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Abstract Background In recent years, lead-induced tricuspid regurgitation (LITR) has attracted increasing attention. At present, there are two commonly used transvalvular methods for pacing lead wires to enter the right ventricle. The first transvalvular approach involves placing the tip of the pacing lead directly through the tricuspid valve into the right ventricle, including “direct-crossing” and “drop-down.” The second transvalvular approach is to bend the pacing lead so that the reflexed lead body crosses the tricuspid valve and then enters the right ventricle, which is “prolapsing.” However, there are no clinical trials to evaluate or compare the effects of the above two different pacing lead transvalvular approaches on tricuspid regurgitation. In this study, we will perform a randomized clinical trial to understand the effect of different transvalvular lead wire transversal techniques on the incidence of tricuspid regurgitation. Methods Three hundred seventy-six subjects with right ventricular single-chamber pacemaker implantation or dual-chamber pacemaker implantation were recruited in the First Affiliated Hospital of Shantou University Medical College. Participants will be randomized into the direct group (“direct-crossing” and “drop-down”) or the bending group (“prolapsing”). The primary objective will be new tricuspid regurgitation or exacerbation of existing tricuspid regurgitation within 1 year of follow-up. Discussion This study aims to verify whether different transvalvular approaches influence the incidence of LITR, and is expected to provide an optimized method for routine pacemaker surgery and improve the long-term prognosis and quality of life of patients. Trial registration Chinese Clinical Trials Registry ChiCTR2100045558. Registered on April 19, 2021.

Abstract Objective Customized nonabsorbable membranes are widely used in severe alveolar bone defects and provide sufficient and precise regenerated bone tissue for subsequent dental implant placement. Although 3D-printed polyetheretherketone (PEEK) meshes have confirmed successful use in clinical cases, the performance of a PEEK mesh is not satisfactory. Compared with PEEK, polyetherketoneketone (PEKK) has better mechanical and processing properties. However, whether PEKK is suitable for making customized membranes remains unclear. The objectives of this study were (1) to evaluate the printing precision, surface characteristics, mechanical characteristics and biocompatibility of the PEKK mesh and (2) to compare the properties of the PEKK and PEEK meshes. Materials and methods Both PEKK and PEEK meshes were designed and manufactured via additive manufacturing technology combined with computer-aided design (CAD). The printing precision was evaluated with a high-resolution extraoral scanner. The surface characteristics were evaluated with a contact angle system and three-dimensional optical microscopy. The mechanical characteristics were evaluated via three-point bending tests and tensile tests. The biocompatibility was evaluated with a CCK-8 assay, live/dead viability assay and qRT-PCT. Results Compared with the PEEK mesh, the PEKK mesh exhibited better control in terms of the thickness and aperture area. Both the PEKK mesh and the PEEK mesh had a hydrophobic surface, but the PEKK mesh had a smoother surface. Compared with the PEEK mesh, the PEKK mesh has better compression and tensile properties. Both the PEKK mesh and the PEEK mesh had good biocompatibility. The proliferation of cells on the PEKK mesh was slightly lower than that on the PEEK mesh. Conclusions Compared with PEEK mesh, PEKK mesh has greater printing accuracy, smoother surfaces, better mechanical properties and similar biocompatibility and is expected to be used in the production of customized barrier membranes for the augmentation of severe bone defects. To ensure the stability of the mesh for clinical application, it is best to control the aperture diameter of the PEKK mesh to less than 2 mm with a thickness of 0.2 μm.

Abstract Background Endometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated. Methods Immunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC. Results A total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P

Abstract Developing highly active and durable air cathode catalysts is crucial yet challenging for rechargeable zinc-air batteries. Herein, a size-adjustable, flexible, and self-standing carbon membrane catalyst encapsulating adjacent Cu/Na dual-atom sites is prepared using a solution blow spinning technique combined with a pyrolysis strategy. The intrinsic activity of the Cu-N4 site is boosted by the neighboring Na-containing functional group, which enhances O2 adsorption and optimizes the rate-determining step of O2 activation (*O2 → *OOH) during the oxygen reduction reaction process. Meanwhile, the Cu-N4 sites are encapsulated within carbon nanofibers and anchored by the carbon matrix to form a C2-Cu-N4 configuration, thereby reinforcing the stability of the Cu centers. Moreover, the introduction of Na-containing functional groups on the carbon atoms significantly reduces the positive charge on their outer shell C atoms, rendering the carbon skeletons less susceptible to corrosion by oxygen species and further preventing the dissolution of Cu centers. Under these multi-type regulations, the zinc-air battery with Cu/Na-carbon membrane catalyst as the air cathode demonstrates long-term discharge/charge cycle stability of over 5000 h. This considerable stability improvement represents a critical step towards developing Cu-N4 active sites modified with the neighboring main-group metal-containing functional groups to overcome the durability barriers of zinc-air batteries for future practical applications.

Abstract Compartmentalization is a vital aspect of living cells to orchestrate intracellular processes. In a similar vein, constructing dynamic and responsive sub-compartments is key to synthetic cell engineering. In recent years, liquid-liquid phase separation via coacervation has offered an innovative avenue for creating membraneless organelles (MOs) within artificial cells. Here, we present a lab-on-a-chip system to reversibly trigger peptide-based coacervates within cell-mimicking confinements. We use double emulsion droplets (DEs) as our synthetic cell containers while pH-responsive elastin-like polypeptides (ELPs) act as the coacervate system. We first present a high-throughput microfluidic DE production enabling efficient encapsulation of the ELPs. The DEs are then harvested to perform multiple MO formation-dissolution cycles using pH as well as temperature variation. For controlled long-term visualization and modulation of the external environment, we developed an integrated microfluidic device for trapping and environmental stimulation of DEs, with negligible mechanical force, and demonstrated a proof-of-principle osmolyte-based triggering to induce multiple MO formation-dissolution cycles. In conclusion, our work showcases the use of DEs and ELPs in designing membraneless reversible compartmentalization within synthetic cells via physicochemical triggers. Additionally, presented on-chip platform can be applied over a wide range of phase separation and vesicle systems for applications in synthetic cells and beyond.

With China's agricultural sector being a major contributor to both the national economy and energy consumption, the rebound effect—the phenomenon where energy efficiency improvements lead to increased energy use—poses significant challenges to sustainable energy use. The motivation for this study stems from the need to understand the extent of this rebound impact and its underlying drivers, particularly in the context of China's agricultural modernization efforts. This study examines the rebound effect of energy consumption in China's agricultural productivity and the factors influencing it over the period from 1990 to 2023. Using a Generalized Method of Moments (GMM) model, this research analyzes the relationship between energy consumption, agricultural productivity, and several influencing factors, including technological innovation, rural-urban migration, and financial development. The results reveal that (1) energy efficiency improvements have led to a significant rebound effect in China's agricultural sector, limiting potential energy savings, (2) technological advancements have mitigated the rebound effect to some extent, but the effect remains substantial, (3) rural-urban migration has contributed to labor shortages, increasing mechanization and energy demand, and (4) financial development has positively influenced both agricultural productivity and energy use, exacerbating the rebound effect. The study suggests that policymakers should focus on developing stricter energy efficiency standards and promoting technological innovations that reduce energy intensity in agriculture, while also addressing labor migration challenges to curb the rebound impact and achieve more sustainable agricultural growth.

Transient Perivascular Inflammation of the\ Carotid Artery (TIPIC) syndrome is uncommon, and cases of TIPIC induced by the targeted drug, sorafenib, are extremely rare. This case report describes a patient with acute myeloid leukemia carrying an FMS‐like tyrosine kinase 3 mutation, who developed TIPIC syndrome, which may have been induced by sorafenib treatment. A 65-year-old woman diagnosed with acute myeloid leukemia experienced severe neck pain and sclerotic blisters on her palms and soles during sorafenib treatment. Carotid ultrasound revealed thickening of the right common carotid artery (RCCA) wall, and magnetic resonance imaging revealed perivascular tissue edema in the distal RCCA. Following clinical and imaging assessments, the patient was diagnosed with TIPIC syndrome. Treatment involved a one-week course of oral steroid therapy with dexamethasone and non-steroidal anti-inflammatory drugs, which led to complete clinical recovery. TIPIC syndrome involves transient nonspecific perivascular inflammation of the carotid adventitia; however, the precise underlying cause remains unclear. In this study, we report a rare case and explore the potential pathophysiological mechanisms through a review of the existing literature.

The deliberately origin mislabeling of sweet cherry causes significantly disruptions to market integrity and consumers' trust. In this study, 153 cherry samples from five provinces in China and the corresponding irrigation water and soil samples were collected. 5 stable isotope ratios (δ13C, δ15N, δ2H, δ18O, 87Sr/86Sr) and 8 multi-element contents (Na, Mg, P, K, Ca, Fe, Zn, Se) of cherry were determined by EA-IRMS and ICP-MS to study isotopic fractionation and elemental enrichment mechanisms for origin traceability. The results show the δ2H and δ18O of cherry exhibit a strong correlated with its irrigation water (r2 > 0.85), while δ15N, 87Sr/86Sr, Fe, Zn and Se contents are related to its cultivated soil (r2 > 0.75), and the δ13C is related to the local microclimate. ANOVA reveals that the regional differences of δ13C, δ2H, δ18O, 87Sr/86Sr as well as Na, Mg, Ca contents of cherry are significant (P

In oil and gas exploration, elucidating the complex interdependencies among geological variables is paramount. Our study introduces the application of sophisticated regression analysis method at the forefront, aiming not just at predicting geophysical logging curve values but also innovatively mitigate hydrocarbon depletion observed in geochemical logging. Through a rigorous assessment, we explore the efficacy of eight regression models, bifurcated into linear and nonlinear groups, to accommodate the multifaceted nature of geological datasets. Our linear model suite encompasses the Standard Equation, Ridge Regression, Least Absolute Shrinkage and Selection Operator, and Elastic Net, each presenting distinct advantages. The Standard Equation serves as a foundational benchmark, whereas Ridge Regression implements penalty terms to counteract overfitting, thus bolstering model robustness in the presence of multicollinearity. The Least Absolute Shrinkage and Selection Operator for variable selection functions to streamline models, enhancing their interpretability, while Elastic Net amalgamates the merits of Ridge Regression and Least Absolute Shrinkage and Selection Operator, offering a harmonized solution to model complexity and comprehensibility. On the nonlinear front, Gradient Descent, Kernel Ridge Regression, Support Vector Regression, and Piecewise Function-Fitting methods introduce innovative approaches. Gradient Descent assures computational efficiency in optimizing solutions, Kernel Ridge Regression leverages the kernel trick to navigate nonlinear patterns, and Support Vector Regression is proficient in forecasting extremities, pivotal for exploration risk assessment. The Piecewise Function-Fitting approach, tailored for geological data, facilitates adaptable modeling of variable interrelations, accommodating abrupt data trend shifts. Our analysis identifies Ridge Regression, particularly when augmented by Piecewise Function-Fitting, as superior in recouping hydrocarbon losses, and underscoring its utility in resource quantification refinement. Meanwhile, Kernel Ridge Regression emerges as a noteworthy strategy in ameliorating porosity-logging curve prediction for well A, evidencing its aptness for intricate geological structures. This research attests to the scientific ascendancy and broad-spectrum relevance of these regression techniques over conventional methods while heralding new horizons for their deployment in the oil and gas sector. The insights garnered from these advanced modeling strategies are set to transform geological and engineering practices in hydrocarbon prediction, evaluation, and recovery.

Essential mineral elements such as zinc and iron play a crucial role in maintaining crop growth and development, as well as ensuring human health. Foxtail millet is an ancient food crop rich in mineral elements and constitutes an important dietary supplement for nutrient-deficient populations. The ZIP (ZRT, IRT-like protein) transporters are primarily responsible for the absorption, transportation and accumulation of Zn, Fe and other metal ions in plants. Here, we identified 14 ZIP transporters in foxtail millet (SiZIP) and systematically characterized their phylogenetic relationships, expression characteristics, sequence variations, and responses to various abiotic stresses. As a result, SiZIPs display rich spatiotemporal expression characteristics in foxtail millet. Multiple SiZIPs demonstrated significant responses to Fe, Cd, Na, and K metal ions, as well as drought and cold stresses. Based on homologous comparisons, expression characteristics and previous studies, the functions of SiZIPs were predicted as being classified into several categories: absorption/efflux, transport/distribution and accumulation of metal ions. Simultaneously, a schematic diagram of SiZIP was drawn. In general, SiZIPs have diverse functions and extensively involve in the transport of metal ions and osmotic regulation under abiotic stresses. This work provides a fundamental framework for the transport and accumulation of mineral elements and will facilitate the quality improvement of foxtail millet.

With the massive participation of new energy in the operation of distribution network (DN), the uncertainties arising from both load and renewable generation have brought challenges to its secure and reliable operation. In this paper, a model of day-ahead and intraday optimal scheduling based on dynamic partitioning (DP) of DN is constructed to realize the refinement of operation in both temporal and spatial dimensions, as well as to improve the reliability of system operation. For the strong fluctuation characteristics of the source-load in DN, the DP is achieved under the premise that the partition structure in each period is tight and the internal power supply has the ability to balance the power fluctuations. In order to improve the regional autonomy of DN, a day-ahead multi-objective optimal scheduling model is constructed based on the DP with the optimization objectives of weak inter-partition power coupling, lowest deficiency rate of flexibility, and lowest operating cost. And a scheme for articulation is proposed to ensure the effective guidance of day-ahead for intraday. Then the intraday dispatch model is constructed by shifting the focus to the incorporate characteristics of DP and quickly smooth the net load fluctuations. Finally, the performance and reliability of the proposed models are verified via case studies.

Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and hyperalgesia. At present, however, the mechanisms underlying the development of morphine analgesic tolerance are not fully understood. This tolerance is influenced by various opioid receptor and kinase protein modifications, such as phosphorylation and ubiquitination. Here, we established a murine morphine tolerance model to investigate whether and how S-nitrosoglutathione reductase (GSNOR) is involved in morphine tolerance. Repeated administration of morphine resulted in the down-regulation of GSNOR, which increased excessive total protein S-nitrosation in the prefrontal cortex. Knockout or chemical inhibition of GSNOR promoted the development of morphine analgesic tolerance and neuron-specific overexpression of GSNOR alleviated morphine analgesic tolerance. Mechanistically, GSNOR deficiency enhanced S-nitrosation of cellular protein kinase alpha (PKCα) at the Cys78 and Cys132 sites, leading to inhibition of PKCα kinase activity, which ultimately promoted the development of morphine analgesic tolerance. Our study highlighted the significant role of GSNOR as a key regulator of PKCα S-nitrosation and its involvement in morphine analgesic tolerance, thus providing a potential therapeutic target for morphine tolerance.

Abstract Objectives Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. Methods Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer–specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. Results In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157–5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). Conclusions Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Abstract Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions. Graphical Abstract

Abstract Background Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). Methods Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. Results A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan–Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P

Summary: Here, we present a protocol for Xenium spatial transcriptomics studies using fixed frozen mouse brain sections. We describe steps for intracardiac perfusion, cryosectioning, and floating section mounting of brain sections, which enable runs on the Xenium analyzer and data delivery. We demonstrate that, in addition to the 10× Genomics-validated formalin-fixed paraffin-embedded (FFPE) and fresh frozen sections, fixed frozen thin brain sections are compatible with the Xenium platform and provide excellent imaging and quantification results for spatially resolved gene expression.For complete details on the use and execution of this protocol, please refer to Ma et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The incidence rate of pyogenic liver abscess caused by multidrug-resistant bacteria has increased in recent years. This study aimed to identify the clinical characteristics and risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria. We conducted a retrospective analysis of the clinical features, laboratory test results, and causes of pyogenic liver abscesses in 239 patients admitted to a tertiary hospital. Multivariable logistic regression was used to identify risk factors for multidrug resistance. Among patients with pyogenic liver abscesses, the rate of infection caused by multidrug-resistant organisms was observed to be 23.0% (55/239), with a polymicrobial infection rate of 14.6% (35/239). Additionally, 71 cases (29.7%) were associated with biliary tract disease. Patients with pyogenic liver abscesses caused by multidrug-resistant organisms had a significantly higher likelihood of polymicrobial infection and increased mortality (7/44 [15.9%] vs. 3/131 [2.3%]; p = .003). The Charlson Comorbidity Index (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.06–1.68), hospitalization (aOR: 10.34, 95% CI: 1.86–60.3) or an invasive procedure (aOR: 9.62; 95% CI: 1.66–71.7) within the past 6 months, and gas in the liver on imaging (aOR: 26.0; 95% CI: 3.29–261.3) were independent risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria. A nomogram was constructed based on the risk factors identified. The nomogram showed high diagnostic accuracy (specificity, 0.878; sensitivity 0.940). Multidrug-resistant organisms causing pyogenic liver abscesses have specific characteristics. Early identification of patients at high risk of infection with multidrug-resistant organisms could help improve their management and enable personalized treatment.

Power flow is an extensively used tool in various operations and planning of power systems. In this paper, we propose an efficient hybrid method for solving the power flow problems in ill-conditioned power systems. This method is implemented in a framework of two-part alternating iteration. In Part I of this method, PV bus voltages are regarded as constant and PQ bus voltages are updated by the Z-bus Gauss method. In Part II of this method, PQ bus loads are equivalent to dynamic admittances, and PV bus voltage angles are updated by Newton’s method. The values of PQ bus voltage magnitudes and PV bus voltage angles are passed between Part I and Part II. The proposed method is validated in well- and ill-conditioned systems and compared with several well-known power flow methods. Results show that the proposed method is robust and efficient to address the issues related with large-scale ill-conditioned power systems and it is not significantly affected by the considered initial guess.

Background: Breast cancer stands as a globally significant contributor to both incidence rates and mortality among women. Approximately 10–15 % of women will face a diagnosis of an advanced yet potentially treatable stage of the disease. When individuals diagnosed with locally advanced breast cancer (LABC) exhibit resistance to preoperative chemotherapy and experience tumor progression, they unfortunately forfeit the opportunity for surgical intervention, thereby diminishing the prospects for a radical cure. Method: We conducted a prospective, single-arm cohort study aimed at evaluating the feasibility of locally modified radical resection for LABC with skin invasion. The primary endpoints encompassed overall survival (OS) and disease-free survival (DFS), whereas the secondary endpoint focused on the quality of life (QoL) among breast cancer patients. Results: Between March 2018 and December 2022, a total of 38 eligible patients were enrolled in this study. The Kaplan-Meier estimates for 1-year, 3-year, and 5-year DFS among all patients were 69.8 %, 53.3 %, and 37.5 %, respectively. Correspondingly, the OS rates were 100.0 %, 85.6 %, and 68.0 %. Both univariate and multivariate analyses revealed that patients with a history of neoadjuvant chemotherapy who exhibited stable or progressive disease had inferior DFS outcomes. Notably, patients demonstrated clinically meaningful and statistically significant enhancements in functional status and overall QoL. However, no notable improvement was observed in specific symptom domains. Conclusion: Patients with locally advanced breast cancer, specifically those presenting with T4 tumors, who undergo surgical intervention followed by postoperative adjuvant therapy, can attain favorable prognostic outcomes and experience an enhanced quality of life.

Primary graft dysfunction (PGD) is a severe form of acute lung injury resulting from lung ischemia/reperfusion injury (I/R) in lung transplantation (LTx), associated with elevated post-transplant morbidity and mortality rates. Neutrophils infiltrating during reperfusion are identified as pivotal contributors to lung I/R injury by releasing excessive neutrophil extracellular traps (NETs) via NETosis. While alveolar macrophages (AMs) are involved in regulating neutrophil chemotaxis and infiltration, their role in NETosis during lung I/R remains inadequately elucidated. Extracellular histones constitute the main structure of NETs and can activate AMs. In this study, we confirmed the significant involvement of extracellular histone-induced M1 phenotype of AMs (M1-AMs) in driving NETosis during lung I/R. Using secretome analysis, public protein databases, and transwell co-culture models of AMs and neutrophils, we identified Cathepsin C (CTSC) derived from AMs as a major mediator in NETosis. Further elucidating the molecular mechanisms, we found that CTSC induced NETosis through a pathway dependent on NADPH oxidase-mediated production of reactive oxygen species (ROS). CTSC could significantly activate p38 MAPK, resulting in the phosphorylation of the NADPH oxidase subunit p47phox, thereby facilitating the trafficking of cytoplasmic subunits to the cell membrane and activating NADPH oxidase. Moreover, CTSC up-regulated and activated its substrate membrane proteinase 3 (mPR3), resulting in an increased release of NETosis-related inflammatory factors. Inhibiting CTSC revealed great potential in mitigating NETosis-related injury during lung I/R. These findings suggests that CTSC from AMs may be a crucial factor in mediating NETosis during lung I/R, and targeting CTSC inhition may represent a novel intervention for PGD in LTx.

Extant mobile game research has paid great attention to men who play mobile games while ignoring female players. Although “willingness to pay” (WTP) is regarded as an important dependent variable in gaming research, few studies have explored this variable from an anthropomorphic perspective. To fill these gaps in the literature, this study aims to study the antecedents of WTP, with a focus on virtual in-game items and the mediating effect of work/play motivation. Based on the determinants of anthropomorphism, this work examines certain aspects of mobile games, including servant role in mobile games, a sense of communion, and the attractiveness of the characters. This study explores the effects of such characteristics on work/play motivation, as well as its influence on WTP. A game called “Love and Producer” was selected for this study, and the feedback from 230 female respondents was analyzed using Structural Equation Modeling (SEM). The results show that the servant role and the attractiveness of the characters affect female players’ desire to work with the characters, and the communion and the attractiveness of the characters affect female players’ desire to play with these characters. The female players’ desire to work and play with the characters directly influenced their willingness to pay for virtual game items. Moreover, the mediating effect that playing games has on female players’ desire to work/play with the characters was also validated. This article introduces new information on female game character design and interactivity in games.

ABSTRACT Bacterial ribonuclease E (RNase E) is vital for posttranscriptional regulation by degrading and processing RNA. The RraA protein inhibits RNase E activity through protein-protein interactions, exerting a global regulatory effect on gene expression. However, the specific role of RraA remains unclear. In this study, we investigated rraA expression in Vibrio alginolyticus ZJ-T and identified three promoters responsible for its expression, resulting in transcripts with varying 5′-UTR lengths. During the stationary phase, rraA was significantly posttranscriptionally inhibited. Deletion of rraA had no impact on bacterial growth in rich medium Luria-Bertani broth with salt (LBS) but resulted in decreased biofilm formation and increased resistance to polymyxin B. Transcriptome analysis revealed 350 differentially expressed genes (DEGs) between the wild type and the rraA mutant, while proteome analysis identified 267 differentially expressed proteins (DEPs). Integrative analysis identified 55 genes common to both DEGs and DEPs, suggesting that RraA primarily affects gene expression at the posttranscriptional level. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis demonstrated that RraA facilitates the conversion of fatty acids, propionic acid, and branched-chain amino acids to acetyl-CoA while enhancing amino acid and peptide uptake. Notably, RraA positively regulates the expression of virulence-associated genes, including those involved in biofilm formation and the type VI secretion system. This study expands the understanding of the regulatory network of RraA through transcriptome analysis, emphasizing the importance of proteomic analysis in investigating posttranscriptional regulation.IMPORTANCERraA is an inhibitor protein of ribonuclease E that interacts with and suppresses its endonucleolytic activity, thereby playing a widespread regulatory role in the degradation and maturation of diverse mRNAs and noncoding small RNAs. However, the physiological functions and associated regulon of RraA in Vibrio alginolyticus have not been fully elucidated. Here, we report that RraA impacts virulence-associated physiological processes, namely, antibiotic resistance and biofilm formation, in V. alginolyticus. By conducting an integrative analysis of both the transcriptome and proteome, we revealed the involvement of RraA in carbon metabolism, amino acid catabolism, and transport, as well as in the type VI secretion system. Collectively, these findings elucidate the regulatory influence of RraA on multiple pathways associated with metabolism and pathogenesis in V. alginolyticus.

Indigenous foods are carriers of traditional native North American food culture and living philosophy. They are featured by the wide varieties in fresh and processed forms, richness in nutrition, flavor, health benefits and diversity in origins, but are usually misunderstood or underrepresented in the modern food systems. Conventional processing and cooking methods are sometimes labor-intensive, less efficient and lack science-based guidelines to prevent unseen safety risks and food loss. Global and regional climate change have caused additional challenges to conventional cooking/processing, and increased native communities’ reliance on externally produced foods, which have resulted in increasing nutritional unbalance and prevalence of diet-related health issues. Current and emerging technologies, such as storage and packaging, drying, safety processing, canning, pickling, and fermentation, which treat foods under optimized conditions to improve the safety and extend the shelf-life, are increasingly used in current food systems. Therefore, exploring these technologies for indigenous foods offers opportunities to better preserve their nutrition, safety, and accessibility, and is critical for the sovereignty and independence of indigenous food systems, and sustainability of indigenous food culture. This mini-review focuses on identifying adoptable processing and preservation technologies for selected traditional indigenous foods in North America, summarizing education, extension, and outreach resources and discussing the current challenges and future needs critical to expanding knowledge about indigenous foods and improving food sovereignty, nutrition security, and health equity.

Herbal extraction residues (HERs) cause serious environmental pollution and resource waste. In this study, a novel green route was designed for the comprehensive reutilization of all components in HERs, taking Magnolia officinalis residues (MOR) as an example. The reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients (magnolol and honokiol) originally remaining in MOR and to make MOR more accessible for hydrolysis. A metal–organic frame material MIL-101(Cr) with a maximum absorption capacity of 255.64 mg g−1 was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions, and 40 g L−1 reducing sugars were obtained with 81.8% enzymatic hydrolysis rate at 10% MOR solid loading. Finally, 382 mg L−1 β-amyrin was produced from MOR hydrolysates by an engineered yeast strain. In total, 1 kg honokiol, 8 kg magnolol, and 7.64 kg β-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB.

In this paper, we present our process design kits (PDKs) component performances for different wavelengths in the visible to near-infrared (VIS-NIR) range on Shanghai Industrial μTechnology Research Institute's (SITRI's) 200 mm silicon nitride (SiN) photonics platform. SiN waveguide platform has emerged as a promising technology due to its low optical loss, relatively high refractive index, and transparency across the VIS-NIR spectrum. The industrialization of SiN platforms requires matured PDKs. On SITRI's 200 mm SiN photonics platform, we developed PDKs using both Plasma-Enhanced Chemical Vapor Deposition (PECVD) and Low-Pressure Chemical Vapor Deposition (LPCVD) processes, with SiN layers of 180 nm and 150 nm thicknesses, respectively. The fabricated waveguides exhibit low propagation loss, ranging from 2.5 dB/cm to 0.34 dB/cm from 532 nm to 860 nm. Additionally, we present a low bending loss which is less than 0.06 dB/90° with a radius of 100 μm. Furthermore, the loss of the linear grating coupler (LGC) is less than 2.6 dB at 785 nm. We have also achieved low-loss splitters, including 1 × 2 multimode interference (MMI) coupler, and directional coupler (DC), with a minimum excess loss of 0.03 dB. Additionally, micro ring resonator with high quality (Q) factors of 146,000 has been demonstrated. Our work on developing these PDKs will open new opportunities for researchers and developers to design and fabricate advanced photonic devices on the SiN platform in SITRI's 200 mm fabrication line.

Objective: To assess the safety and feasibility of ultra-remote robot-assisted laparoscopic hysterectomy using the Edge Multi-Port Endoscopic Surgical Robot MP1000 (Shenzhen Edge Medical Co., Ltd., Shenzhen, China) combined with 5G communication technology. Methods: A case of remote robot-assisted laparoscopic hysterectomy was successfully completed on May 2024 by using the Edge Multi-Port Endoscopic Surgical Robot MP1000 at Zhongnan Hospital of Wuhan University and the People's Liberation Army General Hospital, approximately 1, 200 ​km apart. The procedure was simultaneously broadcast during the 36th Annual Meeting of the International Society for Gynecologic Endoscopy in Conjuction with the Peking University Gynecologic Oncology Summit Forum. Results: A 49-year-old female was hospitalized in the Department of Gynecology of Zhongnan Hospital of Wuhan University for frequent urination for half a year and increased menstrual flow for over a month. The patient was diagnosed with abnormal uterine bleeding caused by multiple uterine leiomyoma and endometrial polyps, combined with moderate anemia. There were no contraindications for surgery, and the patient had surgical indications. On May 2024, the patient underwent a 5G remote robot-assisted laparoscopic hysterectomy and bilateral salpingectomy under general anesthesia. The procedure was successful, with no surgical complications and no interruptions during the live broadcast. The intraoperative blood loss was approximately 20 ​mL, and the surgery lasted about 70 ​min. The bidirectional latency during the operation was around 19 ​ms, with no adverse events related to the robot or the network. The patient recovered well postoperatively and was discharged on the fourth day with no postoperative complications. Conclusion: Preliminary findings indicate that ultra-remote robot-assisted laparoscopic hysterectomy is safe and feasible with the support of 5G communication technology. This surgery represents the first globally broadcast remote procedure in the field of gynecology, marking a new milestone in the stability and safety of China's remote medical technology. Remote robotic surgery is expected to be widely promoted in the future, providing services to patients in areas with limited medical resources.

Abstract Background Discharged psychiatric patients are at higher risk of suicide due to various risk factors in their lives compared to the general population. However, specific problems and needs of these patients after discharge remain unclear. This research constitutes a segment of a broader implementation study designed to formulate an interventional strategy targeting post-discharge suicide among Chinese psychiatric patients. The present study seeks to qualitatively investigate the problems and needs from the perspectives of patients, their lay healthcare supporters (LHSs), and mental health professionals (MPs), aiming to enhance the efficacy of the interventional strategy. Methods This study is part of a larger implementation study based on Shenzhen Kangning Hospital (SKH) in Shenzhen, Guangdong, China. Under the community-based participatory research framework, we recruited discharged psychiatric patients, their LHSs, and MPs as a collaborative community team, and we conducted individual in-depth interviews for patients and LSHs and focus group interviews with MPs. We utilized a thematic analysis approach to identify sub-themes and themes from interviews through systematically coding and analyzing the data. Results A total of 45 participants were recruited for interviews, comprising 17 patients, 8 LHSs, and 20 MPs. We conducted 25 individual in-depth interviews and 3 focus group interviews. Through the interviews, we identified three themes of post-discharge problems: problems related to self, family-related problems, societal and community-related problems. We also identified four themes related to reducing post-discharge suicide: proactive self-management, multifunctional relatives, multifunctional MP group, and a warm society. The tangible support from LHSs and emotional support from MPs are strongly emphasized. Follow-up interventions were identified as the most significant way to addressing these unmet needs. Instrumental support from the community and a caring and non-discriminatory environment for individuals with mental disorders are essential for reducing suicide risk. Conclusions Establishing an integrated mental health care service network that connects psychiatric patients, LHSs, and MPs cross community and societal sectors, with patient-centered follow-up care at its core, is a practical approach to better address patients’ needs and reduce post-discharge suicide. Trial registration Registration number: NCT04907669. Date of registration: May 26th,2021.

Abstract Background Studies have investigated how adults with severe depressive symptoms are more likely to attempt suicide, and these adults often have traumatic experiences and chaotic sleep/wake rhythms. Thus, this study using Latent class analysis aimed to investigate the relationship between childhood trauma class, chronotype, and suicide attempts among emerging adults with severe depressive symptoms. Methods This study was conducted among emerging adults with severe depressive symptoms covering 63 Universities in Jilin Province, China. A total of 1,225 emerging adults (mean age = 19.6 ± 1.78) constructed the final sample. In addition to measuring socio-demographic characteristics, the Childhood Trauma Questionnaire-Short Form, the Single-Item Chronotyping, and a single item for suicide attempts were used to evaluate childhood trauma, chronotype, and suicide attempts, respectively. Latent class analysis was applied to identify the classes of childhood trauma within emerging adults who had severe depressive symptoms. Hierarchical logistic regression models were run to investigate the effects of socio-demographic characteristics, chronotype, and childhood trauma class on suicide attempts. Results Three latent classes were identified: the Low-risk for childhood trauma class, the Neglect class, and the High-risk for childhood abuse class. Those who suffered sexual, emotional, and physical abuse at the same time were divided into the High-risk for childhood abuse class, and were significantly more likely to experience suicide attempts than those in the Neglect class (OR = 1.97, 95%CI = 1.34–2.89, p < 0.001) and the Low-risk for childhood trauma class (OR = 2.28, 95% CI = 1.50-3.46, p

Abstract Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets. Video Abstract

Abstract Idiopathic fertility disorders are associated with mutations in various genes. Here, we report that coiled-coil glutamate-rich protein 1 (CCER1), a germline-specific and intrinsically disordered protein (IDP), mediates postmeiotic spermatid differentiation. In contrast, CCER1 deficiency results in defective sperm chromatin compaction and infertility in mice. CCER1 increases transition protein (Tnp1/2) and protamine (Prm1/2) transcription and mediates multiple histone epigenetic modifications during the histone-to-protamine (HTP) transition. Immiscible with heterochromatin in the nucleus, CCER1 self-assembles into a polymer droplet and forms a liquid-liquid phase-separated condensate in the nucleus. Notably, we identified loss-of-function (LoF) variants of human CCER1 (hCCER1) in five patients with nonobstructive azoospermia (NOA) that were absent in 2713 fertile controls. The mutants led to premature termination or frameshift in CCER1 translation, and disrupted condensates in vitro. In conclusion, we propose that nuclear CCER1 is a phase-separated condensate that links histone epigenetic modifications, HTP transitions, chromatin condensation, and male fertility.

ABSTRACTThe aim of this study was to investigate how the concentration of interleukin-13 (IL-13) affects the regulation of endothelial cell migration after injury. The incubation of recombinant human interleukin-13 (rhIL-13) strongly increased the content of reactive oxygen species (ROS) in HUVECs via the JAK-1/STAT-3/NOX-4 signaling pathway. Antagonizing the high intracellular ROS that was induced by rhIL-13 promoted the migration of HUVECs. Furthermore, IL-13 neutralization not only inhibited intimal hyperplasia, but also promoted the migration of endothelial cells (ECs) after injury. The results suggest that IL-13 inhibition is a potential means of stimulating endothelial cells recovery after injury. Therefore, the attenuation of IL-13 activation may have therapeutic value for vascular disease.

Gully erosion is a severe form of soil erosion, but gully internal erosion processes are poorly understood, especially at the event scale. To investigate gully internal erosion intensity and understand the related gully development mechanism in an agricultural environment with gully head stabilization and vegetation restoration efforts, two successive field investigations were carried out just before and after a prolonged rainfall event in 2021 in the tableland region of China's Loess Plateau. Thirteen gullies were investigated and all experienced gully internal erosion, while most gully boundaries were stable during the heavy rainfall event based on the comparison of the UAV digital orthograph maps (DOMs acquired with Unmanned Aerial Vehicle) before and after the rainfall event. The proportion of gully internal erosion area to gully internal area of the 13 investigated gullies ranged from 3 to 55%, with average areal erosion proportion of the gully sidewall and gully bed of 21% and 36%, respectively. The erosion area of subdrainage units (SDUs) on the gully sidewall was positively correlated to the SDU area, average SDU slope gradient and vegetation type, while the erosion area on the gully bed was positively correlated to the gully area, gully depth and gully bed slope gradient. Gully internal erosion was not significantly correlated with gully drainage area because the connectivity between the upslope and gully areas was interrupted and the effective drainage area of the gully was obviously reduced by soil erosion conservation measures, including terraces on the upslope drainage area, shrub belts, and water barriers. Thus, gully internal erosion is still active under the heavy rainfall storm against the background of the ‘Grain for Green’ and ‘Gully Stabilization and Tableland Protection’ programs, and integrated measures for preventing both gully expansion and gully internal erosion must be further enhanced in the context of climate change.

Femtosecond laser machining offers high precision and minimal thermal impact, making it a promising technique for processing hard and brittle materials like single-crystal diamonds (SCDs). In this study, the femtosecond laser machining process for SCD material was systematically optimized to improve both machining efficiency and quality. Initial single-factor experiments were conducted to explore the effects of key process parameters—laser power, scanning speed, and number of scans—on machining performance. Subsequently, response surface methodology (RSM)-based experiments designed using the Box–Behnken method were employed to comprehensively refine the process. A regression model was developed to analyze the data, and the interaction effects of the parameters were thoroughly evaluated. The validated model identified an optimal set of parameters, resulting in a significant improvement in machining performance. This research provides a comprehensive framework for optimizing femtosecond laser machining processes, offering valuable insights critical for the production of advanced lightweight components in industries such as aerospace, optical instruments, and high-performance electronics.

This paper investigated the fluid–structure interaction vibration response of an aircraft liquid-filled pipeline under external random vibration and internal pulsating pressure. First, the fluid–structure interaction solution is theoretically analyzed, and the advantages and disadvantages of the direct coupling method and the separation coupling method are compared, with the latter chosen as the simulation analysis method in this study. Second, taking the U-shaped oil pipeline of an aircraft engine as an example, simulation modeling was performed to compare and analyze the fluid–structure interaction vibration response of aircraft liquid-filled pipelines under different working conditions, obtaining the vibration response characteristics of stress danger points under various conditions. Finally, a test bench for an aircraft liquid-filling pipeline was built to explore the influence of external random vibrations with different kurtoses, different pipe wall thicknesses and different working conditions on the vibration response danger points of aircraft liquid-filling pipelines, verifying the simulation conclusions and providing a basis for aircraft liquid-filling pipeline design.

In order to solve the problem of frequency modulation power deviation caused by the randomness and fluctuation of wind power outputs, a method of auxiliary wind power frequency modulation capacity allocation based on the data decomposition of a “flywheel + lithium battery” hybrid-energy storage system was proposed. Firstly, the frequency modulation power deviation caused by the uncertainty of wind power is decomposed by the successive variational mode decomposition (SVMD) method, and the mode function is segmented and reconstructed by high and low frequencies. Secondly, a mathematical model is established to maximize the economic benefit of energy storage considering the frequency modulation mileage, and quantum particle swarm optimization is used to solve the target model considering the charging and discharging power of energy storage and the charging state constraints to obtain the optimal hybrid-energy storage configuration. Finally, the simulation results show that, in the step disturbance, the Δfmax of the hybrid-energy storage mode is reduced by 37.9% and 15.3%, respectively, compared with single-energy storage. Under continuous disturbance conditions, compared with the single-energy storage mode, the Δfp_v is reduced by 52.73%, 43.72%, 60.71%, and 47.62%, respectively. The frequency fluctuation range is obviously reduced, and the frequency stability is greatly improved.

BackgroundThe human gut microbiota has been identified as a potentially important factor influencing the development of COVID-19. It is believed that the disease primarily affects the organism through inflammatory pathways. With the aim of improving early diagnosis and targeted therapy, it is crucial to identify the specific gut microbiota associated with COVID-19 and to gain a deeper understanding of the underlying processes. The present study sought to investigate the potential causal relationship between the gut microbiota and COVID-19, and to determine the extent to which inflammatory proteins act as mediators in this relationship.MethodsBidirectional mendelian randomization (MR) and Two-step mediated MR analyses were applied to examine causative associations among 196 gut microbiota, 91 inflammatory proteins and COVID-19. The main analytical method used in the MR was the random effects inverse variance weighted (IVW) method. This was complemented by the Bayesian weighted Mendelian randomization (BWMR) method, which was utilized to test the hypothesis of MR. In order for the results to be deemed reliable, statistical significance was required for both methods. Validation was then carried out using an external dataset, and further meta-analyses were conducted to authenticate that the association was reliable.ResultsResults of our research indicated that seven gut microbiota were actively associated to the COVID-19 risk. Five inflammatory proteins were associated with COVID-19 risk, of which three were positively and two were negatively identified with COVID-19. Further validation was carried out using sensitivity analyses. Mediated MR results revealed that CCL2 was a possible mediator of causality of family Bifidobacteriaceae and order Bifidobacteriales with COVID-19, mediating at a ratio of 12.73%.ConclusionSuggesting a genetic causation between specific gut microbiota and COVID-19, our present research emphasizes the underlying mediating role of CCL2, an inflammatory factor, and contributes to a deeper understanding of the mechanism of action underlying COVID-19.

Introduction: Solute carrier (SLC) transport proteins play a crucial role in maintaining cellular nutrient and metabolite homeostasis and are implicated in various human diseases, making them potential targets for therapeutic interventions. However, the study of SLCs has been limited due to the lack of suitable tools, particularly cell-based substrate uptake assays, necessary for understanding their biological functions and for drug discovery purposes.Methods: In this study, a cell-based uptake assay was developed using a stable isotope-labeled compound as the substrate for SLCs, with detection facilitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay aimed to address the limitations of existing assays, such as reliance on hazardous radiolabeled substrates and limited availability of fluorescent biosensors.Results: The developed assay was successfully applied to detect substrate uptakes by two specific SLCs: L-type amino acid transporter 1 (LAT1) and sodium taurocholate co-transporting polypeptide (NTCP). Importantly, the assay demonstrated comparable results to the radioactive method, indicating its reliability and accuracy. Furthermore, the assay was utilized to screen for novel inhibitors of NTCP, leading to the identification of a potential NTCP inhibitor compound.Discussion: The findings highlight the utility of the developed cell-based uptake assay as a rapid, simple, and environmentally friendly tool for investigating SLCs’ biological roles and for drug discovery purposes. This assay offers a safer alternative to traditional methods and has the potential to contribute significantly to advancing our understanding of SLC function and identifying therapeutic agents targeting SLC-mediated pathways.

Background The aim of this retrospective research was to develop an immune-related genes significantly associated with m5C methylation methylation (m5C-IRGs)-related signature associated with lung adenocarainoma (LUAD). Methods We introduced transcriptome data to screen out m5C-IRGs in The Cancer Genome Atlas (TCGA)-LUAD dataset. Subsequently, the m5C-IRGs associated with survival were certificated by Kaplan Meier (K-M) analysis. The univariate Cox, least absolute shrinkage and selection operator (LASSO) regression, and xgboost.surv tool were adopted to build a LUAD prognostic signature. We further conducted gene functional enrichment, immune microenvironment and immunotherapy analysis between 2 risk subgroups. Finally, we verified m5C-IRGs-related prognostic gene expression in transcription level. Results A total of 76 m5C-IRGs were identified in TCGA-LUAD dataset. Furthermore, 27 m5C-IRGs associated with survival were retained. Then, a m5C-IRGs prognostic signature was build based on the 3 prognostic genes (HLA-DMB, PPIA, and GPI). Independent prognostic analysis suggested that stage and RiskScore could be used as independent prognostic factors. We found that 4104 differentially expressed genes (DEGs) between the 2 risk subgroups were mainly concerned in immune receptor pathways. We found certain distinction in LUAD immune microenvironment between the 2 risk subgroups. Then, immunotherapy analysis and chemotherapeutic drug sensitivity results indicated that the m5C-IRGs-related gene signature might be applied as a therapy predictor. Finally, we found significant higher expression of PPIA and GPI in LUAD group compared to the normal group. Conclusions The prognostic signature comprised of HLA-DMB, PPIA, and GPI based on m5C-IRGs was established, which might provide theoretical basis and reference value for the research of LUAD. Public Datasets Analyzed in the Study TCGA-LUAD dataset was collected from the TCGA ( https://portal.gdc.cancer.gov/ ) database, GSE31210 (validation set) was retrieved from GEO ( https://www.ncbi.nlm.nih.gov/geo/ ) database.

Abstract An important exercise for understanding the emergent behavior in biology is to study it using minimal synthetic systems. Current biomimetic systems involving directed motion and collective migration require at least three components: two immiscible solvents to form an emulsion, and external agent(s), usually surfactants, to give rise to asymmetric interactions and induce transient non‐equilibrium conditions. Here, the most minimal system thinkable, consisting of only two components, is presented, in the form of micron‐sized oil (1‐decanol) droplets dispersed in a finite water reservoir. Spontaneous emergent dynamics within chemically identical droplet populations is reported, in the form of physical differentiation of droplets in a stochastic manner leading to an immediate repulsive behavior amongst their neighbors. Using a microfluidic production platform, fluorescence microscopy experiments, and modelling, it is showed that this cyclic phenomenon of differentiation‐repulsion results from oil droplets entering the air‐water interface leading to Marangoni flows and their coupling with evaporative flux of decanol. The potential of this platform is illustrated by demonstrating control over the event frequency, its use as Marangoni tweezers to trap droplet clusters, and proof‐of‐principle reorganization of multi‐component assemblies. The presented collective behavior with exceptional chemical simplicity makes it amenable for potentially developing self‐assembled biomimetic and bioengineered structures.

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration, however, few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function. We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis. To investigate whether enhancing MET in adult cortex has synapse regenerating potential, we created a knockin mouse line, in which the human MET gene expression and signaling can be turned on in adult (10–12 months) cortical neurons through doxycycline-containing chow. We found that similar to the developing brain, turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons. These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses. Prolonged MET signaling resulted in an increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-D-aspartate (AMPA/NMDA) receptor current ratio, indicative of enhanced synaptic function and connectivity. Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain. These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

Highlights The open hollow structure enhances the accessibility of atomically dispersed Ru sites and improves the diffusion efficiency of catalytic molecules The abundant atomically dispersed Ru sites on the surface of catalyst provide a large number of oxygen adsorption and Li2O2 nucleation sites The lithium–oxygen battery assembled with h-RuNC could catalyze the production of Li2O2 with better dispersion and improve the cycling stability.

Abstract Occult nodal metastasis (ONM) plays a significant role in comprehensive treatments of non-small cell lung cancer (NSCLC). This study aims to develop a deep learning signature based on positron emission tomography/computed tomography to predict ONM of clinical stage N0 NSCLC. An internal cohort (n = 1911) is included to construct the deep learning nodal metastasis signature (DLNMS). Subsequently, an external cohort (n = 355) and a prospective cohort (n = 999) are utilized to fully validate the predictive performances of the DLNMS. Here, we show areas under the receiver operating characteristic curve of the DLNMS for occult N1 prediction are 0.958, 0.879 and 0.914 in the validation set, external cohort and prospective cohort, respectively, and for occult N2 prediction are 0.942, 0.875 and 0.919, respectively, which are significantly better than the single-modal deep learning models, clinical model and physicians. This study demonstrates that the DLNMS harbors the potential to predict ONM of clinical stage N0 NSCLC.

Selective laser melting (SLM) technology has broad prospects for developing magnesium alloys in structural and biomedical applications. The effects of T4 heat treatment on microstructure, mechanical properties and corrosion resistance of as-built AZ91D alloy were investigated. The results showed that after T4 treatment, β-Mg17Al12 phases distributed around the matrix changed from networks to diffuse dots and then disappeared at 420 °C for 1 h. The tensile strength and hardness of AZ91D alloy decreased after T4 treatment. In addition, electrochemical and immersion experiments showed that the corrosion resistance was greatly improved after solution. Compared with the as-built AZ91D alloy, the solution-treat sample exhibited higher corrosion resistance in Hanks' solution, and its corrosion current density was reduced by 70%, hydrogen evolution rate by 57%, and corrosion rate by about 78% in the weightless experiment. In this study, after solution-treat, the corrosion resistance of as-built AZ91D can be significantly improved while meeting the mechanical requirement of degradable alloys, and has great potential for biomedical applications.

The blockchain provides a reliable and scalable method for enabling source-tracing functionality in large-scale Internet of Things (IoT) systems. Traditional blockchain-based source tracing applications are generally based on the hypothesis that the raw data collected by each IoT node are credible and consistent, which however may not always be the truth. As no mechanism ensures the reliability of the original data collected from the IoT devices, these data may be accidently screwed up or maliciously tampered with before they are uploaded on-chain. To address this issue, we propose the Multi-dimensional Certificates of Origin (MCO) method to filter out the potentially incredible data-till all the data uploaded to the chain are credible. To achieve this, we devise the Multi-dimensional Information Cross-Verification (MICV) and Multi-source Data Matching Calculation (MDMC) methods. MICV verifies whether a to-be-uploaded datum is consistent or credible, and MDMC determines which data should be discarded and which data should be kept to retain the most likely credible/untampered ones in the circumstance when data inconsistency appears. Large-scale experiments show that our scheme ensures on the credibility of data and off the chain with an affordable overhead.

Abstract Cold stress affects rice growth and productivity. Defects in the plastid-localized pseudouridine synthase OsPUS1 affect chloroplast ribosome biogenesis, leading to low-temperature albino seedlings and accumulation of reactive oxygen species (ROS). Here, we report an ospus1-1 suppressor, sop10. SOP10 encodes a mitochondria-localized pentatricopeptide repeat protein. Mutations in SOP10 impair intron splicing of the nad4 and nad5 transcripts and decrease RNA editing efficiency of the nad2, nad6, and rps4 transcripts, resulting in deficiencies in mitochondrial complex I, thus decrease ROS generation and rescuing the albino phenotype. Overexpression of different compartment-localized superoxide dismutases (SOD) genes in ospus1-1 reverses the ROS over-accumulation and albino phenotypes to various degrees, with Mn-SOD reversing the best. Mutation of SOP10 in indica rice varieties enhances cold tolerance with lower ROS levels. We find that the mitochondrial superoxide plays a key role in rice cold responses, and identify a mitochondrial superoxide modulating factor, informing efforts to improve rice cold tolerance.

Highlights The [W–O] group with strong adsorption capacity is introduced into CoP to fabricate a bi-functional catalyst towards HER and HzOR. The cell voltage of HzOR coupled electrolyzer with 6W–O–CoP/NF as both anode and cathode catalysts is 1.634 V lower than that of the water splitting system at 100 mA cm−2. A proof-of-concept self-powered H2 production system is assembled to realize the H2 evolution rate of 3.53 mmol cm−2 h−1.

Abstract Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.