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Leaves are the main organ for photosynthesis and organic synthesis in cotton. Leaf shape has important effects on photosynthetic efficiency and canopy formation, thereby affecting cotton yield. Previous studies have shown that LMI1 (LATE MERISTEM IDENTITY1) is the main gene regulating leaf shape. In this study, the LMI1 gene was inserted into the 35S promoter expression vector, and cotton plants overexpressing LMI1 (OE) were obtained through genetic transformation. Statistical analysis of the biological traits of the T1 and T2 populations showed that compared to the wild type (WT), OE plants had significantly larger leaves, thicker stems and significantly greater dry weight. Furthermore, plant sections of the main vein and petiole showed that the numbers of cells in those tissues of OE plants were significantly greater. In addition, RNA-seq analysis revealed the differential expression of genes related to gibberellin synthesis and NAC gene family (genes containing the NAC domain) between the OE and WT plants, suggesting that LMI1 is involved in secondary wall formation and cell proliferation, which promotes stem thickening. Moreover, Gene Ontology (GO) analysis revealed enrichment in the terms of calcium ion binding, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment in the terms of fatty acid degradation, phosphatidylinositol signal transduction system, and cAMP (cyclic adenosine monophosphate) signal pathway. These results suggested that LMI1 OE plants are responsive to gibberellin hormone signals, and have altered messenger signals (cAMP, Ca2+) which amplify this function, to promote stronger aboveground vegetative growth. This study found the LMI1 greatly increased the vegetative growth in cotton, which is the basic requirement for higher yield.

Abstract Porcine circoviruses, particularly porcine circovirus type 2 (PCV2) and porcine circovirus type 3 (PCV3), significantly impact the global pig industry due to their high prevalence and pathogenicity. Conversely, porcine circovirus type 1 (PCV1) and porcine circovirus type 4 (PCV4) currently have low positivity rates. This study aimed to characterize the distribution and epidemiology of porcine circoviruses in Xinjiang, while also analyzing the genetic diversity and evolution of PCV2 and PCV3, which pose the greatest threats to the industry. In this study, we collected blood and tissue samples from 453 deceased pigs across eight regions in Xinjiang Province from 2022 to 2024. We utilized real-time PCR to detect the presence of PCV1, PCV2, PCV3, and PCV4. The positive rates were 15%, 71%, 25%, and 17%, respectively. Genetic analysis showed 9 PCV2 sequences and 12 PCV3 sequences. The capsid protein of PCV2 showed significant variability. In contrast, the amino acid sequences of capsid in PCV3 were relatively stable. Moreover, we predicted antigenic epitopes for PCV3 capsid using IEDB and ElliPro. The findings from this study provide valuable epidemiological data on PCV coinfection in the Xinjiang region and enhance the understanding of virus diversity nationwide. This research may serve as an important reference for the development of strategies to prevent and control porcine circovirus infections.

To address the requirements for safety enhancement, weight reduction, and emission reduction, a novel transformation-induced plasticity-assisted bainitic ferrite (TBF) steel was processed by involving a pre-quenching (PQ) process. This steel was designed with varying PQ temperatures to achieve different fractions of intercritical ferrite and bainite, and its influence on mechanical properties of TBF steels was thoroughly investigated through tensile tests and hole expansion tests. The results demonstrated that the introduction of high-temperature PQ treatment before heat treatment can dramatically accelerate the formation of austenite during the secondary annealing process, thereby facilitating a more sufficient bainitic transformation in the subsequent isothermal process. With the increase of PQ temperature from 750 to 900 °C, abundant intercritical ferrite was replaced by lathy bainite. In comparison with conventional specimens, the high-temperature PQ treatment could reduce the fraction of intercritical ferrite and martensite-austenite (M-A) islands, in favor of delaying the initiation of microvoid and microcrack and improving local formability. In summary, the P-900 specimen exhibited optimal comprehensive mechanical properties, with the highest yield strength of 657 MPa, ultimate tensile strength of 1081 MPa, elongation of 28.7%, and hole expansion ratio of 35.1%.

Abstract Culter alburnus is extensively distributed in various rivers and lakes across China. As a widely adaptive fish species, it has significant economic values and special ecological roles. To meet research demands and provide better genomic resources, in this research, a chromosome-level genome assembly was constructed using HiFi long-reads and Hi-C sequencing data. Compared with the published versions, our genome assembly is of higher quality with only 31 gaps and closer to its true structure and sequence. The genome size was 1.052 Gb, with a contig N50 of 32.92 Mb and a scaffold N50 of 43.09 Mb. 55 contigs were anchored to 24 chromosomes on the basis of Hi-C data. A total of 598.23 Mb of repetitive sequences were annotated and 28,228 protein-coding genes were predicted. Additionally, BUSCO assessment indicated assembly and annotation scores of 98.3% and 99.2%, respectively. This high-quality genome will provide scientific support for excavating the species characteristics of C. alburnus and exploring its molecular mechanisms in response to environmental changes and stress.

Abstract Paternal genome elimination (PGE) is an intriguing but poorly understood reproductive strategy in which females are typically diploid, but males lose paternal genomes. Paternal genome heterochromatin (PGH) occurs in arthropods with germline PGE, such as the mealybug, coffee borer beetles, and booklice. Here, we present evidence that PGH initially occurs during early embryo development at around 15 h post-mating (hpm) in the cotton mealybug, Phenacoccus solenopsis Tinsley. Transcriptome analysis followed by qPCR validation indicated that six histone lysine methyltransferase (KMT) genes are predominantly expressed in adult females. We knocked down these five genes through dsRNA microinjection. We found that downregulation of two KMT genes, PsEZH2-X1 and PsEHMT1, resulted in a decrease of heterochromatin-related methylations, including H3K27me1, H3K27me3, and H3K9me3 in the ovaries, fewer PGH male embryos, and reduced male offspring. For further confirmation, we obtained two strains of transgenic tobacco highly expressing dsRNA targeting PsEZH2-X1 and PsEHMT1, respectively. Similarly, fewer PGH embryos and fewer male offspring were observed when feeding on these transgenic tobacco plants. Overall, we present evidence that PsEZH2-X1 and PsEHMT1 have essential roles in male embryo survival by regulating PGH formation in cotton mealybugs.

Abstract Background Methyl methacrylate (MMA) is a key precursor of polymethyl methacrylate, extensively used as a transparent thermoplastic in various industries. Conventional MMA production poses health and environmental risks; hence, citramalate serves as an alternative bacterial compound precursor for MMA production. The highest citramalate titer was previously achieved by Escherichia coli BW25113. However, studies on further improving citramalate production through metabolic engineering are limited, and phage contamination is a persistent problem in E. coli fermentation. Results This study aimed to construct a phage-resistant E. coli BW25113 strain capable of producing high citramalate titers from glucose. First, promoters and heterologous cimA genes were screened, and an effective biosynthetic pathway for citramalate was established by overexpressing MjcimA3.7, a mutated cimA gene from Methanococcus jannaschii, regulated by the BBa_J23100 promoter in E. coli. Subsequently, a phage-resistant E. coli strain was engineered by integrating the Ssp defense system into the genome and mutating key components of the phage infection cycle. Then, the strain was engineered to include the non-oxidative glycolysis pathway while removing the acetate synthesis pathway to enhance the supply of acetyl-CoA. Furthermore, glucose utilization by the strain improved, thereby increasing citramalate production. Ultimately, 110.2 g/L of citramalate was obtained after 80 h fed-batch fermentation. The citramalate yield from glucose and productivity were 0.4 g/g glucose and 1.4 g/(L·h), respectively. Conclusion This is the highest reported citramalate titer and productivity in E. coli without the addition of expensive yeast extract and additional induction in fed-bath fermentation, emphasizing its potential for practical applications in producing citramalate and its derivatives.

Abstract Background The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them. Methods This study included 1418 highly myopic eyes from 720 participants aged 18 − 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm. Results DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P

Abstract Glycyrrhiza stems and leaves (GSL) are waste products of Glycyrrhiza; however, it has been considered a potential source of flavonoid compounds. In this study, GSL was processed by solid-state fermentation (SSF) to improve the flavonoid content and antioxidant activity. Firstly, a near-infrared (NIR) prediction model for flavonoid content in fermented Glycyrrhiza stems and leaves (FGSL) was established. Next, the effects of SSF on the antioxidant activity and metabolite profile of GSL were investigated. Finally, the possible mechanism of ferment release of flavonoids was explored based on enzyme activity, thermogravimetric analysis, and FTIR spectroscopy. The results revealed that NIR spectroscopy can efficiently analyze flavonoid contents in GSL, with predicted determination coefficient (Rp2) and root mean square error (RMSEP) of 0.9874 and 0.125, respectively. SSF significantly increased the levels of flavonoids, and enhanced the scavenging activities of DPPH radical and hydroxyl radical and reducing power of FGSL. Widely targeted metabolomic analysis showed the detection of 461 differential metabolites were identified after SSF, with 141 metabolites remarkably up-regulated and 320 metabolites of FGSL down-regulated during fermentation. The main types of differential metabolites were phenolic acids and flavonoids, and the destruction of cellulose by SFF was crucial to the release of flavonoids. In conclusion, our study revealed that SSF remarkably improved the phytochemical components of FGSL by increasing enzyme activity and destroying cellulose structure, thereby contributing to the enhancement of antioxidant activity. This study provided a scientific basis for the production of high-value flavonoids from plant materials and offered a novel approach to elucidate the release and conversion of flavonoids. Graphical Abstract

Abstract Background To investigate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) semi-quantitative parameters, including the lesion diameter, maximum standardized uptake value (SUVmax), maximum standardized uptake value corrected for lean body mass (SULmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG), for classifying hepatic echinococcosis. Methods In total, 20 patients with 36 hepatic echinococcosis lesions were included in the study. Overall, these lesions were categorized as hepatic cystic echinococcosis (HCE) or hepatic alveolar echinococcosis (HAE) according to the pathological results. Multiple semi-parameters including the maximum diameter, SUVmax, SULmax, MLV, and TLG were measured to classify HCE and HAE compared with the pathological results. The receiver operator characteristic curve and area under the curve (AUC) of each quantitative parameter were calculated. The Mann–Whitney U test was used to compare data between the two groups. Results In total, 12 cystic lesions and 24 alveolar lesions were identified after surgery. There were significant differences in SUV max, SUL max, MLV, and TLG between the HAE and HCE groups (Z = − 4.70, − 4.77, − 3.36, and − 4.23, respectively, all P 0.05). The best cutoffs of SUV max, SUL max, MLV, and TLG for the differential diagnosis of HAE and HCE were 2.09, 2.67, 27.12, and 18.79, respectively. The AUCs of the four parameters were 0.99, 0.99, 0.85, and 0.94, respectively. The sensitivities were 91.7%, 87.5%, 66.7%, and 85.6%, respectively, and the specificities were 90.1%, 91.7%, 83.3%, and 90.9%, respectively. Conclusion 18F-FDG PET/CT semi-quantitative parameters had significant clinical value in the diagnosis and pathological classification of hepatic echinococcosis and evaluation of clinical treatment.

Abstract Chenopodium album L. (CAL) has many bioactive compounds and pharmacological activities. Fermentation is the preferred modification method of releasing target bioactive. We prepared two crude polysaccharides: SLC (the polysaccharide from the unfermented stem and leaves of CAL) and FSLC (the polysaccharide from the fermented stem and leaves of CAL). In vitro antioxidant and composition of SLC and FSLC were compared, and the effects of FSLC on antioxidant activity in the IPEC-J2 cells model and development-promoting activity in the zebrafish model were evaluated. The results revealed that FSLC possesses stronger DPPH, hydroxyl radical scavenging, and reducing power than SLC. The levels of total polysaccharide, polyphenol, and flavonoid, as well as the molar ratio of glucuronic acid increased in FSLC. Compared with SLC, the relative contents of protocatechuic acid, protocatechualdehyde, gentisic acid, vanillic acid, p-coumaric acid, quercetin, ferulic acid methyl ester, hispidulin, diosmetin, cinnamic acid, isorhamnetin, syringic acid and kaempferol in FSLC increased. In IPEC-J2 cells, antioxidant enzyme activities and GSH levels were significantly increased, while the MDA level was reduced by treatment with 0.25 mg/mL FSLC. In the zebrafish model, treatment with 25 ~ 300 μg/mL of FSLC had no harmful impact on the morphology and viability of embryos at 12 ~72 hpf. At 48 and 60 hpf, treatment with 100 ~ 300 μg/mL FSLC increased the hatching rate of embryos. At 72hpf, treatment with 100 ~ 300 μg/mL FSLC could relieve morphological abnormalities caused by LPS in zebrafish and improve the hatching rate of embryos. Together, these results provide useful information on the potential for applying polysaccharides from the stems and leaves of CAL as natural feed additives to exert its antioxidant and development-promoting functions. Graphical Abstract

Abstract Background Step width is a spatial variable in the frontal plane, defined as the mediolateral distance between the heel (forefoot during sprinting) of bilateral feet at initial contact. Variations in step width may impact the lower limb biomechanics. This systematic review aimed to synthesize the published findings to determine the influence of acute changes in step width on locomotion biomechanics and provide implications for injury prevention and enhanced sports performance. Methods Literature was identified, selected, and appraised in accordance with the methods of a systematic review. Four electronic databases (Web of Science, MEDLINE via PubMed, Scopus, and ScienceDirect) were searched up until May 2023 with the development of inclusion criteria based on the PICO model. Study quality was assessed using the Downs and Black checklist and the measured parameters were summarized. Results Twenty-three articles and 399 participants were included in the systematic review. The average quality score of the 23 studies included was 9.39 (out of 14). Step width changed the kinematics and kinetics in the sagittal, frontal, and transverse planes of the lower limb, such as peak rearfoot eversion angle and moment, peak hip adduction angle and moment, knee flexion moment, peak knee internal rotation angle, as well as knee external rotation moment. Alteration of step width has the potential to change the stability and posture during locomotion, and evidence exists for the immediate biomechanical effects of variations in step width to alter proximal kinematics and cues to impact loading variables. Conclusion Short-term changes in step width during walking, running, and sprinting influenced multiple lower extremity biomechanics. Narrower step width may result in poor balance and higher impact loading on the lower extremities during walking and running and may limit an athlete’s sprint performance. Increasing step width may be beneficial for injury rehabilitation, i.e., for patients with patellofemoral pain syndrome, iliotibial band syndrome or tibial bone stress injury. Wider steps increase the supporting base and typically enhance balance control, which in turn could reduce the risks of falling during daily activities. Altering the step width is thus proposed as a simple and non-invasive treatment method in clinical practice.

Abstract Background Depression is a common mental disorder with a much higher prevalence in women than in men. Although there has been a gradual increase in research on the association between reproductive health and depression, there is still some inconsistency in the evidence of the relationship between pregnancy loss and depression. This study aimed to investigate the relationship between pregnancy loss and depressive symptoms. Methods We analyzed data from the 2007–2020 National Health and Nutrition Examination Survey (NHANES), which included female participants aged 20 to 80 years. Pregnancy loss was determined based on participants’ self-reported number of pregnancies and pregnancy outcomes. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Multivariate logistic regression, smoothed curve fitting, and generalized additive modeling were used to examine the association between pregnancy loss and depression. We also performed sensitivity analyses and subgroup analyses to verify the robustness and specificity of the findings. Results A total of 12,873 female participants were included in our study, of which 1,595 (12.39%) were categorized as depressed. Multivariate logistic regression results indicated that experiencing a pregnancy loss increased the risk of prevalence of depression in women (for 1 loss: OR = 1.31, 95% CI 1.15,1.50; for 2 or more losses: OR = 1.58, 95% CI 1.38, 1.81). When sensitivity analyses were performed, an association between pregnancy loss and depression was found in both multivariate linear regressions with PHQ-9 scores as a continuous variable and multivariate logistic regressions with a threshold of 5 PHQ-9 scores. The association between pregnancy loss and depression remained stable across subgroups. Conclusion Pregnancy loss correlated with elevated PHQ-9 scores and a heightened risk of depression in adult women across the United States. Focusing on the incidence of adverse pregnancy events in the female population may help prevent or early recognize the onset of depression.

AlCoCrFeMo0.05Ni2 high-entropy alloy (HEA) has great potential for high-temperature applications. However, its FCC matrix will decompose during annealing, which seriously limits its high-temperature applications. Here, the lattice distortion, Gibbs free energy change, phonon spectra, density of states, and bond length distribution of the FCC matrix were calculated by first-principles calculations. The findings indicate that the primary barrier to the formation of a single homogeneous solid solution in the alloy is more closely associated with Gibbs free energy rather than the degree of lattice distortion. The vibration frequency of Al is not in sync with the overall structure, making it prone to desolvation at elevated temperatures. Furthermore, an analysis of bond lengths reveals that the Al–Ni bond length is significantly shorter than the theoretical value, facilitating the formation of a (Ni, Al)-rich phase. In contrast, the longer bond lengths of Al–Cr and Al–Mo facilitate the detachment of Cr and Mo from the (Ni, Al)-rich phase, resulting in the formation of (Cr, Mo)-rich phase. This in-depth investigation sheds light on the phase decomposition mechanism of high-entropy alloys, offering valuable insights for future research in this field.

Abstract In traditional Chinese rockery stacking, the peculiarity of the materials and reliance on the personal experience of artisans during the construction process make it challenging to scientifically quantify the structural stress and use scientific methods to ensure the stability of rockery structures and the safety of the construction process. Therefore, the intangible cultural heritage of rockery stacking technology faces the problem of scientific structural inspection and risk estimation during the construction process. This study uses a finite element analysis to evaluate the structural stress of the rockery-stacking site to contribute to the sustainable development and protection of this intangible cultural heritage. After establishing a three-dimensional digital model, mechanical calculations are carried out for the overall structure of the rockery and its different parts. The analysis identifies three types of structural factors in artificial rockeries: contact, structure, and load. It also effectively and intuitively identifies the weak points in the rockery structures and provides an assessment of risks, offering valuable insights for risk prevention and for the construction and maintenance of the structures. These results contribute to the structural safety inspection of traditional Chinese rockery stacking and the structural evaluation of existing rockery heritage.

Abstract Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockades, have been approved for unresectable hepatocellular carcinoma (HCC). However, high resistance rates still limit their efficacy, highlighting the urgent need to understand the underlying mechanisms and develop strategies for overcoming the resistance. In this study, tankyrasel binding protein 1 (TNKS1BP1) was found to interact with tripartite motif containing 21 (TRIM21) and mediated the ubiquitination of CCR4-NOT transcription complex subunit 4 (CNOT4) at the K239 residue via K48 and K6 linkage, which was essential for its tumorigenesis function. Autophagy and lipid reprogramming were identified as two possible mechanisms underlying the pro-tumor effect of TNKS1BP1. Upregulated TNKS1BP1 inhibited autophagy while induced lipid accumulation by inhibiting the JAK2/STAT3 pathway upon the degradation of CNOT4 in HCC. Importantly, knocking down TNKS1BP1 synergized with anti-PD-L1 treatment by upregulating PD-L1 expression on tumor cells via the JAK2/STAT3 pathway, and remodeling the tumor microenvironment by increasing infiltration of tumor-infiltrating lymphocytes as well as augmenting the effect of cytotoxic T lymphocytes. In conclusion, this study identified TNKS1BP1 as a predictive biomarker for patient prognosis and a promising therapeutic target to overcome anti-PD-L1 resistance in HCC.

Abstract Accumulating evidence supports the concept that DNA damage response targeted therapies can improve antitumor immune response by increasing the immunogenicity of tumor cells and improving the tumor immune microenvironment. Ataxia telangiectasia mutated (ATM) is a core component of the DNA repair system. Although the ATM gene has a significant mutation rate in many human cancers, including colorectal, prostate, lung, and breast, it remains understudied compared with other DDR-involved molecules such as PARP and ATR. Here, we found that either gene knockout or drug intervention, ATM inhibition activated the cGAS/STING pathway and augmented MHC class I in CRC cells, and these effects could be amplified by radiation. Furthermore, we found that MHC class I upregulation induced by ATM inhibition is dependent on the activation of the NFκB/IRF1/NLRC5 pathway and independent of STING. Animal experiments have shown increasing infiltration and cytotoxic function of T cells and better survival in ATM-deficient tumors. This work indicated that ATM nonsense mutation predicted the clinical benefits of radiotherapy combined with immune checkpoint blockade for patients with CRC. It also provides a molecular mechanism rationale for ATM-targeted agents for patients with CRC.

Abstract Objectives The geographical environment and military activities in the plateau area pose potential work-related stressors for military personnel, leading to burnout which is an external manifestation of internal energy exhaustion caused by stress. Without countermeasures, this can result in serious military problems. This study aims to examine the association between burnout and occupational stressors among military personnel stationed in the plateau area of China. Material and methods A stratified randomized cluster sampling survey was conducted among 2026 military personnel from 6 different troops stationed in the plateau area of China. The Chinese Maslach Burnout Inventory-General Survey(MBI-GS in Chinese) was administered from March 2022 to December 2023, and data were analyzed using SPSS version 25. Results A total of 2026 military personnel participated in the survey. The mean overall burnout score was 3.37 ± 0.73, with emotional exhaustion at 2.69 ± 0.89, depersonalization at 3.58 ± 0.92, and professional achievement at 3.81 ± 0.85 levels respectively reported by participants on average scale scores ranging from zero to six. Severe level of burnout was reported by 43.2% of participants while medium level of burnout was reported by 54 .3%. Age, education level, length of military service, and household income were identified as important factors influencing burnout. Conclusion This study highlights a relatively high prevalence of burnout among military personnel stationed in plateau areas necessitating attention towards their occupational health particularly focusing on working hours and economic aspects so as to formulate effective policies and implement intervention measures that strengthen career development for soldiers deployed in such regions.

Abstract Objective To investigate the characteristics of eye movement in children with anisometropic amblyopia, and to compare those characteristics with eye movement in a control group. Methods 31 children in the anisometropic amblyopia group (31 amblyopic eyes in group A, 31 contralateral eyes in group B) and 24 children in the control group (48 eyes in group C). Group A was subdivided into groups Aa (severe amblyopia) and Ab (mild-moderate amblyopia). The overall age range was 6–12 years (mean, 7.83 ± 1.79 years). All children underwent ophthalmic examinations; eye movement parameters including saccade latency and amplitude were evaluated using an Eyelink1000 eye tracker. Data Viewer and MATLAB software were used for data analysis. Results Mean and maximum saccade latencies, as well as mean and maximum saccade amplitudes, were significantly greater in group A than in groups B and C before and after treatment (P

Abstract Behçet’s disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein–protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723–0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

Abstract A climatology of stratospheric gravity waves (SGWs) induced by tropical cyclones (TC-SGWs) is necessary for stratospheric aviation safety and accurate numerical weather prediction. Few previous works have characterized the climatology of TC-SGWs, and the relative importance of the source and background wind for TC-SGWs has not been clearly established. Here we present the distribution of TC-SGWs formed over the northwest Pacific Ocean based on 30 years of ERA5 reanalysis data. Using explainable artificial intelligence, we found the background wind in the lower stratosphere to be more important than TCs in controlling the distribution pattern of TC-SGWs. The background wind shear can influence the direction of TC-SGW propagation by refraction and filtering, which influences the distribution pattern of the TC-SGWs. The TC intensity only influences the TC-SGW intensity. Our results provide information on TC-SGW hotspots and suggest the importance of the background wind shear.

Objective For precise and minimally invasive treatment of ossification of the posterior longitudinal ligament of the cervical spine, the lifting segment is minimized, anterior controllable antedisplacement and fusion (ACAF) was refined and improved. In addition, the development of appropriate surgical procedures for the ossification of each segment was rarely reported. Therefore, this study aimed to compare the efficacy and safety of hybrid anterior controlled antedisplacement fusion (Hybrid ACAF) with laminoplasty for multilevel ossification of the posterior longitudinal ligament (OPLL). Methods Between May 2018 and May 2021, 70 patients with multilevel OPLL were divided into a hybrid ACAF group and a laminoplasty group according to surgical methods. All patients were followed up for at least 1 year. Japanese Orthopaedic Association (JOA) score and recovery rate (JOARR), (VAS, NDI) score and C2–C7 Cobb angle, the sagittal vertical axis of the neck (SVA), and complications (cerebrospinal fluid leakage, C5 paralysis, etc.) were compared between the two groups by t test or non‐parametric test. Results The operation time of hybrid ACAF was longer. C5 paralysis and axial pain were more common in the laminoplasty group, while dysphagia and hoarseness were more common in the hybrid ACAF group. At the last follow‐up, the hybrid ACAF group had better recovery and maintenance of cervical lordosis and sagittal plane balance and a higher JOA score and recovery rate than the laminoplasty group. Conclusions Hybrid ACAF can reduce the number of vertebral bodies and expand the decompression range, which is safe, effective, and tailored to local conditions. Compared with laminoplasty, hybrid ACAF is a precise alternative for patients with OPLL.

Abstract Background EEG reactivity is a predictor for neurological outcome in comatose patients after cardiac arrest (CA); however, its application is limited by variability in stimulus types and visual assessment. We aimed to evaluate the prognostic value of the quantitative analysis of EEG reactivity induced by standardized electrical stimulation and for early prognostication in this population. Methods This prospective observational study recruited post-CA comatose patients in Xuanwu Hospital, Capital Medical University (Beijing, China) between January 2016 and June 2023. EEG reactivity to electrical or traditional pain stimulation was randomly performed via visual and quantitative analysis. Neurological outcome within 6 months was dichotomized as good (Cerebral Performance Categories, CPC 1–2) or poor (CPC 3–5). Results Fifty-eight post-CA comatose patients were admitted, and 52 patients were included in the final analysis, of which 19 (36.5%) had good outcomes. EEG reactivity induced with the electrical stimulation had superior performance to the traditional pain stimulation for good outcome prediction (quantitative analysis: AUC 0.932 vs. 0.849, p = 0.048). When using the electrical stimulation, the AUC of EEG reactivity to predict good outcome by visual analysis was 0.838, increasing to 0.932 by quantitative analysis (p = 0.039). Comparing to the traditional pain stimulation by visual analysis, the AUC of EEG reactivity for good prognostication by the electrical stimulation with quantitative analysis was significantly improved (0.932 vs. 0.770, p = 0.004). Conclusions EEG reactivity induced by the standardized electrical stimulation in combination with quantitative analysis is a promising formula for post-CA comatose patients, with increased predictive accuracy.

Abstract Tree-based machine learning algorithms, such as random forest, have emerged as effective tools for estimating fine particulate matter (PM2.5) from satellite observations. However, they typically have unchanged model structures and configurations over time and space, and thus may not fully capture the spatiotemporal variations in the relationship between PM2.5 and predictors, resulting in limited accuracy. Here, we propose geographically and temporally weighted tree-based models (GTW-Tree) for remote sensing of surface PM2.5. Unlike traditional tree-based models, GTW-Tree models vary by time and space to simulate the variability in PM2.5 estimation, and they can output variable importance for every location for the deeper understanding of PM2.5 determinants. Experiments in China demonstrate that GTW-Tree models significantly outperform the conventional tree-based models with predictive error reduced by >21%. The GTW-Tree-derived time-location-specific variable importance reveals spatiotemporally varying impacts of predictors on PM2.5. Aerosol optical depth (AOD) contributes largely to PM2.5 estimation, particularly in central China. The proposed models are valuable for spatiotemporal modeling and interpretation of PM2.5 and other various fields of environmental remote sensing.

Abstract Over the years, obesity has become more commonplace and has had a substantial impact on several medical specialties, including reproductive medicine. The potential correlation between the visceral adiposity index (VAI) and infertility has yet to be determined. Women between the ages of 18 and 45 were included in this cross-sectional study, which was conducted as part of the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2020. Three tertiles were used to group VAI levels. Subgroup analysis and weighted binary logistic regression were employed to investigate the independent relationship between VAI and infertility. Smooth curve fitting was used to explore nonlinear relationships. This cross-sectional study followed the criteria of the STROBE guidelines. Of the 1231 participants, 127 were infertile women aged 18–45 years. A higher VAI was associated with a higher prevalence of infertility (OR = 1.22, 95% CI:1.03–1.45), which remained consistent across all subgroups (p > 0.05 for all interactions). We demonstrated a positive nonlinear association between VAI and infertility using a smooth curve fit. A higher visceral adiposity index level is positively correlated with a higher incidence of infertility among women in the United States. Women who are infertile can be identified using the visceral obesity index, and controlling visceral obesity may help lower the chances of becoming infertile.

Abstract Liver cancer is one of the most common malignant tumors worldwide. Although some progress has been made in the diagnosis and treatment of Hepatocellular carcinoma (HCC), the diagnosis and treatment of HCC is still facing great challenges because of the high mortality rate and poor prognosis of HCC. The purpose of this study was to explore the relationship between adhesion-regulating molecule1 (ADRM1), and liver cancer, and the relationship between prognoses. ADRM1 is highly expressed in tumors and is closely associated with the prognosis of patients with liver cancer. In our previous study, we found that ADRM1 was highly expressed in HCC and was closely related to tumor immune and immune checkpoint levels in HCC. We validated the immune expression of ADRM1 in liver cancer cells using flow cytometry. In hepatocellular carcinoma tissues, miR-891a-5p regulates ADRM1. Upregulation of miR-891a-5p upregulates ADRM1, and downregulation of miR-891a-5p downregulates ADRM1. It is suggested that ADRM1 plays a key role in the occurrence and development of hepatocellular carcinoma. This study is expected to provide new ideas for the research and development of anti-HCC drugs targeting miR-891a-5p/ADRM1. However, further trials are needed to confirm these results and explore the actual results in patients with HCC.

Abstract With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.

Abstract Background With the rapid development of perinatal medicine and neonatal resuscitation technology, neonatal mortality gradually reduces, but sepsis is still a neonatal critical illness and an important cause of death. The onset of sepsis in premature infants is insidious, and the clinical symptoms lack of specificity. The available laboratory tests exhibit limited sensitivity and specificity for diagnosis, and there is a certain degree of time lag. Therefore, it is particularly important to find a method for early detection of severe infection in premature infants. Main body Sepsis is the third leading cause of death with poor prognosis in infants. Early and accurate identification of sepsis are particularly important. Heart rate variability may present before clinical symptoms of sepsis. The study is to summarize the available data on the relationship between heart rate variability and development of sepsis in early infants. We searched six database, PubMed, Web of Science, Embase, Cochrane Library, Wanfang, and CNKI, using the following terms for our search strategy (Infants, Newborn) OR (Newborn Infant) OR (Newborn Infants) OR (Newborns) OR (Newborn) OR (Neonate) OR (Neonates) AND (Sepsis) OR (Bloodstream Infection) OR (Bloodstream Infections) OR (Pyemia) OR (Pyemias) OR (Pyohemia) OR (Pyohemias) OR (Pyaemia) OR (Pyaemias) OR (Septicemia) OR (Septicemias) OR (Blood Poisoning) OR (Blood Poisonings) OR (Severe Sepsis) OR (Sepsis, Severe) AND (Heart Rate Variability). Premature infants would experience the reduction in heart rate variability before clinical symptoms of sepsis present. Conclusion The application of heart rate variability, a noninvasive monitoring method, to the identification and diagnosis of sepsis in premature infants can enable clinicians to identify, diagnose, and treat children with sepsis early, thereby reducing the mortality of premature infants and neurological damage.

Under geological conditions, the initial generation of oil and gas in source rocks reaches saturation before being expelled and migrating, with the adsorption of hydrocarbons by kerogen being a key factor influencing oil saturation. The hydrocarbons produced by pyrolysis interact with kerogen macromolecules. Understanding the solvency and adsorption capacities of solid kerogen organic matter for liquid hydrocarbons can clarify the selective retention of hydrocarbons by source rocks and their characteristics in hydrocarbon generation and expulsion. Aromatic hydrocarbons are crucial components of petroleum hydrocarbons. Based on a three-dimensional model of kerogen, this study employed Autodock software to perform semi-flexible docking calculations between different types of aromatic hydrocarbon molecules (including benzene, polycyclic aromatic hydrocarbons, and their derivatives) and kerogen molecules of varying maturities. The Gibbs free energy required for their binding was calculated to study the characte-risticsof the interaction between aromatic hydrocarbons and kerogen. This study investigated the mechanism of kerogen adsorption of aromatic hydrocarbons at the molecular level, revealing the nature of solid and liquid organic matter interactions. When binding with kerogen of the same maturity, the larger the molecular weight of the polycyclic aromatic hydrocarbons, the greater the number of methyl groups in the compound, and the higher the degree of molecular condensation, the lower the Gibbs free energy required for binding with kerogen molecules. The interaction between aromatic hydrocarbons and kerogen molecules was influenced by three factors: the molecular mass of the aromatic hydrocarbons, the degree of molecular condensation, and the number of methyl groups in the system. After reaching the peak of hydrocarbon generation, kerogen with higher content of aromatic carbon methyl groups showed a stronger adsorption capacity for aromatic hydrocarbons. Polycyclic aromatic hydrocarbons and their derivatives with larger molecular mass and higher degrees of condensation demonstrated stronger binding abilities with kerogen. Conversely, smaller aromatic molecules with conventional connectivity exhibited weaker retention capacities in kerogen, making them more prone to hydrocarbon expulsion, migration, and accumulation into reservoirs.

Highlights The formation of peptide nanocapsules is facilitated by a gradient interface, where the differential solvent concentration drives the peptides to preferentially localize and assemble. The peptide nanocapsules, characterized by their hollow structures, demonstrated potential as carriers for targeted drug delivery.

Abstract Background Embryo implantation remains a critical barrier in assisted reproductive technologies. One of the main causes of unsuccessful embryo implantation is window of implantation (WOI) displacement, particularly in patients with recurrent implantation failure (RIF). Therefore, a reliable diagnostic tool for identifying the optimal WOI is essential. Previous data has suggested that a novel RNA-Seq-based endometrial receptivity testing (ERT) can diagnose WOI, guide personalized embryo transfer (pET), and improve pregnancy outcomes in patients with RIF compared to standard embryo transfer (sET). However, there is still a lack of evidence from randomized controlled trials (RCT) with sufficient power to determine whether pET based on ERT can increase the rate of live births as the primary outcome. Methods This trial is a prospective, single-blind, parallel-group RCT (1:1 ratio of pET versus sET). Infertile women with RIF who intend to undergo frozen-thawed embryo transfer (FET) after preimplantation genetic testing for aneuploidy (PGT-A) with the availability of at least one euploid blastocyst for transfer will be enrolled and assigned into two parallel groups randomly. Participants in the intervention group will undergo ERT and then pET based on the results of ERT, while those in the control group will undergo sET. The primary outcome is live birth rate. Discussion The findings of this study will provide evidence for the effect of pET guided by ERT on pregnancy outcomes in patients with RIF. Trial registration Chinese Clinical Trial Registry ChiCTR2100049041. Registered on 20 July 2021.

Abstract Background Oxidative stress is currently one of the main threats to animal health, and flavonoids in forage have good antioxidant activity. However, the impact of fermentation on flavonoids and their antioxidant activity in forage is still unclear. This study aims to investigate the effect of lactic acid bacteria inoculation on the biological transformation of flavonoids in alfalfa silage fermentation and its relationship with antioxidant activity. Results Compared with the raw materials, silage fermentation can increase the total flavonoid content of alfalfa. The addition of Pediococcus pentosaceus (CP115739.1) and Lactiplantibacillus plantarum (CP115741.1) can significantly increase the total flavonoid content in alfalfa silage (P

Abstract Tumor dormancy is a stage in the growth and development of malignant cells and is one of the biological characteristics of malignant cells. Complex transitions involving dormant tumor cells between quiescent and proliferative states pose challenges for tumor eradication. This paper explores the biological features and molecular mechanisms of tumor dormancy and highlights emerging therapies. The strategies discussed promise innovative clinical potential against malignant tumors. Understanding the mechanisms of dormancy can help provide valuable insights into the diagnosis and treatment of malignant tumors to advance the fight against this world problem.

Abstract Chimeric antigen receptor engineered T (CAR T) cell therapy has developed rapidly in recent years, leading to profound developments in oncology, especially for hematologic malignancies. However, given the pressure of immunosuppressive tumor microenvironments, antigen escape, and diverse other factors, its application in solid tumors is less developed. Urinary system tumors are relatively common, accounting for approximately 24% of all new cancers in the United States. CAR T cells have great potential for urinary system tumors. This review summarizes the latest developments of CAR T cell therapy in urinary system tumors, including kidney cancer, bladder cancer, and prostate cancer, and also outlines the various CAR T cell generations and their pathways and targets that have been developed thus far. Finally, the current advantages, problems, and side effects of CAR T cell therapy are discussed in depth, and potential future developments are proposed in view of current shortcomings.

Abstract Phosphorylated H2AX, known as γH2AX, forms in response to genotoxic insults in somatic cells. Despite the high abundance of H2AX in zygotes, the level of irradiation-induced γH2AX is low at this stage. Another H2A variant, TH2A, is present at a high level in zygotes and can also be phosphorylated at its carboxyl end. We constructed H2AX- or TH2A-deleted mice using CRISPR Cas9 and investigated the role of these H2A variants in the DNA damage response (DDR) of zygotes exposed to γ-ray irradiation at the G2 phase. Our results showed that compared to irradiated wild-type zygotes, irradiation significantly reduced the developmental rates to the blastocyst stage in H2AX-deleted zygotes but not in TH2A-deleted ones. Furthermore, live cell imaging revealed that the G2 checkpoint was activated in H2AX-deleted zygotes, but the duration of arrest was significantly shorter than in wild-type and TH2A-deleted zygotes. The number of micronuclei was significantly higher in H2AX-deleted embryos after the first cleavage, possibly due to the shortened cell cycle arrest of damaged embryos and, consequently, the insufficient time for DNA repair. Notably, FRAP analysis suggested the involvement of H2AX in chromatin relaxation. Moreover, phosphorylated CHK2 foci were found in irradiated wild-type zygotes but not in H2AX-deleted ones, suggesting a critical role of these foci in maintaining cell cycle arrest for DNA repair. In conclusion, H2AX, but not TH2A, is involved in the DDR of zygotes, likely by creating a relaxed chromatin structure with enhanced accessibility for DNA repair proteins and by facilitating the formation of pCHK2 foci to prevent premature cleavage.

Abstract Purpose The index composed of preoperative lymphocytes, albumin, and neutrophils (LANR), a new composite score based on inflammatory response and nutritional status, has been reported to be associated with the prognosis of multiple types of cancer, but the role of LANR in the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated. Patients and methods The data of 142 patients with PDAC who underwent radical resection in the Affiliated Hospital of Jiangnan University from January 2015 to December 2018 were retrospectively analyzed. Receiver Operating Characteristic (ROC) curves were generated to determine the optimal cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting survival. The Kaplan–Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. Results The optimal cut-off value of LANR was 18.145, and a low preoperative LANR was significantly correlated with the location of the tumor (p = 0.047). Multivariate analysis showed that tumor differentiation degree (HR:2.357, 95%CI:1.388–4.003,p = 0.002), lymph node metastasis (HR:1.755, 95%CI: 1.115–2.763, p = 0.015), TNM stage (HR:4.686, 95%CI: 2.958–7.425, p

Abstract Twisted bilayer graphene (tBLG) provides a fascinating platform for engineering flat bands and inducing correlated phenomena. By designing the stacking architecture of graphene layers, twisted multilayer graphene can exhibit different symmetries with rich tunability. For example, in twisted monolayer-bilayer graphene (tMBG) which breaks the C 2z symmetry, transport measurements reveal an asymmetric phase diagram under an out-of-plane electric field, exhibiting correlated insulating state and ferromagnetic state respectively when reversing the field direction. Revealing how the electronic structure evolves with electric field is critical for providing a better understanding of such asymmetric field-tunable properties. Here we report the experimental observation of field-tunable dichotomic electronic structure of tMBG by nanospot angle-resolved photoemission spectroscopy (NanoARPES) with operando gating. Interestingly, selective enhancement of the relative spectral weight contributions from monolayer and bilayer graphene is observed when switching the polarity of the bias voltage. Combining experimental results with theoretical calculations, the origin of such field-tunable electronic structure, resembling either tBLG or twisted double-bilayer graphene (tDBG), is attributed to the selectively enhanced contribution from different stacking graphene layers with a strong electron-hole asymmetry. Our work provides electronic structure insights for understanding the rich field-tunable physics of tMBG.

Abstract Background Cognitive impairment is highly prevalent among patients with chronic kidney disease, who face an increased risk of cognitive decline. The aim of this study was to investigate the relationship between the Geriatric Nutritional Risk Index (GNRI) and cognitive function in older individuals, both with and without chronic kidney disease (CKD). Methods In this study, we analyzed data from 2728 participants in the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Cognitive function was measured using the Consortium to Establish a Registry for the Alzheimer's Disease Word Learning subtest (CERAD W‐L), the animal fluency test (AFT), the digit symbol substitution test (DSST), and the global cognitive z‐score. The GNRI, representing whole‐body nutritional status, was calculated based on serum albumin, body weight, and ideal body weight. We employed weighted multiple linear regression analyses and subgroup analyses to assess the independent association of GNRI with cognitive function in CKD and non‐CKD populations. Smoothing techniques were used to fit curves, and interaction tests were used to assess the robustness and specificity of the findings. Results Our analyses revealed a significant positive association between higher GNRI levels and cognitive function in the older US population (for global z‐score: β = 0.01; 95% confidence interval [CI] = 0.00, 0.01). This association remained consistent across various subgroup analyses, including those for different gender groups, age groups, smoking statuses, diabetes statuses, hypertension statuses, individuals with a BMI below 25, individuals who consumed alcohol, and non‐Hispanic white individuals. Smoothed curve‐fitting analyses indicated that the GNRI was linearly related to cognitive function. No statistically significant interactions were detected among these variables. Conclusion Our findings emphasize the positive association between GNRI and cognitive health in individuals with or without CKD, especially when combined with other risk factors. Consequently, enhancing the nutritional status of the elderly may serve as a viable strategy to thwart the onset of cognitive decline.

As the third‐generation network succeeding artificial neural networks (ANNs), spiking neural networks (SNNs) offer high robustness and low energy consumption. Inspired by biological systems, the limitations of low robustness and high‐power consumption in deep reinforcement learning (DRL) are addressed by introducing SNNs. The Brain Q‐network (BrainQN) is proposed, which replaces the neurons in the classic Deep Q‐learning (DQN) algorithm with SNN neurons. BrainQN is trained using surrogate gradient learning (SGL) and ANN‐to‐SNN conversion methods. Robustness tests with input noise reveal BrainQN's superior performance, achieving an 82.14% increase in rewards under low noise and 71.74% under high noise compared to DQN. These findings highlight BrainQN's robustness and superior performance in noisy environments, supporting its application in complex scenarios. SGL‐trained BrainQN is more robust than ANN‐to‐SNN conversion under high noise. The differences in network output correlations between noisy and original inputs, along with training algorithm distinctions, explain this phenomenon. BrainQN successfully transitioned from a simulated Pong environment to a ball‐catching robot with dynamic vision sensors (DVS). On the neuromorphic chip PAICORE, it shows significant advantages in latency and power consumption compared to Jetson Xavier NX.

IntroductionVerticillium dahliae causes a serious decline in cotton yield and quality, posing a serious threat to the cotton industry. However, the mechanism of resistance to V. dahliae in cotton is still unclear, which limits the breeding of resistant cultivars.MethodsTo analyze the defense mechanisms of cotton in response to V. dahliae infection, we compared the defense responses of two upland cotton cultivars from Xinjiang (JK1775, resistant; Z8,susceptible) using transcriptome sequencing at different infection stages.ResultsThe results revealed a significant differential expression of genes in the two cotton cultivars post V. dahliae infection, with the number of DEGs in JK1775 being higher than that in Z8 at different infection stages of V. dahliae. Interestingly, the DEGs of both JK1775 and Z8 were enriched in the MAPK signaling pathway in the early and late stages of infection. Importantly, the upregulated DEGs in both cultivars were significantly enriched in all stages of the phenylpropanoid metabolic pathway. Some of these DEGs were involved in the regulation of lignin and coumarin biosynthesis, which may be one of the key factors contributing to the resistance of upland cotton cultivars to V. dahliae in Xinjiang. Lignin staining experiments further showed that the lignin content increased in both resistant and susceptible varieties after inoculation with V. dahliae.DiscussionThis study not only provides insights into the molecular mechanisms of resistance to Verticillium wilt in Xinjiang upland cotton but also offers important candidate gene resources for molecular breeding of resistance to Verticillium wilt in cotton.

Summary: Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. In this study, we develop a clinically useful computational pathology platform for NSCLC that can be a foundation for multiple downstream applications and provide immediate value for patient care optimization and individualization. We train the primary multi-class tissue segmentation algorithm on a substantial, high-quality, manually annotated dataset of whole-slide images with lung adenocarcinoma and squamous cell carcinomas. We investigate two downstream applications. NSCLC subtyping algorithm is trained and validated using a large, multi-institutional (n = 6), multi-scanner (n = 5), international cohort of NSCLC cases (slides/patients 4,097/1,527). Moreover, we develop four AI-derived, fully explainable, quantitative, prognostic parameters (based on tertiary lymphoid structure and necrosis assessment) and validate them for different clinical endpoints. The computational platform enables the high-precision, quantitative analysis of H&E-stained slides. The developed prognostic parameters facilitate robust and independent risk stratification of patients with NSCLC.

We deployed 8 surface drifters in the western North Pacific in 2022. By integrating the Global Drifter Program’s data, we analyzed the drifter-based sea surface currents and temperatures during tropical cyclones. The maximum in-situ surface current observed was 0.70 m/s during typhoon Hinnamnor. Our surface drifters provided similar observations as compared to an adjacent Global Drifter Program’s drifter. Furthermore, we investigated float profiling observations during tropical cyclones. Based on Argo float 2903647, the SST decreased by 1.4oC after the passage of typhoon Hinnamnor. This study demonstrates the reliability of our newly deployed surface drifters and exhibits the state-of-the-art capability for in-situ observations of tropical cyclone-ocean interaction.

BackgroundMetabolic abnormalities in the body increase the risk of gallbladder stones and their complications, which brings a great economic and social burden. The relationship between different types and amounts of metabolic abnormalities and gallstone risk in different sexes is poorly documented and controversial.MethodsBased on the baseline survey data of the Chinese Multi-Ethnic Cohort (CMEC) study, 4,075 Chinese adults aged 30–79 years with complete abdominal ultrasound results and metabolic index data. Logistic regression model was used to evaluate the correlation between five metabolic abnormalities and gallstones, and to explore the gender difference.ResultsThe detection rate of gallbladder stones was found to be 7.0%, with a higher rate in women (8.6%) than in men (4.1%). Logistic results showed adjustment odds ratio (ORs) and 95% confidence interval (95% CI) of dysglycemia + hypertension + central obesity in 3 metabolic combinations was 4.459 (1.653, 12.029). The four metabolic combinations, dysglycemia + dyslipidemia + hypertension + central obesity, dysglycemia + dyslipidemia + hypertension + abnormal blood uric acid and dysglycemia + dyslipidemia + central obesity + abnormal blood uric acid adjusted OR and 95%CI were 3.342 (1.459, 7.659), 5.439 (1.555, 19.018) and 2.971 (1.187, 7.435), respectively. Gender-stratified analysis found that “any three or more metabolic abnormalities and their components were associated with gallstone risk, more significantly in women.ConclusionDifferent types and amounts of five metabolic abnormalities were associated with the risk of gallstone development, and the differences were more significant in women than men.

IntroductionFragile X syndrome is an inherited X-linked disorder associated with intellectual disabilities that begin in childhood and last a lifetime. The symptoms overlap with autism spectrum disorder, and the syndrome predominantly affects males. Consequently, FXS research tends to favor analysis of social behaviors in males, leaving a gap in our understanding of other behavioral traits, especially in females.MethodsWe used a mouse model of FXS to analyze developmental, behavioral, neurochemical, and transcriptomic profiles in males and females.ResultsOur behavioral assays demonstrated locomotor hyperactivity, motor impulsivity, increased “approach” behavior in an approach-avoidance assay, and deficits in nest building behavior. Analysis of brain neurotransmitter content revealed deficits in striatal GABA, glutamate, and serotonin content. RNA sequencing of the ventral striatum unveiled expression changes associated with neurotransmission as well as motivation and substance use pathways. Sex differences were identified in nest building behavior, striatal neurotransmitter content, and ventral striatal gene expression.DiscussionIn summary, our study identified sex differences in specific behavioral, neurotransmitter, and gene expression phenotypes and gene set enrichment analysis identified significant enrichment of pathways associated with motivation and drug reward.

Mechanical properties of additively manufactured alloys are momentously affected by the fabrication defects, thus limiting their applications in extreme conditions. Here we report on a near fully dense 316L stainless steel via optimized laser processing parameters. The results reveal that the dynamic mechanical response exhibits much greater sensitivity to defects than the quasi-static one. The densest specimen (porosity

Objective: Receptor-interacting protein kinase 1 (RIPK1) orchestrates the decision between cell survival and cell death in response to tumor necrosis factor (TNF) and other cytokines. Whereas the scaffolding function of RIPK1 is crucial to prevent TNF-induced apoptosis and necroptosis, its kinase activity is required for necroptosis and partially for apoptosis. Although TNF is a proinflammatory cytokine associated with β-cell loss in diabetes, the mechanism by which TNF induces β-cell demise remains unclear. Methods: Here, we dissected the contribution of RIPK1 scaffold versus kinase functions to β-cell death regulation using mice lacking RIPK1 specifically in β-cells (Ripk1β-KO mice) or expressing a kinase-dead version of RIPK1 (Ripk1D138N mice), respectively. These mice were challenged with streptozotocin, a model of autoimmune diabetes. Moreover, Ripk1β-KO mice were further challenged with a high-fat diet to induce hyperglycemia. For mechanistic studies, pancreatic islets were subjected to various killing and sensitising agents. Results: Inhibition of RIPK1 kinase activity (Ripk1D138N mice) did not affect the onset and progression of hyperglycemia in a type 1 diabetes model. Moreover, the absence of RIPK1 expression in β-cells did not affect normoglycemia under basal conditions or hyperglycemia under diabetic challenges. Ex vivo, primary pancreatic islets are not sensitised to TNF-induced apoptosis and necroptosis in the absence of RIPK1. Intriguingly, we found that pancreatic islets display high levels of the antiapoptotic cellular FLICE-inhibitory protein (cFLIP) and low levels of apoptosis (Caspase-8) and necroptosis (RIPK3) components. Cycloheximide treatment, which led to a reduction in cFLIP levels, rendered primary islets sensitive to TNF-induced cell death which was fully blocked by caspase inhibition. Conclusions: Unlike in many other cell types (e.g., epithelial, and immune), RIPK1 is not required for cell death regulation in β-cells under physiological conditions or diabetic challenges. Moreover, in vivo and in vitro evidence suggest that pancreatic β-cells do not undergo necroptosis but mainly caspase-dependent death in response to TNF. Last, our results show that β-cells have a distinct mode of regulation of TNF-cytotoxicity that is independent of RIPK1 and that may be highly dependent on cFLIP.

Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These proteins undergo precise control through diverse post-translational modifications, including ubiquitination, phosphorylation, acetylation, O-GlcNAcylation, SUMOylation, methylation, N-myristoylation, palmitoylation, and oxidative modification. These modifications play pivotal roles in regulating protein stability, activity, localization, and interactions, ultimately influencing both the buildup of iron and lipid peroxidation. In mammalian cells, regulators of ferroptosis typically undergo degradation via two principal pathways: the ubiquitin-proteasome system, which handles the majority of protein degradation, and autophagy, primarily targeting long-lived or aggregated proteins. This comprehensive review aims to summarize recent advances in the post-translational modification and degradation of proteins linked to ferroptosis. It also discusses strategies for modulating ferroptosis through protein modification and degradation systems, providing new insights into potential therapeutic applications for both cancer and non-neoplastic diseases.

Abstract Background During the pandemic, a notable increase in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), conditions that warrant emergent management, was reported. We aimed to investigate the trend of DKA‐ and HHS‐related mortality and excess deaths during the pandemic. Methods Annual age‐standardized mortality rates related to DKA and HHS between 2006 and 2021 were estimated using a nationwide database. Forecast analyses based on prepandemic data were conducted to predict the mortality rates during the pandemic. Excess mortality rates were calculated by comparing the observed versus predicted mortality rates. Subgroup analyses of demographic factors were performed. Results There were 71 575 DKA‐related deaths and 8618 HHS‐related deaths documented during 2006–2021. DKA, which showed a steady increase before the pandemic, demonstrated a pronounced excess mortality during the pandemic (36.91% in 2020 and 46.58% in 2021) with an annual percentage change (APC) of 29.4% (95% CI: 16.0%–44.0%). Although HHS incurred a downward trend during 2006–2019, the excess deaths in 2020 (40.60%) and 2021 (56.64%) were profound. Pediatric decedents exhibited the highest excess mortality. More than half of the excess deaths due to DKA were coronavirus disease 2019 (COVID‐19) related (51.3% in 2020 and 63.4% in 2021), whereas only less than a quarter of excess deaths due to HHS were COVID‐19 related. A widened racial/ethnic disparity was observed, and females exhibited higher excess mortality than males. Conclusions The DKA‐ and HHS‐related excess mortality during the pandemic and relevant disparities emphasize the urgent need for targeted strategies to mitigate the escalated risk in these populations during public health crises.

BackgroundUnder the current pandemic of Corona Virus Disease 2019 (COVID-19), The relationship between fatigue and COVID-19 has been found. Infection with COVID-19 is associated with fatigue long after the acute phase of COVID-19. Understanding the association of thyroid hormones levels with post-COVID condition, such as fatigue, is necessary to improve quality of life.MethodsThis population-based cohort study was conducted in Dalian, China, from December 2022, to March 2023, using a Yidu Core platform in the First Affiliated Hospital of Dalian Medical University, that integrates medical records, laboratory tests, and all diagnosis and treatment information based on patients in hospital. Eligible individuals were 40 patients with COVID-19, Divided them into fatigue group and non-fatigue group following up by telephone using the FS-14 scale after 6 months. The primary outcomes were the diagnoses of fatigue. The association between thyroid hormones levels and post-COVID condition, such as fatigue, was assessed using logistic regression analysis.ResultsCompared with the non-fatigue group, the FT3 level in fatigue group was lower (p

IntroductionThe genus Acronema, belonging to Apiaceae, includes approximately 25 species distributed in the high-altitude Sino-Himalayan region from E Nepal to SW China. This genus is a taxonomically complex genus with often indistinct species boundaries and problematic generic delimitation with Sinocarum and other close genera, largely due to the varied morphological characteristics. MethodsTo explore the phylogenetic relationships and clarify the limits of the genus Acronema and its related genera, we reconstructed a reliable phylogenetic framework with high support and resolution based on two molecular datasets (plastome data and ITS sequences) and performed morphological analyses.ResultsBoth phylogenetic analyses robustly supported that Acronema was a non-monophyletic group that fell into two clades: Acronema Clade and East-Asia Clade. We also newly sequenced and assembled sixteen Acronema complete plastomes and performed comprehensively comparative analyses for this genus. The comparative results showed that the plastome structure, gene number, GC content, codon bias patterns were high similarity, but varied in borders of SC/IR and we identified six different types of SC/IR border. The SC/IR boundaries of Acronema chienii were significantly different from the other Acronema members which was consistent with the type VI pattern in the genus Tongoloa. We also identified twelve potential DNA barcode regions (ccsA, matK, ndhF, ndhG, psaI, psbI, rpl32, rps15, ycf1, ycf3, psaI-ycf4 and psbM-trnD) for species identification in Acronema. The molecular evolution of Acronema was relatively conservative that only one gene (petG) was found to be under positive selection (ω = 1.02489).DiscussionThe gene petG is one of the genes involved in the transmission of photosynthetic electron chains during photosynthesis, which plays a crucial role in the process of photosynthesis in plants. This is also a manifestation of the adaptive evolution of plants in high-altitude areas to the environment. In conclusion, our study provides novel insights into the plastome adaptive evolution, phylogeny, and taxonomy of genus Acronema.