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SUMMARYThe chemical reaction networks (CRNs), which led to the transition on early Earth from geochemistry to biochemistry remain unknown. We show that under mild hydrothermal circumstances, a thermodynamic chemical reaction network including sulfite/sulfate coupled with anaerobic ammonium oxidation (Sammox), might have driven prebiotic peptides synthesis. Peptides comprise 14 proteinogenic amino acids, endowed Sammox-driven CRNs with autocatalysis. The peptides exhibit both forward and reverse catalysis, with the opposite catalytic impact in sulfite- and sulfate-fueled Sammox-driven CRNs, respectively, at both a variable temperature range and a fixed temperature, resulting in seesaw-like catalytic properties. The ratio of sulfite to sulfate switches the catalytic orientation of peptides, resulting in Sammox-driven CRNs that has both anabolic and catabolic reactions at all times. Furthermore, peptides produced from sulfite-fueled Sammox-driven CRNs could catalyze both sulfite-fueled Sammox and Anammox (nitrite reduction coupled with anaerobic ammonium oxidation) reactions. We propose that Sammox-driven CRNs were critical in the creation of life and that Anammox microorganisms that have both Sammox functions are direct descendants of Sammox-driven CRNs.

The level of autophagy in CD11c

We report the draft genome sequence of Thermomonas sp. strain XSG, isolated from a marine sediment. The genome is 3,047,478 bp long with a GC content of 68.5%., We report the draft genome sequence of Thermomonas sp. strain XSG, isolated from a marine sediment. The genome is 3,047,478 bp long with a GC content of 68.5%. Strain XSG was found to be closely related to strain NBRC 101115 of Thermomonas koreensis.

The antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in Wastewater treatment plants (WWTPs) have attracted increasing attention. In this study, the abundance of ARB and resistance genes tet32 and defA1 were investigated using high-throughput sequencing and high-throughput qPCR in water samples collected from the inlet of the biological treatment pool and outlet of Beilun Yandong WWTP in Ningbo, China. The result shows there was a high level of ARGs in the water of both the inlets and outlets in 2017 and 2018, whereas no ARGs were detected after adding a new baffled bioreactor (BBR) water treatment process in 2019. The BBR process uses Bacillus subtilis, B. thuringiensis, B. megaterium, B. licheniformis and B. amyloliquefaciens to effectively eliminate the ARGs in wastewater. Notably, this process did not significantly change the bacterial community structure of outlet water samples. The findings demonstrate an effective new method for removing ARGs from sewage.

The genus Bradyrhizobium is considered to be widespread and abundant group of symbiotic bacteria in many plant-soil ecosystems. However, the ecological versatility of this phylogenetic group remains highly understudied in man-made ecosystems, mainly due to the lack of pure cultures and genomic data. To further expand our understanding of this genus for human health, we analyzed the high quality draft genome of Bradyrhizobium strain BL, isolated from a municipal wastewater treatment plant in Ningbo, China. The Bradyrhizobium sp. BL draft genome has a total size of 7,718,431 bp with an overall G + C content of 46.43%. From a total of 7236 predicted sequences, 7176 and 60 are protein and RNA coding sequences, respectively. Moreover, 63.51% of the predicted genes were assigned into to Clusters of Orthologous Groups (COG) functional categories. The Bradyrhizobium sp. BL genome contains various defense mechanisms against antibiotics that up to predicted 60 antibiotic resistance coding genes. The Bradyrhizobium sp. BL genome contains 237 termed virulence factors coding genes which show its potential pathogenicity. This study provides important insights into the genomic diversity of the genus Bradyrhizobium and provides a foundation for future comparative genomic studies that will generate a better understanding of the antibiotic resistance process.

Objective To study the characteristics of esophageal motility in the patients with different symptoms of nonerosive reflux disease (non-erosive reflux disease, NERD). Methods Eighty-six patients with NERD who visited the Department of Gastroenterology in our hospital from August 2012 to December 2014 were selected. They were all evaluated with upper gastrointestinal endoscopy and high resolution esophageal manometry. Those who had neither definite esophageal mucosal erosion nor Barrett's esophagus at endoscopy were diagnosed as NERD. According to the presence or absence of typical acid reflux and/or heartburn symptoms, patients with NERD were divided into two groups: the typical symptom group (47 cases), and the atypical symptom group (39 cases). High resolution measurement of esophageal pressure was used to evaluate the differences in esophageal dynamic characteristics between patients with different symptoms of NERD. The final results were analyzed with t test and chi-square test. Results Compared with atypical symptom group, both the resting pressure (20.68±1.64mmHg vs 15.79±1.21mmHg respectively, P0.05). Conclusion There is a difference in esophageal motility characteristics between the patients with typical and atypical symptoms of NERD, and the main differences are changes in the resting pressure and residual pressure of LES. DOI: 10.11855/j.issn.0577-7402.2015.12.12

Objective To study the clinical efficacy of digital music gastric electrical pacing for refractory functional dyspepsia concomitant with non-erosive reflux disease, and its effects on mental health and life-quality of the patients. Methods According to the Rome Ⅲ criteria and Montreal consensus in diagnosis of gastroesophageal reflux disease, 50 patients with concomitant refractory functional dyspepsia and non-erosive reflux disease were recruited. The clinical efficacy of digital music gastric electrical pacing were evaluated using the score of clinical symptoms before treatment and 15 days after treatment, and the mental health and life-quality of patients were assessed using symptom checklist 90. Results Main symptoms, including upper abdominal pain, abdominal fullness, early satiety, belching, hiccup, nausea, heartburn, acid reflux (daytime), nocturnal acid reflux, loss of appetite and sleep, were significantly improved 15 days after treatment compared with those of pre-treatment, and there were statistically significant differences (all P

Objective To explore the potential role of HCN2-GLT-1 [hyperpolarization-activated cyclic nucleotide-gated (HCN)-2 channel and astrocytic glutamate transporter 1 (GLT-1)] in co-mediating visceral hyperalgesia at the spinal cord level following exposure to PTSD (posttraumatic stress disorder)-like stress in rats. Methods Adult female SD rats were randomly divided into normal control group (n=14), PTSD group (n=15) and PTSD+CTX group [pretreated with ceftriaxone (CTX), n=15]. The animal model of PTSD was reproduced by using single-prolonged stress (SPS) combined with electric shock. The alteration of visceral sensitivity was evaluated by measuring the viscero-motor response (VMR) to graded colorectal distension (CRD) 7 days after PTSD. The transcription of the gene encoding the GLT-1 was selectively induced by CTX to up-regulate the GLT-1 expression. The expression of spinal HCN2 and the effect of CTX on it were evaluated by immunofluorescence. Results HCN2 expression increased significantly in the spinal cord within 7 days after the exposure to PTSD as compared with that of control group (78.05±6.49 vs 121.12±4.85, P

Objective To investigate the role of anandamide(ANA)-mediated cannabinoid receptor 1(CB1) on the acquisition of visceral hypersensitivity in rats, and explore its underlying mechanism. Methods The visceral hypersensitivity non-noxious/noxious colorectal distension (NNCRD/NCRD) model of rat was reproduced by ovalbumin (OVA) sensitization combined with NNCRD/NCRD. Fifty-four rats were randomly divided into control group (n=7), saline+CRD group (n=7), OVA+CRD+dimethyl sulfoxide (DMSO) group (n=8), OVA+CRD+different concentrations of ANA (0.5, 5.0, 10.0mg/kg) groups (8 each), and OVA+CRD+ANA+AM251 group (n=8). The expression and quantitative assessment of CB1 were monitored by immunoflurorescence and laser scanning confocal analysis. The visceral sensitivity was evaluated by the area under curve (AUC) of myoelectrical activity of abdominal wall muscle. Results By NCRD at 80mmHg, the density of CB1 immunofluorescence intensity was significantly higher in L4–L6 of the spinal cord of the rats in saline+CRD group compared with that in control group (P < 0.05). The expression of CB1 was higher in OVA+CRD+DMSO group than in saline+CRD group (P < 0.05). By NNCRD at 20 mmHg, no statistical difference was found in the AUC of visceromotor reflex (VMR) among various groups (P>0.05). By NCRD at 80mmHg, the VMR-AUC increased obviously in OVA+CRD+DMSO group as compared with that of saline+CRD group, but it decreased significantly in OVA+CRD+high concentration ANA group (P < 0.05). When AM251 was intravenously given, VMR-AUC increased significantly in OVA+CRD+ANA+AM251 group compared with that in OVA+CRD+different concentrations of ANA groups (P < 0.05). Conclusions Intravenous administration of ANA may mitigate the visceral nociception induced by basic OVAsensitization combined with NCRD stimulation in CB1-mediated manner. It indicated that anandamide-mediated CB1 cannabinoid receptor may regulate the development and maintenance of visceral hypersensitivity.

In an attempt to develop potent and selective antitumor agents, a series of 6- and 2-(1-substituted-thio-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-diones were designed and synthesized. The cytotoxicities of these compounds were evaluated in vitro against BEL-7402, HT-29 and SPC-A1 cell lines. The pharmacological results showed that most of the prepared compounds displayed the excellent selective cytotoxicity toward HT-29 cells. From the structure-activity relationships we may conclude that the introduction of a thioether functional group at the 1'-position in the side chain of shikonin is associated with an increase in cytotoxicity.

Sixteen novel 6- and 2-(1-acylsulfanylalkyl)-5,8-dimethoxy-1,4-naphthoquinones were designed and synthesized. Their cytotoxicities were evaluated in vitro against BEL-7402, HT-29 and SPC-A1 cell lines. The pharmacological results showed that most of the prepared compounds displayed the excellent selectivity for HT-29 cell line. Compound 16b exhibited the most potent antitumor activity among the tested compounds.

The calcium-sensing receptor (CaSR), a G protein coupled receptor, is involved in a number of physiological and pathological processes. Embryonic stem cells (ESCs) have a potential role to differentiate into all types of cells. Whether CaSR is functionally expressed in ESCs is unclear. In this study, the expression and distribution of CaSR in 129 mouse ES-D3 cell lines were detected by Western blotting and immunofluorescence; and the intracellular calcium concentration ([Ca(2+)]i) was measured using Laser Confocal Scanning Microscopy. Mouse embryonic stem cells (mESCs) were cultured to embryoid bodies (EBs) and the differentiation of EBs into cardiomyocytes was induced by icariin (ICA). The cardiac specific proteins, a-Actinin and cardiac troponin-I (cTnI), were analyzed by immunofluorescence, and the differentiation rate was analyzed by flow cytometry. The expression of cardiac-specific transcription factors, Nkx2.5 and GATA-4, was detected by Western blotting. We found that the CaSR protein exists in both mESCs and mESC-derived cardiomyocytes (mESC-CMs). Increasing extracellular calcium or neomycin (an agonist of CaSR) increased [Ca(2+)]i and the differentiation rate. These effects were abolished by inhibition of CaSR, phospholipase C, IP3 receptor and Ca(2+) ATPase, or by depletion of the sarcoplasmic reticulum Ca(2+) store, respectively. Activation of CaSR up-regulated protein expression of Nkx2.5 and GATA4 in EBs at an early stage of ICA-induced differentiation. In conclusion, CaSR is functionally expressed in mESCs, and activation of CaSR is involved in the differentiation of mESCs into cardiomyocytes by facilitating the expression of NKx2.5 and GATA-4.

In an attempt to develop potent and selective antitumor agents, a series of 6- and 2-(1-substituted-thio-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-diones were designed and synthesized. The cytotoxicities of these compounds were evaluated in vitro against BEL-7402, HT-29 and SPC-A1 cell lines. The pharmacological results showed that most of the prepared compounds displayed the excellent selective cytotoxicity toward HT-29 cells. From the structure-activity relationships we may conclude that the introduction of a thioether functional group at the 1'-position in the side chain of shikonin is associated with an increase in cytotoxicity.

Background Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is a novel cancer-related gene. While recent studies have reported that the LAPTM4B polymorphism increased the susceptibility of several cancers, the results remain inconclusive. Therefore, we performed a meta-analysis to systematically summarize the possible association. Results The meta-analysis was conducted based on 17 studies in Chinese populations, including 4160 cases and 4148 controls. The relevant studies were searched through electronic databases updated in November 2013. The strength of association between the LAPTM4B polymorphism and susceptibility to multiple cancers was assessed by odds ratio (OR) and 95% confidence interval (95% CI). The meta-analysis results suggested that the LAPTM4B polymorphism was significantly associated with overall susceptibility to multiple cancers in all genetic models (*2 vs. *1, OR = 1.53, 95% CI = 1.37–1.70; *2/2 vs. *1/1, OR = 2.18, 95% CI = 1.72–2.75; *2/1 vs.*1/1, OR = 1.62, 95% CI = 1.41–1.86; *2/1 + *2/2 vs. *1/1, OR = 1.70, 95% CI = 1.47–1.97; *2/2 vs. *2/1 + *1/1, OR = 1.76, 95% CI = 1.50–2.05). Further subgroup analysis revealed a significant association between the LAPTM4B polymorphism and cancer susceptibility in the subgroups stratified by control source, cancer type, histopathologic differentiation, and TNM stage. Conclusions This meta-analysis indicated that the LAPTM4B *2 allele was associated with increasing risk of multiple cancers, tumor initiation and development.