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Abstract Nickel-rich layered oxides are one of the most promising positive electrode active materials for high-energy Li-ion batteries. Unfortunately, the practical performance is inevitably circumscribed by the structural deterioration deriving from the Ni/Li antisite disorder, leading to severe capacity loss and life attenuation. Herein, we propose an economical and facile rejuvenation strategy by employing the magneto-electrochemical synergistic activation targeting the positive electrode in assembled Li-ion batteries. This approach induces a transition of Ni3+ from high-spin to low-spin, reducing the super-exchange interaction of Ni-O-transition metal (TM). Meanwhile, electrochemical reaction drives Li+ from the host material and promotes Ni3+ to reoccupy TM layer, recovering intrinsic Li site and extending cycle life. The strategy demonstrates that low-quality positive electrodes can be converted to high-quality ones. Notably, the method can revitalize an aged Li-ion pouch cell (SiC||NCM811, 8 Ah nominal capacity) via optimizing cation occupancy and increase its capacity by 10% from 6.49 to 7.14 Ah at 1 C, illustrating the benefits of the upcycling process.

Abstract Purpose To develop a comprehensive and validated personalized scoring system based on anatomical characteristics to predict the probability of failure to return to sport after medial patellofemoral ligament reconstruction in patients with patellar dislocation. Methods 312 patients with medial patellofemoral ligament reconstruction in our hospital from 2013 to 2023 were included. Demographic and anatomical characteristics were collected retrospectively. A backward stepwise approach was used to identify independent predictors, and a nomogram was constructed to predict the probability of recurrence. The predictive performance was evaluated by receiver operating characteristic curves, calibration diagram and decision curve analysis. Results Multivariate analysis showed that increased tibial tubercle–trochlear groove (TT-TG) distance, trochlear dysplasia, increased femoral anteversion angle, and patellar alta were independent risk factors for failure of return to sport after medial patellofemoral ligament reconstruction. Validation of this column graph in the training cohort and validation cohort showed strong predictive power, with areas under the curve of 0.850 and 0.844, respectively. The nomogram has good calibration and good clinical practicability. Conclusion The study developed a personalized predictive nomogram with 4 predictors (increased TT-TG distance, trochlear dysplasia, increased femoral anteversion angle, and patellar alta) that allowed surgeons to stratify the risk of failure to return to sport after medial patellofemoral ligament reconstruction and recommend skeletal surgery for patients with these factors. Level of Evidence: Level III.

Abstract An imbalance between the adipogenesis and osteogenesis of bone marrow mesenchymal stem cells (BMSCs) is considered the basic pathogenesis of osteoporosis. Although actin cytoskeleton remodelling plays a crucial role in the differentiation of BMSCs, the role of actin cytoskeleton remodelling in the adipogenesis of BMSCs and postmenopausal osteoporosis (PMOP) has remained elusive. Glia maturation factor-beta (GMFB) has a unique role in remodelling the polymerization/depolymerization cycles of actin. We observed that GMFB expression was increased in bone tissue from both ovariectomized (OVX) rats and PMOP patients. GMFB knockout inhibited the accumulation of bone marrow adipocytes and increased bone mass in the OVX rat model. The inhibition of adipocyte differentiation in GMFB knockout BMSCs was mediated via actin cytoskeleton remodelling and the Ca2+-calcineurin-NFATc2 axis. Furthermore, we found that GMFB shRNA treatment in vivo had favourable effects on osteoporosis induced by OVX. Together, these findings suggest a pathological association of the GMFB with PMOP and highlight the potential of the GMFB as a therapeutic target for osteoporosis patients.

In the context of Industry 4.0, the most important trend in the shipbuilding industry is to efficiently manufacture intelligent and more environmentally friendly ships. This requires the shipbuilding industry to achieve technological innovations in all aspects of the ship's life cycle and accelerate the digital transformation of the industry. Thanks to the development of new-generation information technology, digital twins have received widespread attention and application in the manufacturing industry. The excellent performance of digital twins in monitoring, diagnosis and decision support also provides strong support for the digital transformation of the manufacturing industry. However, the application and development of digital twin technology are constrained when faced with the complex and discrete manufacturing processes in the shipbuilding industry. To address the constraints in the shipbuilding industry, promote the application of digital twin technology, and support the digital transformation of the shipbuilding industry, a statistical analysis of publications linked to the shipbuilding industry and digital twin using the Web of Science and the Scopus are done in this paper. The application and development of digital twin in the shipbuilding industry was systematically analyzed, the problems restricting the development of digital twin in the shipbuilding industry was summarized. Finally, the development trend of digital twin in shipbuilding industry prospects.

Abstract Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabetic periodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. The slow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24–30 Fr while maintaining a balloon pressure of 25–35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16–165) with median estimated blood loss of 2 ml (range 0–150). The median postoperative hospital stay was 3 d (range 1–15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3–100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

This study investigated the relationship between perfectionism and relative deprivation among nursing students in China as well as the mediating role of interpersonal sensitivity and the moderating role of resilience in this relationship. A cross-sectional study design involved 682 nursing students participants from two universities in Henan Province, China, using questionnaires about demographics, perfectionism, relative deprivation, interpersonal sensitivity, and resilience. Descriptive statistics, Pearson's correlation analysis and the PROCESS macro in regression analysis were used for data analysis. Adaptive perfectionism was not significantly correlated with relative deprivation, while maladaptive perfectionism was significantly positively correlated with interpersonal sensitivity, relative deprivation, and resilience. Interpersonal sensitivity mediated the relationship between maladaptive perfectionism and relative deprivation, accounting for 41.07% of the total effect. Moreover, the first half path and direct path of this process were moderated by resilience. These results show that targeted interventions to reduce maladaptive perfectionism, reduce interpersonal sensitivity and improve resilience of nursing students could help reduce their relative deprivation.

Abstract Stress can lead to gut dysbiosis in brain-gut axis disordered diseases as irritable bowel syndrome (IBS), yet the mechanisms how stress transfer from the brain to the gut and disrupt gut microbiota remain elusive. Here we describe a stress-responsive brain-to-gut axis which impairs colonocytes’ mitochondria to trigger gut dysbiosis. Patients with IBS exhibit significantly increased facultative anaerobes and decreased obligate anaerobes, related to increased serum corticotropin-releasing hormone (CRH) level and defected colonocytes’ mitochondria ultrastructure. Mice exposed to acute stress experienced enhanced CRH-CRH receptor type 1 (CRHR1) signaling, which impaired mitochondria and epithelium hypoxia in the colon, subsequently triggered gut dysbiosis. Antagonizing CRHR1 expression to inhibit cAMP/Ras/MAPK signaling or activating mitochondria respiration conferred resilience against stress-induced mitochondria damaging and epithelium hypoxia impairment, ultimately improving gut dysbiosis. These results suggest that the CRH-CRHR1-mitochondria pathway plays a pivotal role in stress-induced gut dysbiosis that could be therapeutically targeted for stress-induced gastrointestinal diseases. Yiming Zhang et.al report that psychological stress activated Corticotropin-releasing hormone (CRH)-CRH receptor type 1 (CRHR1)-mitochondria pathway to trigger gut dysbiosis and reveal CRHR1 upregulation damages mitochondria via cAMP/Ras/MAPK signaling in colonocytes.

Abstract A high‐power, high‐isolation, dual‐polarised planar phased array antenna is presented. Based on a multi‐layer microstrip structure, two sets of polarisation ports are fed through orthogonal slot coupling, achieving high isolation and low cross‐polarisation. Double‐layer radiation patches and cavity interlayers are used to expand the bandwidth and increase the gain. Metal vias are added around microstrip feeders and between array units to suppress surface waves, thereby improving the scanning performance of the phased array. A smooth gradient microstrip structure is designed to improve the power capacity while realising broadband impedance matching. The measured results show that in the 8–10 GHz frequency band, the isolation of the dual polarisation ports is greater than 50 dB, and the impedance bandwidth reaches 22.2%, with active VSWR

In recent years, the incidence of cosmetic injection-induced botulism has remarkably increased due to the frequent usage of botulinum neurotoxin type A (BoNT/A). To mimic and investigate this new clinical type of botulism, we established a novel animal model and evaluated the therapeutic potential of a new drug. Firstly, we injected BoNT/A into the gastrocnemius of rats to induce partial paralysis of the remaining limbs. Then, the intoxicated rats were treated with 3,4-diaminopyridine (3,4-DAP) at different stages of the disease and the forelimbs grasping strength (FGS) was evaluated. We showed that, at the sublethal dose, the FGS began to decrease at 6.00 ​± ​1.86 ​h after injection in rats, from 2.28 ​± ​0.19 ​N to 1.51 ​± ​0.18 ​N, while the FGS declined appeared earlier (4.29 ​± ​0.42 ​h) at the lethal dose, from 2.30 ​± ​0.20 ​N to 1.20 ​± ​0.16 ​N. Treatment with 3,4-DAP respectively at the time of the symptoms onset or 7 days after injection both can temporarily reverse the symptoms of muscle paralysis, indicating that 3,4-DAP may be an effective approach to relieve botulism. Overall, this study provides an available rat model and a promising therapeutic strategy for cosmetic injection-induced botulism.

Abstract Clear cell renal cell carcinoma (ccRCC) is characterized by a high incidence and mortality rate. Despite advancements in therapeutic interventions, the prognosis for renal cancer patients remains suboptimal. Of late, methylation modifications have emerged as promising molecular targets for tumor assessment and treatment, yet their potential has not been fully investigated in the context of ccRCC. Transcriptomic and clinical data were extracted from The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress databases, leading to the identification of 57 methylation-related genes (MRGs). Utilizing DESeq2 analysis, Cox regression analysis, and the LASSO regression algorithm, a Methylation-Related Risk Score (MARS) was constructed. Cluster analysis, Gene Ontology (GO) analysis, clinical feature analysis, immune infiltration analysis, and mutation analysis were further employed to evaluate the model. Our investigation identified six pivotal prognostic MRGs and established a risk score predicated on m6A/m5C/m1A/m7G regulatory factors. This score was validated across two external cohorts and can be utilized to assess individual immune infiltration statuses and predict responses to immunotherapy. Moreover, cluster analysis delineated two distinct m6A/m5C/m1A/m7G gene clusters. We have developed and validated a robust prognostic signature based on genes associated with m6A, m5C, m1A, and m7G modifications. This gene signature demonstrates significant prognostic value in assessing survival outcomes, clinical characteristics, immune infiltration, and responses to immunotherapy in ccRCC patients. This finding provides valuable insights for refining precision treatment strategies.

Although vasculitis and renal involvement might be associated with malignancy, they are rarely associated with lymphoproliferative diseases. We observed a case of immunoglobulin A vasculitis associated with segmental and focal glomerulonephritis in a patient with Angioimmunoblastic T-cell lymphoma. The most interesting aspect of this case is that this patient’s main initial manifestations were skin rash and fever. No significant lymph node enlargement was found at the time. Routine urine examination found positive urine protein, and renal puncture biopsy indicated purpura nephritis. More than one year later, the patient was admitted to the Department of Hematology of our hospital again after finding a mass in the neck. After that, the patient was diagnosed with Angioimmunoblastic T-cell lymphoma by lymph node biopsy. To our great surprise, successful treatment of the underlying malignancy was associated with the remission of glomerulonephritis and cutaneous vasculitis.

Biotechnology has limited effectiveness in terms of removing mixed antibiotics at low temperatures, leading to ecological risks arising from the presence of antibiotics in environmental waters. In this study, the removal of tetracycline (TCs) and sulfonamide (SAs) from antibiotic wastewater was improved by the intermittent electrical stimulation of anaerobic-aerobic-coupled upflow bioelectrochemical reactors (AO-UBERs) at low temperatures. The removal effects of oxytetracycline and tetracycline were 48.6 ± 3.5 % and 71.5 ± 2.9 %, respectively. Under 0.9V, the removal rates of oxytetracycline, tetracycline, and trimethoprim were significantly increased in both the aerobic-cathodic and anaerobic anodic chambers, with a more obvious increase at low temperatures. Compared with the blank control group, the removal efficiency of oxytetracycline, trimethoprim and tetracycline in the electric group was increased by 11.8 ± 2.5 %, 27.8 ± 10.5 % and 11.2 ± 5.8 %. The anaerobic chamber contributed more to the removal of TCs and trimethoprim than the aerobic chamber. Furthermore, electrical stimulation selectively enriched electroactive bacteria (Methylophage and Pleuromonas), drug-resistant bacteria (Proteobacteria), and nitrifying bacteria associated with biodegradation. The abundance of antibiotic-resistance genes is related to the distribution of potential hosts and mobile genetic elements (sul1), and electrical stimulation induces the enrichment of both. This suggests that while potentially effective for treating TCs- and SAs-containing wastewater at low temperatures, AO-UBERs may lead to the accumulation of antibiotic-resistance genes.

Abstract A large concentration gradient originating from sluggish ion transport on the surface of Zn metal anodes will result in uneven Zn2+ flux, giving rise to severe dendrite growth, especially at high current density. Herein, an ion acceleration layer is introduced by a facile separator engineering strategy to realize modulated Zn2+ flux and dendrite‐free deposition. Zinc hexacyanoferrate as the modifying agent featuring strong zincophilicity and rapid diffusion tunnel can enable fast trap for Zn2+ near the electrode surface and immediate transport onto deposition sites, respectively. The ion acceleration effect is substantiated by improved ion conductivity, decreased activated energy, and promoted Zn2+ transference number, which can moderate concentration gradient to guide homogenous Zn2+ flux distribution. As a result, the separator engineering guarantees Zn||Zn symmetrical cells with long‐term stability of 2700 h at 2 mA cm−2, and 1770 h at a large current density of 10 mA cm−2. Moreover, cycling stability and rate capability for full cells with different cathodes can be substantially promoted by the modified separator, validating its superior practical feasibility. This study supplies a new scalable approach to tailoring ion flux near the electrode surface to enable robust Zn metal anodes at a high current density.

PurposeThe inhibition of thrombin has proven to be an efficacious therapeutic approach for managing cardiovascular disease (CVD), with widespread implementation in clinical settings. Oral ingestion of peptides and protein drugs is influenced by gastrointestinal digestive enzymes. We aimed to evaluate the thrombin inhibitory properties of hirudo hydrolysates (HHS) produced by pepsin and propose a comprehensive approach to screen and evaluate thrombin inhibitors.MethodsWe evaluated the in vitro inhibitory properties of the hirudo extract, both before and after hydrolysis with pepsin, toward thrombin. We screened for the most potent thrombin inhibitory peptide (TIP) using nano liquid chromatography-tandem mass spectrometry (Nano LC-MS/MS) coupled with in silico analysis. Next, we employed the thrombin inhibition activity IC50 to investigate the interaction between TIP and thrombin, and conducted in vitro evaluations of its anticoagulant effects (APTT, TT, PT), as well as its ability to inhibit platelet aggregation. Furthermore, we utilized UV-Vis spectroscopy to explore structural changes in thrombin upon binding with TIP and employed molecular dynamics simulations to delve deeper into the potential atomic-level interaction modes between thrombin and TIP.ResultsThe retention rate of thrombin inhibition for HHS was found to be between 60% and 75%. A total of 90 peptides from the HHS were identified using LC-MS/MS combined with de novo sequencing. Asn-Asp-Leu-Trp-Asp-Gln-Gly-Leu-Val-Ser-Gln-Asp-Leu (NDLWDQGLVSQDL, P1) was identified as the most potent thrombin inhibitory peptide after in silico screening (molecular docking and ADMET). Then, the in vitro study revealed that P1 had a high inhibitory effect on thrombin (IC50: 2,425.5 ± 109.7 μM). P1 exhibited a dose-dependent prolongation of the thrombin time (TT) and a reduction in platelet aggregation rate. Both UV-Vis spectroscopy and molecular dynamics simulations demonstrated that P1 binds effectively to thrombin.ConclusionOverall, the results suggested that HHS provides new insights for searching and evaluating potential antithrombotic compounds. The obtained P1 can be structurally optimized for in-depth evaluation in animal and cellular experiments.

Bainbridge–Ropers syndrome (BRPS) is a recently described neurodevelopmental genetic disorder associated with de novo truncating variants in additional sex combs like 3 (ASXL3) on chromosome 18q12.1. Trio-based exome sequencing was conducted on patients admitted to the Children’s Hospital Affiliated to Shandong University and diagnosed with unexplained intellectual disabilities or developmental delay between June 2022 and January 2024. De novo truncation of ASXL3 was identified in four patients, and the pathogenic variants and their de novo status were validated using Sanger sequencing. Comprehensive clinical phenotype–genotype information of all previously reported patients with BRPS was collected and summarized. The common clinical manifestations observed in the four patients included language and intellectual disabilities or psychomotor retardation. Genetic analysis revealed that patient 1 carried a de novo heterozygous variant, c.1667_1668del (p.Thr556Arpfs*3), whereas patient 2 had a novel heterozygous frameshift variant of ASXL3, c.3324del (p.Lys1109Serfs*34). These two variants have not been documented to date. Additionally, patients 3 and 4 exhibited a de novo variant, c.4678C > T (p.Arg1560Ter). Based on the combined assessment of clinical phenotypes and genetic testing results, it was postulated that all four children presented with BRPS syndrome caused by pathogenic variations in ASXL3. The present study complements the range of ASXL3 mutational and phenotypic spectra in the population, highlighting subtle distinctions in clinical manifestations between Chinese patients and other racial groups. The reporting of additional cases will contribute to further elucidating the function of ASXL3 and establishing a solid foundation for clinical diagnosis and treatment.

Abstract Real‐time polymerase chain reaction (RT‐PCR) remains the most prevalent molecular detection technology for sewage analysis but is plagued with numerous disadvantages, such as time consumption, high manpower requirements, and susceptibility to false negatives. In this study, an automated robot‐driven photoelectrochemical (PEC) biosensing platform is constructed, that utilizes the CRISPR/Cas12a system to achieve fast, ultrasensitive, high specificity detection of biological loads in sewage. The Shennong‐1 robot integrates several functional modules, involving sewage sampling and pretreatment to streamline the sewage monitoring. A screen‐printed electrode is employed with a vertical graphene‐based working electrode and enhanced with surface‐deposited Au nanoparticles (NPs). CdTe/ZnS quantum dots (QDs) are further fabricated through the double‐stranded DNA (dsDNA) anchored on Au NPs. Using the cDNA template of Omicron BA.5 spike gene as a model, the PEC biosensor demonstrates excellent analytical performance, with a lower detection limit of 2.93 × 102 zm and an outstanding selectivity at the level of single‐base mutation recognition. Furthermore, the rapid, accurate detection of BA.5 in sewage demonstrates the feasibility of the PEC platform for sewage monitoring. In conclusion, this platform allows early detection and tracking of infectious disease outbreaks, providing timely data support for public health institutions to take appropriate prevention and control measures.

Summary: Organisms integrate circadian and metabolic signals to optimize substrate selection to survive starvation, yet precisely how this occurs is unclear. Here, we show that hepatocyte Period 1 (Per1) is selectively induced during fasting, and mice lacking hepatocyte Per1 fail to initiate autophagic flux, ketogenesis, and lipid accumulation. Transcriptomic analyses show failed induction of the fasting hepatokine Fgf21 in Per1-deficient mice, and single-nucleus multiome sequencing defines a putative responding hepatocyte subpopulation that fails to induce the chromatin accessibility near the Fgf21 locus. In vivo isotopic tracing and indirect calorimetry demonstrate that hepatocyte Per1-deficient mice fail to transit from oxidation of glucose to fat, which is completely reversible by exogenous FGF21 or by inhibiting pyruvate dehydrogenase. Strikingly, disturbing other core circadian genes does not perturb Per1 induction during fasting. We thus describe Per1 as an important mechanism by which hepatocytes integrate internal circadian rhythm and external nutrition signals to facilitate proper fuel utilization.

Existing studies have shown that Astragalus membranaceus (AM) and its active ingredients astragalus polysaccharides, oninon, and astragalus methyl glycosides can attenuate X-ray radiation-induced injury. However, there are no studies on how isoliquiritigenin (ISL) attenuate the bystander effect of bone marrow mesenchymal stem cells (BMSCs) induced by carbon ion radiation therapy for lung cancer. This study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect (RIBE) in BMSCs to elucidate its mechanism of action. In this study, we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro, and the models were successfully treated with carbon ions. In further work, we used flow cytometry, immunofluorescence, Western blot, enzyme-linked immunosorbent assay (ELISA), inhibitor, short hairpin RNA (shRNA), Cell Counting Kit-8 (CCK-8), and other methods to illustrate the mechanism. In the next experiments, we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation damage. The aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo settings. Traditional Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung cancer. These results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.

Bench blasting is commonly used in open-pit mining. Some design parameters such as positions of hole packing and caving holes have great influences on the blasting effects. In this work, with a hybrid discrete-finite element method, numerical simulations of bench blasting are conducted, capturing the whole continuous-discontinuous processes. Considering two engineering cases, the influences of hole packing and caving holes are evaluated. The numerical results not only lead to some improved designs by relocating the packing positions and caving holes but also indicate the reliability of the adopted numerical tools.

Abstract Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5’-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Abstract Objective Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology. Methods U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF). Results OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1β and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results. Conclusions KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA.

Abstract Background Corneal injuries, often leading to severe vision loss or blindness, have traditionally been treated with the belief that limbal stem cells (LSCs) are essential for repair and homeostasis, while central corneal epithelial cells (CCECs) were thought incapable of such repair. However, our research reveals that CCECs can fully heal and maintain the homeostasis of injured corneas in rats, even without LSCs. We discovered that CXCL14, under PAX6’s influence, significantly boosts the stemness, proliferation, and migration of CCECs, facilitating corneal wound healing and homeostasis. This finding introduces CXCL14 as a promising new drug target for corneal injury treatment. Methods To investigate the PAX6/CXCL14 regulatory axis’s role in CCECs wound healing, we cultured human corneal epithelial cell lines with either increased or decreased expression of PAX6 and CXCL14 using adenovirus transfection in vitro. Techniques such as coimmunoprecipitation, chromatin immunoprecipitation, immunofluorescence staining, western blot, real-time PCR, cell colony formation, and cell cycle analysis were employed to validate the axis’s function. In vivo, a rat corneal epithelial injury model was developed to further confirm the PAX6/CXCL14 axis’s mechanism in repairing corneal damage and maintaining corneal homeostasis, as well as to assess the potential of CXCL14 protein as a therapeutic agent for corneal injuries. Results Our study reveals that CCECs naturally express high levels of CXCL14, which is significantly upregulated by PAX6 following corneal damage. We identified SDC1 as CXCL14’s receptor, whose engagement activates the NF-κB pathway to stimulate corneal repair by enhancing the stemness, proliferative, and migratory capacities of CCECs. Moreover, our research underscores CXCL14’s therapeutic promise for corneal injuries, showing that recombinant CXCL14 effectively accelerates corneal healing in rat models. Conclusion CCECs play a critical and independent role in the repair of corneal injuries and the maintenance of corneal homeostasis, distinct from that of LSCs. The PAX6/CXCL14 regulatory axis is pivotal in this process. Additionally, our research demonstrates that the important function of CXCL14 in corneal repair endows it with the potential to be developed into a novel therapeutic agent for treating corneal injuries.

Abstract Background Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of kidney cancer, accounts for approximately 70% to 80% of all cases. Histone deacetylase 10 (HDAC10) belongs to the HDAC class IIb subgroup, one of the histone deacetylases (HDAC) family. Previous studies suggest that HDAC10 may regulate the development of multiple tumor types. The specific molecular mechanisms employed by HDAC10 in the etiology of ccRCC still need to be discovered. Methods The analysis included examining HDAC10 expression levels and their clinical importance within a cohort of inpatients and ccRCC patients documented in the Tumor Genome Atlas (TCGA). Moreover, the biological functions and underlying molecular mechanisms of HDAC10 were investigated. Results HDAC10 showed increased expression in ccRCC tumor tissues. Subsequent analysis revealed overexpression of HDAC10 was associated with advanced clinical phenotype and unfavorable prognosis. The absence of HDAC10 significantly decreased ccRCC cell proliferation and migration capabilities. Mechanistic research suggests that HDAC10 may promote RCC development by activating the Notch-1 pathway and downregulating PTEN expression levels. Conclusion In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.

Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification to facilitate precision medicine. We performed ssGSEA analysis to quantify the pathway activity of RNA splicing in three HCC cohorts. Kaplan–Meier and Cox methods were used for survival analysis. GO and GSEA were performed to analyze pathway enrichment. We confirmed that RNA splicing is significantly correlated with prognosis, and identified an alternative splicing-associated protein LUC7L3 as a potential HCC prognostic biomarker. Further bioinformatics analysis revealed that high LUC7L3 expression indicated a more progressive HCC subtype and worse clinical features. Cell proliferation-related pathways were enriched in HCC patients with high LUC7L3 expression. Consistently, we proved that LUC7L3 knockdown could significantly inhibit cell proliferation and suppress the activation of associated signaling pathways in vitro. In this research, the relevance between RNA splicing and HCC patient prognosis was outlined. Our newly identified biomarker LUC7L3 could provide stratification for patient survival and recurrence risk, facilitating early medical intervention before recurrence or disease progression.

Pumpkin (Cucurbita moschata Duch.) is a versatile crop with strong stress resistance and promising growth potential. Widely cultivated in various regions of China, it ranks among the top crops globally in terms of both planting area and consumption. Known for its pleasant taste and high nutritional value, pumpkin pulp is rich in essential trace elements for the human body. Even after harvest, pumpkin fruit remains metabolically active, requiring its own nutrients to complete the postripening process. Failure to provide proper postharvest storage conditions can lead to excessive water loss and rapid nutrient depletion, resulting in rough, shriveled, and even rotten peel, ultimately diminishing the economic value of the pumpkin. This study aimed to investigate the changes in pumpkin quality and physiological indicators during storage to provide insights to determine optimal consumption and processing periods of pumpkins. The pumpkins were stored at a temperature of 16 ± 2 °C and 60% to 80% humidity during the experiment. The dynamic changes in fruit quality, hardness, respiration rate, malondialdehyde content, level of antioxidant enzymes, and other indicators of two pumpkin cultivars (BM5 and JQ) were assessed during storage, and the correlation among these indicators was evaluated. The results indicated a decrease in the vitamin C content and pulp hardness, whereas the superoxide dismutase and catalase contents initially increased and then decreased, and malondialdehyde and weight loss rates increased over the storage period. The weight loss rate exhibited significant positive and negative correlations with the malondialdehyde content (P < 0.01) of the two cultivars, whereas the vitamin C content showed a significant positive correlation with pulp hardness (P < 0.01). The findings indicate that optimal fruit quality was maintained within 40 days of postharvest storage. This study provides valuable insights into the selection of storable pumpkin cultivars.

BackgroundPrevious studies have suggested a crosstalk between the oral microbiome and esophageal cancer (EC), but the exact relationship is unclear. This study aimed to investigate the causal relationship between changes in the oral microbiome and EC by Mendelian randomization (MR).Materials and methodsIn the study, bidirectional MR analyses were conducted using genome-wide association study data from the oral microbiomes from the 4D-SZ cohort and EC data from the BioBank Japan cohort. Multiple sensitivity tests, including Cochrane’s Q statistic, MR-Egger intercept, and MR-PRESSO, were used to assess and validate the relative stability of the resulting data at various levels.ResultsAmong the 3,117 samples studied, 73 oral microbiomes were found to be statistically causally associated with EC, 38 of which were considered protective factors. According to species analyses, positive results were concentrated in three phyla: Firmicutes (29 species), Patescibacteria (18 species), and Actinobacteria (9 species). It was also determined that Parvimonas micra, Aggregatibacter, and Clostridia had a negative causal relationship, implying that EC caused a decrease in the counts. Following p-value correction, periodonticum_C, unclassified_mgs_3234, and unclassified_mgs_45 were identified as having a strong evidence-grade causal relationship with EC. There was no strong evidence in the results of the inverse MR analyses of EC to the oral microbiome. The sensitivity analysis confirmed the robustness of the findings.ConclusionThis study discovered a bidirectional causal relationship between the oral microbiome and EC, which may provide new insights into the future use of the microbiome for early screening and probiotic therapy.

Podocytes maintain renal filtration integrity when the glomerular filtration barrier (GFB) is integrated. Impairment or attrition of podocytes, leading to compromised GFB permeability, constitutes the primary etiology of proteinuria and is a hallmark pathological feature of diabetic nephropathy (DN). This study centers on Heterogeneous Nuclear Ribonucleoprotein I (HNRNP I), an RNA-binding protein, delineating its role in facilitating DN-induced renal damage by modulating podocyte health. Comparative analyses in renal biopsy specimens from DN patients and high-glucose-challenged podocyte models in vitro revealed a marked downregulation of HNRNP I expression relative to normal renal tissues and podocytes. In vitro assays demonstrated that high-glucose conditions precipitated a significant reduction in podocyte viability and an escalation in markers indicative of apoptosis. Conversely, HNRNP I overexpression was found to restore podocyte viability and attenuate apoptotic indices. IRAK1, a gene encoding a protein integral to inflammatory signaling, was shown to interact with HNRNP I, which promotes IRAK1 degradation. This interaction culminates in suppressing the PI3K/AKT/mTOR signaling pathway, thereby diminishing podocyte apoptosis and mitigating renal damage in DN. This investigation unveils the mechanistic role of HNRNP I in DN for the first time, potentially informing novel therapeutic strategies for DN renal impairment.

ObjectiveThe aim of this study was to investigate the genotypic and clinical phenotypic characteristics of MAX germline mutation–associated pheochromocytoma (PCC) and paraganglioma (PGL).MethodsWe retrospectively analyzed the family investigation data and clinical genetic characteristics of six individuals from three independent families with PCC carrying MAX germline mutations from December 2005 to March 2024. A literature review was then conducted of the six carriers and another 103 carriers from the other 84 families with MAX germline mutations reported previously.ResultsThere were 109 patients in 87 families with all five exons and 53 types of MAX germline mutations. p.R33* (c.97C>T; 21.1%), p.R75* (c.223C>T; 13.8%), and p.A67D (c.200C>A; 7.3%), which accounted for 42.2% of mutations detected, were the most common mutations. Moreover, 101 (92.7%) patients developed PCCs, including 59 bilateral PCCs and 42 unilateral PCCs, and 19 (18.8%) patients showed metastasis. The mean age at diagnosis was 32.8 ± 12.6 (13-80) years. The male-to-female ratio was 1.3:1. In 11 (10.9%) patients, the PCC was accompanied by chest or abdominal PGL, and one other patient had sole head and neck PGL. Nine (8.3%) patients also had functional pituitary adenomas, 11 (10.9%) developed other neuroendocrine tumors (NETs), and 7 (6.4%) presented with concomitant non-NET. Meanwhile, MAX-p.Q82Tfs*89 and p.E158A mutations are reported for the first time in this study.ConclusionMAX germline mutations may cause new types of multiple endocrine neoplasia. A comprehensive baseline assessment of neural crest cell–derived diseases is recommended for all individuals with MAX germline mutations. The risk of bilateral and metastatic PCCs should also be considered.

BackgroundChatGPT is a natural language processing model developed by OpenAI, which can be iteratively updated and optimized to accommodate the changing and complex requirements of human verbal communication. ObjectiveThe study aimed to evaluate ChatGPT’s accuracy in answering orthopedics-related multiple-choice questions (MCQs) and assess its short-term effects as a learning aid through a randomized controlled trial. In addition, long-term effects on student performance in other subjects were measured using final examination results. MethodsWe first evaluated ChatGPT’s accuracy in answering MCQs pertaining to orthopedics across various question formats. Then, 129 undergraduate medical students participated in a randomized controlled study in which the ChatGPT group used ChatGPT as a learning tool, while the control group was prohibited from using artificial intelligence software to support learning. Following a 2-week intervention, the 2 groups’ understanding of orthopedics was assessed by an orthopedics test, and variations in the 2 groups’ performance in other disciplines were noted through a follow-up at the end of the semester. ResultsChatGPT-4.0 answered 1051 orthopedics-related MCQs with a 70.60% (742/1051) accuracy rate, including 71.8% (237/330) accuracy for A1 MCQs, 73.7% (330/448) accuracy for A2 MCQs, 70.2% (92/131) accuracy for A3/4 MCQs, and 58.5% (83/142) accuracy for case analysis MCQs. As of April 7, 2023, a total of 129 individuals participated in the experiment. However, 19 individuals withdrew from the experiment at various phases; thus, as of July 1, 2023, a total of 110 individuals accomplished the trial and completed all follow-up work. After we intervened in the learning style of the students in the short term, the ChatGPT group answered more questions correctly than the control group (ChatGPT group: mean 141.20, SD 26.68; control group: mean 130.80, SD 25.56; P=.04) in the orthopedics test, particularly on A1 (ChatGPT group: mean 46.57, SD 8.52; control group: mean 42.18, SD 9.43; P=.01), A2 (ChatGPT group: mean 60.59, SD 10.58; control group: mean 56.66, SD 9.91; P=.047), and A3/4 MCQs (ChatGPT group: mean 19.57, SD 5.48; control group: mean 16.46, SD 4.58; P=.002). At the end of the semester, we found that the ChatGPT group performed better on final examinations in surgery (ChatGPT group: mean 76.54, SD 9.79; control group: mean 72.54, SD 8.11; P=.02) and obstetrics and gynecology (ChatGPT group: mean 75.98, SD 8.94; control group: mean 72.54, SD 8.66; P=.04) than the control group. ConclusionsChatGPT answers orthopedics-related MCQs accurately, and students using it excel in both short-term and long-term assessments. Our findings strongly support ChatGPT’s integration into medical education, enhancing contemporary instructional methods. Trial RegistrationChinese Clinical Trial Registry Chictr2300071774; https://www.chictr.org.cn/hvshowproject.html ?id=225740&v=1.0

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.

BackgroundAllergic rhinitis (AR) is a complex disease in which gene-environment interactions contribute to its pathogenesis. Epigenetic modifications, such as N6-methyladenosine (m6A) modification of mRNA, play important roles in regulating gene expression in multiple physiological and pathological processes. However, the function of m6A modification in AR and the inflammatory response is poorly understood.MethodsWe used the ovalbumin (OVA) and aluminum hydroxide to induce an AR mouse model. Nasal symptoms, histopathology, and serum cytokines were examined. We performed combined m6A and RNA sequencing to analyze changes in m6A modification profiles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylated RNA immunoprecipitation sequencing qPCR (MeRIP-qPCR) were used to verify differential methylation of mRNAs and the m6A methylation level. Knockdown or inhibition of Alkbh5 in nasal mucosa of mice was mediated by lentiviral infection or IOX1 treatment.ResultsWe showed that m6A was enriched in a group of genes involved in MAPK signaling pathway. Moreover, we identified a MAPK pathway involving Map3k8, Erk2, and Nfκb1 that may play a role in the disrupted inflammatory response associated with nasal inflammation. The m6A eraser, Alkbh5, was highly expressed in the nasal mucosa of AR model mice. Furthermore, knockdown of Alkbh5 expression by lentiviral infection resulted in high MAPK pathway activity and a significant nasal mucosa inflammatory response. Our findings indicate that ALKBH5-mediated m6A dysregulation likely contributes to a nasal inflammatory response via the MAPK pathway.ConclusionTogether, our data show that m6A dysregulation mediated by ALKBH5, is likely to contribute to inflammation of the nasal mucosa via the MAPK signaling pathway, suggesting that ALKBH5 is a potential biomarker for AR treatment.

Food safety comment classification represents a specialized task within the realm of text classification. The objective is to efficiently identify a large volume of food safety comments, aiding relevant authorities in timely food analysis and safety alerts. Traditional methods typically employ one-hot encoding for label processing. However, in real-world situations, classified labels often convey valuable semantic information and guidance. This paper introduces an innovative approach to enhance the classification performance of food safety comments by embedding label information. Initially, we extracted generic sentiment pivot words from various classification labels as label description information. Subsequently, we employ a joint embedding approach to integrate this label description information into the text. This process will pool the expressions of the pivot word into the corresponding sentiment labels in the known domains after averaging to get the embedded expression. This aims to acquire highly detailed self-semantic feature vectors and self-knowledge feature vectors that are integrated with labeled descriptive information. Then, feed the semantic representation of comments and the word-embedded representation of labeled description information into a time-step-based multilayer Bi-LSTM and a step-based multilayer CNN, respectively. Ultimately, we concatenate these two feature vectors to facilitate matching, thereby fusing the self-semantic and self-knowledge features of labeled description information to train a classification model for food safety comments. Experimental results on the food safety comment dataset showcase a noteworthy improvement of 1.74% and 1.27% in Macro_Precision and Macro_F1 metrics, respectively, compared to BERT, BERT-RNN, and BERT-CNN. Through extensive ablation experiments and additional studies, our method effectively embeds labeling information, demonstrating a clear advantage over traditional methods in the task of classifying food safety comments. Doi: 10.28991/HIJ-2024-05-01-013 Full Text: PDF

Lithium-sulfur batteries (LSBs) with high energy densities have been demonstrated the potential for energy-intensive demand applications. However, their commercial applicability is hampered by hysteretic electrode reaction kinetics and the shuttle effect of lithium polysulfides (LiPSs). In this work, an interlayer consisting of high-entropy metal oxide (Cu0.7Fe0.6Mn0.4Ni0.6Sn0.5)O4 grown on carbon nanofibers (HEO/CNFs) is designed for LSBs. The CNFs with highly porous networks provide transport pathways for Li+ and e−, as well as a physical sieve effect to limit LiPSs crossover. In particular, the grapevine-like HEO nanoparticles generate metal-sulfur bonds with LiPSs, efficiently anchoring active materials. The unique structure and function of the interlayer enable the LSBs with superior electrochemical performance, i.e., the high specific capacity of 1381 mAh g−1 at 0.1 C and 561 mAh g−1 at 6 C. This work presents a facile strategy for exploiting high-performance LSBs.

In this paper, to study the mechanical responses of a solid propellant subjected to ultrahigh acceleration overload during the gun-launch process, specifically designed projectile flight tests with an onboard measurement system were performed. Two projectiles containing dummy HTPB propellant grains were successfully recovered after the flight tests with an ultrahigh acceleration overload value of 8100 g. The onboard-measured time-resolved axial displacement, contact stress and overload values were successfully obtained and analysed. Uniaxial compression tests of the dummy HTPB propellant used in the gun-launched tests were carried out at low and intermediate strain rates to characterize the propellant's dynamic properties. A linear viscoelastic constitutive model was employed and applied in finite-element simulations of the projectile-launching process. During the launch process, the dummy propellant grain exhibited large deformation due to the high acceleration overload, possibly leading to friction between the motor case and propellant grain. The calculated contact stress showed good agreement with the experimental results, though discrepancies in the overall displacement of the dummy propellant grain were observed. The dynamic mechanical response process of the dummy propellant grain was analysed in detail. The results can be used to estimate the structural integrity of the analysed dummy propellant grain during the gun-launch process.

Epididymitis or epididymo-orchitis is a common urological condition in males characterized by scrotal pain, swelling, and potential urinary symptoms. Although antibiotics can eliminate the causative pathogens, persistent inflammation may compromise spermatogenesis and steroidogenesis. The testis, an immune-privileged organ, possesses a specialized immune microenvironment that shields germ cells (GCs) from autoimmune attacks and orchestrates immune defenses against pathogens. This review focuses on the complex interplay between immune cells, including macrophages, dendritic cells (DCs), mast cells (MCs), and T cell subsets, in the testis. The roles of these immune cells in infection-induced orchitis were deliberated upon, emphasizing their involvement in inflammation and immune tolerance. Furthermore, the implications of testicular fibrosis and its effect on male infertility are discussed, emphasizing the role of MCs in tissue remodeling. The objective of this review is to expand comprehension of male reproductive health and foster the identification of potential therapeutic targets for epididymo-orchitis.

Abstract Ruthenium (Ru) has been recognized as a prospective candidate to substitute platinum catalysts in water‐splitting‐based hydrogen production. However, minimizing the Ru contents, optimizing the water dissociation energy of Ru sites, and enhancing the long‐term stability are extremely required, but still face a great challenge. Here, we report on creating tungsten oxide‐anchored Ru clusters (Ru–WOx) with electron‐rich and anti‐corrosive microenvironments for efficient and robust seawater splitting. Benefiting from the abundant oxygen vacancy structure in tungsten oxide support, the Ru–WOx exhibits strong Ru–O and Ru–W bonds at the interface. Our study elucidates that the strong Ru–O bonds in Ru–WOx may accelerate the water dissociation kinetics, and the Ru–W bonds will lead to the strong metal–support interaction and electrons transfer from W to Ru. The optimal Ru–WOx catalysts exhibit a low overpotential of 29 and 218 mV at the current density of 10 mA cm−2 in alkaline and seawater media, respectively. The outstanding long‐term stability discloses that the Ru–WOx catalysts own efficient corrosion resistance in seawater electrolysis. We believe that this work offers new insights into the essential roles of electron‐rich and anti‐corrosive microenvironments in Ru‐based catalysts and provide a new pathway to design efficient and robust cathodes for seawater splitting.

A novel textile antenna is proposed to produce an omnidirectional radiation pattern. It can be integrated with clothes as a wristband due to its cylindrical conformal design. The antenna has a resonant cavity fabricated from conductive fabric and filled with cotton fabric. Three edges of the cavity are short-circuited with conductive threads and coupled-fed by a patch coupler fabricated with flexible printed circuit (FPC). Theoretical analysis shows that the proposed antenna is equivalent to a magnetic current loop, which produces a dipole-like radiation pattern when its radius is less than 0.4 wavelengths. Simulated results show that the antenna produces a low specific absorption rate (SAR) when it is loaded on human tissues. Measured results show a bandwidth from 2.36 GHz to 2.52 GHz with an omnidirectional radiation pattern. The peak gain varies between 0.6 dBi and -0.6 dBi within the bandwidth. The small thickness and simple structure of the proposed antenna make it a good candidate for wearable applications.

Inductive power transfer (IPT), as a method of wireless power transfer (WPT) via magnetic induction, can be applied to electric vehicles (EVs) due to its convenience and automation. Interoperability and misalignment tolerance are both major research difficulties for WPT of EVs. This paper proposes a two-channel topology and a coil optimization method, which can improve misalignment tolerance for the unipolar coil (Q) and interoperate with the bipolar coil (DD). Firstly, a topology with phase shift strategy is constructed to increase output ability with Y misalignments and the mathematical model of the proposed topology is established. Secondly, a coil density optimization method is presented to smooth the transmitting mutual inductances fluctuation. Finally, a 1-kW prototype is built to verify the proposed system which can achieve load-independent constant-current charging. With the Y misalignment of 150 mm, the experimental results agree well with the theoretical analysis. The proposed system is able to interoperate with two types of coils and can achieve misalignment tolerance.

Aiming at the problems of low integration of enterprises in various parts of the construction process, low productivity, serious waste of resources, and poor construction safety, this project constructs a framework for optimizing the construction process based on BIM-DT through an in-depth analysis of the characteristics and development status of the digital twin technology and BIM technology. The framework is a complete cycle system, including data management system, BIM modeling system, and digital twin model, which are integrated with each stage of survey and design, construction preparation, construction, and operation and maintenance, respectively. Finally, in the empirical study, the construction phase is taken as the object of study, and the data management system is constructed to comprehensively demonstrate the realization process of each system, and the BP neural network is utilized for fault diagnosis.

Electric vehicles (EVs) wireless charging systems have several different coil types, and each coil type may not be compatible with the others, leading to interoperability issues. Additionally, misalignment may occur between the transmitter and receiver during parking. The interoperability and misalignment tolerance problems of wireless charging for EVs need to be addressed. To solve these problems, a novel asymmetric bipolar coil structure with interoperability and misalignment tolerance is proposed. In this paper, four alternative structures with interoperability and misalignment tolerance characteristics are firstly proposed based on existing coupling structures, and an optimal coupling structure is finally selected through finite element analysis (FEA) of these four structures. An experimental prototype was also fabricated to validate this proposal. The effectiveness of the proposed asymmetric bipolar coil is verified through calculations, simulations, and experiments. The final overall transmission efficiencies obtained are all higher than 85%, regardless of the unipolar, bipolar, and quadrupolar coil structures were the transmitting coils.

A slow-wave half-mode substrate integrated waveguide with a spoof surface plasmon polariton (SW-HMSIW-SSPP) transmission line structure is proposed, analyzed, and demonstrated. Results show longitudinal and lateral size reductions of more than 80% and 73%, respectively, as compared with an equivalent SIW at the same cutoff frequency while maintaining a low attenuation constant of 0.02 dB/mm. By altering the geometric parameters of the SW-HMSIW-SSPP the dispersion curve can be tailored. The dispersion and electromagnetic (EM) field distribution characteristics of the proposed SW-HMSIW-SSPP unit cell and overall structure are analyzed by HFSS simulations and an equivalent circuit, and pertinent performance parameters are compared to those of SW-HMSIW and HMSIW-SSPP structures. A proof-of-concept PCB SW-HMSIW-SSPP sample was fabricated, and measurement results showing a band-pass of 4.8-11.5 GHz are found consistent with simulation results. The SW-HMSIW-SSPP structure has applications in the design of miniaturized microwave circuits.

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease. We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of APP/PS1 mice. Because Alzheimer’s disease affects the entire brain, further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole. Here, we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing, immunostaining, and lightsheet imaging to clarify their spatial distribution. Additionally, to clarify whether the sirtuin 1 (SIRT1)-related pathway plays a regulatory role in neural stem cell-derived exosomes interfering with mitochondrial functional changes, we generated a novel nervous system-SIRT1 conditional knockout APP/PS1 mouse model. Our findings demonstrate that neural stem cell-derived exosomes significantly increase SIRT1 levels, enhance the production of mitochondrial biogenesis-related factors, and inhibit astrocyte activation, but do not suppress amyloid-β production. Thus, neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1α signaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis. In addition, we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease, and that neural stem cell-derived exosome treatment can reverse this effect, indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

Background & Aims: Restoring hepatic and peripheral insulin sensitivity is critical to prevent or reverse metabolic syndrome and type 2 diabetes. Glucose homeostasis comprises in part the complex regulation of hepatic glucose production and insulin-mediated glucose uptake and oxidation in peripheral tissues. We previously identified hepatocyte arginase 2 (Arg2) as an inducible ureahydrolase that improves glucose homeostasis and enhances glucose oxidation in multiple obese, insulin-resistant models. We therefore examined structure-function determinants through which hepatocyte Arg2 governs systemic insulin action and glucose oxidation. Methods: To do this, we generated mice expressing wild-type murine Arg2, enzymatically inactive Arg2 (Arg2H160F) and Arg2 lacking its putative mitochondrial targeting sequence (Arg2Δ1-22). We expressed these hepatocyte-specific constructs in obese, diabetic (db/db) mice and performed genetic complementation analyses in hepatocyte-specific Arg2-deficent (Arg2LKO) mice. Results: We show that Arg2 attenuates hepatic steatosis, independent of mitochondrial localization or ureahydrolase activity, and that enzymatic arginase activity is dispensable for Arg2 to augment total body energy expenditure. In contrast, mitochondrial localization and ureahydrolase activity were required for Arg2-mediated reductions in fasting glucose and insulin resistance indices. Mechanistically, Arg2Δ1-22 and Arg2H160F failed to suppress glucose appearance during hyperinsulinemic-euglycemic clamping. Quantification of heavy-isotope-labeled glucose oxidation further revealed that mistargeting or ablating Arg2 enzymatic function abrogates Arg2-induced peripheral glucose oxidation. Conclusion: We conclude that the metabolic effects of Arg2 extend beyond its enzymatic activity, yet hepatocyte mitochondrial ureahydrolysis drives hepatic and peripheral oxidative metabolism. The data define a structure-based mechanism mediating hepatocyte Arg2 function and nominate hepatocyte mitochondrial ureahydrolysis as a key determinant of glucose oxidative capacity in mammals.

Prefabricated vertical drains combined with heating is a new approach to improving the mechanical properties of soft clay foundations. Rising temperatures cause the formation of concentric and radially aligned soil regions with distinct heterogeneous characteristics. This results in incomplete contact between adjacent soil layers, with the water in the interstices impeding heat transfer and manifesting as a thermal resistance effect. Based on the theory of thermo-hydro-mechanical coupling, a two-dimensional dual-zone axisymmetric marine soft soil model improved by a prefabricated vertical thermo-drain has been established. A generalized incomplete thermal contact model has been proposed to describe the thermal resistance effect at the interface of concentric soil regions. The effectiveness of the numerical solution presented in this paper is verified by comparison with semi-analytical solutions and model experiments. The thermal consolidation characteristics of concentric regions of soil at various depths under different thermal contact models were discussed by comprehensively analyzing the effects of different parameters under various thermal contact models. The outcomes indicate that the generalized incomplete thermal contact model provides a more accurate description of the radial thermal consolidation characteristics of concentric regions of soil. The influence of the thermal conductivity coefficient on the consolidation characteristics of the concentric regions soil is related to the thermal resistance effect.

Background: This paper aims to analyse the active components of Semen cuscutae (SC) by network pharmacology and screen the most stable compounds with tumour necrosis factor-alpha (TNF-α) by molecular docking to explore the mechanisms of SC treatment of recurrent spontaneous abortion (RSA) and provide a theoretical basis for drug development.Methods: The active compounds of SC and the potential inflammatory targets of RSA were obtained from the Traditional Chinese Medicine Systems Pharmacology database and GeneCards, respectively. The RSA-SC target gene interaction network was obtained and visualized using the STRING database and Cytoscape software. GO and KEGG pathway enrichment analyses were obtained from DAVID to further explore the RSA mechanism and therapeutic effects of SC. Interactions between TNF-α and drugs were analysed by molecular docking. Treatment of human trophoblast cells with sesamin and TNF-α was carried out to detect their proliferative and apoptotic abilities, and WB assay was carried out to detect EGFR, PTGS2, and CASP3 protein expression.Results: Ten compounds and 128 target genes were screened from SC, of which 79 overlapped with RSA target inflammatory genes, which were considered potential therapeutic targets. Network pharmacological analysis showed that sesamin, matrine, matrol, and other SC compounds had a good correlation with the inflammatory target genes of RSA. Related genes included PGR, PTGS1, PTGS2, TGFB1, and CHRNA7. Several signalling pathways are involved in the pathogenesis of RSA, such as the TNF-α signalling pathway, HIF-1 signalling pathway, oestrogen signalling pathway, proteoglycans in cancer cells, and FoxO signalling pathway. Molecular docking results suggested that sesamin was the most suitable natural tumour necrosis factor inhibitor (TNFi). Sesamin can promote proliferation and inhibit apoptosis in human trophoblasts by downregulating EGFR and CASP3 expression and upregulating PTGS2 expression.Conclusion: Our findings play an important role and basis for further research into the molecular mechanism of SC treatment of RSA and drug development of TNFi.