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Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches are challenging due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation. The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite. Using a micro-continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60 wt% hydroxyapatite resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite in situ to fit the defect, which is expected to enhance surface contact with surrounding tissue and facilitate biointegration. The antioxidative properties of citrate polymers prevent long-term inflammatory responses. The CSS stimulates osteogenesis in vitro and in vivo. Within 4 weeks in a calvarial critical-sized bone defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Through spatial transcriptomics, we demonstrated the comprehensive biological processes of CSS for prompt osseointegration. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.

Abstract Objectives To develop and validate a quantitative model for predicting serosal invasion based on multi-parameters in preoperative dual-energy CT (DECT). Materials and methods A total of 342 LAGC patients who underwent gastrectomy and DECT from six centers were divided into one training cohort (TC), and two validation cohorts (VCs). Dual-phase enhanced DECT-derived iodine concentration (IC), water concentration, and monochromatic attenuation of lesions, along with clinical information, were measured and collected. The independent predictors among these characteristics for serosal invasion were screened with Spearman correlation analysis and logistic regression (LR) analysis. A quantitative model was developed based on LR classifier with fivefold cross-validation for predicting the serosal invasion in LAGC. We comprehensively tested the model and investigated its value in survival analysis. Results A quantitative model was established using IC, 70 keV, 100 keV monochromatic attenuations in the venous phase, and CT-reported T4a, which were independent predictors of serosal invasion. The proposed model had the area-under-the-curve (AUC) values of 0.889 for TC and 0.860 and 0.837 for VCs. Subgroup analysis showed that the model could well discriminate T3 from T4a groups, and T2 from T4a groups in all cohorts (all p

Abstract Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy, the leading cause of blindness in the working-age population. However, the molecular mechanisms by which disturbed metabolic homeostasis causes vascular dysfunction in diabetic retinopathy remain unclear. O-GlcNAcylation modification acts as a nutrient sensor particularly sensitive to ambient glucose. Here, we observe pronounced O-GlcNAc elevation in retina endothelial cells of diabetic retinopathy patients and mouse models. Endothelial-specific depletion or pharmacological inhibition of O-GlcNAc transferase effectively mitigates vascular dysfunction. Mechanistically, we find that Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), key effectors of the Hippo pathway, are O-GlcNAcylated in diabetic retinopathy. We identify threonine 383 as an O-GlcNAc site on YAP, which inhibits its phosphorylation at serine 397, leading to its stabilization and activation, thereby promoting vascular dysfunction by inducing a pro-angiogenic and glucose metabolic transcriptional program. This work emphasizes the critical role of the O-GlcNAc-Hippo axis in the pathogenesis of diabetic retinopathy and suggests its potential as a therapeutic target.

Background: This study aimed to explore the correlation between hyperglycemia at intensive care unit (ICU) admission and the incidence of acute kidney injury (AKI) in patients after cardiac surgery. Methods: We conducted a retrospective cohort study, in which clinical data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Adults (≥18 years) in the database who were admitted to the cardiovascular intensive care unit after cardiac surgery were enrolled. The primary outcome was the incidence of AKI within 7 days following ICU admission. Secondary outcomes included ICU mortality, hospital mortality, ICU length of stay, and the 28-day and 90-day mortality. Multivariable Cox regression analysis was used to assess the association between ICU-admission hyperglycemia and AKI incidence within 7 days of ICU admission. Different adjustment strategies were used to adjust for potential confounders. Patients were divided into three groups according to their highest blood glucose levels recorded within 24 h of ICU admission: no hyperglycemia (

Understanding the subcellular localization of long non-coding RNAs (lncRNAs) is crucial for unraveling their functional mechanisms. While previous computational methods have made progress in predicting lncRNA subcellular localization, most of them ignore the sequence order information by relying on k-mer frequency features to encode lncRNA sequences. In the study, we develope SGCL-LncLoc, a novel interpretable deep learning model based on supervised graph contrastive learning. SGCL-LncLoc transforms lncRNA sequences into de Bruijn graphs and uses the Word2Vec technique to learn the node representation of the graph. Then, SGCL-LncLoc applies graph convolutional networks to learn the comprehensive graph representation. Additionally, we propose a computational method to map the attention weights of the graph nodes to the weights of nucleotides in the lncRNA sequence, allowing SGCL-LncLoc to serve as an interpretable deep learning model. Furthermore, SGCL-LncLoc employs a supervised contrastive learning strategy, which leverages the relationships between different samples and label information, guiding the model to enhance representation learning for lncRNAs. Extensive experimental results demonstrate that SGCL-LncLoc outperforms both deep learning baseline models and existing predictors, showing its capability for accurate lncRNA subcellular localization prediction. Furthermore, we conduct a motif analysis, revealing that SGCL-LncLoc successfully captures known motifs associated with lncRNA subcellular localization. The SGCL-LncLoc web server is available at http://csuligroup.com:8000/SGCL-LncLoc. The source code can be obtained from https://github.com/CSUBioGroup/SGCL-LncLoc.

Abstract Elastocaloric cooling has experienced fast development over the past decade owing to its potential to reshape the refrigeration industry. While the solid-state elastocaloric refrigerant is emission-free, the efficiency of the state-of-the-art elastocaloric cooling systems is not sufficient yet to reduce carbon emissions during operation. In this study, we double the coefficient of performance, the most commonly used efficiency metric, via the synergy of material-level advances in TiNiCu and the system-level roller-driven mechanism capable of recovering kinetic energy. On the materials level, a 125% improvement in coefficient of performance is illustrated in TiNiCu compared to NiTi, empowered by the B2-B19 martensitic transformation with improved lattice compatibility and the grain boundary strengthening from the nanocrystalline structure. On the system level, owing to the properly sized angular momentum in rotating parts, 78% work recovery efficiency is reported, transcending the theoretical limit previously unattainable without kinetic energy recovery. This confluence of materials and mechanical innovations propels elastocaloric cooling systems into a new realm of efficiency and paves the way for their practical application.

Abstract Background Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging. Methods Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice. Results Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission. Conclusion This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.

Abstract Background Vaccines have revolutionized public health by providing protection against infectious diseases. They stimulate the immune system and generate memory cells to defend against targeted diseases. Clinical trials evaluate vaccine performance, including dosage, administration routes, and potential side effects. ClinicalTrials.gov is a valuable repository of clinical trial information, but the vaccine data in them lacks standardization, leading to challenges in automatic concept mapping, vaccine-related knowledge development, evidence-based decision-making, and vaccine surveillance. Results In this study, we developed a cascaded framework that capitalized on multiple domain knowledge sources, including clinical trials, the Unified Medical Language System (UMLS), and the Vaccine Ontology (VO), to enhance the performance of domain-specific language models for automated mapping of VO from clinical trials. The Vaccine Ontology (VO) is a community-based ontology that was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Our methodology involved extracting and annotating data from various sources. We then performed pre-training on the PubMedBERT model, leading to the development of CTPubMedBERT. Subsequently, we enhanced CTPubMedBERT by incorporating SAPBERT, which was pretrained using the UMLS, resulting in CTPubMedBERT + SAPBERT. Further refinement was accomplished through fine-tuning using the Vaccine Ontology corpus and vaccine data from clinical trials, yielding the CTPubMedBERT + SAPBERT + VO model. Finally, we utilized a collection of pre-trained models, along with the weighted rule-based ensemble approach, to normalize the vaccine corpus and improve the accuracy of the process. The ranking process in concept normalization involves prioritizing and ordering potential concepts to identify the most suitable match for a given context. We conducted a ranking of the Top 10 concepts, and our experimental results demonstrate that our proposed cascaded framework consistently outperformed existing effective baselines on vaccine mapping, achieving 71.8% on top 1 candidate’s accuracy and 90.0% on top 10 candidate’s accuracy. Conclusion This study provides a detailed insight into a cascaded framework of fine-tuned domain-specific language models improving mapping of VO from clinical trials. By effectively leveraging domain-specific information and applying weighted rule-based ensembles of different pre-trained BERT models, our framework can significantly enhance the mapping of VO from clinical trials.

Abstract Microtubule organization in cells relies on targeting mechanisms. Cytoplasmic linker proteins (CLIPs) and CLIP-associated proteins (CLASPs) are key regulators of microtubule organization, yet the underlying mechanisms remain elusive. Here, we reveal that the C-terminal domain of CLASP2 interacts with a common motif found in several CLASP-binding proteins. This interaction drives the dynamic localization of CLASP2 to distinct cellular compartments, where CLASP2 accumulates in protein condensates at the cell cortex or the microtubule plus end. These condensates physically contact each other via CLASP2-mediated competitive binding, determining cortical microtubule targeting. The phosphorylation of CLASP2 modulates the dynamics of the condensate-condensate interaction and spatiotemporally navigates microtubule growth. Moreover, we identify additional CLASP-interacting proteins that are involved in condensate contacts in a CLASP2-dependent manner, uncovering a general mechanism governing microtubule targeting. Our findings not only unveil a tunable multiphase system regulating microtubule organization, but also offer general mechanistic insights into intricate protein-protein interactions at the mesoscale level.

Abstract Damage to renal tubular epithelial cells (RTECs) signaled the onset and progression of sepsis-associated acute kidney injury (SA-AKI). Recent research on mitochondria has revealed that mitophagy plays a crucial physiological role in alleviating injury to RTECs and it is suppressed progressively by the inflammation response in SA-AKI. However, the mechanism by which inflammation influences mitophagy remains poorly understood. We examined how macrophage migration inhibitory factor (MIF), a pro-inflammatory protein, influences the PINK1-Parkin pathway of mitophagy by studying protein–protein interactions when MIF was inhibited or overexpressed. Surprisingly, elevated levels of MIF were found to directly bind to PINK1, disrupting its interaction with Parkin. This interference hindered the recruitment of Parkin to mitochondria and impeded the initiation of mitophagy. Furthermore, this outcome led to significant apoptosis of RTECs, which could, however, be reversed by an MIF inhibitor ISO-1 and/or a new mitophagy activator T0467. These findings highlight the detrimental impact of MIF on renal damage through its disruption of the interaction between PINK1 and Parkin, and the therapeutic potential of ISO-1 and T0467 in mitigating SA-AKI. This study offers a fresh perspective on treating SA-AKI by targeting MIF and mitophagy.

Abstract Background It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients. Methods This cross‐sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high‐sensitive cardiac troponin T (hs‐cTnT) and N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) levels. Results Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs‐cTnT concentrations in postmenopausal females with T2DM (β = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p 0.05). Neither estrogen nor testosterone was correlated with cardiac markers. Conclusions Elevated LH levels were positively and independently associated with increased hs‐cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM.

Abstract Craniopharyngioma (CP) is an intracranial tumor with high mortality and morbidity. Though biologically benign, CP will damage the hypothalamus, inducing comorbidities such as obesity, metabolic syndrome, and cognitive impairments. The roles of gut microbiome and serum metabolome in CP‐associated hypothalamic comorbidities are aimed to be explored. Patients with CP are characterized by increased Shannon diversity, Eubacterium, Clostridium, and Roseburia, alongside decreased Alistipes and Bacteroides. CP‐enriched taxa are positively correlated with dyslipidemia and cognitive decline, while CP‐depleted taxa are negatively associated with fatty liver. Subsequent serum metabolomics identified notably up‐regulated purine metabolism, and integrative analysis indicated an association between altered microbiota and elevated hypoxanthine. Phenotypic study and multi‐omics analysis in the Rax‐CreERT2::BrafV600E/+::PtenFlox/+ mouse model validated potential involvement of increased Clostridium and dysregulated purine metabolism in hypothalamic comorbidities. To further consolidate this, intervention experiments are performed and it is found that hypoxanthine co‐variated with the severity of hypothalamic comorbidities and abundance of Clostridium, and induced dysregulated purine metabolism along with redox imbalance in target organs (liver and brain cortex). Overall, the study demonstrated the potential of increased Clostridium and up‐regulated purine metabolism as signatures of CP‐associated hypothalamic‐comorbidities, and unveiled that elevated Clostridium, dysregulated purine metabolism, and redox imbalance may mediate the development and progression of CP‐associated hypothalamic‐comorbidities.

Summary: Impairment in social communication skills is a hallmark feature of autism spectrum disorder (ASD). The role of G-protein-coupled receptor 158 (GPR158) in ASD remains largely unexplored. In this study, we observed that both constitutive and cell-/tissue-specific knockouts of Gpr158 in pyramidal neurons or the medial prefrontal cortex (mPFC) result in impaired novelty preference, while sociability remains unaffected in male mice. Notably, the loss of GPR158 leads to a significant decline in excitatory synaptic transmission, characterized by a reduction in glutamate vesicles, as well as the expression and phosphorylation of GluN2B in the mPFC. We successfully rescue the phenotype of social novelty deficits either by reintroducing GPR158 in the mPFC of Gpr158 deficient mice or by chemogenetic activation of pyramidal neurons where Gpr158 is specifically ablated. Our findings indicate that GPR158 in pyramidal neurons plays a specific role in modulating social novelty and may represent a potential target for treating social disorders.

BackgroundThe effectiveness and safety of a novel class of hypoglycemic medications known as sodium-glucose cotransporter 2 (SGLT2) inhibitors have not been completely established in relation to acute heart failure (AHF). Consequently, we sought to compare the prognostic and safety outcomes of patients administered SGLT2 inhibitors for the treatment of AHF.MethodsAn extensive search of the Web of Science, PubMed, and EMBASE was conducted for randomized controlled trials and observational studies that have evaluated the use of SGLT2 inhibitors in AHF from the inception of these drugs to the present. We compiled data related to cardiovascular safety and prognosis. Aggregated risk ratios (RR), mean differences (MD), or standardized mean differences (SMD) were generated for all outcomes, with 95% confidence intervals (CIs), to evaluate the predictive significance of SGLT2 inhibitors in patients with AHF.ResultsWe identified 4,053 patients from 13 studies. Patients experienced a substantial reduction in all-cause mortality (RR = 0.82, 95% CI: 0.70–0.96, P = 0.01), readmission rates (RR = 0.85, 95% CI: 0.74–0.98, P = 0.02), the number of heart failure exacerbation events (RR = 0.69, 95% CI: 0.50–0.95, P = 0.02), and the number of rehospitalization events due to heart failure (RR = 0.71, 95% CI: 0.58–0.86, P

Significant research endeavors have focused on microbial fuel cell (MFC) systems within wastewater treatment protocols owing to their unique capacity to convert chemical energy from waste into electricity while maintaining minimal nutrient concentrations in the effluent. While prior studies predominantly relied on empirical investigations, there remains a need to explore modeling and simulation approaches. Assessing MFC systems’ performance and power generation based on real wastewater data is pivotal for their practical implementation. To address this, a MATLAB model is developed to elucidate how MFC parameters and constraints influence system performance and enhance wastewater treatment efficiency. Leveraging actual wastewater data from a municipal plant in Guelph, Canada, six sets of MFC models are employed to examine the relationship between power generation and six distinct parameters (inflow velocity, membrane thickness, internal resistance, anode surface area, feed concentration, and hydraulic retention time). Based on these analyses, the final model projects a total power generation of 50,515.16 kW for the entire wastewater treatment plant in a day, capable of supporting approximately 2530 one-person households. Furthermore, the model demonstrates a notably higher chemical oxygen demand (COD) removal rate (75%) compared to the Guelph WWTP. This comprehensive model serves as a valuable tool for future simulations in similar wastewater treatment plants, providing insights for optimizing performance and aiding in practical applications.

Abstract Background Autophagy is a crucial process of cellular self-destruction and component reutilization that can affect the accumulation of total fatty acids (TFAs) and carotenoids in microalgae. The regulatory effects of autophagy process in a docosahexaenoic acid (DHA) and carotenoids simultaneously producing microalga, Crypthecodinium sp. SUN, has not been studied. Thus, the autophagy inhibitor (3-methyladenine (MA)) and activator (rapamycin) were used to regulate autophagy in Crypthecodinium sp. SUN. Results The inhibition of autophagy by 3-MA was verified by transmission electron microscopy, with fewer autophagy vacuoles observed. Besides, 3-MA reduced the glucose absorption and intracellular acetyl-CoA level, which resulting in the decrease of TFA and DHA levels by 15.83 and 26.73% respectively; Surprisingly, 3-MA increased intracellular reactive oxygen species level but decreased the carotenoids level. Comparative transcriptome analysis showed that the downregulation of the glycolysis, pentose phosphate pathway and tricarboxylic acid cycle may underlie the decrease of acetyl-CoA, NADPH and ATP supply for fatty acid biosynthesis; the downregulation of PSY and HMGCR may underlie the decreased carotenoids level. In addition, the class I PI3K-AKT signaling pathway may be crucial for the regulation of carbon and energy metabolism. At last, rapamycin was used to activate autophagy, which significantly enhanced the cell growth and TFA level and eventually resulted in 1.70-fold increase in DHA content. Conclusions Our findings indicate the mechanisms of autophagy in Crypthecodinium sp. SUN and highlight a way to manipulate cell metabolism by regulating autophagy. Overall, this study provides valuable insights to guide further research on autophagy-regulated TFA and carotenoids accumulation in Crypthecodinium sp. SUN.

PCrNi3MoV steel is a medium-carbon, low-alloy quenched and tempered steel that finds its applications in military gun barrels due to the high wear resistance and ablation resistance. To study the penetration and failure modes of PCrNi3MoV plates impacted by tungsten spheres, tungsten spheres of various diameters (5 mm, 8 mm, and 10 mm) were used to impact PCrNi3MoV steel plates with thicknesses of 6 mm, 9 mm, and 14 mm. The penetration performance of the spheres was analyzed for different velocities, and the ultimate penetration velocity of the plate was obtained. It was found that the primary failure modes of the PCrNi3MoV plate were compression pitting failure and shear failure. Using the dimensional analysis method, a relationship between the bulge height of the steel plate and the fragment velocity, an equation for the ultimate penetration velocity, and a relationship between the target penetration energy and the fragment velocity were obtained. Then, a projectile–target action index was proposed to describe the process of tungsten spheres with different velocities impacting target plates. The results suggested that under the same thickness of the target plate, a larger-diameter fragment required more kinetic energy to obtain the same ultimate penetration effect as a smaller-diameter fragment. The equations obtained through dimensional analysis predicted values that agreed well with experimental values, indicating that these equations can be applied to engineering applications.

This paper proposes a type of double-layer charge liner fabricated using chemical vapor deposition (CVD) that has tungsten as its inner liner. The feasibility of this design was evaluated through penetration tests. Double-layer charge liners were fabricated by using CVD to deposit tungsten layers on the inner surfaces of pure T2 copper liners. The microstructures of the tungsten layers were analyzed using a scanning electron microscope (SEM). The feasibility analysis was carried out by pulsed X-rays, slug-retrieval test and static penetration tests. The shaped charge jet forming and penetration law of inner tungsten-coated double-layer liner were studied by numerical simulation method. The results showed that the double-layer liners could form well-shaped jets. The errors between the X-ray test results and the numerical results were within 11.07%. A slug-retrieval test was found that the retrieved slug was similar to a numerically simulated slug. Compared with the traditional pure copper shaped charge jet, the penetration depth of the double-layer shaped charge liner increased by 11.4% and >10.8% respectively. In summary, the test results are good, and the numerical simulation is in good agreement with the test, which verified the feasibility of using the CVD method to fabricate double-layer charge liners with a high-density and high-strength refractory metal as the inner liner.

Abstract Background Global myopia prevalence poses a substantial public health burden with vision-threatening complications, necessitating effective prevention and control strategies. Precise prediction of spherical equivalent (SE), myopia, and high myopia onset is vital for proactive clinical interventions. Methods We reviewed electronic medical records of pediatric and adolescent patients who underwent cycloplegic refraction measurements at the Eye & Ear, Nose, and Throat Hospital of Fudan University between January 2005 and December 2019. Patients aged 3–18 years who met the inclusion criteria were enrolled in this study. To predict the SE and onset of myopia and high myopia in a specific year, two distinct models, random forest (RF) and the gradient boosted tree algorithm (XGBoost), were trained and validated based on variables such as age at baseline, and SE at various intervals. Outputs included SE, the onset of myopia, and high myopia up to 15 years post-initial examination. Age-stratified analyses and feature importance assessments were conducted to augment the clinical significance of the models. Results The study enrolled 88,250 individuals with 408,255 refraction records. The XGBoost-based SE prediction model consistently demonstrated robust and better performance than RF over 15 years, maintaining an R 2 exceeding 0.729, and a Mean Absolute Error ranging from 0.078 to 1.802 in the test set. Myopia onset prediction exhibited strong area under the curve (AUC) values between 0.845 and 0.953 over 15 years, and high myopia onset prediction showed robust AUC values (0.807–0.997 over 13 years, with the 14th year at 0.765), emphasizing the models' effectiveness across age groups and temporal dimensions on the test set. Additionally, our classification models exhibited excellent calibration, as evidenced by consistently low brier score values, all falling below 0.25. Moreover, our findings underscore the importance of commencing regular examinations at an early age to predict high myopia. Conclusions The XGBoost predictive models exhibited high accuracy in predicting SE, onset of myopia, and high myopia among children and adolescents aged 3–18 years. Our findings emphasize the importance of early and regular examinations at a young age for predicting high myopia, thereby providing valuable insights for clinical practice.

Robotic surgery systems, as emerging minimally invasive approaches, have been increasingly applied for the treatment of esophageal cancer because they provide a high-definition three-dimensional surgical view and mechanical rotating arms that surpass the limitations of human hands, greatly enhancing the accuracy and flexibility of surgical methods. Robot-assisted McKeown esophagectomy (RAME), a common type of robotic esophagectomy, has been gradually implemented with the aim of reducing postoperative complications, improving postoperative recovery and achieving better long-term survival. Multiple centers worldwide have reported and summarized their experiences with the RAME, and some have also discussed and analyzed its perioperative effects and survival prognosis compared with those of video-assisted minimally invasive esophagectomy. Compared to traditional surgery, the RAME has significant advantages in terms of lymph node dissection although there seems to be no difference in overall survival or disease-free survival. With the continuous advancement of technology and the development of robotic technology, further development and innovation are expected in the RAME field. This review elaborates on the prospects of the application and advancement of the RAME to provide a useful reference for clinical practice.

Abstract Background Raising the birth rate can effectively increase the resulting labour supply and minimise the adverse impact of an ageing population on high-quality economic development since the demographic dividend is rapidly declining. The Chinese government has a “three-child” policy in place, yet the fertility rate is still falling. This study intends to investigate the present fertility intentions of female university students and assess the extent to which feminism has affected their intentions. It will next investigate the degree to which and the mechanisms by which the psychosocial factors have an impact on those intentions. Methods A cross-sectional survey of female university students was conducted in Nanjing, China, from February to March 2023. To assure the representativeness of the sample, a technique of stratified proportional sampling, PPS sampling, and convenience sampling was utilized. A total of 1124 valid samples were acquired from female university students in 15 comprehensive universities. The data were mined and analysed by SPSS (version 24.0) and AMOS (version 24.0) software. Results Overall female university students’ fertility intentions are low at this stage, with more than half (53.55%) of them having no clear desire to have children. The level of feminist identity significantly negatively affected the Intensity of desire to have children (-0.32) and child-number desires (-0.7). Psychosocial factors had a greater degree of influence on fertility intentions. The direct effect of the level of feminist identity and the perception of fertility hindrances on childbearing desires was -0.63 and -0.50 respectively, and the direct effect of the perception of fertility supports on childbearing intentions was 0.79. Conclusion The level of feminist identity is significantly and negatively related to childbearing desires. Psychosocial factors have a greater degree of influence on fertility intentions, with the level of feminist identity, the perception of fertility hindrances and the perception of fertility supports all significantly impacting fertility intentions. The findings of this study emphasise the importance of the government providing a full range of social security and employers providing better employee benefits to promote a fertility-friendly society.

Introduction: Mild stenosis [degree of stenosis (DS) < 50%] is commonly labeled as nonobstructive lesion. Some lesions remain stable for several years, while others precipitate acute coronary syndromes (ACS) rapidly. The causes of ACS and the factors leading to diverse clinical outcomes remain unclear.Method: This study aimed to investigate the hemodynamic influence of mild stenosis morphologies in different coronary arteries. The stenoses were modeled with different morphologies based on a healthy individual data. Computational fluid dynamics analysis was used to obtain hemodynamic characteristics, including flow waveforms, fractional flow reserve (FFR), flow streamlines, time-average wall shear stress (TAWSS), and oscillatory shear index (OSI).Results: Numerical simulation indicated significant hemodynamic differences among different DS and locations. In the 20%–30% range, significant large, low-velocity vortexes resulted in low TAWSS (40 dyne/cm2), rapidly expanding the high TAWSS area (averagely increased by 0.46 cm2) in left main artery and left anterior descending artery (LAD), where high OSI areas remained extensive (>0.19 cm2).Discussion: While mild stenosis does not pose any immediate ischemic risk due to a FFR > 0.95, 20%–50% stenosis requires attention and further subdivision based on location is essential. Rapid progression is a danger for lesions with 20%–30% DS near the stenoses and in the proximal LAD, while lesions with 30%–50% DS can cause plaque injury and rupture. These findings support clinical practice in early assessment, monitoring, and preventive treatment.

Segregation of the solidification structure of an immiscible alloy is related to the convection induced by the density differences of the components under gravity during solidification. Here, the solidification of the Al–Bi alloy in both opposing and parallel directions to the gravity force was investigated in situ using radiography and optical flow techniques. A quantitative analysis was performed on the flow, solute, and constitutional undercooling fields at the interface. During upward solidification, a flat solute-enriched layer was observed, with the melt flowing toward the center from both sides of the interface. During downward solidification, the solute-enriched layer was deformed, and solute plumes were observed, with the melt flowing toward the sides from the center of the interface. A high solute concentration gradient enhances the local flow and solute transport. The elongation of the plumes was attributed not only to the convective diffusion of the solute but also to the dispersion of droplet clusters. The forces acting on the droplets were calculated, and it was found that the resultant force on the droplets increased the area of the solute-enriched layer. Convection within the bulk melt and the motion of the droplets have synergistic effects on the flow pattern and solute distribution. Distinct microstructures were observed in opposite directions of solidification owing to the differences in constitutional undercooling and flow instability. This work offers insights into the quantitative measurement and understanding of the multi-physics fields during the solidification process.

BackgroundThe COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact worldwide, leading to widespread morbidity and mortality. Vaccination against COVID-19 is a critical tool in controlling the spread of the virus and reducing the severity of the disease. However, the rapid development and deployment of COVID-19 vaccines have raised concerns about potential adverse events following immunization (AEFIs). Understanding the temporal and spatial patterns of these AEFIs is crucial for an effective public health response and vaccine safety monitoring. ObjectiveThis study aimed to analyze the temporal and spatial characteristics of AEFIs associated with COVID-19 vaccines in the United States reported to the Vaccine Adverse Event Reporting System (VAERS), thereby providing insights into the patterns and distributions of the AEFIs, the safety profile of COVID-19 vaccines, and potential risk factors associated with the AEFIs. MethodsWe conducted a retrospective analysis of administration data from the Centers for Disease Control and Prevention (n=663,822,575) and reports from the surveillance system VAERS (n=900,522) between 2020 and 2022. To gain a broader understanding of postvaccination AEFIs reported, we categorized them into system organ classes (SOCs) according to the Medical Dictionary for Regulatory Activities. Additionally, we performed temporal analysis to examine the trends of AEFIs in all VAERS reports, those related to Pfizer-BioNTech and Moderna, and the top 10 AEFI trends in serious reports. We also compared the similarity of symptoms across various regions within the United States. ResultsOur findings revealed that the most frequently reported symptoms following COVID-19 vaccination were headache (n=141,186, 15.68%), pyrexia (n=122,120, 13.56%), and fatigue (n=121,910, 13.54%). The most common symptom combination was chills and pyrexia (n=56,954, 6.32%). Initially, general disorders and administration site conditions (SOC 22) were the most prevalent class reported. Moderna exhibited a higher reporting rate of AEFIs compared to Pfizer-BioNTech. Over time, we observed a decreasing reporting rate of AEFIs associated with COVID-19 vaccines. In addition, the overall rates of AEFIs between the Pfizer-BioNTech and Moderna vaccines were comparable. In terms of spatial analysis, the middle and north regions of the United States displayed a higher reporting rate of AEFIs associated with COVID-19 vaccines, while the southeast and south-central regions showed notable similarity in symptoms reported. ConclusionsThis study provides valuable insights into the temporal and spatial patterns of AEFIs associated with COVID-19 vaccines in the United States. The findings underscore the critical need for increasing vaccination coverage, as well as ongoing surveillance and monitoring of AEFIs. Implementing targeted monitoring programs can facilitate the effective and efficient management of AEFIs, enhancing public confidence in future COVID-19 vaccine campaigns.

High content Styrene-butadiene-styrene (SBS) modified asphalt binder is commonly used for permeable pavements attribute to reasonable adhesion ability, deformation resistance and toughness. However, due to the large difference in molecular weight between styrene-butadiene-styrene block copolymer and asphalt, the compatibility between SBS and asphalt has always been a key issue restricting its development. To improve the compatibility of high content SBS modified asphalt, the preparation process of high content SBS modified asphalt (shear time, temperature, rate, modifier content) was investigated by orthogonal experimental design method. The effects of modifiers (polyphosphoric acid, montmorillonite, and sulfur) on the physical properties and compatibility of high content SBS modified asphalt were investigated by physical property tests, storage stability tests and dynamic shear rheology tests. The results shows that all three additives have improved the storage stability of high content SBS-modified asphalt, among which, nano montmorillonite has the best comprehensive improvement effect. In addition, the preparation process of high content SBS modified asphalt will also affect its physical properties and compatibility. When the content of MMT and SBS is 2% and 8% respectively, the shear temperature is 170 °C, the shear rate is 4000 rpm, and the shear time is 150 min, the high and low temperature performance of high content SBS modified asphalt is good and the compatibility is the best.

This study employed experimental and finite element modeling approaches to systematically investigate the mechanical damage mechanisms of recycled brick aggregate concrete (RAC) under freeze-thaw cycling conditions. The investigation encompassed analyses at three hierarchical levels: macroscopic, mesoscopic, and microscopic. The influence of recycled brick aggregate (RA) replacement rate and the number of freeze-thaw cycles on RAC's apparent state and mechanical performance was examined at the macroscopic level. Utilizing equipment such as electron microscopes, a comprehensive observation was conducted from mesoscopic and microscopic perspectives to elucidate the evolving patterns of the cementitious matrix, RA, and the interfacial transition zone (ITZ) within RAC during the freeze-thaw cycling process. On the one hand, more excellent internal space was inherent in RA compared to NA, enabling it to effectively accommodate the volumetric expansion resulting from water freezing. It contributed to mitigating the damage to concrete caused by freeze-thaw cycles. On the other hand, RA's rough and porous characteristics facilitated the infiltration of cement particles into its internal structure, forming a robust ITZ with RA. Concurrently, a numerical simulation of RAC's freeze-thaw cycling process was presented. This simulation generated coupled damage maps and load-deflection curves for RAC under various conditions, encompassing different levels of RA replacement rates, freeze-thaw cycle counts, and loading modes. The research results indicated that the inclusion of RA adversely affects the mechanical properties of concrete while concurrently altering the concrete's failure mode and the propagation pathways of internal cracks. Nevertheless, it was worth noting that the introduction of RA, despite diminishing the mechanical performance of concrete, effectively mitigates the rate of performance degradation during the freeze-thaw cycling process. A favorable equilibrium between freeze-thaw resistance and mechanical performance could be achieved when the replacement rate of RA for natural aggregates (NA) fell within the range of 10–30 %. By employing a finite element model to simulate the flexural performance of RAC after freeze-thaw cycles, the deviation range between the simulated and measured values fell within the range of 5.00–8.23 %. This affirmed the model's fitting solid capability and validated its effectiveness in analyzing the RAC structure's freeze-thaw-load coupled damage and lifespan prediction.

Marine microorganisms are primary drivers of the elemental cycling. The interaction between heterotrophic prokaryotes and biomarker (n-alkane) in Kuroshio Extension (KE) remains unclear. Here, we categorize KE into three characteristic areas based on ocean temperatures and nutrient conditions: Cold Water Area (CWA), Mixed Area (MA), and Warm Water Area (WWA). A total of 49 samples were collected during two–year voyage to identify the source of n-alkane and associated degrading microorganisms. Total n-alkane concentrations (Σn–Alk) in surface water (SW) spanned from 1,308 ng L–1 to 1,890 ng L–1, it was significantly higher (Tukey–Kramer test, p

Abstract Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists’ F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

Highlights γ-MnO2 loaded on N-doped biomass carbon from grapefruit peel is firstly developed. The splendid cathodic properties (e.g., coulombic efficiency: ~ 100%, energy density: 553.12 Wh kg−1) are gained. The biomass strategy guaranteed via cytotoxicity test shows a clinical potential. Zn-ion storage efficiency is boosted mainly by regulating Mn–O bond and Mn domains.

Abstract Background Astragaloside IV (As-IV) and Tanshinone IIA (Ta-IIA) are the main ingredients of traditional Chinese medicinal Astragalus membranaceus (Fisch.) Bunge and Salvia miltiorrhiza Bunge, respectively, both of which have been employed in the treatment of cardiovascular diseases. Nevertheless, the efficacy of the combination (Co) of Ta-IIA and As-IV for cardiovascular diseases remain unclear and warrant further investigation. This study aimed to investigate the efficacy and the underlying molecular mechanism of Co in treating myocardial ischemia–reperfusion injury (MIRI). Methods In order to assess the efficacy of Co, an in vivo MIRI mouse model was created by temporarily blocking the coronary arteries for 30 min and then releasing the blockage. Parameters such as blood myocardial enzymes, infarct size, and ventricular function were measured. Additionally, in vitro experiments were conducted using HL1 cells in both hypoxia-reoxygenation model and oxidative stress models. The apoptosis rate, expression levels of apoptosis-related proteins, oxidative stress indexes, and release of inflammatory factors were detected. Furthermore, molecular docking was applied to examine the binding properties of Ta-IIA and As-IV to STING, and western blotting was performed to analyze protein expression of the STING pathway. Additionally, the protective effect of Ta-IIA, As-IV and Co via inhibiting STING was further confirmed in models of knockdown STING by siRNA and adding STING agonist. Results Both in vitro and in vivo data demonstrated that, compared to Ta-IIA or As-IV alone, the Co exhibited superior efficacy in reducing the area of myocardial infarction, lowering myocardial enzyme levels, and promoting the recovery of myocardial contractility. Furthermore, the Co showed more potent anti-apoptosis, antioxidant, and anti-inflammation effects. Additionally, the Co enhanced the inhibitory effects of Ta-IIA and As-IV on STING phosphorylation and the activation of STING signaling pathway. However, the administration of a STING agonist attenuated the protective effects of the Co, Ta-IIA, and As-IV by compromising their anti-apoptotic, antioxidant, and anti-inflammatory effects in MIRI. Conclusion Compared to the individual administration of Ta-IIA or As-IV, the combined treatment demonstrated more potent ability in inhibiting apoptosis, oxidative stress, inflammation, and the STING signaling pathway in the context of MIRI, indicating a more powerful protective effect against MIRI. Graphical Abstract

In this work, a Cu–10Ta alloy with a copper to tantalum mass ratio of 9:1 is prepared using powder metallurgy technology. Physical properties of the alloy, including density, microstructure, melting point, and constant-volume specific heat, are tested. Via the split Hopkinson pressure bar (SHPB) and flyer-plate impact experiments, the relationship between equivalent stress and equivalent plastic strain of the material is studied at temperatures of 298–823 K and under strain rates of 1 × 10−3–5.2 × 103 s−1, and the Hugoniot relationship at impact pressures of 1.46–17.25 GPa and impact velocities of 108–942 m/s is obtained. Evolution of the Cu–10Ta microstructure that occurs during high-strain-rate impact is analyzed. Results indicate that the Cu–10Ta alloy possesses good thermal stability, and at ambient temperatures of up to 50% its melting point, stress softening of less than 15% of the initial strength is observed. A modified J-C constitutive model is employed to accurately predict the variation of yield strength with strain rate. Under strong impact, the copper phase is identified as the primary source of plastic deformation in the Cu–10Ta alloy, while significant deformation of the high-strength tantalum particles is less pronounced. Furthermore, the longitudinal wave speed D is found to correlate linearly with the particle velocity u upon strong impact. Analysis reveals that the sound speed and spallation strength of the alloy increase with increasing impact pressure.

Although deep learning techniques have made significant advances in the field of images, existing methods still face challenges in processing complex, noisy images. In view of the limitation that most denoising models only focus on extracting single scale features, a new denoising network structure is proposed in this paper. Firstly, the channel attention mechanism and convolutional neural network are combined to construct a real image denoising model, and then the parallel multi-scale convolutional neural network is constructed by combining the adaptive dense connected residual block and parallel multi-scale feature extraction module. The results showed that the designed model can reach the stable state only after 121 and 86 iterations on the training set and the test set, and the denoising accuracy of the model is as high as 0.96. In addition, the research model has high computational efficiency and short denoising time when processing noisy images, and the processing time of an image is as low as 0.09s. Therefore, the proposed denoising structure has good denoising performance under different noise levels and types, and this study also provides a new idea for the application of deep learning in image denoising and other image processing tasks.

ABSTRACT Amorphous indium gallium zinc oxide (a-IGZO)-based thin film transistors (TFTs) are increasingly becoming popular because of their potential in futuristic applications, including CMOS technology. Given the demand for CMOS-compatible, ultra-scaled, reliable, and high-performing devices, we fabricate and analyze scaled-channel a-IGZO-TFTs with an optimal double-gate structure, a thin nanosheet-based channel, and an effective high- $\kappa$ dielectric namely HfO2. The reliably reported double gate IGZO nanosheet TFTs (DG-IGZO-NS-TFTs) are tested under positive and negative bias stress at variant temperatures, and the resulting modulations are analyzed critically. The reported DG-IGZO-NSTFTs exhibit a negative side threshold voltage shift ( $\Delta$ Vth) accompanied by an increase in Ion/Ion(0) under negative bias temperature stress (NBTS) at elevated temperatures, which indicates the presence of additional charges. An anomalous negative side shifting of the Vth is observed under positive bias temperature stress (PBTS), where diffused hydrogen atoms are identified as introducing excess n-type carriers into the channel and causing the observed $\Delta$ Vth. The spectroscopic analysis is performed to establish evidence for the assumed mechanisms, and the role of individual gates is investigated in the context of performance variance under temperature-bias stress. Moreover, the partial reversibility of the stress-induced degradation is experimentally established and methodically discussed. Overall, the reported results offer a comprehensive understanding of scaled-channel DG-NS-IGZO-TFTs, which help shape performance-enhancement strategies, control degradation mechanisms, and define appropriate application scenarios.

Recently, a-IGZO has advanced toward the next-generation electronics system because of its compatibility with complementary metal oxide semiconductor (CMOS) and back-end-of-line (BOEL) based systems. A systematic electrical characterization of a-IGZO TFT related to reliability issues, such as positive bias temperature stress (PBTS) and negative bias temperature stress (NBTS), would entitle its integration into novel electronics systems. Unexpectedly, PBTS is characterized by the transition of positive Vth shift to negative Vth shift (ΔVth, the positive shift followed by the stress and temperature activated negative shift). This transition is attributed to charge trapping/trap-site generations and hydrogen migration to the active layer. The ΔVth shift mechanism depends on the temperature and voltage stress. On the other hand, a negative ΔVth shift has been observed during the NBTS operation and could be attributed to the hole trapping at the interface of GI/IGZO. An effective suppression of the gate leakage current has also been observed during reliability tests. Simulation results reveal a pronounced potential at the edges of source and drain regions, and considered the origin of hydrogen migration into the IGZO layer. Thermal image results also reveal the strong temperature/potential distribution at the edges of the source/drain regions, indorsing the simulation results.

Significance Alkaline granites are one of the most important intrusions associated with rare metal and rare earth element mineralization. Progress Recently, alkaline granite-related rare metal and rare earth element deposits have achieved a number of important advances in classification, sources of ore-forming fluids and materials, and enrichment mechanisms. Alkaline granites are usually enriched in high field strength elements (HFSEs) and rare earth elements (REEs). These deposits can be divided into three types based on the relationships between mafic and oreminerals, i.e., arfvedsonite alkaline granite-related Nb-REE deposits, biotite alkaline granite-related Nb-Sn-rich deposits, and nepheline/aegirine syenite-related Nb-U-REE-rich deposits. Mineralization ages of these deposits are concentrated in the Paleozoic-Cenozoic. The deposits are formed in an extensional setting associated with break-up and convergence of continents and supercontinents. Two stages of ore-forming fluids, early-stage magmatic differentiation and late-stage hydrothermal metasomatism, are recognized for the formation of these deposits. Previous studies indicate that ore-forming fluids exsolved from alkaline magmas are characterized by low temperatures, high salinities and rich fluorine, which can lead to the super high enrichment of HFSEs and REEs in alkaline granites. Incompatible elements in parental magmas can be enriched in exsolved fluids and can lead to the formation of rare metal and rare earth element ores due to F-rich fluid fractional crystallization or hydrothermal alteration in the late magmatic stage. The ore-forming materials were dominantly originated from mantle-derived magmas, crust- and mantle-derived magma mixing, or subducted oceanic crust. Conclusions and Prospects Hydrothermal metasomatism and magmatic fractional crystallization are two enrichment mechanisms commonly used to interpret the formation of these deposits. However, most of these deposits are formed by a combination of the two mechanisms.

Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear. Herein, as an extension to our previous investigation, we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins (TYRs) in terms of expression, activity, and stability. The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt (referred to as protein kinase B (PKB))/glycogen synthase kinase 3β (GSK3β)/β-catenin, p-p70 S6 kinase cascades, and protein 38 (p38)/mitogen-activated protein (MAP) kinase (MAPK) and extracellular regulated protein kinases (ERK)/MAPK pathways, after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues. Furthermore, EB exerted repigmentation by stimulating TYR activity in hydroquinone- and N-phenylthiourea-induced TYR inhibitive models, including melanoma cells, zebrafish, and mice. Finally, EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding, TYR-related protein 1 formation, and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes. These data conclude that EB can target TYRs and alter their expression, activity, and stability, thus stimulating their pigmentation function, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

Abstract Previously we isolated three Fusarium strains (a F. sacchari strain namely GXUF-1, and another two F. commune strains namely GXUF-2 and GXUF-3), and we verified that GXUF-3 was able to cause sugarcane root rot to the chewing cane cultivar Badila. Considering that Fusarium spp. are a group of widely distributed fungal pathogens, we tested whether these three Fusarium isolates were able to cause root rot to Badila as well as sugar-making cane cultivar (Guitang42), using a suitable inoculation method established based on infection assays using Badila. We found that the three Fusarium strains were able to cause root rot symptoms to both Badila and Guitang42, to different extents. To better investigate the potential pathogenicity mechanisms, we performed Illumina high-throughput sequencing and analyzed the whole genomic sequence data of these three Fusarium strains. The results reveal that the assembly sizes of the three Fusarium strains were in a range of 44.7–48.2 Mb, with G + C contents of 48.0–48.5%, and 14,154–15,175 coding genes. The coding genes were annotated by multiple public databases, and potential pathogenic genes were predicted using proprietary databases (such as PHI, DFVF, CAZy, etc.). Furthermore, based on evolutionary analysis of the coding sequence, we found that contraction and expansion of gene families occurred in the three Fusarium strains. Overall, our results suggest a potential risk that the root rot disease may occur to the sugar-making canes although it was initially spotted from fruit cane, and provide clues to understand the pathogenic mechanisms of Fusarium spp. causing sugarcane root rot.

Abstract Background The Zhizi Chuanxiong herb pair (ZCHP) can delay pathological progression of atherosclerosis (AS); however, its pharmacological mechanism remains unclear because of its complex components. The purpose of current study is to systematically investigate the anti-AS mechanism of ZCHP. Methods The databases of TCMSP, STITCH, SwissTargetPrediction, BATMAN-TCM, and ETCM were searched to predict the potential targets of ZCHP components. Disease targets associated with AS was retrieved from the GEO database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses were executed using DAVID 6.8. Molecular docking method was employed to evaluate the core target binding to blood components, and animal experiments were performed to test action mechanism. Results A ZCHP-components-targets-AS network was constructed by using Cytoscape, included 11 main components and 52 candidate targets. Crucial genes were shown in the protein–protein interaction network, including TNF, IL-1β, IGF1, MMP9, COL1A1, CCR5, HMOX1, PTGS1, SELE, and SYK. KEGG enrichment illustrated that the NF-κB, Fc epsilon RI, and TNF signaling pathways were important for AS treatment. These results were validated by molecular docking. In ApoE−/− mice, ZCHP significantly reduced intima-media thickness, pulse wave velocity, plaque area, and serum lipid levels while increasing the difference between the end-diastolic and end-systolic diameters. Furthermore, ZCHP significantly decreased the mRNA and protein levels of TNF-α and IL-1β, suppressed NF-κB activation, and inhibited the M1 macrophage polarization marker CD86 in ApoE−/− mice. Conclusion This study combining network pharmacology, molecular biology, and animal experiments showed that ZCHP can alleviate AS by suppressing the TNF/NF-κB axis and M1 macrophage polarization. Graphical Abstract

Scrophulariae Radix (SR), the dried root of Scrophularia ningpoensis Hemsl (S. ningpoensis), has been extensively used as traditional Chinese medicine for thousands of years. However, since the mid-20th century, the traditional processing technology of S. ningpoensis has been interrupted. Therefore, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology, together with a Global Natural Product Social Molecular Networking (GNPS) method, was applied to comprehensively analyze the characteristic changes and mutual transformation of chemical constituents in the differently processed roots of S. ningpoensis, as well as to scientifically elucidate the processing mechanism of differently processed SR. As a result, a total of 149 components were identified. Notably, with the help of the GNPS data platform and MS2 fragment ions, the possible structures of four new compounds (47, 48, 50, and 73) were deduced in differently processed SR samples, in which 47, 48, and 50 are iridoid glycosides, and 73 is a phenylpropanoid glycoside. Five cyclopeptides (78, 86, 97, 99, and 104) derived from leucine (isoleucine) were identified in SR for the first time. The heatmaps analysis results indicated that leucine or isoleucine may be converted to cyclopeptides under the prolonged high-temperature conditions. Moreover, it is found that short-time steaming can effectively prevent the degradation of glycosides by inactivating enzymes. This study provides a new and efficient technical strategy for systematically identifying the chemical components, rapidly discovering the components, and preliminarily clarifying the processing mechanism of S. ningpoensis, as well as also providing a scientific basis for the improvement of the quality standards and field processing of S. ningpoensis.

In the planar flow casting process of amorphous strips, the flow behavior of molten metal and the inclusion content in the crucible are crucial to the morphology and magnetic properties of the material. This study conducts a comparative analysis of the effects of non-immersed and immersed funnels, as well as various funnel structures, on the fluid flow and inclusion removal efficiency in the crucible by integrating numerical and physical models. The findings reveal that for the same pouring flow rate, the diameter of the liquid column in non-immersed pouring conditions is smaller than that of the funnel outlet, leading to a faster injection flow velocity. As a result, the melt in the crucible is subjected to severe impacts, accompanied by an increased possibility of slag entrapment. Conversely, immersed pouring substantially reduces the velocity of the molten metal at the funnel outlet, thereby extending the residence time in the crucible and diminishing the volume of the dead zone. Additionally, the molten metal backflows due to the negative pressure formed in the inner chamber of the funnel. The design of a trumpet-shaped funnel increases the effective volume while reducing the height of the backflow fluid, consequently reducing the velocity of the molten metal at the funnel outlet and prolonging the residence time. Compared to the conventional pouring process with the non-immersed funnel, the outlet velocity is reduced from 1.1 m/s to 0.12 m/s by adopting the immersed funnel with an inverted trapezoidal trumpet structure. This reduction results in a stable flow state, a 9.69% reduction in the dead zone volume fraction, and a 22.96% increase in average inclusion removal efficiency. These improvements demonstrate that a crucible funnel with a well-designed structure and the implementation of an immersion process can significantly improve the metallurgical effects in the planar flow casting process.

Liver fibrosis plays an important role in the progression of liver disease, but there is a severe shortage of direct and efficacious pharmaceutical clinical interventions. Literature research indicates that aspartic acid exhibits hepatoprotective properties. In this paper, 32 target compounds were designed and synthesized utilizing aspartic acid as the lead compound, of which 22 were new compounds not reported in the literature. These compounds were screened for their inhibitory effects on the COL1A1 promoter to assess in vitro anti-liver fibrosis activity and summarized structure–activity relationships. Four compounds exhibited superior potency with inhibition rates ranging from 66.72% to 97.44%, substantially higher than EGCG (36.46 ± 4.64%) and L-Asp (11.33 ± 0.35%). In an LPS-induced inflammation model of LX-2 cells, both 41 and 8a could inhibit the activation of LX-2 cells, reducing the expression of COL1A1, fibronectin, and α-SMA. Upon further investigation, 41 and 8a ameliorated liver fibrosis by inhibiting the IKKβ-NF-κB signaling pathway to alleviate inflammatory response. Overall, the study evaluated the anti-liver fibrosis effects of aspartic acid derivatives, identified the potency of 41, and conducted a preliminary exploration of mechanisms, laying the foundation for the discovery of novel anti-liver fibrosis agents.

The organic coating on the surface is common and the most effective method to prevent metal materials from corrosion. However, the corrosive medium can penetrate the metal surface via micropores, and electrons cannot transfer in the pure resin coatings. In this paper, a new type of anticorrosive and electrically conductive composite coating filled with graphene oxide/carbon nanotube/polyaniline (GO/CNT/PANI) nanocomposites was successfully prepared by in situ polymerization of aniline (AN) on the surface of GO and CNT and using waterborne epoxy resin (WEP) as film-forming material. The structure and morphology of the composite were characterized using a series of characterization methods. The composite coatings were comparatively examined through resistivity, potentiodynamic polarization curves, electrochemical impedance spectroscopy (EIS), and salt spray tests. The results show that the GO/CNT/PANI/WEP composite coating exhibits excellent corrosion resistance for metal substrates and good conductivity when the mass fraction of GO/CNT/PANI is 3.5%. It exhibits a lower corrosion current density of 4.53 × 10−8 A·cm−2 and a higher electrochemical impedance of 3.84 × 106 Ω·cm2, while only slight corrosion occurred after 480 h in the salt spray test. The resistivity of composite coating is as low as 2.3 × 104 Ω·cm. The composite coating possesses anticorrosive and electrically conductive properties based on the synergistic effect of nanofillers and expands the application scope in grounding grids and oil storage tank protection fields.

Detecting and tracking personnel onboard is an important measure to prevent ships from being invaded by outsiders and ensure ship security. Ships are characterized by more cabins, numerous equipment, and dense personnel, so there are problems such as unpredictable personnel trajectories, frequent occlusions, and many small targets, which lead to the poor performance of existing multi-target-tracking algorithms on shipboard surveillance videos. This study conducts research in the context of onboard surveillance and proposes a multi-object detection and tracking algorithm for anti-intrusion on ships. First, this study designs the BR-YOLO network to provide high-quality object-detection results for the tracking algorithm. The shallow layers of its backbone network use the BiFormer module to capture dependencies between distant objects and reduce information loss. Second, the improved C2f module is used in the deep layer of BR-YOLO to introduce the RepGhost structure to achieve model lightweighting through reparameterization. Then, the Part OSNet network is proposed, which uses different pooling branches to focus on multi-scale features, including part-level features, thereby obtaining strong Re-ID feature representations and providing richer appearance information for personnel tracking. Finally, by integrating the appearance information for association matching, the tracking trajectory is generated in Tracking-By-Detection mode and validated on the self-constructed shipboard surveillance dataset. The experimental results show that the algorithm in this paper is effective in shipboard surveillance. Compared with the present mainstream algorithms, the MOTA, HOTP, and IDF1 are enhanced by about 10 percentage points, the MOTP is enhanced by about 7 percentage points, and IDs are also significantly reduced, which is of great practical significance for the prevention of intrusion by ship personnel.

Fibroblastic reticular cells (FRCs) are a subpopulation of stromal cells modulating the immune environments in health and disease. We have previously shown that activation of TLR9 signaling in FRC in fat-associated lymphoid clusters (FALC) regulate peritoneal immunity via suppressing immune cell recruitment and peritoneal resident macrophage (PRM) retention. However, FRCs are heterogeneous across tissues and organs. The functions of each FRC subset and the regulation of TLR9 in distinct FRC subsets are unknown. Here, we confirmed that specific deletion of TLR9 in FRC improved bacterial clearance and survival during peritoneal infection. Furthermore, using single-cell RNA sequencing, we found two subsets of FRCs (CD55hi and CD55lo) in the mesenteric FALC. The CD55hi FRCs were enriched in gene expression related to extracellular matrix formation. The CD55lo FRCs were enriched in gene expression related to immune response. Interestingly, we found that TLR9 is dominantly expressed in the CD55lo subset. Activation of TLR9 signaling suppressed proliferation, cytokine production, and retinoid metabolism in the CD55lo FRC, but not CD55hi FRC. Notably, we found that adoptive transfer of Tlr9-/–CD55lo FRC from mesenteric FALC more effectively improved the survival during peritonitis compared with WT-FRC or Tlr9-/–CD55hi FRC. Furthermore, we identified CD55hi and CD55lo subsets in human adipose tissue-derived FRC and confirmed the suppressive effect of TLR9 on the proliferation and cytokine production in the CD55lo subset. Therefore, inhibition of TLR9 in the CD55lo FRCs from adipose tissue could be a useful strategy to improve the therapeutic efficacy of FRC-based therapy for peritonitis.

Abstract Background Insulin resistance is associated with chronic complications of diabetes, including diabetic peripheral neuropathy (DPN). Estimated glucose disposal rate (eGDR), calculated by the common available clinical factors, was proved to be an excellent tool to measure insulin resistance in large patient population. Few studies have explored the association between eGDR and DPN longitudinally. Therefore, we performed the current study to analyze whether eGDR could predict the risk of DPN. Methods In this prospective study, 366 type 2 diabetes (T2DM) subjects without DPN were enrolled from six communities in Shanghai in 2011–2014 and followed up until 2019–2020. Neuropathy was assessed by Michigan Neuropathy Screening Instrument (MSNI) at baseline and at the end of follow‐up. Findings After 5.91 years, 198 of 366 participants progressed to DPN according to MNSI examination scores. The incidence of DPN in the low baseline eGDR (eGDR

Background: As a scaffold protein, calcium/calmodulin-dependent serine protein kinase (CASK) has been extensively studied in a variety of tissues throughout the body. The Cask gene is ubiquitous in several tissues, such as the neurons, islets, heart, kidneys and sperm, and is mostly localised in the cytoplasm adjacent to the basement membrane. CASK binds to a variety of proteins through its domains to exerting its biological activity. Scope of review: Here, we discuss the role of CASK in multiple tissues throughout the body. The role of different CASK domains in regulating neuronal development, neurotransmitter release and synaptic vesicle secretion was emphasised; the regulatory mechanism of CASK on the function of pancreatic islet β cells was analysed; the role of CASK in cardiac physiology, kidney and sperm development was discussed; and the role of CASK in different tumours was compared. Finally, we clarify the importance of the Cask gene in the body, and how deletion or mutation of the Cask gene can have adverse consequences. Major conclusions: CASK is a conserved gene with similar roles in various tissues. The function of the Cask gene in the nervous system is mainly involved in the development of the nervous system and the release of neurotransmitters. In the endocrine system, an involvement of CASK has been reported in the process of insulin vesicle transport. CASK is also involved in cardiomyocyte ion channel regulation, kidney and sperm development, and tumour proliferation. CASK is an indispensable gene for the whole body, and CASK mutations can cause foetal malformations or death at birth. In this review, we summarise the biological functions and pathological mechanisms of CASK in various systems, thereby providing a basis for further in-depth studies of CASK functions.

Non-small cell lung cancer (NSCLC) is characterized by several molecular alterations that contribute to its development and progression. These alterations include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), and mesenchymal–epithelial transition factor (c-MET). Among these, the hepatocyte growth factor (HGF)/c-MET signaling pathway plays a crucial role in NSCLC. In spite of this, the involvement of the HGF/c-MET signaling axis in remodeling the tumor microenvironment (TME) remains relatively unexplored. This review explores the biological functions of the HGF/c-MET signaling pathway in both normal and cancerous cells, examining its multifaceted roles in the NSCLC tumor microenvironment, including tumor cell proliferation, migration and invasion, angiogenesis, and immune evasion. Furthermore, we summarize the current progress and clinical applications of MET-targeted therapies in NSCLC and discuss future research directions, such as the development of novel MET inhibitors and the potential of combination immunotherapy.

Aiming at the problem that dynamic targets in indoor environments lead to low accuracy and large errors in the localization and position estimation of visual SLAM systems and the inability to build maps containing semantic information, a semantic visual SLAM algorithm based on the semantic segmentation network DeepLabV3+ and LK optical flow is proposed based on the ORB-SLAM2 system. First, the dynamic target feature points are detected and rejected based on the lightweight semantic segmentation network DeepLabV3+ and LK optical flow method. Second, the static environment occluded by the dynamic target is repaired using the time-weighted multi-frame fusion background repair technique. Lastly, the filtered static feature points are used for feature matching and position calculation. Meanwhile, the semantic labeling information of static objects obtained based on the lightweight semantic segmentation network DeepLabV3+ is fused with the static environment information after background repair to generate dense point cloud maps containing semantic information, and the semantic dense point cloud maps are transformed into semantic octree maps using the octree spatial segmentation data structure. The localization accuracy of the visual SLAM system and the construction of the semantic maps are verified using the widely used TUM RGB-D dataset and real scene data, respectively. The experimental results show that the proposed semantic visual SLAM algorithm can effectively reduce the influence of dynamic targets on the system, and compared with other advanced algorithms, such as DynaSLAM, it has the highest performance in indoor dynamic environments in terms of localization accuracy and time consumption. In addition, semantic maps can be constructed so that the robot can better understand and adapt to the indoor dynamic environment.

Craniopharyngioma patients often suffer from a diminished quality of life after surgery, which is usually associated with metabolic disorders and hypothalamic obesity. However, the precise etiology of these conditions remains elusive. To identify the metabolic changes after surgery, we conducted a cross-sectional study using metabolomic and lipidomic analysis to profile metabolic alterations in adult-onset craniopharyngioma patients with postoperative obesity. A cohort of 120 craniopharyngioma patients who had undergone surgery were examined. Differential analyses, including clinical characteristics, serum metabolome, and lipidome, were conducted across distinct body mass index (BMI) groups. Our findings indicated no statistically significant differences in age, sex, and fasting blood glucose among postoperative craniopharyngioma patients when stratified by BMI. However, a noteworthy difference was observed in uric acid and blood lipid levels. Further investigation revealed that alterations in metabolites and lipids were evidently correlated with increased BMI, indicating that postoperative obesity of craniopharyngioma patients affected their whole-body metabolism. Additionally, the multi-omics analysis identified specific metabolites and lipids, including uric acid and DG(18:2/20:4), as contributors to the metabolic disorders associated with postoperative obesity of craniopharyngioma patients. This work provides valuable insight into the involvement of metabolites and lipids in metabolic disorders subsequent to craniopharyngioma surgery.