Tubulointerstitial nephritis antigen-like 1 promotes the progression of liver fibrosis after HCV eradication with direct-acting antivirals.

Although therapies based on direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV) in patients, there is still a high risk of liver fibrosis even after a sustained virological response. Therefore, it is of great clinical importance to understand the mechanism of potential factors that promote liver fibrosis after virological cure by treatment with DAAs. Here, we found that tubulointerstitial nephritis antigen-like 1 (TINAGL1) is significantly increased in HCV-infected hepatocytes and in the liver of patients with liver fibrosis, and that higher TINAGL1 expression persists in HCV-eradicated hepatocytes after treatment with DAAs.

Integrated use of electrochemical anaerobic reactors and genomic based modeling for characterizing methanogenic activity in microbial communities exposed to BTEX contamination.

In soil polluted with benzene, toluene, ethylbenzene, and xylenes (BTEX), oxygen is rapidly depleted by aerobic respiration, creating a redox gradient across the plume. Under anaerobic conditions, BTEX biodegradation is then coupled with fermentation and methanogenesis. This study aimed to characterize this multi-step process, focusing on the interactions and functional roles of key microbial groups involved.

Lycorine esters exert anti-HCoV-OC43 effect through reversibly acylating cysteine residue in the nsp 12 NiRAN domain.

By introducing ester warheads into the hydroxyl groups in lycorine (1), three types of lycorine mono-ester or di-ester analogues were synthesized and evaluated for their antiviral activities against HCoV-OC43. Most of them showed higher selective indexes (SI) than 1, up to nearly 14 times. Using compound 6b as a probe, we firstly demonstrated that lycorine esters directly targeted nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain in the non-structural protein 12 (nsp 12) by reversibly acylating Cys12 to induce the shrink of NiRAN pocket and block the viral replication, different from the known RdRp inhibitors.

Engineering Dual Active Sites and Defect Structure in Nanozymes to Reprogram Jawbone Microenvironment for Osteoradionecrosis Therapy.

Four to eight percent of patients with head and neck cancer will develop osteoradionecrosis of the jaw (ORNJ) after radiotherapy. Various radiation-induced tissue injuries are associated with reactive oxygen and nitrogen species (RONS) overproduction. Herein, Fe doping is used in VO (Fe-VO) nanozymes with multienzyme activities for ORNJ treatment via RONS scavenging.

Engineering microbiomes for enhanced bioremediation.

Bioremediation using synthetic microbiomes offers significant advantages over traditional single-strain-based approaches. In this Perspective, we outline 5 important considerations for the rational design of pollutant-degrading microbiomes for enhanced bioremediation.

Puerarin reduces susceptibility to ventricular arrhythmias and inhibits ferroptosis via Sirt1/Nrf2 signaling in high-fat-diet rats.

Obesity is a significant risk factor for cardiac arrhythmias, and the ferroptosis is closely related to cardiac arrhythmias. This study aimed to investigate whether puerarin (Pue), a natural isoflavone, could reduce the susceptibility to ventricular arrhythmias (VAs) associated with obesity and inhibit ferroptosis, with a particular focus on the Sirt1/Nrf2 signaling pathway. Male rats were randomly divided into three groups: normal chow diet (NC), high-fat diet (HFD), and HFD with Pue treatment (100mg/kg, HFD + Pue).

Target fishing and mechanistic insights of the natural anticancer drug candidate chlorogenic acid.

Chlorogenic acid (CGA) is a natural product that effectively inhibits tumor growth, demonstrated in many preclinical models, and phase II clinical trials for patients with glioma. However, its direct proteomic targets and anticancer molecular mechanisms remain unknown. Herein, we developed a novel bi-functional photo-affinity probe PAL/CGA and discovered mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) was one of the main target proteins of CGA by using affinity-based protein profiling (AfBPP) chemical proteomic approach.

Renal Health Through Medicine-Food Homology: A Comprehensive Review of Botanical Micronutrients and Their Mechanisms.

Background: As an ancient concept and practice, "food as medicine" or "medicine-food homology" is receiving more and more attention these days. It is a tradition in many regions to intake medicinal herbal food for potential health benefits to various organs and systems including the kidney. Kidney diseases usually lack targeted therapy and face irreversible loss of function, leading to dialysis dependence.

Mitigating risks from atrazine drift to soybeans through foliar pre-spraying with a degrading bacterium.

Herbicides play a crucial role in managing weeds in agriculture, ensuring the productivity and quality of crops. However, herbicide drift poses a significant threat to sensitive plants, necessitating the consideration of ecosystem-based solutions to address this issue. In this study, foliar pre-spraying of atrazine-degrading Paenarthrobacter sp.

Rapid screening of indigenous degrading microorganisms for enhancing in-situ bioremediation of organic pollutants-contaminated soil.

Organic pollutants (OPs) have caused severe environmental contaminations in the world and aroused wide public concern. Autochthonous bioaugmentation (ABA) is considered a reliable bioremediation approach for OPs contamination. However, the rapid screening of indigenous degrading strains from in-situ environments remains a primary challenge for the practical application of ABA.

Enhanced growth of wheat in contaminated fields via synthetic microbiome as revealed by genome-scale metabolic modeling.

The relationship between plants and soil microbial communities is complex and subtle, with microbes playing a crucial role in plant growth. Autochthonous bioaugmentation and nutrient biostimulation are promising bioremediation methods for herbicides in contaminated agricultural soils, but how microbes interact to promote biodegradation and plant growth on barren fields, especially in response to the treatment of the herbicide bromoxynil after wheat seedlings, remains poorly understood. In this study, we explored the microbial community reassembly process from the three-leaf stage to the tillering stage of wheat and put forward the idea of using the overlapping results of three methods (network Zi-Pi analysis, LEfSe analysis, and Random Forest analysis) as keystones for the simplification and optimization of key microbial species in the soil.

DipR, a GntR/FadR-family transcriptional repressor: regulatory mechanism and widespread distribution of the dip cluster for dipicolinic acid catabolism in bacteria.

Dipicolinic acid is an essential component of bacterial spores for stress resistance, which is released into the environment after spore germination. In a previous study, a dip gene cluster was found to be responsible for the catabolism of dipicolinic acid in Alcaligenes faecalis JQ135. However, the transcriptional regulatory mechanism remains unclear.

Biodegradation of Cyromazine by sp. M15: Performance, Degradation Pathways, and Key Enzymes.

Cyromazine, a triazine insecticide, raises food safety concerns due to residues in vegetables like cowpeas. Microbial metabolism is key for pesticide elimination, but bacteria efficient in cyromazine degradation are limited, with uncharacterized enzymes. This study isolated a highly efficient cyromazine-degrading bacterium, sp.

Bacterial growth and environmental adaptation via thiamine biosynthesis and thiamine-mediated metabolic interactions.

Understanding the ancestral transition from anaerobic to aerobic lifestyles is essential for comprehending life's early evolution. However, the biological adaptations occurring during this crucial transition remain largely unexplored. Thiamine is an important cofactor involved in central carbon metabolism and aerobic respiration.

Substituted indole derivatives as UNC-51-like kinase 1 inhibitors: Design, synthesis and anti-hepatocellular carcinoma activity.

The five-year survival rate for patients with hepatocellular carcinoma (HCC) is only 20 %, highlighting the urgent need to identify new therapeutic targets and develop potential therapeutic options to improve patient prognosis. One promising approach is inhibiting autophagy as a strategy for HCC treatment. In this study, we established a virtual docking conformation of the autophagy promoter ULK1 binding XST-14 derivatives.

Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway.

The probability of cardiovascular events has been reported lower in rheumatoid arthritis (RA) patients treated with leflunomide. However, the anti-atherosclerotic and cardiovascular protective effects and metabolism of leflunomide are not explored. In this study, we assessed the potential benefits of leflunomide on atherosclerosis and revealed the underlying mechanism.

Corrigendum to "Active components of Dengzhan Shengmai ameliorate cognitive impairment by facilitating hippocampal long-term potentiation via the NMDA receptor-mediated Ca/CaMKII pathway" [J. Pharm. Anal. 14 (2024) 435-438].

[This corrects the article DOI: 10.1016/j.jpha.

Dexborneol Amplifies Pregabalin's Analgesic Effect in Mouse Models of Peripheral Nerve Injury and Incisional Pain.

Pregabalin is a medication primarily used in the treatment of neuropathic pain and anxiety disorders, owing to its gabapentinoid properties. Pregabalin monotherapy faces limitations due to its variable efficacy and dose-dependent adverse reactions. In this study, we conducted a comprehensive investigation into the potentiation of pregabalin's analgesic effects by dexborneol, a neuroprotective bicyclic monoterpenoid compound.

Selectively T cell phosphorylation activation of azvudine in the thymus tissue with immune protection effect.

Thymus is the important immune organ, responsible for T cell development and differentiation. The lower circulating T counts have been observed in patients who died from COVID-19 compared with survivors. Azvudine, also known as FNC, is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 patients.

Berberine prevents against myocardial injury induced by acute β-adrenergic overactivation in rats.

The overactivation of β-adrenergic receptors (β-ARs) can result in acute myocardial ischemic injury, culminating in myocardial necrosis. Berberine (BBR) has exhibited promising potential for prevention and treatment in various heart diseases. However, its specific role in mitigating myocardial injury induced by acute β-AR overactivation remains unexplored.

Characterization of cotinine degradation in a newly isolated Gram-negative strain Pseudomonas sp. JH-2.

Cotinine, the primary metabolite of nicotine in the human body, is an emerging pollutant in aquatic environments. It causes environmental problems and is harmful to the health of humans and other mammals; however, the mechanisms of its biodegradation have been elucidated incompletely. In this study, a novel Gram-negative strain that could degrade and utilize cotinine as a sole carbon source was isolated from municipal wastewater samples, and its cotinine degradation characteristics and kinetics were determined.

Electro-stimulation modulates syntrophic interactions in methanogenic toluene-degrading microbiota for enhanced functionality.

Syntrophy achieved via microbial cooperation is vital for anaerobic hydrocarbon degradation and methanogenesis. However, limited understanding of the metabolic division of labor and electronic interactions in electro-stimulated microbiota has impeded the development of enhanced biotechnologies for degrading hydrocarbons to methane. Here, compared to the non-electro-stimulated methanogenic toluene-degrading microbiota, electro-stimulation at 800 mV promoted toluene degradation and methane production efficiencies by 11.

Reliable Low-Current and Multilevel Memristive Electrochemical Neuromorphic Devices with Semi-Metal Sb Filament.

Memristors are used in artificial neural networks owing to their exceptional integration capabilities and scalability. However, traditional memristors are hampered by limited resistance states and randomness, which curtails their application. The migration of metal ions critically influences the number of conductance states and the linearity of weight updates.