Identification of Coupled Landau and Anomalous Resonances in Space Plasmas.

Wave-particle resonance, a ubiquitous process in the plasma universe, occurs when resonant particles observe a constant wave phase to enable sustained energy transfer. Here, we present spacecraft observations of simultaneous Landau and anomalous resonances between oblique whistler waves and the same group of protons, which are evidenced, respectively, by phase-space rings in parallel-velocity spectra and phase-bunched distributions in gyrophase spectra. Our results indicate the coupling between Landau and anomalous resonances via the overlapping of the resonance islands.

Synergistic integration of MXene nanostructures into electrospun fibers for advanced biomedical engineering applications.

MXene-based architectures have paved the way in various fields, particularly in healthcare area, owing to their remarkable physiochemical and electromagnetic characteristics. Moreover, the modification of MXene structures and their combination with polymeric networks have gained considerable prominence to further develop their features. The combination of electrospun fibers with MXenes would be promising in this regard since electrospinning is a well-established technique that is now being directed toward commercial biomedical applications. The introduction of MXenes into electrospun fibrous frameworks has highlighted outcomes in various biomedical applications, including cancer therapy, controlled drug delivery, antimicrobial targets, sensors, and tissue engineering. Correspondingly, this review describes the employed strategies for the preparation of electrospun configurations in tandem with MXene nanostructures with remarkable characteristics. Next, the advantages of MXene-decorated electrospun fibers for use in biomedical applications are comprehensively discussed. According to the investigations, rich surface functional groups, hydrophilicity, large surface area, photothermal features, and antimicrobial and antibacterial activities of MXenes could synergize the performance of electrospun layers to engineer versatile biomedical targets. Moreover, the future of this path is clarified to combat the challenges related to the electrospun fibers decorated with MXene nanosheets.

Bioinspired Flexible Kevlar/Hydrogel Composites with Antipuncture and Strain-Sensing Properties for Personal Protective Equipment.

Currently, multifunction has become an essential direction of personal protective equipment (PPE), but achieving the protective effect, flexibility, physiological comfort, and intelligent application of PPE simultaneously is still a challenge. Herein, inspired by the meso-structure of rhinoceros skin, a novel strategy is proposed by compounding an ammonium sulfate ((NH4)2SO4) solution soaked gelatin hydrogel with the high weight fraction and vertically interwoven Kevlar fibers to manufacture a flexible and wearable composite with enhanced puncture resistance and strain-sensing properties. After (NH4)2SO4 solution immersion, the hydrogel's tensile strength, toughness, and fracture strain were up to 3.77 MPa, 4.26 MJ/m3, and 305.19%, respectively, indicating superior mechanical properties. The Kevlar/hydrogel composites revealed excellent puncture resistance (quasi-static of 132.06 N and dynamic of 295.05 N), flexibility (138.13 mN/cm), and air and moisture permeability (17.83 mm/s and 2092.73 g m-2 day-1), demonstrating a favorable balance between the protective effect and wearing comfort even after 7 days of environmental exposure. Meanwhile, salt solution immersion endowed the composite with excellent strain-sensing properties at various bending angles (30-90°) and frequencies (0.25-1 Hz) and allowed it to monitor different human motions directly in real-time. The rhinoceros-skin-inspired Kevlar/hydrogel composites provide a simple and economical solution for antipuncture materials that combine high protective effects, a comfortable wearing experience, and good strain-sensing properties, promising multifunctional PPE in the future.

Obstructive sleep apnea and 19 gastrointestinal diseases: a Mendelian randomization study.

Background: Alterations gastrointestinal diseases (GDs) were reported in individuals with obstructive sleep apnea (OSA), however, the genetic background between OSA and GDs is still unclear. Methods: This investigation employed Mendelian randomization (MR) analyses to evaluate the causal effect between OSA and 19 types of GDs (gastroesophageal reflux disease (GERD), ulcerative colitis, celiac disease, Crohn's disease, chronic gastritis, irritable bowel syndrome, primary biliary cholangitis, diverticular disease, gastroduodenal ulcer, acute pancreatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, cirrhosis, calculus of bile duct, calculus of gallbladder, pancreatic cancer, gastric cancer, colorectal cancer, and esophageal cancer). The inverse-variance weighted (IVW) method was used to evaluate the main effects model of causality. Results: This MR study suggests that OSA may play a causal role inflammation-related GDs (GERD, PIVW=5.94×10-9; gastroduodenal ulcer, PIVW=1×10-4; chronic gastritis, PIVW=0.0214; ulcerative colitis, PIVW=0.0296), and gallstones (calculi of the gallbladder, PIVW=0.0429; calculi of the bile duct, PIVW=0.0068). After accounting for obesity, type 2 diabetes, smoking, and alcohol consumption, the multivariate MR (MVMR) analysis identified that OSA is an independent risk factor for GERD, gastroduodenal ulcer, and calculus of the bile duct. The reverse MVMR analysis showed a causal effect of GERD on OSA. Besides, we did not find that the predisposition to OSA was associated with 4 cancers. Conclusion: This MR analysis provides compelling evidence of an independent causal relationship between genetically predicted OSA and an elevated risk of inflammation-related GDs. Besides, no causal association was observed between OSA and cancers. Further studies should be carried out to verify our findings.

Effects of multicomponent exercise on cognitive function in persons with mild cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Multicomponent exercise has the potential to improve cognitive function in people with mild cognitive impairment. However, the effects of multicomponent exercise on specific cognitive subdomains in mild cognitive impairment and the optimal combination of exercise components remain unclear. OBJECTIVE: This systematic review aimed to (a) investigate the effects of multicomponent exercise on different cognitive subdomains in people with mild cognitive impairment and (b) investigate the effects of different combinations of multicomponent exercise on global cognition in people with mild cognitive impairment. DESIGN: A systematic review and meta-analysis. METHODS: Six electronic databases, including PubMed, Medline, EMBASE, Web of Science, Cochrane Library, and CINAHL were systematically searched from inception to January 1st, 2023. Randomized controlled trials assessing the effect of multicomponent exercise interventions on cognitive function in people with mild cognitive impairment were included. The risk of bias was assessed using the Cochrane collaborative bias assessment tool. A random-effects model was used to calculate standardized mean difference. Subgroup analyses, meta-regression, and sensitive analysis were performed. If a meta-analysis was not feasible, studies were synthesized narratively. RESULTS: Twenty studies were identified for systematic review and meta-analysis. Multicomponent exercise significantly improved global cognition [SMD = 1.04; 95 % confidence interval (CI): 0.53, 1.55], cognitive flexibility (SMD = -1.04; 95 % CI: -1.81, -0.27), processing speed (SMD = 0.43; 95 % CI: 0.04, 0.82), verbal fluency (SMD = 0.38; 95 % CI: 0.13, 0.63), attention (SMD = -0.90; 95 % CI: -1.68, -0.12) and memory (SMD = 0.36; 95 % CI: 0.04, 0.69) in mild cognitive impairment. The multicomponent exercise including cardiovascular (exercise that promotes cardiovascular health, such as endurance training or aerobic exercise) and motor (exercises that improve physical abilities, such as balance, coordination, agility, flexibility, etc.) components positively affected global cognition in people with mild cognitive impairment (SMD = 1.06; 95 % CI: 0.55, 1.57). CONCLUSIONS: The findings of this study suggest that multicomponent exercise has a positive impact on various cognitive domains, including global cognition, cognitive flexibility, processing speed, verbal fluency, attention and memory in mild cognitive impairment. Specifically, the combination of exercises including cardiovascular and motor components was found to be effective in improving global cognition. However, further research is needed to investigate the optimal frequency and intensity of the multicomponent exercise intervention, and more detail about exercise combinations of the motor component (not classified in this study) for individuals with mild cognitive impairment. REGISTRATION: The protocol was registered on PROSPERO (CRD42023400302).

Two cases of MPO-ANCA-positive hypertrophic pachymeningitis mimicking as intracranial infection.

Hypertrophic pachymeningitis (HP) is a rare disorder marked by thickening of the dura mater due to diverse etiologies. MPO-ANCA-positive HP represents a variant of AAV confined to the central nervous system, distinguished by the presence of serum MPO antibodies. Distinguishing HP triggered by MPO-ANCA from other causes can be challenging.In this study, we present two cases of MPO-ANCA-positive HP initially misdiagnosed as intracranial infections. Case 1 underwent surgery for chronic suppurative otitis media, with histopathological findings revealing inflammatory changes without definitive suppuration. He was presumed to have a secondary intracranial infection resulting from the surgery. However, his condition deteriorated despite two weeks of antibiotic and antiviral treatment. Case 2 presented with headache and was initially suspected of having intracranial Brucellosis given his serum Brucella positivity. Despite treatment for brucellosis, his symptoms persisted, and he developed visual and hearing impairments. Both patients were ultimately diagnosed with MPO-ANCA-positive HP, exhibiting serum MPO antibody positivity. Their symptoms showed improvement with glucocorticoid and immunosuppressive therapy.Based on these observations, we propose that MPO-ANCA-positive HP may initially present as intracranial infection. For HP patients presenting with headache, mastoiditis, otitis media, and visual loss, it is imperative to conduct ANCA antibody-related tests to enhance diagnostic precision.

Mix-and-Read Digital MicroRNA Analysis Based on Flow Cytometric Counting of Target-Clicked Nanobead Dimer.

A one-step, enzyme-free, and highly sensitive digital microRNA (miRNA) assay is rationally devised based on flow cytometric counting of target miRNA-clicked nanobead dimers via a facile mix-and-read manner. In this strategy, highly efficient miRNA-sandwiched click chemical ligation of two DNA probes may remarkably stabilize and boost the dimer formation between two kinds of fluorescence-coded nanobeads, and the number of as-produced bead dimers will be target dose-responsive, particularly when the trace number of miRNA is much less than that of employed nanobeads. Finally, each fluorescence-coded bead dimer can be easily identified and digitally counted by a powerful flow cytometer (FCM) and accordingly, the amount of target miRNA can be accurately quantified in a digital way. This new digital miRNA assay can be accomplished with a facile mix-and-read operation just by simply mixing the target miRNA with two kinds of preprepared DNA probe-functionalized nanobeads, which do not require any nucleic acid amplification, purification, and complex operation procedures. In spite of the extremely simple one-step operation, benefiting from the low-background but high target-mediated click ligation efficiency, and the powerfully digital statistical capability of FCM, this strategy achieves high sensitivity with a quite low detection limit of 5.2 fM target miRNA as well as high specificity and good generality for miRNA analysis, pioneering a new direction for fabricating digital bioassays.

Chemical speciation and rice uptake of soil molybdenum-Investigation with X-ray absorption spectroscopy and isotope fractionation.

Molybdenum (Mo) contamination of farmland soils poses health risks due to Mo accumulation in crops like rice. However, the mechanisms regulating soil availability and plant uptake of Mo remain poorly understood. This study investigated Mo uptake by rice plants, focusing on Mo speciation and isotope fractionation in soil and rice plants. Soil Mo species were identified as sorbed Mo(VI) and Fe-Mo(VI) using X-ray absorption spectroscopy (XAS). Soil submergence during rice cultivation led to the reductive dissolution of Fe-associated Mo(VI) while increasing sorbed Mo(VI) and Ca-Mo(VI). Soil Mo release to soil solution was a dynamic process involving continuous dissolution/desorption and re-precipitation/sorption. Mo isotope analysis showed soil solution was consistently enriched in heavier isotopes during rice growth, attributed to re-sorption of released Mo and the uptake of Mo by rice plants. Mo was significantly associated with Fe in rice rhizosphere as sorbed Mo(VI) and Fe-Mo(VI), and around 60 % of Mo accumulated in rice roots was sequestrated by Fe plaque of the roots. The desorption of Mo from Fe hydroxides to soil solution and its subsequent diffusion to the root surface were the key rhizosphere processes regulating root Mo uptake. Once absorbed by roots, Mo was efficiently transported to shoots and then to grains, resulting in heavier isotope fractionation during the translocation within plants. Although Mo translocation to rice grains was relatively limited, human exposure via rice consumption remains a health concern. This study provides insights into the temporal dynamics of Mo speciation in submerged paddy soil and the uptake mechanisms of Mo by rice plants.

The epithelial Na+ channel (ENaC) in ovarian granulosa cells modulates Ca2+ mobilization and gonadotrophin signaling for estrogen homeostasis and female fertility.

Ovarian granulosa cells are essential to gonadotrophin-regulated estrogen production, female cycle maintenance and fertility. The epithelial Na+ channel (ENaC) is associated with female fertility; however, whether and how it plays a role in ovarian cell function(s) remained unexplored. Here, we report patch-clamp and Na+ imaging detection of ENaC expression and channel activity in both human and mouse ovarian granulosa cells, which are promoted by pituitary gonadotrophins, follicle stimulating hormone (FSH) or luteinizing hormone (LH). Cre-recombinase- and CRISPR-Cas9-based granulosa-specific knockout of ENaC α subunit (Scnn1a) in mice resulted in failed estrogen elevation at early estrus, reduced number of corpus luteum, abnormally extended estrus phase, reduced litter size and subfertility in adult female mice. Further analysis using technologies including RNA sequencing and Ca2+ imaging revealed that pharmacological inhibition, shRNA-based knockdown or the knockout of ENaC diminished spontaneous or stimulated Ca2+ oscillations, lowered the capacity of intracellular Ca2+ stores and impaired FSH/LH-stimulated transcriptome changes for estrogen production in mouse and/or human granulosa cells. Together, these results have revealed a previously undefined role of ENaC in modulating gonadotrophin signaling in granulosa cells for estrogen homeostasis and thus female fertility.

Lifestyle-specific association between adversity dimensions with group-based mental health trajectories.

BACKGROUND: Childhood adversity (CA) has a substantial correlation with mental health problems. Keeping a healthy lifestyle is essential for mental health interventions; it is unclear, however, how healthy lifestyle affect the relationship between CA and persistent mental health problems. METHODS: This longitudinal study (n = 1112, 54.5 % male) collected the data on CA (measured through three dimensions: threat, deprivation and unpredictability), mental health problems, and lifestyle factors. Group-based multi-trajectory modeling (GBMTM) was utilized to estimate trajectories for three mental health problems (i.e., depression, ADHD and overanxiety). Close friendships, regular physical activity, appropriate sleep duration, shorter screen time, and healthy eating were combined to establish a healthy lifestyle score (which ranges from 0 to 5). Higher scores indicated a healthier lifestyle. RESULTS: Three trajectories of mental health problems were identified: persistently low risk (24.9 %), persistently medium-high risk (50.0 %), and persistently high risk (25.1 %). Multinomial logistic regression showed that high adversity (high-threat: ß = 2.01, P < 0.001; high-deprivation: ß = 1.03, P < 0.001; high-unpredictability: ß = 0.83, P = 0.001; high-overall adversity: ß = 1.64, P < 0.001) resulted in a persistently high risk of mental health problems; these outcomes were maintained after robust control for covariates. Further lifestyle stratification, null associations were observed among children with a healthy lifestyle, irrespective of their gender; however, after controlling for covariates, the above associations remained relatively stable only among boys. LIMITATIONS: The generalizability of our findings is restricted by 1) limited racial diversity and 2) missing data. CONCLUSIONS: This finding underscores the benefits of promoting a healthy lifestyle in children to prevent persistent mental health problems caused by CA.

Effective microorganism combinations improve the quality of compost-bedded pack products in heifer barns: exploring pack bacteria-fungi interaction mechanisms.

BACKGROUND: Compost-bedded pack barns (CBP) are getting huge attention as an alternative housing system for dairy cows due to their beneficial impact on animal welfare. Effective microorganisms (EM) inoculums are believed to enhance compost quality, improve soil structure and benefit the environment. However, little information is available on the impact of incubation with external EM combinations on the barn environment, compost quality and microbial diversity in CBP. This experiment was carried out to investigate the effect of inoculating different combinations of EM [Lactobacillus plantarum (L), Compound Bacillus (B) and Saccharomyces cerevisiae (S)] on compost quality and microbial communities of CBP products, as well as the relationship with the heifers' barn environment. CBP barns were subjected to the following four treatments: CON with no EM inoculum, LB/LS/LBS were Incubated with weight ratios of 1:2 (L: B), 1:2 (L: S), 1:1:1 (L: B: S), respectively. RESULTS: The EM inoculation (LB, LS, LBS) reduced the concentration of respirable particulate matter (PM10 and PM2.5) in the CBP, and decreased the serum total protein and total cholesterol levels in heifers. Notably, LBS achieved the highest content of high-density lipoprotein compared to other treatments. Microbiome results revealed that EM inoculation reduced the bacterial abundance (Chao1 index) and fungal diversity (Shannon & Simpson indexes), while increasing the relative abundance of various bacterial genera (Pseudomonas, Paracoccus, Aequorivita) and fungi (Pestalotiopsis), which are associated with cellulose decomposition that ultimately resulted in accelerating organic matter degradation and humification. Furthermore, high nutrient elements (TK&TP) and low mycotoxin content were obtained with EM inoculation, with LBS showing a particularly pronounced effect. Meanwhile, LBS contributed to a decline in the proportion of fungal pathogen categories but also led to an increase in fungal saprotroph categories. CONCLUSION: Generally, EM inoculation positively impacted compost product quality as organic fertilizer and barn environment by modifying the abundance of cellulolytic bacteria and fungi, while inhibiting the reproduction of pathogenic microbes, especially co-supplementing with L, B and S achieved an amplifying effect.

Risk factors for sternal wound infection after median sternotomy: A nested case-control study and time-to-event analysis.

Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case-control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan-Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan-Meier analyses showed different time-to-SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012-1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094-3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193-4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01-1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036-10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001-1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI.

Cdc14B/Cyclin B1 signaling modulates the pathogenesis of sonic hedgehog subtype medulloblastoma.

Medulloblastoma (MB) is a severe malignancy of the central nervous system that predominantly occurs in the cerebellum of children. Overactivation of the sonic hedgehog (Shh) signaling pathway is the primary cause of the development and progression of Shh subtype MB, although the detailed mechanisms underlying this process remain largely elusive. In this study, we discovered that Shh can promote proliferation in MB cells through non-canonical Hedgehog signaling. This involves Shh binding to Patched 1, disrupting its interaction with Cyclin B1, allowing for nuclear translocation of Cyclin B1, and inducing the activation of genes involved in cell division. Furthermore, we observed that deregulation of Cdc14B leads to the stabilization of the Cyclin B1/CDK1 complex in MB cells through activating Cdc25C, a phosphatase known to help maintain Cyclin B1 stability. Our findings highlight the role of Cdc14B/Cdc25C/CDK1/Cyclin B1 in mediating Hedgehog signaling-driven pathogenesis in MB and have implications for identifying potential therapeutic targets.

The expression of ERAP1 is favorable for the prognosis and immunotherapy in colorectal cancer: a study based on the bioinformatic and immunohistochemical analysis.

BACKGROUND: Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an emerging pharmacological target in cancer immunotherapy. This study was set out to examine the expression profiles and implications for prognosis and immunotherapy of ERAP1 in CRC. METHODS: Based on bioinformatics and immunohistochemical analysis, we analyzed ERAP1 for potential diagnostic and prognostic significance in CRC. Functional enrichment analysis was conducted to detect the pathways associated with ERAP1, thus determining possible mechanisms. ESTIMATE, TIMER, and CIBESORT probed the links between ERAP1 and tumor-infiltrating immune cells. Lastly, we examined how ERAP1 expression correlated with the sensitivity to immunotherapy. RESULTS: Tumor tissues had decreased levels of ERAP1 expression relative to normal tissues. Patients whose ERAP1 expression was low suffered a worse chance of survival. Besides, it was shown that ERAP1 expression was associated with the advanced M stage and pathologic stage. Survival analysis revealed that low ERAP1 expression, age, pathologic stage, T stage, and M stage were independent indicators for unfavorable CRC patients' prognoses. The 1-, 3-, and 5-year OS calibration curves all fit well with the ideal model, suggesting that the age-ERAP1-T-stage-M-stage nomogram is a reliable predictor of OS. Additionally, we discovered that ERAP1 expression was associated with immune response and infiltration of various immune cells, such as down-regulated inhibitory immune cells and up-regulated stimulating immune cells. Sensitivity to PD-1 and CTLA4 inhibitors was associated with high ERAP1 levels. CONCLUSIONS: In summary, ERAP1 has potential as a diagnostic and prognostic biological marker, highlighting new insights into the study of CRC and the design of effective therapies.

Recent advances in plant-derived polysaccharide scaffolds in tissue engineering: A review.

As a natural three-dimensional biopolymer, decellularized plant-derived scaffolds usually comprise various polysaccharides, mostly cellulose, pectin, and hemicellulose. They are characterized by natural biocompatibility and porous structures. The emergence of decellularized purified polysaccharide scaffolds provides an attractive method to overcome the challenges associated with nutrient delivery and biocompatibility, as they serve as optimal non-immune environments for stem cell adhesion and proliferation. To date, limited corresponding literature is available to systemically summarize the development and potential of these scaffolds in tissue engineering. Therefore, the current review summarized the biomimetic properties of plant-derived polysaccharide scaffolds and the latest progress in tissue engineering applications. This review first discusses the advantages of decellularized plant-derived polysaccharide scaffolds by briefly introducing their features and current limitations in clinical applications. Subsequently, the latest progress in emerging applications of regenerative biomaterials is reviewed, followed by a discussion of the studies on the interactions of biomaterials with cells and tissues. Finally, challenges in obtaining reliable scaffolds and possible future directions are discussed.

Advances in the immunoescape mechanisms exploited by alphaherpesviruses.

Alphaherpesviruses, categorized as viruses with linear DNA composed of two complementary strands, can potentially to induce diseases in both humans and animals as pathogens. Mature viral particles comprise of a core, capsid, tegument, and envelope. While herpesvirus infection can elicit robust immune and inflammatory reactions in the host, its persistence stems from its prolonged interaction with the host, fostering a diverse array of immunoescape mechanisms. In recent years, significant advancements have been achieved in comprehending the immunoescape tactics employed by alphaherpesviruses, including pseudorabies virus (PRV), herpes simplex virus (HSV), varicella-zoster virus (VZV), feline herpesvirus (FeHV), equine herpesvirus (EHV), and caprine herpesvirus type I (CpHV-1). Researchers have unveiled the intricate adaptive mechanisms existing between viruses and their natural hosts. This review endeavors to illuminate the research advancements concerning the immunoescape mechanisms of alphaherpesviruses by delineating the pertinent proteins and genes involved in virus immunity. It aims to furnish valuable insights for further research on related mechanisms and vaccine development, ultimately contributing to virus control and containment efforts.

Knockdown of miR-155 alleviates skin damage in rats with chronic spontaneous urticaria by modulating the JAK/STAT signaling pathway.

OBJECTIVE: The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU). METHODS: The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues. RESULTS: Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats. CONCLUSION: Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway.

Accelerometer-Measured Daily Behaviors That Mediate the Association Between Refractive Status and Depressive Disorders.

Purpose: To identify the accelerometer-measured daily behaviors that mediate the association of refractive status with depressive disorders and enhance the understanding of behavioral differences in depression. Methods: Participants with baseline mean spherical equivalent (MSE) and 7-day accelerometer measurements from the UK Biobank were included in this cohort study. Refractive status was categorized as hyperopia and non-hyperopia. Four daily behaviors, including moderate to vigorous intensity physical activity (MVPA), light physical activity (LPA), sedentary, and sleep were recorded between 2013 and 2015. We also assessed 24-hour behavior patterns. Depression cases were defined through both questionnaires and hospital records over 10 years of follow-up. Results: Among 20,607 individuals, every 0.5-diopter increase in MSE was associated with a 6% higher risk of depressive disorders, with hyperopia participants at a higher risk than non-hyperopia participants (odds ratio, 1.14; 95% confidence interval, 1.05-1.23; P = 0.001). MVPA and sleep time significantly correlated with depressive disorders, with odds ratios of 0.79 and 1.14 (P < 0.05). MSE showed significant correlations with all four behaviors. The effects of MVPA and sleep duration on MSE and depressive disorders varied throughout the day. Mediation analyses showed that MVPA and sleep partially mediated the relationship between MSE and depressive disorders, with 35.2% of the association between moderate to high hyperopia and depression mediated by MVPA. Conclusions: Physical activity and sleep significantly mediate the relationship between MSE and depressive disorders. Translational Relevance: The mediation effect of MVPA highlights its therapeutic potential in reducing the risk of depression among individuals with moderate to severe hyperopia. Interventions aimed at increasing daytime MVPA and decreasing daytime sleep could enhance mental health in this vulnerable group.

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure.

BACKGROUND: When massive necrosis occurs in acute liver failure (ALF), rapid expansion of HSCs called liver progenitor cells (LPCs) in a process called ductular reaction is required for survival. The underlying mechanisms governing this process are not entirely known to date. In ALF, high levels of retinoic acid (RA), a molecule known for its pleiotropic roles in embryonic development, are secreted by activated HSCs. We hypothesized that RA plays a key role in ductular reaction during ALF. METHODS: RNAseq was performed to identify molecular signaling pathways affected by all-trans retinoid acid (atRA) treatment in HepaRG LPCs. Functional assays were performed in HepaRG cells treated with atRA or cocultured with LX-2 cells and in the liver tissue of patients suffering from ALF. RESULTS: Under ALF conditions, activated HSCs secreted RA, inducing RARα nuclear translocation in LPCs. RNAseq data and investigations in HepaRG cells revealed that atRA treatment activated the WNT-ß-Catenin pathway, enhanced stemness genes (SOX9, AFP, and others), increased energy storage, and elevated the expression of ATP-binding cassette transporters in a RARα nuclear translocation-dependent manner. Further, atRA treatment-induced pathways were confirmed in a coculture system of HepaRG with LX-2 cells. Patients suffering from ALF who displayed RARα nuclear translocation in the LPCs had significantly better MELD scores than those without. CONCLUSIONS: During ALF, RA secreted by activated HSCs promotes LPC activation, a prerequisite for subsequent LPC-mediated liver regeneration.