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Abstract Background Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors with high mortality and poor prognosis. Its incidence rate is increasing gradually. Tumor necrosis factor receptor-associated factor interacting protein (TRAIP), as a factor related to several tumors, reveals that its gene expression is different between normal tissue and primary tumor of head and neck squamous cell carcinoma using bioinformatics analysis. Method In our study, TCGA database, immunohistochemistry, proliferation assay, colony formation, wound healing assay, Transwell, cell cycle analysis and tumor xenografts model were used to determine the expression and functions of TRAIP in TSCC. Result We found that TRAIP may promote the proliferation, migration and invasion of TSCC. Furthermore, the results of bioinformatics analysis, mass spectrometry and co-immunoprecipitation suggested that DDX39A may be a TRAIP interacting protein. DDX39A has been proven to be an oncogene in several tumors, which may have an important effect on cell proliferation and metastasis in multiple tumors. In addition, the high expression of DDX39A implies the poor prognosis of patients. Our study demonstrated that TRAIP probably interact with DDX39A to regulate cell progression through epithelial-mesenchymal transition and Wnt/β-catenin pathway. In addition, we show that the necessary domain of DDX39A for the interaction between DDX39A and TRAIP region. Conclusion These results indicate that TRAIP is important in occurrence and development of TSCC and is expected to become the new promising therapeutic target.

Abstract Background In posterior lumbar surgery, overweight patients are more prone to intraoperative acquired pressure injury (IAPI) due to bleeding, longer operative time, and increased pressure. The current prevention strategies have limited effects. Methods This was a single-blind, prospective, randomized controlled trial conducted from April 2023 to September 2024. Eligible participants were overweight patients (BMI ≥ 24 kg/m²) scheduled for lumbar posterior surgery under general anesthesia. Patients were randomly assigned to two groups: the micro-movement group and the silicone foam dressing group. The micro-movement group had regular adjustments to the operating table to change the patient’s position and alleviate pressure. The silicone foam dressing group used standard foam dressings at pressure points. Results A total of 277 patients were included in the analysis (137 in the micromovement group and 140 in the silicone foam dressing group). Compared with the silicone foam dressing group (8.6%), the incidence of IAPI in the micromovement group was significantly reduced (2.9%) (P 0.05). Conclusion The micromovement protocol is a safe and effective method for preventing IAPI in overweight patients undergoing posterior lumbar surgery. This simple intervention could significantly improve patient outcomes and reduce healthcare costs associated with IAPI.

Abstract Purpose This study aims to investigate the effects of combining esketamine with sufentanil for postoperative patient-controlled intravenous analgesia (PCIA) in patients undergoing elective impacted tooth surgery or open reduction and internal fixation. Methods In this single-center, prospective, double-blinded, randomized, parallel-controlled trial, 91 patients were randomly divided into two groups. The experimental group (group ES, n = 46) received a combination of sufentanil 1.5 µg/kg and esketamine 1.0 mg/kg, while the control group (group S, n = 45) received sufentanil 2 µg/kg alone for PCIA after surgery. Primary outcome was assessed using the Visual Analogue Scale (VAS) for patients at rest and during mouth opening at 6 h, 12 h, 24 h, and 48 h post-surgery. Secondary outcomes included the Ramsay Sedation Scale (RSS) scores, the Quality of Recovery-15 (QoR-15) scores, patient satisfaction with analgesia, and the occurrence of adverse events within 48 h post-surgery. The frequency of PCIA button presses and the number of patients requiring rescue analgesia were also recorded. Results The resting VAS scores and the mouth-opening VAS scores at 6 h, 12 h, 24 h, and 48 h post-surgery were significantly lower in Group ES than in Group S (P

Plastic pollution is widely present in terrestrial and aquatic ecosystems, and microplastics (MPs) can be detected in organisms. In situ detection methods for MPs in organisms have attracted widespread attention. Traditional imaging characterization methods of MPs, including stereo microscopes and fluorescence microscopy, are typically used to image artificially added microsphere standards under laboratory conditions. However, they cannot specifically identify MPs in biological samples. Thus, there is a need for a detection technique that can provide spatial distribution information of MPs in biological samples as well as measure their quality and quantity. In this perspective, to obtain high-resolution images with chemical composition analysis, we compared ion sources for ionizing plastic macromolecules and mass analyzers for analyzing macromolecules. Matrix-assisted laser desorption/ionization (MALDI) is suitable for imaging characterization, while time-of-flight (TOF) and Orbitrap mass spectrometry are suitable for polymer mass spectrometry analysis. Furthermore, we propose a technique that combines MALDI with TOF or Orbitrap, which holds promise for the in situ imaging of MPs in biological samples.

Excessive underground train-induced vibration becomes a serious environmental problem in cities. To investigate the vibration transfer from an underground train to a building nearby, an explicit-integration time-domain, three-dimensional finite element model is developed. The underground train, track, tunnel, soil layers and a typical multi-story building nearby are all fully coupled in this model. The complex geometries involving the track components and the building are all modelled in detail, which makes the simulation of vibration transfer more realistic from the underground train to the building. The model is validated with in-situ tests data and good agreements have been achieved between the numerical results and the experimental results both in time domain and frequency domain. The proposed model is applied to investigate the vibration transfer along the floors in the building and the influences of the soil stiffness on the vibration characteristics of the track-tunnel-soil-building system. It is found that the building vibration induced by an underground train is dominant at the frequency determined by the P2 resonance and influenced by the vibration modes of the building. The vertical vibration in the building decreases in a fluctuant pattern from the foundation to the top floor due to loss of high frequency contents and local modes. The vibration levels in different rooms at a same floor can be different due to the different local stiffness. A room with larger space thus smaller local stiffness usually has higher vibration level. Softer soil layers make the tunnel lining and the building have more low frequency vibration. The influence of the soil stiffness on the amplification scale along the floors of the building is found to be nonlinear and frequency-dependent, which needs to be further investigated.

Abstract Pseudomonas aeruginosa is a significant opportunistic pathogen, and its complex mechanisms of antibiotic resistance pose a challenge to modern medicine. This literature review explores the advancements made from 1979 to 2024 in understanding the regulatory networks of antibiotic resistance genes in Pseudomonas aeruginosa, with a particular focus on the molecular underpinnings of these resistance mechanisms. The review highlights four main pathways involved in drug resistance: reducing outer membrane permeability, enhancing active efflux systems, producing antibiotic-inactivating enzymes, and forming biofilms. These pathways are intricately regulated by a combination of genetic regulation, transcriptional regulators, two-component signal transduction, DNA methylation, and small RNA molecules. Through an in-depth analysis and synthesis of existing literature, we identify key regulatory elements mexT, ampR, and argR as potential targets for novel antimicrobial strategies. A profound understanding of the core control nodes of drug resistance offers a new perspective for therapeutic intervention, suggesting that modulating these elements could potentially reverse resistance and restore bacterial susceptibility to antibiotics. The review looks forward to future research directions, proposing the use of gene editing and systems biology to further understand resistance mechanisms and to develop effective antimicrobial strategies against Pseudomonas aeruginosa. This review is expected to provide innovative solutions to the problem of drug resistance in infectious diseases.

Abstract Purpose To highlight the safety and efficacy of tocilizumab (TCZ) in Graves’ ophthalmopathy (GO) combined with ocular myasthenia gravis (OMG) patients refractory to steroids and cholinesterase inhibitor (CEI). Methods This was retrospective case series. We reviewed the health records of patients with GO combined with OMG, ten of whom were refractory to corticosteroids and CEI treatment and received intravenous injection of TCZ. Ten patients were treated with four injections of TCZ (intravenously, 8 mg per kilogram of body weight, once a month). We analyzed the efficacy and safety of TCZ treatment for this subset of patients with GO and OMG. Results The main outcomes including quality of life questionnaire in Graves’ orbitopathy (GO-QoL) score, Clinical Activity Score (CAS), Myasthenia Gravis Activities of Daily Living profile (MG-ADL) score, proptosis, diplopia and ptosis were assessed at 3 time points: “Baseline” (before the TCZ injection), “4th month” (after fourth time TCZ injection), “Follow up” (Last follow-up). Comparing parameters at 4th month vs. at baseline, all indicators improved at 4th month including GO-QoL score of visual functioning subscale (82.29 ± 13.71 vs. 35.98 ± 20.66, P

Abstract The purpose of this study is to investigate the improvement in visual acuity when applying Rigid Gas Permeable Contact Lenses (RGPCL) compared to spectacles in patients after surgical treatment for infantile nystagmus syndrome (INS). A total of 33 patients with nystagmus who had nystagmus surgery from October 2020 to July 2021 were enrolled and all were fitted RGPCL. SPSS statistical software was used to analyze the difference between best-corrected visual acuity with spectacle(BCSVA) and best-corrected visual acuity with RGPCL (BCRVA) in these patients. According to the refractive status of each eye, it was grouped into 2 groups. We study the difference between its BCSVA and BCRVA in different groups. In our study, BCRVA was significantly better than BCSVA in all participants (P

Abstract Nonlinear optical responses in two-dimensional (2D) materials can build free-space optical neuromorphic computing systems. Ensuring the high performance and the tunability of the system is essential to encode diverse functions. However, common strategies, including the integration of external electrode arrays or photonic structures with 2D materials, and barely patterned 2D materials, exhibit a contradiction between performance and tunability. Because the unique band dispersions of 2D materials can provide hidden paths to boost nonlinear responses independently, here we introduced a new free-space optical computing concept within a bare molybdenum disulfide array. This system can preserve high modulation performance with fast speed, low energy consumption, and high signal-to-noise ratio. Due to the freedom from the restrictions of fixed photonic structures, the tunability is also enhanced through the synergistic encodings of the 2D cells and the excitation pulses. The computing mechanism of transition from two-photon absorption to synergistic excited states absorption intrinsically improved the modulation capability of nonlinear optical responses, revealed from the relative transmittance modulated by a pump-probe-control strategy. Optical artificial neural network (ANN) and digital processing were demonstrated, revealing the feasibility of the free-space optical computing based on bare 2D materials toward neuromorphic applications.

Abstract Group-III nitride semiconductors such as GaN have various important applications based on their three-dimensional form. Previous work has demonstrated the realization of buckled two-dimensional GaN, which can be used in GaN-based nanodevices. However, the understanding of buckled two-dimensional GaN remains limited due to the difficulties in experimental characterization. Here, for the first time, we have experimentally determined the phonon dispersion of buckled two-dimensional GaN by using monochromatic electron energy loss spectroscopy in conjunction with scanning transmission electron microscopy. A phonon band gap of ~40 meV between the acoustic and optical phonon branches is identified for buckled two-dimensional GaN. This phonon band gap is significantly larger than that of ~20 meV for the tetrahedral-coordinated three-dimensional GaN. Our theoretical calculations confirm this larger phonon band gap. Our findings provide critical insights into the phonon behavior of buckled two-dimensional GaN, which can be used to guide high-performance thermal management in GaN-based high-power devices.

Abstract Background Gastrointestinal (GI) cancers have heavily burdened public health. Few studies reported GI cancer burden among adolescents and young adults (AYA). To address this gap, we explored the burden of GI cancer among people aged 15–39. Methods We retrieved data from the Global Burden of Disease Study 2019 Data Resources. The average annual percent change (AAPC) of rates was calculated by linear regression analysis of the natural logarithm. Bayesian age-period-cohort model was applied to predict the future burden. Results In 2019, there were 171,857 (95% uncertain interval [95% UI]: 157,092–187,974) new GI cancer cases with a rate of 5.79/100,000 (95% UI: 5.29–6.33) and 91,033 (95% UI: 83,156–99,399) deaths at a rate of 3.07/100,000 (95% UI: 2.80–3.35) among AYA. The number of prevalent cases and disability-adjusted life years (DALYs) were 722,573 (95% UI: 660,806–789,476) and 5,151,294 (95% UI: 4,706,065–56,188,77), with rates of 24.35/100,000 (95% UI: 22.27–26.60) and 173.57/100,000 (95% UI: 158.57–189.32) respectively. The overall rates of mortality (AAPC = -1.281, p

Background There remains controversy over the relationship between serum magnesium levels and obesity in type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to assess whether there is any association of serum magnesium levels with obesity and abdominal obesity in T2DM. Methods This cross-sectional, real-world study was conducted in 8,010 patients with T2DM, which were stratified into quintiles according to serum magnesium levels. The clinical characteristics and the prevalence of obesity and abdominal obesity were compared across serum magnesium quintiles in T2DM. Regression analyses were used to evaluate the relationship of serum magnesium with obesity and abdominal obesity in T2DM (clinical trial registration number: ChiCTR1800015893). Results After adjustment for age, sex, and duration of diabetes, the prevalence of obesity and abdominal obesity was significantly declined across magnesium quintiles (obesity: 51.3%, 50.8%, 48.9%, 45.3%, and 43.8%, respectively, P

Abstract Deep close distance coal seam mining is affected by the goaf of upper coal and remaining coal pillar, and the roadway of lower coal is difficult to maintain stability. By means of theoretical analysis, physical simulation test and numerical simulation, this paper analyzes the failure characteristics of roadway in deep close distance coal seam and the evolution law of stress field, and optimizes the reasonable layout of lower coal roadway. The results show that: (1) The analytical formula of the evolution of the floor principal stress difference with depth is derived theoretically, and the distribution law of the shear stress of the rock mass in the floor of the coal seam is obtained. (2) The airway below the goaf can maintain good stability. High stress accumulation phenomenon occurs in the transport roadway below the coal pillar, which can not keep stable. (3) Due to the stress difference under the goaf and the coal pillar, the shear stress increases and the rock mass is damaged, and the left gang of the transport roadway is prone to instability destruction. (4) By comparing the distribution characteristics of plastic zones of transport roadway at different locations, it is determined that the transport roadway is more appropriate to be arranged 45 m below the coal pillar from the goaf.

Abstract Background Anaplastic thyroid carcinoma (ATC) is a rare but the most aggressive type of thyroid carcinoma. Nevertheless, limited advances were made to reduce mortality and improve survival over the last decades. Therefore, identifying novel diagnostic biomarkers and therapeutic targets for ATC patients is still needed. Materials and methods RNA sequencing data and corresponding clinical features were available from GEO and TCGA databases. We integrated WGCNA and PPI network analysis to identify hub genes associated with ATC development, and RT-qPCR was employed for data verification. Univariate and LASSO Cox regression analyses were used to generate prognostic signatures. Results Based on PPI and WGCNA, 6 hub genes were identified, namely KIF2C, PBK, TOP2A, CDK1, KIF20A, and ASPM, which play vital roles in ATC development. Subsequently, RT-qPCR experiments showed that most of these genes were significantly upregulated in CAL-62 cells compared to Nthy-ori 3–1 cells. Moreover, a prognostic signature featuring GPSM2, FGF5, ASXL3, CYP4B1, CLMP, and DUXAP9 was generated, which was also verified by RT-qPCR results and proved as an independent predictor of poorer prognosis of ATC. Additionally, a nomogram incorporating the risk score and clinicopathological parameters was further constructed for accurate prediction of 1-, 3- and 5-year survival probabilities of ATC. Conclusions Our study identified 6 key genes critical to ATC development and constructed a prognostic signature. These findings provide reliable biomarkers and a relatively comprehensive tumorigenesis profile of ATC, which may inform future strategies for clinical diagnosis and pharmaceutical design.

Abstract Background Alzheimer's disease (AD) is a prevalent irreversible neurodegenerative condition marked by gradual cognitive deterioration and neuronal loss. The mammalian Ste20-like kinase (MST1)–Hippo pathway is pivotal in regulating cell apoptosis, immune response, mitochondrial function, and oxidative stress. However, the association between MST1 and mitochondrial function in AD remains unknown. Therefore, this study investigates the effect of MST1 on neuronal damage and cognitive impairment by regulating mitochondrial homeostasis in AD. Methods In this study, 4- and 7-month-old 5xFAD mice were selected to simulate the early and middle stages of AD, respectively; age-matched wild-type mice served as controls for comparative analysis. Adeno-associated virus (AAV) was injected into the hippocampus of mice. Four weeks post-injection, cognitive function, neuronal damage indicators, and mitochondrial morphology, dynamics, oxidative stress, ATP, and apoptosis-related indicators were evaluated. Additionally, RNA-sequencing was performed on the hippocampal tissue of 5xFAD mice and MST1-knockdown 5xFAD mice. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on differentially expressed genes to elucidate the potential mechanism of MST1. In vitro studies were performed to investigate the effects of MST1 on SH-SY5Y model cell viability and mitochondrial function and validate the potential underlying molecular mechanisms. Results MST1 overexpression accelerated neuronal degeneration and cognitive deficits in vivo while promoting oxidative stress and mitochondrial damage. Similarly, in vitro, MST1 overexpression facilitated apoptosis and mitochondrial dysfunction. MST1 knockdown and chemical inactivation reduced cognitive decline, mitochondrial dysfunction, and neuronal degeneration. Mechanistically, MST1 regulated the transcription of mitochondrial genes, including MT-ND4L, MT-ATP6, and MT-CO2, by binding to PGC1α. Moreover, MST1 influenced cellular oxidative stress through the PI3K-Akt-ROS pathway, ultimately disrupting mitochondrial homeostasis and mediating cell damage. Conclusions Cumulatively, these results suggest that MST1 primarily regulates mitochondrial DNA transcription levels by interacting with PGC1α and modulates cellular oxidative stress through the PI3K-Akt-ROS pathway, disrupting mitochondrial homeostasis. This discovery can be exploited to potentially enhance mitochondrial energy metabolism pathways by targeting MST1, offering novel potential therapeutic targets for treating AD. Graphical Abstract

Abstract Natural products-coordinated metal ions to form the nanomedicines are in the spotlight for cancer therapy. Some natural products could be coordinated with metal ions forming nanomedicines via simple and green environmental self-assembly, which not only improved the bioavailability of natural products, but also conferred multiple therapeutic modalities and multimodal imaging. On the one hand, in the weak acidity, glutathione (GSH) and hydrogen peroxide (H2O2) overexpression of tumor microenvironment (TME), such carrier-free nanomedicines could be further enhanced the therapeutic effect via optimizing the species of metal ions. On the other hand, nanomedicines could exert the precise treatment of tumor under the guidance of multiple imaging. Hence, this review summarized the research progress in recent years on the application of natural product-coordinated metal ions in cancer therapy. In addition, the prospects and challenges for the application of natural product-coordinated metal ions were discussed, especially how to improve targeting ability and stability and assess the safety of metal ions, so as to facilitate the clinical translation and application of natural product-coordinated metal ions nanomedicines. Graphical Abstract

Abstract Protein-bound uremic toxins (PBUTs) are the main cause of uremia, but traditional hemodialysis is ineffective in removing them because of their strong ability to bind to human serum albumin (HSA), highlighting the need for new treatments. In this study, first, structure-based docking was used to screen a diverse library of 200,376 virtual compounds against the active sites I and II. After two rounds of docking screening, 3944 candidate molecules were obtained. Second, 23 candidate molecules were obtained after ADMET prediction and toxicity analysis. Five candidate molecules were finally obtained after visual analysis and MM-PBSA calculations. We subsequently assessed their competitive displacement efficiency through a microdialysis experiment, and the results revealed that ZINC000008791789, ZINC000012297018, and ZINC000012296493 are promising binding competitors for PBUTs, as they have higher dialysis efficiency than the optimal displacer LA, approximately double the dialysis efficiency. The other two molecules, ZINC000031161007 and ZINC000004090361, although less efficient than LA, still outperformed the control group. Notably, four of them shared the same molecular scaffold, and three of them contained a flavonoid group. These findings provide a foundation for the development of more effective PBUT binding competitors, potentially benefiting uremia patients in the future.

Abstract Background Standardized training for resident physicians (STRP) is essential for improving their clinical skills. The standardized training for resident physicians in emergency medicine differs from other disciplines, focusing more on knowledge related to medical emergencies and emergency care skills requiring urgency and real-time response. There are specific differences in knowledge content, teaching methods, curriculum design, and career development compared to other specialties. As a national-level teaching base for emergency medicine, our hospital continuously explores and innovates in teaching models, discovering a model more suitable for emergency medicine. Objective This study summarizes practical experience in teaching and assessment integration (TAA), evaluates teaching training effectiveness with the Clinical Thinking Training System (CTTS), and examines integrating this system with innovative teaching and assessment models' impact on resident physicians' clinical abilities. Methods In our study, we selected residents who rotated in our department from July-December 2023 and randomly divided them into a reform group (n = 106) and a control group (n = 104). The reform group received training using the Clinical Thinking Training System (CTTS) while the control group received standard training consistent with the existing STRP framework. We integrate innovative teaching and assessment (TAA) models and the Entrustable Professional Activities (EPAs) scale to assess students' abilities, stratifying by grade level, background, and major to evaluate students' departmental rotation examination (DRE) and EPAs scores. Result The DRE scores and Mini-CEX scores were significantly higher in the reformed group compared to the control group. The final assessments showed the reform group scored significantly higher in first-case documentation and overall clinical thinking decision-making. Specifically, the reform group had significantly higher scores in first-case documentation for second-year, third-year, undergraduate, and graduate students, and non-emergency specialty students. The clinical thinking decision-making scores of the reform group were significantly higher across different years, specialties, and educational backgrounds. All the EPAs results indicated the CTTS improved treatment decision-making abilities among students with different years of training, educational backgrounds, and specialties. Moreover, the ability for continuous patient management improved to some extent among students in different years and with different educational backgrounds. Conclusion The integration of innovative teaching and assessment models with the CTTS is more conducive to improving the examination performance and confidence in professional behavior of resident physicians.

Abstract Objective The incidence of invasive pulmonary aspergillosis (IPA) is increasing gradually. This study analysed the epidemiological characteristics and prognostic factors of patients with IPA and explored the risk factors affecting prognosis. Materials and methods The clinical data and treatment of 92 patients with IPA were retrospectively analysed, and the patients were followed for 12 weeks. Patients were divided into an effective treatment group and an ineffective treatment group, and the risk factors affecting prognosis were discussed. Results A total of 92 patients met the IPA inclusion criteria, and the most common genus of Aspergillus was Aspergillus fumigatus. The incidence of IPA was highest in patients with malignant tumours. IPA often coexisted with infections caused by other pathogens. We divided the patients into an effective treatment group and an ineffective treatment group according to prognosis. Compared with those in the effective treatment group, the procalcitonin (PCT) level, lactate dehydrogenase-to-albumin ratio (LDH/ALB) and neutrophil-to-lymphocyte ratio (NLR) in the ineffective treatment group were greater, the serum albumin level was lower, and the imaging findings revealed less nodules and bronchial wall thickening (P

Abstract Osteonecrosis of the femoral head (ONFH) is a common complication of glucocorticoid (GC) therapy. Recent advances demonstrate that sympathetic nerves regulate bone homeostasis, and GCs lower the sympathetic tone. Here, we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH. GCs activate the glucocorticoid receptor (GR) but hinder the activation of the mineralocorticoid receptor (MR) on neurons in the hypothalamic paraventricular nucleus (PVN). This disrupts the balance of corticosteroid receptors (GR/MR) and subsequently reduces the sympathetic outflow in the PVN. Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone (MPS) daily for 3 days, and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice. Importantly, treatment with a GR inhibitor (RU486) in the PVN promotes the activation of MR and rebalances the ratio of GR and MR, thus effectively boosting sympathetic outflow, as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice. Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head, while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2 (Adrb2) knockout. Furthermore, activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype. Mechanistically, norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) via Adrb2-cyclic AMP response element-binding protein (CREB) signaling. Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice. Thus, GC inhibits sympathetic tone via the hypothalamic descending pathway, which, in turn, acts as a mediator of GC-induced ONFH.

Abstract Prenatal stress exerts long-term impact on neurodevelopment in the offspring, with consequences such as increasing the offspring’s risk of depression in adolescence and early adulthood. S-ketamine can produce rapid and robust antidepressant effects, but it is not clear yet whether and how S-ketamine alleviates depression in prenatally stressed offspring. The current study incestigated the preliminary anti-depression mechanism of S-ketamine in prenatally stressed offspring, particularly with regard to neuroplasticity. The pregnant females were given chronic unpredictable mild stress on the 7th-20th day of pregnancy and their male offspring were intraperitoneally injected with a single dose of S-ketamine (10 mg/kg) on postnatal day 42. Our findings showed that S-ketamine treatment counteracted the development of depression-like behaviors in prenatally stressed offspring. At the cellular level, S-ketamine markedly enhanced neuroplasticity in the CA1 hippocampus: Golgi-Cox staining showed that S-ketamine alleviated the reduction of neuronal complexity and dendritic spine density; Transmission electron microscopy indicated that S-ketamine reversed synaptic morphology alterations. At the molecular level, by western blot and RT-PCR we detected that S-ketamine significantly upregulated the expression of BDNF and PSD95 and activated AKT and mTOR in the hippocampus. In conclusion, prenatal stress induced by chronic unpredictable mild stress leads to depressive-like behaviors and hippocampal neuroplasticity impairments in male offspring. S-ketamine can produce antidepressant effects by enhancing hippocampal neuroplasticity via the BDNF/AKT/mTOR signaling pathway.

Abstract High altitude is characterized by low oxygen, low pressure, and high radiation. When migrates from low to high altitudes, the body’s tissues and organs experience hypoxic stress and will present acoustic adaptation as the protective response. However, the mechanisms of acoustic adaptation at high altitudes remain unclear. In this study, cochlear tissues from Wistar rats were collected at 15, 30, 60, 120, and 180 days after high-altitude migration. Transcriptome sequencing was conducted and DESeq algorithm revealed expression patterns of Differentially Expressed Genes(DEGs) after high altitude migration. Day 60 is a critical stage for cochlear tissue “damage” and “repair” in high-altitude conditions. Transmission Electron Microscopy (TEM) observations of structures also support the findings. A time-series gene co-expression network algorithm was used to investigate gene regulatory patterns and key genes after migration. Immunofluorescence, immunohistochemistry, and qPCR were per-formed for key gene validation and localization. At Day 60, the peak DEG count occurs in rats migrating to high altitude, aligning with the critical phase for cochlear tissue damage and repair at high altitudes. Repair hinges on synaptic plasticity and myelination-linked processes, influencing modules M4 to M6. Module M4’s activation gradually diminishes from its peak. However, the ‘damage’ effect is orchestrated by inflammation-related processes in modules M3 to M5, with module M3’s activation also waning. Key gene module M4, pivotal for repair during this pivotal phase, encompasses Sptbn5, Cldn1, Gfra2, and Lims2 as its core genes. Immunohistochemistry reveals Sptbn5’s presence in cochlear neurons, hair cells, Schwann cells and stria vascularis tissue. Cldn1 and Gfra2 predominantly localize within the cochlear neuron region. These results may suggest new directions for future research on acoustic acclimatization to high altitude.

Abstract Most current studies use body mass index (BMI) or waist circumference (WC) to define obesity, and BMI, which reflects subcutaneous fat independent of visceral fat, is the most commonly used indicator of obesity. WC reflects subcutaneous and visceral fat. This research aims to investigate the effect of obesity on mortality in people with digestive diseases. According to BMI and WC, we divided patients with obesity into the following four groups: general obesity, abdominal obesity, combined obesity, and non-obese. The effects of different obesity types on mortality in a population with digestive diseases were analysed via Cox regression and inverse probability-weighted Cox regression. Our research employed multivariate imputation via the chained equations method to interpolate missing values. A total of 254,445 participants, with a mean age of 57.8 ± 7.8 years, were included in the analysis. Of these participants, 227,111 (89.3%) participants were censored, and 27,334 (10.7%) participants died. Abdominal obesity and combined obesity were independent predictors of mortality in patients with digestive diseases. The combination of BMI and WC was valuable and significant for considering the type of obesity. In addition, our study revealed that sex, socioeconomic status, lifestyle habits, and physical activity were also associated with death in people with digestive disorders. Combined obesity, which is determined by both BMI and WC, is an important factor that influences mortality in a population with digestive diseases, and it plays a stronger role than abdominal obesity alone. These modifiable risk factors for mortality can provide guidance to populations with digestive diseases to avoid poor lifestyles and prolong survival time.

Abstract The dynamic crack propagation trajectories play a crucial role in enhancing our understanding of spatial mechanisms involved in crack expansion. However, visualization of internal cracks under complex crack conditions has always been a challenge. Biological networks have been honed by many cycles of evolutionary selection pressure and are likely to yield reasonable solutions to such combinatorial optimization problems. This study applied the slime mould algorithm to improve the accuracy of internal crack localization in rocks and employed Minimum spanning tree and Gaussian mixture model to construct the crack propagation trajectories. By introducing the concept of bond length, the evolution characteristics of crack levels were effectively characterized. Research results showed that this approach effectively preserves essential crack localization information while mitigating the influence of interfering parameters, providing crack characterization results that exhibit high consistency with actual fracture patterns. The curves of cumulative bond length and relative bond length over time conform to the trend of a Growth/Sigmoidal curve. The strength of the bond was correlated with the temporal process of crack propagation. This result could be helpful for analyzing crack trajectories and predicting rock stability.

Abstract Glioblastoma is one of the most common and aggressive primary brain tumors. The aberration of metabolism is the important character of GBM cells and is tightly related to the malignancy of GBM. We mainly verified the regulatory effects of KHDRBS1, SNORD51 and ZBED6 on pentose phosphate pathway and malignant biological behavior in glioblastoma cells, such as proliferation, migration and invasion. KHDRBS1 and SNORD51 were upregulated in GBM tissues and cells. But ZBED6 had opposite tendency in GBM tissues and cells. KHDRBS1 may improve the stability of SNORD51 by binding to SNORD51, thus elevating the expression of SNORD51. More importantly, SNORD51 can competitively bind to WDR33 with 3’UTR of ZBED6 pre-mRNA which can inhibit the 3’ end processing of ZBED6 pre-mRNA, thereby inhibiting the expression of ZBED6 mRNA. ZBED6 inhibited the transcription of G6PD by binding to the promoter region of G6PD. Therefore, the KHDRBS1/SNORD51/ZBED6 pathway performs an important part in regulating the pentose phosphate pathway to influence malignant biological behavior of GBM cells, providing new insights and potential targets for the treatment of GBM.

Abstract As the COVID-19 epidemic ends in China, it is worth exploring the growth after experiencing the trauma of the epidemic. China has been managing the epidemic for a relatively long time compared to other countries. Many scholars have researched trauma and post-traumatic growth in groups such as doctors and patients. However, little attention has been paid to the post-traumatic growth of ordinary people who experienced the epidemic in the Chinese context and the related influencing factors. Based on the educational system as the research context, this study proposes the effects of proactive personality and social support on PTG in the post-epidemic era through the mediation of meaningfulness of life. To empirically examine the influences of PTG in the post-epidemic era, an online survey of 1210 university students was conducted for data analysis. The analysis results suggest that proactive personality and social support positively influence meaning in life. Proactive personality, social support and meaning in life positively influence post-traumatic growth. Proactive personality and social support social support and proactive personality indirectly influence post-traumatic growth through the mediation of the meaning in life. This research empirically investigated the role of personality, social support, meaning in life, and post-traumatic growth among university students.

Abstract Background Huashi Baidu Formula (HBF) is a clinical formula known for its efficacy against coronavirus disease 2019 (COVID-19). HBF may reduce the number of patients with abnormal serum creatinine while improving respiratory symptoms, suggesting that this formula may have potential for treating acute kidney injury (AKI). However, the protective effect of HBF on AKI has not been definitively confirmed, and the mechanism remains unclear. Therefore, the present study explored the renoprotective effects and molecular mechanisms of HBF and screened for its active ingredients to identify new potential applications of renoprotection by HBF. Methods The present study first assessed the protective effects of HBF on AKI in a DOX-induced mouse model. Then, RNA-seq and bioinformatics analyses were used to explore the related pathological processes and potential molecular mechanisms, which were subsequently validated using qRT-PCR and Western blotting. Furthermore, candidate compounds with potential binding affinity to two pivotal targets, sphingosine kinase 1 (SphK1) and plasminogen activator inhibitor-1 (PAI-1), were screened from the 29 constituents present in the blood using Microscale Thermophoresis (MST). Finally, to identify the active ingredients, the candidate components were re-screened using the SphK1 kinase activity detection system or the uPA/PAI-1 substrate colorimetric assay system. Results In the DOX-induced AKI mouse model, therapeutic administration of HBF significantly reduced the levels of CRE, BUN, TNF-α, IL-1β, IL-6, and UA in plasma and the levels of MDA, T-CHO, and TG in kidney tissue. Additionally, the levels of TP and Alb in plasma and SOD and CAT in the kidney tissue were significantly increased. Histopathological assessment revealed that HBF reduced tubular vacuolation, renal interstitial inflammatory cell infiltration, tubular atrophy, and positive staining of renal interstitial collagen. RNA-seq and bioinformatics analyses showed that oxidative stress, the immune-inflammatory response, and extracellular matrix (ECM) formation could be the pathological processes that HBF targets to exerts its renoprotective effects. Furthermore, HBF regulated the APJ/SPHK1/NF-κB and APJ/PAI-1/TGFβ signaling axes and reduced the phosphorylation levels of NF-κB p65 and SMAD2 and the expression of cytokines and the ECM downstream of the axis. Finally, six SphK1 inhibitors (paeoniflorin, astragalin, emodin, glycyrrhisoflavone, quercetin, and liquiritigenin) and three PAI-1 inhibitors (glycyrrhisoflavone, licochalcone B, and isoliquiritigenin) were identified as potentially active ingredients in HBF. Conclusion In brief, our investigation underscores the renoprotective effect of HBF in a DOX-induced AKI model mice, elucidating its mechanisms through distinct pathological processes and identifying key bioactive compounds. These findings offer new insights for broadening the clinical applications of HBF and unravelling its molecular mode of action.

This study investigates the biomass and carbon fixation rate of Chlorella sp. by the main valuable elements in converter steel slag in F/2 seawater medium. The results indicate that Ca, Mg, P, Si, Fe, and Mn can increase the biomass and carbon fixation rate of Chlorella sp., while Cu, Zn, Cr, and Al can decrease the biomass and carbon fixation rate of Chlorella sp.. Three machine learning methods known as Back Propagation neural network (BPNN), decision tree (DT), and random forest (RF) were applied to construct the prediction model for the carbon fixation rate of Chlorella sp. based on real-life experimental data obtained from single factor experiments. The overall results exhibited that the BPNN model is better than the DT model and RF model to predict the carbon fixation rate of Chlorella sp.. Finally, the maximum carbon fixation rate for Chlorella sp. predicted by BPNN model is 50.86 mg/(L·d), which was 2.46 times that of the control group, under the optimum conditions of Ca 5.77 g/L, Mg 4.74 g/L, P 1.27 g/L, Si 6.31×10−1 g/L, Fe 6.50×10−4 g/L, Mn 5.00×10−5 g/L, Cu 2.51×10−6 g/L, Zn 4.98×10−6 g/L, Cr 0 g/L, and Al 0 g/L in F/2 seawater medium.

Abstract Due to the strong coupling effect between the internal magnetic field and the structural field of the transformer, the magnetic‐structural coupling should be considered in axial vibration process of the winding short‐circuit impact. A 110 kV transformer is taken as the research object. Firstly, the vibration modal characteristics of the transformer are calculated using the classical axial vibration model, and the spatial distribution of the leakage magnetic flux density of the iron core window is obtained based on the image method, which is used as the basis for calculating the excitation electromagnetic force. With the consideration of the non‐linear mechanical characteristic of the pad, the dynamic stiffness equation is analysed and established and the magnetic‐structural coupling correction model is constructed. Finally, the winding vibration amplitudes obtained respectively by the classical model, the magnetic‐structural coupling model, and the magnetic‐structural coupling correction model considering the dynamic stiffness are compared. The results show that, compared with the classical model, the vibration amplitude increment with the magnetic‐structural coupling correction model is less. The dynamic stiffness will hinder the vibration intensification. The magnetic‐structural coupling correction model can provide a more accurate calculation scheme for the winding vibration characteristic analysis.

Abstract Alzheimer’s disease (AD) is a metabolic disorder. Discovering the metabolic products involved in the development of AD may help not only in the early detection and prevention of AD but also in understanding its pathogenesis and treatment. This study investigated the causal association between the latest large-scale plasma metabolites (1091 metabolites and 309 metabolite ratios) and AD. Through the application of Mendelian randomization analysis methods such as inverse-variance weighted (IVW), MR-Egger, and weighted median models, 66 metabolites and metabolite ratios were identified as potentially having a causal association with AD, with 13 showing significant causal associations. During the replication validation phase, six metabolites and metabolite ratios were confirmed for their roles in AD: N-lactoyl tyrosine, argininate, and the adenosine 5’-monophosphate to flavin adenine dinucleotide ratio were found to exhibit protective effects against AD. In contrast, ergothioneine, piperine, and 1,7-dimethyluric acid were identified as contributing to an increased risk of AD. Among them, argininate showed a significant effect against AD. Replication and sensitivity analyses confirmed the robustness of these findings. Metabolic pathway analysis linked “Vitamin B6 metabolism” to AD risk. No genetic correlations were found, but colocalization analysis indicated potential AD risk elevation through top SNPs in APOE and PSEN2 genes. This provides novel insights into AD’s etiology from a metabolomic viewpoint, suggesting both protective and risk metabolites.

Abstract Background Episodic memory naturally deteriorates with age, and its deficits are widely recognized as the most significant feature and the most sensitive indicator of cognitive decline. It has been suggested that adopting a healthy lifestyle can play a protective role in preserving episodic memory. This study aimed to systematically examine the relationship between lifestyle factors (social activities, leisure activities, physical activities, internet use, smoking, alcohol drinking, and sleep quality) and episodic memory in middle-aged and older adults. Methods The current study included 10,392 participants from the Chinese Health and Retirement Longitudinal Survey. A linear mixed model was used to explore the associations between lifestyle factors and episodic memory performance and the age- and sex-specific effects of the association. Results Low-frequency alcohol drinking, higher engagement in social, leisure, and physical activities, increased internet use, and improved sleep quality were associated with better episodic memory performance in middle-aged and older adults. Stratified analyses demonstrated that internet use significantly correlated with episodic memory performance in middle-aged adults but not in older adults. On the other hand, sleep quality showed a significant association with episodic memory performance in women but not in men. Conclusions This study highlights the association between various lifestyle factors and episodic memory performance, with variations observed based on age and sex. Adopting healthy lifestyle factors can have positive effects on episodic memory in middle-aged adults, emphasizing the importance of adhering to healthy lifestyles from middle age onwards to counteract episodic memory decline.

Abstract Defective renal excretion and increased production of uric acid engender hyperuricemia that predisposes to gout. However, molecular mechanisms underlying defective uric acid excretion remain largely unknown. Here, we report a rare genetic variant of gout-unprecedented NUMB gene within a hereditary human gout family, which was identified by an unbiased genome-wide sequencing approach. This dysfunctional missense variant within the conserved region of the NUMB gene (NUMBR630H) underwent intracellular redistribution and degradation through an autophagy-dependent mechanism. Mechanistically, we identified the uric acid transporter, ATP Binding Cassette Subfamily G Member 2 (ABCG2), as a novel NUMB-binding protein through its intracellular YxNxxF motif. In polarized renal tubular epithelial cells (RTECs), NUMB promoted ABCG2 trafficking towards the apical plasma membrane. Genetic loss-of-function of NUMB resulted in redistribution of ABCG2 in the basolateral domain and ultimately defective excretion of uric acid. To recapitulate the clinical situation in human gout patients, we generated a NUMBR630H knock-in mouse strain, which showed marked increases of serum urate and decreased uric acid excretion. The NUMBR630H knock-in mice exhibited clinically relevant hyperuricemia. In summary, we have uncovered a novel NUMB-mediated mechanism of uric acid excretion and a functional missense variant of NUMB in humans, which causes hyperuricemia and gout.

Abstract Background The Mediterranean diet (MD) has shown promising results in preventing type 2 diabetes, particularly in Mediterranean and European populations. However, the applicability of these benefits to non-Mediterranean populations is unclear, with contradictory findings in the literature. Methods In this study, we included 12,575 participants without diabetes at baseline from the China Health and Nutrition Survey (CHNS). Dietary intake was measured by three consecutive 24-h dietary recalls. The Mediterranean diet adherence (MDA) was measured by a score scale that included nine components of vegetables, legumes, fruits, nuts, cereals, fish, red meat, dairy products, and alcohol. New-onset diabetes was defined as self-reported physician-diagnosed diabetes during the follow-up. Results During a median follow-up of 9.0 years, 445 (3.5%) subjects developed diabetes. Overall, there was an inverse association between the MDA score and new-onset diabetes (per score increment, HR 0.83, 95% CI 0.76–0.90). Moreover, age, sex, BMI, and energy intake significantly modified the association between the MDA score and the risk of new-onset diabetes (all P interactions

Abstract Presenilin-associated protein (PSAP) is a mitochondrial proapoptotic protein as established in cell biology studies. It remains unknown whether it involves in neurodegenerative diseases. Here, we explored PASP expression in adult and aged human brains and its alteration relative to Alzheimer-disease (AD)-type neuropathology. In pathology-free brains, light PASP immunoreactivity (IR) occurred among largely principal neurons in the cerebrum and subcortical structures. In the brains with AD pathology, enhanced PSAP IR occurred in neuronal and neuritic profiles with a tangle-like appearance, with PSAP and pTau protein levels elevated in neocortical lysates relative to control. Neuronal/neuritic profiles with enhanced PSAP IR partially colocalized with pTau, but invariably with Amylo-Glo labelled tangles. The neuronal somata with enhanced PASP IR also showed diminished IR for casein kinase 1 delta (Ck1δ), a marker of granulovacuolar degeneration; and diminished IR for sortilin, which is normally expressed in membrane and intracellular protein sorting/trafficking organelles. In old 3xTg-AD mice with β-amyloid and pTau pathologies developed in the brain, PSAP IR in the cerebral sections exhibited no difference relative to wildtype mice. These findings indicate that PSAP upregulation is involved in the course of tangle formation especially in the human brain during aging and in AD pathogenesis.

Abstract Background The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. Methods A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. Results Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p

Abstract Clade A type 2C protein phosphatases (PP2Cs) are crucial components of the abscisic acid (ABA) signaling pathway. Research on clade A PP2Cs has focused more on their roles related to ABA signaling and stress responses than on the molecular mechanisms mediating their effects on plant growth and grain yield. Rice (Oryza sativa L.) is an important food crop worldwide. We previously determined that OsPP2C49, which encodes a rice clade A PP2C family member, negatively controls rice responses to drought, salt, and high-temperature stresses. In this study, we investigated the regulatory effects of OsPP2C49 on ABA responses and rice grain yield. By analyzing potential interactions with core ABA components, including pyrabactin resistance 1 (PYR1)/PYR1-like (PYL)/regulatory component of the ABA receptor (RCAR) and stress-activated protein kinases (SAPKs), we confirmed that OsPP2C49 is involved in the ABA signaling pathway. OsPP2C49 overexpression led to decreased ABA sensitivity and increased rice grain yield; the opposite phenotypes were observed in the ospp2c49 knockout mutants. Therefore, OsPP2C49 negatively regulates ABA responses, but positively modulates rice grain yield. Furthermore, we found that OsPP2C49 can interact with and dephosphorylate five OsSAPKs in vitro. Unlike OsPP2C49, these OsSAPKs positively modulate ABA responsiveness, but negatively affect rice yield. These findings indicate that OsPP2C49 may partially regulate ABA responses and rice grain production by dephosphorylating OsSAPKs. This study preliminarily explored the molecular basis of the regulatory effects of OsPP2C49 on rice plant growth and grain yield.

Abstract Background The incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children is increasing, posing a serious threat to life safety. Intravenous immunoglobulin (IVIG) has demonstrated the ability to modulate the immune system and has shown the potential to treat RMPP. This study evaluated the clinical efficacy and safety of azithromycin combined with IVIG in the treatment of RMPP in children through a meta-analysis. Methods A comprehensive search was conducted in seven databases including PubMed and Cochrane Library, and the studies on the treatment of RMPP in children with azithromycin combined with IVIG were screened. After data extraction, meta-analysis and sensitivity analysis were performed to assess heterogeneity and stability. Results Thirteen randomized controlled trials and two cohort studies were included, totaling 1,142 children. The results of meta-analysis showed a higher clinical efficacy rate (RR = 1.18, 95% CI: 1.11–1.25, P

Abstract Following the 2014 South Napa earthquake near the end of a long drought in Central California, streamflow in Sonoma Creek increased and showed amplified daily fluctuation. However, no such changes occurred in the shallow groundwater. Here we show that the amplified fluctuation reflected increased interaction between the post-seismic rising water table and plant roots in the riparian zone, according to results from numerical simulation constrained by streamflow data and hydraulic properties of riparian sediments. Evapotranspiration during the day kept the water table low beneath the riparian zone, lowering the discharge to the stream. At night, the water table rose and increased discharge to the stream. The study also show substantial spatial difference in earthquake-induced interactions between groundwater and the surface, which may influence our understanding of the spatial scale of earthquake impacts on vegetation and ecosystems.

Abstract Necroptosis and ferroptosis are two distinct forms of necrotic-like cell death in terms of their morphological features and regulatory mechanisms. These two types of cell death can coexist in disease and contribute to pathological processes. Inhibition of both necroptosis and ferroptosis has been shown to enhance therapeutic effects in treating complex necrosis-related diseases. However, targeting both necroptosis and ferroptosis by a single compound can be challenging, as these two forms of cell death involve distinct molecular pathways. In this study, we discovered that KW-2449, a previously described necroptosis inhibitor, also prevented ferroptosis both in vitro and in vivo. Mechanistically, KW-2449 inhibited ferroptosis by targeting the autophagy pathway. We further identified that KW-2449 functioned as a ULK1 (Unc-51-like kinase 1) inhibitor to block ULK1 kinase activity in autophagy. Remarkably, we found that Necrostatin-1, a classic necroptosis inhibitor that has been shown to prevent ferroptosis, also targets the autophagy pathway to suppress ferroptosis. This study provides the first understanding of how necroptosis inhibitors can prevent ferroptosis and suggests that autophagy is a targetable pathway for necroptosis inhibitors to prevent ferroptosis. Therefore, the identification and design of pharmaceutical molecules that target the autophagy pathway from necroptosis inhibitors is a promising strategy to develop dual inhibitors of necroptosis and ferroptosis in clinical application.

This study investigated the effects of fluctuating boundary water levels and surface recharge on groundwater flow within unconfined aquifers. We aimed to understand how changes in recharge patterns and variable boundary water levels, such as those from rivers or canals, affect groundwater levels over time and space. To achieve this, we solved the linearized Boussinesq equation using the time-marching method alongside the generalized integral transformation method. Our analysis focused on how different types of recharge affect groundwater level variations and flow dynamics. We found that boundary effects on groundwater level change propagate from the edges toward the aquifer's center, becoming more pronounced with increased boundary water levels. Over time, the system stabilizes, leading to a steady water table height and flow rate, which depend on the disparity between the boundary water levels. Our analytical model demonstrated flexibility and practical applicability by allowing for the consideration or omission of various influencing factors, thus facilitating complete knowledge about groundwater variations and offering future strategic insights for sustainable groundwater resource management.

Objective: To investigate the effects and mechanisms of Xuebijing injection (XBJ) on Chimeric antigen receptor-T (CAR-T) cell function and its therapeutic potential against CAR-T therapy-associated cytokine storms (CRS). Methods: Anti-CD19 CAR-T cells were established based on FMC63 antibodies. Different doses of XBJ (1 and 10 mg/mL) were added to the culture system. Untreated anti-CD19 CAR-T cells served as negative controls. After 48-h co-culture, the effects of XBJ on CAR-T cell function were assessed. Carboxyfluorescein diacetate succinimidyl ester staining was used to assess the effect of XBJ on CAR-T cell proliferation. Flow cytometry, luciferase reporter gene assays, and real time cellular analysis were employed to evaluate the effects of XBJ on CAR-T cell cytotoxicity in vitro. RNA-sequencing was performed to analyze the effects of XBJ on CAR-T cell gene expression. Network pharmacology predicted potential XBJ therapeutic targets for CRS, which were verified in a THP-1 macrophage inflammation model. Results: XBJ enhanced both the proliferation and tumor killing capacities of CAR-T cells. Transcriptome analysis showed that XBJ treatment affects multiple genes and pathways in CAR-T cells, with differential gene enrichment in multiple cell proliferation and growth factor pathways. Potential targets for CRS control by XBJ were predicted using network pharmacology, and the inhibitory effect of XBJ on the expression of relevant genes was verified using a macrophage model. Conclusion: The results of this study indicate that XBJ can enhance the killing effect of CAR-T cells on tumor cells and that the mechanism is related to the regulation of T cell proliferation and activation. Moreover, XBJ inhibited excessive inflammation associated with CAR-T therapy. However, the current findings remain to be further validated through in vivo experiments.

Abstract Glycerol-based biorefinery can be a highly profitable process by producing highly value-added products such as dihydroxyacetone via combined catalytic strategies. Here, two-enzyme system is adopted for the transformation of glycerol into highly valuable dihydroxyacetone as well as cofactor regeneration at the same time. Glycerol dehydrogenase (GDH) and alcohol dehydrogenase (ADH) are co-immobilized within magnetically separable and spherical mesocellular silica foam (Mag-S-MCF), to prepare NER-(GDH/ADH). In details, GDH and ADH are adsorbed into the mesopores of Mag-S-MCF, and further crosslinked within the mesopores of Mag-S-MCF. The resulting nanoscale enzyme reactors (NER) of crosslinked GDH and ADH molecules within the bottle-neck structured mesopores can effectively prevent larger sized crosslinked enzyme aggregates from being leached out of smaller mesopores, due to the bottle-neck mesopore structure of Mag-S-MCF, as well as stabilize the activity of GDH and ADH upon chemical crosslinking, effectively preventing the denaturation of enzyme molecules. More importantly, the proximity of GDH and ADH molecules within mesopores of NER improves the efficiency of cofactor-mediated dual-enzymatic reactions by relieving mass-transfer limitations and improving cofactor recycling in an effective way, expediting both glycerol oxidation and dihydroxyacetone generation at the same time. As a result, the DHA concentration of NER-(GDH/ADH) and the simple mixture of NER-GDH and NER-ADH were 410 μM and 336 μM, respectively. To the best of our knowledge, this report is the first demonstration of stabilized nanoscale multi-enzyme reactor system, equipped with efficient cofactor regeneration within confined mesopores, for efficient glycerol transformation to high-valued dihydroxyacetone. Graphical Abstract

Abstract Phonon engineering is crucial for thermal management in GaN-based power devices, where phonon-defect interactions limit performance. However, detecting nanoscale phonon transport constrained by III-nitride defects is challenging due to limited spatial resolution. Here, we used advanced scanning transmission electron microscopy and electron energy loss spectroscopy to examine vibrational modes in a prismatic stacking fault in GaN. By comparing experimental results with ab initio calculations, we identified three types of defect-derived modes: localized defect modes, a confined bulk mode, and a fully extended mode. Additionally, the PSF exhibits a smaller phonon energy gap and lower acoustic sound speeds than defect-free GaN, suggesting reduced thermal conductivity. Our study elucidates the vibrational behavior of a GaN defect via advanced characterization methods and highlights properties that may affect thermal behavior.

Abstract Background The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients. Methods A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors. Results In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score

Purpose – This study aimed to facilitate a rapid evaluation of track service status and vehicle ride comfort based on car body acceleration. Consequently, a low-cost, data-driven approach was proposed for analyzing speed-related acceleration limits in metro systems. Design/methodology/approach – A portable sensing terminal was developed to realize easy and efficient detection of car body acceleration. Further, field measurements were performed on a 51.95-km metro line. Data from 272 metro sections were tested as a case study, and a quantile regression method was proposed to fit the control limits of the car body acceleration at different speeds using the measured data. Findings – First, the frequency statistics of the measured data in the speed-acceleration dimension indicated that the car body acceleration was primarily concentrated within the constant speed stage, particularly at speeds of 15.4, 18.3, and 20.9 m/s. Second, resampling was performed according to the probability density distribution of car body acceleration for different speed domains to achieve data balance. Finally, combined with the traditional linear relationship between speed and acceleration, the statistical relationships between the speed and car body acceleration under different quantiles were determined. We concluded the lateral/vertical quantiles of 0.8989/0.9895, 0.9942/0.997, and 0.9998/0.993 as being excellent, good, and qualified control limits, respectively, for the lateral and vertical acceleration of the car body. In addition, regression lines for the speed-related acceleration limits at other quantiles (0.5, 0.75, 2s, and 3s) were obtained. Originality/value – The proposed method is expected to serve as a reference for further studies on speed-related acceleration limits in rail transit systems.

Abstract Improvements in analytical technique and data processing lead to a large deposit of detrital zircon U–Pb and Hf isotopic data in published journal articles, thesis and reports. With the support of Deep‐time Digital Earth Big Science Program, OneSediment Project conducted a team‐working effort to assemble the detrital zircon U–Pb and Hf isotopic data for mainland China and adjacent regions. Entity‐relationship diagram was constructed for detrital zircon data to determine what information need to be collected. Researchers and students from 13 institutions were organized together to fulfil this task and generated 13 detrital zircon datasets. The assembled datasets totally include 6635 samples and 560,596 analyses. The samples were checked in terms of lithology and stratigraphy according to the latest stratigraphic framework. Collected detrital zircon U–Pb and Hf isotopic data were recalculated for the best U–Pb age and εHf(t) values. They can be used to track crustal growth, tectonic evolution, provenance analysis and palaeogeographical change in regional and, when combined with other dataset, global scales.

Abstract Developments of detrital zircon geochronology have resulted in an explosion of publications that report or discuss detrital zircon data. Combined detrital zircon U–Pb ages with Hf isotope analyses from modern and Quaternary sediments have been widely carried out with the aim of characterizing continental crustal evolution and tracing sediment provenance. Although several detrital zircon databases have compiled U–Pb and Hf data on global scale, the dataset of detrital zircon with a special focus on modern sediment has rarely been compiled. Here, we publish a new detrital zircon dataset of modern and Quaternary sediments in China with 59,535 U–Pb ages and 4,971 Hf isotope data, with detailed information of isotope ratios, ages, Th/U, etc. Four types of sediments have been classified according to sedimentary environments, including fluvial, marine, aeolian and alluvial sediments. Preliminary analysis is carried out on these compiled data to provide new insights into sedimentary provenance and crustal evolution in China. Eight age populations are identified corresponding to tectonic–thermal or magmatic events, including 2,300–2,700 Ma, 1,800–2,000 Ma, 700–1,000 Ma, 400–500 Ma, 200–300 Ma, 120–200 Ma, 80–120 Ma and

Abstract Remaining useful life (RUL) is a key indicator for assessing the health status of lithium (Li)-ion batteries, and realizing accurate and reliable RUL prediction is crucial for the proper operation of battery systems. As high-capacity Li batteries have more complex chemical properties, most of the current RUL prediction methods rely mainly on a priori knowledge to make judgments. As a result, prediction accuracy is not high. In this study, we developed a health indicator-capacity (HI-C) dual Gaussian process regression (GPR) model based on incremental capacity analysis (ICA) and optimized its kernel function to achieve accurate RUL prediction for 280 Ah high-capacity Li batteries. Validation against the United States National Aeronautics and Space Administration’s four battery test datasets showed that the use of the HI-C dual GPR model resulted in a mean absolute percentage error and root mean square error of less than 0.02 and 0.04, respectively, for the four battery-rated capacity predictions. Additionally, this model achieved an absolute error of less than five battery failure turns. Compared with a single model, the HI-C dual GPR model not only had high accuracy but also solved the problem that the HI was not measurable in the actual battery operation, which made it more suitable for RUL prediction of Li batteries.

Abstract Pediatric obesity rates have quadrupled in the United States, and deficits in higher-order cognition have been linked to obesity, though it remains poorly understood how deviations from normal body mass are related to the neural dynamics serving cognition in youth. Herein, we determine how age- and sex-adjusted measures of body mass index (zBMI) scale with neural activity in brain regions underlying fluid intelligence. Seventy-two youth aged 9–16 years underwent high-density magnetoencephalography while performing an abstract reasoning task. The resulting data were transformed into the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Whole-brain correlations with zBMI were subsequently conducted to quantify relationships between zBMI and neural activity serving abstract reasoning. Our results reveal that participants with higher zBMI exhibit attenuated theta (4–8 Hz) responses in both the left dorsolateral prefrontal cortex and left temporoparietal junction, and that weaker temporoparietal responses scale with slower reaction times. These findings suggest that higher zBMI values are associated with weaker theta oscillations in key brain regions and altered performance during an abstract reasoning task. Thus, future investigations should evaluate neurobehavioral function during abstract reasoning in youth with more severe obesity to identify the potential impact.