SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression.

Mitochondria are cellular powerhouses that generate energy through the electron transport chain (ETC). The mitochondrial genome (mtDNA) encodes essential ETC proteins in a compartmentalized manner, however, the mechanism underlying metabolic regulation of mtDNA function remains unknown. Here, we report that expression of tricarboxylic acid cycle enzyme succinate-CoA ligase SUCLG1 strongly correlates with ETC genes across various TCGA cancer transcriptomes. Mechanistically, SUCLG1 restricts succinyl-CoA levels to suppress the succinylation of mitochondrial RNA polymerase (POLRMT). Lysine 622 succinylation disrupts the interaction of POLRMT with mtDNA and mitochondrial transcription factors. SUCLG1-mediated POLRMT hyposuccinylation maintains mtDNA transcription, mitochondrial biogenesis, and leukemia cell proliferation. Specifically, leukemia-promoting FMS-like tyrosine kinase 3 (FLT3) mutations modulate nuclear transcription and upregulate SUCLG1 expression to reduce succinyl-CoA and POLRMT succinylation, resulting in enhanced mitobiogenesis. In line, genetic depletion of POLRMT or SUCLG1 significantly delays disease progression in mouse and humanized leukemia models. Importantly, succinyl-CoA level and POLRMT succinylation are downregulated in FLT3-mutated clinical leukemia samples, linking enhanced mitobiogenesis to cancer progression. Together, SUCLG1 connects succinyl-CoA with POLRMT succinylation to modulate mitochondrial function and cancer development.

PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability.

The pyruvate kinase M2 isoform (PKM2) is preferentially expressed in cancer cells to regulate anabolic metabolism. Although PKM2 was recently reported to regulate lipid homeostasis, the molecular mechanism remains unclear. Herein, we discovered an ER transmembrane protein 33 (TMEM33) as a downstream effector of PKM2 that regulates activation of SREBPs and lipid metabolism. Loss of PKM2 leads to up-regulation of TMEM33, which recruits RNF5, an E3 ligase, to promote SREBP-cleavage activating protein (SCAP) degradation. TMEM33 is transcriptionally regulated by nuclear factor erythroid 2-like 1 (NRF1), whose cleavage and activation are controlled by PKM2 levels. Total plasma cholesterol levels are elevated by either treatment with PKM2 tetramer-promoting agent TEPP-46 or by global PKM2 knockout in mice, highlighting the essential function of PKM2 in lipid metabolism. Although depletion of PKM2 decreases cancer cell growth, global PKM2 knockout accelerates allografted tumor growth. Together, our findings reveal the cell-autonomous and systemic effects of PKM2 in lipid homeostasis and carcinogenesis, as well as TMEM33 as a bona fide regulator of lipid metabolism.

Passionfruit Genomic Database (PGD): a comprehensive resource for passionfruit genomics.

Passionfruit (Passiflora edulis) is a significant fruit crop in the commercial sector, owing to its high nutritional and medicinal value. The advent of high-throughput genomics sequencing technology has led to the publication of a vast amount of passionfruit omics data, encompassing complete genome sequences and transcriptome data under diverse stress conditions. To facilitate the efficient integration, storage, and analysis of these large-scale datasets, and to enable researchers to effectively utilize these omics data, we developed the first passionfruit genome database (PGD). The PGD platform comprises a diverse range of functional modules, including a genome browser, search function, heatmap, gene expression patterns, various tools, sequence alignment, and batch download, thereby providing a user-friendly interface. Additionally, supplementary practical tools have been developed for the PGD, such as gene family analysis tools, gene ontology (GO) terms, a pathway enrichment analysis, and other data analysis and mining tools, which enhance the data's utilization value. By leveraging the database's robust scalability, the intention is to continue to collect and integrate passionfruit omics data in the PGD, providing comprehensive and in-depth support for passionfruit research. The PGD is freely accessible via http://passionfruit.com.cn .

Remotely Bonded Bridging Dioxygen Ligands Enhance Hydrogen Transfer in a Silica-Supported Tetrairidium Cluster Catalyst.

A longstanding challenge in catalysis by noble metals has been to understand the origin of enhancements of rates of hydrogen transfer that result from the bonding of oxygen near metal sites. We investigated structurally well-defined catalysts consisting of supported tetrairidium carbonyl clusters with single-atom (apical iridium) catalytic sites for ethylene hydrogenation. Reaction of the clusters with ethylene and H2 followed by O2 led to the onset of catalytic activity as a terminal CO ligand at each apical Ir atom was removed and bridging dioxygen ligands replaced CO ligands at neighboring (basal-plane) sites. The presence of the dioxygen ligands caused a 6-fold increase in the catalytic reaction rate, which is explained by the electron-withdrawing capability induced by the bridging dioxygen ligands, consistent with the inference that reductive elimination is rate-determining. Electronic-structure calculations demonstrate an additional role of the dioxygen ligands, changing the mechanism of hydrogen transfer from one involving equatorial hydride ligands to that involving bridging hydride ligands. This mechanism is made evident by an inverse kinetic isotope effect observed in ethylene hydrogenation reactions with H2 and, alternatively, with D2 on the cluster incorporating the dioxygen ligands and is a consequence of quasi-equilibrated hydrogen transfer in this catalyst. The same mechanism accounts for rate enhancements induced by the bridging dioxygen ligands for the catalytic reaction of H2 with D2 to give HD. We posit that the mechanism involving bridging hydride ligands facilitated by oxygen ligands remote from the catalytic site may have some generality in catalysis by oxide-supported noble metals.

Unveiling the repressive mechanism of a PPS-like regulator (PspR) in polyhydroxyalkanoates biosynthesis network.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a type of polyhydroxyalkanoates (PHA) that exhibits numerous outstanding properties and is naturally synthesized and elaborately regulated in various microorganisms. However, the regulatory mechanism involving the specific regulator PhaR in Haloferax mediterranei, a major PHBV production model among Haloarchaea, is not well understood. In our previous study, we showed that deletion of the phosphoenolpyruvate (PEP) synthetase-like (pps-like) gene activates the cryptic phaC genes in H. mediterranei, resulting in enhanced PHBV accumulation. In this study, we demonstrated the specific function of the PPS-like protein as a negative regulator of phaR gene expression and PHBV synthesis. Chromatin immunoprecipitation (ChIP), in situ fluorescence reporting system, and in vitro electrophoretic mobility shift assay (EMSA) showed that the PPS-like protein can bind to the promoter region of phaRP. Computational modeling revealed a high structural similarity between the rifampin phosphotransferase (RPH) protein and the PPS-like protein, which has a conserved ATP-binding domain, a His domain, and a predicted DNA-binding domain. Key residues within this unique DNA-binding domain were subsequently validated through point mutation and functional evaluations. Based on these findings, we concluded that PPS-like protein, which we now renamed as PspR, has evolved into a repressor capable of regulating the key regulator PhaR, and thereby modulating PHBV synthesis. This regulatory network (PspR-PhaR) for PHA biosynthesis is likely widespread among haloarchaea, providing a novel approach to manipulate haloarchaea as a production platform for high-yielding PHA. KEY POINTS: • The repressive mechanism of a novel inhibitor PspR in the PHBV biosynthesis was demonstrated • PspR is widespread among the PHA accumulating haloarchaea • It is the first report of functional conversion from an enzyme to a trans-acting regulator in haloarchaea.

A Priori Design of Dual-Atom Alloy Sites and Experimental Demonstration of Ethanol Dehydrogenation and Dehydration on PtCrAg.

Single-atom catalysts have received significant attention for their ability to enable highly selective reactions. However, many reactions require more than one adjacent site to align reactants or break specific bonds. For example, breaking a C-O or O-H bond may be facilitated by a dual site containing an oxophilic element and a carbophilic or "hydrogenphilic" element that binds each molecular fragment. However, design of stable and well-defined dual-atom sites with desirable reactivity is difficult due to the complexity of multicomponent catalytic surfaces. Here, we describe a new type of dual-atom system, trimetallic dual-atom alloys, which were designed via computation of the alloying energetics. Through a broad computational screening we discovered that Pt-Cr dimers embedded in Ag(111) can be formed by virtue of the negative mixing enthalpy of Pt and Cr in Ag and the favorable interaction between Pt and Cr. These dual-atom alloy sites were then realized experimentally through surface science experiments that enabled the active sites to be imaged and their reactivity related to their atomic-scale structure. Specifically, Pt-Cr sites in Ag(111) can convert ethanol, whereas PtAg and CrAg are unreactive toward ethanol. Calculations show that the oxophilic Cr atom and the hydrogenphilic Pt atom act synergistically to break the O-H bond. Furthermore, ensembles with more than one Cr atom, present at higher dopant loadings, produce ethylene. Our calculations have identified many other thermodynamically favorable dual-atom alloy sites, and hence this work highlights a new class of materials that should offer new and useful chemical reactivity beyond the single-atom paradigm.

Thyroid-stimulating hormone regulates cardiac function through modulating HCN2 via targeting microRNA-1a.

Previous studies have found microRNA-1 (miR-1) and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) may be involved in the pathogenesis of thyroid hormone (TH) induced cardiac hypertrophy. However, little is known about the role of miR-1 and HCN2 in thyroid stimulation hormone (TSH)-induced cardiac dysfunction. In order to investigate the molecular mechanisms of TSH induced cardiac dysfunction and the role of miR-1/HCN2 in that process, we evaluated the expression of miR-1a/HCN2 in the ventricular myocardium of hypothyroid mice and in TSH-stimulated H9c2 cardiomyocytes. Our data revealed that hypothyroidism mice had smaller hearts, ventricular muscle atrophy, and cardiac contractile dysfunction compared with euthyroid controls. The upregulation of miR-1a and downregulation of HCN2 were found in ventricular myocardium of hypothyroid mice and TSH-stimulated H9c2 cardiomyocytes, indicating that miR-1a and HCN2 may be involved in TSH-induced cardiac dysfunction. We also found that the regulation of miR-1a and HCN2 expression and HCN2 channel activity by TSH requires TSHR, while the regulation of HCN2 expression and HCN2 channel function by TSH requires miR-1a. Thus, our data revealed the potential mechanism of TSH-induced cardiac dysfunction and might shed new light on the pathological role of miR-1a/HCN2 in hypothyroid heart disease.

BAF155 methylation drives metastasis by hijacking super-enhancers and subverting anti-tumor immunity.

Subunits of the chromatin remodeler SWI/SNF are the most frequently disrupted genes in cancer. However, how post-translational modifications (PTM) of SWI/SNF subunits elicit epigenetic dysfunction remains unknown. Arginine-methylation of BAF155 by coactivator-associated arginine methyltransferase 1 (CARM1) promotes triple-negative breast cancer (TNBC) metastasis. Herein, we discovered the dual roles of methylated-BAF155 (me-BAF155) in promoting tumor metastasis: activation of super-enhancer-addicted oncogenes by recruiting BRD4, and repression of interferon α/γ pathway genes to suppress host immune response. Pharmacological inhibition of CARM1 and BAF155 methylation not only abrogated the expression of an array of oncogenes, but also boosted host immune responses by enhancing the activity and tumor infiltration of cytotoxic T cells. Moreover, strong me-BAF155 staining was detected in circulating tumor cells from metastatic cancer patients. Despite low cytotoxicity, CARM1 inhibitors strongly inhibited TNBC cell migration in vitro, and growth and metastasis in vivo. These findings illustrate a unique mechanism of arginine methylation of a SWI/SNF subunit that drives epigenetic dysregulation, and establishes me-BAF155 as a therapeutic target to enhance immunotherapy efficacy.

Anaerobic methane oxidation linked to Fe(III) reduction in a Candidatus Methanoperedens-enriched consortium from the cold Zoige wetland at Tibetan Plateau.

Anaerobic oxidation of methane (AOM) is a microbial process degrading ample methane in anoxic environments, and Ca. Methanoperedens mediated nitrate- or metal-reduction linked AOM is believed important in freshwater systems. This work, via 16S rRNA gene diversity survey and 16S rRNA quantification, found abundant Ca. Methanoperedens along with iron in the cold Zoige wetland at Tibetan Plateau. The wetland soil microcosm performed Fe(III) reduction, rather than nitrate- nor sulphate-reduction, coupled methane oxidation (3.87 µmol d-1 ) with 32.33 µmol Fe(II) accumulation per day at 18°C, but not at 30°C. A metagenome-assembled genome (MAG) recovered from the microcosm exhibits ~74% average nucleotide identity with the reported Ca. Methanoperedens spp. that perform Fe(III) reduction linked AOM, thus a novel species Ca. Methanoperedens psychrophilus was proposed. Ca. M. psychrophilus contains the whole suite of CO2 reductive methanogenic genes presumably involving in AOM via a reverse direction, and comparative genome analysis revealed its unique gene categories: the multi-heme clusters (MHCs) cytochromes, the S-layer proteins highly homologous to those recovered from lower temperature environments and type IV pili, those could confer Ca. M. psychrophilus of cold adaptability. Therefore, this work reports the first methanotroph implementing AOM in an alpine wetland.

Metagenomic insights into the environmental adaptation and metabolism of Candidatus Haloplasmatales, one archaeal order thriving in saline lakes.

The KTK 4A-related Thermoplasmata thrives in the sediment of saline lakes; however, systematic research on its taxonomy, environmental adaptation and metabolism is lacking. Here, we detected this abundant lineage in the sediment of five artificially separated ponds (salinity 7.0%-33.0%) within a Chinese soda-saline lake using culture-independent metagenomics and archaeal 16S rRNA gene amplicons. The phylogenies based on the 16S rRNA gene, and 122 archaeal ubiquitous single-copy proteins and genome-level identity analyses among the metagenome-assembled genomes demonstrate this lineage forming a novel order, Candidatus Haloplasmatales, comprising four genera affiliated with the identical family. Isoelectric point profiles of predicted proteomes suggest that most members adopt the energetically favourable 'salt-in' strategy. Functional prediction indicates the lithoheterotrophic nature with the versatile metabolic potentials for carbohydrate and organic acids as well as carbon monoxide and hydrogen utilization. Additionally, hydrogenase genes hdrABC-mvhADG are linked with incomplete reductive citrate cycle genes in the genomes, suggesting their functional connection. Comparison with the coupling of HdrABC-MvhADG and methanogenesis pathway provides new insights into the compatibility of laterally acquired methanogenesis with energy metabolism in the related order Methanomassiliicoccales. Globally, our research sheds light on the taxonomy, environmental adaptative mechanisms, metabolic potentials and evolutional significance of Ca. Haloplasmatales.

Rhabdonatronobacter sediminivivens gen. nov., sp. nov. isolated from the sediment of Hutong Qagan Soda Lake.

A novel Gram-stain-negative bacterium, designated as IM2376T, was isolated from the sediment of Hutong Qagan Lake in the Ordos, Inner Mongolia Autonomous Region of China. Phylogenetic analysis based on 16S rRNA gene sequence revealed that the strain IM2376T had the highest similarity with Roseinatronobacter thiooxidans DSM 13087T (96.2%) and Rhodobaca bogoriensis LBB1T (96.2%) of the family Rhodobacteraceae. Genomic relatedness analyses showed that strain IM2376T was clearly distinguished from other species in the family Rhodobacteraceae, with average nucleotide identities, average amino acid identities, and in silico DNA-DNA hybridization values not more than 74.1, 68.5, and 20.2%, respectively. The fatty acids were mainly composed of C18:1ω7c (64.9%), iso-C16:0 (16.3%), and C16: 1ω7c/C16:1ω6c (6.0%). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylcholine. The predominant ubiquinone was Q-10 (94.9%). The genomic DNA G + C content was 66 mol%. Based on all these results, strain IM2376T was considered a novel species of a new genus in the family Rhodobacteraceae, for which the name Rhabdonatronobacter sediminivivens gen. nov., sp. nov. is proposed. The type strain of Rhabdonatronobacter sediminivivens is IM2376T (= CGMCC 1.17852T = KCTC 92134T).

Aliidiomarina halalkaliphila sp. nov., a haloalkaliphilic bacterium isolated from a soda lake in Inner Mongolia Autonomous Region, China.

A haloalkaliphilic strain (IM 1326T) was isolated from brine sampled at a soda lake in the Inner Mongolia Autonomous Region, China. Cells of the strain were rod-shaped and motile. Strain IM 1326T was able to grow at 4-42 °C (optimum, 37 °C) with 0-13.0 % (w/v) NaCl concentrations (optimum at 4.0-6.0 %) and at pH 7.5-11.0 (optimum at 9.0-10.0). The 16S rRNA gene phylogenetic analysis revealed that the isolate belongs to the genus Aliidiomarina and is closely related to the type strains of Aliidiomarina sanyensis (95.8 % sequence similarity), Aliidiomarina shirensis (95.7 %), Aliidiomarina iranensis (95.4 %) and Aliidiomarina haloalkalitolerans (95.3 %). The whole genome of strain IM 1326T was sequenced, and the genomic DNA G+C content was 49.7 mol%. Average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values between the isolate and the related Aliidiomarina species were 68.1-84.9 %, 76-78 % and 18.4-20.4 %, respectively. The respiratory quinone was ubiquinone-8. The polar lipid profile included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and one unidentified aminophospholipid. The predominant cellular fatty acids were summed feature 9 (10-methyl-C16 : 0/iso-C17 : 1 ω9c, 22.2 %), iso-C15 : 0 (16.1 %) and iso-C17 : 0 (13.1 %). Based on the results of phylogenetic analysis, genome relatedness, and the physiological and chemotaxonomic properties of the isolate, strain IM 1326T is considered to represent a novel species of the genus Aliidiomarina, for which the name Aliidiomarina halalkaliphila sp. nov. is proposed (type strain IM 1326T=CGMCC 1.17056T=JCM 34227T).

Epidemiology of gaming disorder and its effect on anxiety and insomnia in Chinese ethnic minority adolescents.

BACKGROUND: The growing popularity and frequency of online game use have resulted in a large number of studies reporting various mental problems associated with game abuse in adolescents. In this article, we examined the prevalence of gaming disorder (GD) and explored the associations of GD with anxiety and insomnia symptoms in minority youth in China. METHODS: A total of 1494 students completed the Problematic Online Gaming Questionnaire Short-Form (POGQ-SF), the Generalized Anxiety Disorder 7-item questionnaire (GAD-7), and Athens Insomnia Scale (AIS). Chi-square and binary logistic regression analyses were used to explore the associations between gaming disorder and anxiety/insomnia. RESULTS: A total of 356 (23.83%) respondents reported that they had gaming disorder. Chi-square analysis showed that gender, grade, marital status of parents and exercise situation were significantly associated with GD. Binary logistic regression analysis showed that those who had GD were at significantly higher risk for anxiety and insomnia than those without GD. CONCLUSION: We found a high incidence of GD and a positive association among anxiety, insomnia and GD. Thus, special attention should be paid to those who have suffered from GD. It is worth addressing the adverse effects of GD on anxiety and insomnia.

Analysis of the cause of missed diagnosis in mpMRI/TRUS fusion-guided targeted prostate biopsy.

OBJECTIVES: To investigate the causes of missed diagnosis in mpMRI/TRUS fusion-guided targeted prostate biopsy. METHODS: The clinical data of 759 patients who underwent transperineal prostate biopsy from March 2021 to June 2021 at Nanjing DrumTower Hospital were retrospectively analyzed. Twenty-one patients had MRI contraindications. Ultimately, 738 patients completed mpMRI/TRUS fusion-guided targeted prostate biopsy + 12-core transperineal systematic biopsy after mpMRI and PI-RADS scoring. The pathological diagnoses from targeted and systematic biopsy were compared to evaluate and analyze the reasons for missed diagnoses in targeted biopsy. RESULTS: A total of 388 prostate cancer patients were identified, including 37 (9%) missed diagnoses with targeted biopsy and 44 (11.34%) with systematic biopsy. Between the target biopsy missed diagnosis group and not missed diagnosis group, there was no significant difference in age (71.08 ± 7.11 vs. 71.80 ± 7.94), but PSA (13.63 ± 12.41 vs. 54.54 ± 177.25 ng/ml), prostate volume (61.82 ± 40.64 vs. 44.34 ± 25.07 cm3), PSAD (0.27 ± 0.28 vs. 1.07 ± 2.91), and ISUP grade [1(1) vs. 3(2)] were significantly different. The pathological results of the 37 targeted biopsy missed diagnoses were recompared with MRI: 21 prostate cancers were normal on MRI; 9 cancer areas were abnormal on MRI; and 7 cancer areas on MRI were PI-RADS 3. CONCLUSIONS: Early prostate cancer, large prostate, effect of local anesthesia, doctor-patient cooperation, MRI diagnosis, and operator technology were possible factors for missed diagnosis in targeted biopsy. Improvements imaging technology, greater experience, and personalized biopsy may lead to an accurate pathological diagnosis.

Highly integrated adaptive mechanisms in Spiribacter halalkaliphilus, a bacterium abundant in Chinese soda-saline lakes.

Soda-saline lakes are polyextreme environments inhabited by many haloalkaliphiles, including one of the most abundant Spiribacter species. However, its mechanisms of adaptation are not ecophysiologically characterized. Based on a large-scale cultivation strategy, we obtained a representative isolate of this Spiribacter species whose relative abundance was the highest (up to 15.63%) in a wide range of salinities in the soda-saline lakes in Inner Mongolia, China. This species is a chemoorganoheterotrophic haloalkaliphile. It has a small and streamlined genome and utilizes a wide variety of compatible solutes to resist osmotic pressure and multiple monovalent cation/proton antiporters for pH homeostasis. In addition to growth enhancement by light under microaerobic conditions, cell growth, organic substrate consumption and polyhydroxybutyrate biosynthesis were also improved by inorganic sulfide. Both quantitative RT-PCR and enzymatic assays verified that sulfide:quinone oxidoreductase was upregulated during this process. Metatranscriptomic analysis indicated that all genes related to environmental adaptation were transcribed in natural environments. Overall, this study has identified a novel abundant haloalkaliphile with multiple and highly integrated adaptive strategies and found that inorganic sulfide was able to improve the adaptation of a heterotroph to polyextreme environments.

Co-opting the fermentation pathway for tombusvirus replication: Compartmentalization of cellular metabolic pathways for rapid ATP generation.

The viral replication proteins of plus-stranded RNA viruses orchestrate the biogenesis of the large viral replication compartments, including the numerous viral replicase complexes, which represent the sites of viral RNA replication. The formation and operation of these virus-driven structures require subversion of numerous cellular proteins, membrane deformation, membrane proliferation, changes in lipid composition of the hijacked cellular membranes and intensive viral RNA synthesis. These virus-driven processes require plentiful ATP and molecular building blocks produced at the sites of replication or delivered there. To obtain the necessary resources from the infected cells, tomato bushy stunt virus (TBSV) rewires cellular metabolic pathways by co-opting aerobic glycolytic enzymes to produce ATP molecules within the replication compartment and enhance virus production. However, aerobic glycolysis requires the replenishing of the NAD+ pool. In this paper, we demonstrate the efficient recruitment of pyruvate decarboxylase (Pdc1) and alcohol dehydrogenase (Adh1) fermentation enzymes into the viral replication compartment. Depletion of Pdc1 in combination with deletion of the homologous PDC5 in yeast or knockdown of Pdc1 and Adh1 in plants reduced the efficiency of tombusvirus replication. Complementation approach revealed that the enzymatically functional Pdc1 is required to support tombusvirus replication. Measurements with an ATP biosensor revealed that both Pdc1 and Adh1 enzymes are required for efficient generation of ATP within the viral replication compartment. In vitro reconstitution experiments with the viral replicase show the pro-viral function of Pdc1 during the assembly of the viral replicase and the activation of the viral p92 RdRp, both of which require the co-opted ATP-driven Hsp70 protein chaperone. We propose that compartmentalization of the co-opted fermentation pathway in the tombusviral replication compartment benefits the virus by allowing for the rapid production of ATP locally, including replenishing of the regulatory NAD+ pool by the fermentation pathway. The compartmentalized production of NAD+ and ATP facilitates their efficient use by the co-opted ATP-dependent host factors to support robust tombusvirus replication. We propose that compartmentalization of the fermentation pathway gives an evolutionary advantage for tombusviruses to replicate rapidly to speed ahead of antiviral responses of the hosts and to outcompete other pathogenic viruses. We also show the dependence of turnip crinkle virus, bamboo mosaic virus, tobacco mosaic virus and the insect-infecting Flock House virus on the fermentation pathway, suggesting that a broad range of viruses might induce this pathway to support rapid replication.

Metabolic benefits of inhibition of p38α in white adipose tissue in obesity.

p38 has long been known as a central mediator of protein kinase A (PKA) signaling in brown adipocytes, which positively regulate the transcription of uncoupling protein 1 (UCP-1). However, the physiological role of p38 in adipose tissues, especially the white adipose tissue (WAT), is largely unknown. Here, we show that mice lacking p38α in adipose tissues display a lean phenotype, improved metabolism, and resistance to diet-induced obesity. Surprisingly, ablation of p38α causes minimal effects on brown adipose tissue (BAT) in adult mice, as evident from undetectable changes in UCP-1 expression, mitochondrial function, body temperature (BT), and energy expenditure. In contrast, genetic ablation of p38α in adipose tissues not only markedly facilitates the browning in WAT upon cold stress but also prevents diet-induced obesity. Consistently, pharmaceutical inhibition of p38α remarkably enhances the browning of WAT and has metabolic benefits. Furthermore, our data suggest that p38α deficiency promotes white-to-beige adipocyte reprogramming in a cell-autonomous manner. Mechanistically, inhibition of p38α stimulates the UCP-1 transcription through PKA and its downstream cAMP-response element binding protein (CREB), which form a positive feedback loop that functions to reinforce the white-to-beige phenotypic switch during cold exposure. Together, our study reveals that inhibition of p38α is able to promote WAT browning and confer metabolic benefits. Our study also indicates that p38α in WAT represents an exciting pharmacological target to combat obesity and metabolic diseases.

Salinadaptatus halalkaliphilus gen. nov., sp. nov., a haloalkaliphilic archaeon isolated from salt pond in Inner Mongolia Autonomous Region, China.

A haloalkaliphilic strain XQ-INN 246T was isolated from the sediment of a salt pond in Inner Mongolia Autonomous Region, China. Cells of the strain were rods, motile and strictly aerobic. The strain was able to grow in the presence of 2.6-5.3 M NaCl (optimum concentration is 4.4 M) at 30-50 °C (optimum temperature is 42 °C) and pH 7.0-10.0 (optimum pH is 8.0-8.5). The whole genome sequencing of strain XQ-INN 246T revealed a genome size of 4.52 Mbp and a DNA G+C content of 62.06 mol%. Phylogenetic tree based on 16S rRNA gene sequences and concatenated amino acid sequences of 122 single-copy conserved proteins revealed a robust lineage of the strain XQ-INN 246T with members of related genera of the family Natrialbaceae. The strain possessed the polar lipids of phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester. No glycolipids were detected. Based on phylogenetic analysis, phenotypic characteristics, chemotaxonomic properties and genome relatedness, the isolate was proposed as the type strain of a novel species of a new genus within the family Natrialbaceae, for which the name Salinadaptatus halalkaliphilus gen. nov., sp. nov. is proposed. The type strain is XQ-INN 246T (=CGMCC 1.16692T=JCM 33751T).

microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle.

The metabolic regulation of cell death is sophisticated. A growing body of evidence suggests the existence of multiple metabolic checkpoints that dictate cell fate in response to metabolic fluctuations. However, whether microRNAs (miRNAs) are able to respond to metabolic stress, reset the threshold of cell death, and attempt to reestablish homeostasis is largely unknown. Here, we show that miR-378/378* KO mice cannot maintain normal muscle weight and have poor running performance, which is accompanied by impaired autophagy, accumulation of abnormal mitochondria, and excessive apoptosis in skeletal muscle, whereas miR-378 overexpression is able to enhance autophagy and repress apoptosis in skeletal muscle of mice. Our in vitro data show that metabolic stress-responsive miR-378 promotes autophagy and inhibits apoptosis in a cell-autonomous manner. Mechanistically, miR-378 promotes autophagy initiation through the mammalian target of rapamycin (mTOR)/unc-51-like autophagy activating kinase 1 (ULK1) pathway and sustains autophagy via Forkhead box class O (FoxO)-mediated transcriptional reinforcement by targeting phosphoinositide-dependent protein kinase 1 (PDK1). Meanwhile, miR-378 suppresses intrinsic apoptosis initiation directly through targeting an initiator caspase-Caspase 9. Thus, we propose that miR-378 is a critical component of metabolic checkpoints, which integrates metabolic information into an adaptive response to reduce the propensity of myocytes to undergo apoptosis by enhancing the autophagic process and blocking apoptotic initiation. Lastly, our data suggest that inflammation-induced down-regulation of miR-378 might contribute to the pathogenesis of muscle dystrophy.

[Head and Face Protection of the Health Care Workers in the Operating Room of Peking Union Medical College Hospital during the Corona Virus Disease-19 Pandemic].

Objective To investigate the understanding of the head and face protection of the health care workers in operating room of Peking Union Medical College Hospital during the corona virus disease-19(COVID-19) pandemic.Methods The knowledge of head and face protection of health care workers in the operating room was evaluated based on the non-registered questionnaires for protection measures collected on-line.Results The survey was conducted in two phases.In the first phase(COVID-19 outbreak),153 questionnaires were collected.In the second phase(when Beijing lowered the emergency response to level 3 and normalized the epidemic prevention and control),101 questionnaires were collected.The results showed that 98% of health care workers had used any form of protective devices during the pandemic and anesthesiologists had the highest usage rate(93.0%)of ear-loop face mask with eye shield.During the pandemic,health care workers mainly used goggles(71.2%)for protection to diagnose and treat the patients with fever and ear-loop face mask with eye shield(56.2%)for protection to diagnose and treat the non-fever patients.In the first-and second-phase survey,43% and 68% of health care workers still used protection,and they mainly used face shield(50.0% and 56.5%)and ear-loop face mask with eye shield(56.1% and 68.1%).Conclusions During the pandemic,more than 90% of the health care workers in the operating room of Peking Union Medical College Hospital were aware of head and face protection.Different healthcare workers in the operating room had different choices of head and face protection,and more than 40% of them would still keep such protection during the normalized stage of pandemic prevention and control.