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Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the high-quality genome of the five-pacer viper, Deinagkistrodon acutus , and comparative analyses with other representative snake and lizard genomes. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion, and many viper TEs show brain-specific gene expression along with their nearby genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes and also functional degeneration of genes associated with vision and hearing. Lineage-specific relaxation of functional constraints on respective Hox and Tbx limb-patterning genes supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the ZW sex chromosome pair had undergone at least three recombination suppression events in the ancestor of advanced snakes. These results altogether forge a framework for our deep understanding into snakes’ history of molecular evolution. Snakes have many characteristics that distinguish them from their relatives. Here, Yin et al. sequence the genome of the five-pacer viper, Deinagkistrodon acutus , and use comparative genomic analyses to elucidate the evolution of transposable elements, developmental genes and sex chromosomes in snakes.

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5a-androst-3ß,5,6ß-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the genome of the five-pacer viper, Deinagkistrodon acutus, and comparative analyses with species from other major snake and lizard lineages. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion; in the viper, many TEs may have been rewired into the regulatory network of brain genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes, and also functional degeneration of genes associated with vision and hearing. Many Hox and Tbx limb-patterning genes show evidence of relaxed selective constraints, and their phylogenetic distribution supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the Z and W sex chromosomes had undergone at least three recombination suppression events in the ancestor of advanced snakes, with the W chromosomes showing a gradient of degeneration from basal to advanced snakes. These results forge a framework for our deep understanding into snakes' history of molecular evolution.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (−71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration: ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1

Background: Disease?modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double?blind, parallel?group (three groups), placebo?controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent?to?treat population, adjusted annualized relapse rates were 0.63 (95％ confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95％ CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95％ CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2％, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12?week confirmed disability worsening by 68.1％ compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment?emergent adverse events (TEAEs; 72.2％ in the placebo group, 74.5％ in the teriflunomide 7 mg group, and 69.8％ in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1％, 3.9％, and 11.6％, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China.

When a lambda hyperon was embedded in a nucleus, it can form a hypernucleus. The lifetime and its mass dependence of stable hypernuclei provide information about the weak decay of lambda hyperon inside nuclear medium. This work will introduce the Jefferson Lab experiment (E02-017) which aims to study the lifetime of the heavy hypernuclei using a specially developed fission fragment detection technique, a multi-wire proportional chamber operated under low gas pressure (LPMWPC). Presented here are the method and performance of the reconstruction of fission position on the target foil, the separation of target materials at different regions and the comparison and verification with the Mote Carlo simulation.

Heavy-ion charge-exchange (CE) reactions provide a sensitive probe of isospin dynamics in nuclear collisions. We investigate the reaction \\(^12C(^12C,\\,^12N\\,^+)\\,^12Be\\) at 400--600 A MeV within the ultra-relativistic quantum molecular dynamics model combined with a phase-space coalescence approach. This reaction represents a nontrivial CE channel accompanied by a single \\(^+\\) production in heavy-ion collisions, extending previous studies from lepton-induced to hadronic systems. The \\(^12N\\) fragment is formed via nucleon and meson exchange, whereas \\(^+\\) production is primarily governed by \\(\\) resonance excitation and decay, enabling simultaneous investigations of CE processes and \\(\\)-induced pion production within the same reaction system. We calculate the reaction cross section and analyze the four-momentum distributions of \\(^12N\\) and \\(^+\\). Characteristic phase-space features reflect different production mechanisms and provide guidance for future experimental designs. Additionally, this reaction may serve as a potential pathway for rare-isotope production.