Emerging role of zinc finger protein A20 as a suppressor of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), the third leading cause of cancer-associated mortality worldwide, is a major public health problem. Zinc finger protein A20 (A20), an acute phase response gene, is a potent inhibitor of NF-κB signaling. A20 serves a critical role in liver protection, including limiting inflammation following hepatic injury, stimulating hepatocyte growth, and preventing hepatic ischemia-reperfusion injury. A20 is also involved in different processes, including tumorigenesis, progression, and metastasis through multiple mechanisms. Accumulated studies have reported the clinical implications and biological relevance of A20 in the development and progression of HCC. The underlying mechanisms of A20 in HCC include inhibition of epithelial–mesenchymal transition, protein tyrosine kinase 2 activation and Rac family GTPase 1 activity. Combining liver protection with tumor inhibition is a unique advantage of A20, which has the potential to be a novel treatment for promoting liver regeneration following liver resection in patients with HCC with liver cirrhosis. This review discusses the hepato-protective effect of A20 on hepatocytes and its potential role in cancer development, particularly its suppressor effect on HCC.     

Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation,apoptosis, and oxidative stress

Excessive plasma triglyceride (TG) and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism and is involved in the regulation of oxidative stress. Although inflammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE^−/−) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE^−/− mice. ApoE/Plin5 double knockout (ApoE^−/−Plin5^−/−) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated TG, total cholesterol, and low-density lipoprotein cholesterol levels and reduced high-density lipoprotein cholesterol contents. ApoE^−/−Plin5^−/− exhibited a higher number of inflammatory monocytes and neutrophils, as well as overexpression of cytokines and chemokines linked with an inflammatory response. Consistently, the IκBα/nuclear factor kappa B pathway was strongly activated in ApoE^−/−Plin5^−/−. Notably, apoptosis was dramatically induced by ApoE^−/−Plin5^−/−, as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2. In addition, ApoE^−/−Plin5^−/− contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinases pathways. In vitro, oxidized low-density lipoprotein (ox-LDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress, and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions.     

4‐O‐methylhonokiol protects against diabetic cardiomyopathy in type 2 diabetic mice by activation of AMPK‐mediated cardiac lipid metabolism improvement

Diabetic cardiomyopathy (DCM) is characterized by increased left ventricular mass and wall thickness, decreased systolic function, reduced ejection fraction (EF) and ultimately heart failure. The 4‐O‐methylhonokiol (MH) has been isolated mainly from the bark of the root and stem of Magnolia species. In this study, we aimed to elucidate whether MH can effectively prevent DCM in type 2 diabetic (T2D) mice and, if so, whether the protective response of MH is associated with its activation of AMPK‐mediated inhibition of lipid accumulation and inflammation. A total number of 40 mice were divided into four groups: Ctrl, Ctrl + MH, T2D, T2D + MH. Five mice from each group were sacrificed after 3‐month MH treatment. The remaining animals in each group were kept for additional 3 months without further MH treatment. In T2D mice, the typical DCM symptoms were induced as expected, reflected by decreased ejection fraction and lipotoxic effects inducing lipid accumulation, oxidative stress, inflammatory reactions, and final fibrosis. However, these typical DCM changes were significantly prevented by the MH treatment immediately or 3 months after the 3‐month MH treatment, suggesting MH‐induced cardiac protection from T2D had a memory effect. Mechanistically, MH cardiac protection from DCM may be associated with its lipid metabolism improvement by the activation of AMPK/CPT1‐mediated fatty acid oxidation. In addition, the MH treatment of DCM mice significantly improved their insulin resistance levels by activation of GSK‐3β. These results indicate that the treatment of T2D with MH effectively prevents DCM probably via AMPK‐dependent improvement of the lipid metabolism.     

Dendrite‐Free Flexible Fiber‐Shaped Zn Battery with Long Cycle Life in Water and Air

Fiber‐shaped aqueous rechargeable Zn batteries (FARZBs) show flexibility, good reliability, cost‐effectiveness, high energy/power densities, and high safety that have attracted increasing attention as promising energy storage devices for future wearable applications. However, the development of FARZB is limited by its poor cycling life and inferior charge–discharge performance, mainly suffering from zinc dendrite growth and increasing electrode irreversibility. In this work, dendrite‐free fiber‐shaped Zn//Co₃O₄ rechargeable batteries with a long cycle life tested in water and air, are obtained via tuning the surface binding energy of Zn on the anode using the zincophilic N,O‐functional carbon fiber, as well as engineering the Co₃O₄ cathode with a nanowire array structure. The fiber‐shaped Zn//Co₃O₄ full battery demonstrates remarkable long cycle life in water and air with high energy density, impressive flexibility, and excellent waterproof ability (fully immersed and charged/discharged under water for more than 33 h for 3000 cycles with capacity retention of ≈80%). The reversible electrochemical mechanisms of the FARZBs, without obvious zinc dendrite deposits and structural change of Co₃O₄ nanowires, are confirmed by a series of characterizations. These results demonstrate that the FARZBs are promising power sources for emerging wearable electronics.     

The status of neutral insects,mosquitoes in the food of natural enemies in tea gardens

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The Inhibitory Effects of Nitrogen Deposition on Asymbiotic Nitrogen Fixation are Divergent Between a Tropical and a Temperate Forest

Ecosystems - Asymbiotic nitrogen (N) fixation (ANF) is an important source of N in pristine forests and is predicted to decrease with N deposition. Previous studies revealing N fixation in response...     

The road to lysosome‐related organelles: Insights from Hermansky‐Pudlak syndrome and other rare diseases

Lysosome‐related organelles (LROs) comprise a diverse group of cell type‐specific, membrane‐bound subcellular organelles that derive at least in part from the endolysosomal system but that have unique contents, morphologies and functions to support specific physiological roles. They include: melanosomes that provide pigment to our eyes and skin; alpha and dense granules in platelets, and lytic granules in cytotoxic T cells and natural killer cells, which release effectors to regulate hemostasis and immunity; and distinct classes of lamellar bodies in lung epithelial cells and keratinocytes that support lung plasticity and skin lubrication. The formation, maturation and/or secretion of subsets of LROs are dysfunctional or entirely absent in a number of hereditary syndromic disorders, including in particular the Hermansky‐Pudlak syndromes. This review provides a comprehensive overview of LROs in humans and model organisms and presents our current understanding of how the products of genes that are defective in heritable diseases impact their formation, motility and ultimate secretion.     

In vivo label‐free functional photoacoustic monitoring of ischemic reperfusion

Pressure ulcer formation is a common problem among patients confined to bed or restricted to wheelchairs. The ulcer forms when the affected skin and underlying tissues go through repeated cycles of ischemia and reperfusion, leading to inflammation. This theory is evident by intravital imaging studies performed in immune cell–specific, fluorescent reporter mouse skin with induced ischemia‐reperfusion (I‐R) injuries. However, traditional confocal or multiphoton microscopy cannot accurately monitor the progression of vascular reperfusion by contrast agents, which leaks into the interstitium under inflammatory conditions. Here, we develop a dual‐wavelength micro electro mechanical system (MEMS) scanning–based optical resolution photoacoustic microscopy (OR‐PAM) system for continuous label‐free functional imaging of vascular reperfusion in an IR mouse model. This MEMS‐OR‐PAM system provides fast scanning speed for concurrent dual‐wavelength imaging, which enables continuous monitoring of the reperfusion process. During reperfusion, the revascularization of blood vessels and the oxygen saturation (sO₂) changes in both arteries and veins are recorded, from which the local oxygen extraction ratios of the ischemic tissue and the unaffected tissue can be quantified. Our MEMS‐OR‐PAM system provides novel perspectives to understand the I‐R injuries. It solves the problem of dynamic label‐free functional monitoring of the vascular reperfusion at high spatial resolution.