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Gut symbiotic bacteria are known to be closely related to insect development, nutrient metabolism, and disease resistance traits, but the most important factors leading to changes in these communities have not been well clarified. To address this, we examined the associations between the gut symbiotic bacteria and the host genotype and geographical distribution of Solenopsis invicta in China, where it is invasive and has spread primarily by human-mediated dispersal. Thirty-two phyla were detected in the gut symbiotic bacteria of S. invicta. Proteobacteria were the most dominant group among the gut symbiotic bacteria. Furthermore, the Bray-Curtis dissimilarity matrices of the gut symbiotic bacteria were significantly positively correlated with the geographical distance between the host ant colonies, but this relationship was affected by the social form. The distance between monogyne colonies had a significant effect on the Bray-Curtis dissimilarity matrices of gut symbiotic bacteria, but the distance between polygyne colonies did not. Moreover, the Bray-Curtis dissimilarity matrices were positively correlated with Nei's genetic distance of the host but were not correlated with the COI-based genetic distance. This study provides a scientific basis for further understanding the ecological adaptability of red imported fire ants during invasion and dispersal. IMPORTANCE We demonstrated that gut microbiota composition and diversity varied among populations. These among-population differences were associated with host genotype and geographical distribution. Our results suggested that population-level differences in S. invicta gut microbiota may depend more on environmental factors than on host genotype.
Demyelinating diseases such as multiple sclerosis (MS) are chronic inflammatory autoimmune diseases and involve demyelination and axonal degeneration. Microglia rapidly respond to changes in the environment by altering morphotype and function during the progressive disease stage. Although substantial progress has been made in the drug development for MS, treatment of the progressive forms of the disease remains unsatisfactory. There is great interest in identifying novel agents for treating MS. Lentinus edodes is a traditional food, which can improve physiological function. Lentinan (LNT), a type of polysaccharide extracted from mushroom Lentinus edodes, is an anti-inflammatory and immunomodulatory agent. Here, we studied the remyelination effects of LNT and its therapeutic target in regulating the functions of neuroinflammation. We found that LNT enhanced remyelination and rescued motor deficiency by regulating dectin-1 receptor to inhibit neuroinflammation and microglial cell transformation. LNT promoted the conversion of microglial cells from the M1 status induced by LPS to the M2 status, enhanced the anti-inflammatory markers IL-10 and BDNF, inhibited inflammatory markers TNF-α and IL-1β, and downregulated the microglia activation and oligodendrocyte and astrocyte proliferation by modulating dectin-1. If we injected the dectin-1-specific inhibitor laminarin (Lam), the remyelination effects induced by LNT were completely abolished. Thus, these results suggest that LNT is a novel and potential therapeutic agent that can rescue MS neuroimmune imbalance and remyelination through a dectin-1 receptor-dependent mechanism.
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.
Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.
Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.
Disruptions in microbial metabolite interactions due to gut microbiome dysbiosis and metabolomic shifts may contribute to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and other immune-related conditions. The aryl hydrocarbon receptor (AhR), activated upon binding various tryptophan metabolites, modulates host immune responses. This study investigates whether the metabolic diversity-the concentration distribution-of bacterial indole pathway metabolites can differentiate bacterial strains and classify ME/CFS samples. A fast targeted liquid chromatography-parallel reaction monitoring method at a rate of 4 minutes per sample was developed for large-scale analysis. This method revealed significant metabolic differences in indole derivatives among B. uniformis strains cultured from human isolates. Principal component analysis identified two major components (PC1, 68.9%; PC2, 18.7%), accounting for 87.6% of the variance and distinguishing two distinct B. uniformis clusters. The metabolic difference between clusters was particularly evident in the relative contributions of indole-3-acrylate and indole-3-aldehyde. We further measured concentration distributions of indole derivatives in ME/CFS by analyzing fecal samples from 10 patients and 10 healthy controls using the fast targeted metabolomics method. An AdaBoost-LOOCV model achieved moderate classification success with a mean LOOCV accuracy of 0.65 (Control: precision of 0.67, recall of 0.60, F1-score of 0.63; ME/CFS: precision of 0.64, recall of 0.7000, F1-score of 0.67). These results suggest that the metabolic diversity of indole derivatives from tryptophan degradation, facilitated by the fast targeted metabolomics and machine learning, is a potential biomarker for differentiating bacterial strains and classifying ME/CFS samples. Mass spectrometry datasets are accessible at the National Metabolomics Data Repository (ST002308, DOI: 10.21228/M8G13Q; ST003344, DOI: 10.21228/M8RJ9N; ST003346, DOI: 10.21228/M8RJ9N).
Chemical fertilizer reduction combined with organic fertilizer (organic fertilizer substitution) has a positive impact on crop productivity and sustainable development. However, the effects of short-term organic fertilizer substitution on microbial community structure and functions of sorghum rhizosphere soil and on sorghum yield remain unclear. Herein, this study investigated the short-term effects of organic fertilizer substitution on sorghum soil physicochemical properties, microbial community structure and enzyme activities using Metagenomic sequencing technology.
Tumor mutation burden (TMB) and VHL mutation play a crucial role in the management of patients with clear cell renal cell carcinoma (ccRCC), such as guiding adjuvant chemotherapy and improving clinical outcomes. However, the time-consuming and expensive high-throughput sequencing methods severely limit their clinical applicability. Predicting intratumoral heterogeneity poses significant challenges in biology and clinical settings. Our aimed to develop a self-supervised attention-based multiple instance learning (SSL-ABMIL) model to predict TMB and VHL mutation status from hematoxylin and eosin-stained histopathological images.
The numerous grainboundaries solid electrolyte interface, whether naturally occurring or artificially designed, leads to non-uniform Li metal deposition and consequently results in poor full-battery performance. Herein, a lithium-ion selective transport layer is reported to achieve a highly efficient and dendrite-free lithium metal anode. The layer-by-layer assembled protonated carbon nitride nanosheets present uniform macroscopical structure without grainboundaries. The carbon nitride with ordered pores in basal plane provides high-speed lithium-ion transport channels with low tortuosity. Consequently, the assembled 324 Wh kg-1 pouch cell exhibits 300 stable cycles with a capacity retention of 90.0% and an average Coulombic efficiency up to 99.7%. The ultra-dense Li metal anode makes current collector-free anode possible, achieving high energy density and long cycle life of a 7 Ah cell (506 Wh kg-1, 160 cycles). Thus, it is proved that a macroscopically uniform interface layer with lithium-ion conductive channels could achieve Li metal battery with promising application potential.
Currently, generalized therapy for traumatic optic neuropathy (TON) is lacking. Various strategies have been developed to protect and regenerate retinal ganglion cells (RGCs) after TON. Intravitreal injection of supplements has been approved as a promising approach, although serious concerns, such as low delivery efficacy and pain due to frequent injections, remain. In this study, we tested an injectable thermosensitive hydrogel drug delivery system engineered to deliver ciliary neurotrophic factor (CNTF) and triamcinolone acetonide (TA). The results of rheological studies showed that the prepared drug-loaded hydrogel possessed a suitable mechanical modulus of ∼300 Pa, consistent with that of vitreum. The hydrogel exhibited thermosensitive with sustained drug release performance. In vitro co-culture of the CNTF-loaded hydrogel system with primary RGCs also induced significant axon regeneration, with 38.5% increase in neurite length, indicating the regenerative response of the thermosensitive hydrogel drug delivery system. A Sprague-Dawley rat optic nerve crush model was constructed and applied to determine the neuroprotective and regenerative capacities of the system. The results demonstrated that a single intravitreal injection of the drug-loaded hydrogel (PLGA-PEG-PLGA + TA or PLGA-PEG-PLGA + CNTF) significantly increased RGC survival at both 14 and 28 days. The RGC survival rate was 31.05 ± 1.41% for the drug-loaded hydrogel system (the control group was 16.79 ± 1.50%) at Day 28. These findings suggest that the injectable drug-loaded thermosensitive hydrogel delivery system is a promising therapeutic tool for treating optic nerve degeneration.
Recent observations of superconductivity in infinite-layer nickelates offer insights into high-temperature superconductivity mechanisms. However, defects and dislocations in doped films complicate the realization of superconductivity, limiting current research to superconducting nickelate heterostructures. The lack of research on superconductivity in superlattices composed of ultrathin nickelates severely impedes not only the exploration of the interface effect on superconductivity, but also the utilization of heterostructure engineering for exploring higher superconducting temperature Tc. Here, we demonstrated superconducting infinite-layer nickelate superlattices [(Nd0.8Sr0.2NiO2)8/(SrTiO3)2]10 via topotactic reduction. Our study uncovered that only above a critical thickness can high-quality superlattices be achieved, with structural formation dependent on nickelate layer thickness. The superconducting superlattice showed a Tc of 12.5 K and a 2D superconducting feature, indirectly indicate the intrinsic superconductivity of infinite-layer nickelates. Our study offers promising avenues for delving into the superconducting mechanism and for exploring multilevel interface engineering of infinite-layer nickelates, thus opening new horizons for the study of infinite-layer nickelates.
The rumen microbiota-a symbiont to its host and consists of critical functional substances-plays a vital role in the animal body and represents a new perspective in the study of adaptive evolution in animals. This study used Slide Viewer slicing analysis system, gas chromatography, RT-qPCR and other technologies, as well as 16S and metabolomics determination methods, to measure and analyze the microstructure of rumen epithelium, rumen fermentation parameters, rumen transport genes, rumen microbiota and metabolites in Tibetan sheep and Hu sheep. The results indicate that the rumen nipple height and cuticle thickness of Tibetan sheep are significantly greater than those of Hu sheep (p < 0.01) and that the digestion and absorption of forage are greater. The levels of carbohydrate metabolism, lipid metabolism, and protein turnover were increased in Tibetan sheep, which enabled them to ferment efficiently, utilize forage, and absorb metabolic volatile fatty acids (VFAs). Tibetan sheep rumen metabolites are related to immune function and energy metabolism, which regulate rumen growth and development and gastrointestinal homeostasis. Thus, compared with Hu sheep, Tibetan sheep have more rumen papilla and cuticle corneum, and the synergistic effect of the microbiota and its metabolites is a characteristic and strategy for adapting to high-altitude environments.
A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8+ T cells and reactivated robust antitumor immunity.
JOURNAL/nrgr/04.03/01300535-202603000-00042/figure1/v/2025-06-16T082406Z/r/image-tiff Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain, clear criteria for the stimulation time window and intensity are lacking. Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain, but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical. In this study, ischemic stroke was induced in rats through middle cerebral artery occlusion surgery. Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia, and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation. Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation. Furthermore, the stimulation promoted motor function recovery, reduced cerebral infarction volume in the rat model of ischemic stroke, and induced the expression of brain-derived neurotrophic factor in the ischemic brain. Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume. This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia. Additionally, our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo . These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.
Overactive bladder (OAB) is a common condition that significantly impacts quality of life, particularly among women. Multiple parities may exert long-term adverse impacts on female pelvic floor function, thereby escalating the risk of bladder dysfunction. Nevertheless, the present research results regarding the relationship between parity and OAB demonstrate inconsistency. Therefore, this study employed data from the National Health and Nutrition Examination Survey (NHANES) database spanning the years 2005 to 2018 to examine the relationship between parity and the risk of OAB while considering various influencing factors.
This study aims to identify an optimal model for assessing the recurrence frequency of Budd-Chiari syndrome (BCS) and further analyze the factors contributing to BCS recurrence. A total of 754 patients who were admitted to the Affiliated Hospital of Xuzhou Medical University between January 2015 and July 2022 were included. We constructed 4 different count outcome models: Poisson, negative binomial (NB) model, zero-inflated Poisson (ZIP) model, and zero-inflated negative binomial (ZINB) model. We selected the model with the best fitting performance to explore factors associated with BCS recurrence. Of 754 respondents, 511 reported no recurrence. Log-likelihood ratio tests indicated that the NB model performed better than the Poisson regression model (χ2 = 124.91, P < .001), and the ZINB model outperformed the ZIP model (χ2 = 34.29, P < .001). In the ZINB model, the analysis of the counting process revealed that the variables significantly associated with recurrence frequency included age (odds ratio [OR] = 0.69; 95% confidence interval [CI]: 0.57-0.84), sex (female: OR = 1.77; 95% CI: 1.24-2.55), anticoagulant use (warfarin vs new oral anticoagulants [NOACs]: OR = 2.11, 95% CI: 1.34-3.31; not using anticoagulants vs NOACs: OR = 1.98, 95% CI: 1.20-3.28), absence of cirrhosis (OR = 0.57, 95% CI: 0.40-0.82), and neutrophil count (NEU) (OR = 1.22, 95% CI: 1.04-1.42). The zero-inflated model proved robust in identifying factors influencing BCS recurrence compared with the other models. Influence of sex, surgery, anticoagulation, cirrhosis, hospital duration, apolipoprotein A, and NEU on the recurrence risk and frequency of BCS.
Cronobacter sakazakii is an important neonatal pathogen frequently associated with powdered infant formula. However, the mechanisms by which C. sakazakii adapts to the host environment and establishes systemic dissemination remain poorly understood. Here, we reveal a signal transduction pathway centered on a novel sRNA, CsrN, which facilitates C. sakazakii in utilizing nitrate respiration in response to oxygen-limited environments within the host, thereby enhancing its virulence in vivo. C. sakazakii infection triggers an inflammatory response, leading to the accumulation of host-derived nitrate, a key alternative electron acceptor. The expression of CsrN is induced under anaerobic conditions via the ArcAB two-component regulation system. CsrN subsequently enhances the expression of the narGHJI operon, which encodes a nitrate reductase complex. This promotes the colonization of C. sakazakii in the gastrointestinal tract and benefits its survival within macrophages, ultimately leading to increased systemic bacterial dissemination and virulence in the host. We show that administration of tungstate, a specific inhibitor of nitrate respiration, significantly attenuates C. sakazakii virulence in animal experiments. This work provides novel insights into the survival and pathogenicity mechanisms employed by C. sakazakii in host environments and suggests nitrate respiration as a potential therapeutic target for combating C. sakazakii infections.
Deoxynivalenol (DON), a prevalent mycotoxin in grains and feed, poses a serious threat to animal health by inducing intestinal dysfunction. While some probiotics are known to mitigate DON toxicity, the multifaceted protective effects of Lactobacillus rhamnosus MY-1-a strain with high DON-degradation capacity and a proven safety profile-require comprehensive evaluation. This study aimed to systematically assess the ability of MY-1 to alleviate DON-induced oxidative stress, inflammation, and gut microbiota dysbiosis, and to elucidate its underlying mechanisms.
BACKGROUND: The awareness level of cervical cancer and its correlates among junior high school students is not well documented. This perspectives is crucial to guide cervical cancer prevention in this population. METHODS: In 2023, we conducted an anonymous online self-administered questionnaire survey with 4,089 valid participants randomly selected on a class basis from six junior high schools in six counties/districts across three municipalities in Zhejiang Province. Data were analyzed using univariate and multivariate analyses. RESULTS: 63.9% (1,471/2,303) of female students and 50.4% (900/1,786) of male students were aware of cervical cancer. The results of multivariate analysis showed that: Grade 2(OR = 1.43, 95% CI:1.13–1.83), Grade 3(OR = 1.45, 95% CI:1.12–1.88), being unaware of maternal education level (OR = 0.49, 95% CI:0.32-0. 74), being an only child in the family (OR = 1.43, 95% CI:1.13–1.83), being from average-income(OR = 2.31, 95% CI:1.39–3.87) and low-income family (OR = 2.90, 95% CI:1.56–5.41), having acquaintances with cancer (OR = 2.91, 95% CI:2.31–3.66), awareness of HPV (OR = 3. 74, 95% CI:2.69–5.19), awareness of the HPV vaccine (OR = 2.91, 95% CI:2.24–3.78), concern about developing cervical cancer (OR = 2.02, 95% CI:1.64–2.49), having received HPV and HPV vaccine-related health education at school (OR = 1. 30, 95% CI:1.05–1.61), and believing that there was a need for schools to provide HPV and HPV vaccine-related health education(OR = 1.65, 95% CI:1.20–2.25), are associated with awareness of cervical cancer among female students. Grade 2(OR = 1.66, 95% CI: 1.27–2.17), Grade 3(OR = 1.57, 95% CI: 1.20–2.06), being unware of maternal educational level (OR = 0.58, 95% CI: 0.35–0.96), having acquaintances with cancer(OR = 3.53, 95% CI: 2.77–4.49), awareness of HPV (OR = 4.65, 95% CI: 3.21-6. 73), awareness of the HPV vaccine (OR = 2.41, 95% CI:1.76–3.31), concern about a sexual partner developing cervical cancer(OR = 1.36, 95% CI:1.00-1.83), and believing that there was a need for HPV and HPV vaccine-related health education in schools(OR = 2.15, 95% CI:1.60–2.89), were associated with awareness of cervical cancer among male students. CONCLUSIONS: The rate of awareness of cervical cancer, HPV and the HPV vaccine, and the risk perception of HPV infection among participants is low and should be increased through publicity and education in schools, families and society, in order to raise awareness of prevention of cervical cancer and other diseases caused by HPV infection among adolescents.
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