Microbial nitrogen transformation regulates pathogenic virulence in soil environment.

Soil nitrogen addition induces the generation and proliferation of some bacterial virulence, yet the interactive mechanisms between the two remain unclear. Here we investigated the variation of virulence genes (VGs) abundance during soil nitrogen transformation, and explored the biological mechanism and key pathways involved in the regulation of VGs by nitrogen transformation. The results showed that the diversity and abundance of virulence genes in soil under high nitrogen input (100 mg/kg) were markedly higher than those under low nitrogen input (50 mg/kg), suggesting a trade-off between the prevalence of virulence genes and nitrogen metabolism. Nutritional/metabolic factor, regulation, immune modulation and motility were the dominant virulence types. Linear regression analysis showed that soil nitrogen mineralization and nitrification rate were closely correlated with the abundance of virulence genes, mainly involving adherence, nutritional/metabolic factors and immune modulation (p < 0.05). Structural equations indicated that microbial community succession associated with nitrogen transformation largely contributed to the changes in VGs abundance. Metagenomic analysis revealed that major virulence genes pilE, pchB, and galE were regulated by nitrogen-functional genes gdh, ureC, and amoC, implying that microbial nitrogen transformation influences immune modulation, nutritional/metabolic factors, and adherence-like virulence. The meta-transcriptome reiterated their co-regulation, and the key pathway may be glutamate/urea> α-ketoglutarate/ammonia > pyruvate/amino acid. The outcome provides strong evidence on the linkage between microbial nitrogen transformation and pathogenic virulence factors development in the soil environment, which will aid in the effective suppression of the prevalence of soil pathogenic virulence.

Lignin hydrogenolysis: Tuning the reaction by lignin chemistry.

Replacing fossil resource with biomass is one of the promising approaches to reduce our carbon footprint. Lignin is one of the three major components of lignocellulosic biomass, accounting for 10-35 wt% of dried weight of the biomass. Hydrogenolytic depolymerization of lignin is attracting increasing attention because of its capacity of utilizing lignin in its uncondensed form and compatibility with the biomass fractionation processes. Lignin is a natural aromatic polymer composed of a variety of monolignols associated with a series of lignin linkage motifs. Hydrogenolysis cleaves various ether bonds in lignin and releases phenolic monomers which can be further upgraded into valuable products, i.e., drugs, terephthalic acid, phenol. This review provides an overview of the state-of-the-art advances of the reagent (lignin), products (hydrol lignin), mass balance, and mechanism of the lignin hydrogenolysis reaction. The chemical structure of lignin is reviewed associated with the free radical coupling of monolignols and the chemical reactions of lignin upon isolation processes. The reactions of lignin linkages upon hydrogenolysis are discussed. The components of hydrol lignin and the selectivity production of phenolic monomers are reviewed. Future challenges on hydrogenolysis of lignin are proposed. This article provides an overview of lignin hydrogenolysis reaction which shows light on the generation of optimized lignin ready for hydrogenolytic depolymerization.

Association Between Visceral Obesity and Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Retrospective Study.

Purpose: To investigate the association between visceral obesity and glycemic control in patients with type 2 diabetes mellitus. Patients and Methods: A retrospective analysis involved 714 patients diagnosed with type 2 diabetes mellitus from the National Metabolic Management Center from November 2021 to February 2024. Medical data included sociodemographic data, lifestyle behaviors, and anthropometric and biochemical measurements. Multivariate logistic regression analysis was used to analyze their associations. Results: Among the patients, 251 (35.2%) achieved good glycemic control (HbA1c < 7.0%). On univariate analysis, higher diastolic blood pressure, longer duration of type 2 diabetes mellitus, tobacco smoking, alcohol drinking, insulin treatment, higher levels of fasting plasma glucose, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, and low-density lipoprotein cholesterol, visceral obesity (visceral fat area ≥ 100cm2) and diabetic peripheral neuropathy were all positively correlated with poor glycemic control; female, older age, higher levels of C peptide and serum uric acid were inversely associated with poor glycemic control (all P < 0.05). On multivariate logistic regression analysis, the results suggested that higher diastolic blood pressure [OR: 1.021, 95% CI (1.002, 1.040), P = 0.030], insulin treatment [currently used: OR = 2.156, 95% CI (1.249, 3.724), P = 0.006], higher level of fasting plasma glucose [OR: 1.819, 95% CI (1.598, 2.069), P < 0.001], and visceral obesity [OR: 1.876, 95% CI (1.158, 3.038), P = 0.011] were risk factors for poor glycemic control. Conclusion: This study indicated that visceral obesity (visceral fat area ≥ 100cm2) is positively associated with poor glycemic control, and serves as an independent risk factor for poor glycemic control (HbA1c ≥ 7.0%) in patients with type 2 diabetes mellitus. Screening for visceral obesity should be emphasized, and targeted interventions should be taken to improve glycemic control in patients with type 2 diabetes mellitus.

Association of serum uric acid to serum creatinine ratio with 1-year stroke outcomes in patients with acute ischemic stroke: A multicenter observational cohort study.

BACKGROUND AND PURPOSE: Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function-normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1-year outcomes in patients with acute ischemic stroke (AIS). METHODS: This is a prospective, multicenter observational study. Renal function-normalized SUA levels were determined by calculating the ratio of SUA to SCr. One-year outcomes included stroke recurrence, all-cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1-year stroke outcomes. RESULTS: Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one-unit increase in SUA/SCr corresponded to a 19% decrease in 1-year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1-Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1-year stroke recurrence risks. The trend test indicated significant differences in the 1-year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all-cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1-year stroke recurrence. CONCLUSIONS: In patients with AIS, low SUA/SCr may be an independent risk factor for 1-year stroke recurrence. Changes in SUA/SCr had no significant impact on 1-year poor prognosis and all-cause mortality.

Application of Continuous Care Pattern Based on Information-Motivation-Behavioral Skills Model in out-of-Hospital Rehabilitation of Diabetic Foot Ulceration Patients: A Randomized Controlled Trial.

OBJECTIVE: To explore the effect of information-motivation-behavioral skills model (IMB)-based continuous nursing model on the out-of-hospital rehabilitation of diabetic foot ulceration (DFU) patients, and to provide a theoretical basis for long-term disease management of DFU patients. METHODS: A total of 88 patients with DFU admitted to our Hospital were included in this prospective study. The patients were divided into control and study groups using the random number table method, with 44 cases in each group. Patients in the study group received both routine care and IMB-based continuing care, and the control group received only routine care. RESULTS: At week 1, FBS, PBG (2 h) and HbA1c were significantly decreased in the study group compared with that in the control group (P < .05). At week 3 and 6, blood glucose indicators were significantly improved in both groups compared with week 1 (P < .05). In additional, the number of non-infected patients at week 1 and week 3 in the study group was significantly higher than that in the control group (P < .05). At week 3, the number of cured patients was significantly higher in the study group than that in the control group (P < .05). And the area of ulcer healing in the study group was significantly larger than that in the control group at week 1 and week 3 (P < .05). CONCLUSION: In conclusion, the continuous nursing mode based on IMB can help DFU patients manage blood glucose level, reduce wound infection, and accelerate wound healing, which is worthy of wide clinical application and promotion.

Mechanical property enhancement of flax fibers via supercritical fluid treatment.

The desire for lightweight, carbon-negative materials has been increasing in recent years, particularly as the transportation sector reduces its global carbon footprint. Natural fibers, such as flax fiber and their composites, offer a compelling combination of properties including low density, high specific strength, and carbon negativity. However, because of the low modulus and high variability in performance, natural fibers can't compete with glass fibers as structural reinforcements in polymer composites. In this study, flax technical fibers were treated in supercritical CO2 (scCO2), and the effects of this treatment on the morphology and properties of flax fibers are reported. Treatment in scCO2 successfully resulted in higher fiber modulus and strength by 33% and 40%, respectively. Fiber porosity was reduced by 50% and morphological changes to the fibers were observed. Specifically, fiber lumen collapsed during treatment and micro/mesoporosity was reduced by 27%. Treated flax fibers were used to create 30 vol% unidirectional flax-epoxy composites. ScCO2 treatment raised composite modulus and strength by 33% and 25%, respectively. Because of the dependence between technical fiber size and mechanical properties, the relationship between fiber modulus and fiber size were created and applied to the rule-of-mixtures. This relationship were found to be viable representations of the fiber performance within each composite. Overall, the treatment developed in this study has the potential to significantly improve natural fiber properties, enabling their consideration for use in lightweight, semi-structural composites.

Tick chemosensation and implications for novel control strategies.

Ticks pose a major threat to the health of humans and animals. The use of synthetic acaricides and repellents has raised the concerns of potential health and environmental risks and increasing resistance in ticks. This article highlights the importance of the research on tick chemosensation in developing novel control agents. It provides a review on our current understanding of tick chemosensory system and proposes using chemosensory receptor (CR) genes as molecular targets to discover novel tick control agents. The releases of high-quality tick genomes provide unprecedented opportunities to explore CR gene repertoires. Further functional characterization is necessary to identify the receptors for key chemical cues and signals and unravel whether tick chemosensation involves ionotropic and/or metabotropic mechanisms.

Optimizing resident training in obstetrics and gynecology: a new perspective on the refined Peyton four-step teaching method.

OBJECTIVE: In the surgery-focused field of obstetrics and gynecology (OB-GYN), the development of residents' skills is paramount. This study aims to evaluate the impact of an enhanced Peyton Four-Step Teaching Model on the foundational skill training of first-year OB-GYN residents. METHODS: Utilizing a cohort study design, we assessed 116 first-year residents from the OB-GYN residency program at Shengjing Hospital of China Medical University from June 2021 to June 2023. The 57 residents beginning their training in 2022 were part of the Refined Peyton (RP) group, introduced to the RP method; the 59 residents from 2021 served as the Traditional Teaching-mode (TTM) group, receiving conventional simulation-based instruction. Teaching effectiveness was assessed by comparing theoretical knowledge and skill performance assessments, National Medical Licensing Examination (NMLE) pass rates, direct observation of procedural skills (DOPS) one year post-training, and survey feedback. RESULTS: The theoretical knowledge scores for both groups were comparable at 78.78 ± 4.08 and 78.70 ± 3.83, with no significant difference (P = 0.76). However, the experimental group demonstrated superior performance in skill operation assessments, first-time NMLE pass rates, and DOPS evaluations one year after training [(77.05 ± 5.39) vs. (84.60 ± 5.65), 100.0% (57/57) vs. 86.4% (51/59), and (75.22 ± 3.56) vs. (82.54 ± 3.43)], as well as higher teaching satisfaction scores [(4.63 ± 0.46) vs. (3.92 ± 0.62)], with all differences being statistically significant (P < 0.05). CONCLUSION: The refined Peyton Four-Step Teaching Model significantly improves the immediate acquisition and long-term retention of clinical basic skills among OB-GYN residents, enhancing both teaching efficacy and resident satisfaction.

Analysis of the Aging-Related AP2/ERF Transcription Factor Gene Family in Osmanthus fragrans.

Ethylene-Responsive Factor (ERF) is a key element found in the middle and lower reaches of the ethylene signal transduction pathway. It is widely distributed in plants and plays important roles in plant growth and development, hormone signal transduction, and various stress processes. Although there is research on AP/ERF family members, research on AP2/ERF in Osmanthus fragrans is lacking. Thus, in this work, AP2/ERF in O. fragrans was extensively and comprehensively analyzed. A total of 298 genes encoding OfAP2/ERF proteins with complete AP2/ERF domains were identified. Based on the number of AP2/ERF domains and the similarity among amino acid sequences between AP2/ERF proteins from A. thaliana and O. fragrans, the 298 putative OfAP2/ERF proteins were divided into four different families, including AP2 (45), ERF (247), RAV (5), and SOLOIST (1). In addition, the exon-intron structure characteristics of these putative OfAP2/ERF genes and the conserved protein motifs of their encoded OfAP2/ERF proteins were analyzed, and the results were found to be consistent with those of the population classification. A tissue-specific analysis showed the spatiotemporal expression of OfAP2/ERF in the stems and leaves of O. fragrans at different developmental stages. Specifically, 21 genes were not expressed in any tissue, while high levels of expression were found for 25 OfAP2/ERF genes in several tissues, 60 genes in the roots, 34 genes in the stems, 37 genes in young leaves, 34 genes in old leaves, 32 genes in the early flowering stage, 18 genes in the full flowering stage, and 37 genes in the late flowering stage. Quantitative RT-PCR experiments showed that OfERF110a and OfERF110b had the highest expression levels at the full-bloom stage (S4), and this gradually decreased with the senescence of petals. The expression of OfERF119c decreased first and then increased, while the expression levels of OfERF4c and OfERF5a increased constantly. This indicated that these genes may play roles in flower senescence and the ethylene response. In the subsequent subcellular localization experiments, we found that ERF1-4 was localized in the nucleus, indicating that it was expressed in the nucleus. In yeast self-activation experiments, we found that OfERF112, OfERF228, and OfERF23 had self-activation activity. Overall, these results suggest that OfERFs may have the function of regulating petal senescence in O. fragrans.

Butyrate protects the intestinal barrier by upregulating Fut2 expression via MEK4-JNK signaling pathway activation.

BACKGROUND: Necrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease in neonates. Fucosyltransferase 2 (Fut2) regulates intestinal epithelial cell fucosylation. In this study, we aimed to investigate butyrate-mediated upregulation of Fut2 expression and the underlying mechanisms. METHODS: In vivo and in vitro models were established. SP600125 was used to inhibit the MEK4-JNK pathway, and anisomycin was used to activate the MEK4-JNK pathway. Fut2, occludin, and ZO-1 expressions were assessed. Furthermore, intestinal permeability was analyzed by FITC-Dextran. The expression of proteins in the MEK-4-JNK pathway was examined by western blotting. RESULTS: In vivo, the addition of exogenous butyrate notably upregulated Fut2, occludin, and ZO-1 expressions and reduced intestinal permeability in mice with NEC. Butyrate may increase the phosphorylation of MEK4, JNK, and c-jun, which are key components of the MEK4-JNK pathway. Additionally, SP600125 inhibited their phosphorylation, which was reversed by anisomycin treatment. In vitro, butyrate substantially increased occludin and ZO-1 expressions. Butyrate considerably increased Fut2 expression and markedly upregulated p-MEK4, p-JNK, and p-c-jun expressions. SP600125 administration decreased their expressions, while anisomycin administration increased their expressions. CONCLUSION: Butyrate upregulated Fut2 expression via activation of the MEK4-JNK pathway, improved intestinal barrier integrity, and protected neonatal mice from NEC. IMPACT: We found that exogenous butyrate could improve intestinal barrier integrity and protect against NEC in neonatal mice. Our data showed that exogenous butyrate supplementation upregulated Fut2 expression by activating the MEK4-JNK pathway. Our study provides novel insights into the pathogenesis of NEC, thereby laying an experimental foundation for future clinical research on the use of butyrate in NEC treatment.

Conserved cis-elements enable NODULES WITH ACTIVATED DEFENSE1 regulation by NODULE INCEPTION during nodulation.

Root nodule symbiosis within nitrogen-fixing clade (NFC) plants is thought to have arisen from a single gain followed by massive losses in the genomes of ancestral non-nodulating plants. However, molecular evidence supporting this model is limited. Here, we confirm through bioinformatic analysis that NODULES WITH ACTIVATED DEFENSE1 (NAD1) is present only in NFC plants and is thus an NFC-specific gene. Moreover, NAD1 was specifically expressed in nodules. We identified three conserved nodulation-associated cis-regulatory elements (NACE1-3) in the promoter of LjNAD1 from Lotus japonicus that are required for its nodule specific expression. A survey of NFC plants revealed that NACE1 and NACE2 are specific to the Fabales and Papilionoideae, respectively, while NACE3 is present in all NFC plants. Moreover, we found that Nodule inception (NIN) directly binds to all three NACEs to activate NAD1 expression. Mutation of L. japonicus LjNAD1 resulted in the formation of abnormal symbiosomes with enlarged symbiosome space and frequent breakdown of bacteroids in nodules, resembling phenotypes reported for Medicago truncatula Mtnad1 and Mtnin mutants. These data point to NIN-NAD1 as an important module regulating rhizobial accommodation in nodules. The regulation of NAD1 by NIN in the NFC ancestor represent an important evolutionary adaptation for nodulation.

Insights into the evolutionary and ecological adaption strategies of nirS- and nirK-type denitrifying communities.

Denitrification is a crucial process in the global nitrogen cycle, in which two functionally equivalent genes, nirS and nirK, catalyse the critical reaction and are usually used as marker genes. The nirK gene can function independently, whereas nirS requires additional genes to encode nitrite reductase and is more sensitive to environmental factors than nirK. However, the ecological differentiation mechanisms of those denitrifying microbial communities and their adaptation strategies to environmental stresses remain unclear. Here, we conducted metagenomic analysis for sediments and bioreactor samples from Lake Donghu, China. We found that nirS-type denitrifying communities had a significantly lower horizontal gene transfer frequency than that of nirK-type denitrifying communities, and nirS gene phylogeny was more congruent with taxonomy than that of nirK gene. Metabolic reconstruction of metagenome-assembled genomes further revealed that nirS-type denitrifying communities have robust metabolic systems for energy conservation, enabling them to survive under environmental stresses. Nevertheless, nirK-type denitrifying communities seemed to adapt to oxygen-limited environments with the ability to utilize various carbon and nitrogen compounds. Thus, this study provides novel insights into the ecological differentiation mechanism of nirS and nirK-type denitrifying communities, as well as the regulation of the global nitrogen cycle and greenhouse gas emissions.

Maternal smoking during pregnancy could accelerate aging in the adulthood: evidence from a perspective study in UK Biobank.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is significantly linked to the short- or long-term health of offspring. However, little research has examined whether MSDP affect the aging rate of offspring. METHODS: This study used questionnaires to determine out whether the participants' mothers smoked when they were pregnant. For evaluating aging rate, we used the following several outcome measures: telomere length, frailty index, cognitive function, homeostatic dysregulation score, KDM-age, age-related hospitalization rate, premature death, and life expectancy. RESULT: After adjusting for covariates, we found that the offspring of the MSDP group had significantly shorter telomere length in adulthood by 0.8 % (ß = -0.008,95%CI:-0.009 to -0.006) compared with non-MSDP group. Compared to the non-MSDP group, participants in MSDP group showed higher levels of homeostatic dysregulation (ß = 0.015,95%CI: 0.007-0.024) and were frailer (ß = 0.008,95%CI:0.007-0.009). The KDM age increased by 0.100 due to MSDP (ß = 0.100,95 % CI:0.018-0.181), and the age acceleration of KDM algorithm also increases significantly (ß = 0.101, 95%CI:0.020-0.183). Additionally, we found that the risk of aging-related hospitalizations was significantly higher than the non-MSDP group by 10.4 %(HR = 1.104,95%CI:1.066-1.144). Moreover, MSDP group had a 12.2 % increased risk of all-cause premature mortality (HR = 1.122,95%CI:1.064-1.182) and a significant risk of lung cancer-specific premature mortality increased by 55.4 %(HR = 1.554,95%CI:1.346-1.793). In addition, participants in the MSDP group had significantly decreased cognitive function and shorter life expectancies than those in non-MSDP group. CONCLUSION: Our findings indicated a significant association between MSPD and accelerated aging, elevated hospitalization rates, increased premature mortality rates, and reduced life expectancies in offspring.

LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis.

At present, the role of many long non-coding RNAs (lncRNAs) as tumor suppressors in the formation and development of cervical cancer (CC) has been studied. However, lncRNA prostate cancer gene expression marker 1 (PCGEM1), whose high expression not only aggravates ovarian cancer but also can induce tumorigenesis and endometrial cancer progression, has not been studied in CC. The objective of this study was to investigate the expression and the underlying role of PCGEM1 in CC. The relative expression of PCGEM1 in CC cells was detected by real-time PCR. After the suppression of PCGEM1 expression by shRNA, the changes in the proliferation, migration, and invasion capacities were detected via CCK-8 assay, EdU assay, and colony formation assay wound healing assay. Transwell assay and the changes in expressions of epithelial-to-mesenchymal transition (EMT) markers were determined by western blot and immunofluorescence. The interplay among PCGEM1, miR-642a-5p, and kinesin family member 5B (KIF5B) was confirmed by bioinformatics analyses and luciferase reporter assay. Results showed that PCGEM1 expressions were up-regulated within CC cells. Cell viabilities, migration, and invasion were remarkably reduced after the suppression of PCGEM1 expression by shRNA in Hela and SiHa cells. N-cadherin was silenced, but E-cadherin expression was elevated by sh-PCGEM1. Moreover, by sponging miR-642a-5p in CC, PCGEM1 was verified as a competitive endogenous RNA (ceRNA) that modulates KIF5B levels. MiR-642a-5p down-regulation partially rescued sh-PCGEM1's inhibitory effects on cell proliferation, migration, invasion, and EMT process. In conclusion, the PCGEM1/miR-642a-5p/KIF5B signaling axis might be a novel therapeutic target in CC. This study provides a research basis and new direction for targeted therapy of CC.

Exome sequencing identifies novel genetic variants associated with varicose veins.

BACKGROUND: Varicose veins (VV) are one of the common human diseases, but the role of genetics in its development is not fully understood. METHODS: We conducted an exome-wide association study of VV using whole-exome sequencing data from the UK Biobank, and focused on common and rare variants using single-variant association analysis and gene-level collapsing analysis. FINDINGS: A total of 13,823,269 autosomal genetic variants were obtained after quality control. We identified 36 VV-related independent common variants mapping to 34 genes by single-variant analysis and three rare variant genes (PIEZO1, ECE1, FBLN7) by collapsing analysis, and most associations between genes and VV were replicated in FinnGen. PIEZO1 was the closest gene associated with VV (P = 5.05 × 10-31), and it was found to reach exome-wide significance in both single-variant and collapsing analyses. Two novel rare variant genes (ECE1 and METTL21A) associated with VV were identified, of which METTL21A was associated only with females. The pleiotropic effects of VV-related genes suggested that body size, inflammation, and pulmonary function are strongly associated with the development of VV. CONCLUSIONS: Our findings highlight the importance of causal genes for VV and provide new directions for treatment.

Microglial circ-UBE2K exacerbates depression by regulating parental gene UBE2K via targeting HNRNPU.

Background: Knowledge about the pathogenesis of depression and treatments for this disease are lacking. Epigenetics-related circRNAs are likely involved in the mechanism of depression and have great potential as treatment targets, but their mechanism of action is still unclear. Methods: Circular RNA UBE2K (circ-UBE2K) was screened from peripheral blood of patients with major depressive disorder (MDD) and brain of depression model mice through high-throughput sequencing. Microinjection of circ-UBE2K overexpression lentivirus and adeno-associated virus for interfering with microglial circ-UBE2K into the mouse hippocampus was used to observe the role of circ-UBE2K in MDD. Sucrose preference, forced swim, tail suspension and open filed tests were performed to evaluate the depressive-like behaviors of mice. Immunofluorescence and Western blotting analysis of the effects of circ-UBE2K on microglial activation and immune inflammation. Pull-down-mass spectrometry assay, RNA immunoprecipitation (RIP) test and fluorescence in situ hybridization (FISH) were used to identify downstream targets of circ-UBE2K/ HNRNPU (heterogeneous nuclear ribonucleoprotein U) axis. Results: In this study, through high-throughput sequencing and large-scale screening, we found that circ-UBE2K levels were significantly elevated both in the peripheral blood of patients with MDD and in the brains of depression model mice. Functionally, circ-UBE2K-overexpressing mice exhibited worsened depression-like symptoms, elevated brain inflammatory factor levels, and abnormal microglial activation. Knocking down circ-UBE2K mitigated these changes. Mechanistically, we found that circ-UBE2K binds to heterogeneous nuclear ribonucleoprotein U (HNRNPU) to form a complex that upregulates the expression of the parental gene ubiquitin conjugating enzyme E2 K (UBE2K), leading to abnormal microglial activation and neuroinflammation and promoting the occurrence and development of depression. Conclusions: The findings of the present study revealed that the expression of circUBE2K, which combines with HNRNPU to form the circUBE2K/HNRNPU complex, is increased in microglia after external stress, thus regulating the expression of the parental gene UBE2K and mediating the abnormal activation of microglia to induce neuroinflammation, promoting the development of MDD. These results indicate that circ-UBE2K plays a newly discovered role in the pathogenesis of depression.

Homologous recombination and gene-specific selection co-shape the vertical nucleotide diversity of mangrove sediment microbial populations.

Mangrove sediments host a diverse array of microbial populations and are characterized by high heterogeneity along their vertical depths. However, the genetic diversity within these populations is largely unknown, hindering our understanding of their adaptive evolution across the sediment depths. To elucidate their genetic diversity, we utilized metagenome sequencing to identify 16 high-frequency microbial populations comprised of two archaea and 14 bacteria from mangrove sediment cores (0-100 cm, with 10 depths) in Qi'ao Island, China. Our analysis of the genome-wide genetic variation revealed extensive nucleotide diversity in the microbial populations. The genes involved in the transport and the energy metabolism displayed a high nucleotide diversity (HND; 0.0045-0.0195; an indicator of shared minor alleles with the microbial populations). By tracking the processes of homologous recombination, we found that each microbial population was subjected to different purification selection levels at different depths (44.12% genes). This selection resulted in significant differences in synonymous/non-synonymous mutation ratio between 0-20 and 20-100 cm layers, indicating the adaptive evolutionary process of microbial populations. Furthermore, our assessment of differentiation in the allele frequencies between these two layers showed that the functional genes involved in the metabolic processes of amino acids or cofactors were highly differential in more than half of them. Together, we showed that the nucleotide diversity of microbial populations was shaped by homologous recombination and gene-specific selection, finally resulting in the stratified differentiation occurring between 0-20 and 20-100 cm. These results enhance our cognition of the microbial adaptation mechanisms to vertical environmental changes during the sedimentation process of coastal blue carbon ecosystems.

Screening of [18F]Florbetazine for Aß Plaques and a Head-to-Head Comparison Study with [11C]Pittsburgh Compound-B ([11C]PiB) in Human Subjects.

Positron emission tomography (PET) imaging of amyloid-ß (Aß) has emerged as a crucial strategy for early diagnosis and monitoring of therapeutic advancements targeting Aß. In our previous first-in-human study, we identified that [18F]Florbetazine ([18F]92), featuring a diaryl-azine scaffold, exhibits higher cortical uptake in Alzheimer's disease (AD) patients compared to healthy controls (HC). Building upon these promising findings, this study aimed to characterize the diagnostic potential of [18F]92 and its dimethylamino-modified tracer [18F]91 and further compare them with the benchmark [11C]PiB in the same cohort of AD patients and age-matched HC subjects. The cortical accumulation of these tracers was evident, with no significant radioactivity retention observed in the cortex of HC subjects, consistent with [11C]PiB images (correlation coefficient of 0.9125 and 0.7883 between [18F]Florbetazine/[18F]91 and [11C]PiB, respectively). Additionally, quantified data revealed higher standardized uptake value ratios (SUVR) (with the cerebellum as the reference region) of [18F]Florbetazine/[18F]91 in AD patients compared to the HC group ([18F]Florbetazine: 1.49 vs 1.16; [18F]91: 1.33 vs 1.20). Notably, [18F]Florbetazine exhibited less nonspecific bindings in myelin-rich regions, compared to the dimethylamino-substituted [18F]91, akin to [11C]PiB. Overall, this study suggests that [18F]Florbetazine displays superior characteristics to [18F]91 in identifying Aß pathology in AD. Furthermore, the close agreement between the uptakes in nontarget regions for [18F]Florbetazine and [11C]PiB in this head-to-head comparison study underscores its suitability for both clinical and research applications.

Repairing gut barrier by traditional Chinese medicine: roles of gut microbiota.

Gut barrier is not only part of the digestive organ but also an important immunological organ for the hosts. The disruption of gut barrier can lead to various diseases such as obesity and colitis. In recent years, traditional Chinese medicine (TCM) has gained much attention for its rich clinical experiences enriched in thousands of years. After orally taken, TCM can interplay with gut microbiota. On one hand, TCM can modulate the composition and function of gut microbiota. On the other hand, gut microbiota can transform TCM compounds. The gut microbiota metabolites produced during the actions of these interplays exert noticeable pharmacological effects on the host especially gut barrier. Recently, a large number of studies have investigated the repairing and fortifying effects of TCM on gut barriers from the perspective of gut microbiota and its metabolites. However, no review has summarized the mechanism behand this beneficiary effects of TCM. In this review, we first briefly introduce the unique structure and specific function of gut barrier. Then, we summarize the interactions and relationship amidst gut microbiota, gut microbiota metabolites and TCM. Further, we summarize the regulative effects and mechanisms of TCM on gut barrier including physical barrier, chemical barrier, immunological barrier, and microbial barrier. At last, we discuss the effects of TCM on diseases that are associated gut barrier destruction such as ulcerative colitis and type 2 diabetes. Our review can provide insights into TCM, gut barrier and gut microbiota.

Iodine status and knowledge among pregnant and lactating women in Large City in Northern China after nearly 30 years of the universal salt iodization.

BACKGROUND: With the implementation of the universal salt iodization, the iodine nutrition for children and adults has been appropriate, but pregnant women are still at risk of iodine deficiency. It is of great public health significance to explore the iodine status and knowledge, and influence factors and the appropriate health education methods among pregnant and lactating women. METHODS: From January 2022 to December 2023, at least 50 pregnant women and 50 lactating women were randomly selected from the resident population annually in 16 districts of Tianjin, North China. A total of 1671 pregnant women and 1658 lactating women were recruited. All participants' households salt and random urine samples were collected. A questionnaire was conducted to collect data on iodine related knowledge and behaviors as well as needs of health education from all participants. Logistic regression models were constructed to analyze the factors affecting the iodine related knowledge level. We used the Rasch model and the quadrantal graph to analyze the participants' knowledge level on different iodine-related questions and their needs for health education. RESULTS: The median urine iodine concentration (UIC) of pregnant and lactating women in Tianjin were 152.40 µg/L and 124.60 µg/L. In some districts, the median UIC of pregnant and lactating women below the appropriate range. The iodized salt coverage rate of pregnant and lactating women in Tianjin was 76.12% and 77.40%, respectively. In pregnant and lactating women who did not actively supplement with iodine, the median UIC in those who consumed non-iodized salt were significantly lower than that in those who consumed iodized salt (139.26 µg/L and 154.40 µg/L, P = 0.044; 94.60 µg/L and 123.80 µg/L, P < 0.001). Compared with the low knowledge score group, pregnant women in the high knowledge score group had a higher proportion of iodized salt consumption (71.25% and 78.05%, P = 0.003), and pregnant and lactating women in the high knowledge score group had a higher proportion of actively supplement iodine (44.61% and 55.34%, P < 0.001; 39.26% and 49.78%, P < 0.001). Health education may be the main factor affecting the iodine related knowledge scores for pregnant and lactating women, with adjusted odds ratios (OR) and 95% confidence intervals (CI) of 2.89 (2.30, 3.62) and 2.46 (1.97, 3.07), respectively. Pregnant and lactating women are most expected to acquire knowledge through healthcare professionals (72.11%) and wechat/website (74.91%), respectively. CONCLUSIONS: Pregnant and lactating women in some areas of Tianjin are at risk of iodine deficiency. Iodized salt consumption is an important way to ensure iodine nutrition of the population, and the lack of iodine related knowledge is an important factor affecting the consumption of iodized salt. Health education in different ways can be carried out for different people to improve the acceptance and efficiency of health education.