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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.

To study the quality discrepancy of jujube vinegar brewed from different jujube varieties, six types of jujube vinegar made from different varieties of jujube were evaluated by the analysis of basic physicochemical components (such as pH, total acid, total phenol and total flavone), color, in vitro functional activity (antioxidant capacity and lipid-lowering ability), organic acids, amino acids, and volatile aroma components, combined with electronic nose and sensory evaluation. The results showed that there were significant differences in the quality of jujube vinegar brewed from different jujubes. In terms of physical and chemical analysis, the total acid and total flavonoids of Xinjiang jujube vinegar were the highest, which were 54.87 g/L and 1168.84 mg RE/L, respectively. By contrast, the total phenolic content of Xinjiang Jun-jujube jujube vinegar was the highest, which was 1815.63 mg GAE/L. Henan Lingbao jujube vinegar and Fuping jujube vinegar had better color values. Xinjiang Jujube vinegar showed the best antioxidant and lipid lowering activities. Fuping jujube vinegar had the lowest total organic acid content of 47.07 g/L. Xinjiang gray jujube vinegar and Xinjiang Jun-jujube vinegar had higher essential amino acid and total amino acid content, while Hebei Fuping jujube vinegar had lower amino acid content. A total of 41 volatile aromas were detected in 6 kinds of jujube vinegar, and there were certain differences in the types and contents of volatile aromas contained in different kinds of jujube vinegar. The sensory evaluation showed that all jujubes were suitable for brewing jujube vinegar, among which Xinjiang Hui-jujube vinegar had the best sensory acceptance. In summary, there were certain differences in the quality of 6 kinds of jujube vinegar. The high functional activity of Xinjiang Jun-jujube vinegar made it more suitable as a functional fruit vinegar. Based on the high sensory acceptance of Xinjiang Hui-jujube vinegar, the Xinjiang Hui-jujube would be suitable for the vinegar processing too.

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.

In order to explore the influence of the remaining coal pillar in the upper coal seam on the stress of the floor and the reasonable layout of the mining roadway in the lower coal seam, taking Tangshangou Coal Mine as the research object, the theoretical analysis and numerical simulation methods and a variety of influencing factors were used to construct the collaborative bearing structure model of the remaining coal pillar and the hinged rock block in the upper coal seam and the stress transfer calculation model of the floor, and the stress and influencing factors of the floor under the remaining coal pillar in the upper coal seam are studied. The research shows that the influence of the remaining coal pillars in the upper coal seam on the stress of the floor is mainly vertical stress, and the influence degree decreases with the increase of floor depth. The stress-increasing area of the floor under the remaining coal pillar is ellipsoidal. The influencing factors of the stress-increasing area of the floor are analyzed, and the quantitative relationship between the influence of different factors on the range of the stress-increasing area is obtained. The peak stress of the coal pillar plays a decisive role in the distribution of the stress-increasing area of the floor. According to the stress distribution of the floor and the results of theoretical calculation and numerical simulation, it is determined that the reasonable stagger distance between the 8 coal pillar and the 11−1 coal mining roadway in Tangshangou Coal Mine should be 20—25 m. This study reveals the stress transfer mechanism of the lower floor of the coal pillar left in the upper coal seam, clarifies the distribution and influencing factors of the floor stress increase area, and obtains the determination method of the reasonable stagger value of the roadway-coal pillar, which can provide a theoretical basis for the reasonable layout of the lower coal seam mining roadway.

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.

Background The severe trend of the aging population, the rapid increase in the prevalence of chronic diseases among older adults, and the greater prominence of multimorbidity have posed challenges to the prevention and treatment of chronic diseases in China. Adverse health-related behaviors are modifiable risk factors for chronic diseases. Exploring the latent classes of health-related behaviors in older adults with multimorbidity and their associations with quality of life will help identify the characteristics of their health-related behaviors and uncover risk behaviors affecting the quality of life, providing references for precise health management to improve the quality of life of older adults. Objective To explore the latent classes of health-related behaviors in older adults with multimorbidity and the differences in the quality of life among the different classes. Methods Based on the baseline data from the Community Health and Behavior of the Elderly Panel Study (CHBEPS) conducted by our team in 2021, a total of 1 395 older adults aged 60 years and above with multimorbidity were included as study participants. A self-designed questionnaire was used to collect basic information, including disease status, smoking status, alcohol consumption, and dietary preferences of the participants. The Pittsburgh Sleep Quality Index (PSQI), International Physical Activity Questionnaire-Short-Chinese Version (IPAQ-S-C), and Lubben Social Network Scale-6 (LSNS-6) were used to assess staying up late, physical activity, and social network of the participants, respectively. The EuroQol five-dimensional five-level questionnaire (EQ-5D-5L) was used to measure the quality of life of the participants. Latent class analysis of health-related behaviors among older adults with multimorbidity was conducted using Mplus 8.3 software. Based on the fitted model, the different latent classes of health-related behaviors among older adults with multimorbidity were used as groups, and the Kruskal-Wallis and Wilcoxon rank-sum tests were performed using SPSS 26.0 software to analyze the differences in quality of life among these groups. Results Four latent classes of health-related behaviors were identified among older adults with multimorbidity, which are named the health behavior group (n=280), risk behavior group (n=366), comprehensive behavior group (n=173), and adverse behavior group (n=576). There were statistically significant differences in quality of life among the four latent classes (P

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.