PSTPIP2 protects against alcoholic liver injury and invokes STAT3-mediated suppression of apoptosis.

Alcoholic liver injury (ALI) stands as a prevalent affliction within the spectrum of complex liver diseases. Prolonged and excessive alcohol consumption can pave the way for liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Recent findings have unveiled the protective role of proline serine-threonine phosphatase interacting protein 2 (PSTPIP2) in combating liver ailments. However, the role of PSTPIP2 in ALI remains mostly unknown. This study aimed to determine the expression profile of PSTPIP2 in ALI and to uncover the mechanism through which PSTPIP2 affects the survival and apoptosis of hepatocytes in ALI, using both ethyl alcohol (EtOH)-fed mice and an EtOH-induced AML-12 cell model. We observed a consistent decrease in PSTPIP2 expression both in vivo and in vitro. Functionally, we assessed the impact of PSTPIP2 overexpression on ALI by administering adeno-associated virus 9 (AAV9)-PSTPIP2 into mice. The results demonstrated that augmenting PSTPIP2 expression significantly shielded against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis in EtOH-induced ALI mice. Furthermore, enforcing PSTPIP2 expression reduced hepatocyte apoptosis in a stable PSTPIP2-overexpressing AML-12 cell line established through lentivirus-PSTPIP2 transfection in vitro. Mechanistically, this study also identified signal transducer and activator of transcription 3 (STAT3) as a direct signaling pathway regulated by PSTPIP2 in ALI. In conclusion, our findings provide compelling evidence that PSTPIP2 has a regulatory role in hepatocyte apoptosis via the STAT3 pathway in ALI, suggesting PSTPIP2 as a promising therapeutic target for ALI.

Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study.

PURPOSE: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. METHODS: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. RESULTS: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/µL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. CONCLUSIONS: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

Vergence-Accommodation Conflict: Increased Presbyopia in Virtual Reality.

BACKGROUND: Performance and symptoms in completing a visual search task on a PC monitor and using a head-mounted display (HMD) were compared for different viewing conditions and between users of different ages. PATIENTS AND METHODS: Twenty-three young (M = 30 y, SD = 7 y) and 23 older (M = 52 y, SD = 5 y) participants performed a visual search task presented on a PC monitor. The task was repeated using an HMD for a near and a far virtual viewing distance. Reaction times (RT), detection sensitivity (d'), and symptoms were recorded for the three different viewing conditions. RESULTS: RT and d' were not affected by the viewing condition (p > 0.05). In contrast, symptoms significantly depended on the viewing condition but were, in part, not significantly affected by age. It is interesting to note that although not significant, young participants reported more ocular symptoms than older participants in the near vision task carried out using the HMD. DISCUSSION: HMD increases visual symptoms. However, HMD could be, in part, a remedy to problems when using visual aids for near work, in particular for presbyopes.

Synergistic B and T lymphocyte interaction: prognostic implications in non-small cell lung cancer.

While T-cell-mediated immune responses in solid tumors have been well-established and have driven major therapeutic advances, our understanding of B-cell biology in cancer is comparatively less developed. A total of 60 lung cancer patients were included, of which 53% were diagnosed at an early stage while 47% were diagnosed at an advanced stage. Flow cytometry was used to analyze the proportion of T and B cells in all blood samples, and the levels of human serum cytokines were also assessed. Compared to the control group, cancer patients showed lower frequencies of IgD+CD27+ marginal B cells and CD32+ B cells, and higher frequencies of T cells with lower CD8+ T cells and higher central memory and naïve CD4+ T cells. Additionally, advanced-stage cancer patients exhibited higher levels of cytokines, a higher proportion of effector memory CD8+ T cells, and a lower frequency of CD27+CD28+CD4+/CD8+ T cells. Linear regression analysis revealed significant correlations between cancer stage and the frequency of B and T cell subsets, leukocyte count, and cytokine levels. Survival analysis demonstrated that patients with higher frequency of class-switched B cells had a worse prognosis, while patients with higher frequency of CD8+ effector T cells and lower frequency of CD4+57+ T cells appeared to have a better survival rate. These findings provide valuable insight into the immunological changes that occur during lung cancer progression and have the potential to inform the development of new immunotherapeutic strategies.

Exploring the evolution of T cell function and diversity across different stages of non-small cell lung cancer.

The immune system plays a key role in detecting and fighting cancerous tumors. T cells are a crucial component in both natural and therapeutic cancer immunoediting responses, but it is unclear if they are the primary agents of these processes. In this study, patients with lung lesions detected by CT scan were selected, and their peripheral blood samples were analyzed for T cell population and serum cytokines/chemokines. T cell subtypes (CD3, CD4, CD8, CD27, CD28, CD45, CD45RA, CD57, CCR7, and PD1) and serum cytokines/chemokines (IL-2, IL-6, IL-10, IFN-γ, TGF-ß, TNFα, CXCL1, CXCL9, and CXCL12) were measured by flow cytometry and analysis before surgical resection or other cancer treatments. The frequency of T cell subpopulations in patients with lung cancer (n = 111) corresponded to those seen in patients with T cell exhaustion. As lung cancer progressed, the proportion of effector memory T cells decreased, while the proportion of naive T cells, PD-1, CD57+, CD28+CD27+, CD45RA+, and CD3+CD4+CCR7 increased. Circulating CD8+PD1+ T cells were positively correlated with intra-tumoral PD-L1 expression. Concurrently, serum levels of IL-2, TGF-ß, and CXCL9 decreased, while IL-6, IL-10, IFN-γ, and CXCL12 increased during the progression of lung cancer. In conclusion, T cell dysfunction is associated with cancer progression, particularly in advanced-stage lung cancer, and cancer immunoediting will provide early-stage cancer detection and further therapeutic strategies.

Phyllanthus emblica Fruit Improves Obesity by Reducing Appetite and Enhancing Mucosal Homeostasis via the Gut Microbiota-Brain-Liver Axis in HFD-Induced Leptin-Resistant Rats.

The impact of leptin resistance on intestinal mucosal barrier integrity, appetite regulation, and hepatic lipid metabolism through the microbiota-gut-brain-liver axis has yet to be determined. Water extract of Phyllanthus emblica L. fruit (WEPE) and its bioactive compound gallic acid (GA) effectively alleviated methylglyoxal (MG)-triggered leptin resistance in vitro. Therefore, this study investigated how WEPE and GA intervention relieve leptin resistance-associated dysfunction in the intestinal mucosa, appetite, and lipid accumulation through the microbiota-gut-brain-liver axis in high-fat diet (HFD)-fed rats. The results showed that WEPE and GA significantly reduced tissues (jejunum, brain, and liver) MG-evoked leptin resistance, malondialdehyde (MDA), proinflammatory cytokines, SOCS3, orexigenic neuropeptides, and lipid accumulation through increasing leptin receptor, tight junction proteins, antimicrobial peptides, anorexigenic neuropeptides, excretion of fecal triglyceride (TG), and short-chain fatty acids (SCFAs) via a positive correlation with the Allobaculum and Bifidobacterium microbiota. These novel findings suggest that WEPE holds the potential as a functional food ingredient for alleviating obesity and its complications.

New insights into the stipitate hydnoid fungi Sarcodon, Hydnellum, and the formerly informally defined Neosarcodon, with emphasis on the edible species marketed in Southwest China.

Sarcodon and Hydnellum are two ectomycorrhizal genera of important ecological and economic value in Southwest China, and they are common in the free markets in this region. It was estimated that more than 1,500 tonnes of them were sold as edible per year, but there was little information about the taxonomic placements of these edible mushrooms sold in the markets. Traditional concepts of the two genera have also been challenged recently, and circumscription of Sarcodon and the informally defined clade "Neosarcodon" remained unresolved. In the present study, specimens collected in the field and purchased from the markets in Southwest China were analyzed based on morphological characters and DNA sequences. Phylogeny of the traditional Sarcodon s. lat. and Hydnellum s. lat. was reconstructed from the combined internal transcribed spacer (ITS), nuclear large ribosomal subunit (nLSU) and RNA polymerase II second largest subunit (RPB2) dataset based on expanded samples to reevaluate the taxonomic placements of the two genera. In the present molecular analyses, four distinct clades were recovered and strongly supported: Hydnellum, Neosarcodon, Phellodon and Sarcodon. Neosarcodon is formally introduced as a generic name to include nine species previously placed in Sarcodon, and the delimitation of Sarcodon is revised based on phylogenetic and morphological studies. Phylogenetic analyses also revealed an unexpected species diversity (17 phylogenetic species) of Sarcodon and Hydnellum in the markets; nine phylogenetic species of Sarcodon and eight of Hydnellum were uncovered from the samples collected in the markets. Eight species were resolved in the traditional S. imbricatus complex, with S. imbricatus s.str. being the most common edible stipitate hydnoid fungal species. Three of the edible Hydnellum species (H. edulium, H. subalpinum, and H. subscabrosellum), and five separated from the S. imbricatus complex (Sarcodon flavidus, S. giganteus, S. neosquamosus, S. nigrosquamosus, and S. pseudoimbricatus), are described as new. Three new Chinese records (H. illudens, H. martioflavum, and H. versipelle), and the notable S. imbricatus and S. leucopus are also reported.

Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats.

As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.

Racial and ethnic determinants of psoriatic arthritis phenotypes and disease activity.

OBJECTIVE: Individuals of racially and ethnically diverse backgrounds are underrepresented in psoriatic arthritis (PsA) research/clinical trials, despite evidence that their disease presentation, severity and course may be distinct. Here we aim to describe how race, ethnicity and other socioeconomic factors inform disease characteristics in PsA. METHODS: 817 consecutive patients with PsA from a large, diverse metropolitan area, were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype and activity were all recorded and analyzed. RESULTS: The population was 77.4% non-Hispanic White, 2.2% Black, 7.1% Asian, and 9.9% identified as other races or multiracial, and 11.8% identified as Hispanic. Hispanic and non-White individuals had higher tender joint counts (p= 0.033) with similar swollen joint counts (p= 0.308) and medication use (p= 0.171). They also had high rates of radiographic axial disease. Hispanic individuals were significantly more likely to have higher tender joint counts (p= 0.029), higher RAPID3 scores (p= 0.004), and moderate-severe psoriasis (p= 0.010) compared with non-Hispanic White individuals. CONCLUSION: In this diverse cohort, 22.6% of patients identified as underrepresented racial and/or ethnic groups, mostly Asian or Hispanic. Despite similar swollen joint counts and medication use, non-white individuals have higher tender joint counts compared with white individuals. Phenotypically, they also were more likely to have radiographic axial involvement. These findings may reflect differences in PsA presentation, experience and outcomes in individuals of various racial and ethnic groups, which need to be taken into consideration in clinical care and research design.

Small-molecule antiviral treatments for COVID-19: A systematic review and network meta-analysis.

OBJECTIVE: This study aimed to explore the efficacy and safety of small-molecule antivirals for treating coronavirus disease 2019 (COVID-19). METHODS: Seven databases were searched from their inception to 01 June 2023. The risk of bias in randomised controlled trials and retrospective studies was evaluated individually using the Cochrane risk-of-bias tool and Newcastle Ottawa Scale. RESULTS: In total, 160 studies involving 933 409 COVID-19 patients were evaluated. Compared with placebo or standard of care, proxalutamide demonstrated remarkable efficacy in reducing mortality rates, hospitalisation rates, serious adverse events, and the need for mechanical ventilation. Furthermore, it significantly enhanced both the rate of clinical improvement and expedited the duration of clinical recovery when compared with control groups. In patients with mild-to-moderate COVID-19, proxalutamide exhibited the above advantages, except for mortality reduction. Triazavirin was the most effective treatment for reducing the time required for viral clearance and improving the discharge rate. Leritrelvir and VV116 were ranked first in terms of enhancing the viral clearance rate on days 7 and 14, respectively. Molnupiravir was the most effective treatment for reducing the need for oxygen support. Overall, these findings remained consistent across the various subgroups. CONCLUSIONS: A thorough evaluation of effectiveness, applicable to both mild-to-moderate and unstratified populations, highlights the specific advantages of proxalutamide, nirmatrelvir/ritonavir, triazavirin, azvudine, molnupiravir, and VV116 in combating COVID-19. Additional clinical data are required to confirm the efficacy and safety of simnotrelvir/ritonavir and leritrelvir. The safety profiles of these antivirals were deemed acceptable.

Enhancing self-care education amongst medical students: a systematic scoping review.

BACKGROUND: Reports of emotional, existential and moral distress amongst medical students witnessing death and suffering of patients during their clinical postings have raised awareness on the need for better psycho-emotional support during medical school. Furthermore, the stress experienced by medical students stemming from the rigours of their academic curriculum underlines the need for greater awareness on mental health issues and better self-care practices across medical training. With such programmes lacking in most medical schools, we propose a systematic scoping review (SSR) to map and address our research question, "what is known about self-care education interventions amongst medical students?". METHODS: We adopted the Systematic Evidence-Based Approach to guide a systematic scoping review (SSR in SEBA) of relevant articles published between 1st January 2000 and 30th June 2023 in PubMed, Embase, PsycINFO, ERIC, Google Scholar, and Scopus databases. The included articles were independently and concurrently thematically and content analysed, with complementary categories and themes combined using the Jigsaw Approach. The domains created from the Funnelling Process framed the discussion. RESULTS: A total of 6128 abstracts were identified, 429 full-text articles evaluated, and 147 articles included. The 6 domains identified were definition, topics, pedagogy, influences, outcomes and assessment. Most interventions were promising, though peer-led mindfulness-based interventions showed most promise in enhancing engagement, positively impacting personal wellbeing, and improving patient care. Overall, however, self-care education was poorly recognized, adopted and integrated into curricula. CONCLUSION: Greater dedicated time and conducive practice environments within medical school curricula is required to enhance medical student wellbeing. Host organizations must ensure faculty are appropriately selected to instil the importance of self-care, be trained to assess and personalize self-care interventions and provide longitudinal assessment and support. Further study into assessing self-care capabilities is required.

Phloretin targets SIRT1 to alleviate oxidative stress, apoptosis, and inflammation in deep venous thrombosis.

Deep vein thrombosis (DVT) is a type of venous thromboembolism posing a serious threat to health on a global scale. Phloretin is a potential natural product that has a variety of pharmacological activities. Besides, some Chinese medicines reported that deacetylase sirtuin (SIRT)1 treats DVT by anti-inflammatory and anti-platelet production. However, the specific binding targets and binding modes have not been elaborated. The present study was to investigate whether phloretin attenuates DVT in model rats and oxidized low­density lipoprotein (ox­LDL) induced human umbilical vein endothelial cells (HUVECs), and to explore its potential target. The results revealed that the treatment of phloretin, especially pretreatment of it elevated tissue plasminogen activator (t-PA), superoxide dismutase (SOD), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and cell apoptosis proteins whereas it suppressed plasminogen activator inhibitor (PAI), malondialdehyde (MDA), reactive oxygen species (ROS), fibrinogen (FIB) in DVT rats and cells. Concurrently, phloretin inhibited collagen type I alpha 1 (COL1A1), transforming growth factor-ß1 (TGF-ß1), and inflammatory factors while it enhanced nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase 1 (HO-1). In addition, 20 µM phloretin exerted powerful effective protection in HUVECs with DVT model. Later, the surface plasmon resonance (SPR) confirmed that phloretin has a high affinity with SIRT1. Furthermore, siRNA-SIRT1 transfection abolished the protective effect of phloretin against ox­LDL­induced DVT in HUVECs, indicating that phloretin targets SIRT1 to alleviate oxidative stress, cell apoptosis, and inflammation in DVT rats and HUVECs. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00207-y.

Hesperetin derivative 2a inhibits lipopolysaccharide-induced acute liver injury in mice via downregulation of circDcbld2.

Acute liver injury (ALI) is a complex, life-threatening inflammatory liver disease, and persistent liver damage leads to rapid decline and even failure of liver function. However, the pathogenesis of ALI is still not fully understood, and no effective treatment has been discovered. Recent evidence shows that many circular RNAs (circRNAs) are associated with the occurrence of liver diseases. In this study we investigated the mechanisms of occurrence and development of ALI in lipopolysaccharide (LPS)-induced ALI mice. We found that expression of the circular RNA circDcbld2 was significantly elevated in the liver tissues of ALI mice and LPS-treated RAW264.7 cells. Knockdown of circDcbld2 markedly alleviates LPS-induced inflammatory responses in ALI mice and RAW264.7 cells. We designed and synthesized a series of hesperidin derivatives for circDcbld2, and found that hesperetin derivative 2a (HD-2a) at the concentrations of 2, 4, 8 µM effectively inhibited circDcbld2 expression in RAW264.7 cells. Administration of HD-2a (50, 100, 200 mg/kg. i.g., once 24 h in advance) effectively relieved LPS-induced liver dysfunction and inflammatory responses. RNA sequencing analysis revealed that the anti-inflammatory and hepatoprotective effects of HD-2a were mediated through downregulating circDcbld2 and suppressing the JAK2/STAT3 pathway. We conclude that HD-2a downregulates circDcbld2 to inhibit the JAK2/STAT3 pathway, thereby inhibiting the inflammatory responses in ALI. The results suggest that circDcbld2 may be a potential target for the prevention and treatment of ALI, and HD-2a may have potential as a drug for the treatment of ALI.

Executive functions of obese adolescents / 中国学校卫生

Objective@#To explore of executive function in obese adolescents, so as to provide a reference for executive function enhancement intervention in obese adolescents.@*Methods@#A convenience sample of 1 227 adolescents aged 13-18 years was selected from 2 secondary schools in Taiyuan City during March-April 2023. The Flanker task, N-back task and More odd shifting task was used to compare the different subfunctions of executive function (refreshing function, shifting function, inhibiting function) of 61 obese adolescents and 70 normal weight adolescents. Independent samples t-tests was used for between group comparisons and Cohen s d -tests was used to calculate between group differences in executive function between the two groups of adolescents.@*Results@#Compared with the group of normal weight, time responses of the inhibitory function [(29.73±19.55)ms], the refreshing function [1-back: (1 088.75±275.76)ms, 2-back:( 1 285.44± 355.16)ms] and the shifting function [(380.34±153.18) ms] in the obese group were significantly longer than those in the normal weight group [(14.86±20.27, 888.38±286.57, 1 126.20± 287.43 , 323.12±134.71) ms] ( t =4.26, 4.06, 1.92,2.26, P < 0.05 ); inhibitory function (0.91±0.09) and 1-back (0.73±0.24) were also significantly less correct than in the normal weight group (0.94±0.05, 0.83±0.21) ( t =-2.04, -2.04, P <0.05). Obese adolescents showed moderate adverse effect sizes in the inhibition function ( d =0.746,0.712) and the refresh function 1-back, and smaller adverse effect sizes in the refresh function 2-back and the conversion function( d =0.497,0.398).@*Conclusion@#Obese adolescents have significant executive function deficits, but the degree of adverse varies across sub-functions, with inhibitory function being the core deficit component of executive function in obese adolescents.

Liquiritin apioside alleviates colonic inflammation and accompanying depression-like symptoms in colitis by gut metabolites and the balance of Th17/Treg.

BACKGROUND: Inflammatory bowel disease (IBD) is a significant global health concern that can lead to depression in affected patients. Liquiritin apioside (LA) possesses anti-oxidative and anti-inflammatory properties. However, its anti-inflammatory mechanism in IBD has not been extensively studied. PURPOSE: This study elucidates the pivotal role of LA in alleviating inflammation by regulating gut metabiota-derived metabolites and evaluating its regulative effects on promoting a balance of Th17/Treg cells in colitis mice. METHODS: To evaluate the effect of LA on IBD,16S rRNA gene sequencing and UPLC-QTOF-MS analysis were used to identify the changes of intestinal bacteria and their metabolites. Cytokines levels were determined by ELISA and qPCR, while immune cell ratios were evaluated via flow cytometry. RESULTS: Our findings revealed that LA treatment ameliorated general states of DSS-induced colitis mice and their accompanying depressive behaviors. Moreover, LA restricted the expression of pro-inflammatory cytokines and revised the imbalanced Treg/Th17 differentiation, while promoting SCFAs production in inflamed colon tissues. Fecal microbiota transplantation from LA-fed mice also corrected the imbalanced Treg/Th17 differentiation, indicating that LA-mediated restoration of the colonic Treg/Th17 balance mainly depends on the changes in gut metabolites. CONCLUSION: These results provide scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols, and suggesting that LA could be used as a potential dietary supplement for the prevention and improvement of IBD.

Head-mounted display versus computer monitor for visual attention screening: A comparative study.

Visual attention is crucial to many tasks during working. When it is impaired, the risk of occupational accidents is increased. A potential accident prevention would be the tracking of employees' attentional states to construct break regimes. There is a promising visual attention test administered on a computer monitor (CM) that has several advantages over widely used continuous performance tests in detecting inattentiveness in occupational environments. However, as the setup with a CM is impractical for the use in particular working environments (e.g., lack of space or disturbing exposure to light), the test was implemented into a head-mounted display (HMD). This study aimed to investigate whether the HMD version of the test is a suitable alternative to the CM version. For this purpose, participants (N = 30; 20-29 y) performed both tests. The performance on the HMD was significantly lower than on the CM. Moreover, the performances were compared with normative data recorded with a CM in a previous study. These data significantly differ from the data recorded with the CM in the present study. This emphasizes the importance of a standardized test environment, which could be provided by an HMD. Conclusively, this study revealed that the new VR tool, based on a previous test designed to assess visual skills in a complex visual environment, exhibited good psychometric property regarding the reliability. In additional, no problems were revealed regarding the functionality and usability of the HMD.

N6-methyladenosine-modified circIRF2, identified by YTHDF2, suppresses liver fibrosis via facilitating FOXO3 nuclear translocation.

Circular RNA (circRNA) has been implicated in liver fibrosis and modulated by multiple elusive molecular mechanisms, while the effects of N6-methyladenosine (m6A) modification on circRNA are still elusive. Herein, we identify circIRF2 from our circRNA sequencing data, which decreased in liver fibrogenesis stage and restored in resolution stage, indicating that dysregulated circIRF2 may be closely associated with liver fibrosis. Gain/loss-of-function analysis was performed to evaluate the effects of circIRF2 on liver fibrosis at both the fibrogenesis and resolution in vivo. Ectopic expression of circIRF2 attenuated liver fibrogenesis and HSCs activation at the fibrogenesis stage, whereas downregulation of circIRF2 impaired mouse liver injury repair and inflammation resolution. Mechanistically, YTHDF2 recognized m6A-modified circIRF2 and diminished circIRF2 stability, partly accounting for the decreased circIRF2 in liver fibrosis. Microarray was applied to investigate miRNAs regulated by circIRF2, our data elucidate cytoplasmic circIRF2 may directly harbor miR-29b-1-5p and competitively relieve its inhibitory effect on FOXO3, inducing FOXO3 nuclear translocation and accumulation. Clinically, circIRF2 downregulation was prevalent in liver fibrosis patients compared with healthy individuals. In summary, our findings offer a novel insight into m6A modification-mediated regulation of circRNA and suggest that circIRF2 may be an exploitable prognostic marker and/or therapeutic target for liver fibrosis.

Is Azvudine Comparable to Nirmatrelvir-Ritonavir in Real-World Efficacy and Safety for Hospitalized Patients with COVID-19? A Retrospective Cohort Study.

INTRODUCTION: Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China. METHODS: This retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion (PNANC), time to first nucleic-acid negative conversion (TFNANC), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes. RESULTS: This study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56-3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78-3.60; P = 0.189), PNANC (HR 0.87; 95% CI 0.69-1.09; P = 0.220), length of stay (ß - 0.82; 95% CI - 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer TFNANC (ß 2.53; 95% CI 0.76-4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses. CONCLUSION: Azvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes.

Multi-wavelength multi-direction laser light scattering for cell characterization using machine learning-based methods.

Cell identification and analysis play a crucial role in many biology- and health-related applications. The internal and surface structures of a cell are complex and many of the features are sub-micron in scale. Well-resolved images of these features cannot be obtained using optical microscopy. Previous studies have reported that the single-cell angular laser-light scattering patterns (ALSP) can be used for label-free cell identification and analysis. The ALSP can be affected by cell properties and the wavelength of the probing laser. Two cell properties, cell surface roughness and the number of mitochondria, are investigated in this study. The effects of probing laser wavelengths (blue, green, and red) and the directions of scattered light collection (forward, side, and backward) are studied to determine the optimum conditions for distinguishing the two cell properties. Machine learning (ML) analysis has been applied to ALSP obtained from numerical simulations. The results of ML analysis show that the backward scattering is the best direction for characterizing the surface roughness, while the forward scattering is the best direction for differentiating the number of mitochondria. The laser light having red or green wavelength is found to perform better than that having the blue wavelength in differentiating the surface roughness and the number of mitochondria. This study provides important insights into the effects of probing laser wavelength on gaining information about cells from their ALSP.