Characteristics of broadband lightning emissions associated with terrestrial gamma ray flashes

To characterize lightning processes that produce terrestrial gamma ray flashes (TGFs), we have analyzed broadband (<1 Hz to 30 kHz) lightning magnetic fields for TGFs detected by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) satellite in 2004-2009. The majority (96%) of 56 TGF-associated lightning signals contain single or multiple VLF impulses superposed on a slow pulse that reflects a process raising considerable negative charge within 2-6 ms. Some TGF lightning emissions also contain VLF signals that precede any appreciable slow pulse and that we term precursor sferics. The analyses of 9 TGFs related to lightning discharges with location uncertainty <100 km consistently indicate that TGFs are temporally linked to the early portion of the slow process and associated VLF impulses, and not to precursor sferics. The nearly universal presence of a slow pulse suggests that the slow process plays an important role in gamma ray production. In all cases the slow process raises negative charge with a typical mean current moment of +30 kA km. The resulting charge moment change ranges from small values below +10 C km to a maximum of +200 C km, with an average of +64 C km. The current moment waveform extracted from TGF sferics with single or multiple VLF impulses also shows that the slow process initiates shortly before the major TGF-associated fast discharge. These features are generally consistent with the TGF-lightning sequence reported by Lu et al. (2010), suggesting that the majority of RHESSI TGFs are produced during the upward negative leader progression prevalent in normal polarity intracloud flashes

Metabolite Profiling of adh1 Mutant Response to Cold Stress in Arabidopsis

As a result of global warming, vegetation suffers from repeated freeze-thaw cycles caused by more frequent short-term low temperatures induced by hail, snow, or night frost. Therefore, short-term freezing stress of plants should be investigated particularly in light of the current climatic conditions. Alcohol dehydrogenase (ADH) plays a central role in the metabolism of alcohols and aldehydes and it is a key enzyme in anaerobic fermentation. ADH1 responds to plant growth and environmental stress; however, the function of ADH1 in the response to short-term freezing stress remains unknown. Using real-time quantitative fluorescence PCR, the expression level of ADH1 was analyzed at low temperature (4°C). The lethal temperature was calculated based on the electrolyte leakage tests for both ADH1 deletion mutants (adh1) and wild type (WT) plants. To further investigate the relationship between ADH1 and cold tolerance in plants, low-Mr polar metabolite analyses of Arabidopsis adh1 and WT were performed at cold temperatures using gas chromatography-mass spectrometry. This investigation focused on freezing treatments (cold acclimation group: −6°C for 2 h with prior 4°C for 7 d, cold shock group: −6°C for 2 h without cold acclimation) and recovery (23°C for 24 h) with respect to seedling growth at optimum temperature. The experimental results revealed a significant increase in ADH1 expression during low temperature treatment (4°C) and at a higher lethal temperature in adh1 compared to that in the WT. Retention time indices and specific mass fragments were used to monitor 263 variables and annotate 78 identified metabolites. From these analyses, differences in the degree of metabolite accumulation between adh1 and WT were detected, including soluble sugars (e.g., sucrose) and amino acids (e.g., asparagine). In addition, the correlation-based network analysis highlighted some metabolites, e.g., melibiose, fumaric acid, succinic acid, glycolic acid, and xylose, which enhanced connectedness in adh1 network under cold chock. When considered collectively, the results showed that adh1 possessed a metabolic response to freezing stress and ADH1 played an important role in the cold stress response of a plant. These results expands our understanding of the short-term freeze response of ADH1 in plants

MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression

10.1371/journal.pone.0041523PLoS ONE78

catena-Poly[[(1,10-phenanthroline)lead(II)]bis­(μ-5-chloro-2-hy­droxy­benzoato)]

In the title polymer, [Pb(C7H4ClO3)2(C12H8N2)]n, the Pb(II) ion displays a distorted pseudo-octa­hedral coordination geometry. The metal center is coordinated by six O atoms from four 5-chloro­salicylate ligands and two N atoms from a chelating phenanthroline ligand. The polymeric structure is built up from bridging carboxyl­ate O atoms, forming chains along [100]. The crystal structure is stabilized by π–π inter­actions between the 1,10-phenanthroline and 5-chloro­salicylate ligands, the shortest centroid–centroid separation between neighbouring aromatic rings being 3.652 (1) Å

Infiltrating T lymphocytes and tumor microenvironment within cholangiocarcinoma: immune heterogeneity, intercellular communication, immune checkpoints

Cholangiocarcinoma is the second most common primary liver cancer, and its global incidence has increased in recent years. Radical surgical resection and systemic chemotherapy have traditionally been the standard treatment options. However, the complexity of cholangiocarcinoma subtypes often presents a challenge for early diagnosis. Additionally, high recurrence rates following radical treatment and resistance to late-stage chemotherapy limit the benefits for patients. Immunotherapy has emerged as an effective strategy for treating various types of cancer, and has shown efficacy when combined with chemotherapy for cholangiocarcinoma. Current immunotherapies targeting cholangiocarcinoma have predominantly focused on T lymphocytes within the tumor microenvironment, and new immunotherapies have yielded unsatisfactory results in clinical trials. Therefore, it is essential to achieve a comprehensive understanding of the unique tumor microenvironment of cholangiocarcinoma and the pivotal role of T lymphocytes within it. In this review, we describe the heterogeneous immune landscape and intercellular communication in cholangiocarcinoma and summarize the specific distribution of T lymphocytes. Finally, we review potential immune checkpoints in cholangiocarcinoma

KIF20A activated by transcription factor GATA2 promotes cell growth in hepatitis B virus-related hepatocellular carcinoma

BackgroundElevated evidence suggests that KIF20A plays an important role in hepatocellular carcinoma (HCC) progression. Nevertheless, the underlying mechanism by which KIF20A promotes HCC cell growth are not well understood.MethodsUsing TCGA-LIHC RNAseq and GEO datasets, we assessed the KIF20A expression and patient survival in HCC and hepatitis B virus (HBV)-related HCC. Mutant and CNV analysis were performed to evaluate the genetic alteration of KIF20A in HCC. PPI network and GSEA enrichment was utilized for analyzing the KIF20A-related genes and involved pathways in HCC. To further explore regulatory mechanism in HBV-related HCC, PROMO prediction and luciferase reporter system was utilized for verifying HBx/GATA2/KIF20A binding sites. CCK-8 and flow cytometry were carried out to determine the regulation of GATA2-KIF20A on HBV-related HCC cell proliferation and apoptosis.ResultsKIF20A was significantly upregulated in pan-cancer (including HCC). KIF20A mRNA level was a significant independent predictor of overall survival in HBV-related HCC patients. Genetic alterations analysis revealed the copy number gain and amplification triggered KIF20A upregulation in HCC. In addition, the genes associated with KIF20A expression in HCC was enriched in PLK1 pathway and cell cycle in HCC. HBx might indirectly binds to KIF20A promoter via regulating GATA2. Additionally, transcription factor GATA2 directly binds to the promoter region of KIF20A. Overexpression of GATA2 promotes HepG2.2.15 cell growth and inhibits cell apoptosis via modulating KIF20A.ConclusionsOur findings demonstrated that HBx contributed to cell proliferation by interacting with GATA2 and KIF20A in HBV-related HCC