Age‐associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation ...leads to the redistribution of fat to the intra‐abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β‐oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro‐inflammatory cytokines. In turn, these muscle‐secreted cytokines may exacerbate adipose tissue atrophy, support chronic low‐grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full‐blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the ‘obesity paradox’, could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full‐blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.
Excesses of antibiotic resistance genes (ARGs), which are regarded as emerging environmental pollutants, have been observed in various environments. The incidence of ARGs in drinking water causes ...potential risks to human health and receives more attention from the public. However, ARGs harbored in drinking water remain largely unexplored. In this study, we aimed at establishing an antibiotic resistome catalogue in drinking water samples from a wide range of regions and to explore the potential hosts of ARGs.
A catalogue of antibiotic resistome in drinking water was established, and the host-tracking of ARGs was conducted through a large-scale survey using metagenomic approach. The drinking water samples were collected at the point of use in 25 cities in mainland China, Hong Kong, Macau, Taiwan, South Africa, Singapore and the USA. In total, 181 ARG subtypes belonging to 16 ARG types were detected with an abundance range of 2.8 × 10
to 4.2 × 10
copies of ARG per cell. The highest abundance was found in northern China (Henan Province). Bacitracin, multidrug, aminoglycoside, sulfonamide, and beta-lactam resistance genes were dominant in drinking water. Of the drinking water samples tested, 84% had a higher ARG abundance than typical environmental ecosystems of sediment and soil. Metagenomic assembly-based host-tracking analysis identified Acidovorax, Acinetobacter, Aeromonas, Methylobacterium, Methyloversatilis, Mycobacterium, Polaromonas, and Pseudomonas as the hosts of ARGs. Moreover, potential horizontal transfer of ARGs in drinking water systems was proposed by network and Procrustes analyses.
The antibiotic resistome catalogue compiled using a large-scale survey provides a useful reference for future studies on the global surveillance and risk management of ARGs in drinking water. .
Peritoneal dissemination is the most frequent metastatic route of ovarian cancer. However, due to the high heterogeneity in ovarian cancer, most conventional studies lack parental tumor controls ...relevant to metastases and, thus, it is difficult to trace the molecular changes of cancer cells along with the selection by the abdominal microenvironment. Here, we established an in vivo mouse peritoneal dissemination scheme that allowed us to select more aggressive sublines from parental ovarian cancer cells, including A2780 and SKOV‐3. Microarray and gene profiling analyses indicated that autophagy‐related genes were enriched in selected malignant sublines. Detection of LC3‐II, p62 and autophagic puncta demonstrated that these malignant variants were more sensitive to autophagic induction when exposed to diverse stress conditions, such as high cell density, starvation and drug treatment. As compared with parental A2780, the selected variant acquired the ability to grow better under high‐density stress; however, this effect was reversed by addition of autophagic inhibitors or knockdown of ATG5. When analyzing the clinical profiles of autophagy‐related genes identified to be enriched in malignant A2780 variant, 73% of them had prognostic significance for the survival of ovarian cancer patients. Taken together, our findings indicate that an increase in autophagic potency among ovarian cancer cells is crucial for selection of metastatic colonies in the abdominal microenvironment. In addition, the derived autophagic gene profile can not only predict prognosis well but can also be potentially applied to precision medicine for identifying those ovarian cancer patients suitable for taking anti–autophagy cancer drugs.
Our findings indicate that an increase in autophagic potency among ovarian cancer cells is crucial for selection of metastatic colonies in the abdominal microenvironment. In addition, the derived autophagic gene profile can not only predict prognosis well but can also be potentially applied to precision medicine for identifying those ovarian cancer patients suitable for taking anti–autophagy cancer drugs.
3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production. Halomonas ...bluephagenesis shows the potential as a chassis for competitive bioproduction of various chemicals due to its ability to grow under an open, unsterile and continuous process. Here, we report the strategy for producing 3HP and its copolymer poly(3-hydroxybutyrate-co-3-hydroxypropionate) (P3HB3HP) by the development of H. bluephagenesis. The transcriptome analysis reveals its 3HP degradation and synthesis pathways involving endogenous synthetic enzymes from 1,3-propanediol. Combing the optimized expression of aldehyde dehydrogenase (AldD
), an engineered H. bluephagenesis strain of whose 3HP degradation pathway is deleted and that overexpresses alcohol dehydrogenases (AdhP) on its genome under a balanced redox state, is constructed with an enhanced 1.3-propanediol-dependent 3HP biosynthetic pathway to produce 154 g L
of 3HP with a yield and productivity of 0.93 g g
1,3-propanediol and 2.4 g L
h
, respectively. Moreover, the strain could also accumulate 60% poly(3-hydroxybutyrate-co-32-45% 3-hydroxypropionate) in the dry cell mass, demonstrating to be a suitable chassis for hyperproduction of 3HP and P3HB3HP.
Autophagy, a cellular self-eating mechanism, is important for maintaining cell survival and tissue homeostasis in various stressed conditions. Although the molecular mechanism of autophagy induction ...has been well studied, how cells terminate autophagy process remains elusive. Here, we show that ULK1, a serine/threonine kinase critical for autophagy initiation, is a substrate of the Cul3-KLHL20 ubiquitin ligase. Upon autophagy induction, ULK1 autophosphorylation facilitates its recruitment to KLHL20 for ubiquitination and proteolysis. This autophagy-stimulated, KLHL20-dependent ULK1 degradation restrains the amplitude and duration of autophagy. Additionally, KLHL20 governs the degradation of ATG13, VPS34, Beclin-1, and ATG14 in prolonged starvation through a direct or indirect mechanism. Impairment of KLHL20-mediated regulation of autophagy dynamics potentiates starvation-induced cell death and aggravates diabetes-associated muscle atrophy. Our study identifies a key role of KLHL20 in autophagy termination by controlling autophagy-dependent turnover of ULK1 and VPS34 complex subunits and reveals the pathophysiological functions of this autophagy termination mechanism.
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•ULK1 autophosphorylation promotes its recruitment to KLHL20 for ubiquitination•KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1•KLHL20 mediates autophagy termination by degrading ULK1 and VPS34 complex subunits•Impairment of autophagy termination causes cell death and muscle atrophy
Liu et al. report a function of the Cul3-KLHL20 ubiquitin ligase in a feedback regulation, leading to autophagy termination through the degradation of multiple subunits of ULK1 and VPS34 complexes. This mechanism is important for cell survival and muscle homeostasis.
Background and Aims
The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3–5‐cm HCC over time.
Approach and Results
From ...2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008–2019 (n = 335 in each group) and 2014–2019 (n = 257 in each group) cohorts, respectively. For cohort 2008–2019, during a median follow‐up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65–1.19, p = 0.420), and MWA was inferior to LLR regarding disease‐free survival (DFS) (HR 1.36, 95% CI 1.05–1.75, p = 0.017). For cohort 2014–2019, there was comparable OS (HR 0.85, 95% CI 0.56–1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98–1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1–4.0‐cm HCCs (HR 0.88, 95% CI 0.53–1.47, p = 0.630) and 4.1–5.0‐cm HCCs (HR 0.77, 95% CI 0.37–1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001).
Conclusions
MWA might be a first‐line alternative to LLR for solitary 3–5‐cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
•This is the first report on a series of BiOxCly/BiOmIn heterojunctions.•The BiOxCly/BiOmIn composition was controlled by adjusting the growth parameters.•The BiOxCly/BiOmIn were indirect ...semiconductors with a 1.78–2.95-eV bandgap.•The new photocatalysts removed CV at a much faster rate than TiO2.•Mechanisms were determined by separating the intermediates using HPLC-MS.
A series of BiOxCly/BiOmIn composites were prepared using autoclave hydrothermal methods. The composition and morphologies of the BiOxCly/BiOmIn composites were controlled by adjusting the experimental conditions: the reaction pH value, temperature, and KCl/KI molar ratio. The products were characterized using X-ray diffraction, scanning electron microscopy-electron dispersive X-ray spectroscopy, UV–vis diffuse reflectance spectroscopy, Brunauer–Emmett–Teller specific surface areas, cathodoluminescence, high-resolution transmission electron microscopy, and high-resolution X-ray photoelectron spectroscopy. The photocatalytic efficiencies of composite powder suspensions were evaluated by monitoring the crystal violet (CV) concentrations. In addition, the quenching effects of various scavengers indicated that the reactive O2− played a major role, and OH or h+ played a minor role in CV degradation. The intermediates formed during the decomposition process were isolated, identified, and characterized using high performance liquid chromatography-photodiode array-electrospray ionization-mass spectrometry to elucidate the CV decomposition mechanism.
Staphylococcus aureus and its biofilm have emerged as a significant threat to the safety of dairy products. In recent years, lactic acid bacteria (LAB) bacteriocins have been widely acknowledged as ...the potential natural antibacterial substance in food biopreservation due to their excellent antibacterial effects. However, few LAB bacteriocins with antibacterial and antibiofilm activity against S. aureus have been reported in dairy products. In the present study, a novel bacteriocin LSX01 of Lactobacillus paracasei LS-6 isolated from a traditional fermented yogurt produced in Yunnan, China, was purified and characterized extensively. The LSX01 possessed a molecular weight of 967.49 Da and an AA sequence of LDQAGISYT. The minimum inhibitory concentration of LSX01 against S. aureus_45 was 16.90 μg/mL, which was close to or lower than the previously reported bacteriocins. The LSX01 exhibited an extensive antimicrobial spectrum against both gram-positive and gram-negative bacteria. Moreover, LSX01 exhibited excellent tolerance to heat and acid-base treatments, and sensitivity to the proteolytic enzymes, such as pepsin and proteinase K. Furthermore, the treatment of S. aureus_45 planktonic cells with LSX01 significantly reduced their metabolic activity and disrupted the cell membrane integrity. Scan electron microscopy results demonstrated that LSX01 induced cytoplasmic content leakage and cell deformation. Additionally, biofilm formation of S. aureus_45 was also significantly inhibited by LSX01. Overall, the results suggested that the novel LAB bacteriocin LSX01 possessed antibacterial activity and antibiofilm activity against S. aureus and, hence, could have potential for improving safety of dairy products.
Summary
A major challenge of modern agricultural biotechnology is the optimization of plant architecture for enhanced productivity, stress tolerance and water use efficiency (WUE). To optimize plant ...height and tillering that directly link to grain yield in cereals and are known to be tightly regulated by gibberellins (GAs), we attenuated the endogenous levels of GAs in rice via its degradation. GA 2‐oxidase (GA2ox) is a key enzyme that inactivates endogenous GAs and their precursors. We identified three conserved domains in a unique class of C20 GA2ox, GA2ox6, which is known to regulate the architecture and function of rice plants. We mutated nine specific amino acids in these conserved domains and observed a gradient of effects on plant height. Ectopic expression of some of these GA2ox6 mutants moderately lowered GA levels and reprogrammed transcriptional networks, leading to reduced plant height, more productive tillers, expanded root system, higher WUE and photosynthesis rate, and elevated abiotic and biotic stress tolerance in transgenic rice. Combinations of these beneficial traits conferred not only drought and disease tolerance but also increased grain yield by 10–30% in field trials. Our studies hold the promise of manipulating GA levels to substantially improve plant architecture, stress tolerance and grain yield in rice and possibly in other major crops.
The health crisis due to coronavirus disease 2019 (COVID-19) has shocked the world, with more than 1 million infections and casualties. COVID-19 can present from mild illness to multi-organ ...involvement, but especially acute respiratory distress syndrome. Cardiac injury and arrhythmias, including atrial fibrillation (AF), are not uncommon in COVID-19. COVID-19 is highly contagious, and therapy against the virus remains premature and largely unknown, which makes the management of AF patients during the pandemic particularly challenging. We describe a possible pathophysiological link between COVID-19 and AF, and therapeutic considerations for AF patients during this pandemic.
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