Search

Cross-kingdom herbal miRNA was first reported in 2012. Using a modified herbal extraction protocol, we obtained 73,677,287 sequences by RNA-seq from 245 traditional Chinese Medicine (TCM), of which 20,758,257 were unique sequences. We constructed a Bencao (herbal) small RNA (sRNA) Atlas ( http://bencao.bmicc.cn ), annotated the sequences by sequence-based clustering, and created a nomenclature system for Bencao sRNAs. The profiles of 21,757 miRNAs in the Atlas were highly consistent with those of plant miRNAs in miRBase. Using software tools, our results demonstrated that all human genes might be regulated by sRNAs from the Bencao sRNA Atlas, part of the predicted human target genes were experimentally validated, suggesting that Bencao sRNAs might be one of the main bioactive components of herbal medicines. We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions. Moreover, the decoctosome, a lipo-nano particle consisting of 0.5%-2.5% of the decoction, demonstrated potent medical effects. We propose a Bencao (herbal) Index, including small-molecule compounds (SM), protein peptides (P), nucleic acid (N), non-nucleic and non-proteinogenic large-molecule compounds (LM) and elements from Mendeleev's periodic table (E), to quantitatively measure the medical effects of botanic medicine. The Bencao sRNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine, and may provide potential remedies for the theory and practice of one medicine.

It is generally known that soil organic carbon (SOC) stocks tend to increase with an increase in C input, whereas the C sequestration efficiency (CSE), i.e., the conversion ratio of C input to SOC, differs depending on the amount and type of C input. However, there is still a need to better understand the impact of various fertilization practices on CSE. We studied the data from eight long-term experiments located in the main dryland region of China in order to comprehensively assess the key drivers of CSE in the plow layer considering nearly four decades of various fertilizer treatments, i.e., no fertilizer (CK); chemical nitrogen, phosphorus, and potassium (NPK/NP); chemical fertilizers plus manure (NPKM/NPM/NM); and straw (NPKS/NPS/NS). Our results showed that manure amendment had the most significant fertilization effect on SOC sequestration with an average CSE of 14.9%, which was significantly higher than that of chemical fertilization (9.0%) and straw return treatments (7.9%). In addition, manure amendment also had the highest average SOC increase rate of 684 kg C ha-1 yr-1. Variance partitioning analysis (VPA) illustrated that the CSE of the main dryland region of China was mostly controlled by edaphic characteristics (32.2%), especially the soil C/N ratio and clay content. VPA and structural equation modeling revealed that the magnitude and influencing factors driving CSE varied among different fertilizer treatments. Soil total N was the limiting factor for CSE in the CK treatment, whereas the soil C/N ratio and pH were the main explanatory factors for CSE in the long-term chemical NPK fertilizer treatment. The negative impact of C input from straw was the main driver of CSE under straw return treatments, though C input had a positive effect on the improvement of soil physical properties. However, when considering manure amendments, the improvement of soil nutrients and clay content controlled CSE, underlining the main positive direct effect of soil chemical properties. In a nutshell, our results recommend manure plus chemical fertilizers as a sustainable practice for improving the C sequestration rate and efficiency in dryland cropping systems.

Wei-Ying Diao,1,&ast; Cheng-Long Ding,1,&ast; Bo-Yang Yuan,2 Zan Li,3 Na Sun,4 Jia-Bin Huang5 1Department of Pathology, The First Affiliated Hospital of Jiamusi University, Jimusi City, Heilongjiang Province, 154002, People’s Republic of China; 2Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Jiamusi University, Jimusi City, Heilongjiang Province, 154002, People’s Republic of China; 3Department of Analytical Chemistry Teaching and Research, Jiamusi University, Jiamusi City, Heilongjiang Province, 154002, People’s Republic of China; 4Graduate Department, Jiamusi University, Jiamusi, Heilongjiang Province, 154002, People’s Republic of China; 5Department of Geratology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang Province, 154002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia-Bin Huang Email jiadupinglu54972@163.comIntroduction: We aim to investigate the relationship between HER2 gene phenotype and clinical characteristics, distribution and prognosis of non-small cell lung cancer (NSCLC) patients.Methods: A total of 249 NSCLC patients admitted to the oncology department of our hospital from January 2015 to January 2018 were retrospectively analyzed. The clinicopathological information, CT signs, clinical efficacy and long-term prognosis were collected and compared.Results: A total of 249 NSCLC patients underwent HER2 gene testing, 21 of them (8.43%) complied with HER2 alterations [HER2 (+)], and there were significant differences in tumor stages among patients with different HER2 phenotypes (P< 0.05). Among 21 NSCLC patients with HER2 (+), HER2 gene mutation was found in 17 patients (81%), and HER2 gene amplification in 4 patients (19%). Among the HER2 mutations, 12 cases (57%) were 20 exon mutations, and 5 cases (19%) were other mutations. Analysis of CT signs showed that border lobulation/burr, necrosis sign and pleural depression were correlated with HER2 gene mutation (P< 0.05). The incidence of EGRF mutation in HER (+) patients was significantly lower than that in HER (-) patients (P< 0.05), but there was no significant difference in the incidence of ALK gene mutation among different HER phenotypes (P> 0.05). The disease control rate of HER2 (+) patients was significantly lower than that of HER2 (-) patients, and the 12-month progression-free survival rate and survival rate of HER2 (+) patients were significantly higher than those of HER2 (-) patients (P< 0.05). There was no significant difference in the incidence of ADR among HER2 patients with different phenotypes, but the incidence of ADR (adverse drug reaction) in HER2 (+) patients with Grade 3 or 4 was significantly higher than that in the control group (P< 0.05).Discussion: The incidence of HER2 gene mutations in NSCLC patients is relatively low, but it is far commoner in patients with stage IIIB∼IV, among which exon 20 mutations are the most prevalent. In CT signs, the lesion lobulated sign/spiculated sign, necrosis signs, and pleural depression signs are related to HER2 gene mutations. In addition, HER2 gene mutations play a crucial role in the clinical prognosis and treatment safety of patients.Keywords: non-small cell lung cancer, HER2 genotype, CT signs, afatinib

Yalin Cheng, Ke Chai, Wanrong Zhu, Yuhao Wan, Yaodan Liang, Minghui Du, Yingying Li, Ning Sun, Jiefu Yang, Hua Wang Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Hua WangDepartment of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaTel/Fax +86-10-85133852Email wanghua2764@bjhmoh.cnPurpose: Elderly heart failure (HF) patients have different clinical characteristics and poorer prognosis compared with younger patients. Prognostic risk scores for HF have not been validated well in elderly patients. We aimed to validate the Seattle Heart Failure Model (SHFM) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in an elderly Chinese HF cohort.Patients and Methods: This retrospective study enrolled 675 elderly HF patients (age≥ 70 years) discharged from our hospital between 2012 and 2017. The performance of the two risk scores was evaluated in terms of discrimination, using receiver-operating characteristic analysis, and calibration using a calibration plot and Hosmer–Lemeshow (H-L) test. Absolute risk reclassification was used to compare the two scores.Results: During the mean follow-up time of 32.6 months, 193 patients (28.6%) died, and 1-year mortality was 10.5%. The predicted median 1-year mortality was 8% for the SHFM and 18% for the MAGGIC score. A Kaplan–Meier survival curve demonstrated that event rates of all-cause mortality significantly increased with increasing SHFM and MAGGIC scores. The discriminatory capacity of the SHFM was greater than that of the MAGGIC score (c-statistics were 0.72 and 0.67, respectively; P = 0.05). The calibration plot for the SHFM was better than that for MAGGIC score for 1-year mortality (SHFM: H-L χ2 =8.2, P = 0.41; MAGGIC: H-L χ2 =18.8, P =0.02). Compared with the MAGGIC score, the net reclassification index (NRI) of the SHFM was 2.96% (Z=5.88, P< 0.0001).Conclusion: The SHFM performs better than MAGGIC score, having good discrimination, calibration and risk classification for the prediction of 1-year mortality in elderly Chinese HF patients.Keywords: heart failure, risk score, prognosis, elderly patient

Luyu Zhang,1 Qianqian Zhao,1 Leilei Mao,2 Huanze Li,1 Miaoqing Zhuang,1 Jiayi Wang,1 Yue Liu,1 Meng Qi,3 Xiaoping Du,3 Zengrun Xia,3 Na Sun,4 Qiling Liu,4 Hongfang Chen,1,5,6 Rongqiang Zhang4 1School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 2School of Information Engineering, Chang’an University, Xi’an, Shaanxi, People’s Republic of China; 3Ankang R & D Center of Se-enriched Products, Ankang, Shaanxi, People’s Republic of China; 4School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 5Shaanxi Academy of Tradional Chinese Medicine, Xi’an, Shaanxi, People’s Republic of China; 6Shaanxi Provincial Hospital of Chinese Medicine, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Hongfang ChenShaanxi Academy of Tradional Chinese Medicine, Shaanxi Provincial Hospital of Chinese Medicine, No. 4 Xihua Gate, Xi’an, Shaanxi, 710003; School of Nursing, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang, Shaanxi, 712046, People’s Republic of ChinaEmail 13892881695@163.comRongqiang ZhangSchool of Public Health, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang, Shaanxi, 712046, People’s Republic of ChinaTel/Fax +86-029-38185219Email Zhangrqxianyang@163.comPurpose: Selenophosphate synthetase 2 (SEPHS2) has been shown to regulate selenoprotein biosynthesis by catalyzing the synthesis of active selenium donor selenophosphate. SEPHS2 influences the survival of tumor cells. However, few studies have explored the expression level and prognostic of SEPHS2 in various cancers.Methods: The expression of SEPHS2 in human tumor tissues and normal adjacent tissues was analyzed in The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN databases. Cox regression analysis and Kaplan–Meier curve analysis were performed to analyze the association of SEPHS2 expression with the prognosis of cancer patients. The expression and prognosis of SEPHS2 in gliomas were further verified using the Chinese Glioma Genome Atlas (CGGA) dataset. The relationship between SEPHS2 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens was comprehensively explored using a TCGA cohort. The mechanism by which SEPHS2 regulates tumor progression was explored by using the STRING database. A nomogram was constructed using the R software to predict the overall survival (OS) of patients with brain lower grade glioma (LGG).Results: SEPHS2 was highly expressed in many cancers including LGG. Its high expression was significantly associated with poor OS, disease-free survival (DFS), and progression-free survival (PFS). Univariate and multivariate Cox analyses showed that SEPHS2 was an independent prognostic factor for LGG. Concordance index and calibration curves revealed that the nomogram had good predictive performance (concordance index: 0.791; 95% CI: 0.732– 1). A significant correlation was found between SEPHS2 and immune infiltration, TMB, MSI, and tumor neoantigens across diverse cancers. Enrichment analysis showed that SEPHS2 may regulate the PPAR signaling pathway.Conclusion: SEPHS2 expression regulates tumor development and it is a potential treatment target and prognostic biomarker, especially for lower grade glioma.Keywords: SEPHS2, selenoprotein, cancer, prognosis, biomarker

Xiaotong Song,1,2 Ning Sun,1– 3 Aixia Zhang,1– 3 Lei Lei,1 Xinrong Li,1 Zhifen Liu,1– 3 Yanfang Wang,1 Chunxia Yang,1– 3 Kerang Zhang1 1Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Mental Health, Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Chunxia Yang; Kerang ZhangDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaEmail ychunxia2000@163.com; atomsxmu@vip.163.comObjective: Although the pathogenesis of major depressive disorder (MDD) is still unclear, studies have shown that the dopaminergic system of depressed patients is defective, and that NR4A2 is an important transcription factor affecting the development and maintenance of dopaminergic neurons. As such, NR4A2 levels affected by NR4A2 single nucleotide polymorphisms (SNPs) may be associated with MDD. This study examined whether NR4A2 SNPs are associated with depressive symptoms and antidepressant efficacy.Methods: A total of 441 patients with first-episode depression were enrolled in this study. We analysed three SNPs of NR4A2, using the 17-item Hamilton Depression Rating Scale (HAM-D) and its four factors to obtain scores at baseline and at the end of 6 weeks. UNPHASED software was employed for quantitative character analysis, and SPSS software was adopted for antidepressant efficacy analysis.Results: Patients with rs12803-A exhibited higher scores of retardation symptoms. Patients with the rs834834-C allele and rs834834-CC genotype had higher retardation symptom scores. Patients with rs3769340 exhibited greater antidepressant efficacy.Conclusion: NR4A2 gene polymorphisms are associated with retardation symptoms, somatic symptoms (gastro-intestinal), anxiety-based somatic symptoms, insight, and weight loss in patients with MDD. Additionally, rs3769340 may be a predictor of antidepressant efficacy in patients with major depressive disorder.Keywords: major depressive disorder, NR4A2, single nucleotide polymorphism, antidepressant treatment

The effective utilization of manure in cropland systems is essential to sustain yields and reduce reactive nitrogen (Nr) losses. However, there are still uncertainties regarding the substitution of mineral nitrogen (N) fertilizer with manure in terms of its effects on crop yield and Nr losses. We conducted a comprehensive meta-analysis of wheat, maize, and rice applications in China and discovered that substituting mineral N fertilizer with manure increased wheat and maize yields by 4.9 and 5.5 %, respectively, but decreased rice yield by 1.7 %. The increase of yield is larger at low N application and low mineral N substitution rates ((SR) ≤30 %) for silt soils, warm regions, and acidic soils. High SR (>70 %) decreased rice yield as well as the N use efficiency of wheat and maize. Substitution of mineral N fertilizer with manure resulted in lower NH3 volatilization for wheat (48.7 %), lower N2O and NH3 emissions, and N runoff for maize (12.8, 49.6, and 66.7 %, respectively), and lower total Nr losses for rice (11.3–26.5 %). The loss of Nr was significantly and negatively correlated with soil organic carbon content. The rate of N application, soil properties, and climate were critical factors influencing N2O and NH3 emissions and N leaching, whereas climate or soil properties were the dominant factors influencing response in N runoff. We concluded that in silt soils, warm regions, and neutral soils, a ≤ 50 % substitution of mineral N fertilizer with manure can sustain crop yields while mitigating Nr losses.

Background: Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone. Nevertheless, some diagnoses are difficult, and further investigations are needed for correct tumor subtyping. Besides histochemical investigations, high-mass-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can detect new diagnostic biomarkers and hence improve the diagnostic. Patients and Methods: Formalin-fixed paraffin embedded tissue specimens from clear cell renal cell carcinoma (ccRCC, n = 552), papillary renal cell carcinoma (pRCC, n = 122), chromophobe renal cell carcinoma (chRCC, n = 108), and renal oncocytoma (rO, n = 71) were analyzed by high-mass-resolution MALDI fourier-transform ion cyclotron resonance (FT-ICR) MSI. The SPACiAL pipeline was executed for automated co-registration of histological and molecular features. Pathway enrichment and pathway topology analysis were performed to determine significant differences between RCC subtypes. Results: We discriminated the four histological subtypes (ccRCC, pRCC, chRCC, and rO) and established the subtype-specific pathways and metabolic profiles. rO showed an enrichment of pentose phosphate, taurine and hypotaurine, glycerophospholipid, amino sugar and nucleotide sugar, fructose and mannose, glycine, serine, and threonine pathways. ChRCC is defined by enriched pathways including the amino sugar and nucleotide sugar, fructose and mannose, glycerophospholipid, taurine and hypotaurine, glycine, serine, and threonine pathways. Pyrimidine, amino sugar and nucleotide sugar, glycerophospholipids, and glutathione pathways are enriched in ccRCC. Furthermore, we detected enriched phosphatidylinositol and glycerophospholipid pathways in pRCC. Conclusion: In summary, we performed a classification system with a mean accuracy in tumor discrimination of 85.13%. Furthermore, we detected tumor-specific biomarkers for the four most common primary renal tumors by MALDI-MSI. This method is a useful tool in differential diagnosis and biomarker detection.

Jinjie Yuan,1,2 Ning Sun,1 Xinying Feng,3 Huan He,1 Dong Mei,1 Guanghua Zhu,4 Libo Zhao1 1Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3Phase I Clinical Trials Centre, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, People’s Republic of China; 4Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Libo ZhaoClinical Research Center, Beijing Children’s Hospital, Capital Medical University, 56 Nanlishi Road, Xicheng District, Beijing, 100045, People’s Republic of ChinaEmail libozhao2011@163.comGuanghua ZhuHematology Oncology Center, Beijing Children’s Hospital, 56 Nanlishi Road, Xicheng District, Beijing, 100045, People’s Republic of ChinaEmail guangh.zhu@gmail.comPurpose: The aim of this study was to develop a novel busulfan dosing regimen, based on a population pharmacokinetic (PPK) model in Chinese children, and to achieve better area under the concentration-time curve (AUC) targeting.Patients and Methods: We collected busulfan concentration-time samples from 69 children who received intravenous busulfan prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). A population pharmacokinetic model for busulfan was developed by nonlinear mixed effect modelling and was validated by an external dataset (n=14). A novel busulfan dosing regimen was developed through simulated patients, and has been verified on real patients. Limited sampling strategy (LSS) was established by Bayesian forecasting. Mean absolute prediction error (MAPE) and relative root mean Squared error (rRMSE) were calculated to evaluate predictive accuracy.Results: A one-compartment model with first-order elimination best described the data. GSTA1 genotypes, body surface area (BSA) and aspartate aminotransferase (AST) were found to be significant covariates of Bu clearance, and BSA had significant impact of the volume of distribution. Moreover, two equations were obtained for recommended dose regimens: dose (mg)=34.14×BSA (m2)+3.75 (for GSTA1 *A/*A), Dose (mg)=30.99×BSA (m2)+3.21 (for GSTA1 *A/*B). We also presented a piecewise dosage based on BSA categories for each GSTA1 mutation. A two-point LSS, two hours and four hours after dosing, behaved well with acceptable prediction precision (rRMSE=1.026%, MAPE=6.55%).Conclusion: We recommend a GSTA1-BSA and BSA-based dosing (Q6 h) based on a PPK model for personalizing busulfan therapy in pediatric population. Additionally, an optimal LSS (C2h and C4h) provides convenience for therapeutic drug monitoring (TDM) in the future.Keywords: busulfan, individualized therapy, population pharmacokinetics, HSCT, GST mutations

Yaru Zou,1,2,* Dong Mei,1,* Jinjie Yuan,1,2 Jiaqi Han,1 Jiamin Xu,1 Ning Sun,1 Huan He,1 Changqing Yang,2 Libo Zhao1 1Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China*These authors contributed equally to this workCorrespondence: Libo ZhaoClinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of ChinaTel +86-010-59617018Email libozhao2011@163.comBackground: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. It requires a long and rigorous course of chemotherapy treatments. 6-Mercaptopurine (6-MP) is one of the primary drugs used in chemotherapy. Unfortunately, its efficacy has been limited due to its insolubility, poor bioavailability and serious adverse effects. To overcome these drawbacks, we constructed 6-mercaptopurine (6-MP)-loaded nanomedicines (6-MPNs) with biodegradable poly(lactide-co-glycolide) (PLGA) to enhance the anticancer efficacy of 6-MP.Methods: We prepared the 6-MPNs using a double-emulsion solvent evaporation method, characterizing them for the physicochemical properties. We then investigated the plasma, intestinal region and other organs in Sprague Dawley (SD) rats for pharmacokinetics. Additionally, we evaluated its anticancer efficacy in vitro on the human T leukemia cell line Jurkat and in vivo on the ALL model mice.Results: The 6-MPNs were spherical in shape with uniform particle size and high encapsulation efficiency. The in vitro release profile showed that 6-MPNs exhibited a burst release that a sustained release phase then followed. The apoptosis assay demonstrated that 6-MPNs could improve the in vitro cytotoxicity in Jurkat cells. Pharmacokinetics profiles revealed that 6-MPNs had improved oral bioavailability. Tissue distribution experiments indicated that 6-MPNs increased the duodenum absorption of 6-MP, at the same time having a low accumulation of the toxic metabolites of 6-MP. The in vivo pharmacodynamics study revealed that 6-MPNs could prolong the survival time of the ALL model mice. The prepared 6-MPNs, therefore, have superior properties in terms of anticancer efficacy against ALL with reduced systemic toxicity.Conclusion: Our nanomedicines provide a promising delivery strategy for 6-MP; they offer a simple preparation method and high significance for clinical translation.Keywords: 6-mercaptopurine, nanomedicines, Jurkat cells, acute lymphoblastic leukemia, ALL, bioavailability

Nai Sun,* Wei Zhang,* Jiaying Liu, Xiaochen Yang, Qinjun Chu Department of Anesthesiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinjun ChuDepartment of Anesthesiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, No. 16 Tongbai North Road, Zhongyuan District, Zhengzhou 450007, Henan Province, People’s Republic of ChinaTel/Fax +86 371-67690273Email yxchen615@163.comBackground: Propofol has been proposed to function as a tumor suppressor in various human cancers. In this study, we aimed to investigate the anti-tumor effect of propofol on cervical cancer (CC).Methods: Cell Counting Kit-8 (CCK-8) assay, colony formation assay, flow cytometry analysis, transwell assay and wound healing assay were conducted for cell viability, colony formation, apoptosis, invasion and migration, respectively. Western blot assay was used for protein levels. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for HOX antisense intergenic RNA (HOTAIR), miR-129-5p and RPL14 levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were executed to verify the interaction between miR-129-5p and HOTAIR or RPL14. Murine xenograft model assay was used for the role of propofol in tumor progression in vivo.Results: Propofol treatment suppressed CC cell viability, colony formation, invasion and migration and facilitated apoptosis. Propofol treatment led to a marked reduction in HOTAIR level in CC cells. HOTAIR overexpression promoted cell colony formation, invasion and migration and repressed apoptosis in CC cells and propofol-treated CC cells. For mechanism analysis, HOTAIR positively regulated RPL14 expression via acting as the sponge of miR-129-5p. MiR-129-5p overexpression reversed the impacts of HOTAIR on the malignant behaviors of propofol-treated CC cells. Furthermore, miR-129-5p inhibition accelerated the progression of CC cells, while RPL14 interference rescued the effect. In addition, propofol treatment restrained tumor growth of CC in vivo.Conclusion: Propofol inhibited CC development by modulation of HOTAIR/miR-129-5p/RPL14 axis.Keywords: propofol, cervical cancer, HOTAIR, miR-129-5p, RPL14

Baohua Liu,1,2,* Fei Gao,3,* Jianfeng Zhang,3,* Hongguo Zhou,1 Ning Sun,1 Laiyou Li,1 Libo Liang,2 Ning Ning,2 Qunhong Wu,2 Miaomiao Zhao4 1School of Health Services and Management, Ningbo College of Health Sciences, Ningbo 315100, Zhejiang, People’s Republic of China; 2Department of Social Medicine, School of Health Management, Harbin Medical University, Harbin 150081, Heilongjiang, People’s Republic of China; 3Institute of Food Safety and School Health, Heilongjiang Center for Disease Control and Prevention, Harbin 150030, Heilongjiang, People’s Republic of China; 4Department of Health Management, School of Public Health, Nantong University, Nantong 226019, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qunhong Wu; Miaomiao Zhao Tel +8618686825192; +8618860979901Email wuqunhong@163.com; zhaomiaomiao0201@163.comBackground: Sleep affects a wide array of health outcomes and is associated with the quality of life. Among students, sleep quality is affected by school stage and grade; however, data regarding the different sleep-related problems students experience at different school stages are limited. In this study, we aimed to explore sleep quality among a student sample ranging from elementary school to university level.Methods: Overall, data were examined for 9392 subjects aged 9– 22 years. Information on sociodemographic characteristics and other variables were collected through self-administered questionnaires. Sleep quality on school nights was evaluated using the standard Pittsburgh Sleep Quality Index; global score > 5 was classified as poor sleep quality. For the high school sample, logistic regression analysis was used to estimate associations between sleep quality and certain factors.Results: Of the elementary school, middle school, vocational high school, senior high school, and university students, 7.5%, 19.2%, 28.6%, 41.9%, and 28.5%, respectively, showed poor sleep quality. The high school students reported the highest prevalence of shorter sleep duration (70.8%), day dysfunction (84.7%), and subjective poor sleep quality (17.2%). The elementary school students showed the highest prevalence of poor sleep efficiency (17.9%). The university students showed the highest prevalence of sleep medication use (6.4%). The vocational high school students reported the highest prevalence of sleep latency (6.3%) and sleep disturbance (7.4%). Logistic regression modeling indicated that sleep quality is positively associated with school stage, grade, family atmosphere, academic pressure, and number of friends.Conclusion: Sleep quality and sleep features change greatly from elementary school to university. Interventions to improve sleep quality should consider targeting the specific issues students experience at each school stage. Alarmed by the high prevalence of poor sleep quality among high school students, it is recommended that high school students should be informed of their sleep matter and the consequences.Keywords: different school stages, sleep quality, students, PSQI

Bacteria often reside in sessile communities called biofilms, where they adhere to a variety of surfaces and exist as aggregates in a viscous polymeric matrix. Biofilms are resistant to antimicrobial treatments, and are a major contributor to the persistence and chronicity of many bacterial infections. Herein, we determined that the CpxA-CpxR two-component system influenced the ability of enteropathogenic Yersinia pseudotuberculosis to develop biofilms. Mutant bacteria that accumulated the active CpxR~P isoform failed to form biofilms on plastic or on the surface of the Caenorhabditis elegans nematode. A failure to form biofilms on the worm surface prompted their survival when grown on the lawns of Y. pseudotuberculosis. Exopolysaccharide production by the hms loci is the major driver of biofilms formed by Yersinia. We used a number of molecular genetic approaches to demonstrate that active CpxR~P binds directly to the promoter regulatory elements of the hms loci to activate the repressors of hms expression and to repress the activators of hms expression. Consequently, active Cpx-signalling culminated in a loss of exopolysaccharide production. Hence, the development of Y. pseudotuberculosis biofilms on multiple surfaces is controlled by the Cpx-signalling, and at least in part this occurs through repressive effects on the Hms-dependent exopolysaccharide production.

We report the discovery of a luminous late-time source at the position of the fast blue optical transient (FBOT) AT2018cow on images taken by the Hubble Space Telescope (HST) at 714 d and 1136 d after its explosion. This source is detected at both UV and optical wavelengths and has prominent Hα emission. It has a very stable brightness between the two epochs and a very blue spectral energy distribution (SED) consistent with fλ ∝ λ−4.1 ± 0.1, i.e. the Rayleigh-Jeans tail of a hot blackbody with a very high temperature of log(T/K) > 4.6 and luminosity of log(L/L⊙) > 7.0. This late-time source is unlikely to be an unrelated object in chance alignment, or due to a light echo of AT2018cow. Other possible scenarios also have some difficulties in explaining this late-time source, including companion star(s), star cluster, the survived progenitor star, interaction with circumstellar medium (CSM), magnetar, or delayed accretion in a tidal disruption event (TDE). Long-term and multi-wavelength monitoring will help to resolve its nature and finally reveal the origin of the ‘Cow’.

SN 2019yvr is the second Type Ib supernova (SN) with a possible direct detection of its progenitor (system); however, the spectral energy distribution (SED) of the pre-explosion source appears much cooler and overluminous than an expected helium-star progenitor. Using Hubble Space Telescope (HST) images and MUSE integral-field-unit (IFU) spectroscopy, we find the SN environment contains three episodes of star formation; the low ejecta mass suggests the SN progenitor is most likely from the oldest population, corresponding to an initial mass of 10.4+1.5−1.3 M⊙. The pre-explosion SED can be reproduced by two components, one for the hot and compact SN progenitor and one for a cool and inflated yellow hypergiant (YHG) companion that dominates the brightness. Thus, SN 2019yvr could possibly be the first Type Ib/c SN for which the progenitor’s binary companion is directly detected on pre-explosion images. Both the low progenitor mass and the YHG companion suggest significant binary interaction during their evolution. Similar to SN 2014C, SN 2019yvr exhibits a metamorphosis from Type Ib to Type IIn, showing signatures of interaction with hydrogen-rich circumstellar material (CSM) at >150 d; our result supports enhanced pre-SN mass-loss as an important process for hydrogen-poor stars at the lower mass end of core-collapse SN progenitors.

The conventional wet process of extracting phosphorus using concentrated sulfuric acid produces crude phosphoric acid rich in multiple ions. High-end applications require purification of the crude phosphoric acid by removing the ions at an affordable cost. At low pH, phosphoric acid mainly exists as a neutral molecule. Nanofiltration (NF) membranes have been proposed to remove multivalent ions while allowing acid permeation, based on size and charge factors. However, commercial membranes have not been specially designed for acidic applications, and poor permselectivities were reported. In this work, we developed a novel application of the glutaraldehyde (GA) crosslinked layer-by-layer (LBL) NF membranes based on poly(allylamine hydrochloride) (PAH)/poly(sodium styrene sulfonate) (PSS) for this purpose. We identified that more coating layers contributed to lower surface charges but smaller pores with narrower distributions. The PSS/PAH2.5 membrane with 2.5 bilayers showed high permselectivity of Al rejection up to 97% and P permeation more than 90% at acid permeance of 2.5 L/m2 h bar. The steric sieving was identified as the primary mechanism for rejecting ions; thus, a NF membrane with molecule weight cut-off (MWCO) of 120–230 Da was preferred. The long-term acid stability tests demonstrated that the PSS/PAH system is an excellent candidate of stable chemistry for preparing NF membranes with high permselectivity for phosphoric acid purification. Present research showcases the new NF membranes with great potential for broad applications.

The microbiota are vital for immune homeostasis and provide a competitive barrier to bacterial and fungal pathogens. Here, we investigated how gut commensals modulate systemic immunity and response to viral infection. Antibiotic suppression of the gut microbiota reduced systemic tonic type I interferon (IFN-I) and antiviral priming. The microbiota-driven tonic IFN-I-response was dependent on cGAS-STING but not on TLR signaling or direct host-bacteria interactions. Instead, membrane vesicles (MVs) from extracellular bacteria activated the cGAS-STING-IFN-I axis by delivering bacterial DNA into distal host cells. DNA-containing MVs from the gut microbiota were found in circulation and promoted the clearance of both DNA (herpes simplex virus type 1) and RNA (vesicular stomatitis virus) viruses in a cGAS-dependent manner. In summary, this study establishes an important role for the microbiota in peripheral cGAS-STING activation, which promotes host resistance to systemic viral infections. Moreover, it uncovers an underappreciated risk of antibiotic use during viral infections.

Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA. The released DOX then accumulates in the mitochondria causing cell starvation, reduced migration and apoptosis. The HA+DOX delivery system was also tested in-vivo on osteosarcoma bearing mice. Locally delivered DOX via the HA particles had a stronger tumor eradication effect compared to the controls as seen by PET-CT and immunohistochemical staining of proliferation and apoptosis markers. These results indicate that in addition to systemic chemotherapy, an adjuvant nHA could be used as a carrier for intracellular delivery of DOX for prevention of tumor recurrence after surgical resection in an osteosarcoma. Furthermore, we demonstrate that nHA particles are pivotal in this approach but a combination of nHA with mHA could increase the safety associated with particulate nanomaterials while maintaining similar therapeutic potential.

Wei He,1,2 Yao Luo,1 Jun-Peng Liu,1 Ning Sun,1 Di Guo,1 Ling-Ling Cui,1 Pei-Pei Zheng,1 Si-Min Yao,1 Jie-Fu Yang,1,2 Hua Wang1,2 1Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 2Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Hua Wang; Jie-Fu YangDepartment of Cardiology, Beijing Hospital, National Center of Gerontology, No. 1, Dahua Road, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel +86 13911680467; +86 13601292259Fax +86 10-58115035Email wanghua2764@bjhmoh.cn; yangjiefu2011@126.comObjective: Our study aimed to explore the association between trimethylamine N-oxide and frailty in older adults with cardiovascular disease.Patients and Methods: This cross-sectional study analyzed a total of 451 people aged 65 years or older who underwent comprehensive geriatric assessments. Frailty status was determined using a frailty index constructed with 48 variables according to the cumulative deficits model. Physical frailty and cognitive frailty were also assessed in detail. Fasting plasma TMAO was measured by mass spectrometry.Results: The proportion of frail subjects was 29.9% (135/451). Plasma TMAO levels were significantly higher in frail patients than in nonfrail individuals (4.04 [2.84– 7.01] vs 3.21 [2.13– 5.03] μM; p< 0.001). Elevated plasma TMAO levels were independently associated with the likelihood of frailty (OR 2.12, 95% CI 1.01– 4.38, p=0.046). Dose–response analysis revealed a linear association between the TMAO concentration and the OR for frailty. A 2-unit increase in TMAO was independently correlated with physical frailty (OR 1.23, 95% CI 1.08– 1.41, p for trend 0.002) and cognitive frailty (OR 1.21, 95% CI 1.01– 1.45, p for trend 0.04).Conclusion: Elevated circulating TMAO levels are independently associated with frailty among older adults with cardiovascular disease.Keywords: older adults, frailty, TMAO, cardiovascular disease, physical frailty, cognitive frailty

Qingpeng Zeng,1 Bingzhi Wang,2 Jiagen Li,1 Jun Zhao,1 Yousheng Mao,1 Yushun Gao,1 Qi Xue,1 Shugeng Gao,1 Nan Sun,1 Jie He1 1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Jie HeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing 100021, People’s Republic of ChinaEmail prof.jiehe@gmail.comObjective: Spread through air spaces (STAS) has been reported to be an invasive histological pattern with poor prognosis in lung cancer; however, little is known about its intrinsic risk factors. This work analyzed the correlation between pathological and radiological features and STAS in resected lung adenocarcinomas.Patients and Methods: We retrospectively reviewed 1821 consecutive surgically treated patients with histologically diagnosed lung adenocarcinoma (174 positive for STAS and 1647 negative for STAS) from December 2017 to November 2018 at our institution. Propensity score matching identified 170 well-balanced pairs of patients. The correlations between pathological and radiological features and the presence of STAS were analyzed.Results: Before propensity matching, the incidence rate of STAS was 9.6% in all patients. In matched cohorts, multivariate analysis showed that the presence of STAS was significantly correlated with pure solid nodules (SNs) (p = 0.001) and solid/micropapillary patterns (SMPs) (p = 0.002). The odds ratio for STAS in SN-positive and SMP-positive adenocarcinoma against that in SN-negative and SMP-negative adenocarcinoma was 10.922 (95% confidence interval, 5.826– 20.475; p < 0.001). Tumor differentiation, visceral pleural invasion (VPI), lymphovascular invasion (LVI), invasive adenocarcinoma, and non-lepidic subtype were significantly associated with STAS in the univariate analysis (p < 0.05); however, the differences failed to reach a significant level in the multivariate analysis.Conclusion: We found that STAS was significantly correlated with several invasive clinicopathological patterns. The presence of SNs and SMPs were revealed as independent predictors for STAS, which could offer clinicians clues to identify STAS-positive adenocarcinoma.Keywords: lung adenocarcinoma, spread through air spaces, solid pulmonary nodule

Ning Sun,1,2 Chunxia Yang,1 Xiaoting He,1,3 Zhifen Liu,1 Sha Liu,1 Xinrong Li,1 Yanfang Wang,1 Ruihua Jin,2 Kerang Zhang1 1Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Nursing College of Shanxi Medical University, Taiyuan, People’s Republic of China; 3University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Ruihua Jin; Kerang Zhang Email jrh_xy@163.com; atomsxmu@vip.163.comBackground: Patients suffering from major depressive disorder (MDD) commonly demonstrate lower performance across multiple cognitive domains. Cognitive impairment is an intrinsic characteristic of MDD status and is often influenced by genetic factors. microRNAs (miRNAs or miRs) have been shown to have important implications in the etiology of MDD. Therefore, we aimed to identify and analyze the impact of expression and genetic variation of miR-34b/c on cognitive dysfunction in MDD.Methods: First, we analyzed miR-34c-5p expression in 48 cases of MDD and 54 healthy controls in a Chinese population using qRT-PCR. We assessed the relationship between the level of miR-34c-5p expression and cognitive performance by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test (TMT). Second, in order to characterize allelic effects of miR-34b/c on cognitive performance in MDD patients, we performed genetic association analysis of single-nucleotide polymorphism (SNP) loci of the MIR34B/C genes with cognitive function in a second group consisting of 531 MDD patients and 267 healthy controls.Results: We found a significant negative correlation between the level of miR-34c-5p expression and both the language and delayed memory index scores in patients with MDD. We also found a significant positive correlation between the level of miR-34c-5p expression and the time required to complete tests A and B of the TMT. The interaction between the rs2187473 genotype and the disease was significant for both immediate memory and delayed memory. In the patient group, the rs2187473 CC genotype was significantly associated with higher performance on immediate memory (F = 6.683, p < 0.05) and delayed memory tasks (F = 4.221, p < 0.05).Conclusion: Our findings suggest that changes in miR-34c expression level have important impacts on cognitive function in patients with MDD. In particular, the polymorphism rs2187473 is a potential genetic risk factor for cognitive function in MDD, which may be of clinical use.Keywords: major depressive disorder, MDD, microRNA-34c, single-nucleotide polymorphism, cognitive function

Penghong Liu,1,2 Qi Li,1,2 Aixia Zhang,1 Zhifen Liu,1 Ning Sun,1 Chunxia Yang,1 Yanfang Wang,1 Kerang Zhang1 1Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 2Department of Psychiatry, Shanxi Medical University, Taiyuan 030001, People’s Republic of ChinaCorrespondence: Yanfang Wang; Kerang ZhangDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, People’s Republic of ChinaTel +86-13934556065; +86-18834180209Email Wangyanfang12388@163.com; atomsxmu@vip.163.comObjective: To investigate the regional homogeneity (ReHo) between unipolar depression (UD) and bipolar disorder (BD), and to search for brain imaging markers for distinguishing UD and BD.Methods: A totalof 58 patients who met the diagnosis criteria of UD in DSM–Ⅳ, 40 patients who met the diagnosis criteria of BD in DSM-Ⅳ and 54 healthy controls (HC) completed the resting-state functional magnetic resonance (rs-fMRI) scans. The ReHo of the three groups was compared and Pearson correlation analysis was performed between the ReHo values and the clinical symptoms.Results: (1) Significant differences were found in the right hippocampus, right parahippocampal gyrus, right Inferior orbitofrontal gyrus, right superior temporal gyrus, right inferior temporal gyrus, and right middle occipital gyrus across the three groups. (2) Compared to HC, the ReHo in the right parahippocampal gyrus in UD significantly increased. (3) When compared to HC, the ReHo in the right hippocampus in BD significantly increased. The ReHo in the right middle occipital gyrus decreased. (4) Compared to UD, BD exhibited significantly decreased ReHo in the right inferior temporal gyrus. No correlations were observed between the scores of 24-item Hamilton Depression Rating Scale (HDMD-24), Hamilton Anxiety Scale (HAMA), Young Mania Rating Scale (YMRS), and the ReHo values of altered brain regions between BD and UD.Conclusion: The results suggest that there was a considerable difference in the ReHo of brain among UD, BD, and HCs. ReHo in the right inferior temporal gyrus showed significant differences between BD and UD that might serve as neuroimaging markers to identify BD and UD.Keywords: bipolar depression, unipolar depression, rs-fMRI, regional homogeneity

We have derived high-spatial-resolution metallicity maps covering ∼105 deg2 across the Large Magellanic Cloud (LMC) using near-infrared passbands from the VISTA Survey of the Magellanic Clouds. We attempt to understand the metallicity distribution and gradients of the LMC up to a radius of ∼6 kpc. We identify red giant branch (RGB) stars in spatially distinct Y, (Y − Ks) colour–magnitude diagrams. In any of our selected subregions, the RGB slope is used as an indicator of the average metallicity, based on calibration to metallicity using spectroscopic data. The mean LMC metallicity is [Fe/H] = −0.42 dex (σ[Fe/H] = 0.04 dex). We find the bar to be mildly metal-rich compared with the outer disc, showing evidence of a shallow gradient in metallicity (−0.008 ± 0.001 dex kpc−1) from the galaxy’s centre to a radius of 6 kpc. Our results suggest that the LMC’s stellar bar is chemically similar to the bars found in large spiral galaxies. The LMC’s radial metallicity gradient is asymmetric. It is metal-poor and flatter towards the southwest, in the direction of the Bridge. This hints at mixing and/or distortion of the spatial metallicity distribution, presumably caused by tidal interactions between the Magellanic Clouds.

Bacteria often reside in sessile communities called biofilms, where they adhere to a variety of surfaces and exist as aggregates in a viscous polymeric matrix. Biofilms are resistant to antimicrobial treatments, and are a major contributor to the persistence and chronicity of many bacterial infections. Herein, we determined that the CpxA-CpxR two-component system influenced the ability of enteropathogenic Yersinia pseudotuberculosis to develop biofilms. Mutant bacteria that accumulated the active CpxR~P isoform failed to form biofilms on plastic or on the surface of the Caenorhabditis elegans nematode. A failure to form biofilms on the worm surface prompted their survival when grown on the lawns of Y. pseudotuberculosis. Exopolysaccharide production by the hms loci is the major driver of biofilms formed by Yersinia. We used a number of molecular genetic approaches to demonstrate that active CpxR~P binds directly to the promoter regulatory elements of the hms loci to activate the repressors of hms expression and to repress the activators of hms expression. Consequently, active Cpx-signalling culminated in a loss of exopolysaccharide production. Hence, the development of Y. pseudotuberculosis biofilms on multiple surfaces is controlled by the Cpx-signalling, and at least in part this occurs through repressive effects on the Hms-dependent exopolysaccharide production.

BackgroundPostoperative cognitive dysfunction (POCD) is one of the common postoperative complications in the elderly. The main clinical manifestation is memory impairment, which can cause permanent damage and even dementia in severe cases. However, the pathogenesis of POCD is still unknown. Age and neuroinflammation are known to be closely related to its occurrence, while DNA methylation is very important for transcriptional silencing and neuroinflammation. Consequently, this study intended to establish a mouse model of POCD to explore the role of DNA methylation in regulating the expression of interleukin-1β which participated POCD in aged mice.MethodsPOCD model was established by exploratory laparotomy and evaluated by new object experiment and Y maze test. In addition, ELISA, RT-PCR, Western blotting, immunofluorescence, microglia isolation and flow cytometry methods were used to detect the inflammatory state of dorsal hippocampal after surgery. Moreover, MSP, MeDIP and IL-1β promoter DNA methylation sequencing were used to explore the regulation of DNA methylation on IL-1β in this model. Finally, Golgi staining and Western blotting were used to further explore the role of IL-1β in POCD and its possible mechanisms. ResultsCognitive impairment was observed in aged but not adult mice at 1 day after surgery. There was a significant correlation between the level of IL-1β in dorsal hippocampus and the performance of cognitive function. The microglia in the dorsal hippocampus was activated and the IL-1β promoter DNA methylation was decreased in the aged mice. The increased expression of IL-1β impaired synaptic plasticity and hippocampus-dependent memory formation. Intracerebroventricular administration of IL-1β receptor antagonist could prevent the cognitive impairment of aged mice after surgery, reverse the decrease of dendritic spine density and synapse-associated protein expression induced by surgery.ConclusionDNA methylation regulation may be an important mechanism for greater susceptibility to POCD in aged mice by regulating the expression of IL-1β. IL-1β inhibiting prevented surgery-induced cognitive decline and synaptic plasticity dysfunction. The research also provided a new target for the clinical prevention of the occurrence of POCD in the elderly.

Wenchang Yuan,*,1Zhiwu Yu,*,2Weiqi Song,*,3Yanan Li,4 Zhiyuan Fang,1 Baizhen Zhu,1 Xiaomei Li,1 Hao Wang,5 Wei Hong,6 Ning Sun1,71The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, People’s Republic of China; 2Division of Laboratory Science, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, People’s Republic of China; 3School of Public Health, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China; 4Department of Pharmacy, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, People’s Republic of China; 5School of Pharmacy, Ningxia Medical University, Yinchuan 750004, People’s Republic of China; 6School of Chemistry and Chemical Engineering, North Minzu University, Yinchuan 750021, People’s Republic of China; 7State Key Laboratory of Chemical Biology and Drug Discovery, and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People’s Republic of China*These authors contributed equally to this workBackground: The prevalence of drug-resistant bacterial infections urges the development of new antibacterial agents that possess a mechanism of action different from traditional antibiotics. FtsZ has been recognized as a key functional protein in bacterial cell division and it is currently believed to be a potential target for the development of novel antibacterial agents.Purpose: The primary aim of the study is to screen out an inhibitor targeting at FtsZ and followed to investigate its antibacterial activity and mode of action.Methods: Cell-based cell division inhibitory screening assay, antimicrobial susceptibility test, minimum bactericidal concentration assay, time-killing curve determination, FtsZ polymerization assay, GTPase activity assay, and molecular modeling were performed in the present study.Results: The screening study from a small library consisting of benzimidazole and indole derivatives discovered a compound (CZ74) with an indole-core structure. The compound exhibited strong cell division inhibitory effect. In addition, CZ74 shows high antibacterial potency against a number of tested Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. The minimum inhibitory concentration values obtained were within the range of 2–4 μg/mL. The results of biological study revealed that CZ74 at 2 μg/mL is able to disrupt FtsZ polymerization and inhibit GTPase activity and cell division. From molecular modeling study, CZ74 is found possibly binding into the interdomain cleft of FtsZ protein and then leads to inhibitory effects.Conclusion: This indole-cored molecule CZ74 could be a potential lead compound and could be further developed as a new generation of antibacterial agents targeting FtsZ to combat against multidrug-resistant bacteria.Keywords: indole-core-based derivative, antibacterial, cell division, FtsZ, antibiotic resistant

Wenchang Yuan,1,2,* Jianhua Liu,2,3,* Youchao Zhan,1,* Li Wang,2 Yanqiong Jiang,1 Yanling Zhang,1 Ning Sun,1,4 Ning Hou1,51Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, People’s Republic of China; 2Department of Clinical Laboratory, General Hospital of Xinjiang Military Region, Urumqi 830001, People’s Republic of China; 3Department of Intensive Care Unit, the Fourth Hospital of Changsha, Changsha 410006, People’s Republic of China; 4State Key Laboratory of Chemical Biology and Drug Discovery, and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People’s Republic of China; 5School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China*These authors contributed equally to this work Background: Staphylococcus aureus is among the most common causes of health care- and community-associated infections worldwide. The distributions of different S. aureus clones change over time and also vary geographically. The purpose of this study was to determine the molecular type and antimicrobial resistance profiles of clinical S. aureus strains isolated in Urumqi, Northwestern China.Methods: A total of 605 clinical S. aureus isolates were collected from Xinjiang Military General Hospital, in Urumqi. Protein A-encoding (spa) typing, multilocus sequence typing, staphylococcal chromosomal cassette mec typing, Panton-Valentine leucocidin (pvl) gene detection, and antimicrobial resistance profiling were performed.Results: Among these strains, 271 isolates (44.7%) were methicillin-resistant S. aureus (MRSA) and 334 (55.3%) were methicillin-susceptible S. aureus (MSSA). The MRSA strains consisted of 22 spa types and 14 sequence types (STs). ST239-MRSA-III-t030 (73.1%, 198/271) and ST59-MRSA-IV-t437 (11.8%, 32/271) were the most common, and ST22-MRSA-IV-t309 was the rarest (2.02%, 6/271). The MSSA strains consisted of 93 spa types and 29 STs. ST22, ST121, ST398, ST5, ST7, ST188, and ST15 were the main MSSA STs, and ST22-MSSA-t309 was most common (26.0%, 87/334). The pvl gene was present in 20.3% of all S.aureus strains, and 80.8% (88/99) of ST22-MSSA strains harbored the pvl gene. A total of 85.7% pvl-positive ST22-MSSA strains were spa t309 (85/99), and 87.5% of pvl-positive ST22-MSSA strains were from abscesses or wounds (skin and soft tissue infections). All ST239-MRSA strains were resistant to gentamicin (GEN), levofloxacin (LEV), ciprofloxacin (CIP), moxifloxacin (MXF), rifampicin (RIF), and tetracycline (TET). Among the ST59-MRSA strains, over 70.0% were resistant to erythromycin (ERY), clindamycin (CLI), and TET. ST22-MSSA remained susceptible to most antibiotics, but was resistant to PEN (97.0%), ERY (57.6%), and CLI (15.2%).Conclusion: Our major results indicated that the antimicrobial resistance profiles and pvl genes of S. aureus isolates from Urumqi were closely associated with clonal lineage. ST239-MRSA-III-t030 and pvl-positive ST22-MSSA-t309 were the most common clones in this region of Northwestern China.Keywords: Staphylococcus aureus, methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, pvl gene, molecular typing

Na Sun,1,* Lingzhou Zhao,1,* Jingyi Zhu,2,* Yujie Li,1 Ningning Song,1 Yan Xing,1 Wenli Qiao,1 He Huang,2 Jinhua Zhao11Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People’s Republic of China; 2State Key Laboratory of Material-Oriented Chemical Engineering, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, People’s Republic of China*These authors contributed equally to this work Purpose: Polyethylenimine (PEI) has been widely used as a versatile template to develop multifunctional nanosystems for disease diagnosis and treatment. In this study, we manufactured iodine-131 (131I)-labeled PEI-entrapped gold nanoparticles (Au PENPs) as a novel nanoprobe for single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and radionuclide therapy.Materials and methods: PEI was PEGylated and sequentially conjugated with Buthus martensii Karsch chlorotoxin (BmK CT, a tumor-specific ligand which can selectively bind to MMP2), 3-(4′-hydroxyphenyl)propionic acid-OSu (HPAO), and fluorescein isothiocyanate to form the multifunctional PEI template for entrapment of Au NPs. Then, the PEI surface was radiolabeled with 131I via HPAO to produce the novel nanoprobe (BmK CT-Au PENPs-131I).Results: The synthesized multifunctional Au PENPs before and after 131I radiolabeling were well-characterized as follows: structure, X-ray attenuation coefficient, colloid stability, cytocompatibility, and radiochemical stability in vitro. Furthermore, BmK CT-Au PENPs-131I were suitable for targeted SPECT/CT imaging and radionuclide therapy of tumor cells in vitro and in a xenograft tumor model in vivo.Conclusion: The developed multifunctional Au PENPs are a promising theranostic platform for targeted imaging and treatment of different MMP2-overexpressing tumors.Keywords: polyethylenimine, BmK CT, gold nanoparticles, SPECT/CT imaging, radionuclide therapy

Penghong Liu,1,2 Gaizhi Li,1 Aixia Zhang,1 Ning Sun,1 Lijun Kang,2 Chunxia Yang,1 Yanfang Wang,1 Kerang Zhang11Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 2Department of Psychiatry, Shanxi Medical University, Taiyuan, 030001, People’s Republic of ChinaObjective: It is common that major depressive disorder (MDD) is accompanied by gastrointestinal (GI) symptoms. However, few studies have focused on the clinical characteristics and its possible mechanism, while brain gray matter (GM) structure is important in the pathogenesis of GI symptoms. In this study, we aimed to investigate the basic clinical characteristics and regional GM volume changes in MDD accompanied by GI symptoms.Method: Patients with MDD (n=49) and age, gender, and educational level-matched healthy controls (n=30) were recruited. Patients with MDD were divided into two groups based on the GI status: MDD with (n=27) and without (n=22) GI symptoms. The 24-item Hamilton Depression Rating Scale (HAMD) was administered. T1-weighted anatomical images were obtained and analyzed. Correlation analysis was used to identify the possible associations between changed regional GM volume and GI symptoms and depressive symptoms.Results: The HAMD reductive ratio for 2 weeks of treatment in the GI symptoms group was significantly higher than the non-GI symptoms group (P

Yongyu Bai,1 Kai Sun,1 Xiufang Xing,1 Fengjiang Zhang,1 Na Sun,2 Yibo Gao,1 Ling Zhu,3 Jie Yao,3 Junqiang Fan,3 Min Yan11Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China; 3Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, People’s Republic of ChinaObjective: To study the general efficacy of hydromorphone as a systemic analgesic in postoperative pain management following single-port video-assisted thoracoscopic surgery (VATS) and to explore the optimal administration regimen.Methods: A prospective, randomized, double-blind study was designed and conducted in a tertiary hospital. In total, 157 valid patients undergoing single-port VATS were randomly allocated into three groups. A total of 53 patients received morphine bolus only for postoperative analgesia (Group Mb); 51 patients received a hydromorphone background infusion plus bolus (Group Hb+i), and 53 patients received a hydromorphone bolus only (Group Hb). The primary outcomes were patient-reported static and dynamic pain levels; the secondary outcomes included side effects, sleep quality, and recovery indexes.Results: Patients in Group Hb+i experienced lower pain intensity (approximately 10 out of 100 on the visual analog scale) in both static pain and dynamic pain in the days following surgery (P

Alzheimer’s disease and related dementias (ADRD) remain a public health challenge in developing counties. We developed a needs-based essential care service package (ECSP) for care planning of persons living with dementia (PLWD) using a cross-sectional survey among PLWD in institutions in six cities in China (n= 1,299). Face-to-face interviews were conducted with caregivers of PLWD by trained staff between 2018 and 2019. Care service needs and utilization by the level of cognitive impairment were summarized. The average age of PLWD was 80.7 years. 76% of participants had severe cognitive impairment. The needs-based ECSP with 30 service items would be sufficient in supporting care services of PLWD in China, of which seven items are core care. The selection plan for ECSP at different levels is designed as “General Care Services + Selective Care Services”, in which service items for low-, mid-and high-level care for PLWD are 7+3, 7+6, and 7+10, respectively. The findings provide the first large-scale data on service needs and utilization of PLWD in mainland China. The ECSP for PLWD advanced in the paper was a practicable and effective quantitative management means. It is deserved to application in a large scale.

Asymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiological significance of anthracosis is debatable. Using in situ high mass resolution matrix-assisted laser desorption/ionization (MALDI) fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging analysis, we discovered noxious carbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines, or aromatic amines, in a series of 330 lung cancer patients in highly variable and unique patterns. The characteristic nature of carbon-bound exogenous compound had a strong association with patient outcome, tumor progression, the tumor immune microenvironment, PD-L1 expression, and DNA damage. Spatial correlation network analyses revealed substantial differences in the metabolome of tumor cells compared to tumor stroma depending on carbon-bound exogenous compounds. Overall, the bioactive pool of exogenous compounds is associated with several changes in lung cancer pathophysiology and correlates with patient outcome. Given the high prevalence of anthracosis in the lungs of adult humans, future work should investigate the role of carbon-bound exogenous compounds in lung carcinogenesis and lung cancer therapy.

SN 2014C was an unprecedented supernova (SN) that displayed a metamorphosis from Type Ib to Type IIn over ∼200 d. This transformation is consistent with a helium star having exploded in a cavity surrounded by a dense shell of the progenitor’s stripped hydrogen envelope. For at least 5 yr post-explosion, the ejecta continued to interact with an outer, extended component of circumstellar medium (CSM) that was ejected even before the dense shell. It is still unclear, however, what kind of progenitor could have undergone such a complicated mass-loss history before it produced this peculiar SN. In this paper, we report a new analysis of SN 2014C’s host star cluster based on data from the Hubble Space Telescope (HST). By carefully fitting its spectral energy distribution (SED), we derive a precise cluster age of 20.0+3.5−2.6 Myr, which corresponds to the progenitor’s lifetime assuming coevolution. Combined with binary stellar evolution models, we find that SN 2014C’s progenitor may have been an ∼11-M⊙ star in a relatively wide binary system. The progenitor’s envelope was partially stripped by Case C or Case BC mass transfer via binary interaction, followed by a violent eruption that ejected the last hydrogen layer before terminal explosion. Thus, SN 2014C, in common with SNe 2006jc and 2015G, may be a third example that violent eruptions, with mass-loss rates matching luminous blue variable (LBV) giant eruptions, can also occur in much lower mass massive stars if their envelopes are partially or completely stripped in interacting binaries.

Tremendous progress has been made on boosting the performance of magnetoelecric sensor to detect low frequency magnetic field signal by frequency multiplication based on magnetolectric composites. In this paper, a novel magnetoelectric sensor based on the laminated Metglas/piezoelectric quartz crystal/Metglas composites structure is presented. The Metglas foils are bonded symmetrically on both sides of the X-cut quartz crystal plate with epoxy. Experiments showed that the ME composites sensor was able to achieved a limit of detection of 11 pT for a low frequency magnetic field 1 Hz without any bias field through frequency multiplication method. The noise power spectrum density of the sensor has also been tested to be 3.93·10-6 V/Hz1/2 at 1 Hz. The results indicate that the proposed sensor has favorable features, which provides a cost-effective and high-performance approach for low frequency magnetic field measurement. Keywords: Low frequency, limit of detection, magnetoelectric sensor, piezoelectric quartz crystal.

He W, Luo Y, Liu JP, et al. Clin Interv Aging. 2020;15:1809– 1820. The authors have advised affiliation 2 on page 1809 isincorrect, the text “Peking Union Medical College” shouldread “Graduate School of Peking Union Medical College”. The authors apologize for this error.Read the original article

Background Multiple reports have highlighted important racial and ethnic differences in the degree to which Americans may be vulnerable to severe forms of Covid-19 illness. Whether or not racial or ethnic disparities are related to variations in the underlying burden of comorbidities or other predisposing factors remains unclear.Methods We identified patients diagnosed with Covid-19, based on a positive PCR for SARS-CoV-2, from the electronic health record of a large multi-hospital system located in Southern California. We developed an illness severity score, based on the level of care each patient required (not admitted to the hospital; required hospital admission but never required intensive care; required intensive level care but never intubation; and, required intubation during hospitalization) and assessed for associations with clinical and demographic factors for each patient using ordinal logistic regression.Results A total of 571 patients with Covid-19 were identified a majority of whom were male (56%), with a mean age of 55±21 years. There were 81 (14%) patient who identified as African American, and 101 (18%) as Hispanic. A total of 202 (36%) patients required hospitalization without need for intensive care, 43 (8%) required intensive care without intubation, and 64 (11%) required intubation while also receiving intensive care. Of the total sample, African American race (OR 2.33, 95% CI 1.44-3.78, P=0.001) and Hispanic ethnicity (OR 1.97, 95% CI 1.14-3.12, P=0.004) were associated with greater illness severity.Conclusions Racial and ethnic disparities in the severity of Covid-19 illness persist, even when controlling for baseline comorbidities. It remains unclear if these differences are related to variations in physiologic response to SARS-CoV-2, differential timing of presentation or disparities in care.

© 2018 Institute of Process Engineering, Chinese Academy of Sciences This scale-up study demonstrated the feasibility of an ionic liquid (IL) pretreatment process at 40 kg scale, using the IL 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]) as the solvent. The pretreatment was followed by enzymatic hydrolysis through which the process efficiency for biomass conversion to monomeric sugars was determined. The results show that 43 wt% of switchgrass was dissolved in IL after 2 h of pretreatment at 160 °C with 15 wt% solid loading. A 120 h enzymatic hydrolysis of the pretreated switchgrass results in 96% glucan and 98% xylan conversion. [C2C1Im][OAc] pretreatment has been successfully scaled up to 40 kg with improved sugar titers and yields relative to bench scale (6 kg). The mass flow of the overall process was established and the major scale-up challenges of the process were identified.

Xiao-Ji Lin,1 Li-Meng Cai,2 Zi-Jun Qian,2 Chen-Yi Wang,2 Ni Sun,1 Xiao-Hai Sun,1 He Huang,1 Wen-Jian Guo,1 Hai-Yan Lin,1 Rong-Xin Yao1 1Department of Haematology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 2Science and Technology of Students Association, The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Objective: This study aims to investigate ectopic expression of histone deacetylase 6 (HDAC6) in diffuse large B-cell lymphoma (DLBCL). Methods: This study analyzed patients with DLBCL (n=132) and reactive lymph node hyperplasia (n=32) diagnosed in our hospital from December 2007 to May 2016. Correlation between HDAC6 expression and clinical pathologic features was analyzed by χ2 test. The significant differences between the 5-year overall survival (OS) or progression-free survival (PFS) and high HDAC6 expression as well as DLBCL clinic-pathological features including age, International Prognostic Index (IPI) score, Eastern Cooperative Oncology Group score, lactate dehydrogenase (LDH), and germinal center B-cell-like were assessed by univariate and multivariate analyses. Results: HDAC6 high-expression percentage in DLBCL was significantly higher than that in the control group. The proportion of IPI score of 0–2, 5-year OS, and PFS in the high-expression group, which had lower percentage of patients with increased LDH and β2-microglobulin, were significantly higher than those in the low-expression group. Moreover, HDAC6 mRNA expression in HDAC6 protein low expression was markedly lower than that in protein high expression. The multivariate analysis demonstrated that HDAC6 high expression was an independent prognostic factor for patients with DLBCL. Conclusion: HDAC6 high expression might be a prognostic factor for DLBCL. Keywords: diffuse large B-cell lymphoma, HDAC6, prognosis

Xiwen Liao,1,* Rui Huang,2,* Xiaoguang Liu,1,3 Chuangye Han,1 Long Yu,1,4 Shijun Wang,5 Na Sun,2 Bopei Li,6 Xin Ning,7 Tao Peng1 1Department of Hepatobiliary Surgery, 2Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 3Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 4Department of Hepatobiliary and Pancreatic Surgery, 5Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 6Department of Gastrointestinal Surgery, 7Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China *These authors contributed equally tothis work Background: Alcohol dehydrogenase (ADH) isoenzymes have been reported as a potential diagnostic marker for pancreatic cancer, but their prognostic value in pancreatic cancer remains unclear. The aim of this investigation was to identify the prognostic value of ADH genes in human patients with pancreatic adenocarcinoma (PAAD).Materials and methods: An RNA sequencing dataset and corresponding survival profiles of PAAD were obtained from The Cancer Genome Atlas. Survival analysis and gene set enrichment analysis were used to investigate the prediction value and potential mechanism of ADH genes in PAAD prognosis.Results: Survival analysis of ADH genes suggests that a high expression of ADH1A (adjusted P=0.037, adjusted hazard ratio [HR] =0.627, 95% CI =0.404–0.972) and ADH6 (adjusted P=0.018, adjusted HR =0.588, 95% CI =0.378–0.914) were associated with a significantly decreased risk of death, while a high expression of ADH5 was associated with a significantly increased risk of death (adjusted P=0.043, adjusted HR =1.564, 95% CI =1.013–2.414). Joint effects analysis of three ADH gene prognostic markers suggests that the prognosis difference for any marker combination was more significant than that for any individual marker. The potential mechanism of ADH1A and ADH6 in PAAD prognosis was that a high expression of ADH1A and ADH6 was involved in the P450 pathway and biological processes, while high ADH5 expression was involved in transforming growth factor β regulation-related pathways and biological processes, Wnt, the cell cycle, ErbB, and mitogen-activated protein kinase signaling pathways.Conclusion: Our data suggest that ADH1A, ADH5, and ADH6 expression may be potential prognostic markers of PAAD and in combination have a strong interaction and better predictive value for PAAD prognosis. Keywords: prognostic, alcohol dehydrogenase, pancreatic adenocarcinoma, TCGA, GSEA

BACKGROUND: Orbifloxacin is being widely used in China to treat fish infections in an extra-label manner, which may cause its potential residues in edible tissues. AIMS: The purpose of this study was to determine the disposition kinetics of orbifloxacin in crucian carp (Carassius auratus) following intramuscular administration for its further safe application in aquaculture industry. METHODS: Tissue samples of skin, muscle, kidney, and liver were collected from six crucian carps reared at 25°C at 5, 10, 15, 30, 45 min, 1, 2, 4, 6, 12, 24, 48, 72, and 96 h following a single intramuscular injection at 7.5 mg/kg body weight (BW). The orbifloxacin concentrations in tissues were determined using a high-performance liquid chromatography (HPLC) method with a fluorescence detector, then average concentrations versus time data were subjected to non-compartmental analysis to obtain the kinetic parameters. RESULTS: The peak concentration of 5.68 ± 0.03 µg/g was calculated in kidney at 2 h, followed by muscle (5.51 ± 0.01 µg/g) at 4 h, liver (4.84 ± 0.20 µg/g) at 2 h, and skin (4.27 ± 0.08 µg/g) at 4 h. Area under concentration-time curve was calculated as 79.22, 94.72, 118.65, and 129.02 h·µg/g in kidney, liver, skin, and muscle, respectively. And the elimination half-lives were determined as 18.17, 18.41, 18.77, and 19.11 h in skin, kidney, muscle, and liver, respectively. CONCLUSION: It was shown that orbifloxacin was well distributed into tissues while relatively slowly eliminated in crucian carp reared at 25°C following a single intramuscular injection.

Shu Liu,1,* Fuxi Zhen,2,* Nana Sun,3 Jiayan Chen,1 Yuandong Cao,1 Sheng Zhang,1 Hongyan Cheng,4 Xiaolin Ge,1 Xinchen Sun1 1Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Radiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of General Internal Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Purpose: Previous studies have demonstrated that apparent diffusion coefficient (ADC) values measured by magnetic resonance imaging have prognostic value in patients with esophageal squamous cell carcinoma (ESCC). However, the role of ADC needs to be validated in a cohort of Chinese ESCC patients. This study assessed the role of ADC in predicting the outcome of patients with ESCC treated only by chemoradiation in the People’s Republic of China. Patients and methods: Seventy-three patients with local advanced ESCC were retrospectively analyzed in this study; none of the patients underwent surgery before or after chemoradiation. The ADC values of the primary tumors were determined by magnetic resonance imaging. The ADC values were then correlated with clinicopathological and other radiological parameters. Survival analysis was carried out to determine if ADC had an impact on survival of these patients. Results: The median ADC value of the esophageal cancer tissue was 1.256*10-3 mm2/sec (range: 0.657–2.354*10-3 mm2/sec, interquartile range 0.606*10-3 mm2/sec). No clinicopathological or radiological parameters were associated with the ADC values except the sites of tumor tissues. ADC

Importance: There is an urgent need to improve lung cancer risk assessment as current screening criteria miss a large proportion of cases. Objective: To determine if a panel of selected circulating protein biomarkers can contribute to lung cancer risk assessment and outperform current US screening criteria. Design, Setting and Participants: Pre-diagnostic samples from ever-smoking cases diagnosed within one year of blood collection and smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk-score based on 4 proteins (CA125, CEA, CYFRA 21-1 and Pro-SFTPB). The biomarker score was subsequently validated blindly using absolute risk-estimates in ever-smoking cases diagnosed within one year of blood collection and matched controls from two large European population-based cohorts; the European Prospective Investigation into Cancer and nutrition (EPIC) study and the Northern Sweden Health and Disease Study (NSHDS). Main Outcome and Measures: Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under receiver-operating characteristics curve [AUC], sensitivity and specificity). Results: In the validation study, an integrated risk-prediction model combining smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI: 0.76-0.90) compared to 0.73 (95% CI: 0.64-0.82) for a model based on smoking exposure alone (P=0.003 for difference in AUC). At an overall specificity of 0.83 based on the USPSTF screening criteria, the sensitivity of the integrated risk-prediction model (biomarker) model was 0.63 compared to 0.43 for the smoking model. Conversely, at an overall sensitivity of 0.42 (USPSTF), the integrated risk-prediction model yielded a specificity of 0.95 compared to 0.86 for the smoking model. Conclusions and Relevance: This study provided a proof-of-principle in demonstrating that a panel of circulating protein biomarkers can improve lung cancer risk assessment and may be used to define eligibility for CT-screening.

Copyright © 2018 American Chemical Society. Postconsumer absorbent hygiene products (AHPs), one of the most intractable municipal solid waste (MSW) streams, are generally subjected to landfills, causing urban waste management difficulties and environmental pollution. This study investigated the viability of recycling the cellulose component from postconsumer AHPs, demonstrated the fermentability of obtained cellulosic sugars for bioethanol production, and evaluated the technical feasibility of the process through scale-up. A set of integrated unit operations was developed to effectively upcycle the recovered AHPs into bioproducts. The processes were further optimized and scaled up 50-fold. Up to 83.5% glucose and 46.0% xylose yields were achieved during enzymatic saccharification. The sugars were readily fermentable through separate hydrolysis and fermentation (SHF) as well as simultaneous saccharification and fermentation (SSF) with maximum 89.9% ethanol theoretical yield.

Proteins predicted to be composed of large stretches of coiled-coil structure have often proven difficult to crystallize for structural determination. We have successfully applied EPR spectroscopic techniques to the study of the structure and assembly of full-length human vimentin assembled into native 11 nm filaments, in physiologic solution, circumventing the limitations of crystallizing shorter peptide sequences. Tektins are a small family of highly alpha helical filamentous proteins found in the doublet microtubules of cilia and related structures. Tektins exhibit several similarities to intermediate filaments (IFs): moderate molecular weight, highly alpha helical, hypothesized to be coiled-coil, and homo- and heteromeric assembly into long smooth filaments. In this report, we show the application of IF research methodologies to the study of tektin structure and assembly. To begin in vitro studies, expression constructs for human tektins 1, 2, and 4 were synthesized. Recombinant tektins were produced in E. coli and purified by chromatography. Preparations of tektin 1 successfully formed filaments. The recombinant human tektin 1 was used to produce antibodies which recognized an antigen in mouse testes, most likely present in sperm flagella. Finally, we report the creation of seven mutants to analyze predictions of coiled-coil structure in the rod 1A domain of tektin 1. Although this region is predicted to be coiled-coil, our EPR analysis does not reflect the parallel, in register, coiled-coil structure as demonstrated in vimentin and kinesin. These results document that tektin can be successfully expressed and assembled in vitro, and that SDSL EPR techniques can be used for structural analysis.

Chemistry of molecular sуstems

Protein lysine acetylation is recognized as an important reversible post translational modification in all domains of life. While its primary roles appear to reside in metabolic processes, lysine acetylation has also been implicated in regulating pathogenesis in bacteria. Several global lysine acetylome analyses have been carried out in various bacteria, but thus far there have been no reports of lysine acetylation taking place in the important human pathogen Vibrio cholerae. In this study, we analyzed the lysine acetylproteome of the human pathogen V. cholerae V52. By applying a combination of immuno-enrichment of acetylated peptides and high resolution mass spectrometry, we identified 3,402 acetylation sites on 1,240 proteins. Of the acetylated proteins, more than half were acetylated on two or more sites. As reported for other bacteria, we observed that many of the acetylated proteins were involved in metabolic and cellular processes and there was an over-representation of acetylated proteins involved in protein synthesis. Of interest, we demonstrated that many global transcription factors such as CRP, H-NS, IHF, Lrp and RpoN as well as transcription factors AphB, TcpP, and PhoB involved in direct regulation of virulence in V. cholerae were acetylated. In conclusion, this is the first global protein lysine acetylome analysis of V. cholerae and should constitute a valuable resource for in-depth studies of the impact of lysine acetylation in pathogenesis and other cellular processes.

Chemistry of molecular sуstems