Summary
Tea is the world's widely consumed nonalcohol beverage with essential economic and health benefits. Confronted with the increasing large‐scale omics‐data set particularly the genome sequence ...released in tea plant, the construction of a comprehensive knowledgebase is urgently needed to facilitate the utilization of these data sets towards molecular breeding. We hereby present the first integrative and specially designed web‐accessible database, Tea Plant Information Archive (TPIA; http://tpia.teaplant.org). The current release of TPIA employs the comprehensively annotated tea plant genome as framework and incorporates with abundant well‐organized transcriptomes, gene expressions (across species, tissues and stresses), orthologs and characteristic metabolites determining tea quality. It also hosts massive transcription factors, polymorphic simple sequence repeats, single nucleotide polymorphisms, correlations, manually curated functional genes and globally collected germplasm information. A variety of versatile analytic tools (e.g. JBrowse, blast, enrichment analysis, etc.) are established helping users to perform further comparative, evolutionary and functional analysis. We show a case application of TPIA that provides novel and interesting insights into the phytochemical content variation of section Thea of genus Camellia under a well‐resolved phylogenetic framework. The constructed knowledgebase of tea plant will serve as a central gateway for global tea community to better understand the tea plant biology that largely benefits the whole tea industry.
Organic–inorganic hybrid perovskite single-crystalline thin films (SCTFs) are promising for enhancing photoelectric device performance due to high carrier mobility, long diffusion length, and carrier ...lifetime. However, bulk perovskite single crystals available today are not suitable for practical device application due to the unfavorable thickness. Herein, we report a facile space-confined solution-processed strategy to on-substrate grow various hybrid perovskite SCTFs in a size of submillimeter with adjustable thicknesses from nano- to micrometers. These SCTFs exhibit photoelectric properties comparable to bulk single crystals with low defect density and good air stability. The clear thickness-dependent colors allow fast visual selection of SCTFs with a suitable thickness for specific device application. The present substrate-independent growth of perovskite SCTFs opens up opportunities for on-chip fabrication of diverse high-performance devices.
MicroRNAs (miRs) are involved in lymphoma progression by regulating tumor cell interaction with microenvironment. MiR155 is overexpressed in diffuse large B-cell lymphoma (DLBCL) and its biological ...effect on tumor microenvironment needs to be futher investigated.
MiR155 was detected by quantitative real-time PCR in patients with newly diagnosed DLBCL. The mechanism of action of miR155 on lymphoma progression and tumor microenvironment was examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model.
Serum miR155 was significantly elevated, correlated with tumor miR155 expression, and indicated poor disease outcome in DLBCL. MiR155 overexpression was associated with decreased peripheral blood CD8+T cells and inhibition of T-cell receptor signaling. Of note, EBV-positive patients showed higher serum miR155 than EBV-negative patients. In co-culture systems of B-lymphoma cells with immune cells, miR155 induced Fas-mediated apoptosis of CD8+T cells, which could be targeted by anti-PD-1 and anti-PD-L1 antibodies. Moreover, miR155 enhanced lymphoma cell PD-L1 expression, recruited CD8+T cells by PD-1/PD-L1 interaction and inhibited CD8+T cell function via dephosphorylating AKT and ERK. MiR155-induced AKT/ERK inactivation was more obvious in CD8+T cells co-cultured with EBV-infected B-lymphoma cells. In vivo in a murine xenograft model established with subcutaneous injection of A20 cells, PD-L1 blockade particularly retarded miR155-overexpressing tumor growth, consistent with maintenance of CD8+T cells and their function.
As a oncogenic biomarker of B-cell lymphoma, serum miR155 was related to lymphoma progression through modulating PD-1/PD-L1-mediated interaction with CD8+T cells of tumor microenvironment, indicating the sensitivity of B-cell lymphoma to PD-L1 blockade. Also CD8+T cells could be a therapeutic mediator of immune checkpoint inhibitors in treating EBV-associated lymphoid malignancies.
Mortality from hepatitis B virus (HBV)–related acute‐on‐chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with ...mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV‐related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV‐related ACLF were enrolled in this open‐label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow–derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%‐84.8%) versus 55.6% (95% confidence interval 42.3%‐68.9%) for the SMT group (P = 0.03). There were no infusion‐related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5‐24 of follow‐up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow–derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End‐Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). Conclusion: Peripheral infusion of allogeneic bone marrow–derived MSCs is safe and convenient for patients with HBV‐related ACLF and significantly increases the 24‐week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209–219).
China has pledged to peak carbon emissions before 2030 and strive to achieve carbon neutrality before 2060. However, the significant variations of provincial carbon emissions make it unclear whether ...they can jointly fulfill the national carbon peak and neutrality goal. Thus, this study predicts the emission trajectories at provincial level in China by employing the extended STIRPAT (Stochastic Impacts by Regression on Population, Affluence, and Technology) model to see the feasibility and time of reaching peak carbon emissions and carbon neutrality. We found that most provinces can achieve peak emission before 2030 but challenging to achieve carbon neutrality before 2060, even considering the ecological carbon sink. The provincial neutrality time is concentrated between 2058 and 2070; the sooner the carbon emission peaks, the earlier the carbon neutral will be realized. The aggregated carbon emissions at provincial level show that China can achieve its carbon emission peak of 9.64–10.71 Gt before 2030, but it is unlikely to achieve the carbon neutrality goal before 2060 without carbon capture, utilization, and storage (CCUS). With high CCUS development, China is expected to achieve carbon neutrality in 2054–2058, irrespective of the socio-economic scenarios. With low CCUS development, China's carbon neutrality target will be achieved only under the accelerated-improvement scenario, while it will postpone to 2061 and 2064 under the continued-improvement and the business-as-usual scenarios, respectively.
In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing ...tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance. Emerging roles of the microbiome in tumorigenesis or tumor progression revealed the intricate interactions between inflammatory response, dysbiosis, metabolites, CXCL8, immune cells, and the TME. Studies have shown that CXCL8 directly contributes to TME remodeling, cancer plasticity, and the development of resistance to both chemotherapy and immunotherapy. Further, clinical data demonstrate that CXCL8 could be an easily measurable prognostic biomarker in patients receiving immune checkpoint inhibitors. The blockade of the CXCL8-CXCR1/2 axis alone or in combination with other immunotherapy will be a promising strategy to improve antitumor efficacy. Herein, we review recent advances focusing on identifying the mechanisms between TME components and the CXCL8-CXCR1/2 axis for novel immunotherapy strategies.
Molybdenum disulfide is considered one of the most promising anodes for lithium-ion batteries due to its high specific capacity; however, it suffers from an unstable solid electrolyte interphase. ...Understanding its structural evolution and reaction mechanism upon charging/discharging is crucial for further improvements in battery performance. Herein, the interfacial processes of solid electrolyte interphase film formation and lithiation/delithiation on ultra-flat monolayer molybdenum disulfide are monitored by in situ atomic force microscopy. The live formation of ultra-thin and dense films can be induced by the use of fluoroethylene carbonate as an additive to effectively protect the anode electrodes. The evolution of the fluoroethylene carbonate-derived solid electrolyte interphase film upon cycling is quantitatively analysed. Furthermore, the formation of wrinkle-structure networks upon lithiation process is distinguished in detailed steps, and accordingly, structure-reactivity correlations are proposed. These quantitative results provide an in-depth understanding of the interfacial mechanism in molybdenum disulfide-based lithium-ion batteries.
We report a molecular investigation of a cobalt phthalocyanine (CoPc)‐catalyzed CO2 reduction reaction by electrochemical scanning tunneling microscopy (ECSTM). An ordered adlayer of CoPc was ...prepared on Au(111). Approximately 14 % of the adsorbed species appeared with high contrast in a CO2‐purged electrolyte environment. The ECSTM experiments indicate the proportion of high‐contrast species correlated with the reduction of CoIIPc (−0.2 V vs. saturated calomel electrode (SCE)). The high‐contrast species is ascribed to the CoPc‐CO2 complex, which is further confirmed by theoretical simulation. The sharp contrast change from CoPc‐CO2 to CoPc is revealed by in situ ECSTM characterization of the reaction. Potential step experiments provide dynamic information for the initial stage of the reaction, which include the reduction of CoPc and the binding of CO2, and the latter is the rate‐limiting step. The rate constant of the formation and dissociation of CoPc‐CO2 is estimated on the basis of the in situ ECSTM experiment.
Imaging the electrocatalytic process: The cobalt‐phthalocyanine‐catalyzed CO2 reduction reaction is investigated by electrochemical scanning tunneling microscopy at the molecular scale. The molecular processes of the reaction, including the reduction of CoII, the binding of CO2, and the subsequent process, are revealed.
Genetic studies have elucidated critical roles of Piwi proteins in germline development in animals, but whether Piwi is an actual disease gene in human infertility remains unknown. We report germline ...mutations in human Piwi (Hiwi) in patients with azoospermia that prevent its ubiquitination and degradation. By modeling such mutations in Piwi (Miwi) knockin mice, we demonstrate that the genetic defects are directly responsible for male infertility. Mechanistically, we show that MIWI binds the histone ubiquitin ligase RNF8 in a Piwi-interacting RNA (piRNA)-independent manner, and MIWI stabilization sequesters RNF8 in the cytoplasm of late spermatids. The resulting aberrant sperm show histone retention, abnormal morphology, and severely compromised activity, which can be functionally rescued via blocking RNF8-MIWI interaction in spermatids with an RNF8-N peptide. Collectively, our findings identify Piwi as a factor in human infertility and reveal its role in regulating the histone-to-protamine exchange during spermiogenesis.
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•Hiwi ubiquitination-deficient D-box mutations are detected in azoospermia patients•D-box mutant knockin mice display spermatogenic failure at late spermiogenesis•Stabilized MIWI ties RNF8 up in the cytoplasm to prevent histone ubiquitination•Blocking MIWI-RNF8 interaction functionally rescues defective spermiogenesis
Male infertility in mice and humans can result from mutations that stabilize the Piwi protein in late spermatids: sperm defects are due to aberrant histone retention, not piRNA misregulation.
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