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Abstract Purpose To explore the differences in long-term ankle joint function between one-stage and staged microsurgical repair of open Achilles tendon defects. Methods A retrospective analysis of the surgical treatment and follow-up data of 147 patients with open Achilles tendon defects from January 2007 to September 2023 was conducted. Patients were divided into a one-stage reconstruction group (n = 81) and a staged reconstruction group (n = 66) on the basis of whether one-stage microsurgical repair was used. In the one-stage reconstruction group, 43 patients underwent vascular anastomosed fascia lata free anterolateral thigh perforator flap transplantation for repair, and 38 patients underwent descending genicular artery free flap transplantation with the adductor magnus tendon. In the staged reconstruction group, the sural neurovascular flap was used to repair the soft tissue defect in the heel area in the first stage. In the second stage, 31 patients underwent flexor hallucis longus tendon transfer, and 35 patients underwent peroneus longus muscle tendon transfer with the lateral calcaneal artery. Observations included evaluation of the continuity and healing of the Achilles tendon via colour Doppler ultrasound 3 months postoperatively and assessment of ankle joint function 2 years postoperatively using the American Orthopedic Foot and Ankle Society ankle–hindfoot score (AOFAS) and the Achilles tendon total rupture score (ATRS). Results Three months after surgery, colour Doppler ultrasound revealed good continuity of the Achilles tendon in all patients, with slight thickening and irregular fibre orientation. Two years after surgery, the ATRS and AOFAS scores of the one-stage reconstruction group were superior to those of the staged group (P ATRS

Abstract Objective This study aims to explore the analgesic effects and safety of periarticular injections of methylene blue (MB) combined with a cocktail formulation following total knee arthroplasty (TKA). Methods A total of 70 patients undergoing total knee arthroplasty were selected and divided into two groups based on the cocktail formula used for periarticular infiltration, including the methylene blue group (M group, n = 35) and the control group (C group, n = 35). Both groups underwent spinal anesthesia. At the end of the surgery, the M group received a 0.05% methylene blue combined cocktail for periarticular infiltration block, while the C group received a conventional cocktail infiltration block. Postoperatively, both groups used intravenous patient-controlled analgesia. Then, the rest and movement Numeric Rating Scale (NRS) scores, postoperative sufentanil consumption, postoperative inflammatory markers, and the occurrence of adverse reactions such as wound infection and poor wound healing were compared after postoperative 24 h, 48 h, 72 h, and 7-day, 14-day, 28-day between the two groups. Results The rest and during movement, NRS scores at postoperative 24 h, 48 h, 72 h, 7-day, 14-day, and 28-day were significantly lower in the C group compared with the M group (P 0.05), and neither group experienced complications such as wound infection or poor wound healing. Conclusion Methylene blue combined with a cocktail can be safely used for local infiltration after knee arthroplasty, which reduces postoperative opioid consumption and suppresses the release of inflammatory factors. Moreover, it synergistically enhanced the local anesthetic analgesia and provided sustained pain relief for at least 4 weeks.

Abstract Background Transferrin receptor (TFRC) uptakes iron-loaded transferrin (TF) to acquire iron and regulates tumor development. Nonetheless, the clinical values and the precise functions of TF-TFRC axis in the development of oral squamous cell carcinoma (OSCC) were still undiscovered, especially the impacts of their regional heterogeneous expression. Methods Immunohistochemistry (IHC) was used to analyze the expression of TFRC in 106 OSCC patients. Then the prognostic value of TFRC was compared between high and low worst pattern of invasion (WPOI) patients. OSCC cells with low or high expression of TFRC were constructed, and functional experiments were performed to elucidate the effects of TFRC on the migration and proliferation of OSCC cells. Multi-immunofluorescence was applied to stain TF and tumor-associated neutrophils (TANs). The stimulating effects of TF were compared between normal and high TFRC cells in vitro and across different OSCC patients’ subgroups in our sample bank and TCGA database. Results Higher TFRC was expressed at invasive tumor front (ITF) in OSCC and correlated with WPOI. Only at ITF in patients with WPOI 4–5, TFRC was a prognostic factor. High TFRC promoted migration and proliferation of cancer cells. Additionally, TANs secreted TF outside. Exogenous TF promoted migration and proliferation of cells with high expression of TFRC. Compared to the TANslowTFRClow OSCC patients, TANshighTFRChigh OSCC patients had poorer clinical outcomes. Conclusions Higher expression of TFRC at ITF and TANs-TF-TFRC axis promoted OSCC invasion at ITF by facilitating cell migration and proliferation, which may result from increased cellular iron uptake through regulating iron metabolism.

Abstract Background The relationship between baseline hemoglobin levels and in-hospital mortality in septic patients remains unclear. This study aimed to clarify this association in critically ill patients with sepsis. Methods Patients with sepsis were retrospectively identified from the Medical Information Mart for Intensive Care-IV (MIMIC-IV 2.2) and eICU Collaborative Research Database (eICU-CRD). Multivariate logistic regression analysis and restricted cubic spline regression were used to investigate the association between hemoglobin and the risk of in-hospital mortality. Additionally, a two-part linear regression model was used to determine threshold effects. Stratified analyses were also performed. Results A total of 21,946 patients from MIMIC-IV and 15,495 patients from eICU-CRD were included in the study. In-hospital mortality was 14.95% in MIMIC-IV and 17.40% in eICU-CRD. Multivariate logistic regression showed that hemoglobin was significantly and nonlinearly associated with the risk of in-hospital mortality after adjusting for other covariates. Furthermore, we found a nonlinear association between hemoglobin and in-hospital mortality, with mortality plateauing at 10.2 g/dL. The risk of mortality decreased with increasing hemoglobin levels below 10.2 g/dL but increased when hemoglobin levels exceeded 10.2 g/dL. These findings were validated in the eICU-CRD dataset. Conclusions A nonlinear correlation between hemoglobin levels and in-hospital mortality was observed in patients with sepsis, with a threshold of 10.2 g/DL. These findings suggested that hemoglobin levels below or above the threshold may be associated with worse outcomes, warranting further investigation in prospective studies.

Abstract Frequent forest fires, driven by hotter and drier climates, threaten biodiversity and human health, causing significant economic losses, air pollution, soil erosion, and degeneration. Current active and passive fire protection methods often suffer from environmental pollution, poor flexibility, and limited availability in remote areas. However, fast-acting surface flame retardants for passive forest fire protection, particularly for foliage, are rare. Herein, we report an easily obtainable gelatin-based fire spray, which resulted in 1.8 and 16.3-fold extension in ignition time, 34% and 39% reductions in total heat release, 78% and 92% reductions in fire growth index for dead and fresh leaves, respectively. After the fire warning is suppressed, for instance by rain, the sprayed substances can decompose and provide nitrogen and phosphorus as leaf and soil fertilizers without affecting soil microbial function, which increase plant net photosynthesis by 84% and effective nitrogen and phosphorus by 664% and 140%, respectively. Our green flame retardant and fertilizer material allows for simultaneous tree fire protection and growth.

Abstract Peri-prosthesis osteolysis (PPO) represents the most severe complication of total joint arthroplasty (TJA) surgery and imposes the primary cause of prosthesis failure and subsequent revision surgery. Antiresorptive therapies are usually prescribed to treat PPO, especially for elderly people. Nevertheless, the efficacy of anti-osteoporotic medications remains constrained. Recent therapeutic strategies to promote periprosthetic osseointegration by restoring osteoblast function are considered more effective approaches. However, the precise mechanism underlying the inhibition of osteogenesis triggered by wear particles remains enigmatic. Herein, we demonstrate that wear particles inhibit osteoblast function by inducing ferroptosis to sabotage extracellular mineralization and arouse periprosthetic osteolysis. The suppression of ferroptosis could significantly rescue osteogenesis thus alleviating PPO. Furthermore, Glutathione Peroxidase 4 (GPX4) has been identified as a key target in regulating osteoblastic ferroptosis. By utilizing virtual screening techniques, we have successfully conducted a comprehensive screening of a natural compound known as Urolithin A (UA), which exhibits remarkable inhibition of osteoblastic ferroptosis while simultaneously promoting the process of osteogenesis through its precise targeting mechanism on GPX4. Meanwhile, UA improves the osteolytic conditions significantly in vivo even when the adjunction of titanium (Ti) nanoparticles. This strategy has great potential in treating peri-prosthesis osteolysis and potentially broadens the scope of clinical therapy. Graphical Abstract

Abstract Evidence suggests that complex interactions among the gut microbiome, metabolic abnormalities, and brain have important etiological and therapeutic implications in major depressive disorder (MDD). However, the influence of microbiome-gut-brain cross-talk on cognitive impairment in MDD remains poorly characterized. We performed serum metabolomic profiling on 104 patients with MDD and 77 healthy controls (HCs), and also performed fecal metagenomic sequencing on a subset of these individuals, including 79 MDD patients and 60 HCs. The findings were validated in a separate cohort that included 40 patients with MDD and 40 HCs using serum-targeted metabolomics. Abnormal bile acid metabolism was observed in patients with MDD, which is related to cognitive dysfunction. The following gut microbiota corresponded to changes in bile acid metabolism and enzyme activities involved in the bile acid metabolic pathway, including Lachnospiraceae (Blautia_massiliensis, Anaerostipes_hadrus, Dorea_formicigenerans, and Fusicatenibacter_saccharivorans), Ruminococcaceae (Ruminococcus_bromii, Flavonifractor_plautii, and Ruthenibacterium_lactatiformans), and Escherichia_coli. Furthermore, a combinatorial marker classifier that robustly differentiated patients with MDD from HCs was identified. In conclusion, this study provides insights into the gut-brain interactions in the cognitive phenotype of MDD, indicating a potential therapeutic strategy for MDD-associated cognitive impairment by targeting the gut microbiota and bile acid metabolism.

Abstract The antioxidant protein sulfiredoxin-1 (SRX) is an oncogenic factor that promotes tumor progression, but the regulatory mechanism underlying SRX degradation remains to be understood. Herein, we report that Keap1, the substrate-specific adapter of CRL3 complex, specifically binds and promotes the ubiquitin-mediated degradation of SRX at residue K61. Keap1 knockdown accumulates SRX, which in turn facilitates colorectal cancer (CRC) metastasis by activating the activator protein-1/matrix metalloproteinase 9 (AP-1/MMP9) pathway. CRC-associated Keap1 mutants within the BACK domain lose the capability to ubiquitinate SRX and instead promote CRC metastasis. Moreover, inactivation of Keap1 facilitates CRC tumorigenesis and metastasis in mouse models of tumor xenograft due to SRX accumulation. Clinical sample analysis reveals that Keap1 is downregulated while SRX is overexpressed in CRC, which correlates with poor prognosis. Our findings elucidate a mechanism by which CRL3Keap1 ubiquitin ligase degrades SRX to suppress CRC progression, indicating that the Keap1-SRX axis will guide the targeted therapy towards CRC.

Abstract Schizophrenia is a severe neuropsychiatric disease, but the initiation mechanisms are unclear. Although antipsychotics are effective against positive symptoms, therapeutic interventions for negative symptoms are limited due to the lack of pathophysiological mechanisms. Here we identify synaptotagmin-11 (Syt11) as a potential genetic risk factor and dopamine over-transmission as a mechanism in the development of schizophrenia. Syt11 expression is reduced in individuals with schizophrenia but restored following the treatment with antipsychotics. Syt11 deficiency in dopamine neurons in early adolescence, but not in adults, leads to persistent social deficits and other schizophrenia-like behaviors by mediating dopamine over-transmission in mice. Accordingly, dopamine neuron over-excitation before late adolescence induces persistent schizophrenia-associated behavioral deficits, along with the structural and functional alternations in the mPFC. Notably, local intervention of D2R with clinical drugs presynaptically or postsynaptically exhibits both acute and long-lasting therapeutic effects on social deficits in schizophrenia mice models. These findings not only define Syt11 as a risk factor and DA over-transmission as a potential risk factor initiating schizophrenia, but also propose two D2R-targeting strategies for the comprehensive and long-term recovery of schizophrenia-associated social withdrawal.

Abstract Background For critically ill patients with acute kidney injury (AKI), there remains controversy regarding the predictive factors affecting the discontinuation of continuous renal replacement therapy (CRRT). This study aims to explore factors associated with successful CRRT discontinuation in AKI patients and to develop predictive models for successful discontinuation. Methods We conducted a retrospective study on adult patients with AKI who received CRRT, sourced from the Medical Information Mart for Intensive Care (MIMIC-IV) database. Successful discontinuation of CRRT was defined as no CRRT requirement within 72 h after stopping CRRT. Predictive factors for successful discontinuation of CRRT were analyzed. Additionally, we utilized machine learning algorithms to develop predictive models, including logistic regression (LR), decision tree (DT), random forest (RF), XGBoost, and K-nearest neighbor (KNN). Results A total of 599 patients were included, of whom 475 (79.3%) successfully discontinued CRRT. Urine output, non-renal SOFA score, bicarbonate, systolic blood pressure, and blood urea nitrogen were identified as risk factors for successful CRRT discontinuation. The KNN model exhibited the highest area under the receiver operating characteristic curve (AUC) (0.870), followed by LR (0.739), DT (0.691), RF (0.847), and XGBoost (0.830). When incorporating all available variables, the AUCs for the LR, DT, RF, XGBoost, and KNN models were 0.708, 0.674, 0.875, 0.866, and 0.816, respectively. Considering the performance of the models in both scenarios, the ensemble learning models (RF and XGBoost) were demonstrated superior performance. Conclusions Our results identified factors associated with successful discontinuation of CRRT in AKI patients. Additionally, we developed promising machine learning models which provided a reference for future research.

This study explores the effects of trees on the acoustic and thermal environment in addition to people’s responses to trees in different contexts. Through field measurements conducted during the summer of 2023 at the campus of the Southwest University of Science and Technology in Mianyang, residents’ neutral points were locally found to be 52.2 dBA (acoustic) and 23.8 °C (thermal). Further, at their maximum, the trees were able to reduce heat stress by 4 °C (indicated by the physiologically equivalent temperature—PET) and the noise level by 10 dBA (indicated by the A-weighted sound pressure—LAeq); this was achieved by trees with a crown diameter of 20 m. Subjective acoustic and thermal responses varied depending on the context. Acoustically, their neutral LAeq values toward the sounds of traffic, teaching, sports, and daily life were 46.9, 52.5, 51.0, and 52.7 dBA, respectively. Thermally, pedestrians’ neutral PET values were 24.2, 26.1, 22.3, and 25.1 °C, respectively, under the same conditions. These phenomena might be a consequence of the effects of sound frequencies. Future urban forestry research should focus on planting for environmental quality improvement.

Abstract Magnetic fields from the linear motor, suspended electromagnet, and collector shoe arcing are the three main electromagnetic interference (EMI) sources for the medium–low-speed maglev train interior. Under their collective influence, the field intensity may exceed the standard threshold, consequently affecting the operational reliability of the train system. However, in previous studies, the EMI sources were analyzed separately, and studies regarding the influence of factors such as the motor states and the train body (TB) shielding against arcing EMI were lacking. Therefore, in this paper, all three EMI source are considered, and an EM disturbance source modeling scheme is proposed using the COMSOL software platform. Its effectiveness is demonstrated and the train interior magnetic field is analyzed, primarily with respect to prior simulations and tests. Subsequent analyses enable a comparative assessment of the individual contributions of each EMI source to the overall interference, considering the EMI control standards. The influence of other EMI source parameters, such as different motor states, is analyzed, and the potential for modifying the material composition and structural thickness of the TB is explored to determine the appropriate EMI inhibition strategy.

Abstract Low-dose CT (LDCT) is increasingly recognized as the preferred method for detecting pulmonary nodules. However, distinguishing whether a nodule is benign or malignant often necessitates repeated scans or invasive tissue sampling procedures. Therefore, there is a pressing need for non-invasive techniques to minimize unnecessary interventions. This study aim to investigate the expression profile of exosomal snoRNA in the serum of patients with benign and malignant pulmonary nodules. We identified a total of 278 snoRNAs in serum exosomes, revealing significant differences in snoRNA levels between patients with malignant and benign nodules. Specifically, the upregulated snoRNAs U78 and U37 were validated through qRT-PCR and were found significantly elevated in the serum of patients with malignant pulmonary nodules, positioning them as promising biomarkers for the early detection of lung cancer. This study underscores the potential of serum exosomal U78 and U37 as critical tools for assessing the risk of pulmonary nodules identified through CT screening.

Abstract Background A high body mass index (hBMI) is one of the major risk factors for ischemic stroke (IS), although independent estimates of the global burden and trend of IS attributable to hBMI are unclear. Methods Study data were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study and analysed by age, sex, year, and geographical location. The sociodemographic index (SDI) and the human development index (HDI) were used as indicators of national socioeconomic status. Geographic distributions and trends were assessed by calculating the estimated annual percentage change (EAPC). Associations between the age-standardized death rate (ASMR) or disability-adjusted life year rate (DALY) and socioeconomic status were analysed. Results Deaths and DALYs increased worldwide from 1990–2021, with increases of 95.74% for the former and 133.00% for the latter; the ASMR and ASDR decreased, with an ASMR and ASDR-related EAPCs of -1.10 (95% CI: -1.24–-0.96) and 0.04 (95% CI:-0.47–0.55), respectively; women had greater numbers of deaths and DALYs, and the majority of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by Eastern Europe, North Africa, the Middle East, and Central Asia. The ASMR-related EAPCs were associated with the ASMR in 1990 (R = -0.35, P

Abstract Objective This study aims to compare the efficacy of the Age-adjusted Charlson Comorbidity Index (ACCI) and the Elixhauser-Van Walraven Comorbidity Index (ECI-VW) in predicting mortality risk among patients undergoing heart valve surgery. Methods Clinical data were extracted from the INSPIRE Database using R language. The Receiver Operating Characteristic (ROC) Curve was employed to assess the predictive accuracy of ACCI and ECI-VW for in-hospital all-cause mortality and post-surgical all-cause mortality at 7 and 28 days. Subgroup analysis was conducted to validate the application efficacy, and the optimal cutoff value was identified. Results The study included 996 patients, with 931 survivors and 65 cases of in-hospital all-cause mortality. The area under the curve (AUC) for ACCI in predicting in-hospital all-cause mortality was 0.658 (95% CI: 0.584, 0.732), while the AUC for ECI-vw in predicting the same outcome was 0.663 (95% CI: 0.584, 0.741). For predicting all-cause mortality within 7 days post-surgery, the AUC of ACCI was 0.680 (95% CI: 0.04, 0.56), and for ECI-vw, it was 0.532 (95% CI: 0.353, 0.712). Regarding the prediction of all-cause mortality within 28 days after surgery, the AUC for ACCI was 0.724 (95% CI: 0.622, 0.827), and for ECI-vw, it was 0.653 (95% CI: 0.538, 0.69). Patients were categorized into two groups based on the ACCI cutoff value of 3.5, including Group 1 (ACCI 3.5 points, 173 cases). The overall survival rate for these two patient groups was calculated using the Kaplan-Meier method, revealing that the 28-day postoperative survival rate for patients in Group 1 was significantly higher than that for patients in Group 2 (P

Low temperatures and icing in winter are significant factors that severely affect highway safety and traffic mobility. To enhance the precision and reliability of real-time winter road surface temperature (RST) prediction, a short-term prediction model is developed that harnesses both feature selection and deep learning. Leveraging meteorological data from a mountain highway in Yunnan, China, the key environmental variables affecting road surface temperature were first extracted using a random forest (RF) model for feature selection. These features were then combined with RST data to construct multiple groups of input variable combinations for the prediction model. A short-term prediction model with a 10-minute update frequency was built using a long short-term memory neural network (LSTM), namely RF-LSTM. The best input variable combination and preset parameters for the prediction model were determined through comparative testing with prevalent machine learning models, and the transferability of the prediction model was verified. The results showed that the best input variable combination for the RF-LSTM prediction model was road surface temperature and air temperature. The model recognised that the short-term RST was affected by long and short-term memory characteristics within a two-hour timeframe. When compared to the RF model, backpropagation (BP) neural network model and the standard LSTM model, the proposed model reduces prediction errors by 59.15%, 31.10% and 20.26%, respectively, while the prediction accuracy is 99.13% within an error margin of ±0.5℃. On the verification dataset, the proposed model maintains its time transferability with an average prediction absolute error of 0.0478. In all, the proposed model not only achieves a higher level of precision in real-time RST predictions but also ensures a more consistent and reliable performance under the challenging conditions of high altitude and mountainous terrain, offering enhanced support for traffic safety and road maintenance decision-making.

The performance of a solid oxide fuel cell (SOFC) is strongly associated with the activity and durability of the cathode, where the oxygen reduction reaction occurs. In this study, we report our findings in the development of an Nb-doped PrBa0.8Ca0.2Co2O6−δ (PrBa0.8Ca0.2Co2−xNbxO6−δ, x = 0, 0.025, 0.05, and 0.1, denoted as PBCCNx) perovskite composite as the SOFC cathode. Analyses of X-ray diffraction (XRD) patterns and energy-dispersive transmission electron microscopy (TEM-EDS) images suggest that after being treated at 950 °C in air, PBCCN0.05 mainly contains phases of Ca- and Nb-doped PrBaCo2O6−δ double perovskite, PrCoO3 perovskite with Ca and Nb doping, and Ba3Ca1.18Nb1.82O9−δ. When evaluated as an SOFC cathode, the PBCCN0.05 mixture has shown a low polarization resistance of 0.0074 Ω∙cm2 at 800 °C in La0.8Sr0.2Ga0.8Mg0.2O3 electrolyte symmetrical cells. Accordingly, anode-supported single cells with a configuration of Ni–Zr0.84Y0.16O2−δ (YSZ)/YSZ/Gd0.1Ce0.9O2−δ/PBCCN0.05 display high electrochemical performance, with a peak power density of 1.81 W∙cm−2 and a reasonable durability of 100 h at 800 °C. PBCCN0.05 possesses a higher concentration of oxygen vacancies, a faster oxygen surface adsorption‒dissociation rate, and an increased mass ratio of PrCoO3 perovskite with Ca and Nb doping compared to PrBa0.8Ca0.2Co2O6−δ without Nb doping.

Abstract Background NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P

Abstract Zinc‐based batteries are promising for applications in large‐scale energy storage and other scenarios due to their high voltage, large theoretical capacity, and abundant reserves. Compared to traditional aqueous electrolytes, deep eutectic solvents (DESs) offer advantages such as wide electrochemical window, good stability, and fewer parasitic reactions. They can effectively regulate the growth morphology of zinc deposits and suppress dendrite formation during zinc deposition/stripping processes. However, there is currently a lack of direct observation for underlying mechanisms of zinc deposition/stripping processes in DESs. In this study, combined with electrochemical methods, in‐situ atomic force microscopy (in‐situ AFM) has been utilized to investigate the deposition behavior of zinc metal from ZnCl2 precursor in a deep eutectic solvent composed of choline chloride and ethylene glycol (ethaline). Cyclic voltammetric measurements indicate that zinc deposition is a kinetically controlled process. And in‐situ AFM reveals the hexagonal morphology and layered deposition of zinc on highly oriented pyrolytic graphite (HOPG). Our observations benefit the understanding of the kinetics of zinc deposition/stripping in deep eutectic solvent ethaline at a microscopic level.

Abstract Dynamic pathogen exposure may impact the immunological response to SARS‐CoV‐2 (SCV2). One potential explanation for the lack of severe SCV2‐related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2‐related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat‐to‐human spillover exposures in the region. In this work, serum antibodies to protein constructs from SCV2 and a representative bat coronavirus isolated in Cambodia (RshSTT182) are measured in pre‐pandemic Cambodian human sera using ELISA assays. Of 293 Cambodian samples tested (N = 131 with acute malaria, n = 162 with acute undifferentiated febrile illness), 32 (10.9%) are seropositive for SCV2 based on established Spike and receptor‐binding domain (RBD) cutoffs. Within SCV2 seropositive samples, 16 (50%) have higher antibody levels to antigens from the representative virus RshSTT182 versus SCV2 antigens; competitive binding ELISA assays demonstrate inhibition of reactivity to SCV2 Spike after pre‐incubation with RshSTT182 Spike. Surrogate virus neutralization tests demonstrate that 8/30 (26.7%) SCV2 ELISA positive pre‐pandemic Cambodian samples have neutralizing activity against SCV2, while 14/30 (46.7%) have activity against other SCV2‐related betacoronaviruses. These data suggest that exposure to related betacoronaviruses may elicit cross‐reactive immunity to SCV2 prior to the global pandemic.

Evidence suggests that the gut microbiome may play a role in multiple sclerosis (MS). However, the majority of the studies have focused on gut bacterial communities; none have examined the fungal microbiota (mycobiota) in persons with pediatric-onset multiple sclerosis (POMS). We examined the gut mycobiota in persons with and without POMS through a cross-sectional examination of the gut mycobiota from 46 participants’ stool samples (three groups: 18 POMS, 13 acquired monophasic demyelinating syndromes [monoADS], and 15 unaffected controls). Using metataxonomic sequencing of the fungal internal transcribed spacer region 2, the fungal profiles were compared between participants using visualizations, statistical tests, and predictive analysis. While the mycobiome α- (Shannon and inverse Simpson indices) and β-diversity differed across the three groups [analysis of variance (ANOVA), p

In a mixed traffic environment consisting of connected autonomous vehicles (CAVs) and human-driven vehicles (HVs), platooning intensity serves as a critical metric, quantifying the strength of CAV clustering, with inherent ramifications for traffic flow efficiency. While various definitions of platooning intensity are found in existing literature, many fall short in effectively capturing the strength of CAV clustering in mixed traffic. To address the gap, this study models the vehicle stream of mixed traffic on the single-lane road as a binary sequence and proposes the autocorrelation-based platooning intensity (API) metric. Through theoretical analysis, the proposed API is shown to be an effective indicator for measuring the clustering strength of CAVs. The probability distribution of API through fisher transformation is also derived. This study then moves on to formulate the capacity of mixed traffic, taking into account CAV penetration rate, API, and stochastic headway. Numerical verification of the estimated mixed traffic capacity reveals a negligible error (less than 1%) compared to simulated capacity. Marginal analysis confirms the validity of related propositions, notably that stronger CAV clustering does not always improve traffic capacity due to headway stochasticity. The outcome of this study contributes to the understanding of CAV platooning intensity and offers valuable insights for advancing mixed traffic modeling and management.

Background: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL.Methods: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24.Results: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, β2-microglobulin (β2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P

Data on reinfection in large Asian populations are limited. In this study, we aimed to evaluate the reinfection rate, disease severity, and time interval between the infections in the symptomatic and asymptomatic populations which are firstl infected with BA.2 Omicron Variant. We retrospectively included adult patients with COVID-19 discharged from four designated hospitals between 27 April 2021 and 30 November 2022, who were interviewed via telephone from 29 January to 1 March 2023. Univariable and multivariable analyses were used to explore risk factors associated with reinfection. A total of 16,558 patients were followed up, during the telephone survey of an average of 310.0 days, 1610 (9.72%) participants self-reported reinfection. The mean time range of reinfection was 257.9 days. The risks for reinfection were analysed using multivariable logistic regression. Patients with severe first infection were at higher risk for reinfection (aORs, 2.50; P

Objective The aim of this study was to explore the impact of growth hormone (GH) therapy on the onset and progression of puberty in girls with idiopathic short stature.Methods This study included 541 girls aged between 4.5 and 10.6 years who were receiving GH treatment, monitored over a 22-year follow-up period. Of these, 126 girls have been followed up to the onset of menarche. The participants were divided into two groups: a ISS control group (n = 66) and a group receiving daily GH treatment at a dose of 0.15 iu/kg (n = 60). We assessed the pubertal development and GH usage of these girls every three months.Results (1) There was no significant difference in the onset of puberty between the growth hormone (GH) treatment group and the control group; however, the average duration of puberty was longer in the treatment group compared to the control group. (2) During puberty, there were no significant differences in height growth between the treated and untreated groups. (3) The duration of GH treatment showed a significant negative correlation with the age at onset of gonadal development and the age at menarche in females within the treatment group.Conclusion GH treatment does not seem to accelerate the onset of puberty but may extend its duration, without significantly impacting height growth during puberty. Additionally, longer GH treatment duration is linked to earlier gonadal development and menarche in females.

Background Relapsed/refractory acute lymphoblastic leukemia (R/R ALL) continues to be a major cause of mortality in children worldwide, with around 15% of ALL patients experiencing relapse and approximately 10% eventually dying from the disease. Early identification of R/R ALL in children has posed a longstanding clinical challenge.Method Genetic analysis of survival outcomes in pediatric patients with ALL from the TARGET-ALL dataset revealed five risk score factors identified through the intersection of differential genes (relapse/non-relapse) from the GSE17703 and GSE6092 databases. A risk score equation was formulated using these factors and validated against prognostic data from 46 ALL cases at our institution. Patients from multiple datasets were stratified into high and low-score groups based on this equation. Protein–protein interaction networks (PPI) were then constructed using the intersecting differential genes from all three datasets to identify hub nodes and predict interacting transcription factors. Additionally, genes related to cell pyroptosis with varying expression across these datasets were screened, and a multifactorial ROC curve (incorporating risk score and differential expression of pyroptosis-related genes) was generated. Furthermore, relationships among variables in the predictive model were depicted using a nomogram, and model efficacy was assessed through decision curve analysis (DCA).Results By analyzing the TARGET-ALL, GSE17703, and GSE6092 databases, we developed a prognostic risk assessment model for pediatric ALL incorporating BAG2, EPHA4, FBXO9, SNX10, and WNK1. Validation of this model was conducted using data from 46 pediatric ALL cases obtained from our institution. Following the identification of 27 differentially expressed genes, we constructed a PPI and identified the top 10 hub genes (PTPRC, BTK, LCK, PRKCQ, CD3D, CD27, CD3G, BLNK, RASGRP1, VPREB1). Using this network, we predicted the top 5 transcription factors (HOXB4, MYC, SOX2, E2F1, NANOG). ROC and DCA were conducted on pyroptosis-related genes exhibiting differential expression and risk scores. Subsequently, a nomogram was generated, demonstrating the effectiveness of the risk score in predicting prognosis for pediatric ALL patients.Conclusions We have developed a risk prediction model for pediatric R/R ALL utilizing the genes BAG2, EPHA4, FBXO9, SNX10, and WNK1. This model provides a scientific foundation for early identification of R/R ALL in children.

Ammonia protonic ceramic fuel cells (NH3-PCFCs) are highly appealing energy conversion technologies due to their high efficiency, environmental responsibility, and benign safety features. Nonetheless, progress in NH3-PCFCs is notably impeded by the restricted performance and insufficient lifespan of standard Ni-cermet anodes for ammonia cracking, especially at 550 °C or below. Herein, we report an efficient ammonia cracking layer with a formula of xCo3O4/100-xBaZr0.8Y0.2O3-δ (Co/BZY) (x=10, 20, 30), which is deposited onto the Ni-BaZr0.1Ce0.7Y0.1Yb0.1O3−δ (BZCYYb) anode to significantly enhance the NH3 decomposition catalytic activity, thereby improving the performance and durability of NH3-PCFCs at low temperatures. The cells with the addition of a 20Co/80BZY anode catalytic layer (ACL) exhibit low area-specific resistance (ASR) and promising operational longevity under NH3 conditions. At 550°C, the NH3-PCFCs with a 20Co/80BZY ACL exhibit a high peak power density of 0.626 W cm−2 and promising operation durability. This study provides important guidance for constructing high-performance and durable NH3-PCFCs.

Abstract In plants due to their sessile nature, secondary metabolites are important components against different abiotic and biotic stress, such as extended darkness. For this reason, the variation of secondary metabolite content of the Arabidopsis thaliana HapMap natural population following 0-and 6-d darkness treatment were detected and the raw data of different accessions at two timepoints were deposited in the Zenodo database. Moreover, the annotated secondary metabolites of these samples are presented in this data descriptor, which we believe will be a usefully re-usable resource for future integrative analysis with dark-treated transcripts, proteins or other phenotypic data in order to comprehensively illustrate the multiomic landscape of Arabidopsis in response to the stresses exerted by extended darkness.

Abstract Stroke is the second leading cause of death worldwide, and China has the highest stroke incidence in the world. The systemic inflammatory response index (SIRI), systemic inflammatory response index (SIRI), systemic immune-inflammatory index (SII), neutrophil-to-high-density lipoprotein ratio (NHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) have clinical in predicting the prognosis of acute ischaemic stroke (AIS) patients. No studies have compared the predictive value of these six composite inflammatory markers. This study included 516 AIS patients with AIS symptoms for 2 defining poor prognosis. The results of the univariate analysis showed that all six composite inflammatory indices, SIRI, SII, NHR, NLR, PLR and MLR, were associated with a poor prognosis in patients with AIS. All six composite inflammatory indicators correlated with the short-term prognosis of AIS patients. The six composite inflammation indicators were included in the binary logistic regression, and the results showed that SIRI, NLR and PLR were found to be independent risk factors for poor short-term prognosis in AIS patients. Among the six inflammatory markers, SIRI, NLR and PLR were the most clinically valuable for predicting the short-term prognosis of patients with AIS. Peripheral blood indices are easy to obtain clinically and can provide important clinical value for early prognosis and treatment adjustment.

Abstract As a class of biologically active molecules with significant immunomodulatory and anti-inflammatory effects, anti-inflammatory peptides have important application value in the medical and biotechnology fields due to their unique biological functions. Research on the identification of anti-inflammatory peptides provides important theoretical foundations and practical value for a deeper understanding of the biological mechanisms of inflammation and immune regulation, as well as for the development of new drugs and biotechnological applications. Therefore, it is necessary to develop more advanced computational models for identifying anti-inflammatory peptides. In this study, we propose a deep learning model named DAC-AIPs based on variational autoencoder and contrastive learning for accurate identification of anti-inflammatory peptides. In the sequence encoding part, the incorporation of multi-hot encoding helps capture richer sequence information. The autoencoder, composed of convolutional layers and linear layers, can learn latent features and reconstruct features, with variational inference enhancing the representation capability of latent features. Additionally, the introduction of contrastive learning aims to improve the model's classification ability. Through cross-validation and independent dataset testing experiments, DAC-AIPs achieves superior performance compared to existing state-of-the-art models. In cross-validation, the classification accuracy of DAC-AIPs reached around 88%, which is 7% higher than previous models. Furthermore, various ablation experiments and interpretability experiments validate the effectiveness of DAC-AIPs. Finally, a user-friendly online predictor is designed to enhance the practicality of the model, and the server is freely accessible at http://dac-aips.online .

Abstract Background Omicron variant impacts populations with its rapid contagiousness, and part of patients suffered from persistent symptoms termed as long COVID. The molecular and immune mechanisms of this currently dominant global variant leading to long COVID remain unclear, due to long COVID heterogeneity across populations. Methods We recruited 66 participants in total, 22 out of 66 were healthy control without COVID-19 infection history, and 22 complaining about long COVID symptoms 6 months after first infection of Omicron, referred as long COVID (LC) Group. The left ones were defined as non-long COVID (NLC) Group. We profiled them via plasma neutralizing antibody titer, SARS-CoV-2 viral load, transcriptomic and proteomics screening, and machine learning. Results No serum residual SARS-CoV-2 was observed in the participants 6 months post COVID-19 infection. No significant difference in neutralizing antibody titers was found between the long COVID (LC) Group and the non-long COVID (NLC) Group. Transcriptomic and proteomic profiling allow the stratification of long COVID into neutrophil function upregulated (NU-LC) and downregulated types (ND-LC). The NU-LC, identifiable through a refined set of 5 blood gene markers (ABCA13, CEACAM6, CRISP3, CTSG and BPI), displays evidence of relatively higher neutrophil counts and function of degranulation than the ND-LC at 6 months after infection, while recovered at 12 months post COVID-19. Conclusion The transcriptomic and proteomic profiling revealed heterogeneity among long COVID patients. We discovered a subgroup of long COVID population characterized by neutrophil activation, which might associate with the development of psychiatric symptoms and indicate a higher inflammatory state. Meanwhile, a cluster of 5 genes was manually curated as the most potent discriminators of NU-LC from long COVID population. This study can serve as a foundational exploration of the heterogeneity in the pathogenesis of long COVID and assist in therapeutic targeting and detailed epidemiological investigation of long COVID.

Abstract Background The interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS. Methods We conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample. Results Here we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%–53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet. Conclusions Our findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS.

Abstract Alzheimer’s disease (AD) is the most common cause of dementia characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation. Naringenin (NRG), a natural flavonoid widely present in citrus fruits, has been reported can penetrate the blood-brain barrier and exert anti-inflammatory effects in the central nervous system. Here, we investigate the protective effects of long-term NRG treatment on AD. The novel object recognition test and Morris water maze test reveal that NRG treatment can improve the learning and memory ability of APP/PS1 mice. Besides, we find that NRG can significantly reduce Aβ deposition, microglial and astrocytic activation, and pro-inflammatory cytokine levels in APP/PS1 mice. Results further show that NRG effectively decreases pro-inflammatory cytokines in LPS/Aβ-stimulated BV2 cells. Lastly, the molecular mechanistic study reveals that NRG attenuates neuroinflammatory responses via inhibition of the MAPK signaling pathway in vivo and in vitro. Overall, NRG may emerge as a promising compound for the prevention and treatment of AD.

Abstract C-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki–Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp 2)-C(sp), C(sp 2)-C(sp 2 ), and C(sp 2)-C(sp 3) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products.

Background: Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of recurrence. This study aimed to retrospectively analyze the outcomes of patients treated with hemithyroidectomy (HT) in PTC patients with an exclusive RLN invasion who could not tolerate staged surgery, did not wish to undergo another operation, or had other reasons. Methods: A retrospective review was conducted on 163 patients with PTC and exclusive RLN involvement at our institution between 2013 and 2019. Patients were divided into a total thyroidectomy (TT) group and HT group. The clinicopathologic factors and prognostic outcomes were compared between the two groups. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: gender, age, tumor size, multifocality, central lymph node metastasis (CLNM), and RLN resection. The Kaplan–Meier method was used for a comparison of recurrence outcomes. Results: In the baseline data of the 163 PTC patients, tumor size (p < 0.001), multifocality (p = 0.011), CLNM (p < 0.001), and RLN resection (p < 0.008) in the TT and HT groups differed significantly, whereas age and gender did not differ between the two groups. The TT group reported significantly higher temporary and permanent hypoparathyroidism than the HT group (p < 0.001 and p = 0.042, respectively). With 72-month median follow-up, 11 (6.7%) patients developed recurrence. After propensity score matching, 24 patients with HT and 43 patients with TT were included. Recurrence-free survival (RFS) in the matched samples showed no difference between the TT and HT groups (p = 0.092). Conclusion: Our results indicate that HT may be a feasible treatment for PTC patients with exclusive RLN involvement in specific circumstances without significantly increasing the risk of recurrence. Performing a thorough preoperative examination is crucial to exclude multifocal tumors and lymph node metastasis before undergoing HT.

Abstract The aim of this study was to assess the correlation between gut microbial taxonomy and various ovarian responses to controlled ovarian stimulation. A total of 22 IVF cycles with a follicle-to-oocyte index (FOI)

BackgroundGastric cancer (GC) remains a malignancy with high incidence and mortality rates worldwide. Although branched-chain amino acids (BCAAs) play a crucial role in various physiological and pathological processes, their specific relationship with risk of GC remains unclear.MethodsWe conducted a large-scale prospective cohort from UK Biobank database. We evaluated the relationship between BCAA levels and risk of GC using Cox regression, Kaplan–Meier survival curves, the accelerated failure time (AFT) model, and restricted cubic spline (RCS) analysis.ResultsDuring the follow-up of 12 years, 247,753 participants were included in the study. And the Cox regression analysis revealed that higher levels of isoleucine (HR = 0.65, 95% CI 0.48–0.89; p = 0.007), leucine (HR = 0.57, 95% CI 0.42–0.79; p

The relationship between wetland water level changes and plant community has been a research hotspot. However, the gradient changes and critical influencing factors of plateau lakeshore plants and soils during wet-dry alternation remain unclear. Here, we studied the variations in plants and soils along the Erhai lakeshore across three elevation ranges (1965.0-1965.3m, 1965.3-1965.6m, and 1965.6-1966.4m) during flooding and drought years. Our research aimed to elucidate the interrelationships and mechanisms among hydrology, soil properties, and plant dynamics. The results showed that (1) In drought years, the Shannon-Wiener index of plants significantly decreased across the three elevation ranges, and other plant diversity indices, biomass, and coverage also decreased to varying degrees; (2) except for soil pH, soil water (SW) and nutrient content decreased to varying degrees in the drought year; (3) SW was the primary factor influencing plant biomass, coverage, and diversity in the 1965.0-1965.3m and 1965.3-1965.6m ranges; nitrate nitrogen, C/N ratio, total phosphorus were the primary factors in the 1965.6-1966.4m ranges. The results of structural equation modeling revealed a significant and strong correlation between SW and plant biomass, coverage, and soil pH. This suggests that changes in SW directly impacted plant biomass accumulation, subsequently affecting coverage, and also played a role in regulating soil pH. This study identified the effects of hydrological inter-annual changes on plant communities and highlighted SW as a crucial driver. The strategies proposed in the results protect and improve the diversity and stability of lake ecosystems in Lake Erhai and other similar lakes.

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy involving approximately 80 pathogenic genes. Whole-exome sequencing (WES) and confirmatory Sanger sequencing analysis was applied to identify the disease-causing mutations in a Chinese patient with lower limb weakness. We present an 18-year-old male with a 2.5-year history of progressive lower limb weakness and an unsteady gait. Upon admission, a physical examination revealed hands tremulousness, bilateral calf muscle wasting and weakness, pes cavus, and elevated serum creatine kinase (CK) levels. Electromyography demonstrated axonal neuropathy affecting both upper and lower limbs. A de novo heterozygous missense mutation was identified in the MORC2 gene, NM_001303256.3: c.1199A>G, NP_001290186.1: p.Gln400Arg. Consequently, these clinical and genetic findings suggested a diagnosis of hereditary peripheral neuropathy, CMT type 2Z. Oral mecobalamin and coenzyme Q10 was initiated as subsequent treatment. Our study firstly reports the MORC2 c.1199A>G mutation occurring de novo, highlighting its causal association with CMT2Z, and prompting its reclassification as likely pathogenic. Oral mecobalamin and coenzyme Q10 might be a potential treatment approach for early-stage CMT2Z. We recommend genetic testing for CMT patients to identify the genetic etiology, thereby improving clinical management and facilitating genetic counseling.

The minimum fire extinguishing concentration is a key index for the development of next generation chemical clean fire extinguishing gases, which is usually got by the cup-burner. The fire suppression performance of low concentration of chemical gas is hard to be understood by the available methods. In this work, the fundamental acknowledgement of steady flame surface attacking mechanism by halon functional group is newly discussed by conducting a series of bench scale tests with a cylindrical channel under a varied fluorinated gases. The characteristics of flame propagation under differentiated air atmosphere environmental conditions is obtained. The influence of fluorine-containing gas flow rate on flame propagation speed is clarified. A dimensionless relationship including atomic radius, bond length, polarization degree, molar mass and molar volume are proposed to describe the influence of low concentration of fluorine-containing gas on flame propagation speed. It provides an insight for the understanding of the flame inhibition performance of low concentration halogenated gas.

BackgroundCardiopulmonary bypass (CPB) triggers a strong inflammatory response in cardiovascular surgery patients during the perioperative period. This article mainly focuses on the perioperative application of novel inflammatory biomarkers in cardiovascular surgeries involving CPB.MethodsPatients were divided into a CPB group and a non-CPB group according to whether they underwent CPB during cardiovascular surgery. Novel inflammatory biomarkers and clinical results were recorded. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), platelet × neutrophil/lymphocyte ratio (SII), and monocyte × platelet × neutrophil/lymphocyte ratio (PIV) were calculated. The primary outcomes were perioperative prognosis between the CPB and non-CPB groups. The secondary outcomes included perioperative alterations of novel inflammatory biomarkers in the CPB group and predictive values of novel inflammatory biomarkers for postoperative infection and acute kidney injury.ResultsA total of 332 patients were initially included in the study. Before propensity score matching (PSM), there were 96 patients in the CPB group and 236 patients in the non-CPB group. After PSM, both groups included 58 patients each. Compared with the non-CPB group, the CPB group had a higher proportion of intraoperative transfusion of blood products (63.79% vs. 6.90%, P

Abstract Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.

Abstract Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Abstract Background Appendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer’s disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses. Methods A two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF). Results The present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89–0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85–0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77–0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73–0.89; P

Abstract Background Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10–20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. Methods Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. Results Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58–0.72), specificity as 0.71 (95% CI 0.57–0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66–0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35–3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35–0.69), and the diagnostic odds ratio was 5 (95% CI 2–10). Conclusion CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

Abstract Crystalline white organic light-emitting diodes (C-WOLEDs) are promising candidates for lighting and display applications. It is urgently necessary, however, to develop energy-saving and high-efficiency C-WOLEDs that have stable and powerful emission to meet commercial demands. Here, we report a crystalline host matrix (CHM) with embedded nanoaggregates (NA) structure for developing high-performance C-WOLEDs by employing a thermally activated delayed fluorescence (TADF) material and orange phosphorescent dopants (Phos.-D). The CHM-TADFNA-D WOLED exhibit a remarkable EQE of 12.8%, which is the highest performance WOLEDs based on crystalline materials. The device has a quick formation of excitons and a well-designed energy transfer process, and possesses a fast ramping of luminance and current density. Compared to recently reported high-performance WOLEDs based on amorphous material route, the C-WOLED achieves a low series-resistance Joule-heat loss ratio and an enhanced photon output, demonstrating its significant potential in developing the next-generation WOLEDs.