Diagnostic and Therapeutic Challenges in Lemierre Syndrome: A Case Report Using Metagenomic Next Generation Sequencing.

Lemierre syndrome (LS) is a rare and life-threatening condition predominantly caused by Fusobacterium necrophorum. Currently, there are no standardized clinical guidelines for LS management. Here, we describe the case of a 40-year-old male with fever, productive cough, and dyspnea but no sore throat. Diagnostic radiological examinations revealed multiple pulmonary cavitary nodules and an internal jugular vein occlusion. Metagenomic Next-Generation Sequencing (mNGS) of the alveolar lavage fluid identified Fusobacterium necrophorum, thereby confirming the diagnosis of LS. Intriguingly, the patient exhibited a delayed clinical response despite receiving the appropriate antibiotic. After integrating tigecycline into the treatment to address potential co-infecting bacteria, we observed a marked improvement in his clinical symptoms. Subsequent follow-up over 12 weeks post-discharge revealed complete alleviation of symptoms, and a chest CT scan showed marked regression of the lung lesions.

Responsive Organic Fluorescent Aggregates Based on Ion-π Interactions Away from Fluorescent Conjugated Groups.

Responsive organic luminescent aggregates have a wide range of application fields, but currently there is still a lack of reasonable molecular design strategies. Introducing ion-π interactions into molecules can effectively alter their luminescent properties. However, current research typically focuses on ion localization at luminescent conjugated groups with the strong interaction forces. In this work, we introduce the flexible alkoxy chain spacers between fluorescent conjugated groups and ion-π interaction sites, and then adjust the fluorescence performance of the molecule by changing the strength of ion-π interactions. Bromine ion-based molecules with strong ion-π interactions exhibit high and stable fluorescence quantum yields in crystals and amorphous powders under the external stimuli. Hexafluorophosphate ion-based molecules with weak ion-π interactions have the high fluorescence quantum yield in crystals and very low fluorescence quantum yield in amorphous powders, showing variable fluorescence intensities under external stimuli. This demonstrates a new class of responsive organic luminescent solid-state materials.

Psychosocial adjustment changes and related factors in young and middle-aged patients with first-episode acute myocardial infarction: a longitudinal study.

AIMS: This study aimed to explore the change trend and group heterogeneity of psychosocial adjustment level and to determine its influencing factors among young and middle-aged patients with first-episode acute myocardial infarction (AMI). METHODS AND RESULTS: The Psychosocial Adjustment Scale of Illness was used to assess the psychosocial adjustment level of the patients at 1, 3, and 6 months after discharge, respectively. Data were analyzed using Pearson correlation analysis, generalized estimating equations, and growth mixed models. A total of 233 patients were included, and their psychosocial adjustment scores at the three-time points were 57.18 ± 15.50, 36.17 ± 15.02, and 24.22 ± 12.98, respectively. The trajectories of changes in patients' psychosocial adjustment levels were divided into three latent categories: moderate adjustment improvement group (72.5%), low adjustment improvement group (16.3%), and persistent maladjustment group (11.2%). Among them, predictors of the persistent maladjustment group included no spouse, low monthly family income per capita, normal body mass index, never smoking, never exercising, combined with hyperlipidemia, low social support, submission coping, and high perceived stress. CONCLUSIONS: The psychosocial adjustment level of young and middle-aged patients with first-episode AMI showed an upward trend within 6 months after discharge, and there was group heterogeneity in the change trajectory of psychosocial adjustment level. It is suggested that a multi-center, large-sample longitudinal study should be carried out in the future, and the time of follow-up investigation should be extended to further clarify the change trajectory and influencing factors of psychosocial adjustment of patients with different subtypes, to provide the theoretical basis for formulating targeted intervention programs.

Room­Temperature Antisymmetric Magnetoresistance in van der Waals Ferromagnet Fe3GaTe2 Nanosheets.

Van der Waals (vdW) ferromagnetic materials have emerged as a promising platform for the development of 2D spintronic devices. However, studies to date are restricted to vdW ferromagnetic materials with low Curie temperature (Tc) and small magnetic anisotropy. Here, a chemical vapor transport method is developed to synthesize a high-quality room-temperature ferromagnet, Fe3GaTe2 (c-Fe3GaTe2), which boasts a high Tc = 356 K and large perpendicular magnetic anisotropy. Due to the planar symmetry breaking, an unconventional room-temperature antisymmetric magnetoresistance (MR) is first observed in c-Fe3GaTe2 devices with step features, manifesting as three distinctive states of high, intermediate, and low resistance with the sweeping magnetic field. Moreover, the modulation of the antisymmetric MR is demonstrated by controlling the height of the surface steps. This work provides new routes to achieve magnetic random storage and logic devices by utilizing the room-temperature thickness-controlled antisymmetric MR and further design room-temperature 2D spintronic devices based on the vdW ferromagnet c-Fe3GaTe2.

Exercise promotes brain health: a systematic review of fNIRS studies.

Exercise can induce brain plasticity. Functional near-infrared spectroscopy (fNIRS) is a functional neuroimaging technique that exploits cerebral hemodynamics and has been widely used in the field of sports psychology to reveal the neural mechanisms underlying the effects of exercise. However, most existing fNIRS studies are cross-sectional and do not include exercise interventions. In addition, attributed to differences in experimental designs, the causal relationship between exercise and brain functions remains elusive. Hence, this systematic review aimed to determine the effects of exercise interventions on alterations in brain functional activity in healthy individuals using fNIRS and to determine the applicability of fNIRS in the research design of the effects of various exercise interventions on brain function. Scopus, Web of Science, PubMed, CNKI, Wanfang, and Weipu databases were searched for studies published up to June 15, 2021. This study was performed in accordance with the PRISMA guidelines. Two investigators independently selected articles and extracted relevant information. Disagreements were resolved by discussion with another author. Quality was assessed using the Cochrane risk-of-bias method. Data were pooled using random-effects models. A total of 29 studies were included in the analysis. Our results indicated that exercise interventions alter oxygenated hemoglobin levels in the prefrontal cortex and motor cortex, which are associated with improvements in higher cognitive functions (e.g., inhibitory control and working memory). The frontal cortex and motor cortex may be key regions for exercise-induced promotion of brain health. Future research is warranted on fluctuations in cerebral blood flow during exercise to elucidate the neural mechanism underlying the effects of exercise. Moreover, given that fNIRS is insensitive to motion, this technique is ideally suited for research during exercise interventions. Important factors include the study design, fNIRS device parameters, and exercise protocol. The examination of cerebral blood flow during exercise intervention is a future research direction that has the potential to identify cortical hemodynamic changes and elucidate the relationship between exercise and cognition. Future studies can combine multiple study designs to measure blood flow prior to and after exercise and during exercise in a more in-depth and comprehensive manner.

Effects of dietary cecropin on growth performance, diarrhea rate and intestinal health of nursery Hainan pigs.

Antimicrobial peptides could inhibit the growth of harmful bacteria and promote the growth performance in weaned piglets. Here, we investigated the effects of dietary supplementation with cecropin antimicrobial peptides (CAP) on growth performance, diarrhea rate, intestinal health in nursery Hainan piglets. For this, 120 healthy nursery Hainan male piglets (13.29 ± 0.29 kg, 44 days old) were randomly divided into 5 groups-a control (CON) group (fed a basal diet), an antibiotic control (AC) group (fed a basal diet supplemented with 250 mg/kg colistin sulfate); and 3 experimental groups (provided the basal diet supplemented with 250, 500, or 1,000 mg/kg CAP). Pre-feeding lasted 7 days and the official period lasted 40 days. The results showed that compared with the CON group, dietary supplementation of 500 mg/kg CAP had significantly increased the average daily gain (ADG, p < 0.05), while the feed conversion ratio (FCR) and diarrhea rate were markedly reduced (p < 0.05), serum total protein (TP), albumin, IgA, IgM, and globulin concentrations were significantly increased (p < 0.05), where serum aspartate aminotransferase (AST) level was significantly reduced (p < 0.05), and it also increased the villus height and the villus height-to-crypt depth ratio in the jejunum, reduced the serum D-lactic acid concentrations and diamine oxidase activity, and increased the expression level of ZO-1 and occludin in the jejunum and ileum (p < 0.05), the relative abundance of Firmicutes, Lactobacillus, and Limoslactobacillus in the colon were increased (p < 0.05), whereas that of Streptococcus and Escherichia-Shigella were reduced (p < 0.05). These results indicated that dietary supplementation with 500 mg/kg CAP could improve the growth performance, reduce the diarrhea rate, improve the serum immunity, intestinal health of nursery pigs.

Mass spectrometry-based pseudotargeted metabolomics reveals metabolic variations in a2-induced gastric cancer cell.

Gastric cancer (GC) is one of the most malignant tumors with high morbidity and mortality in the world. Compound a2, a Jiyuan oridonin derivative, exhibited excellent anti-proliferative activity against GC cells. To investigate the gastric cellular response to a2 therapy as a novel drug candidate, we adopted a pseudotargeted metabolomics method to explore metabolic variation in a2-induced MGC-803 gastric cells using liquid chromatography tandem mass spectrometry combined with multivariate statistical analysis. The results showed that a2 treatment induced significant metabolic changes in the levels of aminoacyl-tRNA biosynthesis, alanine, aspartate and glutamate metabolism, pyrimidine metabolism, and tricarboxylic acid cycle, approximately 80% of the metabolites were down-regulated in the low-dose and high-dose groups including aspartate, tryptophan, sedoheptulose 7-phosphate, succinate, 2'-deoxyadenosine, uridine, cytidine, etc. which can provide evidence for a new therapy of GC.

Tailoring the interfacial microenvironment of magnetic metal-organic frameworks using amino-acid-based ionic liquids for lipase immobilization.

Modifying the carrier interface is a promising method to improve the microenvironment of immobilized enzymes and enhance their activity and stability. In this work, using proline as amino acid, magnetic metal-organic frameworks (MOFs) were modified with an amino-acid-based ionic liquid (AAIL) with two hydroxyl groups followed by adsorption of porcine pancreatic lipase (PPL). The activity recovery of the prepared immobilized lipase (MMOF-AAIL/PPL) was up to 162 % higher than that of MMOF-PPL (70.8 %). The Michaelis constant of MMOF-AAIL/PPL was 0.0742 mM lower than that of MMOF-PPL, but the catalytic efficiency was 0.0223 min-1 which was higher than MMOF-PPL. Furthermore, MMOF-AAIL/PPL maintained 85.6 % residual activity after stored for 40 days and its residual activity was 71.9 % while that for MMOF-PPL was 58.8 % after incubated in 6 M urea for 2 h. Particularly, after ten consecutive cycles, the residual activity of MMOF-AAIL/PPL still reached 84.4 %. In addition, the magnetic properties of the support facilitate the separation process which improves the utilization efficiency of immobilized enzymes.

Late-Stage C-H Nitration of Unactivated Arenes by Fe(NO3)3·9H2O in Hexafluoroisopropanol.

Operationally simple and generally applicable arene nitration with cheap and easily accessible chemicals has been a long-sought transformation in the synthetic organic community. In this work, we realized this goal with nontoxic and inexpensive Fe(NO3)3·9H2O as the nitro source and easily recyclable solvent hexafluoroisopropanol as the promotor via a network of hydrogen-bonding interactions. As a result of the relative mildness and high reliability of this protocol, late-stage nitration of various highly functionalized natural products and commercially available drugs was realized.

Identification of potential drug targets for allergic diseases from a genetic perspective: A mendelian randomization study.

BACKGROUND: Allergic diseases typically refer to a heterogeneous group of conditions primarily caused by the activation of mast cells or eosinophils, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma. Asthma, AR, and AD collectively affect approximately one-fifth of the global population, imposing a significant economic burden on society. Despite the availability of drugs to treat allergic diseases, they have been shown to be insufficient in controlling relapses and halting disease progression. Therefore, new drug targets are needed to prevent the onset of allergic diseases. METHOD: We employed a Mendelian randomization approach to identify potential drug targets for the treatment of allergic diseases. Leveraging 1798 genetic instruments for 1537 plasma proteins from the latest reported Genome-Wide Association Studies (GWAS), we analyzed the GWAS summary statistics of Ferreira MA et al. (nCase = 180,129, nControl = 180,709) using the Mendelian randomization method. Furthermore, we validated our findings in the GWAS data from the FinnGen and UK Biobank cohorts. Subsequently, we conducted sensitivity tests through reverse causal analysis, Bayesian colocalization analysis, and phenotype scanning. Additionally, we performed protein-protein interaction analysis to determine the interaction between causal proteins. Finally, based on the potential protein targets, we conducted molecular docking to identify potential drugs for the treatment of allergic diseases. RESULTS: At Bonferroni significance (p < 3.25 × 10-5), the Mendelian randomization analysis revealed 11 significantly associated protein-allergic disease pairs. Among these, the increased levels of TNFAIP3, ERBB3, TLR1, and IL1RL2 proteins were associated with a reduced risk of allergic diseases, with corresponding odds ratios of 0.82 (0.76-0.88), 0.74 (0.66-0.82), 0.49 (0.45-0.55), and 0.81 (0.75-0.87), respectively. Conversely, increased levels of IL6R, IL1R1, ITPKA, IL1RL1, KYNU, LAYN, and LRP11 proteins were linked to an elevated risk of allergic diseases, with corresponding odds ratios of 1.04 (1.03-1.05), 1.25 (1.18-1.34), 1.48 (1.25-1.75), 1.14 (1.11-1.18), 1.09 (1.05-1.12), 1.96 (1.56-2.47), and 1.05 (1.03-1.07), respectively. Bayesian colocalization analysis suggested that LAYN (coloc.abf-PPH4 = 0.819) and TNFAIP3 (coloc.abf-PPH4 = 0.930) share the same variant associated with allergic diseases. CONCLUSIONS: Our study demonstrates a causal association between the expression levels of TNFAIP3 and LAYN and the risk of allergic diseases, suggesting them as potential drug targets for these conditions, warranting further clinical investigation.

Baicalein triggers ferroptosis in colorectal cancer cells via blocking the JAK2/STAT3/GPX4 axis.

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.

Can cerebellar theta-burst stimulation improve balance function and gait in stroke patients? A randomized controlled trial.

BACKGROUND: The cerebellum is a key structure involved in balance and motor control, and has become a new stimulation target in brain regulation technology. Interference theta-burst simulation (iTBS) is a novel simulation mode of repetitive transcranial magnetic simulation. However, the impact of cerebellar iTBS on balance function and gait in stroke patients is still unknown. AIM: The aim of this study was to determine whether cerebellar iTBS can improve function, particularly balance and gait, in patients with post-stroke hemiplegia. DESIGN: This study is a randomized, double-blind, sham controlled clinical trial. SETTING: The study was carried out at the Department of Rehabilitation Medicine in a general hospital. POPULATION: Patients with stroke with first unilateral lesions were enrolled in the study. METHODS: Thirty-six patients were randomly assigned to the cerebellar iTBS group or sham stimulation group. The cerebellar iTBS or pseudo stimulation site is the ipsilateral cerebellum on the paralyzed side, which is completed just before daily physical therapy. The study was conducted five times a week for two consecutive weeks. All patients were assessed before the intervention (T0) and at the end of 2 weeks of treatment (T1), respectively. The primary outcome was the Berg Balance Scale (BBS), while secondary outcome measures included the Fugl Meyer Lower Limb Assessment Scale (FMA-LE), timed up and go (TUG), Barthel Index (BI), and gait analysis. RESULTS: After 2 weeks of intervention, the BBS, FMA-LE, TUG, and BI score in both the iTBS group and the sham group were significantly improved compared to the baseline (all P<0.05). Also, there was a significant gait parameter improvement including the cadence, stride length, velocity, step length compared to the baseline (P<0.05) in the iTBS group, but only significant improvement in cadence was identified in the sham group (P<0.05). Intergroup comparison showed that the BBS (P<0.001), FMA-LE (P<0.001), and BI (P=0.002) in the iTBS group were significantly higher than those in the sham group, and the TUG in the iTBS was significantly lower than that in the sham group (P=0.002). In addition, there were significant differences in cadence (P=0.029), strip length (P=0.046), gain velocity (P=0.002), and step length of affected lower limb (P=0.024) between the iTBS group and the sham iTBS group. CONCLUSIONS: Physical therapy is able to improve the functional recovery in hemiplegic patients after stroke, but the cerebellar iTBS can facilitate and accelerate the recovery, particularly the balance function and gait. Cerebellar iTBS could be an efficient and facilitative treatment for patients with stroke. CLINICAL REHABILITATION IMPACT: Cerebellar iTBS provides a convenient and efficient treatment modality for functional recovery of patients with stroke, especially balance function and gait.

A cellulosomal yeast reaction system of lignin-degrading enzymes for cellulosic ethanol fermentation.

Biofuel production from lignocellulose feedstocks is sustainable and environmentally friendly. However, the lignocellulosic pretreatment could produce fermentation inhibitors causing multiple stresses and low yield. Therefore, the engineering construction of highly resistant microorganisms is greatly significant. In this study, a composite functional chimeric cellulosome equipped with laccase, versatile peroxidase, and lytic polysaccharide monooxygenase was riveted on the surface of Saccharomyces cerevisiae to construct a novel yeast strain YI/LVP for synergistic lignin degradation and cellulosic ethanol production. The assembly of cellulosome was assayed by immunofluorescence microscopy and flow cytometry. During the whole process of fermentation, the maximum ethanol concentration and cellulose conversion of engineering strain YI/LVP reached 8.68 g/L and 83.41%, respectively. The results proved the availability of artificial chimeric cellulosome containing lignin-degradation enzymes for cellulosic ethanol production. The purpose of the study was to improve the inhibitor tolerance and fermentation performance of S. cerevisiae through the construction and optimization of a synergistic lignin-degrading enzyme system based on cellulosome.

Anti-pancreatic cancer activity of cassane diterpenoids isolated from the seeds of Caesalpinia sappan mediated by autophagy activation via ROS/AMPK/mTORC1 pathway.

Three undescribed cassane diterpenoids, caesalpanins D-F (1-3), and seven known ones were isolated from the seeds of Caesalpinia sappan. Structures and absolute configurations of 1-3 were elucidated based on the extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Structurally, compound 1 was the first example of 18-norcassane diterpenoid and 2 was a rare 20-norcassane diterpenoid having an unusual five-membered oxygen bridge between C-10/C-18. The anti-proliferative activity of 1, 3, and 4-10 against PANC-1 cells (pancreatic ductal adenocarcinoma cell line) was evaluated, and phanginin H (4) was found to exhibit anti-cancer activity with IC50 value of 18.13 ± 0.63 µM. Compound 4 inhibited PANC-1 cell growth by arresting the cell cycle at G2/M phase via regulation of cyclin-dependent kinases, and the self-renewal and metastasis of PANC-1 cells by suppressing cancer cell stemness. Furthermore, compound 4 induced ROS generation and subsequently activated autophagy, which was demonstrated by the formation of autophagic vacuoles and dynamic change of autophagic flux. The induced ROS accumulation resulted in AMPK activation and subsequently regulation of mTORC1 activity and ULK phosphorylation, indicating that 4 triggered autophagy through ROS/AMPK/mTORC1 pathway. These findings suggested that 4 might potentially be an autophagy inducer for the therapy of pancreatic cancer.

Association of the triglyceride-glucose index with early-onset atherosclerotic cardiovascular disease events and all-cause mortality: a prospective cohort study.

BACKGROUND: The association between the triglyceride glucose (TyG) index and the risk of early-onset atherosclerotic cardiovascular disease (ASCVD) events or all-cause mortality in young and middle-aged people is not fully elucidated. METHODS: The present study included 64,489 young and middle-aged people who participated in the 2006 Kailuan Study physical examination. Multivariate Cox proportional hazards models and restricted cubic spline curves were used to assess the association of TyG index with early-onset ASCVD events and all-cause mortality. RESULTS: During a median of 11-year follow-up, 1984 (3.08%) participants experienced at least one ASCVD event and 1,392 (2.16%) participants experienced all-cause death. A higher TyG index was significantly associated with a higher risk of early-onset ASCVD events (HR: 1.61, 95% CI 1.38-1.89) and all-cause mortality (HR: 1.39, 95% CI 1.17-1.65), respectively. For each unit increase in TyG index, the risk of early-onset ASCVD events increased by 20%. In addition, there was a non-linear association between the TyG index and early-onset ASCVD events (P for non-linear < 0.01), and a linear association between TyG index and all-cause mortality (P for non-linear = 0.476). CONCLUSIONS: A higher TyG index is significantly associated with an increased incidence of early-onset ASCVD events and all-cause mortality in a young and middle-aged population from North China.

Spartina alterniflora invasion altered phosphorus retention and microbial phosphate solubilization of the Minjiang estuary wetland in southeastern China.

Spartina alterniflora invasion is considered a critical event affecting sediment phosphorus (P) availability and stock. However, P retention and microbial phosphate solubilization in the sediments invaded with or without S. alterniflora have not been fully investigated. In this study, a sequential fractionation method and high-throughput sequencing were used to analyze P transformation and the underlying microbial mechanisms in the sediments of no plant (NP) zone, transition (T) zone, and plant (P) zone. Results showed that except for organic phosphate (OP), total phosphate (TP), inorganic phosphate (IP), and available phosphate (AP) all followed a significant decrease trend from the NP site to the T site, and to the P site. The vertical decrease of TP, IP, and AP was also observed with an increase in soil depth. Among the six IP fractions, Fe-P, Oc-P, and Ca10-P were the predominant forms, while the presence of S. alterniflora resulted in an obvious P depletion except for Ca8-P and Al-P. Although S. alterniflora invasion did not significantly alter the alpha diversity of phosphate-solubilizing bacteria (PSB) harboring phoD gene, several PSB belonging to p_Proteobacteria, p_Planctomycetes, and p_Cyanobacteriota showed close correlations with P speciation and IP fractions. Further correlation analysis revealed that the reduced soil pH, soil TN and soil EC, and the increased soil TOC mediated by the invasion of S. alterniflora also significantly correlated to these PSB. Overall, this study elucidates the linkage between PSB and P speciation and provides new insights into understanding P retention and microbial P transformation in the coastal sediment invaded by S. alterniflora.

TET3 boosts hepatocyte autophagy and impairs non-alcoholic fatty liver disease by increasing ENPP1 promoter hypomethylation.

BACKGROUND: Dysregulated ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family occurs in metabolic reprogramming pathological processes. Nonetheless, the epigenetic mechanisms by which ENPP family impacts NAFLD, also known as metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly appreciated. METHODS: We investigated the causes and consequences of ENPP1 promoter hypomethylation may boost NAFLD using NAFLD clinical samples, as well as revealed the underlying mechanisms using high-fat diet (HFD) + carbon tetrachloride (CCl4) induced mouse model of NAFLD and FFA treatment of cultured hepatocyte. RESULTS: Herein, we report that the expression level of ENPP1 are increased in patients with NAFLD liver tissue and in mouse model of NAFLD. Hypomethylation of ENPP1, is associated with the perpetuation of hepatocyte autophagy and liver fibrosis in the NAFLD. ENPP1 hypomethylation is mediated by the DNA demethylase TET3 in NAFLD liver fibrosis and hepatocyte autophagy. Additionally, knockdown of TET3 methylated ENPP1 promoter, reduced the ENPP1 expression, ameliorated the experimental NAFLD. Mechanistically, TET3 epigenetically promoted ENPP1 expression via hypomethylation of the promoter. Knocking down TET3 can inhibit the hepatocyte autophagy but an overexpression of ENPP1 showing rescue effect. CONCLUSIONS: We describe a novel epigenetic mechanism wherein TET3 promoted ENPP1 expression through promoter hypomethylation is a critical mediator of NAFLD. Our findings provide new insight into the development of preventative measures for NAFLD.

Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

The effect of life events on NSSI: the chain mediating effect of sleep disturbances and PLEs among Chinese college students.

This study aimed to explore the relationship between life events and non-suicidal self-injury (NSSI) in college students, as well as the mediating effect of sleep disturbances and psychotic-like experiences (PLEs). After excluding invalid questionnaires, 5,754 were retained, and the valid efficiency was 75.94%. The subjects were aged 16 to 29 years (M = 19.166; SD = 1.392), with 1,969 males (34.22%) and 3,785 females (65.78%). Life events, sleep disturbances, PLEs, and NSSI were assessed using standard scales. Data were analyzed by Pearson Correlation Analysis and bias-correction percentile Bootstrap method. The results show that (1) life events were significant positive predictors of NSSI, sleep disturbances, and PLEs; (2) sleep disturbances, PLEs, and the chain mediation between the two, were mediators between life events and NSSI. Life events are thus shown to be an important external factor influencing NSSI in university students, and this process is mediated through sleep disturbances, PLEs, and the chain between the two. Interventions for NSSI can therefore be made by improving college students' sleep quality and reducing PLEs.

Melatonin Alleviates BPA-Induced Testicular Apoptosis and Endoplasmic Reticulum Stress.

BACKGROUND: The impact of melatonin on bisphenol A (BPA)-induced testicular apoptosis and endoplasmic reticulum (ER) stress was explored. METHODS: The mice received BPA (50 mg/kg) by gavage for 30 days while being injected with 20 mg/kg melatonin. Protein expressions were detected with western blotting. The Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay measured testicular cell apoptosis. Testosterone was quantified by employing enzyme-linked immunosorbent assay (ELISA). RESULTS: Melatonin promoted the development of seminiferous tubules, restored the orderly arrangement of the germ cells, and increased epithelial layers in the seminiferous tubules in BPA-treated mice. Moreover, in BPA-treated mouse testicular cells, melatonin markedly upregulated melatonin receptor 1A (MTNR1A) and melatonin Receptor 2 (MTNR2) expressions while downregulating ER molecular chaperones glucose-regulated protein 78 (GRP78) and glucose-regulated protein 94 (GRP94). Furthermore, it decreased p-PERK, p-IRE1, and ATF6α, as well as the apoptotic proteins cysteine-containing aspartate-specific proteases-12 (caspase-12) and cleaved cysteine-containing aspartate-specific proteases-3 (cleaved caspase-3), causing the suppression of testicular cell apoptosis. Additionally, melatonin increased the levels of cytochrome P450 17α-hydroxylase/20-lyase (CYP17A1), 17ß-hydroxysteroid dehydrogenase 3 (17ß-HSD3), and 3ß-hydroxysteroid dehydrogenase 4 (3ß-HSD4), in the ER, and elevated testosterone levels in testicular tissue. CONCLUSIONS: Melatonin can significantly alleviate testicular apoptosis and ER stress induced by BPA, which is because of the upregulation of melatonin receptor expression in testicular cells, inhibition of ER stress-related pathways, and enhancement of testosterone synthesis.