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Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide but still lacks specific treatment modalities. The gut microbiota and its metabolites have been shown to be intimately involved in NAFLD development, participating in and regulating disease progression. Trimethylamine N-oxide (TMAO), a metabolite highly dependent on the gut microbiota, has been shown to play deleterious regulatory roles in cardiovascular disease, but the relationship between it and NAFLD lacks validation from basic experiments. This research applied TMAO intervention by constructing fatty liver cell models in vitro to observe its effect on fatty liver cells and potential key genes and performed siRNA interference on the gene to verify the action. The results showed that TMAO intervention promoted the appearance of more red-stained lipid droplets in Oil-red O staining results, increased triglyceride (TG) levels and increased mRNA levels of liver fibrosis-related genes, and also identified one of the key genes, keratin17 (KRT17) via transcriptomics. Following the reduction in its expression level, under the same treatment, there were decreased red-stained lipid droplets, decreased TG levels, decreased indicators of impaired liver function as well as decreased mRNA levels of liver fibrosis-related genes. In conclusion, the gut microbiota metabolite TMAO could promote lipid deposition and fibrosis process via the KRT17 gene in fatty liver cells in vitro. • TMAO promotes lipid deposition in fatty liver cells in vitro. • TMAO promotes the fibrosis process of fatty liver cells in vitro. • KRT17 is the critical gene in the action of TMAO. • Reduced KRT17 expression levels diminish the cell-promoting effect of TMAO. [ABSTRACT FROM AUTHOR]

To understand joint emission reduction (JER) of upstream and downstream firms under a low-carbon operational environment, this study incorporates green technology, remanufacturing, low-carbon promotion, consumer environmental awareness (CEA), and mixed carbon policies (carbon tax + cap-and-trade) into a dynamic framework to investigate JER decisions of the upstream manufacturer and the downstream retailer. Applying the differential game theory, we consider low-carbon goodwill as the state variable and explore members' optimal decisions in four cases, namely, idealized case, noncooperative case, unilateral cost-sharing contract (UCSC) case, and bilateral cost-sharing contract (BCSC) case. Our results show that the noncooperative case leads to a loss of efficiency in joint emission reduction. Although the BCSC is more advantageous than the UCSC in improving the efficiency of JER, a profit redistribution mechanism needs to be included, and the profit distribution ratio should be controlled within a certain interval. Only in this situation do both parties prefer the BCSC. Additionally, the impact of mixed carbon policies and CEA on JER decisions, low-carbon goodwill, profits, and coordination are fully discussed, and it is found that in the face of stricter mixed carbon policies, the downstream retailer plays a moderating role only in cooperative cases. Several practical implications are concluded for JER, contract design, CEA, and carbon policies. Governments and firms can benefit from our research by gaining a deeper understanding of JER. • Differential game is applied to explore joint emission reduction (JER) decisions. • Upstream manufacturer depends on green technology and remanufacturing to realize green production. • Mixed carbon policies and consumer environmental awareness are considered. • Only in cooperative cases does the downstream retailer play a moderating role in JER. [ABSTRACT FROM AUTHOR]

Spinal cord injury often results in chronic loss of micturition control, which is featured by bladder hyperreflexia and detrusor sphincter dyssynergia. Previous studies showed that treatment of capsaicin reduces non-voiding bladder contractions in multiple animal injury models and human patients. However, its underlying neural mechanisms remain largely unknown. Here, by injecting a RetroAAV into the bladder wall, we specifically targeted TRPV1+, a capsaicin receptor, bladder afferent neurons. Morphometric analysis revealed borderline increase of the soma size and significant spinal axon sprouting of TRPV1+ bladder afferent neurons post a complete T8 spinal cord crush. We further demonstrated that chronic chemogenetic inhibition of these DRG neurons improved micturition recovery after SCI by increasing voiding efficiency and alleviating bladder hyperreflexia, along with reduced morphological changes caused by injury. Our study provided novel insights into the structural and functional changes of TRPV1+ bladder afferent post SCI and further supports the clinical use of capsaicin as an effective treatment to improve bladder functions in patients with SCI. • AAV-Retro viral injection mediated chemogenetic manipulation of bladder afferent. • Sprouting of spinal terminations of TRPV1 bladder afferent after SCI. • Chemogenetic inactivation of TRPV1 bladder afferent after SCI improves micturition. • Chemogenetic inactivation of TRPV1 bladder afferent after SCI prevents axon sprouting. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a highly heterogeneous subtype of hematological malignancies with a wide spectrum of cytogenetic and molecular abnormalities, which makes it difficult to manage and cure. Along with the deeper understanding of the molecular mechanisms underlying AML pathogenesis, a large cohort of novel targeted therapeutic approaches has emerged, which considerably expands the medical options and changes the therapeutic landscape of AML. Despite that, resistant and refractory cases caused by genomic mutations or bypass signalling activation remain a great challenge. Therefore, discovery of novel treatment targets, optimization of combination strategies, and development of efficient therapeutics are urgently required. This review provides a detailed and comprehensive discussion on the advantages and limitations of targeted therapies as a single agent or in combination with others. Furthermore, the innovative therapeutic approaches including hyperthermia, monoclonal antibody-based therapy, and CAR-T cell therapy are also introduced, which may provide safe and viable options for the treatment of patients with AML. • Acute myeloid leukemia (AML) is highly heterogeneous with a wide spectrum of cytogenetic and molecular abnormalities. • The emergence of targeted therapeutic approaches expands the medical options and changes the therapeutic landscape of AML. • Drug resistance caused by genomic mutations remain a great challenge. • Combination therapies exhibit superior clinical efficacy and better safety profile in AML. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[ a ]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia–reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation–reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53–BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53–BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated. Possible mechanism of pyroptosis and autophagy mediated by BaP during myocardial ischemia/reperfusion injury. Bap activated AhR translocate into cells and activates downstream p53. As a result, BaP is capable of enhancing the interaction between BNIP3 and Bcl-2 to mediate more "free" Beclin-1 to inhibit autophagosome processing. Ultimately, blockage of autophagy-dependent NLRP3 degradation was shown to aggravate cell pyroptosis during myocardial I/R injury. [Display omitted] • BaP induces potent cardiotoxic effect during myocardial I/R injury. • Bap aggravates pyroptosis in a mechanism of impaired autophagosome clearance. • Bap inhibited autophagosome clearance through Ahr-p53-BNIP3-Beclin-1 axis. [ABSTRACT FROM AUTHOR]

The preservation of ultra high pressure (UHP) and magnetic field (MF) technologies on food have been reported, but the effect of combined treatment (UHP-MF) on aquatic product quality is rarely explored. The purposes of this study were to investigate the effects of UHP-MF treatment on protein properties and quality deterioration of stored Litopenaeus Vannamei. The vacuum-packed shrimps were treated at 200 and 300 MPa for 5 min, then stored in 5 mT MF for 12 days. Results showed the hardness, springiness, chewiness, shear force, L*, a*, b*, and W of muscle were improved by UHP, whereas the texture softening, a* and b* increase, water holding capacity were inhibited during MF storage. On the 12th day, compared with CON group, the cathepsin B, D, H, L activities, TBARS, carbonyl and dityrosine content in UHP 300 -MF group were reduced by 46.67%, 27.26%, 43.10%, 52.00%, 41.30%, 32.86%, and 30.42%, respectively. Furthermore, UHP-MF treatment slow down the accumulation of surface hydrophobicity, myofibril fragmentation index, and trichloroacetic acid-soluble peptide content. Generally, UHP-MF treatment inhibited lipid oxidation, weakened cathepsin activities, delayed protein oxidation and degradation of stored shrimp, retarded quality deterioration and prolonged shelf life of stored shrimp. • Lipid oxidation and enzyme action worsened the protein properties of stored shrimp. • UHP-MF delayed quality deterioration caused by protein oxidation and degradation. • MF aggravated the water loss of stored shrimp. • MF had an adverse effect on the surface color of whole shrimp during storage. • UHP-MF treatment was effective to prolong the shelf life of stored shrimp. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate antibacterial activities and action mode of alkyl gallates against three food-related bacteria. Results show that the length of the alkyl chain plays a critical role in eliciting their antibacterial activities and octyl gallate (GAC8) exhibited an outstanding bactericidal effect against these strains. A possible bactericidal mechanism of GAC8 against E. coli was fully elucidated by analyzing associated changes in cellular functions of E. coli , including assessments of membrane modification and intracellular oxidation state. Our data strongly suggested that GAC8 functions outside and inside the bacterial membrane and causes increased intracellular reactive oxygen species (hydroxyl radicals) and subsequent oxidative damage. We demonstrated that the hydroxyl radical formation induced by GAC8 is the end product of an oxidative damage cellular death pathway involving a transient depletion of NADH, the tricarboxylic acid cycle, intrinsic redox cycling activities, and stimulation of the Fenton reaction. Also, chitosan-based edible films containing GAC8 have unique superiorities for icefish preservation at 4 °C. This research highlights the effectiveness of GAC8 as an attractive antibacterial, which possesses both antioxidant and antibacterial activities and can be used as a multifunctional food additive combined with the benefit of active packaging for food preservations. [Display omitted] • Incorporation of alkyl chains into GA to enhance antibacterial activities. • Antibacterial activities of alkyl gallates were evaluated. • The mode of action of octyl gallate was systemically investigated. • Chitosan film incorporated with GAC8 for efficient preservation of icefish. [ABSTRACT FROM AUTHOR]

• The proposed MR based pseudo negative stiffness control approach is one of the most practical and efficiency semi-active vibration control for stay cable. • Clarify the gain role of pseudo-negative stiffness force in stay cable vibration control in the theoretical asymptotic solution. • Establish a real-time simulation model of the stay cable coupled with time-varying control system. Stay cables are prone to large amplitude vibrations, due to their low inherent damping and high lateral flexibility. In this study, one magnetorheological (MR) damper based programmable intelligent control device is developed to control the vibration of the stay cable more practically and efficiently. The proposed programmable scheme possesses the advantages of low energy consumption, less real time calculation and dynamic input. Its control oriented dynamic model integrated with programmable pseudo negative stiffness (PNS) strategy is built. And its beneficial role in the vibration control is explained in the complex eigenvalue theory analysis of stay cable with MR damper based programmable PNS force. Finally, the simulation of dynamic response of stay cable shows the superiority of programmable control scheme. Its realization demonstrates the feasibility of the single-input programmable PNS scheme experimentally. The dynamic response simulation of stay cable shows that MR damper based PNS scheme can offer better damping performance than conventional control method and its additional damping ratio is 1.63 times higher than that of optimal MR damper passive-on control. [ABSTRACT FROM AUTHOR]