Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity.

The presence of DNA in the cytoplasm is normally a sign of microbial infections and is quickly detected by cyclic GMP-AMP synthase (cGAS) to elicit anti-infection immune responses. However, chronic activation of cGAS by self-DNA leads to severe autoimmune diseases for which no effective treatment is available yet. Here we report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. We find that cGAS acetylation on either Lys384, Lys394, or Lys414 contributes to keeping cGAS inactive. cGAS is deacetylated in response to DNA challenges. Importantly, we show that aspirin can directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, we demonstrate that aspirin can effectively suppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Thus, our study reveals that acetylation contributes to cGAS activity regulation and provides a potential therapy for treating DNA-mediated autoimmune diseases.

Self-Healing Superwetting Surfaces, Their Fabrications, and Properties.

The research on superwetting surfaces with a self-healing function against various damages has progressed rapidly in the recent decade. They are expected to be an effective approach to increasing the durability and application robustness of superwetting materials. Various methods and material systems have been developed to prepare self-healing superwetting surfaces, some of which mimic natural superwetting surfaces. However, they still face challenges, such as being workable only for specific damages, external stimulation to trigger the healing process, and poor self-healing ability in the water, marine, or biological systems. There is a lack of fundamental understanding as well. This article comprehensively reviews self-healing superwetting surfaces, including their fabrication strategies, essential rules for materials design, and self-healing properties. Self-healing triggered by different external stimuli is summarized. The potential applications of self-healing superwetting surfaces are highlighted. This article consists of four main sections: (1) the functional surfaces with various superwetting properties, (2) natural self-healing superwetting surfaces (i.e., plants, insects, and creatures) and their healing mechanism, (3) recent research development in various self-healing superwetting surfaces, their preparation, wetting properties in the air or liquid media, and healing mechanism, and (4) the prospects including existing challenges, our views and potential solutions to the challenges, and future research directions.

NLRP3 Phosphorylation Is an Essential Priming Event for Inflammasome Activation.

Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. We show that NLRP3 inflammasome activation is disrupted in NLRP3-S194A knockin mice. JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly. Importantly, we demonstrate that blocking S194 phosphorylation prevents NLRP3 inflammasome activation in cryopyrin-associated periodic syndromes (CAPS). Thus, our study reveals a key priming molecular event that is a prerequisite for NLRP3 inflammasome activation. Inhibiting NLRP3 phosphorylation could be an effective treatment for NLRP3-related diseases.

The mud-dwelling clam Meretrix petechialis secretes endogenously synthesized erythromycin.

Although lacking an adaptive immune system and often living in habitats with dense and diverse bacterial populations, marine invertebrates thrive in the presence of potentially challenging microbial pathogens. However, the mechanisms underlying this resistance remain largely unexplored and promise to reveal novel strategies of microbial resistance. Here, we provide evidence that a mud-dwelling clam, Meretrix petechialis, synthesizes, stores, and secretes the antibiotic erythromycin. Liquid chromatography coupled with mass spectrometry, immunocytochemistry, fluorescence in situ hybridization, RNA interference, and enzyme-linked immunosorbent assay revealed that this potent macrolide antimicrobial, thought to be synthesized only by microorganisms, is produced by specific mucus-rich cells beneath the clam's mantle epithelium, which interfaces directly with the bacteria-rich environment. The antibacterial activity was confirmed by bacteriostatic assay. Genetic, ontogenetic, phylogenetic and genomic evidence, including genotypic segregation ratios in a family of full siblings, gene expression in clam larvae, phylogenetic tree, and synteny conservation in the related genome region further revealed that the genes responsible for erythromycin production are of animal origin. The detection of this antibiotic in another clam species showed that the production of this macrolide is not exclusive to M. petechialis and may be a common strategy among marine invertebrates. The finding of erythromycin production by a marine invertebrate offers a striking example of convergent evolution in secondary metabolite synthesis between the animal and bacterial domains. These findings open the possibility of engineering-animal tissues for the localized production of an antibacterial secondary metabolite.

Diagnosis and prognosis of breast cancer by high-performance serum metabolic fingerprints.

High-performance metabolic analysis is emerging in the diagnosis and prognosis of breast cancer (BrCa). Still, advanced tools are in demand to deliver the application potentials of metabolic analysis. Here, we used fast nanoparticle-enhanced laser desorption/ionization mass spectrometry (NPELDI-MS) to record serum metabolic fingerprints (SMFs) of BrCa in seconds, achieving high reproducibility and low consumption of direct serum detection without treatment. Subsequently, machine learning of SMFs generated by NPELDI-MS functioned as an efficient readout to distinguish BrCa from non-BrCa with an area under the curve of 0.948. Furthermore, a metabolic prognosis scoring system was constructed using SMFs with effective prediction performance toward BrCa (P < 0.005). Finally, we identified a biomarker panel of seven metabolites that were differentially enriched in BrCa serum and their related pathways. Together, our findings provide an efficient serum metabolic tool to characterize BrCa and highlight certain metabolic signatures as potential diagnostic and prognostic factors of diseases including but not limited to BrCa.

Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

A Fully Automated Online Enrichment and Separation System for Highly Reproducible and In-Depth Analysis of Intact Glycopeptide.

A fully automated online enrichment and separation system for intact glycopeptides, named AutoGP, was developed in this study by integrating three different columns in a nano-LC system. Specifically, the peptide mixture from the enzymatic digestion of a complex biological sample was first loaded on a hydrophilic interaction chromatography (HILIC) column. The nonglycopeptides in the sample were washed off the column, and the glycopeptides retained by the HILIC column were eluted to a C18 trap column to achieve an automated glycopeptide enrichment. The enriched glycopeptides were further eluted to a C18 column for separation, and the separated glycopeptides were eventually analyzed by using an orbitrap mass spectrometer (MS). The optimal operating conditions for AutoGP were systemically studied, and the performance of the fully optimized AutoGP was compared with a conventional manual system used for glycopeptide analysis. The experimental evaluation shows that the total number of glycopeptides identified is at least 1.5-fold higher, and the median coefficient of variation for the analyses is at least 50% lower by using AutoGP, as compared to the results acquired by using the manual system. In addition, AutoGP can perform effective analysis even with a 1-µg sample amount, while a 10-µg sample at least will be needed by the manual system, implying an order of magnitude better sensitivity of AutoGP. All the experimental results have consistently proven that AutoGP can be used for much better characterization of intact glycopeptides.

Integrated transcriptomic and metabolomic analyses reveals anthocyanin biosynthesis in leaf coloration of quinoa (Chenopodium quinoa Willd.).

BACKGROUND: Quinoa leaves demonstrate a diverse array of colors, offering a potential enhancement to landscape aesthetics and the development of leisure-oriented sightseeing agriculture in semi-arid regions. This study utilized integrated transcriptomic and metabolomic analyses to investigate the mechanisms underlying anthocyanin synthesis in both emerald green and pink quinoa leaves. RESULTS: Integrated transcriptomic and metabolomic analyses indicated that both flavonoid biosynthesis pathway (ko00941) and anthocyanin biosynthesis pathway (ko00942) were significantly associated with anthocyanin biosynthesis. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were analyzed between the two germplasms during different developmental periods. Ten DEGs were verified using qRT-PCR, and the results were consistent with those of the transcriptomic sequencing. The elevated expression of phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), 4-coumarate CoA ligase (4CL) and Hydroxycinnamoyltransferase (HCT), as well as the reduced expression of flavanone 3-hydroxylase (F3H) and Flavonol synthase (FLS), likely cause pink leaf formation. In addition, bHLH14, WRKY46, and TGA indirectly affected the activities of CHS and 4CL, collectively regulating the levels of cyanidin 3-O-(3'', 6''-O-dimalonyl) glucoside and naringenin. The diminished expression of PAL, 4CL, and HCT decreased the formation of cyanidin-3-O-(6"-O-malonyl-2"-O-glucuronyl) glucoside, leading to the emergence of emerald green leaves. Moreover, the lowered expression of TGA and WRKY46 indirectly regulated 4CL activity, serving as another important factor in maintaining the emerald green hue in leaves N1, N2, and N3. CONCLUSION: These findings establish a foundation for elucidating the molecular regulatory mechanisms governing anthocyanin biosynthesis in quinoa leaves, and also provide some theoretical basis for the development of leisure and sightseeing agriculture.

Scavenger receptor a is a major homeostatic regulator that restrains drug-induced liver injury.

BACKGROUND AND AIM: Drug-induced liver injury occurs frequently and can be life threatening. Although drug-induced liver injury is mainly caused by the direct drug cytotoxicity, increasing evidence suggests that the interplay between hepatocytes and immune cells can define this pathogenic process. Here, we interrogate the role of the pattern recognition scavenger receptor A (SRA) for regulating hepatic inflammation and drug-induced liver injury. APPROACH AND RESULTS: Using acetaminophen (APAP) or halothane-induced liver injury models, we showed that SRA loss renders mice highly susceptible to drug hepatotoxicity, indicated by the increased mortality and liver pathology. Mechanistic studies revealed that APAP-induced liver injury exaggerated in the absence of SRA was associated with the decreased anti-inflammatory and prosurvival cytokine IL-10 concomitant with excessive hepatic inflammation. The similar correlation between SRA and IL-10 expression was also seen in human following APAP uptake. Bone marrow reconstitution and liposomal clodronate depletion studies established that the hepatoprotective activity of SRA mostly resized in the immune sentinel KCs. Furthermore, SRA-facilitated IL-10 production by KCs in response to injured hepatocytes mitigated activation of the Jun N-terminal kinase-mediated signaling pathway in hepatocytes. In addition, supplemental use of IL-10 with N -acetylcysteine, only approved treatment of APAP overdose, conferred mice improved protection from APAP-induced liver injury. CONCLUSION: We identify a novel hepatocyte-extrinsic pathway governed by the immune receptor SRA that maintains liver homeostasis upon drug insult. Giving that drug (ie, APAP) overdose is the leading cause of acute liver failure, targeting this hepatoprotective SRA-IL-10 axis may provide new opportunities to optimize the current management of drug-induced liver injury.

Inter-algal associations and nutrients linked by Scenedesmus and Desmodesmus structure eukaryotic algal communities.

Eutrophication reduces the variability of the community composition of plankton. However, the mechanisms underlying the diversity and restructuring of eukaryotic algal communities remain unknown. This study analysed the diversity and compositional patterns of algal communities in shallow eutrophic lakes. It investigated how these communities were modified by key genera through mediating inter-algal associations under the influence of abiotic factors. Inter-algal associations explained more variance in algal communities than environmental variables, and variation in composition and diversity was primarily derived from Scenedesmus, Desmodesmus and Cryptomonas, rather than nutrients. Scenedesmus and Desmodesmus were positively correlated with the genera of Chlorophyta and formed the hub of the algal association network. When the relative abundance of Scenedesmus and Desmodesmus increased from 0.41% to 13.74%, communities enriched in biomarkers of Bacillariophyta, Chrysophyceae and Cryptophyta transitioned to communities enriched in biomarkers of Chlorophyta. Moreover, negative associations between the Chlorophyta hub genera and other non-Chlorophyta genera increased. High concentrations of total phosphorus altered the composition of algal communities by increasing the abundance of Scenedesmus and Desmodesmus, which in turn had cascading effects through inter-algal associations. Additionally, algal communities with higher abundances of Scenedesmus and Desmodesmus were more susceptible to the effects of total phosphorus. Our study suggested that inter-algal associations, centred on Scenedesmus and Desmodesmus, had a greater influence on algal diversity and community structure than other factors. Nutrient levels were not a direct driver of algal diversity and community structure adjustments, but acted indirectly by enhancing the influence of Scenedesmus and Desmodesmus.

Activation of a novel α2AAR-spinophilin-cofilin axis determines the effect of α2 adrenergic drugs on fear memory reconsolidation.

Posttraumatic stress disorder (PTSD) after the pandemic has emerged as a major neuropsychiatric component of post-acute COVID-19 syndrome, yet the current pharmacotherapy for PTSD is limited. The use of adrenergic drugs to treat PTSD has been suggested; however, it is hindered by conflicting clinical results and a lack of mechanistic understanding of drug actions. Our studies, using both genetically modified mice and human induced pluripotent stem cell-derived neurons, reveal a novel α2A adrenergic receptor (α2AAR)-spinophilin-cofilin axis in the hippocampus that is critical for regulation of contextual fear memory reconsolidation. In addition, we have found that two α2 ligands, clonidine and guanfacine, exhibit differential abilities in activating this signaling axis to disrupt fear memory reconsolidation. Stimulation of α2AAR with clonidine, but not guanfacine, promotes the interaction of the actin binding protein cofilin with the receptor and with the dendritic spine scaffolding protein spinophilin to induce cofilin activation at the synapse. Spinophilin-dependent regulation of cofilin is required for clonidine-induced disruption of contextual fear memory reconsolidation. Our results inform the interpretation of differential clinical observations of these two drugs on PTSD and suggest that clonidine could provide immediate treatment for PTSD symptoms related to the current pandemic. Furthermore, our study indicates that modulation of dendritic spine morphology may represent an effective strategy for the development of new pharmacotherapies for PTSD.

The combination of high temperature and Vibrio infection worsens summer mortality in the clam Meretrix petechialis by increasing apoptosis and oxidative stress.

The interaction between environmental factors and Vibrio in bivalves is not well understood, despite the widely held belief that pathogen infection and seawater temperature significantly impact summer mortality. In the present study, we conducted simulated experiments to explore the effects of high temperature and Vibrio infection on the clam Meretrix petechialis. The survival curve analysis revealed that the combined challenge of high temperature and Vibrio infection (31°C-vibrio) led to significantly higher clam mortality compared to the groups exposed solely to Vibrio (27°C-vibrio), high temperature (31°C-control), and the control condition (27°C-control). Furthermore, PCoA analysis of 11 immune genes indicated that Vibrio infection predominated during the incubation period, with a gradual equilibrium between these factors emerging during the course of the infection. Additionally, our investigations into apoptosis and autophagy processes exhibited significant induction of mTOR and Bcl2 of the 31°C-vibrio group in the early challenge stage, followed by inhibition in the later stage. Oxidative stress analysis demonstrated a substantial additive effect on malondialdehyde (MDA) and glutathione (GSH) content in the combined challenge group compared to the control group. Comparative transcriptome analysis revealed a significant increase in differentially expressed genes related to immunity, such as complement C1q-like protein, C-type lectin, big defensin, and lysozyme, in the 31°C-vibrio group, suggesting that the synergistic effect of high temperature and Vibrio infection triggers more robust antibacterial immune responses. These findings provide critical insights for understanding the infection process and uncovering the causes of summer mortality.

A new mode for the diagnosis of angioimmunoblastic T-cell lymphoma.

In order to explore a new mode for the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), 31 cases of AITL and 28 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) were used as the study subjects. Identifying T follicular helper (TFH) cells with CD4, CD10, Bcl-6, and PD-1, identifying proliferative B cells with CD20 and EZH2, identifying proliferative follicular dendritic cells (FDCs) with CD21 and CD23, and analyzing the value of TFH/B/FDC proliferation and immunolocalization in the diagnosis of AITL. (1) Outside the inherent lymphoid follicles, simultaneous proliferation of TFH/B/FDC (a new diagnostic mode) were observed in AITL [83.87%; 26/31], with their immunolocalizations in the same site [83.87%; 26/31], while this phenomenon was not observed in 28 cases of PTCL-NOS (P<0.05). (2) The sensitivity and specificity of using this new mode to diagnose AITL were both high (83.87%, 100%), which was superior to CD2 (100%, 0%), CD3 (100%, 0%), CD4 (100%, 32.14%), CD5 (100%, 25%), CD10 (61.9%, 100%), Bcl-6 (42.86%, 100%), PD-1 (83.87%, 96.43%), and its Youden Index (0.84) was the highest. The areas under the curve (AUC) of CD10, Bcl-6, PD-1, and new mode to diagnosis AITL were 0.81, 0.71, 0.90, and 0.92, respectively, while the new mode had the highest AUC. The simultaneous proliferation of TFH/B/FDC cells outside the inherent lymphoid follicles can be used to assist in the diagnosis of AITL, and the simultaneous spatiotemporal proliferation of TFH/B/FDC cells is a specific immunomorphology of AITL.

Eutrophication promotes resource use efficiency and toxin production of Microcystis in a future climate warming scenario.

Addressing the risks of cyanobacterial blooms and toxin production under ongoing and accelerating eutrophication and climate warming is crucial for both water ecosystem services and human health. Therefore, we here explored the interactive effects of eutrophication and warming on freshwater ecosystems, focusing on Microcystis and its cyanotoxin production. We employed a large-scale mesocosm system simulating future climate warming scenarios in concert with varying degrees of nutrient enrichment. We explored the full range of identified cyanobacterial toxins and cyanotoxin-producing genes under different experimental conditions and assessed the effects of both eutrophication and warming on both phytoplankton community structure (algal densities, community stability) and function (resource use efficiency, RUE). We show here that eutrophication increases the RUE of Microcystis and promotes an increase in toxin-producing genes, leading to a substantial increase in the dominance of Microcystis. This increase correlates with enhanced cyanotoxin production, a trend exacerbated under the influence of future climate warming, suggesting interactions between eutrophication and climate warming on Microcystis ecology and cyanotoxin dynamics. Hence, heatwaves and eutrophication lead the phytoplankton community to be dominated by a minority of algal species with higher toxic capacity. In a broader context, our study underscores the urgent need for holistic management strategies, addressing both nutrient control and climate mitigation, to effectively manage the escalating ecological risks associated with cyanobacterial dominance and toxin production.

A nomogram for predicting postpartum post-traumatic stress disorder: a prospective cohort study.

BACKGROUND: Postpartumpost-traumatic stress disorder (PTSD), as a psychological stress disorder, has long-term and widespread harm. Still, compared with other postpartum psychiatric disorders, postpartum PTSD has received relatively littleattention in China. This study aims to investigate the risk factors of postpartum PTSD and to develop a convenient and rapid nomogram screening tool to help clinical staff identify high-risk pregnant womenin time and take preventative and management measures. METHODS: Recruited pregnant women hospitalized for delivery in Qingdao Municipal Hospital and Jinzhou Maternal and Child Health Hospital from November 2022 to October 2023 as convenient samples for the questionnaire survey. Telephone follow-up was conducted 42 days after delivery. After univariate analysis, multicollinearity analysis, and logistic regression analysis, the risk factors of postnatal PTSD were obtained, a prediction model was established, and a nomogram was drawn by R software. G*power3.1.9.7 calculated the effectiveness of the test. The model was validated internally using the Bootstrap approach, and external validation was carried out using a verification group. The accuracy of the model's predictions and its clinical application value were evaluated by the area under the curve, calibration plot, and decision curve analysis. RESULTS: A total of 602 women were recruited in this study, and the incidence of postpartum PTSD was 11.1% (67/602). Multifactorial logistic regression analysis showed that poor self-assessment of sleep status in late pregnancy (OR = 5.336), cesarean section (OR = 2.825), instrumental delivery (OR = 5.994), having fear of labor (OR = 4.857), and a high score of Five Factors Inventory Neuroticism subscale (OR = 1.244) were independent risk factors for developing postpartum PTSD. A high Quality of Relationship Index score (OR = 0.891) was a protective factor for postpartum PTSD. In the training and validation sets, the nomogram model's area under the ROC curve was 0.928 and 0.907, respectively. The calibration curves showed that the nomogram model was well-fitted, and the Decision Curve Analysis indicated that the nomogram model had good value for clinical application. CONCLUSIONS: With its strong predictive capacity, the prediction model built using postpartum PTSD risk factors can help clinical caregivers identify high-risk pregnant women early on and implement timely preventive intervention strategies.

Factor structure and reliability of the symptom measurement of post-stroke depression in the rehabilitation stage.

BACKGROUND: The incidence of Post Stroke Depression (PSD) in the Rehabilitation Stage is high, which can bring serious physical and psychological disorders to patients. However, there is still a lack of targeted tools for screening PSD in the rehabilitation stage. Therefore, the aim of this study was to evaluate the factor structure and reliability of a measurement instrument to screen for PSD in the rehabilitation stage. METHODS: A cross-sectional study was conducted on 780 hospitalized stroke patients who were within the rehabilitation stage from May to August 2020. Exploratory factor analysis (EFA) as well as first- and second-order confirmatory factor analysis (CFA) were performed to evaluate the factor structure of the newly developed Symptom Measurement of Post-Stroke Depression in the Rehabilitation Stage (SMPSD-RS). The reliability and validity of the SMPSD-RS were also verified using several statistical methods. RESULTS: EFA extracted a 24-item, five-factor (cognition, sleep, behavior, emotion, and obsession) model that can clinically explain the symptoms of PSD during the rehabilitation stage. A first-order CFA confirmed the EFA model with good model fit indices, and the second-order CFA further confirmed the five-factor structure model and showed acceptable model fit indices. Acceptable reliability and validity were also achieved by the corresponding indicators. CONCLUSION: The SMPSD-RS was proven to have a stable factor structure and was confirmed to be reliable and valid for assessing PSD symptoms in stroke patients during the rehabilitation stage.

Psychometric characteristics of the Chinese version of the Pregnancy Exercise Attitudes Scale (C-PEAS).

BACKGROUND: Reasonable instruction and promotion of appropriate exercise are crucial to improving the exercise status of pregnant women and safeguarding the health of both mother and fetus. However, there is a lack of validated Pregnancy Exercise Attitude Scales with a complete evaluation system in China. This study aims to assess the validity and reliability of the Pregnancy Exercise Attitude Scale (C-PEAS) in Chinese to give medical professionals a reference for carrying out pregnancy care services and promoting the health of the mother and fetus. METHODS: In this study, the scale was translated, back-translated, and cross-culturally adapted using the Brislin translation model to form the C-PEAS. 528 pregnant women were conveniently selected for the questionnaire survey to evaluate the scale's reliability. The scale's content validity was assessed by the content validity index, while its structural validity was investigated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Cronbach's alpha coefficient, McDonald's omega coefficient, split-half reliability, and retest reliability were used to evaluate the scale's internal consistency. RESULTS: The C-PEAS contains two dimensions with 37 entries. The EFA supports a two-factor structure with a cumulative variance contribution of 62.927%. The CFA model was well fitted (χ2/df = 1.597, RMSEA = 0.048, IFI = 0.955, TLI = 0.952, and CFI = 0.955). The C- PEAS' Cronbach's alpha coefficient was 0.973, and the range of Cronbach's alpha values for the dimensions was 0.976, 0.944. McDonald's omega coefficient was 0.971, the half-point reliability of the scale was 0.856, and the retest reliability was 0.966. CONCLUSIONS: The Chinese version of C-PEAS has good psychometric properties. It can be used as an effective measurement tool to evaluate the attitude of pregnant women to exercise during pregnancy.

Digital exclusion and cognitive impairment in older people: findings from five longitudinal studies.

OBJECTIVES: Older people are more likely to have digital exclusion, which is associated with poor health. This study investigated the relationship between digital exclusion and cognitive impairment in older adults from 23 countries across five longitudinal surveys. DESIGN AND MEASUREMENTS: Digital exclusion is defined as self-reported non-use of the Internet. We assessed cognitive impairment on three dimensions: orientation, memory, and executive function. We used generalized estimation equations fitting binary logistic regression with exchangeable correlations to study the relationship between digital exclusion and cognitive impairment, and apply the minimum sufficiently adjusted set of causally directed acyclic graphs as the adjusted variable. SETTING AND PARTICIPANTS: We pooled a nationally representative sample of older adults from five longitudinal studies, including the China Health and Retirement Longitudinal study (CHARLS), the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS), the Mexican Health and Ageing Study (MHAS) and the Survey of Health, Ageing and Retirement in European (SHARE). RESULTS: We included 62,413 participants from five longitudinal studies. Digital exclusion varied by country, ranging from 21.69% (SHARE) in Denmark to 97.15% (CHARLS) in China. In the original model, digital exclusion was significantly associated with cognitive impairment in all five studies. In the adjusted model, these associations remained statistically significant: CHARLS (Odds ratio [OR] = 2.81, 95% confidence interval [CI] 1.84-4.28, ELSA (1.92 [1.70-2.18]), HRS(2.48[2.28-2.71), MHAS (1.92 [1.74-2.12]), and SHARE (2.60 [2.34-2.88]). CONCLUSION: Our research shows that a significant proportion of older people suffer from digital exclusion, especially in China. Digital exclusion was positively correlated with cognitive impairment. These findings suggest that digital inclusion could be an important strategy to improve cognitive function and reduce the risk of cognitive impairment in older adults.

Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation.

Many cancers evade immune rejection by suppressing major histocompatibility class I (MHC-I) antigen processing and presentation (AgPP). Such cancers do not respond to immune checkpoint inhibitor therapies (ICIT) such as PD-1/PD-L1 [PD-(L)1] blockade. Certain chemotherapeutic drugs augment tumor control by PD-(L)1 inhibitors through potentiation of T-cell priming but whether and how chemotherapy enhances MHC-I-dependent cancer cell recognition by cytotoxic T cells (CTLs) is not entirely clear. We now show that the lysine acetyl transferases p300/CREB binding protein (CBP) control MHC-I AgPPM expression and neoantigen amounts in human cancers. Moreover, we found that two distinct DNA damaging drugs, the platinoid oxaliplatin and the topoisomerase inhibitor mitoxantrone, strongly up-regulate MHC-I AgPP in a manner dependent on activation of nuclear factor kappa B (NF-κB), p300/CBP, and other transcription factors, but independently of autocrine IFNγ signaling. Accordingly, NF-κB and p300 ablations prevent chemotherapy-induced MHC-I AgPP and abrogate rejection of low MHC-I-expressing tumors by reinvigorated CD8+ CTLs. Drugs like oxaliplatin and mitoxantrone may be used to overcome resistance to PD-(L)1 inhibitors in tumors that had "epigenetically down-regulated," but had not permanently lost MHC-I AgPP activity.

The combination of multiple environmental stressors strongly alters microbial community assembly in aquatic ecosystems.

Microorganisms play a critical role in maintaining the delicate balance of ecosystem services. However, the assembly processes that shape microbial communities are vulnerable to a range of environmental stressors, such as climate change, eutrophication, and the use of herbicides. Despite the importance of these stressors, little is known about their cumulative impacts on microbial community assembly in aquatic ecosystems. To address this knowledge gap, we established 48 mesocosm experiments that simulated shallow lake ecosystems and subjected them to warming (including continuous warming (W) and heat waves (H)), glyphosate-based herbicides (G), and nutrient loading (E). Our study revealed that in the control group, both deterministic and stochastic processes codominated the assembly of microbial communities in water, whereas in sediment, the processes were primarily stochastic. Interestingly, the effects of multiple stress factors on assembly in these two habitats were completely opposite. Specifically, stressors promoted the dominance of stochastic processes in water but increased the importance of deterministic processes in sediment. Furthermore, warming amplified the effects of herbicides but exerted an opposite and stronger influence on assembly compared to nutrients, emphasizing the complexity of these mechanisms and the significance of considering multiple stressors. The interaction of some factors significantly affected assembly (p < 0.05), with the effects of WEG being most pronounced in water. Both water and sediment exhibited homogeneous assembly of microbial communities (mean NTI >0), but the phylogenetic clustering of microbial communities in water was more closely related (NTI >2). Our research revealed the response model of microbial community assembly in aquatic ecosystems to multiple environmental stresses, such as agricultural pollution, climate change, and eutrophication, and indicated that microbial community changes in sediment may be an important predictor of lake ecosystem development. This provides scientific evidence that better environmental management can reduce impacts on aquatic ecosystems under the threat of future warming.