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Solid and liquid electrolytes allow for charges or ions to move while keeping anodes and cathodes separate. Separation prevents short circuits from occurring in energy storage devices. Rustomji et al. show that separation can also be achieved by using fluorinated hydrocarbons that are liquefied under pressure. The electrolytes show excellent stability in both batteries and capacitors, particularly at low temperatures. Science , this issue p. eaal4263 Electrolytes based on liquefied gas solvents show excellent conductivity at low temperatures. Electrochemical capacitors and lithium-ion batteries have seen little change in their electrolyte chemistry since their commercialization, which has limited improvements in device performance. Combining superior physical and chemical properties and a high dielectric-fluidity factor, the use of electrolytes based on solvent systems that exclusively use components that are typically gaseous under standard conditions show a wide potential window of stability and excellent performance over an extended temperature range. Electrochemical capacitors using difluoromethane show outstanding performance from –78° to +65°C, with an increased operation voltage. The use of fluoromethane shows a high coulombic efficiency of ~97% for cycling lithium metal anodes, together with good cyclability of a 4-volt lithium cobalt oxide cathode and operation as low as –60°C, with excellent capacity retention.

MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference ( P <0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3′-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase–PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2′- O -methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo , and highlight the therapeutic potential of miR-375 in HCC treatment.

Gamma-ray bursts (GRBs) have been phenomenologically classified into long and short populations based on the observed bimodal distribution of duration 1 . Multi-wavelength and multi-messenger observations in recent years have revealed that in general long GRBs originate from massive star core collapse events 2 , whereas short GRBs originate from binary neutron star mergers 3 . It has been known that the duration criterion is sometimes unreliable, and multi-wavelength criteria are needed to identify the physical origin of a particular GRB 4 . Some apparently long GRBs have been suggested to have a neutron star merger origin 5 , whereas some apparently short GRBs have been attributed to genuinely long GRBs 6 whose short, bright emission is slightly above the detector’s sensitivity threshold. Here, we report the comprehensive analysis of the multi-wavelength data of the short, bright GRB 200826A. Characterized by a sharp pulse, this burst shows a duration of 1 second and no evidence of an underlying longer-duration event. Its other observational properties such as its spectral behaviours, total energy and host galaxy offset are, however, inconsistent with those of other short GRBs believed to originate from binary neutron star mergers. Rather, these properties resemble those of long GRBs. This burst confirms the existence of short-duration GRBs with stellar core-collapse origin 4 , and presents some challenges to the existing models. A gamma-ray burst (GRB) is reported to show a sharp 1-second spike, characteristic of short GRBs, but with other observational properties resembling those of long GRBs. This burst may belong to a class of core-collapse-origin GRBs with genuinely short durations.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1 . Furthermore, we find that the infiltration of POSTN + fibroblasts and SPP1 + macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8 + T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma. Head and neck squamous cell carcinoma (HNSCC) is characterised with high heterogeneity and unfavourable prognosis. Here, the authors perform single cell transcriptomics to investigate the tumour microenvironment features of HNSCC initiation, progression, lymph node metastasis and recurrence.

A better understanding of the mechanisms underlying the action of antidepressants is urgently needed. Moda-Sava et al. explored a possible mode of action for the drug ketamine, which has recently been shown to help patients recover from depression (see the Perspective by Beyeler). Ketamine rescued behavior in mice that was associated with depression-like phenotypes by selectively reversing stress-induced spine loss and restoring coordinated multicellular ensemble activity in prefrontal microcircuits. The initial induction of ketamine's antidepressant effect on mouse behavior occurred independently of effects on spine formation. Instead, synaptogenesis in the prefrontal region played a critical role in nourishing these effects over time. Interventions aimed at enhancing the survival of restored synapses may thus be useful for sustaining the behavioral effects of fast-acting antidepressants. Science , this issue p. eaat8078 ; see also p. 129 Spine formation in the prefrontal cortex is central to the long-term antidepressant effects of ketamine. The neurobiological mechanisms underlying the induction and remission of depressive episodes over time are not well understood. Through repeated longitudinal imaging of medial prefrontal microcircuits in the living brain, we found that prefrontal spinogenesis plays a critical role in sustaining specific antidepressant behavioral effects and maintaining long-term behavioral remission. Depression-related behavior was associated with targeted, branch-specific elimination of postsynaptic dendritic spines on prefrontal projection neurons. Antidepressant-dose ketamine reversed these effects by selectively rescuing eliminated spines and restoring coordinated activity in multicellular ensembles that predict motivated escape behavior. Prefrontal spinogenesis was required for the long-term maintenance of antidepressant effects on motivated escape behavior but not for their initial induction.

As Li-ion battery costs decrease, energy density and thus driving range remains a roadblock for mass-market vehicle electrification. While Li-metal anodes help achieve Department of Energy targets of 500 Wh kg −1 (750 Wh l −1 ), Li Coulombic efficiencies fall below the 99.95+% required for 1,000+ cycles. Here we examine historical electrolyte developments underlying increased Coulombic efficiency and discuss emerging frameworks that support rational strategies to move beyond 99.9%. While multiple electrolytes reach 98–99% Coulombic efficiency over subsets of cycles, achieving >99.9% Coulombic efficiency consistently throughout cycling is an as yet unmet challenge. We analyse important interplays between electrolyte, solid electrolyte interphase composition, plating–stripping kinetics and Li morphology, many of which are only recently being quantified experimentally at the Li interface, and which collectively determine Coulombic efficiency. We also discuss forward-looking strategies that, if mastered, represent new opportunities to refine understanding and support new record values of Coulombic efficiency in the coming years. Irreversibility is one of the biggest obstacles in realizing practical Li-metal batteries. This Review surveys the trends in Coulombic efficiency (CE)—a reversibility indicator—reported for Li-metal batteries over the last five decades, abstracts key CE descriptors and analyses promising strategies to improve CE.

According to the US Department of Energy’s Energy Infomation Administration (EIA) (International Energy Outlook 2017), world energy consumption will increase 28% between 2015 and 2040, rising from 575 quadrillion Btu (∼606 quadrillion kJ) in 2015 to 736 quadrillion Btu (∼776 quadrillion kJ) in 2040. EIA predicts increases in consumption for all energy sources (excluding coal, which is estimated to remain flat)—fossil (petroleum and other liquids, natural gas), renewables (solar, wind, hydropower), and nuclear. Although renewables are the world’s fastest growing form of energy, fossil fuels are expected to continue to supply more than three-quarters of the energy used worldwide. Among the various fossil fuels, natural gas is the fastest growing, with a projected increase of 43% from 2015 to 2040. As the use of fossil fuels increases, the EIA projects world energy-related carbon dioxide emission to grow from ∼34 billion metric tons in 2015 to ∼40 billion metric tonnes in 2040 (an average 0.6% increase per year).

SummaryOur network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433).IntroductionData on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients.MethodsElectronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. All analyses were performed with STATA 12.0 and R software (Version 3.4.4). We estimated the risk ratio (RR) and 95% confidence interval (CI) by combining RRs for fracture effects of included trials.ResultsThere were 54 eligible random control trials (RCTs) with 49,602 participants, including 28,353 patients treated with GLP-1 RAs. Relative to placebo, exenatide (RR, 0.17; 95% CI 0.03–0.67) was associated with lowest risk of fracture among other GLP-1 RAs. Exenatide had the highest probability to be the safest option with regard to the risk of fracture (0.07 ‰), followed by dulaglutide (1.04%), liraglutide (1.39%), albiglutide (5.61%), lixisenatide (8.07%), and semaglutide (18.72%). A statistically significant inconsistency was observed in some comparisons.ConclusionThe Bayesian network meta-analysis suggests that GLP-1 RAs were associated with a decreased bone fracture risk compared to users of placebo or other anti-hyperglycemic drugs in type 2 diabetes mellitus patients, and exenatide is the best option agent with regard to the risk of fracture.

Topological defects can markedly alter nanomaterial properties. This presents opportunities for \"defect engineering,\" where desired functionalities are generated through defect manipulation. However, imaging defects in working devices with nanoscale resolution remains elusive. We report three-dimensional imaging of dislocation dynamics in individual battery cathode nanoparticles under operando conditions using Bragg coherent diffractive imaging. Dislocations are static at room temperature and mobile during charge transport. During the structural phase transformation, the lithium-rich phase nucleates near the dislocation and spreads inhomogeneously. The dislocation field is a local probe of elastic properties, and we find that a region of the material exhibits a negative Poisson's ratio at high voltage. Operando dislocation imaging thus opens a powerful avenue for facilitating improvement and rational design of nanostructured materials.

Batteries will play critical roles in modernizing energy grids, as they will allow a greater penetration of renewable energy and perform applications that better match supply with demand. Applying storage technology is a business decision that requires potential revenues to be accurately estimated to determine the economic viability, which requires models that consider market rules and prices, along with battery and application-specific constraints. Here we use models of storage connected to the California energy grid and show how the application-governed duty cycles (power profiles) of different applications affect different battery chemistries. We reveal critical trade-offs between battery chemistries and the applicability of energy content in the battery and show that accurate revenue measurement can only be achieved if a realistic battery operation in each application is considered. The findings in this work could call for a paradigm shift in how the true economic values of energy storage devices could be assessed. Large variations exist in the revenue prediction of grid-scale storage due to uncertainties in operations of storage technologies. Here the authors integrate the economic evaluation of energy storage with key battery parameters for a realistic measure of revenues.