Efficient photodegradation of perfluoroalkyl substances under visible light by hexagonal ZnIn2S4 nanosheets.

Perfluoroalkyl substances (PFASs) are typical persistent organic pollutants, and their removal is urgently required but challenging. Photocatalysis has shown potential in PFASs degradation due to the redox capabilities of photoinduced charge carriers in photocatalysts. Herein, hexagonal ZnIn2S4 (ZIS) nanosheets were synthesized by a one-pot oil bath method and were well characterized by a series of techniques. In the degradation of sodium p-perfluorous nonenoxybenzenesulfonate (OBS), one kind of representative PFASs, the as-synthesized ZIS showed activity superior to P25 TiO2 under both simulated sunlight and visible-light irradiation. The good photocatalytic performance was attributed to the enhanced light absorption and facilitated charge separation. The pH conditions were found crucial in the photocatalytic process by influencing the OBS adsorption on the ZIS surface. Photogenerated e- and h+ were the main active species involved in OBS degradation in the ZIS system. This work confirmed the feasibility and could provide mechanistic insights into the degradation and defluorination of PFASs by visible-light photocatalysis.

Correlations and consistency of body composition measurement indicators and BMI: a systematic review.

OBJECTIVE: It is critical to accurately determine the level of obesity and health status since overweight/obesity has become a main global public health problem. This systematic review attempted to evaluate the consistency and correlation between body composition measurement indicators and body mass index (BMI) in childhood and adolescence. METHODS: Seven electronic databases (Web of Science, PubMed, Cochrane Library, Embase, CNKI, WANFANG DATA, SinoMed) were searched to collect the literature published since 1999 with the focus on the relationship between body composition measurement indicators and BMI to measure obesity in childhood and adolescence. RESULTS: Among the 28 articles included, 13 articles reported a moderate to very strong correlation between %BF and BMI in obesity measurement (range: 0.49-0.907), while two articles reported a strong to very strong correlation between FM and BMI (range: 0.60-0.86). Six articles reported good to excellent obesity measurement consistency between %BF and BMI (range: 0.441-0.876), one article reported WC (0.58) and WHtR (0.46) in the moderate consistency with BMI, and one article reported a relatively poor to fair consistency between FM and BMI (range: 0.167-0.409). WC, WHtR, and BMI showed the moderate consistency in pre-adolescent children. In pre-adolescence and adolescence, the measurement consistency between %BF and BMI was higher than that between FM and BMI. Gender difference existed in the consistency between %BF and BMI during adolescence. CONCLUSION: A range of body composition indicators such as %BF, WC, WHtR, and FM could provide valuable body composition measurements, complement BMI for obesity assessment in children and adolescents, and facilitate efficient and comprehensive surveillance of childhood obesity. REGISTRATION: PROSPERO CRD42024506932.

An Inhalable Nanoshield for Effective Prevention of Influenza Virus Infections.

Influenza virus (IV) infection currently poses a serious and continuing threat to the global public health. Developing effective prevention strategies is important to defend against infection and spread of IV. Here, we developed a triple-protective nanoshield against IV infection in the lungs, formed by self-assembling DSPE-PEG amphiphilic polymers encapsulating the flu-preventive antiviral drug Arbidol internally. The preventive effect of the nanoshield against virus infection includes increasing the viscosity in the surrounding environment to physically defend against viral entry, forming a hydrated layer to block the interaction between viruses and cells, and inhibiting virus replication. Our finding suggested that a single inhalation of the nanoshield provides effective protection against IV infection for at least 8 h. Thus, this nanoshield may be a potential pandemic protection agent against IV, especially in viral environments, where no prophylactic or therapeutic measures are available.

Eutrophication-induced shifts cause diverse responses in the phoD community of a plateau freshwater lake.

Eutrophication is a critical environmental challenge affecting lakes globally. Mitigating trophic level under endogenous phosphorus release is an unsolved problem in eutrophic lakes. However, understanding the dynamics and assembly of microbial communities encoding the alkaline phosphatase (phoD community) and their responses during trophic transitions in eutrophic lakes is limited. In this study, we compared the composition and assembly mechanisms of phoD communities in four seasons in the Yilong Lake, a shallow lake of the Yunnan-Guizhou Plateau. The lake exhibits slightly eutrophic conditions in summer and mesotrophic conditions in spring, autumn, and winter. By analyzing seasonal variations, we observed that during summer, the relative abundance of Pseudomonas in the water had the highest value, while the Shannon-Wiener index of phoD communities was lowest. Mantel tests showed an increased Bray-Curtis dissimilarity of phoD communities in the water with rising eutrophication, a trend not observed in sediment. Notably, eutrophication heightened the homogeneity selection governing the assembly of phoD communities in water. The co-occurrence networks showed that the OTUs in the summer exhibited closer interconnections than those in other seasons. Additionally, the topological parameters from networks indicated that eutrophication is poised to instigate changes and modulate the dynamics of the microbial phoD community, resulting in markedly distinct seasonal behaviors. pH was identified as a critical factor directly influencing phoD community diversity via partial least squares path modeling (PLS-PM). This study shed light on our understanding of the seasonal dynamics of phoD communities and their pivotal role in phosphorus cycling in eutrophic lakes.

Effect of aortic valve replacement on myocardial perfusion and exercise capacity in patients with severe aortic stenosis.

Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6-12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63 m/s, aortic valve area index 0.45 ± 0.13cm2/m2). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO2). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p < 0.001), with a corresponding 15% increase in myocardial perfusion reserve (MPR) (2.04 ± 0.57 to 2.34 ± 0.68; p = 0.004). Increasing severity of AS, presence of late gadolinium enhancement, lower baseline stress MBF and MPR were associated with a greater improvement in MPR post-AVR. On multivariable analysis low baseline MPR was independently associated with increased MPR post-AVR. There was no significant change in peak VO2 post-AVR, but a significant increase in exercise duration. Change in MPR was associated with change in peak VO2 post AVR (r = 0.346, p = 0.045). Those with the most impaired stress MBF and MPR at baseline demonstrate the greatest improvements in these parameters following AVR and the magnitude of change in MPR correlated with improvement in peak VO2, the gold standard measure of aerobic exercise capacity.

Radix Astragali and Its Representative Extracts for Diabetic Nephropathy: Efficacy and Molecular Mechanism.

Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM). Radix Astragali (RA), a frequently used Chinese herbal medicine in the Leguminosae family, Astragalus genus, with its extracts, has been proven to be effective in DN treatment both in clinical practice and experimental studies. RA and its extracts can reduce proteinuria and improve renal function. They can improve histopathology changes including thickening of the glomerular basement membrane, mesangial cell proliferation, and injury of endothelial cells, podocytes, and renal tubule cells. The mechanisms mainly benefited from antioxidative stress which involves Nrf2/ARE signaling and the PPARγ-Klotho-FoxO1 axis; antiendoplasmic reticulum stress which involves PERK-ATF4-CHOP, PERK/eIF2α, and IRE1/XBP1 pathways; regulating autophagy which involves SIRT1/NF-κB signaling and AMPK signaling; anti-inflammation which involves IL33/ST2 and NF-κB signaling; and antifibrosis which involves TGF-ß1/Smads, MAPK (ERK), p38/MAPK, JNK/MAPK, Wnt/ß-catenin, and PI3K/AKT/mTOR signaling pathways. This review focuses on the clinical efficacy and the pharmacological mechanism of RA and its representative extracts on DN, and we further document the traditional uses of RA and probe into the TCM theoretical basis for its application in DN.

Dynamic functional connections analysis with spectral learning for brain disorder detection.

Dynamic functional connections (dFCs), can reveal neural activities, which provides an insightful way of mining the temporal patterns within the human brain and further detecting brain disorders. However, most existing studies focus on the dFCs estimation to identify brain disorders by shallow temporal features and methods, which cannot capture the inherent temporal patterns of dFCs effectively. To address this problem, this study proposes a novel method, named dynamic functional connections analysis with spectral learning (dCSL), to explore inherently temporal patterns of dFCs and further detect the brain disorders. Concretely, dCSL includes two components, dFCs estimation module and dFCs analysis module. In the former, dFCs are estimated via the sliding window technique. In the latter, the spectral kernel mapping is first constructed by combining the Fourier transform with the non-stationary kernel. Subsequently, the spectral kernel mapping is stacked into a deep kernel network to explore higher-order temporal patterns of dFCs through spectral learning. The proposed dCSL, sharing the benefits of deep architecture and non-stationary kernel, can not only calculate the long-range relationship but also explore the higher-order temporal patterns of dFCs. To evaluate the proposed method, a set of brain disorder classification tasks are conducted on several public datasets. As a result, the proposed dCSL achieves 5% accuracy improvement compared with the widely used approaches for analyzing sequence data, 1.3% accuracy improvement compared with the state-of-the-art methods for dFCs. In addition, the discriminative brain regions are explored in the ASD detection task. The findings in this study are consistent with the clinical performance in ASD.

Causal relationships of grey matter structures in multiple sclerosis and neuromyelitis optica spectrum disorder: insights from Mendelian randomization.

Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple sclerosis and neuromyelitis optica spectrum disorder in observational studies, it is unclear whether these associations indicate causal relationships between these diseases and grey matter changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationships between 202 grey matter imaging-derived phenotypes (33 224 individuals) and multiple sclerosis (47 429 cases and 68 374 controls) as well as neuromyelitis optica spectrum disorder (215 cases and 1244 controls). Our results suggested that genetically predicted multiple sclerosis was positively associated with the surface area of the left parahippocampal gyrus (ß = 0.018, P = 2.383 × 10-4) and negatively associated with the volumes of the bilateral caudate (left: ß = -0.020, P = 7.203 × 10-5; right: ß = -0.021, P = 3.274 × 10-5) and putamen nuclei (left: ß = -0.030, P = 2.175 × 10-8; right: ß = -0.024, P = 1.047 × 10-5). In addition, increased neuromyelitis optica spectrum disorder risk was associated with an increased surface area of the left paracentral gyrus (ß = 0.023, P = 1.025 × 10-4). Conversely, no evidence was found for the causal impact of grey matter imaging-derived phenotypes on disease risk in the opposite direction. We provide suggestive evidence that genetically predicted multiple sclerosis and neuromyelitis optica spectrum disorder are associated with increased cortical surface area and decreased subcortical volume in specific regions. Our findings shed light on the associations of grey matter alterations with the risk of multiple sclerosis and neuromyelitis optica spectrum disorder.

PRL1 interacts with and stabilizes RPA2A to regulate carbon deprivation-induced senescence in Arabidopsis.

Leaf senescence is a developmental program regulated by both endogenous and environmental cues. Abiotic stresses such as nutrient deprivation can induce premature leaf senescence, which profoundly impacts plant growth and crop yield. However, the molecular mechanisms underlying stress-induced senescence are not fully understood. In this work, employing a carbon deprivation (C-deprivation)-induced senescence assay in Arabidopsis seedlings, we identified PLEIOTROPIC REGULATORY LOCUS 1 (PRL1), a component of the NineTeen Complex, as a negative regulator of C-deprivation-induced senescence. Furthermore, we demonstrated that PRL1 directly interacts with the RPA2A subunit of the single-stranded DNA-binding Replication Protein A (RPA) complex. Consistently, the loss of RPA2A leads to premature senescence, while increased expression of RPA2A inhibits senescence. Moreover, overexpression of RPA2A reverses the accelerated senescence in prl1 mutants, and the interaction with PRL1 stabilizes RPA2A under C-deprivation. In summary, our findings reveal the involvement of the PRL1-RPA2A functional module in C-deprivation-induced plant senescence.

Association between City-Level Particulate Matter Exposure and Frailty among Middle-Aged and Older Adults in China.

INTRODUCTION: The effects of exposure to particulate matter and frailty, as well as its exposure-response relationship, have not been effectively explored. This study aimed to explore the association between long-term exposure to particulate matter and frailty state and each dimension in Chinese middle-aged and older adults, in addition to the exposure-response relationship. METHODS: The data were obtained from the National Urban Air Quality Real-Time Dissemination Platform and China Health and Retirement Longitudinal Study (CHARLS). Frailty was measured by a frailty index containing 39 indicators. Annual averages of seven pollutants were calculated from hourly monitoring data. We used multilevel regression modeling to explore the association between long-term exposure to particulate matter and frailty. Meanwhile, we explored the exposure-response relationship based on a multilevel generalized summation model. We performed a sensitivity analysis using a multi-pollution model and a quantile-based g-computation (QGC) model. RESULTS: A total of 15,611 participants were included in the analysis. We find that long-term exposure to PM2.5 was associated with an increased risk of pre-frailty and frailty (all p < 0.05). PMc and PM10 exhibited similar associations. The exposure-response relationship between PM2.5 showed a linear relationship, whereas the exposure-response relationship between PM10, PMc showed a nonlinear relationship. Elevated PM2.5 concentrations showed significant positive associations with the number of chronic disease score, IADL score, and functional limitation status score (all p < 0.05). PM10 and PMc showed similar positive correlations. These results remained robust after sensitivity analyses using a multi-pollution model and QGC model. CONCLUSION: Chronic exposure to particulate matter was significantly associated with increased risk of frailty. The exposure-response relationship between PM2.5 concentration and frailty showed a linear relationship, and the exposure-response relationship between PM10 and PMc showed a nonlinear relationship. Exposure to a mixture of pollutants carried a higher risk of frailty than exposure to a single pollutant.

[Effect of Pterostilbene Regulating Nuclear Factor E2-Related Factor 2 on Apoptosis of Colon Cancer Cells in Vitro].

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2 (Nrf2) in the process of pterostilbene acting on LoVo cells. Methods LoVo cells were treated with different concentrations (5,10,20,40,60,80,100 µmol/L) of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Transwell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochondrial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlorofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic proteins (Bcl2 and Bax) were determined by Western blotting.In addition,cell viability,Nrf2 expression,and apoptosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane. Results Compared with the control group,40,60,80,100 µmol/L pterostilbene reduced the viability of LoVo cells (P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 µmol/L did not show effects on cell viability but inhibited cell migration (P=0.008,P<0.001,P<0.001) and invasion (all P<0.001).Pterostilbene at 40,60,80 µmol/L increased apoptosis (P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization (P=0.026,P<0.001,P<0.001) and reactive oxygen species accumulation (all P<0.001),and down-regulated the expression of phosphorylated Nrf2 (P=0.030,P<0.001,P<0.001),heme oxygenase 1 (P=0.015,P<0.001,P<0.001),and Bcl2 (P=0.039,P<0.001,P<0.001) in LoVo cells.Pterostilbene at 60,80 µmol/L down-regulated Nrf2 expression (P=0.001,P<0.001) and up-regulated Bax expression (both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability (P<0.001),apoptosis (P<0.001),and Nrf2 expression (P=0.022). Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Occult coronary microvascular dysfunction and ischemic heart disease in patients with diabetes and heart failure.

BACKGROUND: Patients with diabetes mellitus (DM) and heart failure (HF) have worse outcomes than normoglycemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify the extent of silent IHD and CMD in patients with DM presenting with HF. METHODS: Prospectively recruited outpatients undergoing assessment into the etiology of HF underwent in-line quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE). RESULTS: Final analysis included 343 patients (176 normoglycemic, 84 with pre-diabetes, and 83 with DM). Prevalence of silent IHD was highest in DM 31% ( 26/83), then pre-diabetes 20% (17/84) then normoglycemia 17%, ( 30/176). Stress MBF was lowest in DM (1.53 ± 0.52), then pre-diabetes (1.59 ± 0.54) then normoglycemia (1.83 ± 0.62). MPR was lowest in DM (2.37 ± 0.85) then pre-diabetes (2.41 ± 0.88) then normoglycemia (2.61 ± 0.90). During follow-up, 45 patients experienced at least one MACE. On univariate Cox regression analysis, MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age, and left ventricular ejection fraction, the associations were no longer significant. CONCLUSION: Patients with DM and HF had higher prevalence of silent IHD, more evidence of CMD, and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for the assessment of silent IHD and CMD in patients with DM presenting with HF.

Shared genetic architecture of cortical thickness alterations in major depressive disorder and schizophrenia.

BACKGROUND: Major depressive disorder (MDD) and schizophrenia (SCZ) are heritable brain disorders characterized by alterations in cortical thickness. However, the shared genetic basis for cortical thickness changes in these disorders remains unclear. METHODS: We conducted a systematic literature search on cortical thickness in MDD and SCZ through PubMed and Web of Science. A coordinate-based meta-analysis was performed to identify cortical thickness changes. Additionally, utilizing summary statistics from the largest genome-wide association studies for depression (Ncase = 268,615, Ncontrol = 667,123) and SCZ (Ncase = 53,386, Ncontrol = 77,258), we explored shared genomic loci using conjunctional false discovery rate (conjFDR) analysis. Transcriptome-neuroimaging association analysis was then employed to identify shared genes associated with cortical thickness alterations, and enrichment analysis was finally carried out to elucidate the biological significance of these genes. RESULTS: Our search yielded 34 MDD (Ncase = 1621, Ncontrol = 1507) and 19 SCZ (Ncase = 1170, Ncontrol = 1043) neuroimaging studies for cortical thickness meta-analysis. Specific alterations in the left supplementary motor area were observed in MDD, while SCZ exhibited widespread reductions in various brain regions, particularly in the frontal and temporal areas. The conjFDR approach identified 357 genomic loci jointly associated with MDD and SCZ. Within these loci, 55 genes were found to be associated with cortical thickness alterations in both disorders. Enrichment analysis revealed their involvement in nervous system development, apoptosis, and cell communication. CONCLUSION: This study revealed the shared genetic architecture underlying cortical thickness alterations in MDD and SCZ, providing insights into common neurobiological pathways. The identified genes and pathways may serve as potential transdiagnostic markers, informing precision medicine approaches in psychiatric care.

Comparative biomechanical analysis of four different tooth- and bone-borne frog appliances for molar distalization : A three-dimensional finite element study.

PURPOSE: The purpose of this study was to analyze the biomechanical effects of four different designs of frog appliances for molar distalization using finite element analysis. METHODS: A three-dimensional finite element model including complete dentition, periodontal ligament, palatine, and alveolar bone was established. Four types of frog appliances were designed to simulate maxillary molar distalization: tooth-button-borne (Type A), bone-borne (Type B), bone-button-borne (Type C), and tooth-bone-borne (Type D) frog appliances. A force of 10 N was applied simulating a screw in the anteroposterior direction. To assess the von Mises stress distribution and the resultant displacements in the teeth and periodontal tissues, geometric nonlinear theory was utilized. RESULTS: Compared to the conventional tooth-borne frog appliance (Type A), the bone-borne frog appliances showed increased first molar distalization with enhanced mesiolingual rotation and distal tipping, but the labial inclination and intrusion of the incisors were insignificant. When replacing the palatal acrylic button with miniscrews (Types B and D), more anchorage forces were transmitted from the first premolar to palatine bone, which was further dispersed by the assistance of a palatal acrylic button (Type C). CONCLUSIONS: Compared to tooth-borne frog appliances, the bone-borne variants demonstrated a clear advantage for en masse molar distalization. The combined anchorage system utilizing palatal acrylic buttons and miniscrews (Type C) offers the most efficient stress distribution, minimizing force concentration on the palatine bone.

Association between metabolic score for insulin resistance and regression to normoglycemia from prediabetes in Chinese adults: A retrospective cohort study.

BACKGROUND: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. METHODS: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. RESULTS: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. CONCLUSION: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.

Lipid A-modified Escherichia coli can produce porcine parvovirus virus-like particles with high immunogenicity and minimal endotoxin activity.

BACKGROUND: A cost-effective Escherichia coli expression system has gained popularity for producing virus-like particle (VLP) vaccines. However, the challenge lies in balancing the endotoxin residue and removal costs, as residual endotoxins can cause inflammatory reactions in the body. RESULTS: In this study, porcine parvovirus virus-like particles (PPV-VLPs) were successfully assembled from Decreased Endotoxic BL21 (BL21-DeE), and the effect of structural changes in the lipid A of BL21 on endotoxin activity, immunogenicity, and safety was investigated. The lipopolysaccharide purified from BL21-DeE produced lower IL-6 and TNF-α than that from wild-type BL21 (BL21-W) in both RAW264.7 cells and BALB/c mice. Additionally, mice immunized with PPV-VLP derived form BL21-DeE (BL21-DeE-VLP) showed significantly lower production of inflammatory factors and a smaller increase in body temperature within 3 h than those immunized with VLP from BL21-W (BL21-W-VLP) and endotoxin-removed VLP (ReE-VLP). Moreover, mice in the BL21-DeE-VLP immunized group had similar levels of serum antibodies as those in the BL21-W-VLP group but significantly higher levels than those in the ReE-VLP group. Furthermore, the liver, lungs, and kidneys showed no pathological damage compared with the BL21-W-VLP group. CONCLUSION: Overall, this study proposes a method for producing VLP with high immunogenicity and minimal endotoxin activity without chemical or physical endotoxin removal methods. This method could address the issue of endotoxin residues in the VLP and provide production benefits.

Positive feedback loop PU.1-IL9 in Th9 promotes rheumatoid arthritis development.

OBJECTIVES: T helper 9 (Th9) cells are recognised for their characteristic expression of the transcription factor PU.1 and production of interleukin-9 (IL-9), which has been implicated in various autoimmune diseases. However, its precise relationship with rheumatoid arthritis (RA) pathogenesis needs to be further clarified. METHODS: The expression levels of PU.1 and IL-9 in patients with RA were determined by ELISA, western blotting (WB) and immunohistochemical staining. PU.1-T cell-conditional knockout (KO) mice, IL-9 KO and IL-9R KO mice were used to establish collagen antibody-induced arthritis (CAIA), respectively. The inhibitor of PU.1 and IL-9 blocking antibody was used in collagen-induced arthritis (CIA). In an in vitro study, the effects of IL-9 were investigated using siRNAs and IL-9 recombinant proteins. Finally, the underlying mechanisms were further investigated by luciferase reporter analysis, WB and Chip-qPCR. RESULTS: The upregulation of IL-9 expression in patients with RA exhibited a positive correlation with clinical markers. Using CAIA and CIA model, we demonstrated that interventions targeting PU.1 and IL-9 substantially mitigated the inflammatory phenotype. Furthermore, in vitro assays provided the proinflammatory role of IL-9, particularly in the hyperactivation of macrophages and fibroblast-like synoviocytes. Mechanistically, we uncovered that PU.1 and IL-9 form a positive feedback loop in RA: (1) PU.1 directly binds to the IL-9 promoter, activating its transcription and (2) Th9-derived IL-9 induces PU.1 via the IL-9R-JAK1/STAT3 pathway. CONCLUSIONS: These results support that the PU.1-IL-9 axis forms a positive loop in Th9 dysregulation of RA. Targeting this signalling axis presents a potential target approach for treating RA.

Integrative genomics reveals the polygenic basis of seedlessness in grapevine.

Seedlessness is a crucial quality trait in table grape (Vitis vinifera L.) breeding. However, the development of seeds involved intricate regulations, and the polygenic basis of seed abortion remains unclear. Here, we combine comparative genomics, population genetics, quantitative genetics, and integrative genomics to unravel the evolution and polygenic basis of seedlessness in grapes. We generated the haplotype-resolved genomes for two seedless grape cultivars, "Thompson Seedless" (TS, syn. "Sultania") and "Black Monukka" (BM). Comparative genomics identified a ∼4.25 Mb hemizygous inversion on Chr10 specific in seedless cultivars, with seedless-associated genes VvTT16 and VvSUS2 located at breakpoints. Population genomic analyses of 548 grapevine accessions revealed two distinct clusters of seedless cultivars, and the identity-by-descent (IBD) results indicated that the origin of the seedlessness trait could be traced back to "Sultania." Introgression, rather than convergent selection, shaped the evolutionary history of seedlessness in grape improvement. Genome-wide association study (GWAS) analysis identified 110 quantitative trait loci (QTLs) associated with 634 candidate genes, including previously unidentified candidate genes, such as three 11S GLOBULIN SEED STORAGE PROTEIN and two CYTOCHROME P450 genes, and well-known genes like VviAGL11. Integrative genomic analyses resulted in 339 core candidate genes categorized into 13 functional categories related to seed development. Machine learning-based genomic selection achieved a remarkable prediction accuracy of 97% for seedlessness in grapevines. Our findings highlight the polygenic nature of seedlessness and provide candidate genes for molecular genetics and an effective prediction for seedlessness in grape genomic breeding.

Limosilactobacillus fermentum HNU312 alleviates lipid accumulation and inflammation induced by a high-fat diet: improves lipid metabolism pathways and increases short-chain fatty acids in the gut microbiome.

A high-fat diet can cause health problems, such as hyperlipidemia, obesity, cardiovascular disease, and metabolic disorders. Dietary supplementation with beneficial microbes might reduce the detrimental effects of a high-fat diet by modulating the gut microbiome, metabolic pathways and metabolites. This study assessed the effects of Limosilactobacillus fermentum HNU312 (L. fermentum HNU312) on blood lipid levels, fat accumulation, inflammation and the gut microbiome in mice on a high-fat diet. The results indicate that L. fermentum HNU312 supplementation to high-fat diet-fed mice led to decreases of 7.52% in the final body weight, 22.30% in total triglyceride, 24.87% in total cholesterol, and 27.3% in low-density lipoprotein cholesterol. Furthermore, the addition of L. fermentum HNU312 significantly reduced the fat accumulation in the liver and adipose tissue by 18.99% and 32.55%, respectively, and decreased chronic inflammation induced by a high-fat diet. Further analysis of the gut microbiome revealed that on the one hand, L. fermentum HNU312 changed the structure of the intestinal microbiota, increased the abundance of beneficial intestinal bacteria related to lipid metabolism, and reversed the enrichment of lipid-related metabolic pathways. On the other hand, L. fermentum HNU312 increased the production of short-chain fatty acids, which can reduce liver inflammation and chronic inflammation induced by a high-fat diet. In summary, by regulating gut microbiota, L. fermentum HNU312 improved lipid metabolism pathways and increased short-chain fatty acids, which reduced body weight, blood lipids, fat accumulation and chronic inflammation caused by high-fat diets. Therefore, L. fermentum HNU312 could be a good candidate probiotic for ameliorating metabolic syndrome.