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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.

Objective: To evaluate the impact of a standardized feeding protocol and donor breast milk (DBM) provision on clinical outcomes in moderate preterm infants (MPT, 29–33 6/7 weeks gestational age). Study Design: A protocol for MPT infants born > 1500 g was implemented clinically to standardize feeding advancements at 30 mL/kg/day. Infants

Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma (HCC). Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis, predicting responses to specific therapies, evaluating prognosis before or after therapy, as well as serving as novel therapeutic targets. Detection and analysis of proteins, metabolites, circulating nucleic acids, circulating tumor cells, and extracellular vesicles in body fluids (e.g., blood and urine) and gut microbiota (e.g., in feces) have excellent capabilities to improve different aspects of management of HCC. Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis, treatment, and monitoring responses of HCC to conventional therapies, most of which may improve diagnosis and management of HCC in the future. This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.

Defense against increasing ultraviolet radiation (UV) 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 analyzed UV responses in the highest-elevation frog, Nanorana parkeri, using integrated approaches. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. Our study revealed new UV-defense systems. Genomic and metabolomic analysis along with large-scale transcriptomic and microRNA profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. Both gene mutations and expression shifts contribute to such UV adaptation. We found that microRNAs 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. Our work demonstrates a genetic framework for evolution of UV-defense in a natural environment.

Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the Web of Science, PubMed, Scopus, Ovid, Cochrane Library, and Embase databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78–0.85), 0.89 (95%CI: 0.85–0.91), and 0.92 (95%CI: 0.89–0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66–0.79)) and a high specificity (0.87 (95%CI: 0.81–0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66–0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66–0.87), 0.80 (95%CI: 0.72–0.87), and 0.86 (95%CI: 0.83–0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.

Non-small cell lung cancer (NSCLC) is a worldwide disease with a high morbidity and mortality rate, which is most derived from its metastasis. Some studies show that the epithelial-mesenchymal transition (EMT) process promotes lung cancer cell migration and invasion, leading to NSCLC metastasis. Total flavonoid aglycones extract (TFAE) isolated from

Protein content is often inadequate in donor breast milk (DBM), resulting in poor growth. The use of protein-enriched target-pooled DBM (DBM+) has not been examined. We compared three cohorts of very low birth weight (VLBW) infants, born ≤ 1500 g: DBM cohort receiving &gt, 1-week target-pooled DBM (20 kcal/oz), MBM cohort receiving ≤ 1-week DBM, and DBM+ cohort receiving &gt, 1-week DBM+. Infants followed a standardized feeding regimen with additional fortification per clinical discretion. Growth velocities and z-scores were calculated for the first 4 weeks (n = 69 for DBM, 71 for MBM, 70 for DBM+) and at 36 weeks post-menstrual age (n = 58, 64, 59, respectively). In total, 60.8% MBM infants received fortification &gt, 24 kcal/oz in the first 30 days vs. 78.3% DBM and 77.1% DBM+. Adjusting for SGA, length velocity was greater with DBM+ than DBM in week 1. Average weight velocity and z-score change were improved with MBM compared to DBM and DBM+, but length z-score decreased similarly across all groups. Incidences of NEC and feeding intolerance were unchanged between eras. Thus, baseline protein enrichment appears safe in stable VLBW infants. Weight gain is greatest with MBM. Linear growth comparable to MBM is achievable with DBM+, though the overall length trajectory remains suboptimal.

Non-small cell lung cancer (NSCLC) is a worldwide disease with high morbidity and mortality, which is most derived from its metastasis. Some researches show that the epithelial-mesenchymal transition (EMT) process promotes lung cancer cells migration and invasion, leading to NSCLC metastasis. Total Flavonoid Aglycones Extract (TFAE) isolated from Scutellaria baicalensis was reported to inhibit tumor growth and induce apoptosis. In this study, we found that baicalein, wogonin, and oroxylin-A were the active compounds of TFAE. After reconstructing with these three compounds (baicalein (65.8%), wogonin (21.2%), and oroxylin-A (13.0%)), the reconstructed TFAE (reTFAE) present inhibitory effect on the EMT process of A549 cells. Then, bioinformatic technology was employed to elucidate the potential pharmacodynamic mechanism network of reTFAE. We identified the relationship between reTFAE and PI3K/Akt signaling pathways, with TWIST1 as the key protein. LY294002, the inhibitor of PI3K/Akt signaling pathway, and knock-down TWIST1 could significantly enhance the efficacy of reTFAE, with increasing expression of epithelial markers and decreasing expression of mesenchymal markers in A549 cells at the same time. Furthermore, stable isotope dimethyl-labeled proteomics technology was conducted to complement the follow-up mechanism that the EMT-inhibition process may be realized through glycolysis pathway. In conclusion, we claim that TWIST1-targeted flavonoids could provide a new strategy to inhibit EMT progress for the treatment of NSCLC.

To explore the possibility of predicting the clinical types of Corona-Virus-Disease-2019 (COVID-19) pneumonia by analyzing the non-focus area of the lung in the first chest CT image of patients with COVID-19 by using automatic machine learning (Auto-ML). 136 moderate and 83 severe patients were selected from the patients with COVID-19 pneumonia. The clinical and laboratory data were collected for statistical analysis. The texture features of the Non-focus area of the first chest CT of patients with COVID-19 pneumonia were extracted, and then the classification model of the first chest CT of COVID-19 pneumonia was constructed by using these texture features based on the Auto-ML method of radiomics, The area under curve(AUC), true positive rate(TPR), true negative rate (TNR), positive predictive value(PPV) and negative predictive value (NPV) of the operating characteristic curve (ROC) were used to evaluate the accuracy of the first chest CT image classification model in patients with COVID-19 pneumonia. The TPR, TNR, PPV, NPV and AUC of the training cohort and test cohort of the moderate group and the control group, the severe group and the control group, the moderate group and the severe group were all greater than 95% and 0.95 respectively. The non-focus area of the first CT image of COVID-19 pneumonia has obvious difference in different clinical types. The AUTO-ML classification model of Radiomics based on this difference can be used to predict the clinical types of COVID-19 pneumonia.

The Himalaya are among the youngest and highest mountains in the world, but the exact timing of their uplift and origins of their biodiversity are still in debate. The Himalayan region is a relatively small area but with exceptional diversity and endemism. One common hypothesis to explain the rich montane diversity is uplift-driven diversification—that orogeny creates conditions favoring rapid in situ speciation of resident lineages. We test this hypothesis in the Himalayan region using amphibians and reptiles, two environmentally sensitive vertebrate groups. In addition, analysis of diversification of the herpetofauna provides an independent source of information to test competing geological hypotheses of Himalayan orogenesis. We conclude that the origins of the Himalayan herpetofauna date to the early Paleocene, but that diversification of most groups was concentrated in the Miocene. There was an increase in both rates and modes of diversification during the early to middle Miocene, together with regional interchange (dispersal) between the Himalaya and adjacent regions. Our analyses support a recently proposed stepwise geological model of Himalayan uplift beginning in the Paleocene, with a subsequent rapid increase of uplifting during the Miocene, finally giving rise to the intensification of the modern South Asian Monsoon.

In 2020, the new type of coronal pneumonitis became a pandemic in the world, and has firstly been reported in Wuhan, China. Chest CT is a vital component in the diagnostic algorithm for patients with suspected or confirmed COVID-19 infection. Therefore, it is necessary to conduct automatic and accurate detection of COVID-19 by chest CT.The clinical classification of patients with COVID-19 pneumonia was predicted by Radiomics using chest CT.From the COVID-19 cases in our institution, 136 moderate patients and 83 severe patients were screened, and their clinical and laboratory data on admission were collected for statistical analysis. Initial CT Radiomics were modeled by automatic machine learning, and diagnostic performance was evaluated according to AUC, TPR, TNR, PPV and NPV of the subjects. At the same time, the initial CT main features of the two groups were analyzed semi-quantitatively, and the results were statistically analyzed.There was a statistical difference in age between the moderate group and the severe group. The model cohort showed TPR 96.9%, TNR 99.1%, PPV98.4%, NPV98.2%, and AUC 0.98. The test cohort showed TPR 94.4%, TNR100%, PPV100%, NPV96.2%, and AUC 0.97. There was statistical difference between the two groups with grade 1 score (P = .001), the AUC of grade 1 score, grade 2 score, grade 3 score and CT score were 0.619, 0.519, 0.478 and 0.548, respectively.Radiomics' Auto ML model was built by CT image of initial COVID -19 pneumonia, and it proved to be effectively used to predict the clinical classification of COVID-19 pneumonia. CT features have limited ability to predict the clinical typing of Covid-19 pneumonia.

Objective: To explore the possibility of predicting the clinical types of Corona-Virus-Disease-2019(COVID-19) pneumonia by analyzing the non-focus area of the lung in the first chest CT image of patients with COVID-19 by using automatic machine learning (Auto-ML).Methods: 136 moderate and 83 severe patients were selected from the patients with COVID-19 pneumonia. The clinical and laboratory data were collected for statistical analysis. The texture features of the Non-focus area of the first chest CT of patients with COVID-19 pneumonia were extracted, and then the classification model of the first chest CT of COVID-19 pneumonia was constructed by using these texture features based on the Auto-ML method of radiomics, The area under curve(AUC), true positive rate(TPR), true negative rate(TNR), positive predictive value(PPV) and negative predictive value(NPV) of the operating characteristic curve (ROC) were used to evaluate the accuracy of the first chest CT image classification model in patients with COVID-19 pneumonia.Result: The TPR, TNR, PPV, NPV and AUC of the training cohort and test cohort of the moderate group and the control group, the severe group and the control group, the moderate group and the severe group were all greater than 95% and 0.95 respectively. Conclusion: The non-focus area of the first CT image of COVID-19 pneumonia has obvious difference in different clinical types. The AUTO-ML classification model of Radiomics based on this difference can be used to predict the clinical types of COVID-19 pneumonia.

Histone deacetylase 6 (HDAC6) plays a key role in a variety of neurological disorders, which makes it attractive drug target for the treatment of Alzheimer's disease, Parkinson's disease, and memory/learning impairment. The selectivity of HDAC6 inhibitors (sHDAC6Is) are widely considered to be susceptible to the sizes of their Cap group and the physicochemical properties of their linker or zinc-binding group, which makes the discovery of new sHDAC6Is extremely difficult. With the discovery of the distinct selectivity between Trichostatin A (TSA) enantiomers, the chirality residing in the connective units between TSA's Cap and linker shows a great impact on its selectivity. However, the mechanism underlining ( S)-TSA's selectivity is still elusive, and the way chirality switches the selective ( S)-TSA to nonselective ( R)-TSA is unknown. In this study, multiple computational approaches were collectively applied to explore, validate, and differentiate the binding modes of two TSA enantiomers in HDACs (especially the HDAC6) at atomic level. First, two nonconservative residues (G200/M205 and Y197/F202 in HDAC1/6) in loop3 and four conservative residues deep inside the hydrophobic binding pocket were discovered as the decisive residues of ( S)-TSA's selectivity toward HDAC6. Then, a novel mechanism underlying the selectivity of ( S)-TSA toward HDAC6 was proposed, which was composed of the trigger by two nonconservative residues F202 and M205 in HDAC6 and a subsequently improved fit of ( S)-TSA deep inside HDAC6's hydrophobic binding pocket. TSA enantiomers were used as a molecular probe to explore the mechanism underlying sHDAC6Is' selectivity in this study. Because of their decisive roles in ( S)-TSA's selectivity to HDAC6, both F202 and M205 in HDAC6 should be especially considered in the discovery of novel sHDAC6Is.

Viviparous (live-bearing) vertebrates have evolved repeatedly within otherwise oviparous (egg-laying) clades. Over two-thirds of these changes in vertebrate reproductive parity mode happened in squamate reptiles, where the transition has happened between 98 and 129 times. The transition from oviparity to viviparity requires numerous physiological, morphological, and immunological changes to the female reproductive tract, including eggshell reduction, delayed oviposition, placental development for supply of water and nutrition to the embryo by the mother, enhanced gas exchange, and suppression of maternal immune rejection of the embryo. We performed genomic and transcriptomic analyses of a closely related oviparous–viviparous pair of lizards ( Phrynocephalus przewalskii and Phrynocephalus vlangalii ) to examine these transitions. Expression patterns of maternal oviduct through reproductive development of the egg and embryo differ markedly between the two species. We found changes in expression patterns of appropriate genes that account for each of the major aspects of the oviparity to viviparity transition. In addition, we compared the gene sequences in transcriptomes of four oviparous–viviparous pairs of lizards in different genera ( Phrynocephalus , Eremias , Scincella , and Sphenomorphus ) to look for possible gene convergence at the sequence level. We discovered low levels of convergence in both amino acid replacement and evolutionary rate shift. This suggests that most of the changes that produce the oviparity–viviparity transition are changes in gene expression, so occasional reversals to oviparity from viviparity may not be as difficult to achieve as has been previously suggested.

With advancements in the care of preterm infants, the goals in nutritional care have expanded from survival and mimicking fetal growth to optimizing neurodevelopmental outcomes. Inadequate nutritional support may be a risk factor for major complications of prematurity; conversely, higher disease burden is a risk for growth restriction. Early complete parenteral nutrition support, including intravenous lipid emulsion, should be adopted, and the next challenge that should be addressed is parenteral nutrition customized to fit the specific needs and metabolism of the extremely preterm infant. Standardized feeding protocols should be adopted.

β2-Microglobulin (β2M), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of β2M in the development of lung emphysema. Here, we found that concentrations of β2M in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 vs. 1.42 ± 0.06 mg/l, P < 0.01). Moreover, the expression of β2M was significantly higher in lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%, P < 0.01). Immunofluorescence showed that β2M was mainly expressed in prosurfactant protein C-positive (pro-SPC+) alveolar epithelial cells and CD14+ macrophages. Exposure to recombinant human β2M and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-β2M antibody. However, anti-β2M antibody did not attenuate the elevated production of IL-1β, IL-6, and TNF-α in A549 cells that were exposed to CSE. Immunofluorescence showed that colocalization of β2M, and the hemochromatosis gene (HFE) protein was observed on A549 cells. These data suggest β2M might participate in the development of lung emphysema through induction of lung epithelial cell senescence and inhibition.

Venom injected into the host plays vital roles in facilitating successful parasitization and development for parasitoid wasps, especially those devoid of polydnavirus, and the abundant venom proteins appear to be most likely involved in parasitization success. Previously, we found the four most abundant venom proteins, including 4-coumarate:CoA ligase-like 4 (4CL4-like), in the Tetrastichus brontispae (Hymenoptera: Eulophidae) venom apparatus. In this study, we cloned, expressed T. brontispae 4CL4-like (Tb4CL4-like) in Escherichia coli, and investigated its immunosuppressive properties. The deduced amino acid sequence for Tb4CL4-like shares high identity at conserved amino acids associated with the acyl-activating enzyme (AAE) consensus motif but shows only &lt, 40% identity with the members in the AAE superfamily. mRNA abundance analysis indicated that Tb4CL4-like was transcribed mainly in the venom apparatus. Recombinant Tb4CL4-like inhibited Octodonta nipae (Coleoptera: Chrysomelidae) pupal cellular encapsulation and spreading by targeting the hemocyte cytoskeleton and reduced the hemocyte-mediated phagocytosis of E. coli in vivo. Moreover, Tb4CL4-like exhibited greater affinity to palmitic acid and linolenic acid based on the molecular docking assay and is hypothesized to be involved in fatty acid metabolism. In conclusion, our results suggest that Tb4CL4-like may be an immunity-related AAE protein that is involved in the regulation of host immunity through fatty acid metabolism-derived signaling pathways.

Cardiac remodeling is an important pathological process ultimately leading to heart failure. Ubiquitin carboxy-terminal hydrolase 1 (UCHL1) is a deubiquitinase that plays a critical role in neurodegenerative diseases and cancer. However, its role in cardiac remodeling in spontaneously hypertensive rats remains unclear. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were administered the UCHL1 inhibitor LDN-57444 (20 μg/kg/day) from 2 months of age for 4 months. Blood pressure, cardiac hypertrophy, fibrosis, inflammation, and oxidative stress were evaluated by the tail-cuff system, echocardiography, and histological analysis. Gene and protein expression levels were examined by real-time PCR and immunoblotting analysis. At 6 months of age, the expression of UCHL at the mRNA and protein levels was significantly upregulated in SHRs compared with WKYs. Moreover, systolic blood pressure, cardiac performance, left ventricular (LV) hypertrophy, fibrosis, inflammation, and superoxide production were significantly increased in SHRs compared with WKYs, and these effects were markedly attenuated by LDN-57444 after 4 months of administration. These beneficial actions were possibly associated with a reduction in blood pressure and inactivation of multiple signaling pathways, including AKT, ERK1/2, STAT3, calcineurin A, TGF-β/Smad2/3, and NF-κB. In conclusion, the results indicate that UCHL1 is involved in hypertensive cardiac remodeling in SHRs, and targeting UCHL1 activity may be a novel potential therapeutic approach for the treatment of hypertensive heart diseases.

The macronutrient composition of target-pooled donor breast milk (DBM) (milk combined strategically to provide 20 kcal/oz) and growth patterns of preterm infants receiving it have not been characterized. Caloric target-pooled DBM samples were analyzed by near-infrared spectroscopy. Weekly growth velocities and anthropometric z-scores were calculated for the first 30 days and at 36 weeks corrected gestational age (CGA) for 69 very low birthweight (VLBW) infants receiving minimum one week of DBM. Samples contained mean 18.70 kcal/oz, 0.91 g/dL protein, 3.11 g/dL fat, 7.71 g/dL carbohydrate (n = 96), less than labeled values by 2.43 kcal/oz and 0.11 g/dL protein (p &lt, 0.001). By week 3, growth reached 16.58 g/kg/day, 0.95 cm/week (length), and 1.01 cm/week (head circumference). Infants receiving &lt, 50% vs. &gt, 50% DBM had similar growth, but infants receiving &gt, 50% DBM were more likely to receive fortification &gt, 24 kcal/oz (83% vs. 51.9% in the &lt, 50% DBM group, p = 0.005). From birth to 36 weeks CGA (n = 60), there was a negative z-score change across all parameters with the greatest in length (&minus, 1.01). Thus, target-pooling does not meet recommended protein intake for VLBW infants. Infants fed target-pooled DBM still demonstrate a disproportionate negative change in length z-score over time.

A 2,340-g male infant is born vaginally at 34 weeks of gestation to a mother with a history of asthma and hyperthyroidism. The pregnancy is overall uncomplicated except for preterm labor, and the delivery is notable for meconium-stained amniotic fluid and unknown group B Streptococcus status treated with 2 doses of penicillin. The infant does well initially with Apgar scores of 8 and 9, but soon develops tachycardia, tachypnea, and hypoxemia; radiography demonstrates respiratory distress syndrome with a small pneumothorax. Nasal cannula is needed to maintain normal oxygen saturations, and septic evaluation result is negative. Examination is notable for the vital signs described before, a barrel-shaped chest, and hyperreflexia. He is started on gavage feeds and treated with phototherapy for hyperbilirubinemia. On day 7 after birth, he suddenly develops worsening tachycardia to the 200s, tachypnea with respiratory distress, and decreased perfusion with mottling. Echocardiography reveals severe cardiac dysfunction, prompting transfer to the cardiac intensive …

Objective To investigate the effect of berberine on endoplasmic reticulum stress PERK apoptosis pathway in HK-2 cells by high fructose. Methods HK-2 cells were grown in DMEM/F12, containing 10% fetal bovine serum (FBS) and divided randomly into four groups: normal control group (Group C); Fructose group (Group F): it contains 25mmol/L fructose culture; Berberine group (Group B): 25mmol/L fructose + 10μmol/L berberine treatment group; TUDCA group (Group T): 25mmol/L fructose +2μmol/L TUDCA culture group; Cells were collected after culturing 24h. The expression of glucose-regulated protein 78 (GRP78), CHOP protein and the phosphorylation levels of PERK, eIF2α were tested by Western blotting. The cell cycles were detected by flow cytometry and the apoptosis of cells were detected by TUNEL staining. Results Western blotting showed that the expression of GRP78 and CHOP protein in group F was significantly higher than that in group C, and the levels of p-PERK and p-eIF2α in group F were significantly higher than those in group F. Compared with group F, GRP78, CHOP, p-PERK and p-eIF2α in group B and T were significantly lower (P0.05). Conclusion Persistent high fructose can activate the intracellular PERK pathway in HK-2 cells, causing endoplasmic reticulum stress. Berberine can inhibit the fructose-induced PERK and eIF2α phosphorylation, down-regulated the expression of GRP78, CHOP protein, thus by regulating PERK Pathways to alleviate cell cycle arrest and reduce cell apoptosis. DOI: 10.11855/j.issn.0577-7402.2017.01.02

Although many cases of genetic adaptations to high elevations have been reported, the processes driving these modifications and the pace of their evolution remain unclear. Many high-elevation adaptations (HEAs) are thought to have arisen in situ as populations rose with growing mountains. In contrast, most high-elevation lineages of the Qinghai-Tibetan Plateau appear to have colonized from low-elevation areas. These lineages provide an opportunity for studying recent HEAs and comparing them with ancestral low-elevation alternatives. Herein, we compare four frogs (three species of Nanorana and a close lowland relative) and four lizards ( Phrynocephalus ) that inhabit a range of elevations on or along the slopes of the Qinghai-Tibetan Plateau. The sequential cladogenesis of these species across an elevational gradient allows us to examine the gradual accumulation of HEA at increasing elevations. Many adaptations to high elevations appear to arise gradually and evolve continuously with increasing elevational distributions. Numerous related functions, especially DNA repair and energy metabolism pathways, exhibit rapid change and continuous positive selection with increasing elevations. Although the two studied genera are distantly related, they exhibit numerous convergent evolutionary changes, especially at the functional level. This functional convergence appears to be more extensive than convergence at the individual gene level, although we found 32 homologous genes undergoing positive selection for change in both high-elevation groups. We argue that species groups distributed along a broad elevational gradient provide a more powerful system for testing adaptations to high-elevation environments compared with studies that compare only pairs of high-elevation versus low-elevation species.

Background Acemannan is a bioactive polysaccharides promoting tissue repair. However, the roles of acemannan in skin wound healing and the underlying molecular mechanisms are largely unclear. Objective The goal of this study is to investigate the positive role of acemannan in cutaneous wound healing and its mechanism. Methods Mouse skin wound model and skin primary fibroblasts were used to demonstrate the positive effect of acemannan on cutaneous wound healing. The expressions of cell proliferation nuclear antigen ki-67, cyclin D1 and activity of AKT/mTOR signaling were analyzed in acemannan-treated fibroblasts and mice. Rapamycin and AKT inhibitor VIII were used to determine the key role of AKT/mTOR signaling in acemannan-promoting cutaneous wound healing. Results We found that acemannan significantly accelerated skin wound closure and cell proliferation. Acemannan promoted the expression of cyclin D1 in cultured fibroblasts, which was mediated by AKT/mTOR signal pathway leading to enhanced activity of the eukaryotic translation initiation factor-4F (eIF4F) and increased translation of cyclin D1. In contrast, pharmaceutical blockade of AKT/mTOR signaling by mTOR inhibitor rapamycin or AKT inhibitor VIII abolished acemannan-induced cyclin D1 translation and cell proliferation. In vivo studies confirmed that the activation of AKT/mTOR by acemannan played a key role in wound healing, which could be reversed by rapamycin. Conclusion Acemannan promoted skin wound healing partly through activating AKT/mTOR-mediated protein translation mechanism, which may represent an alternative therapy approach for cutaneous wound.

Rationale Glycine is the smallest amino acid used in protein synthesis, but it is also a very important precursor for the biosynthesis of other nitrogen-containing metabolites, such as purine nucleosides and nucleotides for synthesis of RNA, DNA etc. Abnormalities in glycine metabolism therefore cause diseases such as cancer. A quick and unambiguous method to trace the metabolites arising from glycine is required for targeting defect points within metabolic networks. Methods This paper describes a method for using 15N-glycine to culture A549 cancer cells for use with high-resolution mass spectrometry (HRMS) and tandem mass spectrometry (HRMS2) that can detect the (M+1)/M pair peaks appearing in the cell metabolites. The 1 Da difference in the pair peaks can be used to point out and identify the nitrogen metabolites of glycine. Results Thirteen nitrogen-containing metabolites derived from glycine were confirmed. Among them were metabolites containing purine, such as adenine, adenosine, AMP, ADP, ATP, S-adenosylmethionine and γ-glutathione; these were the most sensitive to the 15N-glycine-enrichment technique. Therefore, they are promising biomarkers for monitoring the glycine metabolism network. Conclusions The method developed here could be applied to investigations of metabolism of other amino acids, and for drug discovery studies targeting the enzymes related to amino acid metabolism. Copyright © 2015 John Wiley & Sons, Ltd.

A term male infant born via spontaneous vaginal delivery with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively, has an episode of apnea with stiffening and nonsuppressible whole body jerking for 2 minutes, occurring 5 hours after birth. Around 8 hours after birth, he has another episode but with exaggerated startle reflex, lip smacking, and eyelid fluttering. General examination shows no dysmorphic features, and findings are otherwise normal. Initial neurologic examination findings are unremarkable. Continuous electroencephalographic (EEG) monitoring with full neonatal montage is significant for intermittent sharp waves. Over the next day, the infant has 3 episodes of apnea with stiffening and nonsuppressible whole body jerking after each episode. These events are captured but EEG does not show them to be seizures. Initial management with phenobarbital and levetiracetam does not ameliorate spells. His antenatal course is unremarkable. Family history is remarkable for consanguineous parentage of Middle Eastern descent (parents are first cousins of first cousins). Laboratory evaluation including serum and cerebrospinal fluid studies for infectious and metabolic etiologies shows normal findings. Magnetic resonance imaging (MRI) on day 5 after birth reveals normal brain structure with nonspecific hyperintense basal ganglia signal and minimal subdural hemorrhage from the birthing process. Five days later, findings of a repeat MRI with added spectroscopy are normal. ### Diagnosis and Further Progress Given the clinical suspicion for hyperekplexia, the patient was started on a trial of carbamazepine (15 …

The location of invasive infections is difficult to detect in infants, in part due to their inability to localize signs and symptoms. However, identifying the location often significantly alters clinical management by extending the duration of antibiotic therapy or revealing a source requiring surgical intervention. Compared with commonly used first-line imaging techniques such as radiographs and ultrasounds, MRI has higher sensitivity for identifying invasive infections and allows for simultaneous evaluation of multiple foci. We present 2 cases in which whole-body screening MRI was used in neonates to identify invasive sources of infection, including one in which traditional modalities failed to detect multiple clinically significant sources. We posit that whole-body screening MRI merits consideration as a potential first-line imaging method when investigating invasive infections in infants.

In the work reported here, boron source is borax, carbon source is sucrose and the nitrogen source is urea, polymer-network method is applied to prepare the hexagonal boron nitride (h-BN) precursor, and then synthesized the h-BN powders with high purity and high surface area. As the sucrose content is fixed, we study the effect of carbonization temperature on phase composition and adsorption properties of h-BN powders. As the carbonization temperature is fixed, the effect of sucrose content on phase composition and adsorption properties of h-BN powders are studied. The results show that the optimum carbonization temperature is 220°C, and when the sucrose content reach 17.45wt.%, the h-BN powders showed the best adsorption properties.

The effect of NaCl on seedling emergence, plant growth and ion accumulation for two sugar beet cultivars was evaluated. The result showed that seedling emergence in Tianyan309 was much lower than that in KWS3418 in the initial 6 days. High salinity markedly decreased final seedling emergence in both cultivars, especially in Tianyan309, while salinity had no adverse effect on total seedling emergence after the recovery experiment in both cultivars. Low salinity (86 mM NaCl) had no significant effect on shoot and root dry weights, while 171 and 257 mM NaCl inhibited shoot and root dry weights of two cultivars, especially for KWS3418. Concentrations of Na+ and Cl- in leaves were increased with increasing NaCl in both cultivars. There was no significant difference between two cultivars in concentrations of Na+ and Cl- in the leaves at different concentrations of NaCl, except that Cl- concentration in leaves of Tianyan309 was lower than that in KWS3418 at 257 mM NaCl. The characteristic of Cl- uptake and/or accumulation may relate to different salt tolerance of KWS3418 and Tianyan309.

This paper establishes a power planning model based on minimization of the initial investment cost. The model includes the initial investment cost of wind turbines, photovoltaic cells, batteries, and biomass generators, diesel generators, power electronic devices and communications facilities in the objective function. In consideration of some constraint conditions, using the principle of priority of biomass generators, we use the particle swarm algorithm to solve the model. Through the calculation of actual examples, we simulate to find optimal solutions. Finally, we conclude that it should be possible to use biomass power generation and diesel generator power.

PD in cable accessories will inspire EM waves of ultra-high frequency (UHF) at hundreds of MHZ to GHZ. To study the characteristics of EM wave inspired by PD in cable accessories, a three-dimension model of 110kV cable joints is established. Based on the propagation theory of EM waves in coaxial waveguide, finite element method (FEM) is used to analyze the effect of cable joints composite interfaces on UHF signal propagation, and simulation analysis of relations between PD UHF signal's energy distribution, pulse frequency, propagation distance. Simulation results show that the main transmission mode of EM waves is TEM mode in the joints; Energy of EM waves descends rapidly as the PD pulse's frequency increases; Energy of TEM waves descends rapidly with the increasing detection distance. Simulation analysis of UHF signal's propagation characteristics provides the theoretical basis for UHF PD detection in cable accessories.

The characteristics and the synthesis principle of nanocrystalline materials prepared by electrodeposition are summaried in this paper. The research status of nanocrystalline materials and the common methods preparing nanocrystalline materials are reviewed, such as direct current electrodeposition, pulse electrodeposition, composite electrodeposition and jet electrodeposition. Finally, some prospects on development and applications of nanocrystalline materials in material science are proposed in this paper.

Boron nitride nanotubes attract wide interest because of their unique structures as well as super properties. The structures, properties, synthetic methods and application studies are particularly summarized. Since they were discovered, additionally, the prospects for future research and application are proposed. In this paper, advances in researches on Boron Nitride (BN) nanotubes are reviewed, and some of technologies for preparation of BN nanotubes are described. The tip structures of BN nanotubes produced by different technologies are compared and discussed.

β2-Microglobulin (β2M), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of β2M in the development of lung emphysema. Here, we found that concentrations of β2M in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 vs. 1.42 ± 0.06 mg/l, P < 0.01). Moreover, the expression of β2M was significantly higher in lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%, P < 0.01). Immunofluorescence showed that β2M was mainly expressed in prosurfactant protein C-positive (pro-SPC+) alveolar epithelial cells and CD14+ macrophages. Exposure to recombinant human β2M and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-β2M antibody. However, anti-β2M antibody did not attenuate the elevated production of IL-1β, IL-6, and TNF-α in A549 cells that were exposed to CSE. Immunofluorescence showed that colocalization of β2M, and the hemochromatosis gene (HFE) protein was observed on A549 cells. These data suggest β2M might participate in the development of lung emphysema through induction of lung epithelial cell senescence and inhibition.

High specific surface materials were widely applied in water pollution control, air pollution control and recycling of organic solvents due to their excellent physical and chemical properties such as large specific surface area, redox characteristic, high adsorption and desorption speed and large adsorptive capacity. The characteristics of activated carbon fiber, nanometer titanium dioxide and their applications in environmental protection such as air purification, the treatment of drinking water and industrial wastewater and the recycling of organic solvent were investigated in present work.

Objective: This study is designed to measure the current level of Indoor Electromagnetic Radiation (IER) in Chongqing, a municipality of western P.R. China, on which further epidemiological investigation on the relation between the level of IER and certain health effects could be based. Methods: 118 Households in 4 urban residential districts in Chongqing were randomly selected. The IER intensity was measured in each household’s living room at different frequencies under three different conditions. Results: The average electric field intensity measured at the frequency range of 1 MHz- 40 GHz was within the guidelines set by the International Commission on Non Ionizing Radiation Protection (ICNIRP). The electromagnetic field intensity measured at other frequencies were at the lowest range of the acceptable values. The average electric field intensity at the frequency range of 5 Hz - 1 kHz was higher at a standing posture than at a sitting posture with domestic appliances turned off in both cases (P < 0.01). Conclusion: The indoor electromagnetic radiation in Chongqing currently is still within the recommended public exposure limit set by ICNIRP.

The radial basis function (RBF) neural network is superior to other neural network on the aspects of approximation ability, classification ability, learning speed and global optimization etc., it has been widely applied as feedforward networks, its performance critically rely on the choice of RBF centers of network hidden layer node. K-means clustering, as a commonly method used on determining RBF center, has low neural network generalization ability, due to its clustering results are not sensitive to initial conditions and ignoring the influence of dependent variable. In view of this problem, fuzzy clustering and grey relational clustering methods are proposed to substitute K-means clustering, RBF center is determined by the results of fuzzy clustering or grey relational clustering, and some researches of RBF neural networks modeling accuracy are done. Practical modeling cases demonstrate that the modeling accuracy of fuzzy clustering RBF neural networks and grey relational clustering RBF neural networks are significantly better than K-means clustering RBF neural networks, applying of fuzzy clustering or grey relational clustering to determine the basis function center of RBF neural networks hidden layer node is feasible and effective.

In reconfigurable system, hardware task placement algorithms are trying to find rectangle of available reconfigurable logic units in a fast manner. Furthermore, low cost and less fragmentation are another two metrics of high performance algorithm. In previous work we proposed a Transformable Vertexes Information based Algorithm (TVIA) for online task placement in reconfigurable system. In this paper, based on TVIA, we adopt Resource Swap scheme for reuse based hardware task scheduling. Hardware tasks will remain in the reconfigurable device after execution. Only when there is no enough space left for incoming tasks will previous tasks been swapped out from configurable device. This paper discusses the principle and procedure of resource swap management and compares several algorithms using simulation.

This article reviews the synthesis of Si-B-C-N ceramics, and the characteristics and principle of fabricating Si-B-C-N ceramics by using different precursors. So far, there only have two reports on preparation of Si-B-C-N ceramics, which are precursor pyrolysis and mechanical alloying. Therefore, this paper mainly discusses precursor pyrolysis and mechanical alloying. In addition, this paper proposed some prospects on the development and applications of Si-B-C-N ceramics in material science.