Nuclear Receptor Nur77 Facilitates Melanoma Cell Survival under Metabolic Stress by Protecting Fatty Acid Oxidation.

Fatty acid oxidation (FAO) is crucial for cells to overcome metabolic stress by providing ATP and NADPH. However, the mechanism by which FAO is regulated in tumors remains elusive. Here we show that Nur77 is required for the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation activates ERK2 to phosphorylate and induce Nur77 translocation to the mitochondria, where Nur77 binds to TPß, a rate-limiting enzyme in FAO. Although TPß activity is normally inhibited by oxidation under glucose deprivation, the Nur77-TPß association results in Nur77 self-sacrifice to protect TPß from oxidation. FAO is therefore able to maintain NADPH and ATP levels and prevent ROS increase and cell death. The Nur77-TPß interaction further promotes melanoma metastasis by facilitating circulating melanoma cell survival. This study demonstrates a novel regulatory function of Nur77 with linkage of the FAO-NADPH-ROS pathway during metabolic stress, suggesting Nur77 as a potential therapeutic target in melanoma.

Anchoring Carbon Spheres on Titanium Dioxide Modified Commercial Polyethylene (PE) Separator to Suppress Lithium Dendrites for Lithium Metal Batteries.

Lithium dendrites are easily generated for excessively-solved lithium ions (Li+ ) inside the lithium metal batteries, which will lead serious safety issues. In this experiment, carbon spheres (CS) are successfully anchored on TiO2  (CS@TiO2 ) in the hydrothermal polymerization, which is filtrated on the commercial PE separator (CS@TiO2 @PE). The negative charge in CS can suppress random diffusion of anions through electrostatic interactions. Density functional theory (DFT) calculations show that CS contributes to the desolvation of Li+ , thereby increasing the migration rate of Li+ . Furthermore, TiO2  exhibits high affinity to liquid electrolytes and acts as a physical barrier to lithium dendrite formation. CS@TiO2 is a combination of the advantages of CS and TiO2 . As results, the Li+  transference number of the CS@TiO2 @PE separator can be promoted to 0.63. The Li||Li cell with the CS@TiO2 @PE separator exhibits a stable cycle performance for more than 600 h and lower polarization voltage (17 mV) at 1 mA cm-2 . The coulombic efficiency (CE) of the Li||Cu cells employe the CS@TiO2 @PE separator is 81.63% over 130 cycles. The discharge capacity of LiFePO4 ||Li cells based on the CS@TiO2 @PE separator is 1.73 mAh (capacity retention = 91.53% after 260 cycles). Thus, the CS@TiO2 layer inhibits lithium dendrite formation.

Preparation of Surface Dispersed WO3/BiVO4 Heterojunction Arrays and Their Photoelectrochemical Performance for Water Splitting.

In this work, a surface dispersed heterojunction of BiVO4-nanoparticle@WO3-nanoflake was successfully prepared by hydrothermal combined with solvothermal method. We optimized the morphology of the WO3 nanoflakes and BiVO4 nanoparticles by controlling the synthesis conditions to get the uniform BiVO4 loaded on the surface of WO3 arrays. The phase composition and morphology evolution with different reaction precursors were investigated in detail. When used as photoanodes, the WO3/BiVO4 composite exhibits superior activity with photocurrent at 3.53 mA cm-2 for photoelectrochemical (PEC) water oxidation, which is twice that of pure WO3 photoanode. The superior surface dispersion structure of the BiVO4-nanoparticle@WO3-nanoflake heterojunction ensures a large effective heterojunction area and relieves the interfacial hole accumulation at the same time, which contributes to the improved photocurrents together with the stability of the WO3/BiVO4 photoanodes.

Selective Etching of Metal-Organic Frameworks for Open Porous Structures: Mass-Efficient Catalysts with Enhanced Oxygen Reduction Reaction for Fuel Cells.

Fe-Nx-C-based single-atom (SA-Fe-N-C) catalysts have shown favorable oxygen reduction reaction (ORR) activity. However, their application in proton exchange membrane fuel cells is hindered by reduced performance owing to the thick catalyst layer, restricting mass transfer and the O2 supply. Metal-organic frameworks (MOFs) are a promising class of crystal materials, but their narrow pores exacerbate the sluggish mass-transport properties within the catalyst layer. This study developed an approach for constructing an open-pore structure in MOFs via chelation-assisted selective etching, resulting in atomically dispersed Fe atoms anchored on an N, S co-doped carbon framework. The open-pore structure reduces oxygen transport resistance in the membrane electrode assembly (MEA) with unprecedented ORR activity and stability, as evidenced by finite element simulations. In an acidic electrolyte, the OP-Fe-NC catalyst shows a half-wave potential of 0.89 V vs RHE, surpassing Pt/C by 20 mV, and a current density of 29 mA cm-2 at 0.9 ViR-free in the MEA. This study provides an effective structural strategy for fabricating electrocatalysts with high mass efficiency and atomic precision for energy storage and conversion devices.

Adjacent Copper Single Atoms Promote C-C Coupling in Electrochemical CO2 Reduction for the Efficient Conversion of Ethanol.

The electrochemical CO2 reduction reaction (CO2RR) using renewable electricity is one of the most promising strategies for reaching the goal of carbon neutrality. Multicarbonous (C2+) products have broad applications, and ethanol is a valuable chemical and fuel. Many Cu-based catalysts have been reported to be efficient for the electrocatalytic CO2RR to C2+ products, but they generally offer limited selectivity and current density toward ethanol. Herein, we proposed a silica-mediated hydrogen-bonded organic framework (HOF)-templated approach to preparing ultrahigh-density Cu single-atom catalysts (SACs) on thin-walled N-doped carbon nanotubes (TWN). The content of Cu in the catalysts prepared by this method could be up to 13.35 wt %. It was found that the catalysts showed outstanding performance for the electrochemical CO2RR to ethanol, and the Faradaic efficiency (FE) of ethanol increased with the increase in Cu-N3 site density. The FE of ethanol over the catalysts with 13.35 wt % Cu could reach ∼81.9% with a partial current density of 35.6 mA cm-2 using an H-type cell, which is the best result for electrochemical CO2RR to ethanol to date. In addition, the catalyst could be stably used for more than 25 h. Experimental and density functional theory (DFT) studies revealed that the adjacent Cu-N3 active sites (one Cu atom coordinates with three N) were the active sites for the reaction, and their high density was crucial for the high FE of ethanol because the adjacent Cu-N3 sites with a short distance could promote the C-C coupling synergistically.

Amplification-Free Detection of SARS-CoV-2 Down to Single Virus Level by Portable Carbon Nanotube Biosensors.

The rapid and sensitive detection of trace-level viruses in a simple and reliable way is of great importance for epidemic prevention and control. Here, a multi-functionalized floating gate carbon nanotube field effect transistor (FG-CNT FET) based biosensor is reported for the single virus level detection of SARS-CoV-2 virus antigen and RNA rapidly with a portable sensing platform. The aptamers functionalized sensors can detect SARS-CoV-2 antigens from unprocessed nasopharyngeal swab samples within 1 min. Meanwhile, enhanced by a multi-probe strategy, the FG-CNT FET-based biosensor can detect the long chain RNA directly without amplification down to single virus level within 1 min. The device, constructed with packaged sensor chips and a portable sensing terminal, can distinguish 10 COVID-19 patients from 10 healthy individuals in clinical tests both by the RNAs and antigens by a combination detection strategy with an combined overall percent agreement (OPA) close to 100%. The results provide a general and simple method to enhance the sensitivity of FET-based biochemical sensors for the detection of nucleic acid molecules and demonstrate that the CNT FG FET biosensor is a versatile and reliable integrated platform for ultrasensitive multibiomarker detection without amplification and has great potential for point-of-care (POC) clinical tests.

Superhydrophilic and Superaerophobic Ru-Loaded NiCo Bimetallic Hydroxide Achieves Efficient Hydrogen Evolution over All pH Ranges.

Realizing an effective, binder-free, and super-wetting electrocatalyst for the hydrogen evolution reaction (HER) at full pH is essential for the creation of clean hydrogen. In this study, the Ru-loaded NiCo bimetallic hydroxide (Ru@NiCo-BH) catalyst was prepared by spontaneous redox reaction. The chemical interaction between Ru NPs and NiCo-BH by the Ru-O-M (M=Ni, Co) interface bond, the electron-rich Ru active site, and the multi-channel nickel foam carrier make the superhydrophilic and superaerophobic surface advantageous for mass transfer in the HER process. Therefore, Ru@NiCo-BH has remarkable HER activity, with low overpotential of 29, 68 and 80 mV, a 10 mA cm-2 current density can be obtained in alkaline, neutral and acidic electrolytes respectively. This work provides a reference for the rational development of universal electrocatalysts for hydrogen evolution in the all pH ranges through simple design strategies.

Stuttering as a signal of encephalopathy associated with toripalimab in a pancreatic ductal adenocarcinoma patient: a case report.

BACKGROUND: Immune checkpoint inhibitor (ICI) combined with chemotherapy has exhibited promising results in small sample studies of pancreatic cancer patients. The efficacy of toripalimab, a programmed cell death protein 1 (PD-1) monoclonal antibody has been explored in the previous studies and it was established that immune-related adverse events (irAEs) associated with administration of this drug deserve proper attention and adequate management. CASE PRESENTATION: A 43-year-old female patient with advanced pancreatic ductal adenocarcinoma (PDAC) was treated with toripalimab in combination with gemcitabine and nab-paclitaxel (T-GA) as the first-line treatment. She developed immune-related encephalopathy with stuttering as the main clinical symptom and Magnetic resonance imaging (MRI) showed multiple cerebral white matter demyelination changes, concomitant with asymptomatic cardiac enzyme elevation and hypothyroidism. The symptoms resolved after the discontinuation of toripalimab and corticosteroid treatment. CONCLUSIONS: Stuttering might be an early sign of neurotoxicity which can be easily neglected during the treatment. These findings provide guidance for the identification of these rare and occult neurological irAEs (n-irAEs) in the clinical practice.

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.

Metal-Organic Framework-Derived Graphene Mesh: a Robust Scaffold for Highly Exposed Fe-N4 Active Sites toward an Excellent Oxygen Reduction Catalyst in Acid Media.

This study demonstrates a special ultrathin N-doped graphene nanomesh (NGM) as a robust scaffold for highly exposed Fe-N4 active sites. Significantly, the pore sizes of the NGM can be elaborately regulated by adjusting the thermal exfoliation conditions to simultaneously disperse and anchor Fe-N4 moieties, ultimately leading to highly loaded Fe single-atom catalysts (SA-Fe-NGM) and a highly exposed morphology. The SA-Fe-NGM is found to deliver a superior oxygen reduction reaction (ORR) activity in acidic media (half-wave potential = 0.83 V vs RHE) and a high power density of 634 mW cm-2 in the H2/O2 fuel cell test. First-principles calculations further elucidate the possible catalytic mechanism for ORR based on the identified Fe-N4 active sites and the pore size distribution analysis. This work provides a novel strategy for constructing highly exposed transition metals and nitrogen co-doped carbon materials (M-N-C) catalysts for extended electrocatalytic and energy storage applications.

Highly Efficient Cu-Porphyrin-Based Metal-Organic Framework Nanosheet as Cathode for High-Rate Li-CO2 Battery.

The lithium-carbon dioxide (Li-CO2 ) battery as a novel metal-air battery has a high specific energy density and unique CO2 conversion ability. However, its further development is limited by incomplete product decomposition resulting in poor cycling and rate performance. In this work, Cu-tetra(4-carboxyphenyl) porphyrin (Cu-TCPP) nanosheets are prepared through the solvothermal method successfully. An efficient Li-CO2 battery with Cu-TCPP as catalyst achieves a high discharge capacity of 20393 mAh g-1 at 100 mA g-1 , a long-life cycle of 123 at 500 mA g-1 , and a lower overpotential of 1.8 V at 2000 mA g-1 . Density functional theory calculation reveals that Cu-TCPP has higher adsorption energy of CO2 and Li2 CO3 compared with TCPP, and a large number of electrons gather near the Cu-N4 active sites in Cu-TCPP. Therefore, the excellent CO2 capture ability of the porphyrin ligand and the synergic catalytic effect of Cu atom in Cu-TCPP promote the thermodynamics and kinetics of CO2 reduction and evolution processes.

PICALM exerts a role in promoting CRC progression through ERK/MAPK signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor in gastrointestinal tract with high incidence and mortality. In this study, the functions and potential mechanism of phosphatidylinositol-binding clathrin assembly protein (PICALM) in CRC were preliminarily explored. METHODS: Based on the Cancer Genome Atlas database and immunohistochemistry staining, revealing that the expression level of PICALM in CRC tissues was higher than that in adjacent normal tissues. RESULTS: Moreover, loss-of-function and gain-of-function assays in HCT 116 and RKO cells found that PICALM promotes proliferation and migration of CRC cells and inhibits apoptosis. Consistently, knockdown of PICALM inhibited tumorigenicity of CRC cells in vivo. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that knockdown of PICALM resulted in the enrichment of MAPK signaling pathway. Treatment of CRC cells with MAPK inhibitor reversed the effects of PICALM overexpression on proliferation and apoptosis. In addition, overexpression of PICALM upregulated the protein levels of ERK1/2 (p-ERK1/2), MEK1/2 (p-MEK1/2), p38 (p-p38) and JNK (p-JNK), and these effects were partially alleviated by the treatment of MAPK inhibitor. CONCLUSIONS: In summary, the study presented the new discovery that PICALM promoted CRC progression through ERK/MAPK signaling pathway, which drew further interest regarding its clinical application as a promising therapeutic target.

Recent Advances in the Research of Photo-Assisted Lithium-Based Rechargeable Batteries.

The application of solar energy is crucial for alleviating the energy crisis and achieving sustainable development. In recent years, photo-assisted rechargeable batteries have attracted researchers because they can directly convert and store solar energy in the batteries. And it also can be used like a normal battery without light illumination. Photo-assisted lithium-based batteries have received more attention than other energy storage systems due to their higher energy density and relatively mature development. This Review focuses on the design of various photo-assisted lithium-based batteries including Li-ion, Li-S, Li-O2 , Li-CO2 and Li-I batteries, as well as the working mechanism of photoelectrodes in these battery systems. The basic understanding and challenge of photo-assisted lithium-based batteries are also discussed. At last, perspectives for the photoelectrode development are provided in the summary to advance photo-assisted energy storage systems.

The Core/Shell Structure P Doped MoS2 @Ni3 S2 Nanorods Array for High Current Density Hydrogen Evolution in Alkaline and Acidic Electrolyte.

Electrocatalysis is the most promising strategy to generate clean energy H2 , and the development of catalysts with excellent hydrogen evolution reaction (HER) performance at high current density that can resist strong alkaline and acidic electrolyte environment is of great significance for practical industrial application. Therefore, a P doped MoS2 @Ni3 S2 nanorods array (named P-NiMoS) was successfully synthesized through successive sulfuration and phosphorization. P-NiMoS presents a core/shell structure with a heterojunction between MoS2 (shell) and Ni3 S2 (core). Furthermore, the doping of P modulates the electronic structure of the P-NiMoS; the electrons transfer from the t2g orbital of Ni element to the eg empty orbital of Mo element through the Ni-S-Mo bond at the Ni3 S2 and MoS2 heterojunction, facilitating the hydrogen evolution reaction. As a result, P-NiMoS exhibits excellent HER activity; the overpotential is 290 mV at high current density of 250 mA cm-2 in alkaline electrolyte, which is close to Pt/C (282 mV@250 mA cm-2 ), and P-NiMoS can stably evolve hydrogen for 48 h.

The cytokines IL-21 and GM-CSF have opposing regulatory roles in the apoptosis of conventional dendritic cells.

Interleukin-21 (IL-21) has broad actions on T and B cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive α-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive transfer of wild-type CD4+ T cells caused more severe colitis with increased DCs and interferon-γ (IFN-γ)-producing CD4+ T cells in Il21r(-/-)Rag2(-/-) mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2(-/-) mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response.

Aprotic Lithium-Carbon Dioxide Batteries: Reaction Mechanism and Catalyst Design.

In recent years, the combustion of fossil fuels leads to the release of a large amount of CO2 gas, which induces the greenhouse effect and the energy crisis. To solve these problems, researchers have turned their focus to a novel Li-CO2 battery (LCB). LCB has received much attention because of its high theoretical energy density and reversible CO2 reduction/evolution process. So far, the emerging LCB still faces many challenges derived from the slow reaction kinetics of discharge products. In this review, the latest status and progress of LCB, especially the influence of the structure design of cathode catalysts on the battery performance, are systematically elaborated. This review summarizes in detail the existing issues and possible solutions of LCB, which is of high research value for further promoting the development of Li-Air battery.

Associations of Social Capital with Mental Disorder Prevalence, Severity, and Comorbidity among U.S. Adolescents.

OBJECTIVE: To examine cross-sectional associations between social capital constructs and 1) adolescent lifetime mental disorders, 2) severity of functional impairment, and 3) psychiatric comorbidity. METHOD: Data were from the National Comorbidity Survey Adolescent Supplement, a nationally representative mental health survey of 6,483 U.S. adolescents aged 13-18 years. Information from fully-structured diagnostic interviews, including adolescent and caregiver reports, was used to measure seven social capital constructs and lifetime DSM-IV mental disorders (mood, anxiety, behavior, substance use and eating disorder classes). Disorder severity was divided into severe vs. mild/moderate. Comorbidity was measured as the number of different classes of lifetime mental disorders. RESULTS: Adjusted for socio-demographics and caregivers' mental health, the most consistent associations with adolescent mental disorder were for supportive friendships (any disorder OR = 0.95, 95%CI = 0.91-0.99), family cohesion (OR = 0.81, 95%CI = 0.75-0.86), school bonding (OR = 0.76, 95%CI = 0.71-0.81), and extracurricular participation (OR = 0.90, 95%CI = 0.86-0.95), although results differed by disorder class. Caregiver-reported neighborhood trust and reciprocity and caregiver community involvement were less consistently associated with mental disorder. Medium levels of adolescent-reported affiliation with neighbors was associated with lower odds of mood (OR = 0.81, 95%CI = 0.66-0.98) and anxiety (OR = 0.78, 95%CI = 0.64-0.96) disorder, while high levels were associated with higher odds of behavior disorder (OR = 1.47, 95%CI = 1.16-1.87). Several associations were stronger for severe vs. mild/moderate disorder and with increasing comorbidity. CONCLUSION: Although we cannot infer causality, our findings support the notion that improving actual and/or perceived social capital, especially regarding friendships, family, and school, (e.g., through multimodal interventions) could aid in the prevention and treatment of both individual adolescent mental disorders and psychiatric comorbidity.

Headache and mental disorders in a nationally representative sample of American youth.

The objective of this study is to examine the association between headache and mental disorders in a nationally representative sample of American youth. We used the National Comorbidity Survey-Adolescent Supplement to assess sex-specific prevalence of lifetime migraine and non-migraine headache using modified International Headache Society criteria and examine associations between headache subtypes and DSM-IV mental disorders. Adolescent report (n = 10,123) was used to identify headache subtypes and anxiety, mood, eating, and substance use disorders. ADHD and behavior disorder were based on parent report (n = 6483). Multivariate logistic regression analyses controlling for key demographic characteristics were used to examine associations between headache and mental disorders. Headache was endorsed by 26.9% (SE = 0.7) of the total sample and was more prevalent among females. Youth with headache were more than twice as likely (OR 2.74, 95% CI 1.94-3.83) to meet criteria for a DSM-IV disorder. Migraine, particularly with aura, was associated with depression and anxiety (adjusted OR 1.90-2.90) and with multiple classes of disorders. Adolescent headache, particularly migraine, is associated with anxiety, mood, and behavior disorders in a nationally representative sample of US youth. Headache is highly prevalent among youth with mental disorders, and youth with headache should be assessed for comorbid depression and anxiety that may influence treatment, severity, and course of both headache and mental disorders.

Superstable and Large-Scalable Organosilica-Micellar Hybrid Nanosystem via a Confined Gelation Strategy for Ultrahigh-Dosage Chemotherapy.

Although various drug nanocarriers have been developed for treating solid tumors, their clinical transformation is greatly limited by the difficulties in quantity production and unpredictable in vivo toxic effects. Herein, a facile "confined-gelation" strategy is developed to quantity-produce intelligent pluronic organosilica micelles (designated as IPOMs) with an undetectable critical micelle concentration (CMC), which features the self-assembly induced core confinement by block copolymers, the inner hydrolysis-condensation of silane to the oligomer skeleton, and oxidative cross-linking of disulfide skeleton to core gelation. The docetaxel-loaded IPOMs (DTX@IPOMs) with precise glutathione (GSH) responsiveness not only display an ultrahigh tolerated dose (360 mg/kg) in healthy Kunming mice model but also exhibit a remarkable tumor inhibition efficacy in both subcutaneous and orthotopic mice tumor models upon an extraordinarily large dosage (50 mg/kg). The present confined-gelation strategy provides a novel pathway to design and quantity-produce low-toxic and high-efficacy organic-inorganic hybrid nanodrugs in future clinical transformations.

Identification and Functional Analysis of lncRNAs Responsive to Hypoxia in Eospalax fontanierii.

Subterranean rodents could maintain their normal activities in hypoxic environments underground. Eospalax fontanierii, as one kind of subterranean rodent found in China can survive very low oxygen concentration in labs. It has been demonstrated that long non-coding RNAs (lncRNAs) have important roles in gene expression regulations at different levels and some lncRNAs were found as hypoxia-regulated lncRNAs in cancers. We predicted thousands of lncRNAs in the liver and heart tissues by analyzing RNA-Seq data in Eospalax fontanierii. Those lncRNAs often have shorter lengths, lower expression levels, and lower GC contents than mRNAs. Majors of lncRNAs have expression peaks in hypoxia conditions. We found 1128 DE-lncRNAs (differential expressed lncRNAs) responding to hypoxia. To search the miRNA regulation network for lncRNAs, we predicted 471 and 92 DE-lncRNAs acting as potential miRNA target and target mimics, respectively. We also predicted the functions of DE-lncRNAs based on the co-expression networks of lncRNA-mRNA. The DE-lncRNAs participated in the functions of biological regulation, signaling, development, oxoacid metabolic process, lipid metabolic/biosynthetic process, and catalytic activity. As the first study of lncRNAs in Eospalax fontanierii, our results show that lncRNAs are popular in transcriptome widely and can participate in multiple biological processes in hypoxia responses.