Evaluation of the safety and efficacy of cosmetics ingredient Spherulites Paeony Superior Retinol.

BACKGROUND: Microencapsulation of hydroxypinacolone retinoate (HPR) can improve its application in cosmetics. OBJECTIVE: To investigate the safety and efficacy of Spherulites Paeony Superior Retinol, a HPR microcapsule containing 5%-10% peony seed oil, 0.01%-1% epigallocatechin gallatyl glucoside (ECGG), and 0.1%-1% HPR. METHODS: The safety of Spherulites Paenoy Superior Retinol was evaluated with zebrafish embryo self-rotation irritation test and developmental toxicity test. SymRenew™ HPR was used as a reference. The skin care efficacies of Spherulites Paenoy Superior Retinol were evaluated using zebrafish embryos covering antioxidation, anti-inflammation, blood circulation, whitening, wound healing, skin barrier protection, Type I collagen, elastin, and 5α-reductase genes expression activities. RESULTS: The irritation test revealed that 250 µg/mL Spherulites Paenoy Superior Retinol did not, while 20 µg/mL SymRenew™ HPR significantly (p < 0.05) increased zebrafish embryo self-rotation frequency. The developmental toxicity test found the teratogenicity index (half lethal concentration/half toxicity concentration) of Spherulites Paenoy Superior Retinol and SymRenew™ HPR were 1.9 and 3.1, respectively. The efficacy analysis results showed that 5 µg/mL Spherulites Paenoy Superior Retinol significantly (p < 0.05) exerted 7.1% anti-ROS, 20% anti-inflammation, 14% enhanced blood circulation, 10% suppressed melanin synthesis, 9% enhanced tail fin regeneration, 72% elicited skin barrier protection activity, enhanced the expression of Type I collagen genes col1a1, col1a2, and col1a2 by 34%, 51%, and 42%, respectively, and elastin gene elna by 46%, and suppressed the expression of 5α-reductase genes srd5a1, srd5a2a, and srd5a2b by 52%, 15%, and 30%, respectively. CONCLUSION: This study demonstrated that Spherulites Paenoy Superior Retinol is a safe cosmetic ingredient with multi-skin care efficacies.

From cradle to grave: Deciphering sex-specific disruptions of the nervous and reproductive systems through interactions of 4-methylbenzylidene camphor and nanoplastics in adult zebrafish.

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 µg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish.

Selecting Monoclonal Cell Lineages from Somatic Reprogramming Using Robotic-Based Spatial-Restricting Structured Flow.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

Plasma GFAP as a prognostic biomarker of motor subtype in early Parkinson's disease.

Parkinson's disease (PD) is a heterogeneous movement disorder with different motor subtypes including tremor dominant (TD), indeterminate and postural instability, and gait disturbance (PIGD) motor subtypes. Plasma glial fibrillary acidic protein (GFAP) was elevated in PD patients and may be regarded as a biomarker for motor and cognitive progression. Here we explore if there was an association between plasma GFAP and different motor subtypes and whether baseline plasma GFAP level can predict motor subtype conversion. Patients with PD classified as TD, PIGD or indeterminate subtypes underwent neurological evaluation at baseline and 2 years follow-up. Plasma GFAP in PD patients and controls were measured using an ultrasensitive single molecule array. The study enrolled 184 PD patients and 95 control subjects. Plasma GFAP levels were significantly higher in the PIGD group compared to the TD group at 2-year follow-up. Finally, 45% of TD patients at baseline had a subtype shift and 85% of PIGD patients at baseline remained as PIGD subtypes at 2 years follow-up. Baseline plasma GFAP levels were significantly higher in TD patients converted to PIGD than non-converters in the baseline TD group. Higher baseline plasma GFAP levels were significantly associated with the TD motor subtype conversion (OR = 1.283, P = 0.033) and lower baseline plasma GFAP levels in PIGD patients were likely to shift to TD and indeterminate subtype (OR = 0.551, P = 0.021) after adjusting for confounders. Plasma GFAP may serve as a clinical utility biomarker in differentiating motor subtypes and predicting baseline motor subtypes conversion in PD patients.

Multispectral detection of dietary fiber content in Chinese cabbage leaves across different growth periods.

Multispectral imaging, combined with stoichiometric values, was used to construct a prediction model to measure changes in dietary fiber (DF) content in Chinese cabbage leaves across different growth periods. Based on all the spectral bands (365-970 nm) and characteristic spectral bands (430, 880, 590, 490, 690 nm), eight quantitative prediction models were established using four machine learning algorithms, namely random forest (RF), backpropagation neural network, radial basis function, and multiple linear regression. Finally, a quantitative prediction model of RF learning algorithm is constructed based on all spectral bands, which has good prediction accuracy and model robustness, prediction performance with R2 of 0.9023, root mean square error (RMSE) of 2.7182 g/100 g, residual predictive deviation (RPD) of 3.1220 > 3.0. In summary, this model efficiently detects changes in DF content across different growth periods of Chinese cabbage, which offers technical support for vegetable sorting and grading in the field.

Significantly enhanced uranium extraction by intelligent light-driven nanorobot catchers with precise controllable moving trajectory.

Uranium, as the most essential resource for nuclear power production, provides 13% of global electricity demand, has attracted considerable attention. However, it is still a great challenge for uranium extraction from natural water like salt lakes as the background of high salinity and low concentration (3.3 ∼ 330 ppb). Meanwhile, current uranium extraction strategies are generally focus on extraction capacity or selectivity but neglect to enhance extraction rate. In this work, we designed a novel kind of NIR-driven intelligent nanorobots catchers (MSSA-AO) with amidoxime as claws for uranium capture, which showed almost 100% extraction rate and an ultrafast extraction rate. Importantly, high extraction capacity (221.5 mg g-1) and selectivity were taken into consideration as well as good regeneration performance. Furthermore, amidoxime NRCs boosted in extraction amount about 16.7% during the first 5 min with self-driving performance. Overall, this work suggests a new strategy for ultrafast extraction of uranium from natural water with low abundance selectively by self-propelled NRCs, showing great possibility in outdoor application and promising for meeting huge energy needs globally.

Microbial methanogenesis in aerobic water: A key driver of surface methane enrichment in a deep reservoir.

Significant amounts of the greenhouse gas methane (CH4) are released into the atmosphere worldwide via freshwater sources. The surface methane maximum (SMM), where methane is supersaturated in surface water, has been observed in aquatic systems and contributes significantly to emissions. However, little is known about the temporal and spatial variability of SMM or the mechanisms underlying its development in artificial reservoirs. Here, the community composition of methanogens as major methane producers in the water column and the mcrA gene was investigated, and the cause of surface methane supersaturation was analyzed. In accordance with the findings, elevated methane concentration of SMM in the transition zone, with an annually methane emission flux 2.47 times higher than the reservoir average on a large and deep reservoir. In the transition zone, methanogens with mcrA gene abundances ranging from 0.5 × 103-1.45 × 104 copies/L were found. Methanobacterium, Methanoseata and Methanosarcina were the three dominate methanogens, using both acetic acid and H2/CO2 pathways. In summary, this study contributes to our comprehension of CH4 fluxes and their role in the atmospheric methane budget. Moreover, it offers biological proof of methane generation, which could aid in understanding the role of microbial methanogenesis in aerobic water.

Longitudinal evolution and plasma biomarkers for excessive daytime sleepiness in Parkinson's disease.

BACKGROUND: Excessive daytime sleepiness (EDS) is one of the most frequent non-motor symptoms in Parkinson's disease (PD); however, the pathogenesis of EDS is unclear, and there is a lack of information on plasma biomarkers for EDS in PD. We aimed to investigate the plasma biomarkers of EDS in a large PD cohort. METHODS: A total of 159 PD patients were included in the prospective cohort study and followed up annually for three years. Plasma biomarkers including glial fibrillary acidic protein, amyloid-beta, p-tau181, and neurofilament light chain (NfL), were measured using an ultrasensitive single-molecule array (SimoaTM) technology at each visit. EDS was evaluated using the Epworth Sleepiness Scale (ESS). RESULTS: The frequency of EDS in PD increased from 15.1% at baseline to 25.0% after three years. The mean ESS scores increased from 5.1 [Standard Deviation (SD): 4.8] at baseline to 6.1 [SD: 5.5] at the third year of follow-up. At baseline, compared with patients with PD without EDS, those with EDS were more likely to be male, had poorer cognitive performance, and more severe motor and non-motor symptoms. The adjusted generalized estimating equations models showed that higher plasma NfL levels (OR 1.047 [1.002-1.094], p = 0.042) were associated with EDS during follow-ups. The adjusted linear mixed-effects model showed that higher plasma NfL levels (ß 0.097 [0.012-0.183], p = 0.026) were associated with ESS scores during follow-ups. CONCLUSIONS: Higher plasma NfL levels were associated with EDS in PD, indicating an association between neuro-axonal degeneration and EDS in PD.

Remediation of 2,4-dichlorophenol-contaminated soil by electrokinetic delivery of persulfate technology.

2,4-Dichlorophenol (2,4-DCP) is difficult to degrade rapidly in the environment due to its stable chemical properties, so it was easy to lead to serious chlorophenol pollution in soil. Consequently, a remediation method which is efficient, safe, and economical is required. In this study, electrokinetic (EK) remediation was used to transfer sodium persulfate (Na2S2O8) into soil to degrade 2,4-DCP, and the effect of several factors (including the addition location of Na2S2O8, applied voltage, and running time) on the remediation efficiency was explored. The concentration of Na2S2O8, residual efficiency of 2,4-DCP and distribution characteristics of pH, and electrical conductivity were analyzed. The results showed that the cathode was the optimal position to add Na2S2O8. Under this condition, Na2S2O8 was uniformly distributed in the whole soil column through electromigration. The optimal removal efficiency of 2,4-DCP in soil by adding Na2S2O8 was approximately 26% when the voltage gradient was 1.0 V/cm and the operating time was 9 days, which was mainly due to the degradation of S2O82-.

Relationship between plasma NFL and disease progression in Parkinson's disease: a prospective cohort study.

OBJECTIVE: We aimed to examine the longitudinal change of plasma neurofilament light chain (NFL) level and explore its diagnostic and prognostic implications in Parkinson's disease (PD). METHODS: A total of 184 patients with early PD who completed 5-year annually repeated clinical assessments were included. Plasma NFL at baseline, 1 year, and 2 year were examined, which were quantified using the ultrasensitive Simoa technology. At baseline, blood from 86 sex- and age-matched healthy controls (HC) were obtained for comparison. RESULTS: Plasma NFL in PD patients at baseline was significantly higher than those in HC (P = 0.046), and significantly increased after 2 years (P = 0.046). Receiver operating characteristic curve indicated that a plasma NFL cut-off value of 10.79 pg/mL resulted in 39.7% sensitivity and 84.0% specificity, with an area under the curve of 0.635, to distinguish PD from HC (P < 0.001). Linear mixed-effect models indicated that baseline plasma NFL (> 9.24 pg/mL) correlated with a greater increase in the Unified Parkinson's Disease Rating Scale III (estimate = 0.651, P = 0.001) and Hoehn & Yahr stage (estimate = 0.072, P < 0.001), and also correlated with a greater decrease in the Montreal Cognitive Assessment (estimate = - 0.387, P < 0.001) during follow-up visits. CONCLUSIONS: Plasma NFL exhibits a tendency to increase with disease progression, and elevated baseline plasma NFL can serve as a predictor for accelerated motor deterioration and cognitive decline in PD. However, plasma NFL does not have high accuracy to distinguish individuals with early-stage PD from HC.

Prevalence and prognostic significance of malnutrition in early-stage multiple system atrophy.

Background: Malnutrition is associated with poor survival in some diseases. However, the nutritional status in multiple system atrophy (MSA) is unknown, and the significance of malnutrition for the prediction of mortality in MSA has not been well established. Objective: We aimed to determine the prevalence of malnutrition and the prognostic value of malnutrition in patients with early-stage MSA. Methods: Patients diagnosed with early phase MSA (disease duration<3 years) were recruited, and they were followed every year until May 2023. The nutritional status of patients with MSA was assessed using the Controlling Nutritional Status (CONUT) score and Geriatric Nutritional Risk Index (GNRI). Kaplan-Meier survival analysis and Cox regression model were used to assess the prognostic value of malnutrition in MSA. Results: A total of 224 patients with probable MSA (106 MSA died and 118 were still alive) and 213 matched healthy controls (HCs) were enrolled. According to COUNT score and GNRI, patients with MSA had higher prevalence of malnutrition than HCs (44.6% vs. 14.1 and 17.9% vs. 0.9%, respectively). The median survival from symptom onset in patients with MSA in the malnutrition group was shorter than those in the normal-nutrition group (5.98 vs. 7.06 years, p = 0.012) by COUNT score. Additionally, malnutrition increased the risk of mortality in patients with MSA (HR = 1.556, p = 0.030) and MSA-P (HR = 1.973, p = 0.042) by COUNT score. Interpretation: Malnutrition was common in patients with early-stage MSA. Malnutrition increased the risk of mortality in patients with MSA, and early nutritional supplementation should be taken into consideration.

Freezing of gait in Parkinson's disease with glucocerebrosidase mutations: prevalence, clinical correlates and effect on quality of life.

Objectives: Mutations in glucocerebrosidase (GBA1) can change the clinical phenotype of Parkinson's disease (PD). This study aimed to explore the clinical characteristics of freezing of gait (FOG) in PD patients with GBA1 mutations. Methods: A whole-exome sequencing analysis was used to identify the GBA1 mutations (pathogenic or likely pathogenic) and exclude other PD-related gene mutations. A forward binary logistic regression model was conducted to identify the associated factors of FOG. The stepwise multiple linear regression analysis models were used to explore the effect of FOG on quality of life. Results: The prevalence of FOG in patients with GBA1 mutations (30/95, 31.6%) was significantly higher than those in patients without GBA1 mutations (152/760, 20%) (p = 0.009). A higher (i.e., worse) Unified PD Rating Scale part III score (OR = 1.126, 95%CI = 1.061-1.194, p < 0.001) and a lower (i.e., worse) Montreal Cognitive Assessment score (OR = 0.830, 95%CI = 0.713-0.967, p = 0.017) were significantly associated with FOG in PD patients with GBA1 mutations. The presence of FOG was significantly associated with the decreased (i.e., worse) score of PD Questionnaire 39 after adjustment for sex, age, disease duration, motor score, and non-motor score (B = 14.981, p = 0.001). Conclusion: FOG is a relatively common disabling symptom in PD patients with GBA1 mutations, which is affected by motor disability and cognitive decline. Quality of life is reduced in patients with FOG and GBA1 mutations.

Effects of Cascade Reservoirs on Spatiotemporal Dynamics of the Sedimentary Bacterial Community: Co-occurrence Patterns, Assembly Mechanisms, and Potential Functions.

Dam construction as an important anthropogenic activity significantly influences ecological processes in altered freshwater bodies. However, the effects of multiple cascade dams on microbial communities have been largely overlooked. In this study, the spatiotemporal distribution, co-occurrence relationships, assembly mechanisms, and functional profiles of sedimentary bacterial communities were systematically investigated in 12 cascade reservoirs across two typical karst basins in southwest China over four seasons. A significant spatiotemporal heterogeneity was observed in bacterial abundance and diversity. Co-occurrence patterns in the Wujiang Basin exhibited greater edge counts, graph density, average degree, robustness, and reduced modularity, suggesting more intimate and stronger ecological interactions among species than in the Pearl River Basin. Furthermore, Armatimonadota and Desulfobacterota, identified as keystone species, occupied a more prominent niche than the dominant species. A notable distance-decay relationship between geographical distance and community dissimilarities was identified in the Pearl River Basin. Importantly, in the Wujiang Basin, water temperature emerged as the primary seasonal variable steering the deterministic process of bacterial communities, whereas 58.5% of the explained community variance in the neutral community model (NCM) indicated that stochastic processes governed community assembly in the Pearl River Basin. Additionally, principal component analysis (PCA) revealed more pronounced seasonal dynamics in nitrogen functional compositions than spatial variation in the Wujiang Basin. Redundancy analysis (RDA) results indicated that in the Wujiang Basin, environmental factors and in Pearl River Basin, geographical distance, reservoir age, and hydraulic retention time (HRT), respectively, influenced the abundance of nitrogen-related genes. Notably, these findings offer novel insights: building multiple cascade reservoirs could lead to a cascading decrease in biodiversity and resilience in the river-reservoir ecosystem.

Bifidobacterium mitigates autoimmune hepatitis by regulating IL-33-induced Treg/Th17 imbalance via the TLR2/4 signaling pathway.

The present work aims to evaluate the efficacy of Live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules (LCBLECs), a probiotic drug containing Bifidobacterium, in the treatment of autoimmune hepatitis (AIH). In this study, a mouse model of experimental autoimmune hepatitis (EAH) was established to investigate the effects of LCBLECs on AIH. The results showed that LCBLECs improved dysbiosis of gut microbiota, reduced liver injury, restored liver function, and maintained Treg/Th17 balance in EAH mice. In addition, LCBLECs restored Treg/Th17 balance in EAH mice by downregulating IL-33 production. Besides, LCBLECs also suppress IL-33 upregulation in EAH mice by inhibiting the TLR2/4 signaling pathway. Furthermore, LCBLECs also mitigated dysbiosis of gut microbiota and enhanced the efficacy of conventional treatment for AIH patients. To sum up, our findings revealed that LCBLECs exerted therapeutic effects on EAH mice by improving Treg/Th17 imbalance in an IL-33-dependent manner via the TLR2/4 signaling pathway and relieved the clinical symptoms of AIH patients, indicating Bifidobacterium supplementation with LCBLECs might be a potential adjuvant therapy for AIH treatment.

Investigation of the Relationship between Apolipoprotein E Alleles and Serum Lipids in Alzheimer's Disease: A Meta-Analysis.

Prior studies have yielded mixed findings concerning the association between apolipoprotein E(APOE)-ε4 and serum lipids in patients with Alzheimer's disease (AD) and healthy individuals. Some studies suggested a relationship between APOEε4 and serum lipids in patients with AD and healthy individuals, whereas others proposed that the APOEε4 allele affects lipids only in patients with AD. Our study aimed to investigate whether APOE alleles have a distinct impact on lipids in AD. We conducted a comprehensive search of the PubMed and Embase databases for all related studies that investigate APOE and serum lipids of AD from the inception to 30 May 2022. Elevated total cholesterol (TC) and low-density lipoprotein (LDL) levels were found in APOEε4 allele carriers compared with non-carriers. No significant differences were found for high-density lipoprotein (HDL) and triglyceride (TG) levels in APOEε4 allele carriers compared to non-carriers. Notably, elevated TC and LDL levels showed considerable heterogeneity between patients with AD and healthy controls. A network meta-analysis did not find a distinct effect of carrying one or two APOEε4 alleles on lipid profiles. Higher TC and LDL levels were found in APOEε4 allele carriers compared with non-carriers, and the difference was more significant in patients with AD than in healthy controls.

Plasma glial fibrillary acidic protein as a biomarker of disease progression in Parkinson's disease: a prospective cohort study.

BACKGROUND: Reactive astrogliosis has been demonstrated to have a role in Parkinson's disease (PD); however, astrocyte-specific plasma glial fibrillary acidic protein (GFAP)'s correlation with PD progression remains unknown. We aimed to determine whether plasma GFAP can monitor and predict PD progression. METHODS: A total of 184 patients with PD and 95 healthy controls (HCs) were included in this prospective cohort study and followed-up for 5 years. Plasma GFAP, amyloid-beta (Aß), p-tau181, and neurofilament light chain (NfL) were measured at baseline and at 1- and 2-year follow-ups. Motor and non-motor symptoms, activities of daily living, global cognitive function, executive function, and disease stage were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) part III, UPDRS-I, UPDRS-II, Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Hoehn and Yahr (H&Y) scales at each visit, respectively. RESULTS: Plasma GFAP levels were higher in patients with PD (mean [SD]: 69.80 [36.18], pg/mL) compared to HCs (mean [SD]: 57.89 [23.54], pg/mL). Higher levels of GFAP were observed in female and older PD patients. The adjusted linear mixed-effects models showed that plasma GFAP levels were significantly associated with UPDRS-I scores (ß: 0.006, 95% CI [0.001-0.011], p = 0.027). Higher baseline plasma GFAP correlated with faster increase in UPDRS-I (ß: 0.237, 95% CI [0.055-0.419], p = 0.011) and UPDRS-III (ß: 0.676, 95% CI [0.023-1.330], p = 0.043) scores and H&Y stage (ß: 0.098, 95% CI [0.047-0.149], p < 0.001) and faster decrease in MoCA (ß: - 0.501, 95% CI [- 0.768 to - 0.234], p < 0.001) and FAB scores (ß: - 0.358, 95% CI [- 0.587 to - 0.129], p = 0.002). Higher baseline plasma GFAP predicted a more rapid progression to postural instability (hazard ratio: 1.009, 95% CI [1.001-1.017], p = 0.033). CONCLUSIONS: Plasma GFAP might be a potential biomarker for monitoring and predicting disease progression in PD.

Fecal microbiota transplantation regulates TFH/TFR cell imbalance via TLR/MyD88 pathway in experimental autoimmune hepatitis.

Objective: Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. Intestinal flora disturbance in AIH is closely related to TFH/TFR cell imbalances. As a new method of microbial therapy, the role of fecal microbiota transplantation (FMT) in AIH remains elusive. Here, we attempted to verify the functional role and molecular mechanism of FMT in AIH. Methods: An experimental autoimmune hepatitis (EAH) mouse model was established to mimic the characteristics of AIH. H&E staining was used to detect histological features in mouse liver tissues. Serological tests were employed to identify several liver function biomarkers. Flow cytometry was utilized to examine the status of TFH/TFR cell subsets. Western blotting was used to evaluate TLR pathway-associated protein abundance. RT‒qPCR was applied to evaluate Treg cell markers and inflammation marker levels in mouse liver tissues. Results: There was significant liver inflammation and dysregulated TFR/TFH cells with elevated levels of liver inflammation-associated biomarkers in EAH mice. Interestingly, transferring therapeutic FMT into EAH mice dramatically reduced liver injury and improved the imbalance between splenic TFR and TFH cells. FMT treatment also reduced elevated contents of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in EAH mice. Furthermore, therapeutic FMT reversed the increased levels of IL-21 while promoting IL-10 and TGF-ß cytokines. Mechanistically, FMT regulated TFH cell response in EAH mice in a TLR4/11/MyD88 pathway-dependent manner. Conclusion: Our findings demonstrated that liver injury and dysregulation between TFR and TFH cells in EAH might be reversed by therapeutic FMT via the TLR4/11-MyD88 signaling pathway.

Genome-wide analyses identify NEAT1 as genetic modifier of age at onset of amyotrophic lateral sclerosis.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) demonstrate great heterogeneity in the age at onset (AAO), which is closely related to the course of disease. However, most genetic studies focused on the risk of ALS, while the genetic background underlying AAO of ALS is still unknown. METHODS: To identify genetic determinants influencing AAO of ALS, we performed genome-wide association analysis using a Cox proportional hazards model in 2,841 patients with ALS (Ndiscovery = 2,272, Nreplication = 569) in the Chinese population. We further conducted colocalization analysis using public cis-eQTL dataset, and Mendelian randomization analysis to identify risk factors for AAO of ALS. Finally, functional experiments including dual-luciferase reporter assay and RT-qPCR were performed to explore the regulatory effect of the target variant. RESULTS: The total heritability of AAO of ALS was ~ 0.24. One novel locus rs10128627 (FRMD8) was significantly associated with earlier AAO by ~ 3.15 years (P = 1.54E-08, beta = 0.31, SE = 0.05). This locus was cis-eQTL of NEAT1 in multiple brain tissues and blood. Colocalization analysis detected association signals at this locus between AAO of ALS and expression of NEAT1. Furthermore, functional exploration supported the variant rs10128627 was associated with upregulated expression of NEAT1 in cell models and patients with ALS. Causal inference suggested higher total cholesterol, low-density lipoprotein, and eosinophil were nominally associated with earlier AAO of ALS, while monocyte might delay the AAO. CONCLUSIONS: Collective evidence from genetic, bioinformatic, and functional results suggested NEAT1 as a key player in the disease progression of ALS. These findings improve the current understanding of the genetic role in AAO of ALS, and provide a novel target for further research on the pathogenesis and therapeutic options to delay the disease onset.

Environmental Factors Affecting the Diversity and Composition of Environmental Microorganisms in the Shaoxing Rice Wine Producing Area.

Shaoxing rice wine is a notable exemplar of Chinese rice wine. Its superior quality is strongly correlated with the indigenous natural environment. The results indicated that Firmicutes (75%), Actinobacteria (15%), Proteobacteria (5%), and Bacteroidetes (3%) comprised the prevailing bacterial groups. Among the main bacterial genera, Lactobacillus was the most abundant, accounting for 49.4%, followed by Lactococcus (11.9%), Saccharopolyspora (13.1%), Leuconostoc (4.1%), and Thermoactinomyces (1.1%). The dominant fungal phyla were Ascomycota and Zygomycota. Among the dominant genera, Saccharomyces (59.3%) prevailed as the most abundant, followed by Saccharomycopsis (10.7%), Aspergillus (7.1%), Thermomyces (6.2%), Rhizopus (4.9%), Rhizomucor (2.2%), and Mucor (1.3%). The findings demonstrate that the structure of the bacterial and fungal communities remains stable in the environment, with their diversity strongly influenced by climatic conditions. The continuous fluctuations in environmental factors, such as temperature, air pressure, humidity, rainfall, and light, significantly impact the composition and diversity of microbial populations, particularly the dominant bacterial community.

Spatiotemporal variations and dominated environmental parameters of nitrous oxide (N2O) concentrations from cascade reservoirs in southwest China.

Anthropogenic activity has caused rivers and reservoirs to become sources of nitrous oxide (N2O), which is thought to play an important role in global climate change. There are thermal and DO stratification in deep-water reservoirs with long hydraulic retention time, which change N2O production mechanism compared with shallow-water reservoirs. To promote our understanding of the relationship of N2O production in reservoirs at different depths, spatiotemporal variations in water environmental factors and N2O from cascade reservoirs of Chaishitan (CST), Longtan (LT), Yantan (YT) and Dahua (DH) reservoirs in the Zhujiang River were detected, and the LT and YT reservoirs were compared as representatives of deep-water and shallow-water reservoirs in April and July 2019. The average N2O concentrations in the LT and YT reservoirs were 22.82 ± 2.21 and 21.55 ± 1.65 nmol L-1, respectively. During spring and summer, the WT (water temperature) and DO (dissolved oxygen) concentrations in the YT reservoir were well mixed. In contrast, the LT reservoir, as a deep-water reservoir, had thermal and DO stratifications in both the shallow and middle water, especially in the summer when the solar radiation intensity was high. During summer stratification, the DO concentration in the LT reservoir showed obvious spatial variation, ranging from 1.23 to 9.84 mg L-1, while the DO concentration in the YT reservoir showed very little variation, ranging from 6.45 to 7.09 mg L-1. Structural equation modeling results showed that NH4+ was the main determinant of the N2O concentration in the YT reservoir, and DO was the most influential factor of the N2O concentration in the LT reservoir. These results suggest significant variations in the factors influencing N2O concentration among reservoirs. Additionally, the mechanisms of N2O production differ between deep-water and shallow-water reservoirs. This study highlights the spatio-temporal variations and influential factors contributing to N2O concentration. Furthermore, it discusses the production mechanisms of N2O in different types of reservoirs. These findings contribute to our understanding of N2O distribution in hydropower systems and provide valuable data for the management of hydropower facilities and research on greenhouse gas emissions.