Establishment and Evaluation of a Noninvasive Metabolism-Related Fatty Liver Screening and Dynamic Monitoring Model: Cross-Sectional Study.

BACKGROUND: Metabolically associated fatty liver disease (MAFLD) insidiously affects people's health, and many models have been proposed for the evaluation of liver fibrosis. However, there is still a lack of noninvasive and sensitive models to screen MAFLD in high-risk populations. OBJECTIVE: The purpose of this study was to explore a new method for early screening of the public and establish a home-based tool for regular self-assessment and monitoring of MAFLD. METHODS: In this cross-sectional study, there were 1758 eligible participants in the training set and 200 eligible participants in the testing set. Routine blood, blood biochemistry, and FibroScan tests were performed, and body composition was analyzed using a body composition instrument. Additionally, we recorded multiple factors including disease-related risk factors, the Forns index score, the hepatic steatosis index (HSI), the triglyceride glucose index, total body water (TBW), body fat mass (BFM), visceral fat area, waist-height ratio (WHtR), and basal metabolic rate. Binary logistic regression analysis was performed to explore the potential anthropometric indicators that have a predictive ability to screen for MAFLD. A new model, named the MAFLD Screening Index (MFSI), was established using binary logistic regression analysis, and BFM, WHtR, and TBW were included. A simple rating table, named the MAFLD Rating Table (MRT), was also established using these indicators. RESULTS: The performance of the HSI (area under the curve [AUC]=0.873, specificity=76.8%, sensitivity=81.4%), WHtR (AUC=0.866, specificity=79.8%, sensitivity=80.8%), and BFM (AUC=0.842, specificity=76.9%, sensitivity=76.2%) in discriminating between the MAFLD group and non-fatty liver group was evaluated (P<.001). The AUC of the combined model including WHtR, HSI, and BFM values was 0.900 (specificity=81.8%, sensitivity=85.6%; P<.001). The MFSI was established based on better performance at screening MAFLD patients in the training set (AUC=0.896, specificity=83.8%, sensitivity=82.1%) and was confirmed in the testing set (AUC=0.917, specificity=89.8%, sensitivity=84.4%; P<.001). CONCLUSIONS: The novel MFSI model was built using WHtR, BFM, and TBW to screen for early MAFLD. These body parameters can be easily obtained using a body fat scale at home, and the mobile device software can record specific values and perform calculations. MFSI had better performance than other models for early MAFLD screening. The new model showed strong power and stability and shows promise in the area of MAFLD detection and self-assessment. The MRT was a practical tool to assess disease alterations in real time.

Studying temperature's impact on Brassica napus resistance to identify key regulatory mechanisms using comparative metabolomics.

To investigate the effects of temperature on Brassica napus (canola) resistance to Leptosphaeria maculans (LM), the causal agent of blackleg disease, metabolic profiles of LM infected resistant (R) and susceptible (S) canola cultivars at 21 °C and 28 °C were analyzed. Metabolites were detected in cotyledons of R and S plants at 48- and 120-h post-inoculation with LM using UPLC-QTOF/MS. The mock-inoculated plants were used as controls. Some of the resistance-related specific pathways, including lipid metabolism, amino acid metabolism, carbohydrate metabolism, and aminoacyl-tRNA biosynthesis, were down-regulated in S plants but up-regulated in R plants at 21 °C. However, some of these pathways were down-regulated in R plants at 28 °C. Amino acid metabolism, lipid metabolism, alkaloid biosynthesis, phenylpropanoid biosynthesis, and flavonoid biosynthesis were the pathways linked to combined heat and pathogen stresses. By using network analysis and enrichment analysis, these pathways were identified as important. The pathways of carotenoid biosynthesis, pyrimidine metabolism, and lysine biosynthesis were identified as unique mechanisms related to heat stress and may be associated with the breakdown of resistance against the pathogen. The increased susceptibility of R plants at 28 °C resulted in the down-regulation of signal transduction pathway components and compromised signaling, particularly during the later stages of infection. Deactivating LM-specific signaling networks in R plants under heat stress may result in compatible responses and deduction in signaling metabolites, highlighting global warming challenges in crop disease control.

"Bottom-up" and "top-down" strategies toward strong cellulose-based materials.

Cellulose, as the most abundant natural polymer on Earth, has long captured researchers' attention due to its high strength and modulus. Nevertheless, transferring its exceptional mechanical properties to macroscopic 2D and 3D materials poses numerous challenges. This review provides an overview of the research progress in the development of strong cellulose-based materials using both the "bottom-up" and "top-down" approaches. In the "bottom-up" strategy, various forms of regenerated cellulose-based materials and nanocellulose-based high-strength materials assembled by different methods are discussed. Under the "top-down" approach, the focus is on the development of reinforced cellulose-based materials derived from wood, bamboo, rattan and straw. Furthermore, a brief overview of the potential applications fordifferent types of strong cellulose-based materials is given, followed by a concise discussion on future directions.

Radix Isatidis polysaccharide (RIP) alleviates QX-genotype infectious bronchitis virus-induced interstitial nephritis through the Nrf2/NLRP3/Caspase-3 signaling pathway.

Interstitial nephritis is the primary cause of mortality in IBV-infected chickens. Our previous research has demonstrated that Radix Isatidis polysaccharide (RIP) could alleviate this form of interstitial nephritis. To explore the mechanism, SPF chickens and chicken embryonic kidney cells (CEKs) were pre-treated with RIP and subsequently infected with QX-genotype IBV strain. Kidneys were sampled for transcriptomic and metabolomic analyses, and the cecum contents were collected for 16S rRNA gene sequencing. Results showed that pre-treatment with RIP led to a 50 % morbidity reduction in infected-chickens, along with decreased tissue lesion and viral load in the kidneys. Multi-omics analysis indicated three possible pathways (including antioxidant, anti-inflammatory and anti-apoptosis) which associated with RIP's efficacy against interstitial nephritis. Following further validation both in vivo and in vitro, the results showed that pre-treatment with RIP could activate the antioxidant transcription factor Nrf2, stimulate antioxidant enzyme expression, and consequently inhibit oxidative stress. Pre-treatment with RIP could also significantly reduce the expression of NLRP3 inflammasome and apoptosis-associated proteins (including Bax, Caspase-3, and Caspase-9). Additionally, RIP was also observed to promote the growth of beneficial bacteria in the intestine. Overall, pretreatment with RIP can alleviate QX-genotype IBV-induced interstitial nephritis via the Nrf2/NLRP3/Caspase-3 signaling pathway. This study lays the groundwork for the potential use of RIP in controlling avian infectious bronchitis (IB).

PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation.

Senescence of nondividing neurons remains an immature concept, with especially the regulatory molecular mechanisms of senescence-like phenotypes and the role of proteins associated with neurodegenerative diseases in triggering neuronal senescence remaining poorly explored. In this study, we reveal that the nucleolar polyglutamine binding protein 3 (PQBP3; also termed NOL7), which has been linked to polyQ neurodegenerative diseases, regulates senescence as a gatekeeper of cytoplasmic DNA leakage. PQBP3 directly binds PSME3 (proteasome activator complex subunit 3), a subunit of the 11S proteasome regulator complex, decreasing PSME3 interaction with Lamin B1 and thereby preventing Lamin B1 degradation and senescence. Depletion of endogenous PQBP3 causes nuclear membrane instability and release of genomic DNA from the nucleus to the cytosol. Among multiple tested polyQ proteins, ataxin-1 (ATXN1) partially sequesters PQBP3 to inclusion bodies, reducing nucleolar PQBP3 levels. Consistently, knock-in mice expressing mutant Atxn1 exhibit decreased nuclear PQBP3 and a senescence phenotype in Purkinje cells of the cerebellum. Collectively, these results suggest homologous roles of the nucleolar protein PQBP3 in cellular senescence and neurodegeneration.

Organocatalytic Atroposelective Synthesis of Axially Chiral Indolyl Ketosulfoxonium Ylides.

Despite recent advancements in catalytic synthesis of axial chirality, reports on non-biaryl atropisomers remain limited because of the stringent steric requirements necessary to establish effective rotational brakes. In this study, we present a novel class of monoaryl atropisomers, indolyl ketosulfoxonium ylides, and describe an organocatalytic protocol for their synthesis. We discovered that a chiral phosphoric acid (CPA) serves as an effective catalyst for the highly enantioselective iodination of ortho-aminophenylethynyl sulfoxonium ylides. Under the optimized reaction conditions, a strong preference for the intended iodination process over the competing protonation was observed. Subsequently, intramolecular amide cyclization enabled the formation of sterically congested indole fragments. Furthermore, the synthetic utility of the products was demonstrated by showcasing versatile transformations into other chiral scaffolds with complete retention of optical purity.

N-Heterocyclic Carbene-Catalyzed Asymmetric SN2 Alkylation via Noncovalent Activation.

The field of asymmetric catalysis has been developed by exploring noncovalent interactions, particularly within N-heterocyclic carbene-mediated processes. Despite challenges due to the limited number of compatible electrophiles (predominantly π-acceptors), this study introduces the first asymmetric α-alkylation of 3-aryl oxindoles using Csp3 electrophiles. The innovative protocol integrates diverse oxindoles and alkyl, allyl, and propargyl electrophiles, achieving high yields and enantioselectivities. Preliminary mechanistic explorations support a noncovalent catalytic mechanism, enhancing the tool kit for constructing complex chiral molecules with potential applications.

Predicting metformin efficacy in improving insulin sensitivity among women with polycystic ovary syndrome and insulin resistance: a machine learning study.

OBJECTIVE: Metformin is clinically effective in treating polycystic ovary syndrome (PCOS) with insulin resistance (IR), while its efficacy varies among individuals. This study aims to develop a machine learning model to predict the efficacy of metformin in improving insulin sensitivity among women with PCOS and IR. METHODS: This is a retrospective analysis of a multicenter, randomized controlled trial involving 114 women diagnosed with PCOS and IR. All women received metformin treatment for 4 months. We incorporated 27 baseline clinical variables of the women into the construction of our machine learning model. We firstly compared four commonly used feature selection methods to screen valuable clinical variables. Then we used the valuable variables as inputs to evaluate the performance of five machine learning models, including k-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), and Extreme Gradient Boosting (Xgboost), in predicting the efficacy of metformin. RESULTS: Among the five machine learning models, SVM performed the best with an area under the receiver operating characteristic curve (AUC) of 0.781 (95% confidence interval [CI]: 0.772-0.791). The key predictive variables identified were homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and low-density lipoprotein cholesterol (LDL-C). CONCLUSION: The developed machine learning model could be applied to to predict the efficacy of metformin in improving insulin sensitivity among women with PCOS and IR. The result could help doctors evaluate the efficacy of metformin in advance, optimize treatment plans, and thereby enhance overall clinical outcomes.

STING coordinates resolution of inflammation during wound repair by modulating macrophage trafficking through STAT3.

Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-α+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING-STAT3-chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts. STING regulates the macrophage trafficking through STAT3 in wound healing.

A near-infrared ratiometric fluorescent probe for the sensing and imaging of sulfur dioxide derivatives in living systems.

As a reactive sulfur species, sulfur dioxide (SO2) and its derivatives play crucial role in various physiological processes, which can maintain redox homeostasis at normal levels and lead to the occurrence of many diseases at abnormal levels. So, the development of a suitable fluorescent probe is a crucial step in advancing our understanding of the role of SO2 derivatives in living organisms. Herein, we developed a near-infrared fluorescent probe (SP) based on the ICT mechanism to monitor SO2 derivatives in living organisms in a ratiometric manner. The probe SP exhibited excellent selectivity, good sensitivity, fast response rate (within 50 s), and low detection limit (1.79 µM). In addition, the cell experiment results suggested that the SP has been successfully employed for the real-time monitoring of endogenous and exogenous SO2 derivatives with negligible cytotoxicity. Moreover, SP was effective in detecting SO2 derivatives in mice.

Propyl acetate protects intestinal barrier during parenteral nutrition in mice and Caco-2 cells.

BACKGROUND: Gut microbiota dysbiosis induces intestinal barrier damage during parenteral nutrition (PN). However, the underlying mechanisms remain unclear. This study aimed to investigate gut microbiota dysbiosis, luminal short-chain fatty acids, and autophagy in a mouse model and how these short-chain fatty acids regulate autophagy. METHODS: Eight-week-old male specific-pathogen-free mice were randomly divided into a Chow group (standard diet and intravenous normal saline infusion) and a PN group (continuous infusion of PN nutrient solution) for 7 days. Caco-2 cells were also treated with intestinal rinse solutions from Chow and PN mouse models. RESULTS: Compared with the Chow group, the PN group exhibited increased Proteobacteria and decreased Firmicutes, correlating with decreased propyl acetate. In the PN group, intestinal tissue exhibited elevated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, LC3II protein levels, and Atg3 and Atg7 messenger RNA levels. P62 protein levels were decreased, indicating an increase of autophagy flux in the PN group. In the Caco-2 cell model, cells treated with PN solution plus propyl acetate exhibited increased Claudin-1 and occluding along with decreased interleukin-6 and tumor necrosis factor α compared with those treated with PN solution alone. Propyl acetate addition inhibited the AMPK-mammalian target of rapamycin (mTOR) pathway, mitigating the excessive autophagy induced by the PN intestinal rinse solution in Caco-2 cells. CONCLUSION: PN led to a significant reduction in propyl acetate levels in the intestine, excessive activation of autophagy, and barrier dysfunction. Propyl acetate inhibited excessive autophagy via the AMPK/mTOR signaling pathway and protected the intestinal barrier during PN.

Controlled bioorthogonal activation of Bromodomain-containing protein 4 degrader by co-delivery of PROTAC and Pd-catalyst for tumor-specific therapy.

The precise and safe treatment of bioorthogonal prodrug system is hindered by separate administration of prodrug and its activator, which often results in poor therapeutic effects and severe side effects. To address above issues, we herein construct a single bioorthogonal-activated co-delivery system for simultaneous PROTAC prodrug (proPROTAC) delivery and controlled, site-specific activation for tumor-specific treatment. In this co-delivery system (termed AuPLs), prodrug (proPROTAC) and water-soluble Pd-catalyst are first encapsulated by gold nanocubes (AuNCs), which are further coated with a layer of phase-change material (lauric acid/stearic acid, LA/SA). Below 39 °C, the solid state of LA/SA prevents the activation of Pd-mediated bioorthogonal reaction due to the solidification of Pd-catalyst and proPROTAC. Nevertheless, once over 42 °C, the phase change of LA/SA into liquid state, enabled by the photothermal effect of AuNCs, triggers the simultaneous release of proPROTAC and Pd-catalyst and initiates the in situ bioorthogonal reaction for proPROTAC activation. In the tumor-bearing mouse models, the systemic administration of AuPLs results in the accumulation in tumor region, where the photothermal effect activates and controls the tumor-specific bioorthogonal reaction to degrade BRD4 protein, leading to anti-tumor effects with minimized side effects. Overall, the co-delivery proPROTAC and Pd-catalyst and controlled activation by photothermal effects provide a precise way for biorthogonal-based anticancer prodrugs.

Production of high calorific value hydrogen-rich combustible gas by supercritical water gasification of straw assisted by machine learning.

This article reveals the basic laws of straw supercritical water gasification (SCWG) and provides basic experimental data for the effective utilization of straw. The paper studied the impact of three operational conditions on the production of high-calorific value hydrogen-rich combustible gases through SCWG of straw within a quartz tube reactor. The findings reveal that elevated reaction temperatures, extended residence times, and reduced feedstock concentrations favor the SCWG of straw. When combustible gas contains carbon dioxide, the maximum low heating value (LHV) of the gas is 21 MJ/Nm3. Upon removing carbon dioxide, the LHV of the gas reached 38 MJ/Nm3. Subsequently, a machine learning (ML) model was developed to forecast gas yield and LHV during the SCWG process. The results demonstrate that the model exhibits robust generalization capabilities. ML can be extensively applied to forecast biomass SCWG processes across various operational conditions.

A self-powered theranostic DNA nanodevice for amplification of both intracellular microRNA imaging and photodynamic therapy.

While numerous methods exist for diagnosing tumors through the detection of miRNA within tumor cells, few can simultaneously achieve both tumor diagnosis and treatment. In this study, a novel graphene oxide (GO)-based DNA nanodevice (DND), initiated by miRNA, was developed for fluorescence signal amplification imaging and photodynamic therapy in tumor cells. After entering the cells, tumor-associated miRNA drives DND to Catalyzed hairpin self-assembly (CHA). The CHA reaction generated a multitude of DNA Y-type structures, resulting in a substantial amplification of Ce6 fluorescence release and the generation of numerous singlet oxygen (1O2) species induced by laser irradiation, consequently inducing cell apoptosis. In solution, DND exhibited high selectivity and sensitivity to miRNA-21, with a detection limit of 11.47 pM. Furthermore, DND discriminated between normal and tumor cells via fluorescence imaging and specifically generated O21 species in tumor cells upon laser irradiation, resulting in tumor cells apoptosis. The DND offer a new approach for the early diagnosis and timely treatment of malignant tumors.

Effects of O2 on accumulation of nitrous and elemental sulfur and microbial community structure in double short-cut sulfur autotrophic denitrification system.

Understanding the effect of O2 on the accumulation characteristics of NO2--N and S0 in the sulfur autotrophic denitrification (DSSADN) system is crucial for enhancing the denitrification efficiency of partial nitrification-anammox using DSSADN. The results revealed that in an environment without O2 entry, the NO2--N accumulation efficiency (NiAE) and S0 accumulation efficiency (S0AE) of the DSSADN system reached 89.40 % and 93.41 %, respectively. Once system entered O2, ORP value kept increasing. When ORP increased to -59.9 mV (DO = 0.1 mg/L), soxB and nirK gene expression rose and as well NiAE and S0AE continuously decreased to 48.13 % and 29.35 %. When ORP was above 30.9 mV (DO >0.2 mg/L) but below 81.0 mV (DO<0.4 mg/L), narG gene expression reduced and the relatively high sqr gene expression allowed NiAE and S0AE remained at 45.08 % and 33.31 %. O2 promoted the synergistic effect of Thiobacillus and Azoarcus without the proliferation of nitrite oxidizing bacteria.

Construction and anti-pancreatic cancer activity of selenium nanoparticles stabilized by Prunella vulgaris polysaccharide.

Selenium nanoparticles (SeNPs), as a potential cancer therapeutic agent, have attracted extensive attention due to their high anticancer activity and low toxicity. Polysaccharides could be the modifiers and stabilizers to improve the stability and dispersibility of SeNPs in aqueous solution. This study aimed to investigate the physicochemical characterization, stability, and anti-pancreatic cancer cell activities of SeNPs stabilized by a heteroxylan PVP3-1 extracted from the clusters of Prunella vulgaris Linn. Our results showed that PVP3-1 with Mw of 154 kDa was composed of →4)-ß-D-Xylp(1→, →2, 4)-ß-D-Xylp(1→, t-α-L-Araf(1→ and 4-MeO-α-D-GlcpA(1→. Red, zero-valent, and uniform spherical SeNPs with an average diameter of about 60 nm and high stability in aqueous solution were constructed successfully by polysaccharide PVP3-1. Anti-pancreatic cancer cell activity assays showed that PVP3-1-SeNPs could inhibit the proliferation and migration of pancreatic cancer cells in vitro. Furthermore, PVP3-1-SeNPs induced apoptosis and autophagy of pancreatic cancer cells through inhibiting mTOR signaling pathway. In conclusion, these results indicated that PVP3-1-SeNPs could be potential anti-tumor nanoparticles for treating pancreatic cancer.

[Meridian massage in the treatment of cervical spondylotic radiculopathy].

OBJECTIVE: To observe the clinical efficacy of meridian massage in the treatment of cervical spondylotic radiculopathy. METHODS: Sixty-four patients with cervical radiculopathy treated from March 2020 to June 2023 were divided into the observation group and the treatment group, with 32 cases in each group. The observation group received conventional treatment, including 14 males and 18 females with an average age of (41.34±7.23) years old ranging from 32 to 55 years old;the disease duration ranged from 9 to 17 months with an average of (14.23±3.56) months;C5 and C6 nerve root compression occurred in 12 cases, C7 nerve root compression occurred in 17 cases, C8 nerve root compression occurred in 3 cases. The treatment group received massage therapy on the basis of conventional treatment, including 17 males and 15 females with an average age of (40.86±6.97) years old ranging from 30 to 54 years old;the disease duration ranged from 8 to 18 months with an average of (15.43±3.48) months;C5 and C6 nerve root compression occurred in 14 cases, C7 nerve root compression occurred in 16 cases, C8 nerve root compression occurred in 2 cases. The clinical efficacy was evaluated by visual analogue scale(VAS), neck disability index(NDI) and clinical assessment scale for cervical spondylosis(CASCS) before and after 2-week treatment, and the range of motion of cervical spine was compared before and after treatment. RESULTS: After 2-week treatment, the VAS and NDI scores of the treatment group and the observation group decreased, while the CASCS scores increased(P<0.001). After 2-week treatment, the VAS and NDI scores were lower and the CASCS scores were higher in the treatment group than those of the observation group(P<0.001). Comparing with those before treatment, the range of motion of flexion, extension, left flexion, right flexion, left rotation and right rotation after 2-week treatment increased in two groups(P<0.05). Comparing with the observation group, the range of motion of flexion, extension, left flexion, right flexion, left rotation and right rotation increased more significantly in the treatment group(P<0.05). CONCLUSION: Meridian massage is effective in the treatment of cervical Spondylotic radiculopathy, which can effectively relieve neck pain, improve clinical symptoms and improve patient satisfaction.

Evaluating the protective effectiveness and risk factors of ursodeoxycholic acid on COVID-19 among outpatients.

Objective: This study aimed to assess the chemopreventive effect of ursodeoxycholic acid (UDCA) against COVID-19 and to analyze infection risk factors, symptoms, and recovery in outpatients with UDCA exposure. Methods: The study enrolled outpatients prescribed UDCA from the Second Affiliated Hospital of Chongqing Medical University, China, between 01 July 2022, and 31 December 2022. Data on demographics, comorbidities, and drug combinations were collected using electronic medical records. COVID-19 infection, symptoms, severity, prognosis, vaccinations, and UDCA administration were surveyed by telephone interviews. UDCA non-users served as controls and were matched in a 1:2 ratio with UDCA users using propensity score matching with the nearest neighbor algorithm. Infection rates, symptomatology, severity, and prognosis were compared between matched and control cohorts, and risk factors and infection and recovery symptoms were analyzed in UDCA-exposed outpatients. Results: UDCA-exposed outpatients (n = 778, 74.8%) and matched UDCA users (n = 95, 74.2%) showed significantly lower SARS-CoV-2 infection rates than control patients (n = 59, 92.2%) (p < 0.05). The matched UDCA group exhibited substantially lower fever, cough, sore throat, and fatigue rates than controls (p < 0.05). Participants with UDCA exposure generally experienced mild symptoms, while those without UDCA had moderate symptoms. The matched UDCA group also had significantly shorter durations of fever and cough (p < 0.05). Risk factors such as age over 60, less than 1 month of UDCA administration, diabetes mellitus, and coronary artery disease significantly increased SARS-CoV-2 infection rates (p < 0.05), while smoking led to a decrease (p < 0.05). Hypertension was associated with a prolonged COVID-19 recovery (p < 0.05), while smoking, vaccination, and fatty liver disease were associated with shorter recovery periods (p < 0.05). The main symptoms in the full UDCA cohort were fever, cough, and sore throat, with fatigue, cough, and hyposthenia being the most persistent. Conclusion: UDCA demonstrated chemopreventive effect against SARS-CoV-2 in outpatients by significantly reducing infection incidence and mitigating COVID-19 symptoms, severity, and recovery duration. Old age, short UDCA course, and comorbidities such as diabetes mellitus and CAD increased infection rates, while hypertension prolonged recovery. Smoking, vaccination, and fatty liver disease reduced infection rates and shortened recovery. UDCA had minimal impact on symptom types. Larger and longer-term clinical studies are needed further to assess UDCA's effectiveness in COVID-19 prevention or treatment.

ADH4-a potential prognostic marker for hepatocellular carcinoma with possible immune-related implications.

OBJECTIVE: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. METHODS: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. RESULTS: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. CONCLUSION: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.