Differential T-cell profiles determined by Hepatitis B surface antigen decrease among people with Human Immunodeficiency Virus /Hepatitis B Virus coinfection on treatment.

BACKGROUND: Several studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear. METHODS: Global and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison. RESULTS: HBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4+ T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4+ T cells and heightened HLA-DR and T-bet in CD8+ T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DR+CD4+, Ki67+CD4+, PD-1+CD4+, CD38+CD8+, HLA-DR+CD8+, TIM-3+CD8+, HBV-specific CD4+ T cell secreting IFN-γ and IL-2, and specific CD8+ T cell secreting IFN-γ and IL-2, correlated with HBsAg decrease. CONCLUSION: The decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4+ and CD8+ T cells phenotypes, offering a novel perspective on a functional HBV cure.

The role of reproductive tract extracellular vesicles on boar sperm function.

Extracellular vesicles (EVs) are abundant in reproductive tract fluids and serve as important mediators of paracrine communication, influencing the function of gametes. Sperm undergo development in the male reproductive tract and exert their function within the female reproductive tract, engaging in interactions with various types of EVs present throughout the reproductive system. Previous studies have demonstrated that both male and female reproductive tract EVs can impact sperm function by transferring regulatory cargoes to them. Nevertheless, inconsistencies of previous research regarding the effects of EVs on sperm function, coupled with a lack of investigation into the influence of female reproductive tract EVs on sperm fertilization, have left the true role and underlying mechanisms of reproductive tract EVs on sperm function largely unexplored. Given that pigs represent significant economic livestock and serve as an ideal biomedical model for human diseases, this review aims to provide a comprehensive summary of the current knowledge regarding reproductive tract EVs and their influence on boar sperm function, while highlighting their potential roles. We anticipate that this review will facilitate future research on reproductive tract EVs and their impact on sperm function, contributing to improved animal reproductive efficiency and advancements in the treatment of male infertility.

Targeted Therapy of Osteoarthritis via Intra-Articular Delivery of Lipid-Nanoparticle-Encapsulated Recombinant Human FGF18 mRNA.

Fibroblast growth factor 18 (FGF18) emerges as a promising therapeutic target for osteoarthritis (OA). In this study, a novel articular cavity-localized lipid nanoparticle (LNP) named WG-PL14 is developed. This optimized formulation has a nearly 30-fold increase in mRNA expression as well as better articular cavity enrichment compared to commercial lipids MC3 when performing intra-articular injection. Then, a mRNA sequence encoding recombinant human FGF18 (rhFGF18) for potential mRNA therapy in OA is optimized. In vitro assays confirm the translation of rhFGF18 mRNA into functional proteins within rat and human chondrocytes, promoting cell proliferation and extracellular matrix (ECM) synthesis. Subsequently, the therapeutic efficacy of the LNP-rhFGF18 mRNA complex is systematically assessed in a mouse OA model. The administration exhibits several positive outcomes, including an improved pain response, upregulation of ECM-related genes (e.g., AGRN and HAS2), and remodeling of subchondral bone homeostasis compared to a control group. Taken together, these findings underscore the potential of localized LNP-rhFGF18 mRNA therapy in promoting the regeneration of cartilage tissue and mitigating the progression of OA.

The regulatory effect and mechanism of traditional Chinese medicine on the renal inflammatory signal transduction pathways in diabetic kidney disease: A review.

Inflammatory injury is a critical factor in the occurrence and development of diabetic kidney disease (DKD). Signal transduction pathways such as the nuclear factor kappa beta (NF-κB), mitogen-activated protein kinase (MAPK), NOD-like receptor protein 3, and Smads are important mechanisms of inflammatory kidney injury in DKD, and the NF-κB pathway plays a key role. The inflammatory factor network formed after activation of the NF-κB pathway connects different signaling pathways and exacerbates renal inflammatory damage. Many traditional Chinese medicine compounds, single agents, effective components and active ingredients can regulate the expression of key molecules in the signaling pathways associated with inflammatory injury, such as transforming growth factor-ß activated kinase 1, NF-κB, p38MAPK, NOD-like receptor protein 3, and Smad7. These treatments have the characteristics of multiple targets and have multiple and overlapping effects, which can treat DKD kidney inflammation and injury through multiple mechanisms and apply the "holistic concept" of traditional Chinese medicine.

Association between dietary antioxidant indices and hypertension among Chinese adults.

The effect of dietary antioxidants on blood pressure (BP) regulation and hypertension risk remains largely unknown. This study aimed to comprehensively assess the impacts of dietary antioxidants on systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), and hypertension risk among Chinese adults. The cross-sectional study assessed data from 12,046 Chinese adults, evaluating dietary antioxidant quality scores (DAQS) and total antioxidant capacity (DTAC) via a validated food frequency questionnaire. MAP was derived using the formula DBP + (0.412 ×PP), with PP calculated as SBP - DBP. The relationship between DAQS, DTAC, and hypertension prevalence was analyzed using multivariable logistic regression. Among participants not taking antihypertensive medications, those in the highest groups of DTAC and DAQS had significantly lower SBP, DBP, MAP, and PP compared to those in the lowest groups (all p-trends <0.001). Relative to the lowest quintile (Q1) of DTAC (adjusted odds ratios (OR) for hypertension decreased in Q2 (OR 0.90, 95%CI 0.79-1.03), Q3 (OR 0.65, 95% CI 0.56-0.76), Q4 (OR 0.51, 95% CI 0.43-0.60), and Q5 (OR 0.38, 95% CI 0.31-0.46) (p trend <0.001). For DQAS, hypertension OR of category 5 was 0.38 (95% CI 0.32-0.46) compared to that of category 1. Increased vitamin A, Zinc, and selenium intake correlated with reduced hypertension risk. A significant non-linear DTAC and linear DAQS relationships were observed and hypertension risk. Antioxidant-rich diets markedly lowered SBP, DBP, MAP, PP, and hypertension risk.

METTL protein family: focusing on the occurrence, progression and treatment of cancer.

Methyltransferase-like protein is a ubiquitous enzyme-like protein in the human body, with binding domains for nucleic acids, proteins and other small molecules, and plays an important role in a variety of biological behaviours in normal organisms and diseases, characterised by the presence of a methyltransferase-like structural domain and a structurally conserved SAM-binding domain formed by the seven-stranded ß-fold structure in the center of the protein. With the deepening of research, the METTL protein family has been found to be abnormally expressed in a variety of tumor diseases, and the clarification of its relationship with tumor diseases can be used as a molecular therapeutic target and has an important role in the prognosis of tumors. In this paper, we review the structure, biological process, immunotherapy, drug-targeted therapy, and markers of the METTL protein family to provide new ideas for the diagnosis and treatment of tumors.

Fluorescence of europium activated by molecular-like silver clusters for the detection of alkaline phosphatase activity.

Alkaline phosphatase (ALP) is abnormally expressed in some cancers and promotes the growth, metastasis, and invasion of cancer cells. The detection of ALP is of great significance for both pathological study and clinical detection. In this work, a europium (Eu)-based fluorescence detection sensor was prepared in a mild reaction condition. LaF3:Eu nanoparticles was mixed with ethylene imine polymer (PEI) and Ag+ ions. PEI was used as stabilizer and reducing agent, and Ag+ ions were reduced as molecular-like silver clusters (ML-Ag NCs). The fluorescence of LaF3:Eu nanoparticles was enhanced by ML-Ag NCs through energy transfer. When ascorbic acid 2-phosphate (AAP) was hydrolyzed to ascorbic acid (AA) in the presence of ALP, AA reduced Ag+ ions to silver nanoparticles (Ag NPs) and quenched the fluorescence of LaF3:Eu/PEI/Ag. The activity of ALP was detected by measuring the fluorescence intensity of Eu3+ at 618 nm. In the concentration range from 2.0 to 16.0 U/L, the fluorescence intensity ratio ((F0-F)/F0) had a linear relationship with the logarithm of ALP concentration. The limit of detection (LOD) was 1.3 U/L. Moreover, the ALP activity was detected successfully in cancer cells by this method. The sensing platform has application potential in the detection of ALP activity in biological systems.

Peroxymonosulfate promoted dioxygen activation with Mn(II)-nitrilotriacetic acid complexes for sulfadiazine degradation.

In the field of peroxymonosulfate (PMS) activation technology, there is a pressing need to reduce PMS consumption and enhance its utilization rate. The present study demonstrates that the introduction of dissolved oxygen (DO) into the Mn(II)-nitrilotriacetic acid (NTA)-activated PMS system significantly enhances the degradation efficiency of sulfadiazine and increases the PMS utilization rate from approximately 15.0 to 41.3 %. Mechanistic analysis reveals that the Mn(II)-NTA/PMS system generates sulfate radicals as well as intermediate valent manganese species in the absence of DO; while in the presence of DO, Mn(II) is oxidized to Mn(III) by dioxygen to form superoxide anions and Mn(III), which can be further oxidized by PMS to higher valence states such as Mn(V) and Mn(VII). Consequently, the production of free radicals decreases while intermediate valent manganese species become more abundant. Additionally, O2•- can also reduce both Mn(VII) and Mn(IV) back to their lower oxidation state (Mn(II)). The cooperative interactions between these active species enhance the efficiency of catalytic cycles of manganese species. Moreover, the influence of multiple factors, the degradation products, and their associated toxicity assessment were investigated. Overall, this research provides valuable insights into the design of highly efficient PMS and DO activation systems.

Partial asynchrony of coniferous forest carbon sources and sinks at the intra-annual time scale.

As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.

The pan-tandem repeat map highlights multiallelic variants underlying gene expression and agronomic traits in rice.

Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding.

The Association of Neonatal Gut Microbiota Community State Types with Birth Weight.

BACKGROUND: while most gut microbiota research has focused on term infants, the health outcomes of preterm infants are equally important. Very-low-birth-weight (VLBW) or extremely-low-birth-weight (ELBW) preterm infants have a unique gut microbiota structure, and probiotics have been reported to somewhat accelerate the maturation of the gut microbiota and reduce intestinal inflammation in very-low preterm infants, thereby improving their long-term outcomes. The aim of this study was to investigate the structure of gut microbiota in ELBW neonates to facilitate the early identification of different types of low-birth-weight (LBW) preterm infants. METHODS: a total of 98 fecal samples from 39 low-birth-weight preterm infants were included in this study. Three groups were categorized according to different birth weights: ELBW (n = 39), VLBW (n = 39), and LBW (n = 20). The gut microbiota structure of neonates was obtained by 16S rRNA gene sequencing, and microbiome analysis was conducted. The community state type (CST) of the microbiota was predicted, and correlation analysis was conducted with clinical indicators. Differences in the gut microbiota composition among ELBW, VLBW, and LBW were compared. The value of gut microbiota composition in the diagnosis of extremely low birth weight was assessed via a random forest-machine learning approach. RESULTS: we briefly analyzed the structure of the gut microbiota of preterm infants with low birth weight and found that the ELBW, VLBW, and LBW groups exhibited gut microbiota with heterogeneous compositions. Low-birth-weight preterm infants showed five CSTs dominated by Enterococcus, Staphylococcus, Klebsiella, Streptococcus, Pseudescherichia, and Acinetobacter. The birth weight and clinical indicators related to prematurity were associated with the CST. We found the composition of the gut microbiota was specific to the different types of low-birth-weight premature infants, namely, ELBW, VLBW, and LBW. The ELBW group exhibited significantly more of the potentially harmful intestinal bacteria Acinetobacter relative to the VLBW and LBW groups, as well as a significantly lower abundance of the intestinal probiotic Bifidobacterium. Based on the gut microbiota's composition and its correlation with low weight, we constructed random forest model classifiers to distinguish ELBW and VLBW/LBW infants. The area under the curve of the classifiers constructed with Enterococcus, Klebsiella, and Acinetobacter was found to reach 0.836 by machine learning evaluation, suggesting that gut microbiota composition may be a potential biomarker for ELBW preterm infants. CONCLUSIONS: the gut bacteria of preterm infants showed a CST with Enterococcus, Klebsiella, and Acinetobacter as the dominant genera. ELBW preterm infants exhibit an increase in the abundance of potentially harmful bacteria in the gut and a decrease in beneficial bacteria. These potentially harmful bacteria may be potential biomarkers for ELBW preterm infants.

A pan-TE map highlights transposable elements underlying domestication and agronomic traits in Asian rice.

Transposable elements (TEs) are ubiquitous genomic components and hard to study due to being highly repetitive. Here we assembled 232 chromosome-level genomes based on long-read sequencing data. Coupling the 232 genomes with 15 existing assemblies, we developed a pan-TE map comprising both cultivated and wild Asian rice. We detected 177 084 high-quality TE variations and inferred their derived state using outgroups. We found TEs were one source of phenotypic variation during rice domestication and differentiation. We identified 1246 genes whose expression variation was associated with TEs but not single-nucleotide polymorphisms (SNPs), such as OsRbohB, and validated OsRbohB's relative expression activity using a dual-Luciferase (LUC) reporter assays system. Our pan-TE map allowed us to detect multiple novel loci associated with agronomic traits. Collectively, our findings highlight the contributions of TEs to domestication, differentiation and agronomic traits in rice, and there is massive potential for gene cloning and molecular breeding by the high-quality Asian pan-TE map we generated.

Risk factors of falls in rural elderly of Ningxia in China: a prospective cohort study.

OBJECTIVES: To identify risk factors associated with falls in older people in rural China. METHODS: A prospective cohort study was conducted across 27 villages in the rural areas of Ningxia, China. After excluding individuals younger than 60 years, a total of 758 out of the initial 822 participants were ultimately included for the collection of baseline information. Participants were followed up through telephone calls or face-to-face interviews at 3rd, 6th and 12th months following the baseline investigation. The Cox proportional hazards regression model was used to examine risk factors of falls. RESULTS: A total of 758 participants underwent baseline information surveys, and all samples were included in the Cox model analysis. The study found that being woman (RR=1.879, 95% CI: 1.313 to 2.668), smoking (RR=1.972, 95% CI: 1.238 to 3.143), use of painkillers (RR=1.700, 95% CI: 1.226 to 2.356) and higher systolic blood pressure (SBP) (RR=1.081, 95% CI: 1.013 to 1.154) were associated with higher risk of falls among the elderly in rural China. After excluding those who were lost to follow-up or deceased, 738 participants completed the follow-up. There were 341 men (46.2%) and 397 women (53.8%), with an average age of 66.8±5.0 years. The fall rate in study area was 23.8% during the follow-up period. CONCLUSIONS: The fall rate among the elderly in rural China was higher than other areas. Our findings revealed that being woman, smoking, medication usage, elevated SBP and people with a higher body mass index were risk factors for developing falls.

Longitudinal associations between intergroup contact and intergroup trust among adolescents in ethnic regions of China.

Intergroup trust is a crucial psychological foundation for promoting ethnic unity and maintaining social stability. This study explored the dynamic relationship between intergroup contact and trust among adolescents in ethnic regions of China and sought to uncover the mechanisms behind this relationship. Through a two-wave longitudinal survey of 679 adolescents, employing the Intergroup Contact Experience Scale, the Intergroup Trust Scale, and the UCLA Loneliness Scale, the study yielded several findings: (1) Over the year, a significant increase in intergroup contact was observed among the adolescents. Notably, junior high students demonstrated a marked rise in intergroup trust, whereas no significant change was discernible in high school students. (2) Cross-lagged analysis indicated that early intergroup contact significantly predicted subsequent intergroup trust and loneliness. Initial loneliness also forecasted future intergroup trust, yet early intergroup trust did not predict later intergroup contact or loneliness. (3) Loneliness served as a partial mediator in the longitudinal link between intergroup contact and trust among these adolescents. These findings reinforce the premise that in China's ethnic regions, intergroup contact is a precursor to intergroup trust, both directly enhancing trust among adolescents and indirectly by reducing loneliness.

Radiomics predict the WHO/ISUP nuclear grade and survival in clear cell renal cell carcinoma.

OBJECTIVES: This study aimed to assess the predictive value of radiomics derived from intratumoral and peritumoral regions and to develop a radiomics nomogram to predict preoperative nuclear grade and overall survival (OS) in patients with clear cell renal cell carcinoma (ccRCC). METHODS: The study included 395 patients with ccRCC from our institution. The patients in Center A (anonymous) institution were randomly divided into a training cohort (n = 284) and an internal validation cohort (n = 71). An external validation cohort comprising 40 patients from Center B also was included. Computed tomography (CT) radiomics features were extracted from the internal area of the tumor (IAT) and IAT combined peritumoral areas of the tumor at 3 mm (PAT 3 mm) and 5 mm (PAT 5 mm). Independent predictors from both clinical and radiomics scores (Radscore) were used to construct a radiomics nomogram. Kaplan-Meier analysis with a log-rank test was performed to evaluate the correlation between factors and OS. RESULTS: The PAT 5-mm radiomics model (RM) exhibited exceptional predictive capability for grading, achieving an area under the curves of 0.80, 0.80, and 0.90 in the training, internal validation, and external validation cohorts. The nomogram and RM gained from the PAT 5-mm region were more clinically useful than the clinical model. The association between OS and predicted nuclear grade derived from the PAT 5-mm Radscore and the nomogram-predicted score was statistically significant (p < 0.05). CONCLUSION: The CT-based radiomics and nomograms showed valuable predictive capabilities for the World Health Organization/International Society of Urological Pathology grade and OS in patients with ccRCC. CRITICAL RELEVANCE STATEMENT: The intratumoral and peritumoral radiomics are feasible and promising to predict nuclear grade and overall survival in patients with clear cell renal cell carcinoma, which can contribute to the development of personalized preoperative treatment strategies. KEY POINTS: The multi-regional radiomics features are associated with clear cell renal cell carcinoma (ccRCC) grading and prognosis. The combination of intratumoral and peritumoral 5 mm regional features demonstrated superior predictive performance for grading. The nomogram and radiomics models have a broad range of clinical applications.

Activation of H2O2-HCO3- by Ca2Co2O5 for pollutant degradation.

The bicarbonate-activated hydrogen peroxide (BAP) system is widely studied for organic pollutant degradation in wastewater treatment. Ca2Co2O5, a heterogeneous catalyst containing multivalent cobalt including Co(II) and Co(III), was herein investigated as a BAP activator, and Acid Orange 7 (AO7) was used as a model pollutant. Ca2Co2O5 exhibited good activation performance. The degradation rate and the initial rate constant of the Ca2Co2O5-activated BAP system were 5.4 and 11.2 times as high as the BAP system, respectively. The removal rate of AO7 reached 90.9% in 30 min under optimal conditions (AO7 20 mg/L, Ca2Co2O5 0.2 g/L, H2O2 1 mM, NaHCO3 5 mM, pH 8.5, 25℃). The Ca2Co2O5 catalyst exhibited good stability and recyclability, retaining 85% of AO7 removal rate in the fifth run. Compared to the BAP system, a lower dosage of H2O2 was required and a higher initial concentration of pollutants allowed for effective degradation in the Ca2Co2O5-BAP system. X-ray photoelectron spectroscopy was used to analyze the catalytic mechanism. The analysis showed that the good catalytic performance of Ca2Co2O5 attributes to its high proportion of oxygen vacancies and Co(III) species, and the presence of Ca. The active species O2•-, •OH, and 1O2 are responsible for the degradation, as indicated by the quenching experiments. The degradation mechanism of AO7 was speculated based on UV-Vis spectral analysis and the identification of degradation intermediates. The azo form, naphthalene and benzoic rings in the AO7 structure are destroyed in the decomposition. This research provides a feasible approach to designing effective and reusable BAP activators for pollutant degradation in wastewater treatment.

Fluorescence sensing of water in various organic solvents based on a novel cyclic polymer.

A sensor capable of sensing of water in various organic solvents ranging from water-soluble to water-miscible solvents is still a challenging task. In this research, a cyclic polymer fluorescence chemosensor (CPFC) has been developed for sensing of water by turn-on model in 9 organic solvents and turn-off model in DMA, where the broadest concentration range and the lowest detection limit was obtained for water in DMA (10 %-90 %) and dioxane (0.011 %), respectively. The sensing mechanism is explored by theory calculation and experimental investigation. The amphiphilic nature endows the polymer probe with great potential for measuring various contaminants from aqueous and nonaqueous mediums. Furthermore, the present search highlights the potential applications of cyclic polymer as fluorescence probes in the field of sensing.

Etiological Mechanisms and Genetic/Biological Modulation Related to PTH1R in Primary Failure of Tooth Eruption.

Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.