Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma.

BACKGROUND: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. METHODS: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. RESULTS: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. CONCLUSIONS: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).

Amorphous Chloride Solid Electrolytes with High Li-Ion Conductivity for Stable Cycling of All-Solid-State High-Nickel Cathodes.

Solid electrolytes (SEs) are central components that enable high-performance, all-solid-state lithium batteries (ASSLBs). Amorphous SEs hold great potential for ASSLBs because their grain-boundary-free characteristics facilitate intact solid-solid contact and uniform Li-ion conduction for high-performance cathodes. However, amorphous oxide SEs with limited ionic conductivities and glassy sulfide SEs with narrow electrochemical windows cannot sustain high-nickel cathodes. Herein, we report a class of amorphous Li-Ta-Cl-based chloride SEs possessing high Li-ion conductivity (up to 7.16 mS cm-1) and low Young's modulus (approximately 3 GPa) to enable excellent Li-ion conduction and intact physical contact among rigid components in ASSLBs. We reveal that the amorphous Li-Ta-Cl matrix is composed of LiCl43-, LiCl54-, LiCl65- polyhedra, and TaCl6- octahedra via machine-learning simulation, solid-state 7Li nuclear magnetic resonance, and X-ray absorption analysis. Attractively, our amorphous chloride SEs exhibit excellent compatibility with high-nickel cathodes. We demonstrate that ASSLBs comprising amorphous chloride SEs and high-nickel single-crystal cathodes (LiNi0.88Co0.07Mn0.05O2) exhibit ∼99% capacity retention after 800 cycles at ∼3 C under 1 mA h cm-2 and ∼80% capacity retention after 75 cycles at 0.2 C under a high areal capacity of 5 mA h cm-2. Most importantly, a stable operation of up to 9800 cycles with a capacity retention of ∼77% at a high rate of 3.4 C can be achieved in a freezing environment of -10 °C. Our amorphous chloride SEs will pave the way to realize high-performance high-nickel cathodes for high-energy-density ASSLBs.

Stable All-Solid-State Lithium Metal Batteries Enabled by Machine Learning Simulation Designed Halide Electrolytes.

Solid electrolytes (SEs) with superionic conductivity and interfacial stability are highly desirable for stable all-solid-state Li-metal batteries (ASSLMBs). Here, we employ neural network potential to simulate materials composed of Li, Zr/Hf, and Cl using stochastic surface walking method and identify two potential unique layered halide SEs, named Li2ZrCl6 and Li2HfCl6, for stable ASSLMBs. The predicted halide SEs possess high Li+ conductivity and outstanding compatibility with Li metal anodes. We synthesize these SEs and demonstrate their superior stability against Li metal anodes with a record performance of 4000 h of steady lithium plating/stripping. We further fabricate the prototype stable ASSLMBs using these halide SEs without any interfacial modifications, showing small internal cathode/SE resistance (19.48 Ω cm2), high average Coulombic efficiency (∼99.48%), good rate capability (63 mAh g-1 at 1.5 C), and unprecedented cycling stability (87% capacity retention for 70 cycles at 0.5 C).

Trace Doping of Multiple Elements Enables Stable Cycling of High Areal Capacity LiNi0.5 Mn1.5 O4 Cathode.

High-voltage spinel cobalt-free LiNi0.5 Mn1.5 O4 (LNMO) is one of the most promising cathode candidates for next-generation lithium-ion batteries (LIBs) due to its high specific capacity, high operating voltage, and low cost. However, inferior electronic conductivity, transition metal dissolution, and fast capacity degradation of LNMO, especially in high mass loading for high areal capacity, are the critical material challenges for its practical application. Herein, trace multiple Cr-Fe-Cu elements doping of LiNi0.45 Cr0.0167 Fe0.0167 Cu0.0167 Mn1.5 O4 (CFC0.5-LNMO) cathode is achieved by a blow-spinning strategy to exhibit very stable cycling at a practical level of areal capacity up to 3 mAh cm-2 . It is demonstrated that the Cu, Fe, and Cr doping into the LNMO lattice can suspend the Mn dissolution and improve the Li ion diffusivity and electronic conductivity of the LNMO host. As a result, the obtained CFC0.5-LNMO cathode exhibits an excellent rate performance (1.75 mAh cm-2 at 1C) and long cycling stability under an areal capacity of 3 mAh cm-2 (78% capacity retention over 300 cycles at 0.5C).

Alternative splicing patterns reveal prognostic indicator in muscle-invasive bladder cancer.

BACKGROUND: Bladder cancer is one of the most lethal malignancy in urological system, and 20-25% of bladder cancer patients are muscle invasive with unfavorable prognosis. However, the role of alternative splicing (AS) in muscle-invasive bladder cancer (MIBC) remains to be elucidated. METHODS: Percent spliced in (PSI) data obtained from the Cancer Genome Atlas (TCGA) SpliceSeq database (n = 394) were utilized to evaluate the AS events in MIBC. Prognosis-associated AS events were screened out by univariate Cox regression. LASSO Cox regression was used to identify reliable prognostic patterns in a training set and further validated in a test set. Splicing regulatory networks were constructed by correlations between PSI of AS events and RNA expression of splicing factors. RESULTS: As a result, a total of 2589 prognosis-related AS events in MIBC were identified. Pathways of spliceosomal complex (FDR = 0.017), DNA-directed RNA polymerase II, core complex (FDR = 0.032), and base excision repair (FDR = 0.038) were observed to be significantly enriched. Additionally, we noticed that most of the prognosis-related AS events were favorable factors. According to the LASSO and multivariate Cox regression analyses, 15-AS-based signature was established with the area under curve (AUC) of 0.709, 0.823, and 0.857 at 1-, 3-, and 5- years, respectively. The MIBC patients were further divided into high- and low-risk groups based on median risk sores. Interestingly, we observed that the prevalence of FGFR3 with mutations and focal amplification was significantly higher in low-risk group. Functional and immune infiltration analysis suggested potential signaling pathways and distinct immune states between these two groups. Moreover, splicing correlation network displayed a regulatory mode of prognostic splicing factors (SF) in MIBC patients. CONCLUSIONS: This study not only provided novel insights into deciphering the possible mechanism of tumorgenesis and pathogenesis but also help refine risk stratification systems and potential treatment of decision-making for MIBC.

Scallion-Inspired Graphene Scaffold Enabled High Rate Lithium Metal Battery.

Graphene-based one-dimensional macroscopic assemblies (GBOMAs) have attracted great attention and extensive efforts have been devoted to enabling great progress. However, their applications are still restricted to less functionalized electronics, and the superior potentials remain scarce. Herein, inspired by natural scallion structure, a novel strategy was introduced to effectively improve battery performances through the mesoscale scallion-like wrapping of graphene. The obtained RGO/Ag-Li anodes demonstrated an ultralow overpotential of ∼11.3 mV for 1800 h at 1 mA cm-2 in carbonate electrolytes, which is superior to those of the most previous reports. Besides, this strategy can also be further expanded to the high mass loading of various cathode nanomaterials, and the resulting RGO/LiFePO4 cathodes exhibited remarkable rate performance and cycle stability. This work opens a new avenue to explore and broaden the applications of GBOMAs as scaffolds in fabricating full lithium batteries via maximizing their advantages derived from the unique structure and properties.

The Plasmid pEX18Gm Indirectly Increases Caenorhabditis elegans Fecundity by Accelerating Bacterial Methionine Synthesis.

Plasmids are mostly found in bacteria as extrachromosomal genetic elements and are widely used in genetic engineering. Exploring the mechanisms of plasmid-host interaction can provide crucial information for the application of plasmids in genetic engineering. However, many studies have generally focused on the influence of plasmids on their bacterial hosts, and the effects of plasmids on bacteria-feeding animals have not been explored in detail. Here, we use a "plasmid-bacteria-Caenorhabditis elegans" model to explore the impact of plasmids on their host bacteria and bacterivorous nematodes. First, the phenotypic responses of C. elegans were observed by feeding Escherichia coli OP50 harboring different types of plasmids. We found that E. coli OP50 harboring plasmid pEX18Gm unexpectedly increases the fecundity of C. elegans. Subsequently, we found that the plasmid pEX18Gm indirectly affects C. elegans fecundity via bacterial metabolism. To explore the underlying regulatory mechanism, we performed bacterial RNA sequencing and performed in-depth analysis. We demonstrated that the plasmid pEX18Gm upregulates the transcription of methionine synthase gene metH in the bacteria, which results in an increase in methionine that supports C. elegans fecundity. Additionally, we found that a pEX18Gm-induced increase in C. elegans can occur in different bacterial species. Our findings highlight the plasmid-bacteria-C. elegans model to reveal the mechanism of plasmids' effects on their host and provide a new pattern for systematically studying the interaction between plasmids and multi-species.

Blow-Spinning Enabled Precise Doping and Coating for Improving High-Voltage Lithium Cobalt Oxide Cathode Performance.

Lithium cobalt oxide (LiCoO2) possesses an attractive theoretical specific capacity (274 mAh g-1) and high discharge voltage (∼4.2 V vs Li+/Li). However, only a half of the theoretical capacity of LiCoO2 is available in commercialized lithium ion batteries because of the intrinsic structural instability and detrimental interface of LiCoO2 at the charging voltage over 4.2 V. Here, a facile blow-spinning synthetic method is developed to realize precise doping and simultaneous self-assembly coating of LiCoO2 particles, achieving a record performance among present LiCoO2 cathodes. Owing to the spatial confinement effect of microfibers fabricated by blow-spinning, homogeneously Mn and La doped in the LiCoO2 host and uniformly Li-Ti-O segregated at the LiCoO2 surface can be realized in every batch of samples. It is demonstrated that the Mn and La codoping can suspend the intrinsic instability and increase the Li+ diffusivity of the LiCoO2 host, and the Ti-based coating can stabilize the interface of LiCoO2 particles at the charging voltage up to 4.5 V. As a result, the obtained comodified LiCoO2 cathode shows the best rate performance (1.85 mAh cm-2 at 2C) and longest cycling stability under an areal capacity of 2.04 mAh cm-2 (83% capacity retention over 300 cycles at 0.3C), in comparison to previously reported LiCoO2 cathodes.

Low Cost Metal Carbide Nanocrystals as Binding and Electrocatalytic Sites for High Performance Li-S Batteries.

Lithium sulfur (Li-S) batteries are considered as promising energy storage systems for the next generation of batteries due to their high theoretical energy densities and low cost. Much effort has been made to improve the practical energy densities and cycling stability of Li-S batteries via diverse designs of materials nanostructure. However, achieving simultaneously good rate capabilities and stable cycling of Li-S batteries is still challenging. Herein, we propose a strategy to utilize a dual effect of metal carbide nanoparticles decorated on carbon nanofibers (MC NPs-CNFs) to realize high rate performance, low hysteresis, and long cycling stability of Li-S batteries in one system. The adsorption experiments of lithium polysulfides (LiPS) to MC NPs and corresponding theoretical calculations demonstrate that LiPS are likely to be adsorbed and diffused on the surface of MC NPs because of their moderate chemical bonding. MC NPs turn out to have also an electrocatalytic role and accelerate electrochemical redox reactions of LiPS, as proven by cyclic voltammetry analysis. The fabricated Li-S batteries based on the W2C NPs-CNFs hybrid electrodes display not only high specific capacity of 1200 mAh/g at 0.2C but also excellent rate performance and cycling stability, for example, a model setup can be operated at 1C for 500 cycles maintaining a final specific capacity of 605 mAh/g with a degradation rate as low as 0.06%/cycle.

Metal-Organic Frameworks and Their Derived Materials as Electrocatalysts and Photocatalysts for CO2 Reduction: Progress, Challenges, and Perspectives.

Excessive CO2 emission due to a large amount of fossil fuel utilization has become a widespread concern, which causes both environmental and energy problems. To solve these issues, electrocatalytic and photocatalytic reduction of CO2 to produce value-added chemicals have gained immense attention. Recently, metal-organic frameworks (MOFs) and their derived materials with high specific surface areas, controllable pore structures, and tunable chemical properties exhibit promising performance among the reported catalytic materials for CO2 conversion. This review describes the recent advances on the rational design and synthesis of MOF-based electrocatalysts and photocatalysts for CO2 reduction. The importance of the catalytic processes is highlighted, followed by systematic understanding of MOF-based catalysts for CO2 reduction through electrochemical and photochemical approaches. Special emphasis of this review is to introduce basic catalyst design strategies and synthesis methods as well as their resulting electrocatalysts and photocatalysts. One of the major goals is to elucidate the structures and properties that link to their catalytic activity, selectivity, and stability towards to CO2 reduction. We also outline the challenges in this research area and propose the potential strategies for the rational design and synthesis of high-performance catalysts.

Prawn Shell Derived Chitin Nanofiber Membranes as Advanced Sustainable Separators for Li/Na-Ion Batteries.

Separators, necessary components to isolate cathodes and anodes in Li/Na-ion batteries, are consumed in large amounts per year; thus, their sustainability is a concerning issue for renewable energy storage systems. However, the eco-efficient and environmentally friendly fabrication of separators with a high mechanical strength, excellent thermal stability, and good electrolyte wettability is still challenging. Herein, we reported the fabrication of a new type of separators for Li/Na-ion batteries through the self-assembly of eco-friendly chitin nanofibers derived from prawn shells. We demonstrated that the pore size in the chitin nanofiber membrane (CNM) separator can be tuned by adjusting the amount of pore generation agent (sodium dihydrogen citrate) in the self-assembly process of chitin nanofibers. By optimizing the pore size in CNM separators, the electrochemical performance of the LiFePO4/Li half-cell with a CNM separator is comparable to that with a commercialized polypropylene (PP) separator. More attractively, the CNM separator showed a much better performance in the LiFePO4/Li cell at 120 °C and Na3V2(PO4)3/Na cell than the PP separator. The proposed fabrication of separators by using natural raw materials will play a significant contribution to the sustainable development of renewable energy storage systems.

Free-Standing Copper Nanowire Network Current Collector for Improving Lithium Anode Performance.

Lithium metal is one of the most attractive anode materials for next-generation lithium batteries due to its high specific capacity and low electrochemical potential. However, the poor cycling performance and serious safety hazards, caused by the growth of dendritic and mossy lithium, has long hindered the application of lithium metal based batteries. Herein, we reported a rational design of free-standing Cu nanowire (CuNW) network to suppress the growth of dendritic lithium via accommodating the lithium metal in three-dimensional (3D) nanostructures. We demonstrated that as high as 7.5 mA h cm(-2) of lithium can be plated into the free-standing copper nanowire (CuNW) current collector without the growth of dendritic lithium. The lithium metal anode based on the CuNW exhibited high Coulombic efficiency (average 98.6% during 200 cycles) and outstanding rate performance owing to the suppression of lithium dendrite growth and high conductivity of CuNW network. Our results demonstrate that the rational nanostructural design of current collector could be a promising strategy to improve the performance of lithium metal anode enabling its application in next-generation lithium-metal based batteries.

Large-Scale Syntheses of Zinc Sulfide⋠(Diethylenetriamine)0.5 Hybrids as Precursors for Sulfur Nanocomposite Cathodes.

Nanostructured metal sulfide-amine hybrid materials have attracted attention because of their unique properties and versatility as precursors for functional inorganic nanomaterials. However, large-scale synthesis of metal sulfide-amine hybrid nanomaterials is limited by hydrothermal and solvothermal preparative reaction conditions; consequently, incorporation of such materials into functional nanomaterials is hindered. An amine molecule-assisted refluxing method was used to synthesize highly uniform zinc sulfide⋅(diethylenetriamine)0.5 (ZnS⋅(DETA)0.5 ) hybrid nanosheets and nanobelts in a large scale. The obtained ZnS⋅(DETA)0.5 hybrid nanomaterials can be used as efficient precursors to fabricate functional ZnS nanomaterials and carbon encapsulated sulfur (S@C) nanocomposite cathodes for Li-S batteries.

Scalable template synthesis of resorcinol-formaldehyde/graphene oxide composite aerogels with tunable densities and mechanical properties.

Resorcinol-formaldehyde (RF) and graphene oxide (GO) aerogels have found a variety of applications owing to their excellent properties and remarkable flexibility. However, the macroscopic and controllable synthesis of their composite gels is still a great challenge. By using GO sheets as template skeletons and metal ions (Co(2+), Ni(2+), or Ca(2+)) as catalysts and linkers, the first low-temperature scalable strategy for the synthesis of a new kind of RF-GO composite gel with tunable densities and mechanical properties was developed. The aerogels can tolerate a strain as high as 80% and quickly recover their original morphology after the compression has been released. Owing to their high compressibility, the gels might find applications in various areas, for example, as adsorbents for the removal of dye pollutants and in oil-spill cleanup.

Critical role of checkpoint kinase 1 in spinal cord injury-induced motor dysfunction in mice.

Spinal cord injury (SCI) is a devastating neurotraumatic condition characterized by severe motor dysfunction and paralysis. Accumulating evidence suggests that DNA damage is involved in SCI pathology. However, the underlying mechanisms remain elusive. Although checkpoint kinase 1 (Chk1)-regulated DNA damage is involved in critical cellular processes, its role in SCI regulation remains unclear. This study aimed to explore the role and potential mechanism of Chk1 in SCI-induced motor dysfunction. Adult female C57BL/6J mice subjected to T9-T10 spinal cord contusions were used as models of SCI. Western blotting, immunoprecipitation, histomorphology, and Chk1 knockdown or overexpression achieved by adeno-associated virus were performed to explore the underlying mechanisms. Levels of p-Chk1 and γ-H2AX (a cellular DNA damage marker) were upregulated, while ferroptosis-related protein levels, including glutathione peroxidase 4 (GPX4) and x-CT were downregulated, in the spinal cord and hippocampal tissues of SCI mice. Functional experiments revealed increased Basso Mouse Scale (BMS) scores, indicating that Chk1 downregulation promoted motor function recovery after SCI, whereas Chk1 overexpression aggravated SCI-induced motor dysfunction. In addition, Chk1 downregulation reversed the SCI-increased levels of GPX4 and x-CT expression in the spinal cord and hippocampus, while immunoprecipitation assays revealed strengthened interactions between p-Chk1 and GPX4 in the spinal cord after SCI. Finally, Chk1 downregulation promoted while Chk1 overexpression inhibited NeuN cellular immunoactivity in the spinal cord after SCI, respectively. Collectively, these preliminary results imply that Chk1 is a novel regulator of SCI-induced motor dysfunction, and that interventions targeting Chk1 may represent promising therapeutic targets for neurotraumatic diseases such as SCI.

Runx2 Suppresses Astrocyte Activation and Astroglial Scar Formation After Spinal Cord Injury in Mice.

After spinal cord injury, astrocytes undergo a reactive process and form an astroglial scar, which impedes the regeneration of axons. The role of Runx2 in promoting the transformation of astrocytes in the central nervous system is well-established. However, it remains unclear whether Runx2 also plays a role in the development of astroglial scar, and the precise underlying mechanism has yet to be identified. Recently, our study using cell culture and animal models has demonstrated that Runx2 actually suppresses astrocyte activation and the formation of astroglial scar following injury. The initial results demonstrated an increase in the expression of Runx2 in astrocytes following in vivo injury. Subsequently, the overexpression of Runx2 resulted in the inhibition of astrocyte activation, reduction in the total area of astroglial scar, and restoration of neural function after 14 days of injury. However, these effects were reversed by CADD522. These findings indicate that Runx2 could potentially serve as a therapeutic intervention for spinal cord injury (SCI). Furthermore, our findings suggest that the Nuclear-matrix-targeting signal (NMTS) of Runx2 is associated with its effect. In summary, the study's results propose that targeting Runx2 may be a promising treatment approach for reactive astrocytes and astroglial scar in the recovery of SCI.

The Life-History Traits of Soil-Dwelling Nematode (Acrobeloides Sp.) Exhibit More Resilience to Water Restriction Than Caenorhabditis Elegans.

In the context of climate warming, the intensity and frequency of drought occurrences are progressively increasing. However, current research on the impacts of drought on the life history traits and physiological activities of animals rarely encompass soil animals that play crucial roles within soil ecosystems. Therefore, this study focused on a soil nematode species (Acrobeloides sp.) and a model nematode (Caenorhabditis elegans) to investigate whether nematodes adjust the trade-off of their life history traits to confront arid environments, utilizing a Petri dish experiment. Subsequently, we assessed the resilience of the two nematode species to moisture variations by comparing the extent of changes in various indicators (i.e., life history traits, physiological trait, and oxidative stress) of nematodes before and after drought and rehydration. The results revealed that both nematode species are capable of adapting to arid environments by altering the trade-off between life-history traits. Specifically, they reduce reproductive investment and bodymass while maintaining lifespan, thus responding to drought conditions. Follow-up rehydration experiments post-drought stress highlighted that soil-dwelling nematode exhibit a superior recovery capacity in response to moisture fluctuations in comparison to the model nematode. To the best of our knowledge, this is the first investigation into life history of drought adaptation within soil-dwelling nematode. Moreover, the findings hold significant implications for the exploration of drought adaptation and its mechanisms in soil-dwelling animals.

Tumor grade-associated genomic mutations in Chinese patients with non-small cell lung cancer.

Background: Lung cancer is the most prevalent cancer worldwide and accounts for approximately 20% of cancer-related death in China every year. High-grade lung cancer poses a significant threat to patients, and developing a novel treatment for these patients requires an understanding of its underlying mechanism. Methods: Chinese patients with lung cancer were enrolled. The tumor samples were collected by surgery or puncture and applied for next-generation sequencing. A panel of pan-cancer genes was targeted, and the sequencing depth was set to over 1,000 to improve the sensitivity of detecting mutations. Short-length mutations (substitution, insertion, and deletion), copy number variation, and gene fusion were called. Gene mutations were compared between low-grade, middle-grade, and high-grade tumors using Fisher's exact test. The enriched pathways in each grade of tumors were also inferred. Results: The study included 173 Chinese patients with non-small cell lung cancer, of whom 98 (56.6%) patients were female and 75 (43.4%) were male, with a mean age of 56.8 years. All patients were microsatellite stable; 66.4% were at the early stages (Stages 0, I, and II) with a tumor mutational burden of approximately 2.5 (confidence interval = [0, 48.3]). Compared to low-grade tumors, high-grade tumors had a significantly higher percentage of mutations in TP53 (75.9% vs 34.4%, p = 1.86e-3) and PIK3CA (24.1% vs. 0%, p = 3.58e-3). Pathway analysis found that high-grade tumors were enriched with mutations in bacterial invasion of epithelial cells (31% vs. 0%, p = 5.8e-4), Epstein-Barr virus infection (79.3% vs. 37.5%, p = 1.72e-3), and the Wnt signaling pathway (75.9% vs. 34.4%, p = 1.91e-3). High-grade tumors had a significantly higher tumor mutational burden than low-grade tumors (p-value = 0.0017). However, actionable mutations with high-level evidence were lower in high-grade tumors. Conclusion: Patients with high-grade tumors from lung cancer may be more affected by bacteria and Epstein-Barr virus than low-grade tumors. High-grade tumors were specially mutated in TP53 and PIK3CA and may benefit more from immunotherapy. Further research on the underlying mechanism of high-grade lung cancer is necessary to develop new therapeutic options. Lung cancer, tumor grade, genomic mutations, Epstein-Barr virus, pathway analysis.

Hybrid Nano-Phase Ion/Electron Dual Pathways of Nickel/Cobalt-Boride Cathodes Boosting Intercalation Kinetics for Alkaline Batteries.

Nickel-based hydroxides and their derivatives exhibit relatively low capacities and unsatisfactory durability as cathode materials for rechargeable alkaline batteries. In this work, a hybrid NiCo-B nanosheet cathode, integrating electrolyte ion-shuttling channels and electron-transferring networks into a metal-organic framework (MOF), was devised delicately. In the structure, the hybrid ion/electron dual pathways were constructed by NiCo-MOF frameworks and NiCo-B interpenetration networks. It revealed that nano-phase electron-transferring pathways in the MOF obviously boosted ion intercalation kinetics. The as-obtained hybrid NiCo-B nanosheets as cathode materials exhibited reversible capacity as high as 280 mA h g-1 at a current density of 1 A g-1 and excellent rate capability with a capacity retention of 78% from 1 to 10 A g-1. After 2000 charge/discharge cycles at 4 A g-1, the capacity still remained at 94% of the initial one. A full battery assembled with a hybrid NiCo-B cathode and a Fe2O3 anode showed a high capacity of 250 mA h g-1 and a considerable stability of 89% after 1000 cycles. Ragone plots indicated the highest energy density of 409 W h kg-1 and the lowest power density of 1.5 kW kg-1, outperforming other aqueous batteries. It revealed that a syngenetic structure of ion/electron hybrid dual pathways integrated into an MOF could be a potential strategy to optimize ion intercalation electrode materials for alkaline batteries.

The LINC00261/MiR105-5p/SELL axis is involved in dysfunction of B cell and is associated with overall survival in hepatocellular carcinoma.

Background: Previous studies have been reported the immune dysfunction of various live tissues. However, the potential molecular mechanism of post-transcriptional regulation of immune related genes in hepatocellular carcinoma (HCC) is still not clear. We tried to identify crucial immune related biomarkers associated with HCC patients' outcomes and to reveal the transcriptional regulation. Method: The fractions of 22 immune cells in tumor and adjacent tissues were estimated by CIBERSORT. Kruskal-Wallis test and differentially expressed analyzes were used for comparative studies. Cox proportional hazard regression model, Kaplan-Meier estimates and Log-rank test were used for survival analyses. Results: From The Cancer Genome Atlas (TCGA), the gene, lncRNA and miRNA expression profiles of 379 HCC samples with clinical information were used for comparative studies. Eleven adaptive and innate immune cell types were significantly altered in HCC samples, including B cell memory, regulatory T cells and follicular helper T cells. Differentially expressed competing endogenous RNA (ceRNA) network associated with patients' overall survival was identified. Then, the novel pathway, including LINC00261, MiR105-5p and selectin L(SELL) was found and may be potential novel biomarkers for patients' outcomes and immunotherapy. Furthermore, SELL was significantly positively correlated (correlation coefficients: 0.47-0.69) with 12 known gene signatures of immunotherapy except for programmed cell death 1 (PDCD1). Conclusions: Our findings could provide insights into the selection of novel LINC00261/MiR105-5p/SELL pathway which is associated with overall survival and may impact on efficacy of immunotherapy in HCC.