cases underwent laparoscopic transumbilical extended incision, successfully extracting the intestines and removing the foreign bodies without converting to open surgery. Compared to Six cases undergoing traditional open surgery during the same period, the postoperative fasting time and postoperative hospital stay in the laparoscopic group were 4 (5 ± 3.65) days and 5.5 (5 ± 7.5) days, respectively, while in the traditional open surgery group, they were 5 (4.25 ± 6) days and 6 (5 ± 8.6) days, respectively; the differences were statistically significant (P

Abstract Deep learning models demonstrate impressive performance in rapidly predicting urban floods, but there are still limitations in enhancing physical connectivity and interpretability. This study proposed an innovative modeling approach that integrates convolutional neural networks with weighted cellular automaton (CNN-WCA) to achieve the precise and rapid prediction of urban pluvial flooding processes and enhance the physical connectivity and reliability of modeling results. The study began by generating a rainfall-inundation dataset using WCA and LISFLOOD-FP, and the CNN-WCA model was trained using outputs from LISFLOOD-FP and WCA. Subsequently, the pre-trained model was applied to simulate the flood caused by the 20 July 2021 rainstorm in Zhengzhou City. The predicted inundation spatial distribution and depth by CNN-WCA closely aligned with those of LISFLOOD-FP, with the mean absolute error concentrated within 5 mm, and the prediction time of CNN-WCA was only 0.8% that of LISFLOOD-FP. The CNN-WCA model displays a strong capacity for accurately predicting changes in inundation depths within the study area and at susceptible points for urban flooding, with the Nash-Sutcliffe efficiency values of most flood-prone points exceeding 0.97. Furthermore, the physical connectivity of the inundation distribution predicted by CNN-WCA is better than that of the distribution obtained with a CNN. The CNN-WCA model with additional physical constraints exhibits a reduction of around 34% in instances of physical discontinuity compared to CNN. Our results prove that the CNN model with multiple physical constraints has significant potential to rapidly and accurately simulate urban flooding processes and improve the reliability of prediction.

A method of ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-TSQ MS) was used to study the products of protopanaxadiol ginsenoside Rb1 and protopanaxatriol ginsenoside Rg1 in simulated digestion solution in vitro for researching the digestion characteristics of ginsenoside. The resullt showed that ginsenoside Rd, Rg3, Rg5, and Rk1 are found in the digestion products of ginsenoside Rb1. In addition, ginsenoside F2 is found in the simulated intestinal juice, suggesting that it is the peculiar degradation product. Therefore, the degradation pathways of ginsenoside Rb1 are as follows: ginsenoside Rb1→ginsenoside Rd→insenoside Rg3→ginsenoside Rg5/Rk1，ginsenoside Rb1→ginsenoside Rd→ginsenoside F2. In the digestive fluids of Rg1, both F1 and Rh1 are identified. The degradation pathways of ginsenoside Rg1 are determined to be: ginsenoside Rg1→ginsenoside F1 and ginsenoside Rg1→ginsenoside Rh1. The results showed that the contents of degradation products in simulated saliva, simulated gastric juice and simulated intestinal juice change with the digestion time. The digestion products ginsenoside Rd, Rg3, Rg5 and Rk1 of ginsenoside Rb1 are the highest after 2-6 h of simulated gastric juice digestion. Ginsenoside F2 is only produced in simulated intestinal juice to digest, in simulated intestinal juice to digest after 4 h content to the maximum. In simulated intestinal fluid, the degradation products of ginsenosides Rb1 and Rg1 are the highest at 4-6 h of digestion. Ginsenoside Rg1 is degraded in the mock digest to generate F1 and Rh1. Degradation products in simulated saliva, gastric juice and intestinal juice content gradually increased, in simulated gastric juice to digest its content reached the highest after 2 h. The degradation of ginsenosides in simulated saliva is milder compared to simulated gastric juice and simulated intestinal juice. However, the degradation products in simulated gastric juice are more abundant than in simulated intestinal juice. In the process of digestion, ginsenoside Rg1 degrades more easily than Rb1. Ginsenosides Rg1 and Rb1 are hydrolyzed in the digestive tract to produce a variety of small molecular saponins, which provide an important chemical and biological basis for the development and utilization of ginsenosides.

Abstract Current therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness. To address this limitation, our focus was on CD132, a subunit common to six inflammatory factor receptors implicated in SLE. Our study revealed heightened CD132 expression in SLE patients’ lymphocytes, contributing to the production of pro-inflammatory cytokines and immunoglobulins. We developed a novel humanized anti-CD132 monoclonal antibody, named as 2D4. 2D4 efficiently blocked IL-21 and IL-15, with limited effectiveness against IL-2, thereby suppressing T and B cells without disrupting immune tolerance. In the mouse immunization model, 2D4 virtually inhibited T cell-dependent, antigen-specific B-cell response. In lupus murine models, 2D4 mitigated inflammation by suppressing multiple pro-inflammatory cytokines and anti-dsDNA antibody titers, also diminishing proteinuria and glomerulonephritis. Compared to Belimumab, 2D4 exhibited superior efficacy in ameliorating the inflammatory state and preserving renal function. Moreover, 2D4 exhibited the ability to inhibit the production of pro-inflammatory factors and autoantibodies in PBMCs from individuals with SLE, highlighting its therapeutic potential for SLE individuals. Potent, 2D4 has the potential to significantly improve clinical outcomes in SLE and other complex autoimmune disorders.

Gold–Platinum (Au–Pt) alloy demonstrates considerable promise as a material for spacecraft proof mass, due to its ultra-low magnetic susceptibility. This study systematically investigates the effect of heat treatment on the microstructure evolution, magnetic properties, and mechanical performance of the Au72Pt28 alloy. The results indicate that the Pt-rich phase can be precipitated by discontinuous precipitation (DP) and continuous precipitation (CP) reactions. There is a competition between the two precipitation behaviors of Pt-rich phase, which is closely related to their diffusion path. With increasing ageing time and temperature, the discontinuous precipitates gradually coarsen and extend from grain boundaries into grain interior, while the Pt-rich phase nanoparticles precipitated by CP reaction uniformly distribute in the grain interior. Besides, the volume fraction of Pt-rich phase gradually increases, resulting in the increase of magnetic susceptibility. The coarsening of discontinuous precipitates is the main reason for the decrease in the nanoindentation hardness, and it increases rapidly due to a large number of intragranular Pt-rich phase nanoparticles.

Abstract Objective To study the clinical effectiveness of visual laryngoscopy combined with fiberoptic bronchoscopy-guided double-lumen endotracheal tube intubation in thoracic surgery patients with predicted difficult airways in thoracic surgery airways. Methods We randomly divided 162 patients with predicted difficult airways who required double-lumen tracheal intubation for thoracic surgery and randomly divided them into the video laryngoscopy group (Group VL, n = 54),fiberoptic bronchoscopy group (Group F, n = 54), and video laryngoscopy combined with fiberoptic bronchoscopy group (Group FVL, n = 54) according to the randomized number table method. Then, the success rate of the first intubation, the duration of intubation, the duration of positioning, the degree of exposure of the vocal cords (Cormack-Lehane grade), and the adverse reactions during intubation were recorded and analyzed. Results The success rate of first-time intubation was significantly higher in the FVL group than in the F and VL groups (92.6% vs. 87.0% vs. 53.7%, P

Abstract Atherosclerosis (AS) is the leading cause of coronary heart disease, which is the primary cause of death worldwide. Recent studies have identified disulfidptosis as a new type of cell death that may be involved in onset and development of many diseases. However, the role of disulfidptosis in AS is not clear. In this study, bioinformatics analysis and experiments in vivo and in vitro were performed to evaluate the potential relationship between disulfidptosis and AS. AS-related sequencing data were obtained from the Gene Expression Omnibus (GEO). Bioinformatics techniques were used to evaluate differentially expressed genes (DEGs) associated with disulfidptosis-related AS. Hub genes were screened using least absolute shrinkage and selection operator (LASSO) and random forests (RF) methods. In addition, we established a foam cell model in vitro and an AS mouse model in vivo to verify the expressions of hub genes. In addition, we constructed a diagnostic nomogram with hub genes to predict progression of AS. Finally, the consensus clustering method was used to establish two different subtypes, and associations between subtypes and immunity were explored. As the results, 9 disulfidptosis-related AS DEGs were identified from GSE28829 and GSE43292 datasets. Evaluation of DEGs using LASSO and RF methods resulted in identification of 4 hub genes (CAPZB, DSTN, MYL6, PDLIM1), which were analyzed for diagnostic value using ROC curve analysis and verified in vitro and in vivo. Furthermore, a nomogram including hub genes was established that accurately predicted the occurrence of AS. The consensus clustering algorithm was used to separate patients with early atherosclerotic plaques and patients with advanced atherosclerotic plaques into two disulfidptosis subtypes. Cluster B displayed higher levels of infiltrating immune cells, which indicated that patients in cluster B may have a positive immune response for progression of AS. In summary, disulfidptosis-related genes including CAPZB, DSTN, MYL6, and PDLIM1 may be diagnostic markers and therapeutic targets for AS. In addition, these genes are closely related to immune cells, which may inform immunotherapy for AS.

Abstract Fat accumulation, de novo lipogenesis, and glycolysis are key drivers of hepatocyte reprogramming and the consequent metabolic dysfunction-associated steatotic liver disease (MASLD). Here we report that obesity leads to dysregulated expression of hepatic protein-tyrosine phosphatases (PTPs). PTPRK was found to be increased in steatotic hepatocytes in both humans and mice, and correlates positively with PPARγ-induced lipogenic signaling. High-fat-fed PTPRK knockout male and female mice have lower weight gain and reduced hepatic fat accumulation. Phosphoproteomic analysis in primary hepatocytes and hepatic metabolomics identified fructose-1,6-bisphosphatase 1 and glycolysis as PTPRK targets in metabolic reprogramming. Mechanistically, PTPRK-induced glycolysis enhances PPARγ and lipogenesis in hepatocytes. Silencing PTPRK in liver cancer cell lines reduces colony-forming capacity and high-fat-fed PTPRK knockout mice exposed to a hepatic carcinogen develop smaller tumours. Our study defines the role of PTPRK in the regulation of hepatic glycolysis, lipid metabolism, and tumour development in obesity.

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.