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The bulk properties and chemical reactivity of disordered Pt-Ni alloys in the A1 (fcc) structure are investigated using different methods: Virtual Crystal Approximation (VCA), Korringa–Kohn–Rostoker Coherent Potential Approximation (KKR-CPA), and large explicit supercells generated using Super-Cell Random Approximates (SCRAPs). While VCA predicts lattice constants that closely follow Vegard’s law, the large supercells and KKR-CPA predict lattice constants that are consistently larger than Vegard’s law. KKR-CPA results closely agree with those from the large supercells for the disordered alloys, producing similar projected density of states and magnetic moment across the composition range. For instance, while VCA predicts the disordered alloys to be non-magnetic at a Pt concentration (xPt) ≥ 0.5, KKR-CPA and SCRAPs predict the disordered alloys to remain ferromagnetic to higher Pt concentrations. As xPt decreases, the adsorption of H becomes more exothermic on bulk-terminated (111) surfaces but less exothermic on Pt monolayer-terminated (111) surfaces due largely to strain effects. (111) surfaces cut from the large supercells predict average H adsorption energies on the disordered alloys similar to those on the ordered phases of the same compositions, while VCA predicts H adsorption to be more exothermic.

To compare the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) versus laparoscopic partial nephrectomy (LPN) for large angiomyolipomas (AMLs). We retrospectively evaluated 150 patients who were treated with either RAPN or LPN for large angiomyolipomas from 2014 to 2018. Propensity score matching was performed on age, gender, BMI, Charlson Comorbidity Index, tumour side and size, preoperative eGFR and RENAL score. In total, 63 and 87 patients underwent RAPNs and LPNs, respectively. There were more large and complex AMLs in the RAPN cohort, with the median tumour maximal diameters and RENAL scores differing between the two groups (8 versus 7 cm and 9 versus 8, P = 0.01). After matching, the median warm ischemic time was significantly shorter in the RAPNs versus the LPNs (17 versus 22 min, P = 0.001). The rate of intraoperative complications in the RAPNs appeared lower than the LPNs (3.2% versus 8.1%). The median postoperative length of stay was significantly shorter in the RAPN cohort than the LPNs (P = 0.001). Twelve months after surgery, RAPNs received a 94.6% renal function prevention; while this was 90.8% in LPNs (P = 0.001). Subgroup analysis indicated that prior selective arterial embolization (SAE) was related to better renal function preservation in the RAPN cohort (P = 0.01). No recurrence occurred in either of the two cohorts. RAPN is a safe and effective alternative to LPNs for large AMLs with a shorter warm ischemic time and higher renal preservation rate. Recurrence was equivalent in both RAPNs and LPNs.

To improve the accuracy of bearing fault recognition, a novel bearing fault diagnosis (PAVMD-EE-PNN) method based on parametric adaptive variational mode decomposition (VMD), energy entropy, and probabilistic neural network (PNN) is proposed in this paper. In view of the effect of VMD on signal decomposition effect affected by the number of preset decomposition modes, a central frequency screening method is proposed to determine the number of decomposition modes of the VMD method. The parametric adaptive VMD method is used to decompose the bearing fault signal into a series of intrinsic mode function (IMF) components. The energy entropy of IMF components is calculated to form an eigenvector, which is input into the PNN model for training to obtain a fault recognition model with maximum output probability. The actual bearing vibration data are obtained and used to test and verify the effectiveness of the PAVMD-EE-PNN method. The experimental results show that the PAVMD-EE-PNN method can effectively and accurately identify the fault type, and the fault recognition effect is better than contrast fault diagnosis methods.

A crystalline iceplant-like nano-NaVPO4F@graphene composite is successfully synthesized by a freeze-drying process. Graphene forms a lamellar structure wherein NaVPO4F nanoparticles are uniformly adhered to the surface of graphene. The composite displays an intercalation-type reaction mechanism and excellent cycling and rate performance.

Although oxygen is a common ligand in supported metal catalysts, its coordination has been challenging to elucidate. We now characterize a diiridium complex that has been previously shown by X-ray diffraction crystallography to incorporate a μ-η1:η1-peroxo ligand. We observe markedly enhanced intensity at 788 cm-1 in the Raman spectrum of this complex, which is a consequence of bonding of the peroxo ligand but does not shift upon 18O labeling. Electronic structure calculations at the density functional theory level suggest that this increase in Raman intensity results from bands associated with rocking of CH2 substituents directly attached to P(Ph)2 groups coupling with the O-O band. These results provide part of the foundation for understanding oxygen ligands on a silica-supported tetrairidium carbonyl cluster stabilized with bulky electron-donating phosphine ligands [p-tert-butyl-calix[4]arene(OPr)3(OCH2PPh2) (Ph = phenyl; Pr = propyl)]. Reaction of the cluster with O2 also led to the growing in of a Raman band at 788 cm-1, similar to that in the diiridium complex and also assigned to the bonding of a bridging peroxo ligand. Infrared spectra recorded as the supported cluster reacted in sequential exposures to (i) H2, (ii) O2, (iii) H2, and (iv) CO indicate that two bridging peroxo ligands were bonded irreversibly per tetrairidium cluster, replacing bridging carbonyl ligands without altering either the cluster frame or the phosphine ligands. X-ray absorption near edge and infrared spectra include isosbestic points signifying a stoichiometrically simple reaction of the cluster with O2, and mass spectra of the effluent gas show that CO2 formed by oxidation of one terminal CO ligand per cluster as H2 (and not H2O) formed, evidence that hydride ligands had been present on the cluster following treatment (i). The understanding of how O2 reacts with the metal polyhedron provides a foundation for understanding of how oxidation catalysis may proceed on the surfaces of noble metals.

Background: The growing popularity and frequency of online games use has resulted in a large number of studies reporting various mental problems associated with its abuse in adolescents. In this article, we examined the prevalence of pathological online games use (POGU) and explored the associations of the POGU with anxiety and insomnia symptoms with minority youth in China.Methods: 1494 students completed a questionnaire of Problematic Online Gaming Questionnaire Short-Form (POGQ-SF), Generalized Anxiety Condition iems (GAD-7), and the Athens Insomnia Scale (AIS). Chi-square and binary logistic regression analysis were used to explore the association between pathological online games and anxiety/insomnia. Results: 356 (23.83%) respondents reported they had pathological online games use. Chi-square analysis shows that gender, grade, marital status of parents and exercise situation were significantly associated with POGU. Binary logistic regression analysis showed that those who had POGU were at significantly higher risk for anxiety and insomnia, compared to those who without POGU.Conclusion: We found a high incidence of POGU and a positive association among anxiety, insomnia and POGU. Thus, special focus should be paid to those who have suffered POGU. And, it is worth addressing the adverse effects of POGU on anxiety and insomnia.

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

Understanding hot carrier dynamics between plasmonic nanomaterials and its adsorbate is of great importance for plasmon‐enhanced photoelectronic processes such as photocatalysis, optical sensing and spectroscopic analysis. However, it is often challenging to identify specific dominant mechanisms for a given process because of the complex pathways and ultrafast interactive dynamics of the photoelectrons. Here, using CO2 reduction as an example, the underlying mechanisms of plasmon‐driven catalysis at the single‐molecule level using time‐dependent density functional theory calculations is clearly probed. The CO2 molecule adsorbed on two typical nanoclusters, Ag20 and Ag147, is photoreduced by optically excited plasmon, accompanied by the excitation of asymmetric stretching and bending modes of CO2. A nonlinear relationship has been identified between laser intensity and reaction rate, demonstrating a synergic interplay and transition from indirect hot‐electron transfer to direct charge transfer, enacted by strong localized surface plasmons. These findings offer new insights for CO2 photoreduction and for the design of effective pathways toward highly efficient plasmon‐mediated photocatalysis., Upon illumination, hot electrons generated by the plasmon decay around the silver clusters transfer into the molecular orbitals of CO2, resulting in activation of the asymmetrical stretching and bending mode of CO2 and leading to its final splitting. Cooperative interaction and transition from indirect hot‐electron transfer to direct charge transfer cause the nonlinear relationship between laser intensity and reaction rate.

Microorganisms play an essential role in sulfide removal. Alkaline absorption solution facilitates the sulfide’s dissolution and oxidative degradation, so haloalkaliphile is a prospective source for environmental-friendly and cost-effective biodesulfurization. In this research, 484 sulfide oxidation genes were identified from the metagenomes of the soda-saline lakes and a haloalkaliphilic heterotrophic bacterium Halomonas salifodinae IM328 (=CGMCC 22183) was isolated from the same habitat as the host for expression of a representative sequence. The genetic manipulation was successfully achieved through the conjugation transformation method, and sulfide: quinone oxidoreductase gene (sqr) was expressed via pBBR1MCS derivative plasmid. Furthermore, a whole-cell catalyst system was developed by using the engineered strain that exhibited a higher rate of sulfide oxidation under the optimal alkaline pH of 9.0. The whole-cell catalyst could be recycled six times to maintain the sulfide oxidation rates from 41.451 to 80.216 µmol·min−1·g−1 dry cell mass. To summarize, a whole-cell catalyst system based on the engineered haloalkaliphilic bacterium is potentiated to be applied in the sulfide treatment at a reduced cost.

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.

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.

Cold seeps are globally widespread seafloor ecosystems that feature abundant methane production and flourishing chemotrophic benthic communities. Chemical evidence indicates that cold seep methane is largely biogenic; however, the primary methane-producing organisms and associated pathways involved in methanogenesis remain elusive. This work detected methane production when glycine betaine (GBT) or trimethylamine (TMA) was added to the sediment microcosms of the Formosa cold seep, South China Sea. The methane production was suppressed by antibiotic inhibition of bacteria, while GBT was accumulated. This suggests that the widely used osmoprotectant GBT could be converted to cold seep biogenic methane via the synergistic activity of bacteria and methanogenic archaea because archaea are not sensitive to antibiotics and no bacteria are known to produce ample methane (mM). 16S rRNA gene diversity analyses revealed that the predominant bacterial and archaeal genera in the GBT-amended methanogenic microcosms included Oceanirhabdus and Methanococcoides. Moreover, metagenomic analyses detected the presence of grdH and mtgB genes that are involved in GBT reduction and demethylation, respectively. Two novel species were obtained, including bacterium Oceanirhabdus seepicola, which reduces GBT to TMA, and a methanogenic archaeon, Methanococcoides seepicolus, which produces methane from TMA and GBT. The two strains reconstituted coculture efficiently converted GBT to methane at 18°C; however, at 4°C addition of dimethylglycine (DMG), the GBT demethylation product, was necessary. Therefore, this work demonstrated that GBT is the precursor not only of the biogenic methane but also of the cryoprotectant DMG to the microorganisms at the Formosa cold seep. IMPORTANCE Numerous cold seeps have been found in global continental margins where methane is enriched in pore waters that are forced upward from sediments. Therefore, high concerns have been focused on the methane-producing organisms and the metabolic pathways in these environments because methane is a potent greenhouse gas. In this study, GBT was identified as the main precursor for methane in the Formosa cold seep of the South China Sea. Further, synergism of bacteria and methanogenic archaea was identified in GBT conversion to methane via the GBT reduction pathway, while methanogen-mediated GBT demethylation to methane was also observed. In addition, GBT-demethylated product dimethyl glycine acted as a cryoprotectant that promoted the cold seep microorganisms at cold temperatures. GBT is an osmoprotectant that is widely used by marine organisms, and therefore, the GBT-derived methanogenic pathway reported here could be widely distributed among global cold seep environments.

Objective: To evaluate the health impact of current and alternative patterns of rice consumption in Chinese adult men (40–79 years of age).Methods: We applied a risk–benefit assessment (RBA) model that took into account the health effects of selenium (Se), cadmium (Cd), and inorganic arsenic (i-As). The health effects included the prevention of prostate cancer associated with exposure to Se, and an increased risk of lung, bladder, and skin cancer for i-As and chronic kidney disease (CKD) for Cd. We defined the baseline scenario (BS) as the current individual mean daily consumption of rice in the population of interest and two alternative scenarios (AS): AS1 = 50 g/day and AS2 = 200 g/day. We estimated the health impact for different age groups in terms of change in Disability-Adjusted Life Years (ΔDALY).Results: The BS of rice consumption was 71.5–105.4 g/day in different age groups of adult men in China. We estimated that for AS1, the mean ΔDALY was −2.76 to 46.2/100,000 adult men of 40–79 years old. For AS2, the mean ΔDALY was 41.3 to 130.8/100,000 individuals in this population group.Conclusion: Our results showed that, based on associated exposure to selenium, cadmium, and i-As in rice, the current consumption of rice does not pose a risk to adult men in China. Also, a lower (50 g/day) or higher (200 g/day) rice consumption will not bring larger beneficial effects.

In recent years, outliers caused by manual operation errors and equipment acquisition failures often occur, bringing challenges to big data analysis. In view of the difficulties in identifying and correcting outliers of multi-source data, an intelligent identification and order-sensitive correction method of outliers from multi-data sources based on historical data mining was proposed. First, an intelligent identification method of outliers of single-source data is proposed based on neural tangent kernel K-means (NTKKM) clustering. The original data is mapped to high-dimensional feature space using Neural Tangent Kernel, where the features of outliers are acquired by K-means clustering to realize the accurate identification of outliers. Second, an order-sensitive missing value imputation framework for multi-source data (OMSMVI) was proposed. The similarity graph of sources with missing data was constructed based on multidimensional similarity analysis, and the filling order decision was transformed into an optimization problem to realize the optimal filling order decision of missing values in multi-source data. Finally, a neighborhood-based imputation (NI) algorithm is proposed. Based on the traditional KNN filling algorithm, neighboring nodes of sources with missing data are flexibly selected to the achieve accurate correction of outliers. The case experiment was operated on actual power grid data, and the results show that the proposed clustering method can identify outliers more accurately, and the determined optimal imputation sequence has higher accuracy, which provide a feasible new idea for the identification and correction of outliers in the process of data preprocessing.

A novel Gram-stain negative bacterium, designated IM2376T, was isolated from the sediment of Hutong Qagan Lake in Ordos, Inner Mongolia Autonomous Region of China. The strain IM2376T had the highest similarity with Roseinatronobacter thiooxidans DSM 13087T (96.18%) and Rhodobaca bogoriensis LBB1T (96.18%) of the family Rhodobacteraceae according to 16S rRNA gene sequence comparison. Genomic relatedness analyses showed that strain IM2376T was clearly distinguished from other species in the family Rhodobacteraceae, with average nucleotide identities, amino acid identities and in silico DNA-DNA hybridization values not more than 74.1%, 68.5% and 20.2%. The fatty acid was mainly composed of C18:1ω7c (64.86%), iso-C16:0 (16.33%) and C16: 1ω7c/C16:1ω6c (6.02%). The major polar lipid was diphosphatidyl glycerol, phosphatidylglycerol and phosphatidylcholine. The predominant ubiquinone was Q-10 (94.9%) and Q-11 (5.1%). The DNA G + C was 66 mol%. Based on all these results, strain IM2376T was considered to be 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 is IM2376T (= CGMCC 1.17852T).

Atomically dispersed supported catalysts are drawing wide attention because they offer properties different from those of conventional catalysts, with maximally efficient use of the metals. However...

The adsorption of cyclohexane, benzene, and alkyl-substituted benzene derivatives is studied on rutile TiO2(110) by a combination of molecular beam dosing, temperature-programmed desorption, and density functional theory (DFT). An inversion analysis is used to extract the coverage-dependent desorption energies from TiO2(110). The values of the suitable prefactors are derived from simple statistical mechanical models assuming different limits in the adsorbate mobility on the surface. The prefactor values determined using the vibrational frequencies from DFT calculations corroborate this analysis and show that the adsorbates are mobile in one or two dimensions on a corrugated TiO2(110) surface. The adsorption of benzene derivatives is found to be dominated by the dative Lewis acid–base interactions of the π system with the surface Ti ions. While the desorption energy generally increases with increasing the length and the number of substituents, the difference between the desorption energies decreases as the...

Objective Recent studies have shown that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family of extracellular ligands, plays an important role in the prevention of obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD). Considering that thyroid hormone (TH) has profound effects on whole-body energy metabolism, we speculate that circulating Nrg4 levels might be altered in patients with hyperthyroidism. Design and methods A total of 129 hyperthyroid patients and 100 healthy subjects were recruited. Of them, 39 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism. Serum Nrg4 levels were determined using the ELISA method. To further confirm the relationship between TH and Nrg4, C57BL/6 mice were treated with T3 and quantitative real-time PCR was performed to detect Nrg4 gene expression. Results Serum Nrg4 levels were significantly elevated in hyperthyroid patients as compared with normal controls (3.84 ± 1.63 vs 2.21 ± 1.04 ng/mL, P P 3 was further confirmed by animal and cell culture experiments. Conclusions Serum Nrg4 levels were increased in patients with hyperthyroidism. The liver and white adipose tissue might be primary sources contributing to elevated serum Nrg4 concentrations.

Rhodium gem-dicarbonyl complexes, Rh(CO)2, bonded within the pore structure of zeolite HY and formed by the reaction of Rh(CO)2(acac) (acac = acetylacetonato) with OH groups on the zeolite surface were converted in >95% yield to Rh4(CO)12 by reaction with CO + water at 308 K, and the process was reversed by treatment of the supported clusters in helium at 353 K. The chemistry of these reactions was characterized by IR and X-ray absorption spectra recorded during the changes and by density functional theory. The cluster formation is driven by the water gas shift half-reaction, leading to generation of CO2 and zeolite surface protons, and the reverse reaction proceeds via the half-reaction that completes the cycle of the water gas shift reaction. Thus, the overall process is cyclic–catalytic. The yield in the synthesis of Rh4(CO)12 is the highest reported, and the high selectivity is facilitated by the confining environment for the clusters in the zeolite supercages and the low density of OH groups on the z...

Although ticagrelor has been demonstrated to possess an anti-atherosclerosis (AS) effect, its underlying mechanism remains unclear. In the present study, it was investigated whether ticagrelor reduces oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell apoptosis, an initial step for the development of AS, and alleviates AS in apolipoprotein-E-deficient (ApoE−/−) mice by inhibiting the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9). The human endothelial cell line EAhy926 was treated with ox-LDL, ox-LDL + ticagrelor (40 µmol/l) and ox-LDL + ticagrelor (60 µmol/l) for 24 h. Cell apoptosis was detected using Annexin V-fluorescein isothiocyanate/propidium iodide staining. The expression levels of PCSK9, apoptosis-associated proteins and signaling pathways were determined by reverse transcription-quantitative polymerase chain reaction and western blotting. ApoE−/− mice fed a high-fat diet were used to induce an AS model. After 20 weeks, ApoE−/− mice were randomly assigned to receive saline or ticagrelor intragastrically for 10 days. The formation of atherosclerotic plaques was detected by hematoxylin and eosin staining. The expression of PCSK9 in the arterial tissues was measured by immunohistochemistry. The results demonstrated that treatment with ticagrelor was able to decrease ox-LDL-induced apoptosis in a concentration-dependent manner (40 µmol/l vs. ox-LDL, 17.58±2.66 vs. 27.25±5.54%; 60 µmol/l vs. ox-LDL, 12.26±1.54 vs. 27.25±5.54%). The mRNA and protein expression level of PCSK9 significantly decreased following treatment with ticagrelor, accompanied with upregulation of B-cell lymphoma (Bcl) 2 and downregulation of Bcl-2 associated X, apoptosis regulator, caspase-3, p38, phosphorylated-(p) p38, p-c-Jun N-terminal kinases (JNK), p-extracellular signal-regulated kinases and the ratio of p-JNK to JNK. Histological analysis of arterial tissues revealed ticagrelor markedly decreased the atherosclerotic plaque area and inhibited the expression of PCSK9. The present results suggested that ticagrelor may alleviate AS via downregulation of PCSK9-mediated endothelial cell apoptosis, which may be JNK-dependent.

In the field of aerospace remote sensing, the errors of optical element surface shape and position misalignment are often mixed together in the off-axis reflection system, which directly affects the accuracy of simulation analysis of computer aided alignment , and reduces the quality and efficiency of the optical system alignment. In order to solve this problem, there propose a surface shape data conversion algorithm, which can convert and process the surface shape data of optical elements. Combined with Code V, we can calculate and remove the influence of the surface shape error on the image quality of the system, and achieve optical alignment of off-axis reflection system fast with high precision. Verified analysis, the accuracy of this algorithm is higher than the traditional inversion Zernike polynomial fitting method, and reduction accuracy is better than 90%. In addition, the surface shape data conversion algorithm can also achieve restore of non-circular optical elements (such as ellipse, rectangle, shading and other arbitrary shapes) in the optical simulation software with high precision, which can provide more accurate results for optical system with high precision and rapid.

BackgroundArchaea were originally discovered in extreme environments, and thrive in many extreme habitats including soda lakes with high pH and salinity. Characteristic and diverse archaeal community played a significant role in biogeochemical cycles; however, the archaeal community and their functions are still less-studied in the intricate sediment of soda lakes. ResultsIn this article, the archaeal community of the deep sediment (40-50 cm depth) of five artificially-separated ponds with a salinity range from 7.0% to 33.0% in a soda saline lake was systematically surveyed using culture-independent metagenomics combined with the next-generation sequencing of the archaeal 16S rRNA amplicons. Nine archaeal phyla were detected, which accounted for 2.2% to 35.73% of microbial community in the five deep sediments. Besides the well-known class Halobacteria, one novel archaeal order (Candidatus Natranaeroarchaeales) of the class Thermoplasmata was even more abundant than Halobacteria in some deep sediment samples. Of 69 dereplicated archaeal metagenome-assembled genomes (MAGs), 30 MAGs belonged to Ca. Natranaeroarchaeales. Different genera of the Ca. Natranaeroarchaeales preferred to inhabit in the different salinities, and the divergent halophilic adaptation strategies (salt-out or salt-in) suggested the fast evolution adaptation within this lineage. Most high-quality MAGs had the genes of Wood-Ljungdahl pathway, organic acid fermentation and sulfur respiration, suggesting the putative functions in carbon fixation and sulfur reduction. Interestingly, heterodisulfide reductase and F420-non-reducing hydrogenase complex HdrABC-MvhADG were widely distributed in Ca. Natranaeroarchaeales and may play the core roles in energy metabolism from hydrogen. The regeneration of CoM-S-S-CoB was coupled to succinate or 2-oxoglutarate production in Ca. Natranaeroarchaeales instead of methanogenesis in the close related Methanomassiliicoccales. It suggested that methyl-coenzyme M reductase in Methanomassiliicoccales may be laterally transferred from other methanogens. ConclusionA novel archaeal order Ca. Natranaeroarchaeales of Thermoplasmata was found by culture-independent approaches. This order was the most abundant archaeal lineage in the deep sediment of soda lakes, with the characteristic environmental adaptation and biogeochemical potentials in carbon fixation and sulfur reduction. The difference in fermentation products coupled to energy metabolism between methanogens and Ca. Natranaeroarchaeales provided additional insights into the origination of methanogenesis in Thermoplasmata from the energy metabolism perspective.

Background and Objective Personality disorders are frequently associated with insomnia and depression, but little is known about the inter-relationships among these variables. Therefore, this study examined these inter-relationships and the possible mediating effect of insomnia on the association between specific personality pathologies and depression severity. Methods There were 138 study participants, including 69 individuals with depression and 69 healthy controls. The main variables were measured by the Hamilton Depression Rating Scale-24 (HAMD-24), Athens Sleep Insomnia Scale (AIS), and the Personality Diagnostic Questionnaire (PDQ-4+). Multivariate linear regression and mediation analysis were conducted. Results With the exception of the antisocial personality score, all the PDQ-4+ scores and AIS scores were significantly higher in the depression group than in the healthy control group (p < 0.001). In the total sample, all personality pathology scores (p < 0.001), except the antisocial personality score, had significant positive correlations with the AIS scores and HAMD-24 scores, and the AIS scores and HAMD-24 scores were positively correlated (r = 0.620, p < 0.001). Regression analysis revealed that borderline personality, passive-aggressive personality, and insomnia positively predicted the severity of depression, after adjusting for sociodemographic covariates, and that insomnia partially mediated the associations of borderline personality and passive-aggressive personality with depression severity. Conclusions Borderline personality, passive-aggressive personality, and insomnia tend to increase the severity of depression, and the effect of borderline and passive-aggressive personality on depression severity may be partially mediated by insomnia. This is the first study to report these findings in a Chinese sample, and they may help researchers to understand the pathways from specific personality pathologies to the psychopathology of depression better, which should be useful for designing interventions to relieve depression severity, as the impact of specific personality pathology and insomnia should be considered.

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).

Aiming at the distortion of the output current caused by non-ideal switching characteristics in the position sensorless control system of permanent magnet synchronous motors (PMSM), which will lead to deviations in rotor position detection, a method of current zero crossing detection is carried out in this paper and it successfully decreases the dead zone's impact on high-frequency square wave(HFSW) injection in position sensorless control system. Compared with the scheme without dead zone compensation, it effectively improves the current waveform distortion and reduces the steady-state error and phase lag of the system. Both simulation and experimental results verify the correctness of the strategy and good performance of the system.

Small RNAs guard CRISPR-Cas The microbial adaptive immunity system CRISPR-Cas benefits microbes by warding off genetic invaders, but it also inflicts a fitness cost because of occasional autoimmune reactions, rendering CRISPR loci evolutionarily unstable. Li et al. identified previously unnoticed toxin-antitoxin RNA pairs embedded within diverse CRISPR-Cas loci. The antitoxin RNA mimics a CRISPR RNA and repurposes the CRISPR immunity effector to transcriptionally repress a toxin RNA that would otherwise arrest cell growth by sequestering a rare transfer RNA. These small RNAs thus form a symbiosis with CRISPR, rendering CRISPR addictive to the host despite its fitness cost. These findings reveal how CRISPR-Cas can operate as a selfish genetic element. Science , this issue p. eabe5601

Objective: The aim of the study was to gain updated data on SHS exposure among pregnant women in Chongqing city, one of the four municipalities of China. Study Design and Setting: Pregnant women attending routine ultrasound checks at an obstetrics and gynecology center voluntarily participated in the survey of SHS exposure. Some participants were also invited to have saliva cotinine tests using a NicAlert kit. The pulsatility index (PI) of the umbilical artery was compared between the SHS and non-SHS groups. Results: A total of 548 pregnant women (74.82 and 25.18% at 12 and 24 weeks' gestation, respectively) participated in the survey from July to November 2019. SHS exposure was reported by 29.44% of participants. “Workplace” was listed as the top location for SHS exposure. Twenty-three of the 31 participants who tested cotinine-negative in their saliva samples self-reported SHS exposure in the survey questionnaire. However, two of the eight participants who tested cotinine-positive in their saliva samples self-reported SHS-exposure negative. The mean PI in the SHS group is higher than that in the non-SHS group (1.10 vs. 1.02) in fetuses at 24 weeks' gestation. However, the PI may not be suitable as an index for SHS exposure at 12 weeks' gestation due to frequent absent or reversed diastolic flow. Conclusion: The first survey on SHS exposure in pregnant women that combines a questionnaire, saliva cotinine tests, and ultrasound flow index analysis has been performed in China and provided valuable data for ensuing studies.

Under pathological conditions, the Janus kinase (JAK)/STAT signaling pathway can regulate the proliferation, differentiation and migration of tumor cells, including colorectal cancer (CRC). CRC is the third major types of cancer among males and the second among females worldwide. In China, CRC is the fifth common cancer among both males and females. Western blotting, flow cytometry, RNA interference, immunoprecipitation, xenografts models, and immunohistochemical staining were carried out to evaluate the possible mechanisms of acton of ruxolitinib. The present data suggested that ruxolitinib can suppress CRC cell proliferation by inducing apoptosis. Firstly, JAK1/2-STAT1 was identified as the target of ruxolitinib. Then, ruxolitinib downregulated myeloid cell leukemia-1 (Mcl-1) mRNA level and decreased its protein level, which enabled Bak to trigger CRC apoptosis. Furthermore, ruxolitinib exerted potent activity against CRC xenograft growth in vivo. High expression of phosphorylated STAT1 (S727) was also confirmed in 44 pairs of human colon carcinoma and adjacent normal tissues. Taken together, the results showed that ruxolitinib decreased JAK1/2-STAT1-Mcl-1 protein level and effectively suppressed CRC cell proliferation in vitro and in vivo. Therefore, ruxolitinib could be a promising anticancer agent for CRC treatment.

OBJECTIVE To report perioperative outcomes in robot-assisted radical cystectomy and laparoscopic radical cystectomy. PATIENTS AND METHODS Between January 2010 and July 2019, 298 patients with bladder cancer underwent robotic-assisted radical cystectomy (RARC) (n = 172) and laparoscopic radical cystectomy (LRC) (n = 126) at our institution were enrolled in the retrospective study. The demographic, perioperative, and complication data were collected and analyzed. RESULTS The RARC group had less operative duration (P

Renal cancer is one of the most common malignancies in urological tumors; it is necessary to develop a noninvasive and highly targeted thermal ablation method for the treatment of renal tumors. IR780 has been shown to be an effective photothermal agent for tumor thermal ablation. This study was designed to explore the feasibility of applying hyaluronic acid-IR780 nanoparticles (HA-IR780 NPs) for targeted thermal ablation of renal tumors using an in situ renal tumor model. The size of the nanoparticles was 172±8.2 nm; it showed a stable spherical nanostructure with good monodispersity. HA-IR780 NPs showed high photothermal efficiency, with the 20 μg/mL HA-IR780 NPs showing a maximum temperature increase of 24.5°C with 6 min of 808 nm laser irradiation. NIR imaging showed that the nanoparticles exhibited targeted accumulation in renal tumor tissues. The treatment efficacy of the HA-IR780 NPs showed that renal tumors treated with the HA-IR780 NPs and laser irradiation were effectively ablated. Our results showed that the HA-IR780 nanoparticles that mediated the photothermal effect could generate tumor-specific heat for the destruction of a renal tumor in a minimally invasive way, which provides a novel strategy for thermal ablation of renal tumors.

Although oxygen is a common ligand in supported metal catalysts, its coordination has been challenging to elucidate. We now characterize a diiridium complex that has been previously shown by X-ray diffraction crystallography to incorporate a μ-η

We have performed an extensive computational investigation of the potential energy surfaces for the reactions of SO

Resulting in the error of rotor position estimation, harmonics of high-frequency response incremental (HFI) current are generated by the nonlinear characteristics of inductance. In this paper, a new high-frequency square wave injection (HFSWI) scheme considering the variation of the inductance is proposed and implemented. Compared with the conventional one, the key is to establish a new model of high-frequency square wave injection method with the change of inductance, and improve the conventional rotor position signal observer. And with the new scheme, the harmonics of HFI current generated by the dynamic change of the inductance have been successfully suppressed. Both computer simulation and experimental results verify that the proposed strategy exhibits good capability in harmonic suppression and retain the accuracy of estimated angle.

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., Author summary Replication of positive-strand RNA viruses, which infect plants and animals, depends on many cellular resources. These viruses subvert cellular membranes and co-opt host proteins to build replication compartments that produce the viral progeny. The viral replication process also requires cellular metabolites and energy in the form of ATP. Using plant host as well as the model host yeast, the authors discovered that tomato bushy stunt tombusvirus (TBSV) co-opts the fermentation pathway to facilitate the local generation of ATP within the replication compartments. TBSV replication induces high expression of pyruvate decarboxylase (Pdc1) and alcohol dehydrogenase (Adh1) fermentation enzymes. With the help of the viral replication protein, TBSV recruits Pdc1 and Adh1 into the viral replication compartment. The authors propose that compartmentalization of the fermentation pathway gives an evolutionary advantage for tombusviruses by facilitating rapid and efficient replication in the infected hosts. The authors also showed that the replication of five other plant viruses depends on the fermentation pathway in plants.

Phosphoenolpyruvate (PEP)/pyruvate interconversion is a major metabolic point in glycolysis and gluconeogenesis and is catalyzed by various sets of enzymes in different Archaea groups. In this study, we report the key enzymes that catalyze the anabolic and catabolic directions of the PEP/pyruvate interconversion in Haloferax mediterranei. The in silico analysis showed the presence of a potassium-dependent pyruvate kinase (PYK(Hm) [HFX_0773]) and two phosphoenol pyruvate synthetase (PPS) candidates (PPS(Hm) [HFX_0782] and a PPS homolog protein named PPS-like [HFX_2676]) in this strain. Expression of the pyk(Hm) gene and pps(Hm) was induced by glycerol and pyruvate, respectively; whereas the pps-like gene was not induced at all. Similarly, genetic analysis and enzyme activities of purified proteins showed that PYK(Hm) catalyzed the conversion from PEP to pyruvate and that PPS(Hm) catalyzed the reverse reaction, while PPS-like protein displayed no function in PEP/pyruvate interconversion. Interestingly, knockout of the pps-like gene led to a 70.46% increase in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production. The transcriptome sequencing (RNA-Seq) and quantitative reverse transcription-PCR (qRT-PCR) results showed that many genes responsible for PHBV monomer supply and for PHBV synthesis were upregulated in a pps-like gene deletion strain and thereby improved PHBV accumulation. Additionally, our phylogenetic evidence suggested that PPS-like protein diverged from PPS enzyme and evolved as a distinct protein with novel function in haloarchaea. Our findings attempt to fill the gaps in central metabolism of Archaea by providing comprehensive information about key enzymes involved in the haloarchaeal PEP/pyruvate interconversion, and we also report a high-yielding PHBV strain with great future potentials. IMPORTANCE Archaea, the third domain of life, have evolved diversified metabolic pathways to cope with their extreme habitats. Phosphoenol pyruvate (PEP)/pyruvate interconversion during carbohydrate metabolism is one such important metabolic process that is highly differentiated among Archaea. However, this process is still uncharacterized in the haloarchaeal group. Haloferax mediterranei is a well-studied haloarchaeon that has the ability to produce polyhydroxyalkanoates (PHAs) under unbalanced nutritional conditions. In this study, we identified the key enzymes involved in this interconversion and discussed their differences with their counterparts from other members of the Archaea and Bacteria domains. Notably, we found a novel protein, phosphoenolpyruvate synthetase-like (PPS-like), which exhibited high homology to PPS enzyme. However, PPS-like protein has evolved some distinct sequence features and functions, and strikingly the corresponding gene deletion helped to enhance poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) synthesis significantly. Overall, we have filled the gap in knowledge about PEP/pyruvate interconversion in haloarchaea and reported an efficient strategy for improving PHBV production in H. mediterranei.

Aiming at the acoustic noise and electromagnetic interference (EMI) caused by high-frequency square wave injection (HFSWI) in the position sensorless control system of interior permanent magnet synchronous motor (IPMSM), a new high-frequency injection scheme based on random algorithm is proposed and implemented in the paper. Compared with the conventional scheme, the key is to employ a no-periodic modulation on the injected signal to broaden the spectrum of current. With the adoption of the random HFSWI, harmonic peaks can be reduced, therefore the acoustic noise and EMI caused by HFSWI can be effectively solved. Based on the principle of random HFSWI scheme, two different random algorithms are considered and compared in the paper. Markov chain-based HFSWI scheme can reduce the harmonic peak by at least 12dB. Both computer simulation and experimental results verify that the proposed strategy exhibits good capability in harmonic suppression and retain the accuracy of estimated angle.

Lei Zheng,1,2,* Huanhuan Zhou,1,2,* Liwei Guo,3 Xiaoling Xu,2 Shengjie Zhang,2 Weizhen Xu,2,4 Weimin Mao1,2,4 1Department of Oncology, The First Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang, China; 2Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; 4Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province, Hangzhou, Zhejiang, China *These authors contributed equally to this work Background: Previously, we reported that high expression of nipped-B-like protein (NIPBL) was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer (NSCLC). Moreover, loss of NIPBL decreased lung cancer cells proliferation, migration, invasion and promoted apoptosis as well as sensitivity to chemotherapeutic agents. However, the deep mechanisms were not explored.Purpose: The objective of this study was to identify the role of NIPBL in DNA damage response, as well as autophagy pathway, so as to interpret the mechanisms of how NIPBL knockdown enhances the chemosensitivity of lung cancer cell.Methods: Cells (NCI-H1299 and NCI-H1650) were transfected by specific siRNAs before immunofluorescence and single-cell gel electrophoresis, which were mainly used to observe the differences of DNA damage in different groups. Additionally, protein were obtained and then analyzed by western blot and mass spectroscopy.Results: In this study, we found that knockdown of NIPBL resulted in accumulation of phosphorylated H2AX (γ-H2AX) foci and higher levels of DNA damage, as revealed by comet assay. Western blot assay revealed that loss of NIPBL decreased expression of ATM/ATR, Rad3-related protein and Ku70/Ku80, but increased expression of LC3-B and depletion of p62. Using mass spectroscopy, we identified eight proteins that were significantly differentially expressed upon NIPBL knockdown. Gene Ontology analysis revealed that these proteins are mainly involved in DNA repair, mismatch repair, and binding to damaged DNA. The expression changes in two of the proteins, MSH2 and STAT1, were verified by Western blotting in NIPBL-knockdown cells.Conclusions: In summary, these results reflected that loss of NIPBL impairs the DNA damage response and promotes autophagy. And NIPBL suppression may represent a novel strategy for preventing chemotherapy resistance in lung cancer. Keywords: nipped-B-like protein, lung cancer, DNA damage response, double-strand break, autophagy

Catalysts consisting of isolated metal atoms on oxide supports have attracted wide attention because they offer unique catalytic properties, but their structures remain largely unknown because the metals are bonded at various, heterogeneous surface sites. Now, by using highly crystalline MgO as a support for metal sites made from a mononuclear organoiridium precursor and investigating the surface species with X-ray absorption spectroscopy, atomic resolution electron microscopy, and electronic structure theory, we have differentiated among the MgO surface sites for iridium bonding. The results demonstrate the contrasting structures and catalytic properties of samples, even including those incorporating iridium at loadings as low as 0.01 wt % and showing that the latter are nearly ideal in the sense of having almost all the Ir atoms at equivalent surface sites, with each Ir atom bonded to three oxygen atoms of the MgO surface. These supported molecular catalysts are modeled accurately with density functiona...

Motor bearing is subjected to the joint effects of much more loads, transmissions, and shocks that cause bearing fault and machinery breakdown. A vibration signal analysis method is the most popular technique that is used to monitor and diagnose the fault of motor bearing. However, the application of the vibration signal analysis method for motor bearing is very limited in engineering practice. In this paper, on the basis of comparing fault feature extraction by using empirical wavelet transform (EWT) and Hilbert transform with the theoretical calculation, a new motor bearing fault diagnosis method based on integrating EWT, fuzzy entropy, and support vector machine (SVM) called EWTFSFD is proposed. In the proposed method, a novel signal processing method called EWT is used to decompose vibration signal into multiple components in order to extract a series of amplitude modulated–frequency modulated (AM-FM) components with supporting Fourier spectrum under an orthogonal basis. Then, fuzzy entropy is utilized to measure the complexity of vibration signal, reflect the complexity changes of intrinsic oscillation, and compute the fuzzy entropy values of AM-FM components, which are regarded as the inputs of the SVM model to train and construct an SVM classifier for fulfilling fault pattern recognition. Finally, the effectiveness of the proposed method is validated by using the simulated signal and real motor bearing vibration signals. The experiment results show that the EWT outperforms empirical mode decomposition for decomposing the signal into multiple components, and the proposed EWTFSFD method can accurately and effectively achieve the fault diagnosis of motor bearing.

Understanding hot carrier dynamics between plasmonic nanomaterials and its adsorbate is of great importance for plasmon‐enhanced photoelectronic processes such as photocatalysis, optical sensing and spectroscopic analysis. However, it is often challenging to identify specific dominant mechanisms for a given process because of the complex pathways and ultrafast interactive dynamics of the photoelectrons. Here, using CO2 reduction as an example, the underlying mechanisms of plasmon‐driven catalysis at the single‐molecule level using time‐dependent density functional theory calculations is clearly probed. The CO2 molecule adsorbed on two typical nanoclusters, Ag20 and Ag147, is photoreduced by optically excited plasmon, accompanied by the excitation of asymmetric stretching and bending modes of CO2. A nonlinear relationship has been identified between laser intensity and reaction rate, demonstrating a synergic interplay and transition from indirect hot‐electron transfer to direct charge transfer, enacted by strong localized surface plasmons. These findings offer new insights for CO2 photoreduction and for the design of effective pathways toward highly efficient plasmon‐mediated photocatalysis.

A typical manufacturing system requiring a high degree of automation usually includes warehouse, AGV, CNC, assembly line and laser marking equipment. Among them, AGV plays an important role on the overall operating quality and operating efficiency. This paper studies AGV control strategy under the background of the typical manufacturing system. Firstly the two modes of AGV motion path are defined; the flow chart of AGV movement between any two points in the system is analyzed, and the AGV communication module in the minimum operation mode is designed; finally, control programs for several main scenarios are proposed based on PLC ladder diagram. The outcome helps the optimization of AGV control decision relating to a bottom operation layer of any manufacturing system.

Growing evidence suggests that hepatic macrophages play an important role in tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells, and promoting hepatocyte proliferation. Understanding the role of macrophages in the pathogenesis of liver injury will help pave the way to future therapeutics. Here, we investigated whether macrophage p38α plays a regulatory role in the tissue repair following d-galactosamine (GalN)/tumor necrosis factor-α (TNF-α)-induced acute liver injury. We found that macrophage p38α-deficient mice displayed decreased mortality and relieved liver injury as evident from less apoptosis, accelerated regeneration, decreased granulocytes recruitment, monocytes infiltration, and cytokine production after GalN/TNF-α treatment. Mechanistically, we found that p38 signaling was activated by lipopolysaccharide/interferon-γ treatment but not by inteleukin-4 stimulation, while pharmaceutical inhibition of p38α induced a shift in polarization from M1 macrophages to M2 macrophages. Together, our results indicated that macrophage p38α signaling is involved in the pathogenesis of liver injury induced by GalN/TNF-α, and inhibition of p38α signaling in macrophage could ameliorate liver injury and accelerate regeneration, probably by promoting the polarization of macrophages from the M1 phenotype to the M2 phenotype.

Nuclear receptors (NRs) regulate gene transcription by recruiting coregulators, involved in chromatin remodeling and assembly of the basal transcription machinery. The NR-associated protein ligand-dependent corepressor (LCoR) has previously been shown to suppress hepatic lipogenesis by decreasing the binding of steroid receptor coactivators to thyroid hormone receptor. However, the role of LCoR in adipogenesis has not been established. Here, we show that LCoR expression is reduced in the early stage of adipogenesis in vitro. LCoR overexpression inhibited 3T3-L1 adipocyte differentiation, whereas LCoR knockdown promoted it. Using an unbiased affinity purification approach, we identified CCAAT/enhancer-binding protein β (C/EBPβ), a key transcriptional regulator in early adipogenesis, and corepressor C-terminal binding proteins as potential components of an LCoR-containing complex in 3T3-L1 adipocytes. We found that LCoR directly interacts with C/EBPβ through its C-terminal helix-turn-helix domain, required for LCoR's inhibitory effects on adipogenesis. LCoR overexpression also inhibited C/EBPβ transcriptional activity, leading to inhibition of mitotic clonal expansion and transcriptional repression of C/EBPα and peroxisome proliferator-activated receptor γ2 (PPARγ2). However, LCoR overexpression did not affect the recruitment of C/EBPβ to the promoters of C/EBPα and PPARγ2 in 3T3-L1 adipocytes. Of note, restoration of PPARγ2 or C/EBPα expression attenuated the inhibitory effect of LCoR on adipogenesis. Mechanistically, LCoR suppressed C/EBPβ-mediated transcription by recruiting C-terminal binding proteins to the C/EBPα and PPARγ2 promoters and by modulating histone modifications. Taken together, our results indicate that LCoR negatively regulates early adipogenesis by repressing C/EBPβ transcriptional activity and add LCoR to the growing list of transcriptional corepressors of adipogenesis.