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The mechanisms by which HBV diversity can occur both within the individual host and at a population level are also discussed.Approximately 7-9% of people develop posttraumatic stress disorder in their lifetime, but standard pharmacological treatment or psychotherapy shows a considerable individual variation in their effectiveness. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) hold promise for the treatment of posttraumatic stress disorder. The objective of this meta-analysis was to summarize the existing evidence on the therapeutic effects of these brain stimulation treatments on posttraumatic core symptoms. We systematically retrieved articles published between 1st January 2000 and 1st January 2020 comparing the effects of active with sham stimulation or no intervention in posttraumatic patients from eight databases. Random-effects model was used for meta-analysis. Meta-regression and subgroup meta-analysis was performed to investigate the influence of stimulation dose and different stimulation protocols, respectively. 20 studies were included in this review, where of 11 randomized controlled trials were subjected to quantitative analysis. Active stimulation demonstrated significant reductions of core posttraumatic symptoms with a large effect size (Hedge's g = -0.975). Subgroup analysis showed that both excitatory and inhibitory rTMS of the right dorsolateral prefrontal cortex led to symptom reductions with a large (Hedges' g = -1.161, 95% CI, -1.823 to -0.499; p = 0.015) and medium effect size (Hedges' g = -0.680, 95% CI -0.139 to -0.322; p ≤ 0.001) respectively. Results further indicated significant durability of symptom-reducing effects of treatments during a two to four weeks period post stimulation (Hedges' g = -0.909, 95% CI -1.611 to -0.207; p = 0.011). rTMS of the right dorsolateral prefrontal cortex appears to have a positive effect in reducing core symptoms in patients with posttraumatic stress disorder.Liver fibrosis is a global health problem currently without clinically approved drugs. It is characterized by the excessive accumulation of extracellular matrix (ECM) mainly produced by activated hepatic stellate cells (HSCs). Uncovering the mechanisms underlying the fibrogenic responses in HSCs may have profound translational implications. Erythropoietin-producing hepatocellular receptor B2 (EphB2) is a receptor tyrosine kinase that has been indicated to be a novel profibrotic factor involved in liver fibrogenesis. In the present study, we investigated the effects of miR-451 and miR-185 on the expression of EphB2 and their roles in liver fibrogenesis both in vitro and in vivo. We found that EphB2 upregulation is a direct downstream molecular event of decreased expression of miR-451 and miR-185 in the process of liver fibrosis. Moreover, miR-451 was unexpectedly found to upregulate miR-185 expression at the post-transcriptional level by directly targeting the nuclear export receptor exportin 1 (XPO-1) and synergistically suppress HSCs activation with miR-185. To investigate the clinical potential of these miRNAs, miR-451/miR-185 agomirs were injected individually or jointly into CCl4-treated mice. The results showed that coadministration of these agomirs synergistically alleviated liver fibrosis in vivo. These findings indicate that miR-451 and miR-451/XPO-1/miR-185 axis play important and synergistic regulatory roles in hepatic fibrosis partly through co-targeting EphB2, which provides a novel therapeutic strategy for the treatment of hepatic fibrosis.Central nervous system (CNS) disorders represent a broad spectrum of brain ailments with short- and long-term disabilities, and nanomedicine-based approaches provide a new therapeutic approach to treating CNS disorders. A variety of potential drugs have been discovered to treat several neuronal disorders; however, their therapeutic success can be limited by the presence of the blood-brain barrier (BBB). Furthermore, unique immune functions within the CNS provide novel target mechanisms for the amelioration of CNS diseases. Recently, various therapeutic approaches have been applied to fight brain-related disorders, with moderate outcomes. Among the various therapeutic strategies, nanomedicine-based immunotherapeutic systems represent a new era that can deliver useful cargo with promising pharmacokinetics. These approaches exploit the molecular and cellular targeting of CNS disorders for enhanced safety, efficacy, and specificity. In this review, we focus on the efficacy of nanomedicines that utilize immunotherapy to combat CNS disorders. Furthermore, we detailed summarize nanomedicine-based pathways for CNS ailments that aim to deliver drugs across the BBB by mimicking innate immune actions. Overview of how nanomedicines can utilize multiple immunotherapy pathways to combat CNS disorders.The programmed cell death protein 1 (PD-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. PD-1 antibodies can block the interaction of PD-1 with its ligands (PD-L1 and PD-L2), restore T cells activation, and elicit antitumor activity. In this paper, we reported a novel PD-1 monoclonal antibody (mAb) CS1003, which is a humanized IgG4 PD-1 mAb generated by conventional hybridoma technology, and currently being developed in multiple clinical trials as monotherapy or in combination with other anticancer agents. We showed that CS1003 bound to recombinant human, cynomolgus monkey, and mouse PD-1 with EC50 values of 0.1757, 0.2459, and 0.3664 nM, respectively. CS1003 blocked PD-1 interaction with its ligands, dose-dependently enhanced T cell proliferation and secretion of cytokines (IL-2 and IFN-γ) to the levels comparable to the reference antibody pembrolizumab. Intraperitoneal administration of CS1003 (0.1, 0.5, 2.5 mg/kg, once every 3 days) dose-dependently suppressed the growth of MC38-hPD-L1 colon cancer in hPD-1 knock-in mice. Pharmacokinetics (PK) study revealed a linear PK profile within the dose range of 2-18 mg/kg following single intravenous administration in cynomolgus monkey. check details These data provide a comprehensive preclinical characterization of CS1003 that supports its clinical development for cancer immunotherapy.