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Dewey's philosophy of education was heavily criticized by the Chinese Communist Party in the 1950s, which led many to believe that Dewey's education was in complete opposition to that of the CCP. However, this study intends to prove that Dewey had a tremendous influence on the early CCP members of the 1920s. Dewey's Chinese visit closely coincided highly with the time of the reception of Marxism in China and the eventual establishment of the CCP. Both founders of the CCP had close personal relationships with Dewey, and Chen even tried to practice Dewey's educational ideas in Southern China. As a graduate of a normal school, Mao Zedong also read and practiced Dewey's educational philosophy. Many other CCP members read Dewey in the 1920s and then became left-wing revolutionaries. Though Dewey himself did not stand with Marxism, his idea that education is an agent of social reform paved the way for Marxism in China in theoretical and practical aspects. When an educational theory is spread abroad, it is often not accepted in a fundamentalist way, but rather in a process of collision and integration with the local tradition.

Abstract This study aims to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker for cardiovascular mortality among cancer patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES). From the NHANES dataset (2007–2018), we analyzed 4974 cancer survivors, investigating the prognostic significance of NLR for all-cause, cardiovascular, and cancer-specific mortality. Survival outcomes were analyzed using Cox regression and Kaplan–Meier methods. Optimal NLR cutoffs were identified as 2.61 for differentiating the higher NLR group from lower NLR group. Elevated NLR levels significantly correlated with increased all-cause mortality (HR 1.11, 95% CI 1.07–1.14, P

Abstract Background The pretherapeutic differentiation of subtypes of primary intracranial germ cell tumours (iGCTs), including germinomas (GEs) and nongerminomatous germ cell tumours (NGGCTs), is essential for clinical practice because of distinct treatment strategies and prognostic profiles of these diseases. This study aimed to develop a deep learning model, iGNet, to assist in the differentiation and prognostication of iGCT subtypes by employing pretherapeutic MR T2-weighted imaging. Methods The iGNet model, which is based on the nnUNet architecture, was developed using a retrospective dataset of 280 pathologically confirmed iGCT patients. The training dataset included 83 GEs and 117 NGGCTs, while the retrospective internal test dataset included 31 GEs and 49 NGGCTs. The model’s diagnostic performance was then assessed with the area under the receiver operating characteristic curve (AUC) in a prospective internal dataset (n = 22) and two external datasets (n = 22 and 20). Next, we compared the diagnostic performance of six neuroradiologists with or without the assistance of iGNet. Finally, the predictive ability of the output of iGNet for progression-free and overall survival was assessed and compared to that of the pathological diagnosis. Results iGNet achieved high diagnostic performance, with AUCs between 0.869 and 0.950 across the four test datasets. With the assistance of iGNet, the six neuroradiologists’ diagnostic AUCs (averages of the four test datasets) increased by 9.22% to 17.90%. There was no significant difference between the output of iGNet and the results of pathological diagnosis in predicting progression-free and overall survival (P = .889). Conclusions By leveraging pretherapeutic MR imaging data, iGNet accurately differentiates iGCT subtypes, facilitating prognostic evaluation and increasing the potential for tailored treatment. Graphical Abstract

Abstract Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.

Abstract We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752–0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer–Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Abstract The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study’s primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46–1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49–1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00–2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61–0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60–0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37–0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83–1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.

Operating system (OS) security has been considered as a critical layer within the comprehensive security framework of computer information systems. Mandatory access control (MAC) mechanisms such as SELinux and AppArmor have been employed to strengthen OS security. However, significant challenges have been encountered in the application of MAC in practice, primarily involving the complexity of security policy configuration, which has demanded specialized expertise and often resulted in coarse-grained protection measures. Aimed at enhancing the process of generating security policies for AppArmor, an automated access control policy generation method was proposed based on large language models (LLM). The process began with a static analysis of the target application to extract preliminary security policy rules. Subsequently, the application was extensively executed to gather logs that achieved maximum code coverage. Large models, in conjunction with the gathered log information, static analysis outcomes, and few-shot learning, were utilized to autonomously generate security policies for applications. This approach significantly reduced the dependence on security experts, lowered manual labor costs, and diminished the subjectivity and complexity associated with manual security policy configurations. The efficacy of this methodology was demonstrated through a comparative analysis between the AppArmor security policies generated by this framework and the default policies, focusing on the policies’ correctness, completeness, and succinctness. The experimental findings reveal that the generated policies are not only comprehensive and succinct but also do not impede the normal operation of the application. These results underscore the effectiveness of the proposed method in streamlining the security policy generation process and enhancing the quality of the policies.

Abstract Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3’s role in CKD’s narrative and position it as a promising therapeutic contender.

Abstract Background Triple-negative breast cancer (TNBC) is characterized by its high metastatic potential, which results in poor patient survival. Cancer-associated fibroblasts (CAFs) are crucial in facilitating TNBC metastasis via induction of mitochondrial biogenesis. However, how to inhibit CAF-conferred mitochondrial biogenesis is still needed to explore. Methods We investigated metastasis using wound healing and cell invasion assays, 3D-culture, anoikis detection, and NOD/SCID mice. Mitochondrial biogenesis was detected by MitoTracker green FM staining, quantification of mitochondrial DNA levels, and blue-native polyacrylamide gel electrophoresis. The expression, transcription, and phosphorylation of peroxisome-proliferator activated receptor coactivator 1α (PGC-1α) were detected by western blotting, chromatin immunoprecipitation, dual-luciferase reporter assay, quantitative polymerase chain reaction, immunoprecipitation, and liquid chromatography-tandem mass spectrometry. The prognostic role of PGC-1α in TNBC was evaluated using the Kaplan–Meier plotter database and clinical breast cancer tissue samples. Results We demonstrated that PGC-1α indicated lymph node metastasis, tumor thrombus formation, and poor survival in TNBC patients, and it was induced by CAFs, which functioned as an inducer of mitochondrial biogenesis and metastasis in TNBC. Shikonin impeded the CAF-induced PGC-1α expression, nuclear localization, and interaction with estrogen-related receptor alpha (ERRα), thereby inhibiting PGC-1α/ERRα-targeted mitochondrial genes. Mechanistically, the downregulation of PGC-1α was mediated by synthase kinase 3β-induced phosphorylation of PGC-1α at Thr295, which associated with neural precursor cell expressed developmentally downregulated 4e1 recognition and subsequent degradation by ubiquitin proteolysis. Mutation of PGC-1α at Thr295 negated the suppressive effects of shikonin on CAF-stimulated TNBC mitochondrial biogenesis and metastasis in vitro and in vivo. Conclusions Our findings indicate that PGC-1α is a viable target for blocking TNBC metastasis by disrupting mitochondrial biogenesis, and that shikonin merits potential for treatment of TNBC metastasis as an inhibitor of mitochondrial biogenesis through targeting PGC-1α.

Abstract Dielectric capacitors offer great potential for advanced electronics due to their high power densities, but their energy density still needs to be further improved. High-entropy strategy has emerged as an effective method for improving energy storage performance, however, discovering new high-entropy systems within a high-dimensional composition space is a daunting challenge for traditional trial-and-error experiments. Here, based on phase-field simulations and limited experimental data, we propose a generative learning approach to accelerate the discovery of high-entropy dielectrics in a practically infinite exploration space of over 1011 combinations. By encoding-decoding latent space regularities to facilitate data sampling and forward inference, we employ inverse design to screen out the most promising combinations via a ranking strategy. Through only 5 sets of targeted experiments, we successfully obtain a Bi(Mg0.5Ti0.5)O3-based high-entropy dielectric film with a significantly improved energy density of 156 J cm−3 at an electric field of 5104 kV cm−1, surpassing the pristine film by more than eight-fold. This work introduces an effective and innovative avenue for designing high-entropy dielectrics with drastically reduced experimental cycles, which could be also extended to expedite the design of other multicomponent material systems with desired properties.

Abstract Background The geographic patterns of plant diversity in the Qinghai-Tibet Plateau (QTP) have been widely studied, but few studies have focused on wetland plants. This study quantified the geographic patterns of wetland plant diversity in the QTP through a comprehensive analysis of taxonomic, phylogenetic and functional indices. Methods Based on a large number of floras, monographs, specimens and field survey data, we constructed a comprehensive dataset of 1,958 wetland plant species in the QTP. Species richness (SR), phylogenetic diversity (PD), functional diversity (FD), net relatedness index (NRI) and net functional relatedness index (NFRI) were used to assess the taxonomic, phylogenetic and functional diversity of wetland plants. We explored the relationships between the diversity indices and four categories of environmental variables (i.e. energy-water, climate seasonality, topography and human activities). We used four diversity indices, namely endemic species richness, weighted endemism, phylogenetic endemism and functional endemism, together with the categorical analysis of neo- and paleo-endemism (CANAPE), to identify the endemic centers of wetland plants in the QTP. Results SR, PD and FD were highly consistent and showed a decreasing trend from southeast to northwest, decreasing with increasing elevation. The phylogenetic structure of wetland plant assemblages in most parts of the plateau is mainly clustered. The functional structure of wetland plant assemblages in the southeast of the plateau is overdispersed, while the functional structure of wetland plant assemblages in other areas is clustered. Energy-water and climate seasonality were the two most important categories of variables affecting wetland plant diversity. Environmental variables had a greater effect on the functional structure of wetland plants than on the phylogenetic structure. This study identified seven endemic centres, mainly in the Himalayas and Hengduan Mountains. Conclusions Climate and topography are the main factors determining the geographic distribution of wetland plant diversity at large scales. The majority of grid cells in the QTP with significant phylogenetic endemism were mixed and super-endemism. At large scales, compared to climate and topography, human activities may not have a negative impact on wetland plant diversity in the QTP.

Over the last few decades, ultrafast laser processing has become a widely used tool for manufacturing microstructures and nanostructures. The real-time monitoring of laser material processing provides opportunities to inspect processes and provide feedback. To date, in-situ and real-time monitoring of laser material processing has rarely been performed. To this end, we propose dual-path snapshot compressive microscopy (DP-SCM) for high-speed, large field-of-view, and high-resolution imaging for in-situ and real-time ultrafast laser processing. In the evaluation of DP-SCM, the field of view, lateral resolution, and imaging speed were measured to be 2 mm, 775 nm, and 500 fps, respectively. In ultrafast laser processing, the laser scanning process is observed using a DP-SCM system when translating the sample stage and scanning the focused femtosecond laser. Finally, we monitored the development of a self-organized nanograting structure to validate the potential of our system for unveiling new material mechanisms. The proposed method serves as an add-up (plug-and-play) module for any imaging setup and has vast potential for opening new avenues for high-throughput imaging in laser material processing.

Abstract A long-standing hypothesis proposes that certain RNA(s) must exhibit structural roles in microtubule assembly. Here, we identify a long noncoding RNA (TubAR) that is highly expressed in cerebellum and forms RNA–protein complex with TUBB4A and TUBA1A, two tubulins clinically linked to cerebellar and myelination defects. TubAR knockdown in mouse cerebellum causes loss of oligodendrocytes and Purkinje cells, demyelination, and decreased locomotor activity. Biochemically, we establish the roles of TubAR in promoting TUBB4A–TUBA1A heterodimer formation and microtubule assembly. Intriguingly, different from the hypomyelination-causing mutations, the non-hypomyelination-causing mutation TUBB4A-R2G confers gain-of-function for an RNA-independent interaction with TUBA1A. Experimental use of R2G/A mutations restores TUBB4A–TUBA1A heterodimer formation, and rescues the neuronal cell death phenotype caused by TubAR knockdown. Together, we uncover TubAR as the long-elusive structural RNA for microtubule assembly and demonstrate how TubAR mediates microtubule assembly specifically from αβ-tubulin heterodimers, which is crucial for maintenance of cerebellar myelination and activity.

Abstract Pathological cardiac hypertrophy is an important cause of heart failure(HF). Recent studies reveal that glucagon-like peptide-1 receptor (GLP1R) agonists can improve mortality and left ventricular ejection fraction in the patients with type 2 diabetes and HF. The present study aims to investigate whether semaglutide, a long-acting GLP1R agonist, can ameliorate cardiac hypertrophy induced by pressure overload, and explore the potential mechanism. The rats were performed transverse aortic constriction (TAC) to mimic pressure overload model. The rats were divided into four groups including Sham, TAC, TAC + semaglutide, and TAC + semaglutide + HCQ (hydroxychloroquine, an inhibitor of mitophagy). The rats in each experimental group received their respective interventions for 4 weeks. The parameters of left ventricular hypertrophy(LVH) were measured by echocardiography, Hematoxylin–eosin (HE) staining, western-blot and immunohistochemistry (IHC), respectively. The changes of mitophagy were reflected by detecting cytochrome c oxidase subunit II (COXII), LC3II/LC3I, mitochondria, and autophagosomes. Meanwhile, NLRP3, Caspase-1, and interleukin-18 were detected to evaluate the activation of NLRP3 inflammasome in each group. The results suggest that LVH, impaired mitophagy, and activation of NLRP3 inflammasome were present in TAC rats. Semaglutide significantly reduced LVH, improve mitophagy, and down-regulated NLRP3 inflammatory signal pathway in TAC rats. However, the reversed effect of semaglutide on cardiac hypertrophy was abolished by HCQ, which restored the activation of NLRP3 inflammasome suppressed by improved mitophagy. In conclusion, semaglutide ameliorates the cardiac hypertrophy by improving cardiac mitophagy to suppress the activation of NLRP3 inflammasome. Semaglutide may be a novel potential option for intervention of cardiac hypertrophy induced by pressure overload.

Abstract Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), has caused substantial economic losses to the global swine industry due to the lack of effective commercial vaccines and drugs. There is an urgent need to develop alternative strategies for PRRS prevention and control, such as antiviral drugs. In this study, we identified ursonic acid (UNA), a natural pentacyclic triterpenoid from medicinal herbs, as a novel drug with anti-PRRSV activity in vitro. Mechanistically, a time-of-addition assay revealed that UNA inhibited PRRSV replication when it was added before, at the same time as, and after PRRSV infection was induced. Compound target prediction and molecular docking analysis suggested that UNA interacts with the active pocket of PTPN1, which was further confirmed by a target protein interference assay and phosphatase activity assay. Furthermore, UNA inhibited PRRSV replication by targeting PTPN1, which inhibited IFN-β production. In addition, UNA displayed antiviral activity against porcine epidemic diarrhoea virus (PEDV) and Seneca virus A (SVA) replication in vitro. These findings will be helpful for developing novel prophylactic and therapeutic agents against PRRS and other swine virus infections.

Abstract Background Patients with spinal cord injury have a relatively high risk for bladder cancer and often complicated with bladder cancer in advanced stages, and the degree of aggressiveness of malignancy is high. Most of the literature is based on disease clinical features while, our study reviews the clinical characteristics and molecular mechanisms of spinal cord injury patients with bladder cancer, so that it might help clinicians better recognize and manage these patients. Method We searched PubMed, Web of Science and Embase, using retrieval type like (“Neurogenic Lower Urinary Tract Dysfunction” OR “Spinal cord injury” OR “Spinal Cord Trauma”) AND (“bladder cancer” OR “bladder neoplasm” OR “bladder carcinoma” OR “Urinary Bladder Neoplasms” OR “Bladder Tumor”). In Web of Science, the retrieval type was searched as “Topic”, and in PubMed and Embase, as “All Field”. The methodological quality of eligible studies and their risk of bias were assessed using the Newcastle-Ottawa scale. This article is registered in PROSPERO with the CBD number: CRD42024508514. Result In WOS, we searched 219 related papers, in PubMed, 122 and in Embase, 363. Thus, a total of 254 articles were included after passing the screening, within a time range between 1960 and 2023. A comprehensive analysis of the data showed that the mortality and incidence rates of bladder cancer in spinal cord injury patients were higher than that of the general population, and the most frequent pathological type was squamous cell carcinoma. In parallel to long-term urinary tract infection and indwelling catheterization, the role of molecules such as NO, MiR 1949 and Rb 1. was found to be crucial pathogenetically. Conclusion This review highlights the risk of bladder cancer in SCI patients, comprehensively addressing the clinical characteristics and related molecular mechanisms. However, given that there are few studies on the molecular mechanisms of bladder cancer in spinal cord injury, further research is needed to expand the understanding of the disease.

Abstract Purpose To investigate whether the mixed approach is a safe and advantageous way to operate laparoscopic right hemicolectomy. Methods A retrospective study was performed on 316 patients who underwent laparoscopic right hemicolectomy in our center. They were assigned to the middle approach group (n = 158) and the mixed approach group (n = 158) according to the surgical approaches. The baseline data like gender、age and body mass index as well as the intraoperative and postoperative conditions including operation time, blood loss, postoperative hospital stay and complications were analyzed. Results There were no significant differences in age, sex, BMI, ASA grade and tumor characteristics between the two groups. Compared with the middle approach group, the mixed approach group was significantly lower in terms of operation time (217.61 min vs 154.31 min, p

Abstract Background To investigate the clinical effects of double-dose (4 mg) aflibercept treatment in neovascular age-related macular degeneration (nAMD), compared with the standard-dose (2 mg) treatment. Methods A total of 108 eyes from 97 patients with nAMD and received intravitreal aflibercept 2 mg and/or 4 mg treatment were retrospectively reviewed. The changes of central macular thickness (CMT)/ pigmental epithelium detachment height and the recurrence rate of exudation during the 12-month follow-up were compared between the 2 mg group and the 4 mg group. Self-control comparisons (2 mg switch to 4 mg) were also made between two regimens. Results Compared with the 2 mg group, tendencies of lower intraretinal fluid incidence and more CMT reduction were observed in the 4 mg group. The later one was also observed when eyes switching from 2 mg to 4 mg regimen. The median remission interval was 5 months in the 4 mg group, 2 months longer than the 3 months in the 2 mg group (P = 0.452). Injections needed in the 4 mg group were 3.644 ± 1.670, less than the 4.286 ± 2.334 injections in the 2 mg group within 12 months as well (P = 0.151). However, no associated vision benefits were gained from the double-douse regimen. No markedly increased-intraocular pressure events, or other adverse events were found in two groups. Conclusions Compared to the aflibercept 2 mg treatment in nAMD, tendencies of anatomic gains and relieving treatment burden were brought by the aflibercept 4 mg treatment. This study may have additional importance, given the further application of high-dose aflibercept in real-world settings.

Abstract With the popularity of smart terminals, wearable electronic devices have shown great market prospects, especially high-sensitivity pressure sensors, which can monitor micro-stimuli and high-precision dynamic external stimuli, and will have an important impact on future functional development. Compressible flexible sensors have attracted wide attention due to their simple sensing mechanism and the advantages of light weight and convenience. Sensors with high sensitivity are very sensitive to pressure and can detect resistance/current changes under pressure, which has been widely studied. On this basis, this review focuses on analyzing the performance impact of device structure design strategies on high sensitivity pressure sensors. The design of structures can be divided into interface microstructures and three-dimensional framework structures. The preparation methods of various structures are introduced in detail, and the current research status and future development challenges are summarized.

Unreduced gametes through chromosome doubling play a major role in the process of plant polyploidization. Our previous work confirmed that Camellia oleifera can produce natural 2n pollen, and it is possible to induce the 2n pollen formation by high temperature treatment. This study focused on the optimization of the 2n pollen induction technique and the mechanisms of high temperature-induced 2n pollen formation in C. oleifera. We found that the optimal protocol for inducing 2n pollen via high temperature was to perform 45 °C with 4 h at the prophase I stage of the pollen mother cells (PMCs). Meanwhile, high temperature significantly decreased the yield and fertility of 2n pollen. Through the observation of meiosis, abnormal chromosome and cytological behaviour was discovered under high-temperature treatment, and we confirmed that the formation of 2n pollen is caused by abnormal cell plate. Based on weighted gene co-expression network analysis, fifteen hub genes related to cell cycle control were identified. After male flower buds were exposed to heat shock, polygalacturonase gene (CoPGX3) was significantly upregulated. We inferred that high temperature causes the CoPGX3 gene to be overexpressed and that CoPGX3 is redistributed into the cytosol where it degrades cytoplasmic pectin, which leads to an abnormal cell plate. Furthermore, abnormal cytokinesis resulted in the formation of dyads and triads, and PMCs divided to produce 2n pollen. Our findings provide new insights into the mechanism of 2n pollen induced by high temperature in a woody plant and lay a foundation for further ploidy breeding of C. oleifera.

As an important subclass of metal–organic frameworks (MOFs), anion-pillars MOFs (APMOFs) have recently exhibited exceptional performances in separation and purification processes. The adjustment of pore sizes and environments of APMOFs can be finely tuned through judicious combination of organic ligands, anion pillars, and metal ions. Compared to widely investigated anion pillars, organic ligands are more crucial as they allow for a broader range of pore sizes and environments at the nanometer scale. Furthermore, different from the bidentate ligand-based APMOFs that typically form three-dimensional (3D) frameworks with pcu topology, APMOFs constructed using multidentate nitrogen­(N)-containing ligands (with a coordination number ≥ 3) offer opportunities to create APMOFs with diverse topologies. The larger dimensions and possible distortion of multidentate N-containing ligands prove advantageous for addressing multi-component hydrocarbon separations encompassing a broad spectrum of dynamic diameters. Therefore, this Review summarizes the structural characteristics of multidentate ligand-based APMOFs and their enhanced performances for gas separation and purification processes. Additionally, it discusses current challenges and prospects associated with constructing multidentate ligand-based APMOFs while providing prospects. This critical review will provide valuable insights and guides for designing and developing advanced multidentate ligand-based APMOF adsorbents.

This study aimed to explore the efficacy of a multimodal analgesic regimen during the perioperative period for male patients undergoing knee replacement surgery. A total of 80 male patients scheduled for elective knee replacement surgery in our hospital’s orthopedic department from March 2022 to March 2023 were selected through digital randomization. They were equally divided into a control group (received a conventional analgesic protocol) and an observation group (treated with a multimodal analgesic protocol that included patient-controlled analgesia (PCA), ultrasound-guided nerve block and physical analgesia). Parameters such as postoperative celecoxib capsule dosage, Visual Analog Scale (VAS) scores at 6, 12, 24 and 72 hours after surgery, levels of neurotransmitters and stress markers at the time of surgery, 24 hours post-surgery, and 72 hours post-surgery, sleep quality scores, the timing of first ambulation, and the overall incidence of adverse reactions were compared between the groups. After intervention, the observation group showed a statistically significant reduction in the dosage of celecoxib capsules compared to the control group (p < 0.05). VAS scores in the observation group were significantly lower than those in the control group at all measured time points. Furthermore, levels of substance P (SP), beta-endorphin (β-EP), 5-hydroxytryptamine (5-HT), cortisol (Cor), C-reactive protein (CRP) and white blood cell (WBC) counts in the observation group were significantly lower than those in the control group at 24- and 72-hours post-surgery. The incidence of adverse reactions was also significantly lower in the observation group (p < 0.05). We conclude that implementing a multimodal analgesic protocol in the perioperative period could significantly reduce pain, regulate neurotransmitter and stress levels, and enhance sleep quality in the early postoperative phase of male patients undergoing knee replacement surgery.

Abstract Oxygen is essential for aerobic organisms, but little is known about its role in antiviral immunity. Here, we report that during responses to viral infection, hypoxic conditions repress antiviral-responsive genes independently of HIF signaling. EGLN1 is identified as a key mediator of the oxygen enhancement of antiviral innate immune responses. Under sufficient oxygen conditions, EGLN1 retains its prolyl hydroxylase activity to catalyze the hydroxylation of IRF3 at proline 10. This modification enhances IRF3 phosphorylation, dimerization and nuclear translocation, leading to subsequent IRF3 activation. Furthermore, mice and zebrafish with Egln1 deletion, treatment with the EGLN inhibitor FG4592, or mice carrying an Irf3 P10A mutation are more susceptible to viral infections. These findings not only reveal a direct link between oxygen and antiviral responses, but also provide insight into the mechanisms by which oxygen regulates innate immunity.

Abstract Background In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat. Results This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens. Conclusion This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.

Abstract Background Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. Methods This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017–2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018–2021) and another from center 2 (n = 43, 2020–2021), were utilized to assess the signature’s association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. Results Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. Conclusion This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC’s MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

Abstract Background Porcine acute diarrhea syndrome coronavirus (SADS-CoV) is one of the novel pathogens responsible for piglet diarrhea, contributing to substantial economic losses in the farming sector. The broad host range of SADS-CoV raises concerns regarding its potential for cross-species transmission. Currently, there are no effective means of preventing or treating SADS-CoV infection, underscoring the urgent need for identifying efficient antiviral drugs. This study focuses on evaluating quercetin as an antiviral agent against SADS-CoV. Results In vitro experiments showed that quercetin inhibited SADS-CoV proliferation in a concentration-dependent manner, targeting the adsorption and replication stages of the viral life cycle. Furthermore, quercetin disrupts the regulation of the P53 gene by the virus and inhibits host cell cycle progression induced by SADS-CoV infection. In vivo experiments revealed that quercetin effectively alleviated the clinical symptoms and intestinal pathological damage caused by SADS-CoV-infected piglets, leading to reduced expression levels of inflammatory factors such as TLR3, IL-6, IL-8, and TNF-α. Conclusions Therefore, this study provides compelling evidence that quercetin has great potential and promising applications for anti- SADS-CoV action.

Summary: FOXA1 serves as a crucial pioneer transcription factor during developmental processes and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites; however, the regulatory mechanisms governing molecular dynamics and activity of FOXA1 remain elusive. Here, we show that mitotic kinase Aurora B specifies the different DNA binding modes of FOXA1 and guides FOXA1 biomolecular condensation in mitosis. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to liberate the specific, but not the non-specific, DNA binding. Interestingly, the phosphorylation of S221 attenuates the FOXA1 condensation that requires specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivation and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.

Abstract In this letter, novel methods for quickly generating frequency hopping (FH) sequences with good out‐of‐phase peak aperiodic Hamming auto‐correlation (PAHAC) property are proposed. Compared with brute‐force search algorithm, the proposed algorithms have an obvious advantage on their time complexity. Results show that the algorithms can generate FH sequences with optimal/quasi‐optimal PAHAC performance in all tested cases.

BackgroundOur study was designed to determine the incidence and risk factors of severe acute high-altitude illness (AHAI) in healthy adults first entering the northern Tibetan Plateau of over 5,000 m.MethodsIn our prospective observational study, we enrolled 500 people who were scheduled for fast ascension to the northern Tibetan Plateau. The primary outcome variable was severe AHAI, defined as the presence of serious symptoms that could not be ameliorated by general treatment and required evacuation to lower altitudes. According to the inclusion and exclusion criteria, a cohort of 383 healthy people was included in the statistical analysis. We calculated the incidence of severe AHAI, identified the risk factors, and the differences in the most severe symptoms experienced.ResultsSixty-eight people were diagnosed with severe AHAI, and the incidence was 17.8%. Compared to individuals without severe AHAI, those with severe AHAI were more likely to be over the age of 40 years, of Han Chinese nationality, and living at an altitude of

Increased anthropogenic activities over the last decades have led to a gradual increase in cadmium content in the soil, which, due to its high mobility in soil, makes Cd accumulation in plants a serious threat to the health of animals and humans. Plant hormones including melatonin (Mel) and brassinosteroids (BR) are known to provide tolerance against various abiotic stresses. In this work, the role of combined and separate exogenous application of Mel and BR on Cd stress in cherry tomato plants was examined. Cd stress significantly reduced tomato growth by inducing oxidative stress and reduced K+ uptake in roots and shoots. Combined application of Mel and BR reduced detrimental effects of Cd in tomato by (i) reducing Cd accumulation in the shoot; (ii) increasing the activities of different antioxidants (SOD, CAT, APX, GR); (iii) triggering higher expression of genes relating to Cd vacuolar sequestration (Na+/H+ EXCHANGER, SlNHX1; NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 6, SlNRAMP6), and Cd transport and detoxification (HEAVY-METAL-ASSOCIATED 3, SlHMA3; PLANT CADMIUM RESISTANT 2, SlPCR2); and (iv) improving plant K+ homeostasis and contents in root and shoot. The latter trait was associated with the reduced gene expression of K+-permeable outward rectifying channel (SlGORK3), and transcriptional upregulation of high affinity potassium transporter 5 (SIHAK5) under Cd stress. A separate application of Mel and BR showed tissue-specific regulation of tomato growth and Cd tolerance by regulating antioxidant activities, K+ uptake, Cd uptake, and translocation from root to shoot and their endogenous contents. Melatonin per se was more effective in improving Cd tolerance in shoot while beneficial BR effects were more pronounced in roots, and their combined application was effective in both tissues. Taken together, reported results show tissue-specific regulation of Cd tolerance by Mel and BR in cherry tomato plants and demonstrate the efficiency of combined Mel + BR treatment as a practical tool to reduce Cd accumulation and mitigate its negative effects on plant growth.

IntroductionWearable exoskeletons are emerging technologies for providing movement assistance and rehabilitation for people with motor disorders. In this study, we focus on the specific gait pathology dropfoot, which is common after a stroke. Dropfoot makes it difficult to achieve foot clearance during swing and heel contact at early stance and often necessitates compensatory movements.MethodsWe developed a soft ankle exoskeleton consisting of actuation and transmission systems to assist two degrees of freedom simultaneously: dorsiflexion and eversion, then performed several proof-of-concept experiments on non-disabled persons. The actuation system consists of two motors worn on a waist belt. The transmission system provides assistive force to the medial and lateral sides of the forefoot via Bowden cables. The coupling design enables variable assistance of dorsiflexion and inversion at the same time, and a force-free controller is proposed to compensate for device resistance. We first evaluated the performance of the exoskeleton in three seated movement tests: assisting dorsiflexion and eversion, controlling plantarflexion, and compensating for device resistance, then during walking tests. In all proof-of-concept experiments, dropfoot tendency was simulated by fastening a weight to the shoe over the lateral forefoot.ResultsIn the first two seated tests, errors between the target and the achieved ankle joint angles in two planes were low; errors of

Introduction: The study proposes a method for evaluating stress distribution in high-altitude Tibetan Plateau railway tunnels using high-precision radar satellite time-series interferometric synthetic aperture radar technology.Methods: To effectively monitor and prevent geological hazards during the construction process, this method i employed, as it serves as a component of advanced geological prediction and surrounding rock deformation monitoring technology for high-altitude tunnels, particularly in the Dongelu Tunnel of the China–Tibet Railway. The study utilizes time-series interferometric synthetic aperture radar to obtain deformation information for Dongelu Tunnel area between 2022 and 2023 from Sentinel- 1A orbit images. This quantitatively investigates the upper mountain body and line-of-sight direction along the tunnel. The deformation characteristics are correlated with high-frequency and high-precision automated vertical displacement monitoring results, determining the spatiotemporal distribution of tunnel deformation. In this study, a model that determines the vertical stress state of the Dongelu Tunnel under loading near the entrance and evaluates its health status was established.Results: The results show that the surface deformation of the mountain above the tunnel axis develops slowly and is relatively small, with a maximum vertical deformation rate of 1–3 mm/year. The average stress on the tunnel arch is 5.54 MPa, with a fluctuation range of 0.01 MPa. Temporal Q9 changes in various parts of the tunnel are periodic, with maximum fluctuations observed in December 2022. The study reveals inconsistent surface settlement of the tunnel arch and mountain above it, causing minor vertical stress changes. As the tunnel construction progresses, vertical stress variation shows periodicity because of an initial imbalance in internal stress within the mountain. Stress fluctuations near the tunnel entrance occur during the initial excavation phase, gradually diminishing as the project progresses and internal stress stabilizes.Discussion: The proposed tunnel monitoring and stability assessment method can reduce its impact on engineering construction and provide guidance for advanced geological prediction.

Summary: Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigate the antiviral RNA interference pathway in bat cells and discover that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs upon Sindbis virus infection that are missing in human cells. Disruption of Dicer function results in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors, such as retinoic acid-inducible gene I, with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.

Precipitation strengthening stands as a paramount strategy for enhancing the mechanical properties of FeNi-based alloys. Conventional precipitates used for strengthening typically contain only two major constituent elements selected from Ni, Al, and Ti. However, knowledge about the intrinsic properties and strengthening mechanisms of multicomponent precipitates remains limited. Here, we propose introducing novel multicomponent L12-type precipitates containing palladium (Pd) to strengthen FeNi-based alloys. The strengthened FeNi alloy achieves an eightfold increase in strength compared to the FeNi matrix while maintaining good ductility. Using meticulous micro-characterization and energy-dispersive X-ray spectroscopy (EDS) techniques, in conjunction with first-principles calculations, this study investigated the effects of Pd addition on the thermodynamic stability, morphology, coherency, and strengthening mechanisms of the precipitates. Results indicate that the addition of Pd induces the nucleation of L12-type precipitates, increases their ductility, and eliminates anisotropy in the shear modulus of the precipitates. Excessive Pd content can alter the shape of precipitates from spherical to acicular due to increased interfacial mismatch between the precipitates and the FeNi matrix. These insights shed light on the impact of Pd addition on the intrinsic properties of L12-type precipitates, offering a promising pathway for the design of advanced FeNi-based alloys with optimized mechanical performance.

Ribosomes mediate protein synthesis, which is one of the most energy-demanding activities within the cell, and mitochondria are one of the main sources generating energy. How mitochondrial morphology and functions are adjusted to cope with ribosomal defects, which can impair protein synthesis and affect cell viability, is poorly understood. Here, we used the fission yeast Schizosaccharomyces Pombe as a model organism to investigate the interplay between ribosome and mitochondria. We found that a ribosomal insult, caused by the absence of Rpl2702, activates a signaling pathway involving Sty1/MAPK and mTOR to modulate mitochondrial morphology and functions. Specifically, we demonstrated that Sty1/MAPK induces mitochondrial fragmentation in a mTOR-independent manner while both Sty1/MAPK and mTOR increases the levels of mitochondrial membrane potential and mitochondrial reactive oxygen species (mROS). Moreover, we demonstrated that Sty1/MAPK acts upstream of Tor1/TORC2 and Tor1/TORC2 and is required to activate Tor2/TORC1. The enhancements of mitochondrial membrane potential and mROS function to promote proliferation of cells bearing ribosomal defects. Hence, our study reveals a previously uncharacterized Sty1/MAPK-mTOR signaling axis that regulates mitochondrial morphology and functions in response to ribosomal insults and provides new insights into the molecular and physiological adaptations of cells to impaired protein synthesis.