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Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis. Here, we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis (RA). Among them, decreased expression of RNA binding motif protein 25 (RBM25) was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages. Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes (including Il1b, Il6, and Cxcl10) was coupled with histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac modifications as well as hypoxia inducible factor-1α (HIF-1α) activity. Furthermore, RBM25 directly bound to and mediated the 14thexon skipping of ATP citrate lyase (Acly) pre-mRNA, resulting in two distinct Acly isoforms, Acly Long (Acly L) and Acly Short (Acly S). In proinflammatory macrophages, Acly L was subjected to protein lactylation on lysine 918/995, whereas Acly S did not, which influenced its affinity for metabolic substrates and subsequent metabolic activity. RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform, enhancing glycolysis and acetyl-CoA production for epigenetic remodeling, macrophage overactivation and tissue inflammatory injury. Finally, macrophage-specific deletion of RBM25 led to inflammaging, including spontaneous arthritis in various joints of mice and inflammation in multiple organs, which could be relieved by pharmacological inhibition of Acly. Overall, targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.

The shock in diabetes often requires rapid and adequate fluid administration, however, we report an anomalous case of fulminant type 1 diabetes mellitus (FT1DM) in which the patient’s condition worsened following fluid administration. In May 2020, a 29-year-old male presented with blood glucose of 89.8 mmol/L and diabetic ketoacidosis after a week of gastroenteritis. The diagnosis was finalized after C-peptide and Hemoglobin A1c (HbA1c) measurement. The patient was admitted with shock and received a positive fluid balance of 2800 ml in 5 h, but his condition deteriorated and progressed to multi-organ failure. This study attempts to explain the possible mechanisms and focuses on high-risk factors associated with FT1DM. Therefore, meticulous monitoring and individualized fluid administration strategies are crucial for the management of FT1DM. This case provides beneficial insights for clinical treatment of this condition.

ABSTRACTThe study examines two types of pre-service teachers’ teaching motivation and perceptions of teacher morality in China through the following three research questions: (1) What are pre-service teachers’ teaching motivations and perceptions of teacher morality? (2) What is the relationship between pre-service teachers’ perceptions of teaching motivation and teacher morality? (3) What are the differences between the two groups of pre-service teachers, and what factors influence their perceptions? Data are drawn from questionnaires on teacher morality in China and the FIT-Choice Scale, completed by 300 pre-service teachers, and semi-structured interviews with 25 pre-service teachers. The analyses of the findings reveal that pre-service teachers showed a high degree of teaching motivation and generally agreed with the Chinese state’s teacher morality requirements. This study suggests a “moral-motivation-reciprocity” framework for understanding pre-service teachers’ teaching motivation and perceptions of teacher morality in China.

The Luan River is the most important water system in north-eastern Hebei Province, China and is located in the transitional zone of the Eastern Yan Mountains, North China Plain and Songliao Plain. The well-developed river terraces of its tributary, the Yixun River, provide excellent information for studying neotectonics and climate change. There are seven terraces in the lower reaches of the Yixun River, numbered T7–T1. The optically stimulated luminescence dating results of 23 samples show that terraces T7–T2 formed at 111.36±5.83 ka, 78.20±4.45 ka, 65.29±4.15 ka, 56.44±3.07 ka, 40.08±2.66 ka, and 13.14±0.76 ka, respectively. A comparison with the oxygen isotope curves of deep-sea sediments reveals that the sediment formation of each terrace corresponded to cold periods of marine isotope stages MIS 4 and MIS 2 and the relatively cold periods of MIS 5e, MIS 3, and MIS 1. Since the Late Pleistocene, the incision rate of the Yixun River has ranged from 0.371–1.740 mm/a. During the formation of T7–T6, T5–T4, T4–T3, and T3–T2, the incision rate was low. However, in the two stages during which T6–T5 and T2–T1 formed (13.14±0.76 ka to 0.58±0.08 ka and 10.79±0.64 ka to 0.16±0.01 ka), these rates reached 1.554 mm/a and 1.592–1.740 mm/a, respectively. At approximately 30 ka, the activity of the Langying Fault increased, leading to footwall uplift. The river gathered in the north of Langying to form the ancient Erdaowan Lake, which resulted in the drying of the river in the lower reaches of the Yixun River during the last glacial maximum without forming river deposits. In the Early Holocene, headward erosion in the lower reaches of the Yixun River was enhanced, which resulted in the disappearance of the lake, and incised meandering formed due to increased neotectonism. Based on the analyses of river incision and the formation of ancient lakes and incised meandering, it was inferred that there have been three periods of strong tectonism in the river basin since the Late Pleistocene.

We compared heart rate variability (HRV) indices between people living with HIV (PLWH) and HIV-negative individuals to ascertain the independent association between HIV infection and reduced HRV, and further investigated whether distinct clinical laboratory profiles exist between PLWH with and without reduced HRV.

Ciphertext-policy attribute-based encryption (CP-ABE) for the cloud-assisted E-health system can effectively serve patients and healthcare professionals to achieve fine-grained sharing of health records. However, the problem of private key abuse could pose a security threat to patient data, while most of traceable CP-ABE schemes only can implement white-box traceability, which means that the traitor tracing problem cannot be solved thoroughly. Considering that malicious users or authority may forge the decryption device without getting caught, in this article, a black-box accountable CP-ABE is provided, which can identify the owner of the faked decryption device and the malicious activity of the authority. The authority will submit the tuple related with the user to the auditor for tracing the user’s identity. To avoid users from being framed by authority, the full decryption key should be generated by the interaction between the user and the authority. Namely, the user embeds a secret value in the key, which is used to generate an auditing ciphertext by the auditor for monitoring the malicious behavior of the authority. Furthermore, the indistinguishability under chosen-plaintext attack (IND-CPA) security of the proposed scheme is proven based on the $q$-type assumption, and the performance analysis indicates that the proposed scheme has more secure functionalities and no significant loss of efficiency.

Macrophages play a critical role in the immune homeostasis and host defense against invading pathogens. However, uncontrolled activation of inflammatory macrophages leads to tissue injury and even fuels autoimmunity. Hence the molecular mechanisms underlying macrophage activation need to be further elucidated. The effects of epigenetic modifications on the function of immune cells draw increasing attention. Here, we demonstrated that lysine-specific demethylase 5B (KDM5B), a classical transcriptional repressor in stem cell development and cancer, was required for the full activation of NF-κB signaling cascade and pro-inflammatory cytokine production in macrophages. KDM5B deficiency or inhibitor treatment protected mice from immunologic injury in both collagen-induced arthritis (CIA) model and endotoxin shock model. Genome-wide analysis of KDM5B-binding peaks identified that KDM5B was selectively recruited to the promoter of Nfkbia, the gene encoding IκBα, in activated macrophages. KDM5B mediated the H3K4me3 modification erasing and decreased chromatin accessibility of Nfkbiagene locus, coordinating the elaborate suppression of IκBα expression and the enhanced NF-κB-mediated macrophage activation. Our finding identifies the indispensable role of KDM5B in macrophage-mediated inflammatory responses and provides a candidate therapeutic target for autoimmune and inflammatory disorders.

Exploring the current runoff characteristics after the large-scale implementation of the Grain for Green (GFG) project and investigating its sensitivities to potential drivers are crucial for water resource prediction and management. Based on the measured runoff data of 62 hydrological stations in the Weihe River Basin (WRB) from 2006 to 2018, we analyzed the temporal and spatial runoff characteristics in this study. Correlation analysis was used to investigate the relationships between different runoff indicators and climate-related factors. Additionally, an improved Budyko framework was applied to assess the sensitivities of annual runoff to precipitation, potential evaporation, and other factors. The results showed that the daily runoff flow duration curves (FDCs) of all selected hydrological stations fall in three narrow ranges, with the corresponding mean annual runoff spanning approximately 1.50 orders of magnitude, indicating that the runoff of different hydrological stations in the WRB varied greatly. The trend analysis of runoff under different exceedance frequencies showed that the runoff from the south bank of the Weihe River was more affluent and stable than that from the north bank. The runoff was unevenly distributed throughout the year, mainly in the flood season, accounting for more than 50.00% of the annual runoff. However, the trend of annual runoff change was not obvious in most areas. Correlation analysis showed that rare-frequency runoff events were more susceptible to climate factors. In this study, daily runoff under 10%–20% exceeding frequencies, consecutive maximum daily runoff, and low-runoff variability rate had strong correlations with precipitation, aridity index, and average runoff depth on rainy days. In comparison, daily runoff under 50%–99% exceeding frequencies, consecutive minimum daily runoff, and high-runoff variability rate had weak correlations with all selected impact factors. The sensitivity analysis results suggested that the sensitivity of annual runoff to precipitation was always higher than that to potential evaporation. The runoff about 87.10% of the selected hydrological stations were most sensitive to precipitation changes, and 12.90% were most sensitive to other factors. The spatial pattern of the sensitivity analysis indicated that in relatively humid southern areas, runoff was more sensitive to potential evaporation and other factors, and less sensitive to precipitation.

With the globalization of industrial development, use of unsafe water has become a major problem of morbidity and mortality in various countries. Chlorination and ozone disinfection to remove disease-causing microbes can only be done in energy-rich regions and is impractical for most parts of the planet. In this study, natural non-toxic hydrogel loaded with bimetallic peroxide (CeCuOx) has been designed with H2O2self-supply and synergistic effect-mediated cascade Fenton-like catalytic chemistry for high-efficiency water disinfection. The CeCuOxcould in situdecompose to H2O2and bimetallic oxide by responding to the weakly acidic water body, followed by direct •OH generation via Ce / Cu synergistic-enhanced Fenton-like catalytic reaction, which significantly improved the antibacterial activity without any assistance of O2and external energy. Moreover, the well-proportioned pore structures of gel endow good bacteria adhesion and allow for long-term release of nano-catalyst, significantly promoting the antibacterial activity. Superior water disinfection efficiency was achieved at extremely low dose of 0.075 g active CeCuOxand no harmful byproducts were formed, which was superior to those previously reported works. Therefore, the bimetallic peroxide nanocatalytic gel provides a simple efficient, low-cost and affordable path in the field of water disinfection.

Creating a cleaner, more sustainable, low-carbon energy system is the essential prerequisite for the coordinated governance of pollution reduction and carbon reduction (CGPRCR). This paper focuses on the impact of the pilot policy of the new energy demonstration city on CGPRCR. Based on the research purpose, this paper takes the Whole Process Governance Theory as the theoretical foundation, and employs panel data of 280 prefecture-level cities from 2011 to 2020. The transmission mechanism of new energy demonstration city policy aims at advancing CGPRCR is analyzed by using the DID model. The impact of city heterogeneity on policy effects is examined from the perspective of multidimensional heterogeneity. The findings indicate that: (1) The implementation of the new energy demonstration city policy can greatly contribute to the CGPRCR. This finding remains valid even after conducting a series of robustness tests, such as PSM-DID and placebo test; (2) The mechanism test demonstrates that the policy can optimize the industrial structure, encourage the development of green technologies, and strengthen environmental regulations, all of which can empower the entire governance process and indirectly support the CGPRCR; (3) The policy has a more noticeable impact on the CGPRCR in eastern cities, large cities, and cities with better innovation foundations.

The role of serum albumin (ALB) has been extensively studied in patients with cancer; however, research on its effect on bone metastasis in these patients remains limited. This study aimed to investigate the relationship between serum ALB and alkaline phosphatase (ALP) levels in patients with tumors. Using data from the National Health and Nutrition Examination Survey 2011 to 2018, we assessed the correlation between serum ALB and ALP levels using a weighted multivariate linear regression model, whereas a weighted generalized additive model and smooth curve fitting were used to address potential nonlinearities. A total of 1876 patients with cancer were included in our study. In the subgroup analysis stratified by sex, race/ethnicity, and liver disease, the negative correlation of ALB with ALP remained for most groups, except in blacks (β = −1.755, 95%CI: [−3.848, 0.338], P = .103) and patients with gout (β = −0.676, 95%CI: [−2.061, 0.709], P = .340). In black people and patients with gout, the relationship between ALB and ALP showed an inverted U-shaped curve, with an inflection point at approximately 42 g/dL. Our study showed an inverse correlation between ALB and ALP levels in most patients with tumors, but not in black patients and those with gout. The measurement of ALB levels can serve as a screening tool for bone metastases while guiding therapeutic intervention strategies.

Inconclusive results have been reported in studies evaluating the association between HIV infection and subclinical atherosclerosis. Unsolved issues include whether the increased atherosclerosis burden observed in some studies is attributed to greater prevalence of traditional risk factors or HIV infection. Therefore, we evaluated the association of HIV infection with subclinical atherosclerosis as assessed by carotid artery intima-media thickness, while controlling for the effects of traditional risk factors as operationalised by the Framingham risk score (FRS).

AbstractThe spatial resolution of Chinese Gaofen-3 (GF-3) Synthetic Aperture Radar (SAR) image, a pixel size of 500 m at azimuth/flight direction for Global Observation (GLO) and 100 m for Wide ScanSAR (WSC) modes, is relatively coarse, and waves shorter than 100 m are undetectable. In this study, SAR images collected under typhoon conditions by the GF-3 mission are exploited for wave retrieval purposes. In detail, six imagery collected during 2017 and 2018 over the China Seas captured four typhoons. The GLO and WSC modes images are collocated with simulated wave fields using a numeric wave model, called WAVEWATCH-III (WW3) and are processed using a machine learning method to retrieve sea surface waves. In this work, the criterion for the training completion in the process of machine learning is set as 0.15 m of Root mean Square Error (RMSE) for the Significant Wave Height (SWH). Then, the retrieved SWH is compared with measurements collected by the Jason-2 altimeter, showing a 0.61 m RMSE. The proposed algorithm is shown to outperform empirical approaches developed to retrieve the SWH using GF-3 SAR imagery acquired in the GLO and WSC imaging modes.

Supplemental digital content is available in the text.

Human taeniasis, caused by Taeniatapeworms, is a global parasitic disease with significant implications for public health and food safety. These tapeworms can grow to considerable sizes and potentially impact the microecology of the host gut. Despite their importance, the effects of Taeniainfection on host gut microbiota haven’t been thoroughly investigated. In this study, we conducted a cross-sectional analysis of the gut microbiome in patients infected with Taenia asiatica(n= 87) compared to healthy controls (n= 79) in the Dali cohort, China. We also performed a longitudinal assessment of microbial changes following deworming in a subset of patients (n= 24). Our findings reveal a significant shift in gut microbial composition, characterized by increased alpha-diversity and an enrichment of Prevotella-driven enterotypes in infected patients compared to healthy controls. The stability of these microbial features post-deworming varied widely among individuals and was lower in those with lower initial alpha diversity and Prevotella-enterotype before deworming. We observed a significant depletion of Bifidobacteriumspecies in infected individuals, regardless of enterotypes, and these prebiotics did not recover post-deworming. Metabolic network analysis and in vitroexperiments suggest that the reduction of Bifidobacteriumwas linked to metabolic competition for ecological niches or nutrients, particularly stachyose, from other microbes rather than the parasitism itself. Furthermore, our machine learning analysis demonstrated that taxa associated with Bifidobacteriumin stachyose metabolism could robustly predict infection but could not predict deworming. This study highlights the substantial impact of taeniasis on the human gut microbiome and overall gut health.

Background: The correlation between the preoperative splenic area measured on CT scans and the overall survival (OS) of early-stage non-small cell lung cancer (NSCLC) patients remains unclear. Methods: A retrospective discovery cohort and validation cohort consisting of consecutive NSCLC patients who underwent resection and preoperative CT scans were created. The patients were divided into two groups based on the measurement of their preoperative splenic area: normal and abnormal. The Cox proportional hazard model was used to analyse the correlation between splenic area and OS. Results: The discovery and validation cohorts included 2532 patients (1374 (54.27%) males; median (IQR) age 59 (52–66) years) and 608 patients (403 (66.28%) males; age 69 (62–76) years), respectively. Patients with a normal splenic area had a 6% higher 5-year OS (n = 727 (80%)) than patients with an abnormal splenic area (n = 1805 (74%)) (p= 0.007) in the discovery cohort. A similar result was obtained in the validation cohort. In the univariable analysis, the OS hazard ratios (HRs) for the patients with abnormal splenic areas were 1.32 (95% confidence interval (CI): 1.08, 1.61) in the discovery cohort and 1.59 (95% CI: 1.01, 2.50) in the validation cohort. Multivariable analysis demonstrated that abnormal splenic area was independent of shorter OS in the discovery (HR: 1.32, 95% CI: 1.08, 1.63) and validation cohorts (HR: 1.84, 95% CI: 1.12, 3.02). Conclusion: Preoperative CT measurements of the splenic area serve as a prognostic indicator for early-stage NSCLC patients, offering a novel metric with potential implications for personalized therapeutic strategies in top-tier oncology research.

Gram-negative bacteria, containing toxic proinflammatory and pyrogenic substances [endotoxin or lipopolysaccharide (LPS)], can lead to infection and associated serious diseases, such as sepsis and septic shock. Development of antimicrobial materials with intrinsically endotoxin adsorption activity can prevent the release of bacterial toxic components while killing bacteria. Herein, a series of imidazolium-type polyurethane (PU) foams with antimicrobial properties were synthesized. The content effects of cationic moieties on the antimicrobial activities against Gram-negative Escherichia coliand Pseudomonas aeruginosaand Gram-positive Staphylococcus aureusas well as the endotoxin adsorption property were investigated. The obtained PU foams show slightly higher efficiency against two Gram-negative strains than for Gram-positive one and high absorbability of LPS. A wound healing test using P. aeruginosaand its isolated LPS-treated mice as the models further demonstrated that imidazolium-type PU foams combine both antibacterial and endotoxin adsorption properties and may have a potential application as an antimicrobial wound dressing in a clinical setting.

Ferrocene (Fc)-containing imidazolium type ionic liquids (ILs) and corresponding poly(ionic liquid) (PIL) membranes with tunable antibacterial activity based on electrochemical redox reaction and host-guest chemistry were developed. The effect of Fc moiety on the antimicrobial activities against both Staphylococcus aureus (S. aureus)and Escherichia coli (E. coli)was studied by minimum inhibitory concentration (MIC). The presence of Fc groups highly enhanced the antibacterial efficiency of Fccontaining ILs because of the generation of reactive oxygen species (ROS). The electrochemical oxidation of Fc to Fc+and the formation of inclusion complexes between Fc and β-CD via host-guest interactions decreased the antibacterial activities of ILs and PIL membranes. The antibacterial activities may be recovered in some extent upon the electrochemical reduction of Fc+to Fc or the exclusion of the Fc out of the cavity of β-CD. Furthermore, all the Fc-containing PIL membranes showed relatively low hemolysis activities and none cytotoxicity toward human cells, indicating clinical feasibility in topical applications.

Nano‐catalytic bacterial killing provides new opportunities to address ever‐increasing antibiotic resistance. However, the intrinsic catalytic activity usually depends on a much lower pH conditions (pH = 2–5) than that in the weakly acidic bacterial microenvironments (pH = 6–7) for reactive oxygen species production by Fenton reactions. Herein, a MnSiO3‐based pH‐ultrasensitive “in situ structure transformation” is first reported to significantly promote the adhesion between material and bacteria, and shorten the diffusion distance (<20 nm) to compensate ultra‐short life (<200 ns) of ·OH generated by Mn2+‐mediated Fenton‐like reaction, finally enhancing its nano‐catalytic antibacterial performance in weakly acidic conditions. A separated spray bottle is further designed to achieve in situ gelation at the wound site, which demonstrates excellent shape adaptability to complicated and rough surfaces of wounds, allowing for long‐term nano‐catalyst release. As a result, bacterial‐infected wound healing is efficiently promoted. Herein, the in situ sprayed nano‐catalytic antibacterial gel presents a promising paradigm for bacterial infection treatment. MnSiO3‐based “in situ structure transformation” strategy is introduced to design a sprayed gel for pH‐ultrasensitive nano‐catalytic antibacterial therapy, which demonstrates high antibacterial efficacy in the very weakly acidic bacterial microenvironment and excellent shape adaptability to complicated and rough surface of wounds, allowing for long‐term nano‐catalyst release and efficiently promoting bacterial‐infected wound healing with high biocompatibility.

A redox hydrogel was prepared from the ferrocene (Fc) modified amino acid, phenylalanine (Phe, F), and utilized to construct an immunosensing platform for the label-free detection of a cancer biomarker prostate specific antigen (PSA). The synthesized hydrogel contains a large number of Fc moieties, which imparts the hydrogel with redox properties. The hydrogel modified electrode displays a pair of reversible redox peaks, indicating the facile electron transfer of Fc in the hydrogel at the electrode surface. After the immobilization of the anti-PSA antibody onto the hydrogel modified electrode surface and the capture of PSA molecules, the redox current at the electrode was suppressed significantly due to the blocking of the electron transfer at the electrode surface by the formed immuno-complex. The current change was proportional to the concentration of PSA detected in the range from 1 pg mL−1to 10 ng mL−1with a detection limit of 0.5 pg mL−1. The proposed immunosensor is simple with a low cost and high sensitivity, which could find wide clinical applications.

No relevant conflicts of interest to declare.

Introduction:Although steady improvements to chemotherapeutic treatments have helped cure 80% of childhood B-cell acute lymphoblastic leukemia (B-ALL) cases, chemotherapy has proven to be less effective in treating the majority of adult patients, the equivalent rate for adults remains poor at 30-40%, with relapse representing the leading cause of mortality in both children and adults. Development of chemo-resistance is a crucial factor contributing to relapse, therefore understanding the biological mechanisms underlying this resistance is imperative for discovering innovative treatment strategies. Relapse specific/enriched genetic alterations in the emergence of clones that have gained a selective advantage under the pressure of specific chemotherapeutics. We previously performed longitudinal whole-exome sequencing analysis in diagnosis/relapse pairs from adult patients with B-ALL revealed relapse-specific mutations in NR3C1 gene, encoding the glucocorticoid receptor (GCR), are frequently detected. Furthermore, the mutations of NR3C1 identified in relapsed B-ALL patients all resulted in haploinsufficiency for NR3C1. In this study, we sought to delineate whether reduced expression of NR3C1 could give rise to chemo-resistance in B-ALL and elucidate the mechanism responsible for the resistance.

Recent studies have illustrated the significance of some proinflammatory factors in regulating embryonic hemtopoietic stem cells (HSCs) production ,such as TNFα、IFNγ and TLR4.Il6 is a powerful proinflammatory cytokine that plays a pivotal role in the regulation of immunity,hematopoiesis and other physiological processes.Il6-deficient mice leads to impaired survival and self-renewal of HSCs and early progenitors.Whereas Il6 signaling regulates aspects of adult hematopoiesis,little is known about its role in the developmental specification of HSCs.This has led us to explore the impact of loss of Il6 signaling on embryonic HSC emergence by injecting specific antisense morpholinos (MOs) into zebrafish embryos at 1-2 cell stage.