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Recent studies show that liver X receptor (LXR) agonists exert significant antitumor effects in a variety of tumor cell lines including hepatocellular carcinoma (HCC). But the molecular mechanisms underlying LXR antitumor activity are not fully understood. In this study we investigated the effect of LXR agonist T0901317 (T317) on HCC development and its relationship with RalA binding protein 1 (RALBP1)-associated EPS domain containing 2 (REPS2)/epidermal growth factor receptor (EGFR) signaling axis. We showed that T317 (0.1-0.5 μM) dose-dependently increased REPS2 expression in normal hepatocytes (BNLCL.2 and LO2) and HCC cells (HepG2 and Huh-7). Using promoter activity assay and chromatin immunoprecipitation (CHIP) assay we demonstrated that T317 enhanced REPS2 expression at the transcriptional level via promoting the binding of LXR protein to the LXR-response element (LXRE) in the REPS2 promoter region. We showed that the inhibitory effect of T317 on the proliferation and migration of HCC cells was closely related to REPS2. Moreover, we revealed that T317 (400 nM) increased expression of REPS2 in HepG2 cells, thus inhibiting epidermal growth factor (EGF)-mediated endocytosis of EGFR as well as the downstream activation of AKT/NF-κB, p38MAPK, and ERK1/2 signaling pathways. Clinical data analysis revealed that REPS2 expression levels were inversely correlated with the development of HCC and reduced REPS2 expression associated with poor prognosis, suggesting that REPS2 might be involved in the development of HCC. In conclusion, this study provides new insights into the potential mechanisms of LXR agonist-inhibited HCC.

Enantiopure vicinal diols are important building blocks used in the synthesis of fine chemicals and pharmaceutical compounds. Diol dehydrogenase (DDH) mediated stereoselective oxidation of racemic vicinal is an efficient way to prepare enantiopure vicinal diols. In this study, four new bacterial DDHs (AnDDH from Anoxybacillus sp. P3H1B, HcDDH from Hazenella coriacea, GzDDH from Geobacillus zalihae and LwDDH from Leptotrichia wadei) were mined from the GenBank database and expressed in E. coli T7. The four DDHs were purified and biochemically characterized for oxidation activity toward (R)-1-phenyl-1,2-ethanediol, with the optimal reaction condition of pH9.0 (AnDDH), 10.0 (HcDDH) and 11.0 (GzDDH and LwDDH) and the temperatures at 40°C (AnDDH), 50°C (HcDDH) and 60°C (GzDDH and LwDDH), respectively. The four enzymes were stable at the pH from 7.0 to 9.0 and below 40°C. Kinetic parameters of four DDHs showed that the HcDDH from Hazenella coriacea had high activity toward a broad range of vicinal diols. A series of racemic vicinal diols were successfully resolved by recombinant E. coli (HcDDH-NOX) resting cells co-expression of an NADH oxidase (NOX), affording (S)-diols and (1S, 2S)-trans-diols in ≥99% ee. The synthetic potential of HcDDH was proved by E. coli (HcDDH-NOX) via kinetic resolution of racemic trans-1,2-indandiol on a 100 ml scale reaction, (S, S)- trans-1,2-indandiol was prepared in 46.7% yield and >99% ee. In addition, asymmetric reduction of four α-hydroxy ketones (10-300 mmol•L-1) by E. coli (HcDDH-GDH) resting cells resulted in >99% ee and 69-98% yields of (R)-vicinal diols. The current research expands the toolbox of DDHs to synthesize chiral vicinal diols and demonstrated that the mined HcDDH is a potential enzyme in the synthesis of a broad range of chiral vicinal diols.

Magnetic hyperthermia therapy (MHT) is a highly promising therapeutic modality, mainly applied to deal with cancers and malignant tumors. To gain efficient magnetic hyperthermia therapy, magnetic nanoparticles (Fe3O4) with improved heating efficiency are necessary. In this work, magnetite nanoparticles anchored on graphene oxide (GO/Fe3O4) have been synthesized via chemical precipitation method, and anti-cancer drug have been introduced to form GO/Fe3O4 loaded with doxorubicin hydrochloride (GO/Fe3O4-DXR) composite nanoparticles. X-ray diffraction analysis has been carried out to characterized the crystal structure of GO/Fe3O4 nanoparticles with different mass ratios. Fourier transform infrared spectroscopy (FTIR) confirmed the presence of doxorubicin hydrochloride (DRX) in GO/Fe3O4-DXR, while the structure of GO/Fe3O4 nanoparticles with different mass ratios are studied by Transmission electron microscopy (TEM). And the heating efficacy of GO/Fe3O4-DXR nanoparticles were. investigated suitable for magnetic hyperthermia therapy under safe alternating magnetic fields (80 kHz, 30 kA m−1). Besides, the DXR loading and release data of GO/Fe3O4-DXR have been tested via ultraviolet–visible spectroscopy (UVVIS) in presence of the AC field. The above characteristics conform to temperature requirements of magnetic materials on medical applications, which infers that GO/Fe3O4 -DXR particles show promising talent as targeted drug carriers and thermoseeds in MHT.

Silicon, to be a potential anode material of LIBs, possesses a pretty high lithium storage capacity. However, the structural integrity can be destructed by its huge volume expansion through cycles, which results in a large capacity attenuation. Meanwhile, the poor electrochemical performance of silicon-based anodes can be attributed to its poor conductance which reduces the reaction kinetics. According to the above challenges, core-shell structured silicon-nickel nanoparticles have been dispersed on 3D intertwined carbon nanotube networks (Si@Ni-NP/CNTs) via nitric acid pre-treatment and amino functionalization. The nickel-plated shell outside silicon core nanoparticles (Si@Ni-NP) can play a certain supporting role to prevent the volume expansion of silicon, which finally brings down the degree of powdering. Especially, the 3D framework composed of intertwined carbon nanotubes can efficiently provide not only an ample buffer space during intercalation/deintercalation but also a more stable conductive network to increase ion/electron transfer rate. Due to the above improvements in structural stability and reaction kinetics, Si@Ni-NP/CNTs reveal a reversible capacity of 1008 mAh g−1 with a 98% capacity retention over 100 cycles at a current density of 100 mA g−1. Under different current densities in rate test, the specific capacity recovery rate can reach 92%. The novel structure enables Si@Ni-NP/CNTs excellent stability under cycles and various rates, as a promising anode material of LIBs.

Lithium-sulfur batteries are considered to be an ideal high-performance rechargeable lithium battery. However, some problems have seriously hindered the practical application of lithium-sulfur batteries. A simple one-step hydrothermal method has been applied to design nitrogen-doped graphene aerogel (N-GA) with three different nitrogen sources. Subsequently, sulfur was encapsulated in N-GA by chemical deposition method to synthesize sulfur encapsulated in N-GA (N-GA/S) composites. Among them, the N-GA1/S composite with sulfur content reaching 75.5 wt% has a discharge specific capacity of 723.9 mAh g−1 after 100 cycles at 0.7 C, and the capacity retention rate is up to 87.4% while the coulombic efficiency still remains 98%. The outstanding electrochemical performance is owing to the good coating of sulfur by nitrogen-doped graphene aerogel, the improvement of the conductivity of the graphene skeleton by nitrogen doping, and the strong adsorption capacity of the doped nitrogen atom to lithium polysulfide. The graphene skeleton also helps to reduce the volume effect while charging and discharging. Furthermore, the proportion of pyridinic-N in N-GA1/S composites is higher than that in the two other composites, and it has a better adsorption capacity for lithium polysulfide.

The methyltransferase-like 3 (Mettl3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for RNA N6-methyladenosine (m6A) modification, which plays an important role in gene post-transcription modulation. Although RNA m6A is enriched in mammalian neurons, its regulatory function in nociceptive information processing remains elusive. Here, we reported that Complete Freund's Adjuvant (CFA)-induced inflammatory pain significantly decreased global m6A level and m6A writer Mettl3 in the spinal cord. Mimicking this decease by knocking down or conditionally deleting spinal Mettl3 elevated the levels of m6A in ten-eleven translocation methylcytosine dioxygenases 1 (Tet1) mRNA and TET1 protein in the spinal cord, leading to production of pain hypersensitivity. By contrast, overexpressing Mettl3 reversed a loss of m6A in Tet1 mRNA and blocked the CFA-induced increase of TET1 in the spinal cord, resulting in the attenuation of pain behavior. Furthermore, the decreased level of spinal YT521-B homology domain family protein 2 (YTHDF2), an RNA m6A reader, stabilized upregulation of spinal TET1 because of the reduction of Tet1 mRNA decay by the binding to m6A in Tet1 mRNA in the spinal cord after CFA. This study reveals a novel mechanism for downregulated spinal cord METTL3 coordinating with YTHDF2 contributes to the modulation of inflammatory pain through stabilizing upregulation of TET1 in spinal neurons.

Background and aims Endoscopic diagnosis of early esophageal squamous cell cancer (ESCC) is complicated and dependent on operators' experience. This study aimed to develop an artificial intelligence (AI) model for automatic diagnosis of early ESCC. Methods Non-magnifying and magnifying endoscopic images of normal/noncancerous lesions, early ESCC, and advanced esophageal cancer (AEC) were retrospectively obtained from Qilu Hospital of Shandong University. A total of 10,988 images from 5075 cases were chosen for training and validation. Another 2309 images from 1055 cases were collected for testing. One hundred and four real-time videos were also collected to evaluate the diagnostic performance of the AI model. The diagnostic performance of the AI model was compared with endoscopists by magnifying images and the assistant efficiency of the AI model for novices was evaluated. Results The AI diagnosis for non-magnifying images showed a per-patient accuracy, sensitivity, and specificity of 99.5%, 100%, 99.5% for white light imaging, and 97.0%, 97.2%, 96.4% for optical enhancement/iodine straining images. Regarding diagnosis for magnifying images, the per-patient accuracy, sensitivity, and specificity were 88.1%, 90.9%, and 85.0%. The diagnostic accuracy of the AI model was similar to experts (84.5%, P = 0.205) and superior to novices (68.5%, P = 0.005). The diagnostic performance of novices was significantly improved by AI assistance. When it comes to the diagnosis for real-time videos, the AI model showed acceptable performance as well. Conclusions The AI model could accurately recognize early ESCC among noncancerous mucosa and AEC. It could be a potential assistant for endoscopists, especially for novices.

Chiral β-amino alcohols are privileged scaffolds frequently found in pharmaceutically active molecules and natural products. Aminohydroxylation of olefins is one of the most powerful strategies to access chiral vicinal amino alcohols. However, the direct regio- and stereoselective aminohydroxylation of olefins to unprotected enantioenriched β-amino alcohols remains a long-standing challenge. Herein, we report that a novel one-pot four-enzyme [styrene monooxygenase (SMO)/epoxide hydrolase (EH)/alcohol dehydrogenase (ADH)/ω-transaminase (TA)] biocatalytic cascade efficiently catalyzes the direct transformation of readily available styrenyl olefins into unprotected 2-amino-2-phenyl ethanols in good yields and excellent enantioselectivity. In vitro cascade biocatalysis aminohydroxylation of styrenyl olefins was first investigated by the combined four enzymes (SMO/EH/ADH/TA) with a trace amount of NADH (0.02 mM) and pyridoxal-5′-phosphate (0.1 mM), affording both enantiomers of β-amino alcohols 5a–j in 13.9–98.7% conversions and 86–99% ee. Whole-cell-based cascade biocatalysis was achieved by using the constructed recombinant Escherichia coli pairwise combinations and single tailor-made whole-cell biocatalyst without an additional NADH cofactor; (R)- and (S)-β-amino alcohols 5a–j could be obtained in 14.6–99.7% conversions and 86–99% ee. Moreover, the preparative experiments of this new cascade biocatalysis were demonstrated by the single tailor-made whole-cell biocatalyst [E. coli (CGS-DEM) and E. coli (CGS-DEB)] with the substrates 1a–b and 1h in an aqueous-organic two-phase system, affording chiral β-amino alcohols [(R)- or (S)-5a–b, h] in good yields (50.9–64.3%) and excellent ee (>99%).

Owing to the high energy density and rich resource, Li–S batteries are now considered as a promising direction in energy storage. Nevertheless, the electrochemical properties of sulfur host materials have been limited by the large volume changes during cycles, the dissolution of polysulfides in an electrolyte, and the insulating properties of lithium polysulfides. Based on the above conclusions, a novel cathode material of graphene nanosheet@spherical ordered mesoporous carbon/sulfur nanocomposite (GNs@s-OMC/S) where s-OMC/S was wrapped by GNs has been synthesized in this article and delivers superior cycle stability. According to the tests, GNs@s-OMC/S provides a capacity of 1159 mAh g−1 at a 0.4 C discharge rate. In addition, even at a high rate of 4 C, the discharge capacity of GNs@s-OMC/S can also remain 767 mAh g−1, representing a fantastic rate performance and high specific capacity. It can be ensured that the narrow channels provided by s-OMC and the graphene entrapment with high conductivity enhance the electrochemical performance of the cathode.

Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg-1 protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in >99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78-94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L-1 ) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.

Background and aims Add-on devices have been widely used in clinical practice. The aim of this meta-analysis was to compare the adenoma detection rate between Endocuff-assisted colonoscopy (EAC) and cap-assisted colonoscopy (CAC). Methods PubMed, EMBASE, SCOPUS, and Cochrane databases were searched. Outcomes included adenoma detection rate, cecal intubation rate, cecal intubation time, and withdrawal time. Dichotomous data were pooled to obtain the odds ratio or risk ratio. Continuous data were pooled using the mean difference. Results Of the 240 articles reviewed, six randomized controlled trials were included, with a total of 1994 patients. In the meta-analysis, no statistical difference in adenoma detection rate was detected between EAC and CAC (47.0% vs 45.1%; P = 0.33). EAC significantly improved detection rate of diminutive adenomas/polyps compared with CAC (P = 0.01). Cecal intubation was achieved in 96.5% in EAC group and 97.9% in CAC group (P = 0.04). Besides, no statistical difference was found in cecal intubation time (P = 0.86), withdrawal time (P = 0.88), small adenomas/polyps (P = 0.60), or large adenomas/polyps (P = 0.95). Conclusion EAC and CAC have their respective merits. EAC significantly improve the detection of diminutive adenomas/polyps. CAC was better in cecal intubation rate.

Xinyue Zhang,1– 3,* Jinan Guo,4,5,* Parham Jabbarzadeh Kaboli,2,6 Qijie Zhao,2 Shixin Xiang,2 Jing Shen,2,6 Yueshui Zhao,2,6 Fukuan Du,2,6 Xu Wu,2,6 Mingxing Li,2,6 Huijiao Ji,2,6 Xiao Yang,2 Zhangang Xiao,2,6 Qinglian Wen1,3 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People’s Republic of China; 4The Department of Urology, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of South University of Science and Technology of China, Shenzhen Urology Minimally Invasive Engineering Center, Shenzhen, Guangdong, People’s Republic of China; 5Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, Shenzhen, Guangdong, People’s Republic of China; 6South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhangang XiaoLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, People’s Republic of ChinaEmail zhangangxiao@swmu.edu.cnQinglian WenDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of ChinaEmail wql73115@163.comObjective: The Warburg effect, also known as aerobic glycolysis, plays a dominant role in the development of gastrointestinal (GI) cancers. In this study, we analyzed the expression of key genes involved in the Warburg effect in GI cancers and investigated the effect of suppressing the Warburg effect in vitro in liver cancer cell lines.Methods: The Cancer Genome Atlas (TCGA) RNA-Seq data were used to determine gene expression levels, which were analyzed with GraphPad Prism 7.00. Genetic alterations were queried with cBioPortal. The influence of the Warburg effect on liver cancer cell viability, migration and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was determined by means of MTT, transwell and GAPDH activity assays.Results: The levels of expression of genes associated with the Warburg effect were increased in tumors. To our knowledge, this is the first report of upregulated expression of CUEDC2, HMGB2, PFKFB4, PFKP and SIX1 in liver cancer. Clinically, overexpression of these genes was associated with significantly worse overall survival of liver cancer patients. In vitro, selective inhibition of GADPH suppressed the growth and metastasis of Huh-7, Bel7404 and Hep3B hepatocellular carcinoma cell lines.Conclusion: The Warburg effect may play an important role in GI cancers, especially in liver cancer.Keywords: Warburg effect, gastrointestinal cancers, liver cancer, bioinformatics, GAPDH

Background: Serum uric acid (SUA) has been revealed to be positively associated with the body composition parameters in hemodialysis patients, but few studies have investigated that in patients on peritoneal dialysis (PD). The aim of this study was to identify the relationship between SUA and appendicular skeletal muscle mass (ASM) and the effect of their interaction on mortality in PD patients. Methods: This was a single-center retrospective cohort study. Patients who underwent multifrequency bioelectrical impedance analysis between January 1, 2013, and December 31, 2016, and had data on SUA values were enrolled. All patients were followed up until December 31, 2019. Results: In total, 802 prevalent PD patients (57.9% male), with mean age of 46.2 ± 14.2 years were enrolled. The average SUA and ASM were 6.8 ± 1.3 mg/dL and 21.2 ± 4.9 kg. According to multiple linear regression models, SUA was positively associated with relative ASM in middle-aged and older PD patients (standardized coefficients [β] 0.117; 95% confidence interval [CI] 0.027, 0.200; p = 0.010). Further sex-stratified analysis showed that the association existed only in males (β 0.161; 95% CI 0.017, 0.227; p = 0.023). Moreover, the presence of hyperuricemia was found to predict lower risk of all-cause mortality (hazard ratio [HR] 0.514, 95% CI 0.272, 0.970; p = 0.040) only in patients with lower relative ASM. And, the adjusted HR of every 1 mg/dL elevated SUA level was 0.770 (95% CI 0.609, 0.972; p = 0.028) for all-cause mortality in the lower relative ASM subgroup. Conclusions: There exists a positive association between the SUA and ASM, and the ASM significantly affected the association between SUA and all-cause PD mortality.

Helicobacter pylori (H. pylori) infections are of serious concern due to the associated risk of gastric cancer. However, many patients have poor medication and therapy compliance, which makes it difficult to eradicate their infections. This points to the need for stronger educational interventions aimed at enhancing compliance, thus increasing the potential for treatment success. As such, this study conducted a meta-analysis to clarify the effects of enhanced patient education (EPE) programs for H. pylori.We searched electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) on health education for patients infected with H. pylori from inception to June 2021. The primary outcome was the eradication rate of H. pylori, while the secondary outcomes included the incidence of individual adverse symptoms, treatment compliance, clinical symptom remission after treatment, and patient satisfaction. We used the fixed or random-effects model to pool the risk ratio (RR), with 95% confidence interval. We also conducted sensitivity and subgroup analyses.Our search returned seven relevant studies across a total of 1,433 patients. Compared with controls, EPE was significantly associated with improved H. pylori eradication rates (RR = 1.16, 95%CI: 1.04-1.29, p = 0.006) and patient compliance (RR = 1.48, 95%CI: 1.14-1.93, p = 0.003). A subgroup analysis also showed that EPE benefits were consistent across patients with different eradication programs, WeChat intervention plans, and intervention frequencies (p 0.05). However, there were no significant differences in the total adverse effects, common side effects (diarrhea, nausea, abdominal pain, taste disorder, and skin rash), or discontinuation rate (p 0.05).Patient education is inexpensive, safe, and convenient. In this context, our findings suggest that enhanced educational interventions have positive effects on both the H. pylori eradication rate and adherence among infected patients, and thus constitute promising complements to clinical treatment regimens.

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 μM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

Xiao-Xiao Yang,1,2 Chao Yang,2 Li Wang,2 Ying-Bo Zhou,2 Xiang Yuan,2 Nan Xiang,2 Yi-Ping Wang,3 Xiao-Mei Li1,2 1School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2The First Affiliated Hospital of USTC, Department of Rheumatology and Immunology, University of Science and Technology of China, Hefei, People’s Republic of China; 3Westmead Institute for Medical Research, University of Sydney, Sdyney, NSW, 2145, AustraliaCorrespondence: Xiao-Mei Li Email lixiaomei@ustc.edu.cnObjective: Although extensive research has been carried out on CD4+T cells infiltrating the labial glands in patients with primary Sjögren’s Syndrome (pSS), it is still unclear how CD4+T cells remain in the labial gland tissue and develop into tissue resident cells. The aim of this study was to investigate the molecular mechanism by which CD4+T reside in labial glandular tissue of pSS patients.Methods: Lymphocyte infiltration in labial salivary glands (LSG) of pSS patients was detected by H&E staining. Expression of sphingosine-1-phosphate receptor 1 (S1PR1) in LSG was examined by Immunohistochemistry. Immunofluorescence analyses were utilized to detect the co-expression of CD4, CD69 and S1PR1 in T cells of LSG of pSS patients. Expression of gene S1pr1 in peripheral blood CD4+T cells of healthy controls and pSS patients was detected by quantitative real-time PCR (QPCR). QPCR was used to examine the expression of gene S1pr1, Klf2, and Cd69 in the CD4+T cells that were co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33.Results: S1PR1 was expressed in the infiltrating monocytes in LSG of pSS patients, and S1PR1 was weakly or even not expressed in cytoplasm of CD4+CD69+TRM cells of LSG in patients with pSS. Expression of gene S1pr1 in peripheral blood CD4+T cells of pSS patients was about three-fifths of that of healthy controls (P < 0.05). Expression of genes S1pr1 (P < 0.001) and Klf-2 (P < 0.001) was significantly decreased, and the expression of gene Cd69 (P < 0.05) was significantly increased in peripheral blood CD4+T cells of pSS patients co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33.Conclusion: Our study suggests that the decrease of S1pr1 gene expression may provide a molecular basis for promoting the tissue retention and development of CD4+CD69+TRM cells.Keywords: primary Sjogren’s syndrome, S1PR1, CD4+TRM

Using conventional endoscope to perform endoscopic submucosal dissection (ESD) is difficult because of the one-handed operation and blind dissection caused by gravity. Poor visualization of the submucosal plane causes ESD to be associated with a high risk of bleeding and perforation. This study aimed to develop a novel ESD-assistive robot system and to evaluate its efficacy.A novel flexible auxiliary single-arm transluminal endoscopic robot (FASTER) was developed. A total of 36 artificial lesions in ex vivo porcine stomachs were removed using the FASTER-assisted ESD method (n = 18) and the conventional ESD method (n = 18). Lesions were 2 cm or 4 cm in diameter, located on the anterior and posterior walls of the antrum. Primary outcome measurements were dissection time and dissection speed.The dissection time in FASTER-assisted ESD was significantly shorter than that in conventional ESD (7 min vs 13 min, p = 0.012), mainly because of the faster dissection speed (148.6 vs 97.0 mmFASTER significantly increased the dissection speed by providing proper traction and achieving good submucosal vision. This new device is expected to facilitate ESD in clinical practice.

Objective Although extensive research has been carried out on CD4+T cells infiltrating the labial glands in patients with primary Sjögren’s Syndrome (pSS), it is still unclear how CD4+T cells remain in the labial gland tissue and develop into tissue resident cells. The aim of this study was to investigate the molecular mechanism by which CD4+T reside in labial glandular tissue of pSS patients. Methods Lymphocyte infiltration in labial salivary glands (LSG) of pSS patients was detected by H&E staining. Expression of sphingosine-1-phosphate receptor 1 (S1PR1) in LSG was examined by Immunohistochemistry. Immunofluorescence analyses were utilized to detect the co-expression of CD4, CD69 and S1PR1 in T cells of LSG of pSS patients. Expression of gene S1pr1 in peripheral blood CD4+T cells of healthy controls and pSS patients was detected by quantitative real-time PCR (QPCR). QPCR was used to examine the expression of gene S1pr1, Klf2, and Cd69 in the CD4+T cells that were co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33. Results S1PR1 was expressed in the infiltrating monocytes in LSG of pSS patients, and S1PR1 was weakly or even not expressed in cytoplasm of CD4+CD69+TRM cells of LSG in patients with pSS. Expression of gene S1pr1 in peripheral blood CD4+T cells of pSS patients was about three-fifths of that of healthy controls (P < 0.05). Expression of genes S1pr1 (P < 0.001) and Klf-2 (P < 0.001) was significantly decreased, and the expression of gene Cd69 (P < 0.05) was significantly increased in peripheral blood CD4+T cells of pSS patients co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33. Conclusion Our study suggests that the decrease of S1pr1 gene expression may provide a molecular basis for promoting the tissue retention and development of CD4+CD69+TRM cells.

Background The ITA° is the gold standard for skin tone classification. Different skin tones are often associated with different skin characteristics and issues. Different skin types are often associated with different skin characteristics and issues in China. Aims To study the population's skin color distribution and accompanying skin problems according to the ITA° classification standard. Methods A total of 1092 women aged 22-42 years were recruited in 7 cities in China. All biophysical parameter measurements (SM, CM, TWEL, pH, R2, GLOSS_DSCT, MEXA, ERYTH, ITA°; 9 indexes total) were quantified with noninvasive instruments. All volunteers provided consent before enrollment. Result The main skin color categories were light (II), very light (I), intermediate (III), and tan (IV). The results demonstrated that the characteristics of the facial skin based on the ITA° were significantly different among cities and age groups and were associated with different skin issues. Conclusions Lighter skin was associated with worse skin elasticity; intermediate skin was associated with worse skin hydration content and was most prone to being oily; and darker skin was associated with poor barrier function. Established principal component regression (PCR) indicated that pH, gloss GLOSS_DSC, MEXA, ERYTH, TEWL, and SM had significant effects on the ITA°.

Dysfunctions of gene transcription and translation in the nociceptive pathways play the critical role in development and maintenance of chronic pain. Circular RNAs (circRNAs) are emerging as new players in regulation of gene expression, but whether and how circRNAs are involved in chronic pain remain elusive. We showed here that complete Freund's adjuvant-induced chronic inflammation pain significantly increased circRNA-Filip1l (filamin A interacting protein 1-like) expression in spinal neurons of mice. Blockage of this increase attenuated complete Freund's adjuvant-induced nociceptive behaviors, and overexpression of spinal circRNA-Filip1l in naive mice mimicked the nociceptive behaviors as evidenced by decreased thermal and mechanical nociceptive threshold. Furthermore, we found that mature circRNA-Filip1l expression was negatively regulated by miRNA-1224 via binding and splicing of precursor of circRNA-Filip1l (pre-circRNA-Filip1l) in the Argonaute-2 (Ago2)-dependent manner. Increase of spinal circRNA-Filip1l expression resulted from the decrease of miRNA-1224 expression under chronic inflammation pain state. miRNA-1224 knockdown orAgo2overexpression induced nociceptive behaviors in naive mice, which was prevented by the knockdown of spinal circRNA-Filip1l. Finally, we demonstrated that a ubiquitin protein ligase E3 componentn-recognin 5 (Ubr5), validated as a target of circRNA-Filip1l, plays a pivotal role in regulation of nociception by spinal circRNA-Filip1l. These data suggest that miRNA-1224-mediated and Ago2-dependent modulation of spinal circRNA-Filip1l expression regulates nociception via targetingUbr5, revealing a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain.SIGNIFICANCE STATEMENTcircRNAs are emerging as new players in regulation of gene expression. Here, we found that the increase of circRNA-Filip1l mediated by miRNA-1224 in an Ago2-dependent way in the spinal cord is involved in regulation of nociception via targetingUbr5. Our study reveals a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain.

A novel one-pot epoxide hydrolase/alcohol dehydrogenase/transaminase cascade process for the asymmetric ring opening of racemic epoxides to enantiopure β-amino alcohols is reported. The product (S)-β-amino alcohols were obtained in 97–99% ee and 79–99% conversion from readily available racemic epoxides.

The biological effects of nanoparticles are of great importance for the in-depth understanding of safety issues in biomedical applications. Induction of autophagy is a cellular response after nanoparticle exposure. Bismuth sulfide nanoparticles (Bi2S3 NPs) are often used as a CT contrast agent because of their excellent photoelectric conversion ability. Yet there has been no previous detailed study other than a cell toxicity assessment. In this study, three types of Bi2S3 NPs with different shapes (Bi2S3 nano rods (BSNR), hollow microsphere Bi2S3 NPs (BSHS) and urchin-like hollow microsphere Bi2S3 NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi2S3 NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi2S3 NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi2S3 NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi2S3 NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi2S3 NPs, autophagy blockage may still substantially influence cell fate and thus significantly impact their biomedical applications, and that surface topography is a key factor regulating their biological response.

The use of the phenicol antibiotic florfenicol in livestock can select for the optrA gene, which also confers resistance to the critically important oxazolidinone antibiotic linezolid. However, the occurrence and dissemination of florfenicol and linezolid cross-resistance genes in anaerobic treatment systems for livestock waste are unknown. Herein, the phenotypes and genotypes (optrA, fexA, fexB, and cfr) of florfenicol and linezolid cross-resistance were investigated in 339 enterococci strains isolated from lab- and full-scale mesophilic anaerobic digestion systems treating swine waste. It was found that optrA, fexA, and fexB were frequently detected in isolated enterococci in both systems by PCR screening, whereas cfr was not detected. The most abundant gene was optrA, which was detected in 73.5% (n = 50) and 38.9% (n = 23) of enterococci isolates in the full-scale influent and effluent, respectively. Most strains carried more than two resistance genes, and the average percentage of co-occurrence of optrA/fexA was 16.6%. Based on minimum inhibitory concentrations of the enterococci strain phenotypes, 85.7%, 77.5%, and 77.5% of strains in influent were resistant to chloramphenicol, florfenicol, and linezolid, respectively, while 56.3%, 65.2%, and 13% in the effluent isolates were found, respectively, which was consistent with the genotype results. The phenotypes and genotypes of florfenicol and linezolid resistance were relative stable in the enterococci isolated from the influent and effluent in lab-scale anaerobic digestion system. The findings signify the enterococci isolates harboring the optrA gene remained in effluents of both full- and lab-scale swine waste anaerobic digestion system; hence, effective management strategies should be implemented to prevent the discharge of antibiotic resistance from the livestock waste treatment systems.

Magnons are being currently developed as qubits for quantum storage and information processing. Here, in this work, we focus on a hybrid quantum system containing two antiferromagnets, and entanglement between magnons in the antiferromagnets can be generated through strong coupling mediated by the same microwave mode. Moreover, we numerically simulate the process with feasible parameters. The influence of the system parameters, such as the magnon-photon coupling rate, detuning, bias magnetic field and dissipation of entanglement, are discussed. By adjusting some of the experimental parameters, we show that two antiferromagnets can produce a large entanglement, which is a result that has not been previously found in other quantum systems. Our findings may provide a potential platform for the completion of related quantum tasks in the future.

To screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic β-amino alcohols. A new strain named Arthrobacter sp. TYUT010-15 with the (R)-selective deamination activity of cyclic β-amino alcohol has been isolated from nature via a high throughput solid-phase screening method. The reaction conditions of TYUT010-15 were optimized. Using the resting cell of TYUT010-15 as the catalyst, kinetic resolution of trans-2-aminocyclopentanol, trans-2-aminocyclohexanol and cis-1-amino-2-indanol was carried out to afford (1S, 2S)-trans-2-aminocyclopentanol, (1S, 2S)-trans-2-aminocyclohexanol and (1R, 2S)-cis-1-amino-2-indanol in > 99% ee and 49.6–50% conversion. Four aromatic β-amino alcohols and two amines were also resolved, (S)-β-amino alcohols and (R)-amines were obtained in > 99% ee. Preparation experiment was conducted with 200 mM (23.2 g L−1) racemic trans-2-aminocyclohexanol, yielding the desired (1S, 2S)-trans-2-aminocyclohexanol in 40% isolated yield, > 99% ee and 5.8 g L−1 d−1 space time yields. This study provides a high throughput solid-phase method for screening of bacteria with cyclic amino alcohol deamination activity and a first example for practical preparation of chiral cyclic β-amino alcohol by Arthrobacter sp. TYUT010-15.

We in this paper derive the expression of the least square solution with the least norm to the system of generalized Sylvester quaternion matrix equations $$\begin{aligned} A_1X = E_1 ,\quad XB_1 = E_2, \quad C_1Y = E_3 ,\quad YD_1 = E_4,\quad A_2XB_2+C_2YD_2=E_5, \end{aligned}$$ where X, Y are unknown quaternion matrices and the others are given quaternion matrices.

Rationally surface optimization is considered to improve both energy capacity and structure stability in rechargeable batteries. A novel structure of copper coated silicon nanoparticles encapsulated in carbon cages (Si@Cu@CC) is synthesized by feasible methods of reduction and pyrolysis. The obtained composite exhibits a superior reversible capacity of 1724.3 mAh g−1 after 50 cycles at 0.1 A g−1, and the coulombic efficiency (CE) is 98.13%. It also maintains 1201.6 mAh g−1 even at the current density of 2 A g−1. The copper shell as a mechanical support layer wraps around the silicon nanoparticle can relieve the inner stress caused by the volumetric change. The exterior of Si@Cu particles is continuous network of carbon cages, which not only improves the conductivity of electrodes but also provides abundant transport channels for electrons and ions. The particular structure and the synergistic effect of copper and carbon have very important influence on the gorgeous properties of this composites.

In the field of speed sensorless control of permanent magnet synchronous motors, it is difficult to accurately estimate the speed via a single algorithm for full speed range because there are many non-ideal factors when the algorithms are realized. In this paper, high frequency pulse signal injection method is applied in the low speed region, and dual EKF is used in the medium and high speed region. The switching of these two algorithms is achieved by the weighted averaging rule. This hybrid estimation strategy avoids detecting the back-electromotive force which is hard to be measured in low-speed region, and also avoids the adverse effects of the filter delay in the mid-high speed region. Therefore, it enables the sensorless control effective over the full speed range. Moreover, the dual EKF algorithm can estimate the motor parameters with a relatively small amount of calculation. Validity and effectiveness of the proposed scheme is shown in the simulation results.

In the daul PWM converter system of permanent magnet synchronous generator, the passivity can achieve global asymptotic stability and improve the robustness to external disturbances of the system. However, the power ripple on the grid-side is still large. Aiming at this problem, an model predictive control with fixed switching frequency is proposed in this paper. The mathematical model of the grid-side converter is established and analyzed, then the cost functions of the model predictive control is selected based on the active and the reactive power error. Furthermore, according to the analysis and the derivation of the cost function, SVPWM technique is applied to achieve the fixed switching frequency, so as to reduce the switching losses. The simulation and the experimental results show that the proposed model predictive control scheme can depress the power ripple on the grid-side effectively.

Post-herpetic neuralgia (PHN) is a well-established clinical problem with potential severe personal and socioeconomic implications. GTP cyclohydrolase 1 (GCH1) gene, which encodes the rate-limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated to be associated with neuropathic pain in previous animal and human studies. The rs3783641 (T > A) single-nucleotide polymorphism (SNP) in the GCH1 gene is functional. Here we examine the association between rs3783641 and PHN. A total of 292 subjects including 103 PHN patients, 87 herpes zoster (HZ) patients and 102 healthy controls were enrolled in this study. The rs3783641 polymorphisms were detected via the high-resolution melting curve (HRM) method. There were statistical differences between PHN group and the other two groups in genotype distribution (P = 0.029 and 0.017, respectively) and allele frequency (P = 0.032 and 0.005, respectively) of rs3783641. The proportion of subjects with AA genotype in the PHN group was significantly lower compared to HZ group and control group (P = 0.026 and 0.016, respectively). The frequency of A allele was lower in the PHN group than in control group (P = 0.005), and the frequency of T allele in the PHN group was higher than in HZ group and control group (P = 0.001 and 0.003, respectively). The results of this study suggest that the rs3783641 SNP in the GCH1 gene is associated with PHN, and the AA genotype showed a protective effect in PHN.

Background— There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. Methods and Results— The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p =0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10–2.24; P =0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. Conclusions— OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01306526.

To quantify regional sources contributing to submicron particulate matter (PM1) pollution in haze episodes, on-line measurements combining two modeling methods, namely, positive matrix factorization (PMF) and backward Lagrangian particle dispersion modeling (LPDM), were conducted for the period of one month in urban Nanjing, a city located in the western part of Yangtze River Delta (YRD) region of China. Several multi-day haze episodes were observed in December 2013. Long-range transport of biomass burning from the southwestern YRD region largely contributed to PM1 pollution with more than 25% of total organics mass in a lasting heavy haze. The LPDM analysis indicates that regional transport is a main source contributing to secondary low-volatility production. The high-potential source regions of secondary low-volatility production are mainly located in areas to the northeast of the city. High aerosol pollution was mainly contributed by regional transport associated with northeastern air masses. Such regional transport on average accounts for 46% of total NR-PM1 with sulfate and aged low-volatility organics being the largest fractions (>65%).

Although proton pump inhibitors (PPIs) have been used widely, acid-related diseases are still associated with a huge burden on the health care system. Recently, the efficacy and safety of a new acid suppressant named vonoprazan in the treatment of acid-related diseases have been evaluated by a series of studies. As a novel potassium-competitive acid blocker, vonoprazan may provide reversible acid suppression by preventing K+ from binding to gastric H+/K+-ATPase. It has been clinically used for the short-term treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease and Helicobacter pylori (H. pylori) infection in Japan. The healing rate of GERD and gastric ulcers by vonoprazan is more than 95 and 90%, respectively; also, it is effective in curing PPI-resistant GERD. It increases H. pylori eradication rate to more than 88% as part of both first-line and second-line therapy. It is also effective in the eradication of clarithromycin-resistant H. pylori strains. All of these short-term studies show vonoprazan is safe and well-tolerated. As a safe and effective acid inhibitor, vonoprazan might be a novel alternative in the treatment of acid-related diseases.

Background To investigate the effects of twice daily short-message-based re-education (SMRE) before taking medicine for Helicobacter pylori (H pylori) eradication. Materials and methods Treatment-naive patients with H pylori infection were prescribed 14-day quadruple regimen consisting of lansoprazole 30 mg, colloidal bismuth pectin 200 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily. Patients were randomly allocated to SMRE group or control group. Patients in control group received oral and written instructions at outpatient clinic. In contrast, patients in the SMRE group received extra short messages including dosage and time of administration twice daily. Successful H pylori eradication was assessed using the 13 C-urea breath test 6 weeks after treatment. The compliance, adverse events, and patient satisfaction were also analyzed. Results A total of 310 patients were enrolled in the intention-to-treat (ITT) and 283 in the per-protocol (PP) analysis. For young patients, the eradication rates were significantly higher in SMRE group than those in control group in PP analysis (88.6% vs 71.2%, P = 0.036), while for patients of all age groups, the eradication rate improvements were not statistically significant. The eradication rates in SMRE group and control group were 74.2% and 67.7% (P = 0.211) in ITT analysis and 82.1% and 73.4% (P = 0.078) in PP analysis, respectively. The compliance in SMRE group was significantly better than that in control group (84.8% vs 72.8%, P = 0.011). Conclusions Twice daily SMRE could improve the eradication rate in young population, as well as the compliance with treatment during H pylori eradication.

Objective: To systematically evaluate the intervention effect of virtual reality technology on patients recovering from traumatic brain injury. Methods: The computer retrieved CNKI, VIP, Wan Fang, Embase, The Cochrane Library and PubMed database, and collected randomized controlled trials of virtual reality technology combined with routine rehabilitation training and simple routine rehabilitation training on patients recovering from traumatic brain injury. The retrieval period was from the establishment of the database to July 2019. Two researchers independently screened the literature, extracted the data and evaluated the risk of bias in the included studies. RevMan 5.3 software was used for analysis. Results: A total of 7 articles were included. Meta-analysis results showed that virtual reality technology could significantly improve balance function (mean difference (MD) = 3.72, 95% confidence interval (CI) (2.61, 4.83), P < 0.001), daily living ability (MD = 11.87, 95% CI (10.42, 13.32), P < 0.001), and exercise ability (MD = 3.83, 95% CI (2.30, 5.36), P < 0.001). In the aspect of posture control ability, the trajectory motion length, trajectory velocity and peripheral area were improved (standardised mean difference (SMD) = −0.80, 95% CI (−1.19, −0.41), P < 0.0001), (SMD = −0.95, 95% CI (−1.45, −0.45), P = 0.0002), (SMD = −0.69, 95% CI (−1.11, −0.26), P = 0.001). Conclusion: Virtual reality technology can significantly improve the balance function, daily living ability, motor function and postural control ability of patients recovering from cerebral trauma. Limited by the quantity and quality of the included studies, the above conclusions need to be verified by more high-quality studies.

Volatile organic compounds (VOCs) is an important precursor of photochemical ozone pollution (O3) in the atmosphere. Their concentration variation directly affects the characteristics of the ozone pollution. The concentration, speciation of VOCs, ozone and its precursors in Nanjing were analyzed and measured using online gas detection systems in August 2013. VOCs/NOx discriminant method was used to get the sensitive control factors of ozone. The results showed that the averaged volume fraction of VOCs was 52. 05 x 10(-9), and the largest one reached 200 x 10(-9) in Nanjing urban district. The order of volume fraction of each species VOCs was alkaneoxygen-containing VOCsalkenearomatics. The averaged concentration of ozone was 76.5 microg x m(-1) and the exceeding concentration of hourly standard was 5.9%. The change trends of ozone precursors VOCs and NOx were basically identical and Ozone showed the obvious negative correlation during the period of high concentrations of ozone. There were some differences in the concentrations of the same VOCs in different ozone concentration periods. The ozone generation in Nanjing urban district was sensitive to VOCs, and Nanjing belonged to VOCs control area in summer.