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Abstract Background The spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF) indicates a prethrombic state that ultimately progresses into thrombus formation. A comprehensive understanding of specific plasma metabolomics characteristics may protect AF patients from thrombus, particularly in the early stage. Objectives Through the investigation of metabolic pathways, we endeavor to uncover the metabolomic characteristics associated with SEC states, and to examine the differential metabolites by which may exert their influence on thrombotic states. Methods Patients with AF were enrolled, and the participants were divided into three groups based on the results of the echocardiogram: non-SEC, low-SEC and high-SEC group. Samples were collected and subjected to non-targeted metabolomics analysis. The analytical process included data quality control, metabolite difference analysis, component analysis, Kegg cluster analysis, etc. Results Our metabolic phenotype revealed a clear differential metabolic pattern between the SEC and non-SEC. Specifically, we identified 35 and 142 significantly differential metabolites in venous and atrial plasma, respectively, suggesting that SEC may be involved in pervasive metabolic dysregulation and that the degree of metabolic dysregulation in atrial plasma is more severe than that in venous blood. Conclusion Patients with SEC have a significantly different metabolic pattern compared to those without SEC. Our work promoted the understanding of mechanism of the occurrence and development of SEC, facilitated the screening of the target metabolites for its therapeutic intervention, and provided evidence for the prevention and treatment of SEC or thrombosis in AF. Our work also provided new directions for subsequent research in related fields. In conclusion, our study not only provides a theoretical basis for understanding the occurrence and development of SEC in AF, but also provides recommendations for the daily diet of AF patients with SEC, such as a balanced intake of essential amino acids, avoiding excessive intake of benzoic acid, and intake of appropriate inositol. Clinical trial number Not applicable.

The present study examined the evolution of interfacial microstructure and on the element distribution of GH4169/GH3039 dissimilar joints by laser welding under different preheating temperatures. The results indicated that the microstructure observed in the interface layer on the GH4169 side exhibited distinct layers, namely diffusion layer and transition layer, which varied depending on the varied preheating temperature. Within the weld seam (WS), two types of dendrites were predominantly present: lath-like columnar dendrite and cellular dendrite. In the GH3039 side, the grain structure was mainly dominated by columnar dendrites, exhibits perpendicular growth to the fusion line and demonstrates a certain epitaxial growth morphology. Moreover, excessive preheating temperature intensified the migration of elements and phase transition behavior. As the preheating temperature increased, the low-angle grain boundaries (LAGBs) percentage decreased from 13% to 9.4%. The average grain size of the WS at room temperature, 200 °C and 400 °C is 44.1 μm, 53.3 μm and 58.2 μm, respectively. This paper provides a basis for tuning microstructure and element behavior via preheating temperature optimization in laser welding of dissimilar GH4169/GH3039 for further engineering application.

Aluminum (Al) toxicity poses a significant constraint on field crop yields in acid soils. Zinc finger protein 36 (ZFP36) is well-documented for its pivotal role in enhancing tolerance to both drought and oxidative stress in rice. This study unveils a novel function of ZFP36 modulated by abscisic acid (ABA)-dependent mechanisms, specifically aimed at alleviating Al toxicity in rice. Under Al stress, the expression of ZFP36 significantly increased through an ABA-dependent pathway. Knocking down ZFP36 heightened Al sensitivity, while overexpressing ZFP36 conferred increased resistance to Al stress. Additionally, our investigations revealed a physical interaction between ZFP36 and pyruvate dehydrogenase kinase 1 in rice (OsPDK1). Biochemical assays further elucidated that OsPDK1 phosphorylates ZFP36 at the amino acid site 73–161. Subsequent experiments demonstrated that ZFP36 positively regulates the expression of ascorbate peroxidases (OsAPX1) and OsALS1 by binding to specific elements in their upstream segments in rice. Through genetic and phenotypic analyses, we unveiled that OsPDK1 influences ABA-triggered antioxidant defense to alleviate Al toxicity by interacting with ZFP36. In summary, our study underscores that pyruvate dehydrogenase kinase 1 (OsPDK1) phosphorylates ZFP36 to modulate the activities of antioxidant enzymes via an ABA-dependent pathway, influencing tolerance of rice to soil Al toxicity.

Abstract Net primary productivity (NPP) is an important parameter reflecting vegetation growth, and water is one of the necessary factors for vegetation growth. Investigating the mutual influence between NPP and water is significant for ensuring the stable development of the ecological environment. This study focuses on the Yangtze River Basin (YRB) as the research area, and based on medium-resolution imaging spectrometer (MODIS) data, climate data, and gravity recovery and climate experiment (GRACE) data, the spatiotemporal evolution characteristics of vegetation NPP and terrestrial water storage (TWS) in the YRB from 2000 to 2022 are explored and analyzes the mutual influence of NPP with climate factors and TWS. The results show that vegetation NPP (4.10 gC·m−2·a−1) and TWS (0.55 mm) in the YRB have exhibited an increasing trend from 2000 to 2022, with a strong correlation between the two, which is related to recent environmental policies. Analysis of the impact of climate factors on NPP reveals that temperature and TWS significantly positively impact NPP changes. Furthermore, comparisons between NPP and TWS indicate that changes in TWS substantially promote plant growth. In addition, the comparison between NPP and TWS indicates that changes in TWS have an important promoting effect on plant growth. Surface water (SWS) and soil water (SM) have a significant promoting effect on plant growth, but with a strong lag, while the consumption of groundwater (GWS) has been promoting plant growth without significant lag.

Abstract The cementation of desert aeolian sand is a key method to control land desertification and dust storms, so an economical, green and durable process to reach the binding between sand grains needs to be searched. The method based on the microbially induced calcite precipitation (MICP) appeared in recent years as a promising process that proved its efficiency. The feasibility of the MICP technique to treat aeolian sand composed by low clay content, fine particles, low water content and characterized by weak permeability was demonstrated in the present paper. The effects of initial dry density, cementation number and curing time on the permeability and strength of MICP-treated aeolian sand were investigated using permeability tests and unconfined compressive strength (UCS) tests. The microstructure of aeolian sand was observed by scanning electron microscopy (SEM) tests and X-ray diffraction (XRD), aiming to reveal the solidification principle of MICP. The tests result indicated that when the initial dry density and the cementation number rose, the hydraulic conductivity of aeolian sand decreased while the mechanical strength given by UCS values improved. When the initial dry density was 1.65 g/cm3, the curing time was 3 h and the cementation number reached 20, the hydraulic conductivity and UCS reached 0.00151 cm/s and 1050.30 kPa, respectively. With increasing curing time, the hydraulic conductivity first decreased, followed by an increase, while the UCS exhibited an up and then a downtrend. Furthermore, the correlation between UCS values and the CaCO3 content reached a high R 2 value equal to 0.912, which confirmed that the cementation occurred in sandy material and governed the soil strengthening. Indeed, the calcium carbonate crystals observed by SEM and XRD enhanced the friction between particles when they wrapped around the sand grains surface, while carbonates reduced the soil permeability when filling the pores and sticking the sand particles together. Finally, the theoretical and scientific knowledge brought by the present study should help in managing sand in desert areas.

Abstract Background Rapid sequence intubation (RSI) is a crucial step in the resuscitation process for critically ill patients, and the judicious use of sedative drugs during RSI significantly influences the clinical outcomes of patients. Ketamine is a commonly used anesthetic sedative; however, its impact on the mortality of patients undergoing RSI has yielded inconsistent findings. Therefore, we conducted a systematic review and meta-analysis investigating ketamine’s role in RSI to provide insights into selecting appropriate sedatives for critically ill patients. Methods In this systematic review and meta-analysis, we conducted a systematic search on MEDLINE (PubMed), Embase, and Cochrane Central Register of Controlled Trials, without restricting to randomized controlled trials (RCTs) or cohort studies. The search was performed from inception until Dec 12, 2023, with no language restrictions. All studies comparing the use of sedatives, including ketamine, and documenting in-hospital mortality were included in this study. Results A total of 991 studies were identified, out of which 15 studies (5 RCTs and 10 cohort studies) involving 16,807 participants fulfilled the inclusion criteria. No significant impact on in-hospital mortality was observed with the use of ketamine compared to other drugs during RSI (OR 0.90, 95%CI 0.72 to 1.12). Low-quality evidence suggested that ketamine might reduce mortality within the first seven days of hospitalization (OR 0.42, 95%CI 0.19 to 0.93), but it may also have a potential effect on prolonging ICU-free days at day 28 (MD -0.71, 95%CI -1.38 to -0.05). There were no significant differences in the results of the other RSI-related outcomes, such as physiological function and adverse events. Conclusions Based on existing studies, ketamine showed no significant difference compared to other sedatives in terms of in-hospital mortality, physiological impact, and side effects following RSI. However, it may reduce mortality within 7 days while probably prolong the length of stay in the ICU. Trial registration CRD42023478020.

Abstract Background Recent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The present study sought to investigate the potential influence of paternal use of donepezil, a specific reversible central acetylcholinesterase inhibitor that activates the cholinergic system to promote cognition, on offspring. Results In this study, male rats were bred after 21 days of oral donepezil administration at a dose of 4 mg/kg to generate F1 offspring. Both male and female F₁ offspring displayed enhanced performance in learning and short-term memory tests, including novel object recognition, Y maze, and operant learning. Transcriptomic analysis revealed notable alterations in genes associated with the extracellular matrix in the hippocampal tissue of the F1 generation. Integration with genes related to intelligence identified potential core genes that may be involved in the observed behavioral enhancements. Conclusions These findings indicate that prolonged paternal exposure to donepezil may enhance the learning and memory abilities of offspring, possibly by targeting nonneural, extracellular regions. Further research is required to fully elucidate any potential transgenerational effects.

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 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 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.

IntroductionThe CD16A protein encoding gene FcγRIIIa (FCGR3A) and its potential ligand Fibrinogen-like protein 2 (FGL2) are involved in various cell physiological activities on the extracellular surface. Aberrant expression of these genes has been linked to tumorigenesis.MethodsTo assess the prognostic significance of FCGR3A and FGL2 transcription expression in glioma and explore their roles in glioma initiation and progression, we utilized multiple online databases, including TCGA, GEPIA, CGGA, cBioPortal, TISCH, LinkedOmics, Ivy Glioblastoma Atlas Project, and Human Protein Atlas.ResultsOur analysis revealed that FCGR3A and FGL2 expression was significantly correlated with clinical variables such as age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. A strong correlation was also observed between the transcriptional expression levels of FCGR3A and FGL2. High expression of both genes predicted poor prognosis in primary and recurrent glioma patients, particularly those with lower grade gliomas. Cox regression analysis further confirmed that elevated expression of FCGR3A and FGL2 were independent prognostic factors for shorter overall survival in glioma patients. Gene co-expression network analysis suggested that FCGR3A, FGL2, and their co-expressed genes were involved in inflammatory activities and tumor-related signaling pathways. Additionally, tissue microarrays from glioma patients at Tiantan Hospital showed significantly higher FCGR3A protein expression in high-grade gliomas compared to low-grade gliomas.DiscussionIn conclusion, our findings suggest that FCGR3A and FGL2 could serve as promising prognostic biomarkers and potential therapeutic targets for glioma patients.

Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.

Fulminant myocarditis (FM) is characteristically associated with rapid progressive decline in cardiac function and high mortality, with rapid onset of hemodynamic dysfunction and severe arrhythmias. In this report, we describe a case concerning a patient clinically diagnosed with FM, marked by rapid progression leading to intractable ventricular fibrillation and subsequent cardiac arrest. Conventional cardiopulmonary resuscitation (CCPR) was performed 120 min before extracorporeal membrane oxygenation (ECMO) was initiated. This critical situation was effectively addressed through the utilization of extracorporeal cardiopulmonary resuscitation (ECPR). By providing sustained cardiopulmonary support, effective hemodynamics were obtained. Eventually, the patient made a full recovery, and discharged without neurologic complications on hospital day 13.

ABSTRACT Background The hiatal ligament, as the anatomical landmark for the completion of total mesorectal excision (TME) for ultra‐low rectal cancer, represents a continuation of the longitudinal muscle of the rectum. It receives vascular supply from the median sacral artery and contains lymphatic vessels. In cases where ultra‐low rectal cancer is located in the posterior rectal wall, the hiatal ligament may theoretically serve as an anatomical region susceptible to direct tumor cell spread or distant metastasis. Objective To evaluate the effect of circumferential tumor location (CTL) on postoperative survival of low rectal cancer and to determine the effect of total hiatal ligament excision (THLE) on the prognosis of patients with posterior rectal cancer. Methods Patients with ultra‐low rectal cancer who underwent laparoscopic surgery between March 2014 and October 2021 were enrolled in this study. Propensity score matching (PSM) analysis was used to compare the clinicopathological characteristics and prognosis of patients in the posterior group and the non‐posterior group. Prognostic factors were identified using COX regression. PSM analysis was also used in the posterior tumor subgroup to compare the clinicopathological characteristics and prognosis of patients in the hiatal ligament traditional transection (HLTT) and THLE groups. Results After PSM, OS, and DFS were comparable between the posterior and non‐posterior groups. Similarly, no difference was noted in the local recurrence rate between the two groups (p = 0.23). The prognosis of ultra‐low rectal cancer was not affected by CTL. However, the local recurrence rate was significantly lower in the THLE group compared with the HLTT group (p = 0.023). Multivariate analysis of the posterior group identified CRM, TNM stage III, and HLTT as independent risk factors for local recurrence‐free survival. Conclusions CTL is not a prognostic risk factor for low rectal cancer. In posterior wall tumors, THLE significantly reduces the local recurrence rate for low rectal cancer.

Background The planting of mangroves is extensively used to control the invasive plant Spartina alterniflora in coastal wetlands. Different plant species release diverse sets of small organic compounds that affect rhizosphere conditions and support high levels of microbial activity. The root-associated microbial community is crucial for plant health and soil nutrient cycling, and for maintaining the stability of the wetland ecosystem. Methods High-throughput sequencing was used to assess the structure and function of the soil bacterial communities in mudflat soil and in the rhizosphere soils of S. alterniflora, mangroves, and native plants in the Oujiang estuarine wetland, China. A distance-based redundancy analysis (based on Bray–Curtis metrics) was used to identify key soil factors driving bacterial community structure. Results S. alterniflora invasion and subsequent mangrove afforestation led to the formation of distinct bacterial communities. The main soil factors driving the structure of bacterial communities were electrical conductivity (EC), available potassium (AK), available phosphorus (AP), and organic matter (OM). S. alterniflora obviously increased EC, OM, available nitrogen (AN), and NO3−-N contents, and consequently attracted copiotrophic Bacteroidates to conduct invasion in the coastal areas. Mangroves, especially Kandelia obovata, were suitable pioneer species for restoration and recruited beneficial Desulfobacterota and Bacilli to the rhizosphere. These conditions ultimately increased the contents of AP, available sulfur (AS), and AN in soil. The native plant species Carex scabrifolia and Suaeda glauca affected coastal saline soil primarily by decreasing the EC, rather than by increasing nutrient contents. The predicted functions of bacterial communities in rhizosphere soils were related to active catabolism, whereas those of the bacterial community in mudflat soil were related to synthesis and resistance to environmental factors. Conclusions Ecological restoration using K. obovata has effectively improved a degraded coastal wetland mainly through increasing phosphorus availability and promoting the succession of the microbial community.

Perfluorooctanoic acid (PFOA), a perfluoroalkyl compound, is linked to congenital heart diseases, though its underlying mechanisms remain unclear. We hypothesized that PFOA induces cardiac defects through the inhibition of the Keap1/Nrf2 pathway, leading to oxidative damage in cardiomyocytes. In this study, zebrafish embryos exposed to PFOA showed significant cardiac malformations and dysfunction, characterized by excessive reactive oxygen species (ROS), malondialdehyde (MDA) production, decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. Additionally, we observed dysregulation in the expression of key cardiac development genes (vmhc, gata4, nkx2.5, and sox9b). PFOA also reduced the expression of keap1, nrf2, and ho-1. After overexpression of Nrf2, levels of ROS and MDA decreased, while levels of SOD, CAT, and GSH-Px increased. Additionally, cardiomyocyte apoptosis and cardiac malformations were alleviated. These findings have suggested that PFOA induces oxidative stress through Keap1/Nrf2 pathway inhibition, ultimately leading to cardiac defects.

Herein, the efficiently high‐power pulsed Raman lasers with wavelength above 2.1 μm are experimentally demonstrated relying on the stimulated Raman scattering. A tailored high‐power noise‐like pulse (NLP) fiber laser system centered at ≈1953 nm with a maximum output power of ≈10.9 W is served as the pump source. By directly pumping a section of highly Ge‐doped silica fiber, the first pulsed Raman laser (centered at≈2139 nm) and the second pulsed Raman laser (centered at ≈2353 nm) with maximum output powers of ≈3.8 and ≈0.25 W are obtained, respectively, which represent the highest output powers of NLP at these wavelength regions, to the best of knowledge. Moreover, a high spectral purity of ≈94.3% of the first Raman laser is obtained, which indicates the significantly potential application of NLP in pulsed Raman laser. The midinfrared NLP fiber laser source will have potential applications in transparent polymer materials processing and midinfrared spectroscopy.

ABSTRACT Background Surveillance approaches with high sensitivity and specificity for hepatocellular carcinoma (HCC) are still urgently needed. Previous studies have shown that methylation of GNB4 and Riplet can effectively diagnose HCC. Aims This study plan to analyze the performance of a blood test for detecting HCC using GNB4 and Riplet methylation. Methods and Results This study mainly investigated the analytical performance of the dual‐target HCC blood test (DT‐HBT), including cut‐off value, limit of detection (LOD), precision, analytical specificity, and coincidence rate. In addition, the detection performance for HCC was validated in 1030 clinical plasma samples (214 HCC and 816 non‐HCC). Plasma samples from 25 HCC patients after hepatectomy were collected to assess the feasibility of the kit for postoperative recurrence monitoring. All analytical performance of the DT‐HBT met prespecified requirements. The LOD for GNB4, Riplet, and β‐actin was 1% methylation/100 copies/μL with cut‐offs of 43, 43, and 35, respectively. The DT‐HBT showed excellent precision, within 5% CV. It had a specificity of 91.5% for detecting other cancers, and 100% for breast, lung, and bladder cancer. No cross‐reactions were observed with 9 potential interfering substances. The DT‐HBT achieved a 100% coincidence rate in detecting reference and clinical samples. The clinical performance study found that the kit showed a sensitivity of 81.7% for stage I HCC, and an overall sensitivity and specificity of 87.4% and 92.3%, respectively. The detection sensitivity for postoperative recurrent patients was 95.8%, with a specificity of 100%. Conclusion The analytical performance of the DT‐HBT met prespecified criteria. It provided HCC patients with a reliable and high‐performing new blood test for the HCC diagnosis and surveillance. Trial Registration ClinicalTrials.gov identifier: NCT05685524

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.

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.

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 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 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.

Abstract Iso-butene (iso-C4H8) is an important raw material in chemical industry, whereas its efficient separation remains challenging due to similar molecular properties of C4 olefins. The ideal adsorbent should possess simultaneous high uptakes for 1,3-butadiene (C4H6) and n-butene (n-C4H8) counterparts, endowing high efficiency for iso-C4H8 separation in adsorption columns. Herein, a sulfate-pillared adsorbent, SOFOUR-DPDS-Ni (DPDS = 4,4′-dipyridyldisulfide), is reported for the efficient iso-C4H8 separation from binary and ternary C4 olefin mixtures. The rigidity in pore sizes and shapes of SOFOUR-DPDS-Ni exerts the molecular sieving of iso-C4H8, while exhibiting high C4H6 and n-C4H8 uptakes. The benchmark Henry’s selectivity for C4H6/iso-C4H8 (2321.8) and n-C4H8/iso-C4H8 (233.5) outperforms most reported adsorbents. Computational simulations reveal the strong interactions for C4H6 and n-C4H8. Furthermore, dynamic breakthrough experiments demonstrate the direct production of high-purity iso-C4H8 (>99.9%) from C4H6/iso-C4H8 (50/50, v/v), n-C4H8/iso-C4H8 (50/50, v/v), and C4H6/n-C4H8/iso-C4H8 (50/15/35, v/v/v) gas-mixtures.

Abstract Background Skin cutaneous melanoma (SKCM) is a highly lethal cancer, ranking among the top four deadliest cancers. This underscores the urgent need for novel biomarkers for SKCM diagnosis and prognosis. Anoikis plays a vital role in cancer growth and metastasis, and this study aims to investigate its prognostic value and mechanism of action in SKCM. Methods Utilizing consensus clustering, the SKCM samples were categorized into two distinct clusters A and B based on anoikis-related genes (ANRGs), with the B group exhibiting lower disease-specific survival (DSS). Gene set enrichment between distinct clusters was examined using Gene Set Variation Analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results We created a predictive model based on three anoikis-related differently expressed genes (DEGs), specifically, FASLG, IGF1, and PIK3R2. Moreover, the mechanism of these prognostic genes within the model was investigated at the cellular level using the single-cell sequencing dataset GSE115978. This analysis revealed that the FASLG gene was highly expressed on cluster 1 of Exhausted CD8( +) T (Tex) cells. Conclusions In conclusion, we have established a novel classification system for SKCM based on anoikis, which carries substantial clinical implications for SKCM patients. Notably, the elevated expression of the FASLG gene on cluster 1 of Tex cells could significantly impact SKCM prognosis through anoikis, thus offering a promising target for the development of immunotherapy for SKCM.

MAFB is essential for regulating male-type urethral differentiation, and especially, its variation can contribute to hypospadias in mice. However, the potential mechanism is still unclear. Here we observed that the basic leucine zipper (bZIP) transcription factor MAFB and CCAAT/enhancer-binding protein alpha (CEBPA) could promote human urothelium SV-HUC-1 growth. Moreover, MAFB and CEBPA expression were reduced in the prepuce tissues of hypospadias patients. Based on transcriptome sequencing analysis and Western blot, MAFB knockdown was found to suppress CEBPA protein expression and repress Wnt/β-catenin signaling in urothelium cells. Meanwhile, we observed blocked cell-cycle progression from the G1 to the S phase, inhibited cell proliferation, and activated apoptosis. Furthermore, MAFB could facilitate CEBPA transcription and regulate the proliferation of urothelium. The above results indicated that MAFB-mediated inhibition of urothelial SV-HUC-1 growth resulted from inhibiting the Wnt/β-catenin signaling pathway by down-regulating CEBPA. Our findings provide new insight into the understanding of genes associated with hypospadias and the pathogenic mechanism of this disorder.

In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.

There is growing recognition among researchers and stakeholders about the significant impact of artificial intelligence (AI) technology on classroom instruction. As a crucial element in developing AI literacy, AI education in K-12 schools is increasingly gaining attention. However, most existing research on K-12 AI education relies on experiential methodologies and suffers from a lack of quantitative analysis based on extensive classroom data, hindering a comprehensive depiction of AI education's current state at these educational levels. To address this gap, this article employs the advanced semantic understanding capabilities of large language models (LLMs) to create an intelligent analysis framework that identifies learning theories, pedagogical approaches, learning tools, and levels of AI literacy in AI classroom instruction. Compared with the results of manual analysis, analysis based on LLMs can achieve more than 90% consistency. Our findings, based on the analysis of 98 classroom instruction videos in central Chinese cities, reveal that current AI classroom instruction insufficiently foster AI literacy, with only 35.71% addressing higher-level skills such as evaluating and creating AI. AI ethics are even less commonly addressed, featured in just 5.1% of classroom instruction. We classified AI classroom instruction into three categories: conceptual (50%), heuristic (18.37%), and experimental (31.63%). Correlation analysis suggests a significant relationship between the adoption of pedagogical approaches and the development of advanced AI literacy. Specifically, integrating Project-based/Problem-based learning (PBL) with Collaborative learning appears effective in cultivating the capacity to evaluate and create AI.

Investigating methods for the detection of internal voids within road structures is a critical measure to ensure the safety and integrity of roadway operations. The purpose of this research is to investigate on the identification method of internal voids in pavement based on improved knowledge distillation technology. Ground penetrating radar data in three dimensions were extensively collected to capture the internal voids present within roadways, and this data was subsequently validated through in-situ verification. The echo characteristics of ground penetrating radar for areas with road voids were analyzed, and a dataset containing 1700 images of these internal voids was established. A YOLOv8 model improvement method was proposed, and a model for the detection of internal road voids was constructed based on the improved YOLO v8 framework. To further refine the model's performance, a knowledge distillation method based on multiple guidance from teacher assistants was developed. A stochastic learning approach was integrated, resulting in the establishment of a model optimized by this stochastic learning scheme for the identification of internal road voids. The results demonstrate that the presence of overfitting during the training phase of the void identification model can restrict its performance within a certain domain. The proposed stochastic learning-optimized, multi-teacher assistant guided knowledge distillation model, adeptly harnesses the performance benefits of both the teacher and assistant models by means of knowledge transfer, consequently achieving a significant improvement in the detection of internal road voids.

There is a growing demand for wood as a sustainable energy source and an essential carbon sink for ecosystems. Wood formation is a dynamic process involving plant radial growth in various stages, including vascular cambial cell proliferation, xylem mother cell differentiation and expansion, secondary cell wall thickening, and programmed cell death. Wood formation is controlled by highly complex molecular regulatory networks. Identifying and analyzing the molecular mechanisms regulating key target genes is crucial for further characterizing how wood is formed. This article summarizes the current knowledge regarding wood formation and the underlying molecular regulatory mechanisms.

ABSTRACTThe surface shot peening treatment was carried out on the as-cast SiCw/Al composites, and the distribution of the residual stresses in the surface matrix was measured, the X-ray diffraction method for the yield strength of the surface matrix of the composites was established to explore the strengthening effect of the surface shot peening. The results show that the surface matrix of the composites after shot peening shows a large compressive residual stress state, and the FWHM, that is, the microstructure strengthening effect, is significantly increased., resulting in an increase in the yield strength of the surface matrix of the composites.

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.