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A meta-analysis of all reported cases (n=85) has shown that EBER+ LELCC is strongly associated with the female sex, younger age, and exhibited predominantly glandular differentiation (P=0.001, 0.012, and less then 0.001, respectively). Patients with EBER- LELCC were more likely to have viral hepatitis and cirrhosis (P=0.003 and 0.005, respectively). Genetic analysis demonstrated that EBER- LELCC was significantly associated with pTERT and TP53 mutations (P=0.033 and 0.008, respectively). In conclusion, LELCC is genetically distinct from intrahepatic cholangiocarcinoma. EBER- LELCC may exhibit a different pathogenesis from EBER+ LELCC. High programmed death-ligand 1 expression in LELCC has implications for potential immunotherapeutic strategies.Prenatal environment significantly influences mammalian fetal development and adverse in utero conditions have life-long consequences for the offspring health. Research has revealed that a wide variety of prenatal stress factors lead to increased risk of vulnerability to neuropsychiatric disorders in the individuals. Multiple mediators are involved in stress transfer from mother to the developing fetus, with stress hormone cortisol being a chief player. Further, the developmental programming effects of prenatal stress have been observed in the form of alterations in the offspring brain at different levels. This review covers stress transfer mediators such as cortisol, serotonin, maternal cytokines, reactive oxygen species (ROS) and the maternal microbiota, and their role in fetal programming. Prenatal stress leads to alterations in the offspring brain at multiple levels, from molecular and cellular to structural. These alterations eventually result in lasting phenotypic alterations such as in the offspring behavior and cognition. Different brain alterations induced by prenatal stress such as in neural pruning processes, neural circuit formation, brain structural connectivity and epigenetic systems regulating neural gene expression are under focus in the second part of the review. The latter constitutes a key molecular mechanism involved in prenatal stress effects and has been discussed in more detail.Microvascular hyperpermeability is a leading mechanism responsible for occurrence of edema in remote organs and tissues in patients with burn injury. Accumulated evidence has shown that exosomes can be transported into target cells, where they are capable of regulating biological functions and physiology. Of exosomal proteins contributing to enhanced inflammation and vascular permeability, S100 calcium binding protein A9 (S100A9) has received increasing attention. Here we hypothesized that S100A9-containing serum exosomes of patients with burn injury contribute to pathogenesis of hyperpermeability of microvascular structure in lung by transferring signaling molecules into it and activating downstream signaling pathways, ultimately leading to disruption of the tight junctions (TJs) and endothelial barrier. A use of enzyme-linked immunosorbent assay revealed that total serum concentrations of S100A9 were significantly augmented in burn injury patients in comparison to normal controls. With use of human pulmonarat blocking exosomes’ access to HPMECs could hold a promise strategy for treatment of lung edema resulting from burn injuries.Phytic acid or Myo-inositol hexakisphosphate is an essential compound for the rice plants. It remains in the form of phytate, a mixed salt of different mineral cations, in the seeds. The phytate breaks down during germination and provides the inorganic phosphorus and mineral ions to the seedlings. However, humans do not get the benefit of those essential ions from rice consumption due to the absence of phytase in the gut. We envisaged down-regulating ITPK, the gene behind the phytic acid biosynthesis so that its low amount would facilitate a greater amount of free mineral ions in the endosperm. Since there are six homologues of rice ITPK, we studied their expression in seeds. Additionally, we undertook an in-silico analysis of the homologous proteins. Binimetinib Considering the results, we selected ITPK-2 for its RNAi-mediated embryo-specific down-regulation to obtain the low phytate rice. We obtained a 37% reduction of phytic acid content accompanied by a nearly three-fold enhancement of inorganic phosphorus in the transgenic seeds. Additionally, the iron and zinc content increased in polished rice grains compared to the wild type. The results also showed that reduced phytic acid content did not affect the germination potential and seedling growth of the transgenic rice.Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4+ T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC50 = 12.46 ± 1.300 µM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 µM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.The present study explored the therapeutic potential of hydrogen sulfide (H2S) in restoring aging-induced loss of cardioprotective effect of remote ischemic preconditioning (RIPC) along with the involvement of signaling pathways. The left hind limb was subjected to four short cycles of ischemia and reperfusion (IR) in young and aged male rats to induce RIPC. The hearts were subjected to IR injury on the Langendorff apparatus after 24 h of RIPC. The measurement of lactate dehydrogenase, creatine kinase and cardiac troponin served to assess the myocardial injury. The levels of H2S, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible factor (HIF-1α) were also measured. There was a decrease in cardioprotection in RIPC-subjected old rats in comparison to young rats along with a reduction in the myocardial levels of H2S, CBS, CSE, HIF-1α, and nuclear cytoplasmic Nrf2 ratio. Supplementation with sodium hydrogen sulfide (NaHS, an H2S donor) and l-cysteine (H2S precursor) restored the cardioprotective actions of RIPC in old hearts.