The highest-elevation frog provides insights into mechanisms and evolution of defenses against high UV radiation.

Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri. Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri. Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.

A randomised controlled study on the effects of hernial sac stump fenestration on ultrasound seroma prevention in laparoscopic Type III inguinal hernia repair.

BACKGROUND: The incidence of ultrasound seromas has significantly increased after large hernial sac surgery. Several methods are available for preventing ultrasound seromas, but the clinical results are poor. It has also been demonstrated that hernial sac stump fenestration during laparoscopic incisional hernia repair surgery can significantly decrease the incidence of ultrasound seromas. MATERIALS AND METHODS: Ninety patients aged 18-75 years who were treated in our hospital for primary Type III indirect inguinal hernia from March 2017 to March 2018 were randomised to a preventive fenestration group and a control group. All patients underwent transabdominal preperitoneal repair. The number of ultrasound seromas in the inguinal regions and ultrasound seroma volume on day 6 and months 1 and 3 after surgery in the two groups were compared. The secondary outcomes included length of surgery, urinary retention, acute pain, chronic pain, length of hospitalisation, recurrence rate and other complications. RESULTS: There were no significant differences in demographic characteristics. Ultrasound seroma incidence and ultrasound seroma volume on day 6 and months 1 and 3 after surgery were significantly lower in the preventive fenestration group than that in the control group. There were no significant differences in the length of hospitalisation or incidence of acute pain or urinary retention between the two groups. CONCLUSIONS: Hernial sac stump fenestration after hernial sac transection in inguinal hernia repair surgery is a simple method that can effectively reduce post-operative ultrasound seromas.

Expression of α2-Na/K-ATPase in C57BL/6J Mice Inner Ear and Its Relationship with Age-related Hearing Loss.

K+ cycling in the cochlea is critical to maintain hearing. Many sodium-potassium pumps are proved to participate in K+ cycling, such as Na/K-ATPase. The α2-Na/K-ATPase is an important isoform of Na/K-ATPase. The expression of α2-Na/K-ATPase in the cochlea is not clear. In this study, we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR, and the α2-Na/K-ATPase expression pattern was confirmed in the inner ear. It was found α2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging (4-, 14-, 26- and 48-weeks old mice). We suspected that, the down-regulation of α2-Na/K-ATPase expression might be associated with the remodeling of K+ cycling, degeneration of morphological structure and decrease of hearing function in aging C57 mice. In conclusion, we speculated that the reduction of α2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.

Early oral nutrition improves postoperative ileus through the TRPA1/CCK1-R-mediated mast cell-nerve axis.

BACKGROUND: The mechanism of early oral nutrition that regulates the mast cell-nerve axis to improve postoperative ileus (POI) remains unclear. This study aims to investigate whether early oral nutrition can improve POI through Transient receptor potential ankyrin-1 (TRPA1)/cholecystokinin 1 receptor (CCK1-R) in the mast cell-nerve axis. METHODS: Experiment 1: Male Sprague-Dawley (SD) rats were randomly divided into the TRPA1 inhibitor + oral nutrition group (TI + ON + POI), oral nutrition group (ON + POI), POI group (POI) and sham surgery group (Sham). Nine rats in each group were treated. Experiment 2: Primary cultures of mast cells and dorsal root ganglion cells were created, and a non-contact co-culture system was established. The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. The results of expression of TRPA1, CCK1-R and histamine in colon tissue, portal vein blood, supernatant or dorsal root ganglia, intestinal transport test and mast cell morphology were analysed. RESULTS: In experiment 1, Early oral nutrition could alleviate the degranulation and activation of mast cells and alleviate the inflammatory reaction of intestinal wall muscles (P<0.05). Early oral nutrition improved POI by stabilizing mast cells with TRPA1. TRPA1 inhibitor decreased CCK1-R concentrations in portal vein blood and CCK1-R expression in colonic smooth muscle (P<0.05). In experiment 2, the change in mast cell function regulated the secretion of CCK1-R by neurons, CCK1-R negatively regulated the degranulation and activation of mast cells (P<0.05), and mast cells positively regulated the expression of TRPA1 protein in DRG (P<0.05). CONCLUSIONS: Early enteral nutrition can improve POI through the TRPA1/CCK1-R-mediated mast cell-nerve axis. TRPA1 positively regulates CCK1-R to stabilize mast cells, but TRPA1 is not the target of the downstream CCK1-R pathway.

Comparison of multi-modal early oral nutrition for the tolerance of oral nutrition with conventional care after major abdominal surgery: a prospective, randomized, single-blind trial.

BACKGROUND & AIMS: Early oral nutrition (EON) has been shown to improve recovery of gastrointestinal function, length of stay and mortality after abdominal surgery; however, early oral nutrition often fails during the first week after surgery. Here, a multi-modal early oral nutrition program is introduced to promote recovery of gastrointestinal function and tolerance of oral nutrition. METHODS: Consecutive patients scheduled for abdominal surgery were randomized to the multimodal EON group or a group receiving conventional care. The primary endpoint was the time of first defecation. The secondary endpoints were outcomes and the cost-effectiveness ratio in treating infectious complications. The rate of infectious-free patients was regarded as the index of effectiveness. RESULTS: One hundred seven patients were randomly assigned to groups. Baseline characteristics were similar for both groups. In intention-to-treat analysis, the success rate of oral nutrition during the first week after surgery in the multimodal EON group was 44 (83.0%) versus 31 (57.4%) in the conventional care group (P = 0.004). Time to first defecation, time to flatus, recovery time of bowel sounds, and prolonged postoperative ileus were all less in the multimodal EON group (P < 0.05). The median postoperative length of stay in the multimodal EON group was 8 days (6, 12) versus 10 days (7, 18) in the conventional care group (P < 0.001). The total cost of treatment and nutritional support were also less in the multi-modal early oral nutrition group (P < 0.001). The effectiveness was 84.9 and 79.9% in the multimodal EON and conventional care group, respectively (P = 0.475). However, the cost-effectiveness ratio was USD 537.6 (506.1, 589.3) and USD 637.8 (593.9, 710.3), respectively (P < 0.001). CONCLUSION: The multi-modal early oral nutrition program was an effective way to improve tolerance of oral nutrition during the first week after surgery, decrease the length of stay and improve cost-effectiveness after abdominal surgery. TRIAL REGISTRATION: Registration number: ChiCTR-TRC-14004395 . Registered 15 March 2014.

Impact of nutritional support that does and does not meet guideline standards on clinical outcome in surgical patients at nutritional risk: a prospective cohort study.

OBJECTIVE: To investigate the impact of nutritional support on clinical outcomes in patients at nutritional risk who receive nutritional support that meets guideline standards and those who do not. METHODS: This prospective cohort study enrolled hospitalized patients from the Second Affiliated Hospital of Kunming Medical University from February 2010 to June 2012. The research protocols were approved by the university's ethics committee, and the patients signed informed consent forms. The clinical data were collected based on nutritional risk screening, administration of enteral and parenteral nutrition, surgical information, complications, and length of hospital stay. RESULTS: During the study period, 525 patients at nutritional risk were enrolled in the cohorts. Among patients who received nutritional support that met the guideline standards (Cohort 1), the incidence of infectious complications was lower than that in patients who did not meet guideline standards (Cohort 2) (17.1 % vs. 26.9 %, P = 0.01). Subgroup analysis showed that individuals who received a combination of parenteral nutrition (PN) and enteral nutrition (EN) for 7 or more days had a significantly lower incidence of infectious complications (P = 0.001) than those who received only PN for 7 or more days or those who received nutritional support for less than 7 days or at less than 10 kcal/kg/d. Binary logistic regression analysis showed that, after adjusting for confounding factors, nutritional support that met guideline standards for patients with nutritional risk was a protective factor for complications (OR: 0.870, P < 0.002). CONCLUSIONS: In patients at nutritional risk after abdominal surgery, nutritional support that meets recommended nutrient guidelines (especially regimens involving PN + EN ≥ 7 days) might decrease the incidence of infectious complications and is worth recommending; however, well-designed trials are needed to confirm our findings. Nutritional support that does not meet the guideline standards is considered clinically undesirable.

Genome-wide scans for candidate genes involved in the aquatic adaptation of dolphins.

Since their divergence from the terrestrial artiodactyls, cetaceans have fully adapted to an aquatic lifestyle, which represents one of the most dramatic transformations in mammalian evolutionary history. Numerous morphological and physiological characters of cetaceans have been acquired in response to this drastic habitat transition, such as thickened blubber, echolocation, and ability to hold their breath for a long period of time. However, knowledge about the molecular basis underlying these adaptations is still limited. The sequence of the genome of Tursiops truncates provides an opportunity for a comparative genomic analyses to examine the molecular adaptation of this species. Here, we constructed 11,838 high-quality orthologous gene alignments culled from the dolphin and four other terrestrial mammalian genomes and screened for positive selection occurring in the dolphin lineage. In total, 368 (3.1%) of the genes were identified as having undergone positive selection by the branch-site model. Functional characterization of these genes showed that they are significantly enriched in the categories of lipid transport and localization, ATPase activity, sense perception of sound, and muscle contraction, areas that are potentially related to cetacean adaptations. In contrast, we did not find a similar pattern in the cow, a closely related species. We resequenced some of the positively selected sites (PSSs), within the positively selected genes, and showed that most of our identified PSSs (50/52) could be replicated. The results from this study should have important implications for our understanding of cetacean evolution and their adaptations to the aquatic environment.

Deciphering the signature of selective constraints on cancerous mitochondrial genome.

In accordance with the hypothesis that cancer formation is a process of somatic evolution driven by natural selection, signature of positive selection has been detected on a number of cancer-related nuclear genes. It remains, however, controversial whether a similar selective pressure has also acted on mitochondrial DNA (mtDNA), a small molecule in mitochondrion that may play an important role in tumorigenesis by altering oxidative phosphorylation. To better understand the mutational pattern on cancerous mtDNA and decipher the genetic signature left by natural selection, a total of 186 entire mitochondrial genomes of cancerous and adjacent normal tissues from 93 esophageal cancer patients were obtained and extensively studied. Our results revealed that the observed mutational pattern on the cancerous mtDNAs might be best explained as relaxation of negative selection. Taking into account an additional 1,235 cancerous (nearly) complete mtDNA sequences retrieved from the literature, our results suggested that the relaxed selective pressure was the most likely explanation for the accumulation of mtDNA variation in different types of cancer. This notion is in good agreement with the observation that aerobic glycolysis, instead of mitochondrial respiration, plays the key role in generating energy in cancer cells. Furthermore, our study provided solid evidence demonstrating that problems in some of the published cancerous mtDNA data adequately explained the previously contradictory conclusions about the selective pressure on cancer mtDNA, thus serving as a paradigm emphasizing the importance of data quality in affecting our understanding on the role of mtDNA in tumorigenesis.

A mitogenomic perspective on the ancient, rapid radiation in the Galliformes with an emphasis on the Phasianidae.

BACKGROUND: The Galliformes is a well-known and widely distributed Order in Aves. The phylogenetic relationships of galliform birds, especially the turkeys, grouse, chickens, quails, and pheasants, have been studied intensively, likely because of their close association with humans. Despite extensive studies, convergent morphological evolution and rapid radiation have resulted in conflicting hypotheses of phylogenetic relationships. Many internal nodes have remained ambiguous. RESULTS: We analyzed the complete mitochondrial (mt) genomes from 34 galliform species, including 14 new mt genomes and 20 published mt genomes, and obtained a single, robust tree. Most of the internal branches were relatively short and the terminal branches long suggesting an ancient, rapid radiation. The Megapodiidae formed the sister group to all other galliforms, followed in sequence by the Cracidae, Odontophoridae and Numididae. The remaining clade included the Phasianidae, Tetraonidae and Meleagrididae. The genus Arborophila was the sister group of the remaining taxa followed by Polyplectron. This was followed by two major clades: ((((Gallus, Bambusicola) Francolinus) (Coturnix, Alectoris)) Pavo) and (((((((Chrysolophus, Phasianus) Lophura) Syrmaticus) Perdix) Pucrasia) (Meleagris, Bonasa)) ((Lophophorus, Tetraophasis) Tragopan))). CONCLUSIONS: The traditional hypothesis of monophyletic lineages of pheasants, partridges, peafowls and tragopans was not supported in this study. Mitogenomic analyses recovered robust phylogenetic relationships and suggested that the Galliformes formed a model group for the study of morphological and behavioral evolution.