Distinct Assembly Processes Structure Planktonic Bacterial Communities Among Near- and Offshore Ecosystems in the Yangtze River Estuary.

The estuarine system functions as natural filters due to its ability to facilitate material transformation, planktonic bacteria play a crucial role in the cycling of complex nutrients and pollutants within estuaries, and understanding the community composition and assembly therein is crucial for comprehending bacterial ecology within estuaries. Despite extensive investigations into the composition and community assembly of two bacterial fractions (free-living, FLB; particle-attached, PAB), the process by which bacterioplankton communities in these two habitats assemble in the nearshore and offshore zones of estuarine ecosystems remains poorly understood. In this study, we conducted sampling in the Yangtze River Estuary (YRE) to investigate potential variations in the composition and community assembly of FLB and PAB in nearshore and offshore regions. We collected 90 samples of surface, middle, and bottom water from 16 sampling stations and performed 16S rRNA gene amplicon analysis along with environmental factor measurements. The results unveiled that the nearshore communities demonstrated significantly greater species richness and Chao1 indices compared to the offshore communities. In contrast, the nearshore communities had lower values of Shannon and Simpson indices. When compared to the FLB, the PAB exhibit a higher level of biodiversity and abundance. However, no distinct alpha and beta diversity differences were observed between the bottom, middle, and surface water layers. The community assembly analysis indicated that nearshore communities are predominantly shaped by deterministic processes, particularly due to heterogeneous selection of PAB; In contrast, offshore communities are governed more by stochastic processes, largely due to homogenizing dispersal of FLB. Consequently, the findings of this study demonstrate that nearshore and PAB communities exhibit higher levels of species diversity, while stochastic and deterministic processes exert distinct influences on communities among near- and offshore regions. This study further sheds new light on our understanding of the mechanisms governing bacterial communities in estuarine ecosystems.

miR-210-5p Promotes Pulmonary Hypertension by Blocking ATP2A2.

AIM: Aberrant expression of ATPase sarcoplasmic/endoplasmic retic Ca2+ transporting 2 (ATP2A2) has attracted attention for its pathophysiologic role in pulmonary hypertension (PH). Several miRNAs, including miR-210-5p, have also been reported to be pathogenic factors in PH, but their exact mechanisms remain unknown. This study aimed to elucidate the potential mechanisms of miR-210-5p and ATP2A2 in MCT-induced PH. METHODS: Eighteen Sprague-Dawley rats were randomly divided into two groups-monoclonal (MCT) group and control group-and then administered MCT (60 mg/kg) and saline, respectively. mPAP, PVR, RVHI, WT%, and WA% were significantly increased in PH rats after 3 weeks, confirming that the modeling of PH rats was successful. Subsequently, we determined the expression of ATP2A2 and miR-210-5p in lung tissues using WB and qRT-PCR methods. We established an in vitro model using BMP4 and TGF-ß1 treatment of pulmonary artery smooth muscle cells (PASMCs) and examined the expression of ATP2A2 and miR-210-5p using the same method. To further elucidate the regulatory relationship between ATP2A2 and miR-210-5p, we altered the expression level of miR-210-5p and detected the corresponding changes in ATP2A2 levels. In addition, we demonstrated the relationship by dual luciferase experiments. Finally, the effect of silencing ATP2A2 could be confirmed by the level of cell membrane Ca2+ in PAMSCs. RESULTS: Up-regulation of miR-210-5p and down-regulation of ATP2A2 were observed in the MCT group compared with the control group, which was confirmed in the in vitro model. In addition, elevated miR-210-5p expression decreased the level of ATP2A2 while increasing the proliferation of PASMCs, and the results of the dual luciferase assay further confirmed that ATP2A2 is a downstream target of miR-210-5p. Additionally, silencing ATP2A2 resulted in increased cytoplasmic Ca2+ levels in PAMSCs. CONCLUSION: In MCT-induced PH, miR-210-5p promotes pulmonary vascular remodeling by inhibiting ATP2A2.

Design, synthesis and biological evaluation of Thiazolo[3, 2-a]Pyrimidine derivatives as novel RNase H inhibitors.

Targeting Ribonuclease H (RNase H) has been considered a viable strategy for HIV therapy. In this study, a series of novel thiazolo[3, 2-a]pyrimidine derivatives were firstly designed and synthesized as potential inhibitors of HIV-1 RNase H. Among these compounds, A28 exhibited the most potent inhibition against HIV-1 RNase H with an IC50 value of 4.14 µM, which was about 5-fold increase in potency than the hit compound A1 (IC50 = 21.49 µM). To gain deeper insights into the structure-activity relationship (SAR), a CoMFA model was constructed to yield reasonable statistical results (q2 = 0.658 and R2 = 0.969). Results from magnesium ion chelation experiments and molecular docking studies revealed that these thiazolopyrimidine inhibitors may exert their inhibitory activity by binding to an allosteric site on RNase H at the interface between subunits p51 and p66. Furthermore, this analog demonstrated favorable physicochemical properties. Our findings provide valuable groundwork for further development of allosteric inhibitors targeting HIV-1 RNase H.

Analysis of spiritual well-being status and influencing factors in patients with esophageal cancer: a cross-sectional study.

OBJECTIVE: To understand the status of spiritual well-being in patients with esophageal cancer and analyze its influencing factors. METHODS: A total of 187 patients with esophageal cancer (EC) from two grade A hospitals in Chengdu were selected and investigated by general data questionnaire, chronic disease function evaluation-spirituality scale 12 (FACIT-SP-12), general well-being scale (GWB), and Anderson symptom assessment scale gastrointestinal tract (MDASI-GI). RESULTS: The spiritual well-being score of patients with esophageal cancer was (25.13 ± 9.63). Spiritual well-being was positively correlated with general well-being and negatively correlated with symptom burden (P < 0.01). The results of multiple stepwise linear regression analysis showed that hobbies, disease stage, general well-being, and symptom burden were the main influencing factors for the spiritual well-being of esophageal cancer patients (P < 0.05), explaining 49.0% of the total variation. CONCLUSIONS: The spiritual well-being of patients with esophageal cancer is lower than the middle level, In addition, whether there is a hobby in life, disease stage, subjective well-being, and symptom burden are the main factors affecting the spiritual well-being of patients with EC. It is suggested that medical staff should take targeted care measures according to the influencing factors, so as to improve the spiritual well-being level of patients and improve the quality of life of patients.

Cost-related medication nonadherence in adults with COPD in the United States 2013-2020.

BACKGROUND: Cost-related medication nonadherence (CRN) is associated with poor prognosis among patients with chronic obstructive pulmonary disease (COPD), a population that requires long-term treatment for secondary prevention. In this study, we aimed to estimate the prevalence and sociodemographic characteristics of CRN in individuals with COPD in the US. METHODS: In a nationally representative survey of US adults in the National Health Interview Survey (2013-2020), we identified individuals aged ≥18 years with a self-reported history of COPD. Cross-sectional study. RESULTS: Of the 15,928 surveyed individuals, a weighted 18.56% (2.39 million) reported experiencing CRN, including 12.50% (1.61 million) missing doses, 13.30% (1.72 million) taking lower than prescribed doses, and 15.74% (2.03 million) delaying filling prescriptions to save costs. Factors including age < 65 years, female sex, low family income, lack of health insurance, and multimorbidity were associated with CRN. CONCLUSIONS: In the US, one in six adults with COPD reported CRN. The influencing factors of CRN are multifaceted and necessitating more rigorous research. Targeted interventions based on the identified influencing factors in this study are recommended to enhance medication adherence among COPD patients.

The impact of glucocorticoids therapy on cutaneous wounds in Kawasaki disease: A meta-analysis of randomized controlled trials.

Kawasaki disease (KD) is one of the most challenging diseases that is defined as an acute vasculitis that affects the coronary arteries primarily in children. It causes complications if left untreated at early stages, ultimately leading to death. Corticosteroids have been recognized to treat and cause great impact on the patients with KD. Glucocorticoid is one of the main corticosteroids that are being used to treat KD and cutaneous wounds. However, ineffectiveness of a few glucocorticoids can limit the efficacy of this treatment. This study particularly aimed to elucidate the impact of glucocorticoids on cutaneous wounds in KD. To perform the meta-analysis, a comprehensive literature survey was conducted to unveil the studies and research conducted on Kawasaki patients that revealed different glucocorticoids in the form of specific interventions influencing KD. The literature was searched using numerous keywords, screened and data was extracted to perform the meta-analysis and then it was conducted using the metabin function of R package meta. A total of 2000 patients from both intervention and control groups were employed to carry out the meta-analysis to analyse and evaluate the impact of glucocorticoids on curing KD and cutaneous wounds in patients. The results disclosed that glucocorticoids along with other steroids, mainly IVIG (intravenous immunoglobulin), was an effective intervention to patients suffering from Kawasaki. The results depicted significant outcomes with the values (risk ratio [RR]: 1.08, 95% confidence interval [CI]: 0.58-2.00, p < 0.01) and enlightened the fact that adopting different glucocorticoids may significantly improve the efficacy of skin lesions along with KD. Hence, interventions of glucocorticoids must be utilized in the clinical practice to reduce the incidence of skin wounds and adverse effects caused due to KD.

Advances in Bio-Optical Imaging Systems for Spatiotemporal Monitoring of Intestinal Bacteria.

Vast and complex intestinal communities are regulated and balanced through interactions with their host organisms, and disruption of gut microbial balance can cause a variety of diseases. Studying the mechanisms of pathogenic intestinal flora in the host and early detection of bacterial translocation and colonization can guide clinical diagnosis, provide targeted treatments, and improve patient prognosis. The use of in vivo imaging techniques to track microorganisms in the intestine, and study structural and functional changes of both cells and proteins, may clarify the governing equilibrium between the flora and host. Despite the recent rapid development of in vivo imaging of intestinal microecology, determining the ideal methodology for clinical use remains a challenge. Advances in optics, computer technology, and molecular biology promise to expand the horizons of research and development, thereby providing exciting opportunities to study the spatio-temporal dynamics of gut microbiota and the origins of disease. Here, this study reviews the characteristics and problems associated with optical imaging techniques, including bioluminescence, conventional fluorescence, novel metabolic labeling methods, nanomaterials, intelligently activated imaging agents, and photoacoustic (PA) imaging. It hopes to provide a valuable theoretical basis for future bio-intelligent imaging of intestinal bacteria.

The Valorization of Wastes and Byproducts from Cruciferous Vegetables: A Review on the Potential Utilization of Cabbage, Cauliflower, and Broccoli Byproducts.

The management of vegetable waste and byproducts is a global challenge in the agricultural industry. As a commonly consumed vegetable crop, cruciferous vegetables marked higher amounts of wastage during their supply chain processes, with a significant contribution from cabbage, cauliflower, and broccoli. Therefore, the sustainable and resource-efficient utilization of discarded materials is crucial. This review explores potential applications of cruciferous vegetable waste and byproducts, spotlighting cabbage, cauliflower, and broccoli in food, medicinal, and other industries. Their significance of being utilized in value-added applications is addressed, emphasizing important biomolecules, technologies involved in the valorization process, and future aspects of practical applications. Cabbage, cauliflower, and broccoli generate waste and low-processing byproducts, including leaves, stems, stalks, and rot. Most of them contain high-value biomolecules, including bioactive proteins and phytochemicals, glucosinolates, flavonoids, anthocyanins, carotenoids, and tocopherols. Interestingly, isothiocyanates, derived from glucosinolates, exhibit strong anti-inflammatory and anticancer activity through various interactions with cellular molecules and the modulation of key signaling pathways in cells. Therefore, these cruciferous-based residues can be valorized efficiently through various innovative extraction and biotransformation techniques, as well as employing different biorefinery approaches. This not only minimizes environmental impact but also contributes to the development of high-value-added products for food, medicinal, and other related industries.

Joint association of diabetes mellitus and inflammation status with biological ageing acceleration and premature mortality.

BACKGROUND: We aimed to investigate the associations of diabetes mellitus (DM) and C-reactive protein (CRP) with biological ageing acceleration and mortality risk. METHODS: We analyzed data from 41,634 adults with CRP and DM at baseline. Subjects were categorized into high CRP (>3 mg/L) and low CRP (≤3 mg/L) groups. The cross-sectional endpoints of the study were biological ageing indicators Klemera-Doubal method BioAge acceleration (KDMAccel) and Phenotypic age acceleration (PhenoAgeAccel), and the follow-up endpoints were all-cause mortality and cardiovascular mortality. RESULTS: In adults with high CRP, compared with those without DM, PhenoAgeAccel increased by 1.66 years (95 % CI: 1.38-1.93), and 8.74 years (95 % CI: 8.25-9.22) in adults with prediabetes and DM, respectively (p for interaction <0.001). Using the CRPlow/non-DM group as a reference, adults in the CRPhigh/non-DM, CRPlow/DM, and CRPhigh/DM groups had significantly advanced biological ageing. Compared to adults without DM, low CRP, and no ageing acceleration, the multivariable-adjusted HRs (95%CIs) of all-cause and cardiovascular mortality in those with DM, CRP, and ageing acceleration were 3.22 (2.79-3.72), and 3.57 (2.81-4.54), respectively. CONCLUSIONS: These findings suggest that the joint presence of low-grade inflammation and DM might be associated with higher odds of biological ageing acceleration and premature mortality.

Decreased cobalamin sensitivity and biological aging acceleration in the general population.

BACKGROUND: The evidence on the association between cobalamin (Cbl) and aging or relevant outcomes is limited and controversial. We aimed to investigate the relationships between cobalamin intake- and function-related biomarkers and biological aging. METHODS: The study encompassed 22,812 participants aged 20 years and older from the National Health and Nutrition Examination Survey. A panel of biomarkers or algorithms was used to assess biological aging, including Klemera-Doubal Age Acceleration (KDMAccel), Phenotypic age acceleration (PhenoAgeAccel), telomere length, α-Klotho, and PhenoAge advancement. Weighted generalized linear regression analysis was used to assess the associations between cobalamin-intake biomarkers (serum cobalamin, cobalamin intake from food, cobalamin supplement use, serum methylmalonic acid [MMA], and homocysteine [Hcy]) and function-related biomarkers (functional cobalamin deficiency and cobalamin insensitivity index). RESULTS: Among the 22,812 individuals, the weighted mean (SE) age was 48.3 (0.2) years and 48.0% were males. Unexpectedly, serum and dietary cobalamin as well as serum MMA and Hcy levels were positively associated with most indicators of biological aging. Cobalamin sensitivity was assessed by the combination of binary Cbllow/high and MMAlow/high or Hcylow/high (cutoff values: 400 pg/mL for cobalamin, 250 nmol/L for MMA, and 12.1 µmol/l for Hcy) and a newly constructed cobalamin insensitivity index (based on the multiplicative term of serum cobalamin and serum MMA or Hcy). The multivariable-adjusted ß (95%CIs) of KDMAccel in the MMAlowCbllow, MMAlowCblhigh, MMAhighCbllow, and MMAhighCblhigh groups were reference, 0.27 (0.03 to 0.51), 0.85 (0.41 to 1.29), and 7.97 years (5.77 to 10.17) respectively, which were consistent for the combination of serum Hcy and cobalamin. Both cobalamin insensitivity indices were robustly associated with biological aging acceleration in a dose-response pattern (each p < 0.001). CONCLUSIONS: Decreased cobalamin sensitivity but not cobalamin insufficiency might be associated with biological aging acceleration. Further studies would improve understanding of the underlying mechanisms between decreased cobalamin sensitivity and biological aging acceleration.

Homocysteine Metabolism, Subclinical Myocardial Injury, and Cardiovascular Mortality in the General Population.

Background: Homocysteine (Hcy) is a recognized cardiovascular disease (CVD) risk factor linked with atherosclerosis. However, the association between Hcy and myocardial injury is little known. Objectives: This study aimed to examine the associations between Hcy metabolism, subclinical myocardial injury, and cardiovascular mortality. Methods: We included 10,871 participants without diagnosed CVD. Generalized linear regression was used to investigate the relationship between Hcy-related indicators (plasma total Hcy [tHcy], vitamin B12, and folate) and myocardial injury biomarkers (high-sensitivity troponin T [hs-cTnT], high-sensitivity troponin I [hs-cTnI] measured using 3 assays [Abbott, Siemens, and Ortho], and N-terminal pro-B-type natriuretic peptide [NT-proBNP]). Results: Among 10,871 participants, the weighted mean levels for tHcy, folate, and vitamin B12 were 8.58 µmol/L, 32.43 nmol/L, and 447.08 pmol/L, respectively. Plasma tHcy levels were positively associated with elevated hs-cTnT, hs-cTnI, and NT-proBNP, whereas folate and vitamin B12 were not inversely related to myocardial injury biomarkers. Multivariable-adjusted odds ratios for elevated hs-cTnT (19 ng/L) and NT-proBNP (125 pg/mL) per doubling of tHcy were 2.80 (95% CI: 1.17-6.73; P < 0.001) and 1.58 (95% CI: 1.20-2.08; P < 0.001), respectively. The associations of tHcy levels with elevated hs-cTnI (Abbott: 28 ng/L; Siemens: 46.5 ng/L; Ortho: 11 ng/L) were consistent. Indirect effects of tHcy on cardiovascular mortality risk via hs-cTnT and NT-proBNP explained up to 26.6% and 12.3% of the total effect, respectively. Conclusions: Plasma tHcy, not folate or vitamin B12, is significantly associated with elevated hs-cTnT, hs-cTnI, and NT-proBNP in adults without CVD. Subclinical myocardial injury may substantially mediate Hcy-related cardiovascular mortality risk.

The association between serum methylmalonic acid, cobalamin-related biomarkers, and long-term mortality risk in cancer survivors: a prospective cohort study.

BACKGROUND: Elevated serum methylmalonic acid (MMA), a marker of cobalamin (vitamin B12) deficiency, has been linked to cancer progression. However, the impact of MMA or cobalamin on mortality risk in cancer survivors remains unknown. OBJECTIVES: To explore the relationship between MMA, serum, dietary, and supplement of cobalamin, MMA metabolism-related genes, and poor prognosis in adult cancer survivors. METHODS: We analyzed data from 1988 cancer survivors aged ≥20 y. Patients were selected from the National Health and Nutrition Examination Survey and followed up until December 31, 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for mortality risk assessment. Genomic analysis identified MMA metabolism-related genes linked to early death in a 33-cancer-type cohort from The Cancer Genome Atlas. RESULTS: Among 1988 participants, 872 deaths occurred over a 10-year follow-up. Higher serum MMA levels were significantly linked to increased long-term mortality risk (tertile 3 compared with tertile 1: adjusted HR: 1.37; 95% CI: 1.11, 1.70; P-trend < 0.001). No associations were found between serum, dietary, and supplement of cobalamin and cancer survivor mortality (each P-trend > 0.143). However, MMA-associated mortality was notable in patients without deficiency. When combining cobalamin and MMA categories, multivariate-adjusted HR (95% CI) for all-cause mortality was 2.06 (95% CI: 1.60, 2.65) in participants with >250 nmol/L and cobalamin >295.1 pmol/L compared with those with MMA ≤250 nmol/L and cobalamin >295.1 pmol/L. Moreover, reduced transcriptional levels of MMA metabolism-related genes, indicating decreased mitochondrial MMA metabolism capability, are linked to an unfavorable prognosis in certain cancer types. CONCLUSIONS: Serum MMA was associated with long-term mortality risk in adult cancer survivors, which was more significant among individuals with higher levels of serum cobalamin. These findings suggest that mortality related to MMA was attributed to the insufficient flux of MMA metabolism, not cobalamin deficiency.

Association of adverse childhood experiences with poor health condition among middle-aged and elderly adults in the United States: A nationally retrospective cohort study.

BACKGROUND: The specific effects of adverse childhood experiences (ACEs) in adulthood and senectitude were less known. We aim to examine the relationship between early ACEs and overall health condition as well as specific dimensions in the middle-aged and elderly population. METHODS: In the 2019-2021 Behavioral Risk Factor Surveillance System Study, robust Poisson regression models were used to estimate the relationship between ACE exposure and current health status among adults aged 45 ≥ years. RESULTS: Of the 195,472 participants, 53.8 % were female and the mean age was 65.0 years. Compared to populations without ACE, ACE exposures were more significantly associated with depression (PR: 2.03, 95 %CI: 1.94-2.21), frequent mental health (PR: 1.85, 95 %CI: 1.74-1.97) and subject cognitive decline (PR: 1.99, 95 %CI:1.85-2.14) than with physical health (PR: 1.37, 95 %CI: 1.32-1.44), with dose-response patterns. The association with mental disorder was especially significant among the elderly population. CONCLUSION: Early ACEs are associated with adverse health outcomes that persist into later life, particularly mental disorders and cognitive decline. Poor mental health may indirectly influence associations with ACEs and cognitive decline as well as physical health. Our findings emphasize the importance of lifelong psychological screening and support for the ACE-exposed middle-aged and elderly population.

Water masses influence the variation of microbial communities in the Yangtze River Estuary and its adjacent waters.

The Yangtze River estuary (YRE) are strongly influenced by the Kuroshio and terrigenous input from rivers, leading to the formation of distinct water masses, however, there remains a limited understanding of the full extent of this influence. Here the variation of water masses and bacterial communities of 58 seawater samples from the YRE and its adjacent waters were investigated. Our findings suggested that there were 5 water masses in the studied area: Black stream (BS), coastal water in the East China Sea (CW), nearshore mixed water (NM), mixed water in the middle and deep layers of the East China Sea (MM), and deep water blocks in the middle of the East China Sea (DM). The CW mass harbors the highest alpha diversity across all layers, whereas the NM mass exhibits higher diversity in the surface layer but lower in the middle layers. Proteobacteria was the most abundant taxa in all water masses, apart from that, in the surface layer masses, Cyanobacterium, Bacteroidota, and Actinobacteriota were the highest proportion in CW, while Bacteroidota and Actinobacteriota were the highest proportion in NM and BS; in the middle layer, Bacteroidota and Actinobacteriota were dominant phylum in CW and BS masses, but Cyanobacterium was main phylum in NM mass; in the bottom layer, Bacteroidota and Actinobacteriota were the dominant phylum in CW, while Marininimicrobia was the dominated phylum in DM and MM masses. Network analysis suggests water masses have obvious influence on community topological characteristics, moreover, community assembly across masses also differ greatly. Taken together, these results emphasized the significant impact of water masses on the bacterial composition, topological characteristics and assembly process, which may provide a theoretical foundation for predicting alterations in microbial communities within estuarine ecosystems under the influence of water masses.

linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability.

Adipose tissue remodeling and dysfunction, characterized by elevated inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2D) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here, we describe the functions of linc-ADAIN (adipose anti-inflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans. We demonstrate that linc-ADAIN knockdown (KD) increases KLF5 and interleukin-8 (IL-8) mRNA stability and translation by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, leads to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo. KD of linc-ADAIN in human adipose stromal cell (ASC) hTERT adipocytes implanted into mice increases adipocyte size and macrophage infiltration compared to implanted control adipocytes, mimicking hallmark features of obesity-induced adipose tissue remodeling. linc-ADAIN is an anti-inflammatory lincRNA that limits adipose tissue expansion and lipid storage.

Impact of gut microbiota on nonalcoholic fatty liver disease: insights from a leave-one-out cross-validation study.

Introduction: Enteric dysbacteriosis is strongly associated with nonalcoholic fatty liver disease (NAFLD). However, the underlying causal relationship remains unknown. Thus, the present study aimed to investigate the relationship between gut microbiota and NAFLD using Mendelian randomization (MR) and analyze the target genes potentially regulated by specific microbiota. Methods: Bidirectional two-sample MR analysis was performed using inverse variance weighted (IVW) supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Data were pooled from gut microbiota and NAFLD association studies. The least absolute shrinkage, selection operator regression, and the Support Vector Machine algorithm were used to identify genes regulated by these intestinal flora in NAFLD. The liver expression of these genes was verified in methionine choline-deficient (MCD) diet-fed mice. Results: IVW results confirmed a causal relationship between eight specific gut microbes and NAFLD. Notably, the order Actinomycetales, NB1n, the family Actinomycetaceae, Oxalobacteraceae and the genus Ruminococcaceae UCG005 were positively correlated, whereas Lactobacillaceae, the Christensenellaceae R7 group, and Intestinibacter were negatively correlated with NAFLD onset. In NAFLD, these eight bacteria regulated four genes: colony-stimulating factor 2 receptor ß, fucosyltransferase 2, 17-beta-hydroxysteroid dehydrogenase 14, and microtubule affinity regulatory kinase 3 (MAPK3). All genes, except MARK3, were differentially expressed in the liver tissues of MCD diet-fed mice. Discussion: The abundance of eight gut microbiota species and NAFLD progression displayed a causal relationship based on the expression of the four target genes. Our findings contributed to the advancement of intestinal microecology-based diagnostic technologies and targeted therapies for NAFLD.

C5aR antagonist inhibits LPS-induced inflammation in human gingival fibroblasts via NF-κB and MAPK signaling pathways

Abstract Objective Abnormal complement activation is associated with periodontitis. W54011 is a novel non-peptide C5aR antagonist (C5aRA) that exhibits favorable anti-inflammatory effects in various inflammatory models. However, whether W54011 inhibits periodontitis has not yet been fully elucidated. To address this, we have investigated the probable anti-inflammatory mechanism of W54011 in LPS-treated inflammation in human gingival fibroblasts (HGFs). Methodology HGFs were isolated from healthy gingival tissue samples using the tissue block method and were identified with immunofluorescence staining. The CCK8 assay and reverse transcription-PCR (RT-PCR) were used to select the optimal induction conditions for Lipopolysaccharide (LPS) and C5aRA (according to supplementary data S1, S2 and S3). The levels of inflammatory cytokines, C5aR, and the activation of NF-κB/MAPK signaling pathways were determined by RT-quantitative PCR (RT-qPCR) and Western blotting. Results Immunofluorescence results showed that vimentin and FSP-1 were positive in HGFs and Keratin was negative in HGFs. Immunofluorescence staining demonstrated that C5aRA inhibited LPS-stimulated nuclear translocation of p-p65. RT-qPCR and Western blotting showed that C5aRA reduced the expression of IL-1β, IL-6, TNF-α, C5aR, p-p65, p-IκBα, p-JNK, p-c-JUN, and TLR4 in LPS-induced HGFs. Conclusion These findings suggested that C5aRA attenuated the release of inflammatory cytokines in LPS-induced HGFs by blocking the activation of the NF-κB and MAPK signaling pathways.