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Trefoil Factor 1 (TFF1, also named pS2), which serves as the gastrointestinal mucosal protector, is known as gastric-specific tumor suppressor gene. However, the genetic variants of TFF1 are still not well studied. In our study, we aim to explore the effects of tagging single nucleotide polymorphisms (tagSNPs) of TFF1 on risk and prognosis of gastric cancer. Seven tagSNPs of TFF1 gene were first analyzed in the discovery set, which was consisted of 753 cases and 950 cancer-free controls. Then, the validation set (940 cases and 1,042 controls) was used for further evaluation. Moreover, we also tested the relation between these tagSNPs and prognosis of gastric cancer (GC). A series of experiments were performed to investigate the underlying mechanisms. We found that rs3761376 AA in the promoter region of TFF1, could reduce the expression of TFF1 by affecting the binding affinity of estrogen receptor 1 (ESR1, ERα), and thereby increased the risk of GC (1.29, 1.08-1.53). Moreover, the rs3761376 AA genotype was also found associated with worse prognosis among patients receiving 5-FU based chemotherapy after surgery (1.71, 1.18-2.48). Further functional assays demonstrated that TFF1 could increase the chemosensitivity of 5-FU by modulating NF-κB targeted genes. These results identified the effect of rs3761376 on TFF1 expression, which accounted for the correlation with susceptibility and prognosis of GC; and this genetic variant may be a potential biomarker to predict the risk and survival of GC.

Background Coronavirus disease 2019 (COVID-19) has spread to the world. Whether there is an association between lifestyle behaviors and the acquisition of COVID-19 remains unclear. Methods In this case-control study, we recruited 105 patients with SARS-CoV-2 infection as a case group from the Wuhan Tongji Hospital (Wuhan, China). For each case two control subjects were recruited. Participants were randomly selected from communities in Wuhan and matched for sex, age (± 2yrs), and pre-existing comorbidities (hypertension and diabetes). Results A total of 105 patients diagnosed with COVID-19 and 210 controls were included. Compared with control group, the case group had higher proportions of lack of sleep (30.5% vs. 14.8%, P = 0.001) and increased physical activities (56.2% vs. 32.9%, P < 0.001). And patients in the case group were more likely to have alopecia (28.6% vs. 10.0%, P < 0.001) than people from the control group. Overall, we found that lack of sleep [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 1.03–2.39)], physical activities (≥ 5 times a week) (adjusted OR 2.05, 95%CI 1.39–3.02) and alopecia (adjusted OR 1.73, 95%CI 1.13–2.66) were independent risk factors for COVID-19 infection. Conversely, low-dose alcohol intake ( Conclusions Individual lifestyle behaviors and health status can affect the occurrence of COVID-19.

Supplemental material, Author_response_1 for Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies by Fengyuan Li, Rulan Yin and Qiang Guo in Therapeutic Advances in Respiratory Disease

Supplemental material, PRISMA-2009-Flow-Diagram-MS-Word for Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies by Fengyuan Li, Rulan Yin and Qiang Guo in Therapeutic Advances in Respiratory Disease

Supplemental material, Reviewer_2_v.1 for Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies by Fengyuan Li, Rulan Yin and Qiang Guo in Therapeutic Advances in Respiratory Disease

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a worldwide pandemic named coronavirus disease 2019 (COVID-19). The disease progression and mortality rates of patients with COVID-19 are higher in males than in females. Hence, we explored the potential mechanism of the COVID-19 gender disparity and searched for potential alternative therapeutic agents as unmet medical needs for male patients with COVID-19. Methods: We collected clinical data from 1339 COVID-19 patients and analyzed androgen receptor (AR) chromatin binding and expression patterns by ChIP-seq and scRNA-seq data. Moreover, we studied the androgen-induced expression of ACE-2 and TMPRSS2, two key proteins for SARS-CoV-2 cellular entry and infection and the blockage of these two key proteins with our AR antagonist Proxalutamide (GT0918) in normal lung cells, cancer cells derived from prostate and lung cancers. Furthermore, we examined the effect of GT0918 on inducible nitric oxide synthase (iNOS) and Tumor necrosis factor-alpha (TNF-α), the macrophage-activation markers, in mouse macrophage cells. Results: We demonstrated higher rates of disease progression and mortality of male COVID-19 patients. The mechanism of the gender disparity may result from the androgen-AR activation in male patients with COVID-19. We revealed that androgen-AR activation induced the expression of ACE2 and TMPRSS2 under the androgen-dependent condition in cells derived from prostate and lung cancer, which was inhibited by the blockage of AR signaling with AR antagonist GT0918. Importantly, GT0918 also inhibited the expression of macrophage activation markers iNOS and TNF-α, the biomarkers for macrophage polarization. These results support the role of androgen-AR signaling in the disease progression and mortality in male patients with COVID-19.

Supplemental material, PRISMA-2009-Checklist-MS-Word for Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies by Fengyuan Li, Rulan Yin and Qiang Guo in Therapeutic Advances in Respiratory Disease

Supplemental material, Supplement_Materials_1 for Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies by Fengyuan Li, Rulan Yin and Qiang Guo in Therapeutic Advances in Respiratory Disease

Ten new species of the spider family Psilodercidae Machado, 1951 are described from tropical East Asia, including five species found in China: Sinoderces luohanensis Li & Li, sp. nov. (♂♀), S. xueae Li & Li, sp. nov. (♂♀), S. taichi Li & Li, sp. nov. (♂♀), S. wenshanensis Li & Li, sp. nov. (♂♀), S. aiensis Li & Li, sp. nov. (♂♀); three are from Laos: S. khanensis Li & Li, sp. nov. (♂♀), S. phathaoensis Li & Li, sp. nov. (♂♀), S. kieoensis Li & Li, sp. nov. (♂); and the rest are from Thailand: S. saraburiensis Li & Li, sp. nov. (♂), S. dewaroopensis Li & Li, sp. nov. (♂♀). Types of all new species are deposited in the Institute of Zoology, Chinese Academy of Sciences in Beijing, China.

High-fat/high-fructose diet plus intermittent hypoxia exposure (HFDIH) causes metabolic disorders such as insulin resistance, obesity, nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. The purpose of this study is to examine the effects and understand the mechanism of action of Lactobacillus rhamnosus GG culture supernatant (LGGs) on HFDIH-induced metabolic dysfunction. Mice were fed high-fat:high-fructose diet for 15 weeks. After 3 weeks of feeding, the mice were exposed to chronic intermittent hypoxia for the next 12 weeks (HFDIH), and LGGs was supplemented over the entire experiment. HFDIH exposure significantly led to metabolic disorders. LGGs treatment showed significant improvements in indices of metabolic disorders including fat mass, energy expenditure, glucose intolerance, insulin resistance, increased hepatic steatosis and liver injury. HFDIH mice markedly increased adipose inflammation and adipocyte size, and reduced circulating adiponectin, which was restored by LGGs treatment. LGGs treatment increased hepatic FGF21 mRNA expression and circulating FGF21 protein levels, which were associated with increased hepatic PPARα expression and fecal butyrate concentration. In addition, HFDIH-induced hepatic fat accumulation and apoptosis were significantly reduced by LGGs supplementation. In summary, LGGs treatment increased energy expenditure and insulin sensitivity and prevented metabolic abnormalities in HFDIH mice, and this is associated with the FGF21-adiponectin signaling pathway. LGGs may be a potential prevention/treatment strategy in subjects with the metabolic syndrome.

Aims. We have established a procedure for uncut Roux-en-Y gastrojejunostomy after laparoscopic distal gastrectomy. This study aimed to evaluate the safety and technical feasibility of the procedure for patients with distal gastric cancer according to the short-term outcomes. Methods. Two hundred and twenty-eight consecutive patients who underwent a laparoscopic distal gastrectomy with uncut Roux-en-Y gastrojejunostomy from September 2014 to August 2018 were reviewed retrospectively. All the laparoscopic operations were performed successfully without conversion to open surgery. Results. The mean operative duration was 178.28 ± 32.82 minutes, the mean anastomotic process duration was 28.22 ± 7.50 minutes, the average blood loss was 48.97 ± 29.16 mL, and the overall number of lymph nodes harvested was 37.16 ± 11.47. The mean time of out-of-bed ambulation, anal exsufflation, liquid-diet intake, and duration of hospital stay were 41.99 ± 18.37 hours, 69.57 ± 23.17 hours, 5.06 ± 1.09 days, and 8.77 ± 2.42 days, respectively. Fifteen patients suffered postoperative complications, and the overall incidence rate was 6.58% (15/228). Seventeen patients experienced afferent recanalization, the mean time of which was 11 months after the operation. Conclusion. The laparoscopic uncut Roux-en-Y reconstruction is safe and technically feasible, and it has inspiring short-term outcomes for patients undergoing distal gastrectomy.

Background Chronic alcohol intake increases circulating endotoxin levels causing excessive inflammation that aggravates the liver injury. (E)-2,3-dimethoxy-4'-methoxychalcone (L6H21), a derivative of chalcone, has been found to inhibit inflammation in cardiac diseases and nonalcoholic fatty liver disease. However, the use of L6H21 in alcoholic liver disease to inhibit exotoxin-associated inflammation has not been explored. In this study, we examined the effects of L6H21 on EtOH + LPS-induced hepatic inflammation, steatosis, and liver injury and investigated the underlying mechanisms. Methods C57BL6 mice were treated with 5% EtOH for 10 days, and LPS was given to the mice 6 hours before sacrificing. One group of mice was supplemented with L6H21 with EtOH and LPS. RAW264.7 cells were used to analyze the effects of L6H21 on macrophage activation. Results EtOH + LPS treatment significantly increased hepatic steatosis and serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), which were reduced by L6H21 treatment. EtOH + LPS treatment increased hepatic inflammation, as shown by the increased hepatic protein levels of Toll-like receptor-4, p65, and p-IκB, and increased oxidative stress, as shown by protein carbonyl levels and reactive oxygen species formation, which were reduced by L6H21 treatment. In addition, L6H21 treatment markedly inhibited EtOH + LPS-elevated hepatic protein levels of NLRP3, cleaved caspase-1, cleaved IL-1β, and caspase-1-associated apoptosis. Conclusions Our results demonstrate that L6H21 treatment inhibits EtOH + LPS-induced liver steatosis and injury through suppression of NLRP3 inflammasome activation. L6H21 may be used as an alternative strategy for ALD prevention/treatment.

Background Laparoscopic proximal gastrectomy (LPG) with double-tract reconstruction (DTR) is performed as a function-preserving surgery for patients with adenocarcinoma of esophagogastric junction. However, whether LPG with DTR has postoperative advantages over laparoscopic total gastrectomy (LTG) is debatable. To evaluate benefits of LPG with DTR, we compared short-term surgical outcomes between LPG with DTR and LTG for adenocarcinoma of esophagogastric junction (AEG). Methods Twelve patients who underwent LPG with DTR for AEG between February 2016 and August 2017 were included. Twenty-four patients who underwent LTG in the same period were matched to LPG with DTR cases for demographics, comorbidities, tumor characteristics, and tumor node metastasis stage. Short-term surgical outcomes were compared between the two groups. Results Demographics of the LPG with DTR group and LTG group were comparable. The number of harvested lymph nodes in the LPG with DTR group was less than that in the LTG group, and the amount of estimated blood loss, the operative time, the days of gas-passing, start of diet, postoperative hospital stay were not significantly different between the groups. Furthermore, the postoperative reflux symptom in the LPG with DTR group was not significantly different with that in the LTG group. However, the increasing percentages of the serum albumin, total protein, and hemoglobin levels in the LPG with DTR group were significantly higher than those in the LTG group. Conclusions This study reveals that LPG with DTR may be a valuable procedure for the treatment of AEG because it has the advantages over LTG in terms of postoperative serum albumin, total protein, and hemoglobin.

Background and aims Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic Lactobacillus rhamnosus GG (LGG) on hepatic BA synthesis, liver injury, and fibrosis in bile duct ligation (BDL) and multidrug resistance protein 2 knockout (Mdr2-/- ) mice. Approach and results Global and intestine-specific farnesoid X receptor (FXR) inhibitors were used to dissect the role of FXR. LGG treatment significantly attenuated liver inflammation, injury, and fibrosis with a significant reduction of hepatic BAs in BDL mice. Hepatic concentration of taurine-β-muricholic acid (T-βMCA), an FXR antagonist, was markedly increased in BDL mice and reduced in LGG-treated mice, while chenodeoxycholic acid, an FXR agonist, was decreased in BDL mice and normalized in LGG-treated mice. LGG treatment significantly increased the expression of serum and ileum fibroblast growth factor 15 (FGF-15) and subsequently reduced hepatic cholesterol 7α-hydroxylase and BA synthesis in BDL and Mdr2-/- mice. At the molecular level, these changes were reversed by global and intestine-specific FXR inhibitors in BDL mice. In addition, LGG treatment altered gut microbiota, which was associated with increased BA deconjugation and increased fecal and urine BA excretion in both BDL and Mdr2-/- mice. In vitro studies showed that LGG suppressed the inhibitory effect of T-βMCA on FXR and FGF-19 expression in Caco-2 cells. Conclusion LGG supplementation decreases hepatic BA by increasing intestinal FXR-FGF-15 signaling pathway-mediated suppression of BA de novo synthesis and enhances BA excretion, which prevents excessive BA-induced liver injury and fibrosis in mice.

Accelerating the carrier transfer and increasing the effective reaction site on the surface of photocatalyst are important measures to improve the hydrogen production of composite photocatalyst. Herein, through simultaneous carbonization and phosphorization strategies, a Ni-based metal-organic frameworks (MOFs) derived method is presented to prepare a promising cost-effective Ni–P@C cocatalyst and couple with S-vacancy ZnIn2S4 (Vs-ZIS) for boosting photocatalytic activity. In this system, abundant S vacancies are induced to the surface of ZnIn2S4 ultrathin sheets (4 nm thickness) to capture photoinduced electrons, thus avoiding the recombination of carriers on the surface of ZnIn2S4. Furthermore, Ni–P is introduced to enhance the transfer of photogenerated electrons and increase the reaction site, and the synthesized Ni–P@C cocatalyst is developed to act as electronic container where the carbon framework with graphitic sp2 hybridized structures enables strong electronic interactions at the interface layer. The Ni–P@C/Vs-ZIS-2 photocatalyst exhibits a robust H2 evolution rate of 11,064 μmol g−1 h−1, higher than Vs-ZIS (1542 μmol g−1 h−1) and ZIS (398 μmol g−1 h−1), and the apparent quantum efficiency of Ni–P@C/Vs-ZIS-2 is 12.4%. This study uncovers the role of surface S-vacancy of the ultrathin two-dimensional catalyst ZnIn2S4 coupling with Ni–P@C cocatalyst in affecting electron transfer and reaction site, opening new opportunities for achieving efficient hydrogen production.

Three new species of Luzonacera Li & Li, 2017 are described: L.francescoballarini Li & Li, sp. n. (♂♀), L.lattuensis Li & Li, sp. n. (♂♀) and L.peterjaegeri Li & Li, sp. n. (♂♀). Prior to this study, the genus was known by two species, both from Luzon Island, Philippines. So far, the genus and all five species are endemic to Luzon Island and can be found in dry or humid caves in a dark environment.

High fructose feeding changes fibroblast growth factor 21 (FGF21) regulation. Lactobacillus rhamnosus GG (LGG) supplementation reduces fructose-induced non-alcoholic fatty liver disease (NAFLD). The aim of this study was to determine the role of FGF21 and underlying mechanisms in the protective effects of LGG.FGF21 knockout (KO) mice and C57BL/6 wild type (WT) mice were fed 30% fructose for 12 weeks. LGG was administered to the mice in the last 4 weeks during fructose feeding. FGF21-adiponectin (ADPN)-mediated hepatic lipogenesis and inflammation were investigated.FGF21 expression was robustly increased after 5-weeks of feeding and significantly decreased after 12-weeks of feeding in fructose-induced NAFLD mice. LGG administration reversed the depressed FGF21 expression, increased adipose production of ADPN, and reduced hepatic fat accumulation and inflammation in the WT mice but not in the KO mice. Hepatic nuclear carbohydrate responsive-element binding protein (ChREBP) was increased by fructose and reduced by LGG, resulting in a reduction in the expression of lipogenic genes. The methylated form of protein phosphatase 2A (PP2A) C, which dephosphorylates and activates ChREBP, was upregulated by fructose and normalized by LGG. Leucine carboxyl methyltransferase-1, which methylates PP2AC, was also increased by fructose and decreased by LGG. However, those beneficial effects of LGG were blunted in the KO mice. Hepatic dihydrosphingosine-1-phosphate, which inhibits PP2A, was markedly increased by LGG in the WT mice but attenuated in the KO mice. LGG decreased adipose hypertrophy and increased serum levels of ADPN, which regulates sphingosine metabolism. This beneficial effect was decreased in the KO mice.LGG administration increases hepatic FGF21 expression and serum ADPN concentration, resulting in a reduced ChREBP activation through dihydrosphingosine-1-phosphate-mediated PP2A deactivation, and subsequently reversed fructose-induced NAFLD. Thus, our data suggest that FGF21 is required for the beneficial effects of LGG in reversal of fructose-induced NAFLD.

Three new species of the genus Flexicrurum Tong & Li, 2007, from Hainan Island, China are described: F.wuzhishanensesp. nov. (♂♀), F.yangjiaosp. nov. (♂♀), and F.qishisp. nov. (♂♀). A key to males of species of Flexicrurum is provided. Additionally, the female of F.minutum Tong & Li, 2007, is described for the first time. To date, the genus is endemic to Hainan Island, China. Types are deposited in the Institute of Zoology, Chinese Academy of Sciences (IZCAS) in Beijing.

Enhanced light absorption, improved separation of photoelectrons and holes, and controllable electron transfer paths are important ways to improve photocatalyst performance. In this work, a convenient but more efficient method is adopted to prepare composite photocatalysts integrating narrow gap semiconductors and zeolitic imidazolate frameworks (ZIFs). We chose ZIF-67, a typical ZIF, as the model and integrate it with CdS to self-assemble into highly crystalline ZIF-67@CdS composites. Extensive characterization methods (e.g., XRD, FE-SEM, UV–vis DRS, Raman, XPS, HRTEM, TEM, M–S, EIS and FT-IR) were applied to understand the correlations between performance and interface structure and morphology of the composite catalysts. Results demonstrate that the performances of the composite catalysts were greatly improved. ZIF2@CdS100 with optimized particle size (200 nm), limited shell thickness (less than 100 nm) and the shape of sugar gourd strings with Z-scheme interface structures was the best. Its H2 evolution rate and degradation rate constant of methylene blue (MB) under visible light irradiation were up to 6.7 and 3.1 times over those of bare CdS nanorods, respectively. Possible mechanisms of structure-morphology-performance were proposed. Optimizing the size and shape of composites can be used to regulate the morphology and interface structures of the composite catalysts to enhance their visible light photocatalytic activities.

Sixteen new Althepus species of the spider family Ochyroceratidae are reported from Southeast Asia: A. bamensis Li et Li sp. nov., A. changmao Li et Li sp. nov., A. dongnaiensis Li et Li sp. nov., A. guan Li et Li sp. nov., A. maechamensis Li et Li sp. nov., A. menglaensis Li et Li sp. nov., A. naphongensis Li et Li sp. nov., A. natmataungensis Li et Li sp. nov. (male only), A. phadaengensis Li et Li sp. nov., A. shanhu Li et Li sp. nov., A. suayaiensis Li et Li sp. nov. (male only), A. tadetuensis Li et Li sp. nov., A. tanhuang Li et Li sp. nov., A. thanlaensis Li et Li sp. nov., A. tharnlodensis Li et Li sp. nov. (female only), and A. viengkeoensis Li et Li sp. nov.

Four new species of the spider genus Leclercera Deeleman-Reinhold, 1995 from the spider family Ochyroceratidae Fage, 1912 are described from Nepal: L. nagarjunensis Li et Li sp. nov., L. niuqu Li et Li sp. nov. (male only), L. sidai Li et Li sp. nov. and L. zhaoi Li et Li sp. nov. Leclercera mulcatus (Brignoli, 1973) comb.n. is transferred from the genus Psiloderces Simon, 1892. All new species were collected in leaf litter of moist forests, often close to the streams or lakes, which suggest an ecological preference for moist environments. A taxonomic identification key for male Leclercera is provided. Types of all new species are deposited in the Institute of Zoology, Chinese Academy of Sciences (IZCAS-Ar 34327–34339) in Beijing, China.

The ecological health of aquaculture water is threatened by wasted fish feed and herbicides. In order to study the effect of prometryn and fish feed on Microcystis aeruginosa growth based on Monod and Logistic functions, four different concentrations of prometryn (0, 50, 100 and 200 μg L−1) and two different dosages of fish feed (0.075 g, 0.15 g; d

Complete surgical resection remains the predominant treatment modality for primary gastrointestinal stromal tumors (GISTs). No therapeutic consensus exists for 2-5 cm gastric GISTs. We compared the efficacy, safety, and prognosis of laparoscopic and endoscopic surgeries in the treatment of relatively small (2-5 cm) intraluminal gastric GISTs.We collected 101 patients with relatively small intraluminal gastric GISTs who had integrated clinicopathological data and underwent laparoscopic or endoscopic resection (laparoscopic group n = 66; endoscopic group n = 35). Clinicopathological characteristics, perioperative data, and long-term oncological outcomes were retrospectively analyzed. Comparative analysis of clinicopathological data in the two groups was performed by using a chi-square test, Fisher's exact test, and Student's t-test. Recurrence-free survival (RFS) was analyzed by the log-rank test.All clinicopathological characteristics had no significant difference between the two groups. Patients in the endoscopic group had shorter operation time (P 0.001), postoperative hospital stay (P 0.001), time to a liquid diet (P 0.01), and time to a semi-liquid diet (P 0.01), and lower hospital charges (P 0.001), compared to those in the laparoscopic group. Four patients (6.1%) in the laparoscopic group and one patient (2.9%) in the endoscopic group had perioperative complications, but with no significant difference. Recurrence occurred in 6 patients (9.1%) and 2 patients (5.7%) in the laparoscopic and endoscopic groups, respectively. There was no significant difference in RFS between the two groups.Endoscopic resection is a feasible and safe treatment modality for patients with relatively small (2-5 cm) intraluminal gastric GISTs. Due to faster recovery and lower cost, endoscopic resection is more suitable for elderly and weak patients, or patients with a poor financial situation.

Sea-level change has been viewed as a primary driver in the formation of biodiversity. Early studies confirmed that Plio-Pleistocene sea-level changes led to the isolation and subsequent genetic differentiation of Southeast (SE) Asian organisms over short geological timescales. However, long-time consequences of sea-level fluctuations remain unclear. Herein, we analyze the evolutionary history of Althepus (spiders) whose distribution encompasses Indo-Burma and the Sunda shelf islands to understand how sea-level changes over shallow and deep timescales effected their history. Our integrative analyses, including phylogeny, divergence times, ancestral area reconstruction and diversification dynamics, reveal an intricate pattern of diversification, probably triggered by sea-level fluctuations during the Paleocene-Eocene and Plio-Pleistocene. The timing of one early divergence between the Indo-Burmese and Sundaic species coincides with late Paleocene and early Eocene high global sea levels, which induced the formation of inland seaways in the Thai-Malay Peninsula. Subsequent lowered sea levels could have provided a land bridge for its dispersal colonization across the Isthmus of Kra. Analyses suggest that Plio-Pleistocene sea-level rises contributed to recent divergence of many species. Thus, our findings cannot reject the hypothesis that sea-level changes during the Paleocene-Eocene and Plio-Pleistocene played a major role in generating biodiversity in SE Asia; sea-level changes can act as "species pumps".

Autophagy serves as a protective mechanism to degrade damaged organelles and proteins. Acute alcohol exposure is known to activate the hepatic autophagy response, whereas chronic alcohol exposure slows autophagosome formation along with an elevation of gut-derived endotoxin. In the current study, we examined whether lipopolysaccharide (LPS) administration decreased autophagic response in the liver of mice treated by short-term alcohol and whether activation of autophagy by rapamycin attenuates EtOH-LPS-induced liver steatosis and injury. We demonstrated that ten-day alcohol feeding primed the liver to LPS-induced lipid accumulation and liver injury with significantly increased hepatic steatosis and serum AST level as well as hepatic cellular NF-κB activation. LPS increased alcohol-mediated reactive oxygen species (ROS) formation while reducing autophagy activation. These deleterious effects were attenuated by rapamycin administration in mice. The protective effects of rapamycin are associated with decreased cellular MD2/TLR4 expression and interaction in Raw264.7 cells. Taken together, our results demonstrated that enhanced gut-derived LPS decreases the hepatic autophagosome numbers in response to alcohol exposure, and activation of autophagy by rapamycin protects from EtOH-LPS-induced liver injury, probably through reduced macrophage expression and interaction of TLR4/MD2 signaling complex.

Trefoil Factor 1 (TFF1, also named pS2), which serves as the gastrointestinal mucosal protector, is known as gastric-specific tumor suppressor gene. However, the genetic variants of TFF1 are still not well studied. In our study, we aim to explore the effects of tagging single nucleotide polymorphisms (tagSNPs) of TFF1 on risk and prognosis of gastric cancer. Seven tagSNPs of TFF1 gene were first analyzed in the discovery set, which was consisted of 753 cases and 950 cancer-free controls. Then, the validation set (940 cases and 1,042 controls) was used for further evaluation. Moreover, we also tested the relation between these tagSNPs and prognosis of gastric cancer (GC). A series of experiments were performed to investigate the underlying mechanisms. We found that rs3761376 AA in the promoter region of TFF1, could reduce the expression of TFF1 by affecting the binding affinity of estrogen receptor 1 (ESR1, ERα), and thereby increased the risk of GC (1.29, 1.08-1.53). Moreover, the rs3761376 AA genotype was also found associated with worse prognosis among patients receiving 5-FU based chemotherapy after surgery (1.71, 1.18-2.48). Further functional assays demonstrated that TFF1 could increase the chemosensitivity of 5-FU by modulating NF-κB targeted genes. These results identified the effect of rs3761376 on TFF1 expression, which accounted for the correlation with susceptibility and prognosis of GC; and this genetic variant may be a potential biomarker to predict the risk and survival of GC.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of digestive tract. In the past, tissue biopsy was the main method for the diagnosis of GISTs. Although, circulating tumor DNA (ctDNA) detection by next-generation sequencing (NGS) may be a feasible and replaceable method for diagnosis of GISTs. We retrospectively analyzed the data for ctDNA and tissue DNA detection from 32 advanced GIST patients. We found that NGS obviously increased the positive rate of ctDNA detection. ctDNA detection identified rare mutations that were not detected in tissue DNA detection. Tumor size and Ki-67 were significant influencing factors of the positive rate of ctDNA detection and concordance between ctDNA and tissue DNA detection. In all patients, the concordance rate between ctDNA and tissue DNA detection was 71.9%, with moderate concordance, but the concordance was strong for patients with tumor size > 10 cm or Ki-67 > 5%. Tumor size, mitotic figure, Ki-67, and ctDNA mutation type were the significant influencing factors of prognosis, but only tumor size and ctDNA mutation type, were the independent prognostic factors for advanced GIST patients. We confirmed that ctDNA detection by NGS is a feasible and promising method for the diagnosis and prognosis of advanced GIST patients. Mol Cancer Ther; 17(1); 290–6. ©2017 AACR.

Reduced graphene oxide/poly(3,4-ethylene-dioxythiophene):poly(4-styrenesulfonate) (r-GO/PEDOT:PSS) composite films have been prepared by in situ reducing graphene oxide (GO)/PEDOT:PSS films prepared via a simple wet-chemical route. The as-prepared films have been characterized by X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and field emission scanning electron microscopy (FESEM). The in-plane electrical conductivity and Seebeck coefficient of the films have been measured at room temperature, and a maximum power factor is ∼32.6 μW/m K 2 for a 3 wt% GO/PEDOT:PSS film after reduction, which is about 1.5 times as high as that of a neat PEDOT:PSS film prepared by the same method.

We measure the effective flexure width of a pair of microelectromechanical systems (MEMSs) by measuring their change in comb drive capacitance upon deflection from applied voltage. This effective width is the value that a corresponding model must have in order to match the performance of the true device. Due to process variations, small changes in width from layout have been shown to increase stiffness by as much as 100%. Existing measurement methods can be costly, have unknown accuracy, are not amenable to industrial-scale batch testing, depend on the measurements of additional quantities, and so on. Our electrical probing method appears to address many of these issues. Our method requires an actuating voltage and capacitance sensing of a pair of MEMS that only differ in layout flexure width. We test our method using a low-cost capacitance meter and compare our results against a high-cost scanning electron microscope technique. We achieve nanometer scale uncertainty.

To investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.A cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.Patients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(RThe imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.