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Objectives: The emergence and dissemination of colistin-resistant Enterobacterales has become a major global public-health threat. Here we investigated the genomic and phylogenetic characteristics of a multidrug-resistant Klebsiella pneumoniae strain (KP4823) carrying the mcr-1 gene recovered from a urinary tract infection in China., Methods: Antimicrobial susceptibility of K. pneumoniae KP4823 was determined by broth microdilution. Whole genomic DNA was extracted and sequenced using Oxford Nanopore MinION and Illumina NovaSeq 6000 platforms. Hybrid assembly with long and short reads was performed using Unicycler, and the genome was annotated using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). The sequence type (ST), capsular type, and antimicrobial resistance and virulence genes were identified from the genome sequence. Core genome multilocus sequence typing (cgMLST) analysis was performed by BacWGSTdb 2.0 server., Results: Klebsiella pneumoniae KP4823 was resistant to colistin, ceftazidime, cefepime, cefotaxime, fosfomycin and aztreonam. The complete genome sequence of KP4823 consists of five contigs comprising 5 445 519 bp, including one chromosome and four plasmids. The isolate was assigned to ST101 with capsular serotype KL106. Several antimicrobial resistance genes were identified, including the colistin resistance gene mcr-1, which was located on a 34 685-bp IncX4 plasmid. The closest relative of K. pneumoniae KP4823 was another ST101 isolate (08EU827) recovered from Sweden in 2008, which differed by 191 cgMLST loci., Conclusion: Our study reports the genome sequence of a multidrug-resistant mcr-1-carrying K. pneumoniae in China. These data may help to understand the antimicrobial resistance mechanisms, genomic features and transmission dynamics of colistin resistance in clinical settings., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cardiovascular disease (CVD), reported to relate with climate change, is the leading cause of global mortality and morbidity. Since the relevant information is quite limited from suburbs and countryside in developing and underdeveloped countries, there are no studies that focused on morbidity through diurnal temperature range (DTR) for these regions. This is the first study to evaluate the short-term effect of DTR on CVD hospital admission in suburban farmers, as well as to identify vulnerable subpopulations. Daily time series data of CVD hospital admissions on suburban farmers of Qingyang, China, and meteorological data from 2011 to 2015 were collected, and a distributed lag non-linear model (DLNM) combined with a quasi-Poisson generalized additive regression model (GAM) was used to examine the exposure-response relationship and delayed effect between DTR and CVD hospital admissions. Stratified analyses by age and gender were performed and extreme DTR effects were examined. Non-linear relation between DTR and CVD hospital admissions was observed, and whether DTR lower or higher than the reference (13 °C, 50 th percentile) had adverse effect while lower DTR have slightly higher impact. Also, both extreme low and extreme high DTR had adverse effect. Besides, adults (age < 65) and males were more vulnerable to the effects of DTR compared with the old (age ≥ 65) and females, respectively. This study provides evidence that not only high DTR but also low DTR had adverse effects on CVD which should be paid attention to. Adults and males were more vulnerable among suburban farmers. The results are inconsistent with the studies from urban and indicate differences between urban and suburban residents. Multiple factors such as occupations, risk awareness, and lifestyles could have a significant influence on CVD morbidity, and further study is needed to explore more evidence., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A practical route to 2-(2-(2-methyl-1,3-dioxolan-2-yl)ethyl)cyclohexan-1-one was developed, featuring the use of inexpensive starting materials/reagents and readily attainable reaction conditions. The overall transformation was achieved in 53% yield with one chromatographic purification via NaOH-mediated aldol condensation, ethylene glycol protection of the ketone group in the presence of HC(OEt) 3 /concd HCl, saturation of the C=C bond and the benzene ring with Al-Ni alloy in aqueous KOH, and oxidation of the intermediate cyclohexanol with aqueous NaClO/TEMPO/KBr., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Detection of epidermal growth factor receptor (EGFR) is one real dilemma owing to the non-sufficient tissue for testing EGFR mutations in lung adenocarcinoma. A model for predicting EGFR mutations would be helpful for clinical decisions in those patients. A retrospective cohort of 1,196 patients diagnosed with lung adenocarcinoma was investigated between December 1, 2017, and December 31, 2019, in Renji Hospital, Shanghai, China. All patients were tested for EGFR mutations (amplification refractory mutation system, n=1,144; next-generation sequencing, n=52). Of 1,196 patients with lung adenocarcinoma, 944 met the inclusion criteria. A nomogram model was developed based on 567 patients and validated in 377 patients. Variables associated with EGFR mutations were age, sex, smoking history, lepidic predominant subtype, solid predominant subtype, mucinous adenocarcinoma, Ki67 expression, lobulation, solid texture in radiology, and pleural retraction. The nomogram based on the model performed well in the development group (c-index 0.789, 95% CI: 0.751-0.827), and the validation group (c-index 0.809, 95% CI: 0.771-0.847). At the probability cut-point of 0.7, the diagnostic efficiency was 82.7% in patients with NGS liquid biopsy. Decision curve analysis further confirmed the clinical usefulness of the nomogram, which showed that predicting the EGFR mutations probability applying this nomogram would be better than having all patients or none patients use this nomogram. A high probability group (>0.7) by nomogram model may suggest a high possibility of EGFR mutation, if tissue is limited, NGS-based ctDNA with liquid biopsy could be implemented effectively.

Metal-complexed dyes are harmful to the environment and human health because they contain heavy metals and complex organic ligands. It is difficult to separate and recover these dyes from wastewater owing to their complex components and poor selectivity of common adsorbents. In this study, a novel surface molecularly imprinted polymer (SMIP) was prepared using 4-vinyl pyridine as the functional monomer and polystyrene resin as the carrier. SMIP showed better adsorption performance than non-imprinted polymer (SNIP) in the whole pH range with the best adsorption capacity at pH 1.5. The correlation coefficients (R 2 ) fitted by Langmuir and Temkin models were greater than 0.97, and the adsorption was a spontaneous exothermic process. The pseudo-second-order and Elovich models fitted the adsorption kinetic curves well. The adsorption capacity of SMIP was approximately 20% higher than that of SNIP in the salt concentration ranging from 2 to 80 mg/L. In selective adsorption experiments, the relative selectivity coefficients (I) of SMIP for competitors were all greater than 2.41, and the Cr (Ⅲ) components of ACB GGN played a more important role in the recognition performance of SMIP than the sulfonic groups. Adsorption mechanism tests revealed that although the adsorption of ACB GGN by SMIP mainly relied on electrostatic attraction, hydrophobic interactions, π-π conjugation, and Cr (Ⅲ) coordination were also involved. These results show that SMIP has excellent selective adsorption properties for ACB GGN and a promising application potential in the treatment of metal-complexed dye wastewater., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Digestive endoscopy and surgery are the primary invasive methods for the clinical treatment of necrotizing pancreatitis. However, there are relatively few studies evaluating the effectiveness and safety of these two methods., Methods: Randomized controlled trials (RCTs) on endoscopic and surgical treatment of necrotizing pancreatitis published from January 2000 to December 2020 were searched in the PubMed, Medline, Embase, China Biology Medicine Disc (CBM), and WanFang databases. The Cochrane System Review Manual was adopted to evaluate the quality of the included literature, and Review Manager 5.3 was used for data analysis., Results: Ten articles were included in this meta-analysis, involving a total of 401 patients, including 188 in the endoscopy group and 213 in the surgery group. Meta-analysis results revealed that the clinical remission rate (CRR) [odds ratio (OR) =1.30, 95% confidence interval (CI): 0.58-2.92, P=0.52], new organ failure rate (OFR) (OR =0.53, 95% CI: 0.26-1.09, P=0.08), abdominal bleeding rate (ABR) (OR =0.62, 95% CI: 0.33-1.15, P=0.13), and intensive care unit (ICU) stay time (IST) [mean deviation (MD) =-7.33, 95% CI: -16.76 to 2.11, P=0.13] were not significantly different between the endoscopy and surgery groups. In the endoscopy group, the mortality rate (OR =0.56, 95% CI: 0.31-1.02, P=0.05), intestinal fistula rate (IFR) or gastrointestinal perforation rate (GPR) (OR =0.50, 95% CI: 0.26-0.99, P=0.05), and pancreatic fistula rate (PFR) (OR =0.09, 95% CI: 0.04-0.23, P<0.00001) were markedly lower compared to the surgery group., Discussion: There was no obvious difference in the clinical efficacy of endoscopic and surgical treatment of necrotizing pancreatitis. However, endoscopy can greatly reduce the incidence of postoperative death and major complications in patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-516). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Objectives: This study explores the concentration and role of glucagon-like peptide-1 (GLP-1) in calcific aortic valve disease (CAVD). Background: Calcific aortic valve disease is a chronic disease presenting with aortic valve degeneration and mineralization. We hypothesized that the level of GLP-1 is associated with CAVD and that it participates in the calcification of aortic valve interstitial cells (AVICs). Methods: We compared the concentration of GLP-1 between 11 calcific and 12 normal aortic valve tissues by immunohistochemical (IHC) analysis. ELISA was used to measure GLP-1 in serum of the Control ( n = 197) and CAVD groups ( n = 200). The effect of GLP-1 on the calcification of AVICs and the regulation of calcific gene expression were also characterized. Results: The GLP-1 concentration in the calcific aortic valves was 39% less than that in the control non-calcified aortic valves. Its concentration in serum was 19.3% lower in CAVD patients. Multivariable regression analysis demonstrated that GLP-1 level was independently associated with CAVD risk. In vitro , GLP-1 antagonized AVIC calcification in a dose- and time-dependent manner and it down-regulated RUNX2, MSX2, BMP2, and BMP4 expression but up-regulated SOX9 expression. Conclusions: A reduction in GLP-1 was associated with CAVD, and GLP-1 participated in the mineralization of AVICs by regulating specific calcific genes. GLP-1 warrants consideration as a novel treatment target for CAVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xiao, Zha, Zhang, Wu, Chen, Yang, Yang and Liu.)

Background: The coronavirus disease 2019 (COVID-19) has induced a worldwide epidemiological event with a high infectivity and mortality. However, the predicting biomarkers and their potential mechanism in the progression of COVID-19 are not well known., Objective: The aim of this study is to identify the candidate predictors of COVID-19 and investigate their underlying mechanism., Methods: The retrospective study was conducted to identify the potential laboratory indicators with prognostic values of COVID-19 disease. Then, the prognostic nomogram was constructed to predict the overall survival of COVID-19 patients. Additionally, the scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of the most important prognostic indicators in lungs and peripherals, respectively., Results: In total, 304 hospitalized adult COVID-19 patients in Wuhan Jinyintan Hospital were included in the retrospective study. CEA was the only laboratory indicator with significant difference in the univariate (P < 0.001) and multivariate analysis (P = 0.020). The scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of CEA in lungs and peripherals, respectively. The results revealed the potential roles of CEA were significantly distributed in type II pneumocytes of BALF and developing neutrophils of PBMCs, participating in the progression of COVID-19 by regulating the cell-cell communication., Conclusion: This study identifies the prognostic roles of CEA in COVID-19 patients and implies the potential roles of CEACAM8-CEACAM6 in the progression of COVID-19 by regulating the cell-cell communication of developing neutrophils and type II pneumocyte.

To explore the photosynthetic response of short-term high-temperature treatments to the leaves of different grape varieties (Shenyue and Shenfeng), we performed 45°C treatments on annual potted grapes in an artificial climate chamber to simulate the summer high-temperature period. We measured the rapid A-Ci response curve, 1,5-ribulose bisphosphate carboxylase/oxygenase (Rubisco) activity and chlorophyll a fluorescence. Photosynthetic performance-related parameters of grapevine leaves were found to be adversely affected by high temperature; the maximum rates of carboxylation of Rubisco and ribulose diphosphate regeneration and Rubisco activity were all significantly reduced. The JI of the JIP-test curve disappeared under high-temperature treatment, and the K peak appeared, indicating that the oxygen-evolving complex (OEC) had been destroyed. Principal component analysis showed that PSII activity (F v /F m , DF ABS , φ Eo , ABS/RC) was greatly affected by high temperature. It was also found that the Rubisco activity and OEC destruction strength were greater in one of the cultivars, and we were able to determine heat resistance based on the phenotype and photosynthetic performance. It can be seen from the above that Shenyue leaves have higher heat tolerance and stronger photosynthetic performance than Shenfeng leaves. This shows that photosynthetic performance is strongly correlated with a grapevine's tolerance to abiotic stress., (© 2021 American Society for Photobiology.)

Purpose: Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) overexpression has been reported in various types of cancers. The purpose of this study is to clarify the role of NUCKS, underlying the involvement of non-small-cell lung cancer, in the progression of lung cancer., Methods: The small interfering ribonucleic acid (siRNA) of NUCKS was transfected into a lung cancer cell line (NCI-H460, A549, NCI-H1299 and NCI-H1975). Functional experiments (MTT assay, Annexin V-FITC/PI double staining assay, colony formation assay, wound healing assay and Transwell assay) were performed to measure the effects of NUCKS on lung cancer cell viability, migration, invasion and apoptosis., Results: NUCKS was found to be up-regulated in lung cancer cells. Knockdown of NUCKS significantly altered lung cancer cell apoptosis, proliferation colony formation, invasion and migration. Moreover, knockdown of NUCKS attenuated the activation of the PI3K/AKT pathway in lung cancer cells., Conclusion: NUCKS was overexpressed in lung cancer cells and played an important role in lung cancer by increasing cell growth through the PI3K/AKT signalling pathway. This in vitro study suggested NUCKS should be evaluated in a clinical setting as a novel biomarker and potential therapeutic target for lung cancer.

Introduction: Osteoporosis is one of the important bone abnormalities in chronic kidney disease-mineral and bone disorder (CKD-MBD) and still lacks a sensitive biomarker to diagnose. Fibroblast growth factor 21 (FGF21) can stimulate bone loss in patients with diabetes and increase in CKD patients. In this study, we investigated whether FGF21 could serve as a biomarker to predict osteoporosis in a haemodialysis cohort., Methods: We recorded demographic information, biochemical data, and serum FGF21 and FGF23 levels and measured the CT attenuation values of 339 haemodialysis patients from two large medical centres. We assessed the correlation of CT attenuation values with serum FGF21 and FGF23 levels and tested whether they were independent factors for osteoporosis. ROC curves were constructed to compare the prognostic value of FGF21 and FGF23 for osteoporosis., Results: Based on the CT attenuation value, serum FGF21 levels were higher in our osteoporosis group (median 640.86 pg/ml vs. 245.46 pg/ml, P ˂ 0.01). Meanwhile, FGF21 (r = -0.136, P < 0.05) and FGF23 (r = -0.151, P < 0.05) were both negatively associated with osteoporosis. Moreover, FGF21 (β = -0.067, P < 0.05) was an independent factor for osteoporosis. Furthermore, FGF21 combined with age yielded a marked specificity (90.5 %) and sensitivity (61.8 %) in predicting osteoporosis of haemodialysis patients with less residual renal function., Conclusions: FGF21 has a positive relationship with the incidence of osteoporosis in patients on haemodialysis. FGF21 combined with age is a good predictive biomarker for osteoporosis in patients on haemodialysis, especially those with less residual renal function.

Cardiovascular disease (CVD) has been a major threat to global public health. The association between temperature and CVD has been widely studied and reported in cities in developed countries. However, information from developing countries, especially from suburbs and countryside, is quite limited. In this study, the daily time series data on CVD hospital admissions in farmers in the suburbs of Tianshui, China, and the meteorological data from 2012 to 2015, were collected; besides, a quasi-Poisson regression with a distributed-lag non-linear model (DLNM) was used to explore the impact of local daily mean temperature on CVD hospital admissions in suburban farmers. This study found that, first, from 2011 to 2015, a total of 30,611 person-times of CVD hospital admissions in farmers were recorded; second, there was a "J-shaped" relation between temperature and CVD hospital admissions, and both low and high temperature increased the risk of hospital admission, but the impact of high temperature was greater; third, compared with the minimum hospitalization temperature (MHT) at 0.3 °C, during 0 to 21 lag days, the cumulative relative risk (RR) for extreme cold and heat (1st and 99th percentile of temperature, respectively) was 1.117 (95% CI 0.941-1.325) and 1.740 (95% CI 1.302-2.327), respectively, and that of moderate cold and heat (5st and 95th percentile of temperature, respectively) was 1.029 (95% CI 0.958-1.106) and 1.572 (95% CI 1.210-2.042), respectively; fourth, compared with male and ≥ 65 years groups, the risk for low temperature was greater for female and < 65 years groups, the risk for high temperature was just the opposite; last, about 21.04% of CVD hospital admissions burden were attributed to the ambient temperature, and most of (about 19.26%) were caused by moderate heat. In Tianshui, alongside with extreme temperature, the moderate temperature might be an important risk factor for CVD hospital admissions in suburban farmers., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Due to their highly porous structures, metal organic framework materials are widely used in analytic areas. In this paper, Cr-metal organic framework (MIL-101(Cr)) modified electrode was prepared and then was used as electrochemical sensor for the detection of bisphenol A (BPA). By using one kind of surfactant of cetyltrimethylammonium bromide (CTAB), the analytic performances of MIL-101 (Cr) towards BPA detection were greatly improved. Compared with pure MIL-101 (Cr), the differential pulse voltammetry (DPV) behavior of CTAB/MIL-101 (Cr) was improved 3.0 times in the presence of BPA. The hydrophobic long chain alkanes of CTAB can improve the enrichment and electrochemical oxidation for BPA. The CTAB/MIL-101 (Cr) sensor exhibited a linear range from 20 to 350 nM and a low detection limit of 9.95 nM (LOD = 3s b /S) and showed good reproducibility, stability and selectivity. Finally, real samples of dusts from E-waste recycling area in South China were collected and the CTAB/MIL-101 (Cr) sensor demonstrated satisfactory results for BPA detection from these dust samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Iodic acid (HIO 3 ) is known to form aerosol particles in coastal marine regions, but predicted nucleation and growth rates are lacking. Using the CERN CLOUD (Cosmics Leaving Outdoor Droplets) chamber, we find that the nucleation rates of HIO 3 particles are rapid, even exceeding sulfuric acid-ammonia rates under similar conditions. We also find that ion-induced nucleation involves IO 3 - and the sequential addition of HIO 3 and that it proceeds at the kinetic limit below +10°C. In contrast, neutral nucleation involves the repeated sequential addition of iodous acid (HIO 2 ) followed by HIO 3 , showing that HIO 2 plays a key stabilizing role. Freshly formed particles are composed almost entirely of HIO 3 , which drives rapid particle growth at the kinetic limit. Our measurements indicate that iodine oxoacid particle formation can compete with sulfuric acid in pristine regions of the atmosphere., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Reactive iodine plays a key role in determining the oxidation capacity, or cleansing capacity, of the atmosphere in addition to being implicated in the formation of new particles in the marine boundary layer. The postulation that heterogeneous cycling of reactive iodine on aerosols may significantly influence the lifetime of ozone in the troposphere not only remains poorly understood but also heretofore has never been observed or quantified in the field. Here, we report direct ambient observations of hypoiodous acid (HOI) and heterogeneous recycling of interhalogen product species (i.e., iodine monochloride [ICl] and iodine monobromide [IBr]) in a midlatitude coastal environment. Significant levels of ICl and IBr with mean daily maxima of 4.3 and 3.0 parts per trillion by volume (1-min average), respectively, have been observed throughout the campaign. We show that the heterogeneous reaction of HOI on marine aerosol and subsequent production of iodine interhalogens are much faster than previously thought. These results indicate that the fast formation of iodine interhalogens, together with their rapid photolysis, results in more efficient recycling of atomic iodine than currently considered in models. Photolysis of the observed ICl and IBr leads to a 32% increase in the daytime average of atomic iodine production rate, thereby enhancing the average daytime iodine-catalyzed ozone loss rate by 10 to 20%. Our findings provide direct field evidence that the autocatalytic mechanism of iodine release from marine aerosol is important in the atmosphere and can have significant impacts on atmospheric oxidation capacity., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Vitis vinifera × Vitis labrusca 'Shenhua' is a tetraploid grape, a Franco-american species. This study first published the complete chloroplast genome of Vitis vinifera × Vitis labrusca 'Shenhua' was assembled. The chloroplast genome is 160928 bp in length, including a large single copy region (89,148 bp), a small single-copy region (19,072 bp) and a pair of inverted repeats of 26,354 bp. The chloroplast genome encodes 133 genes, comprising 88 CDSs, 37 tRNA genes and 8 rRNA genes. The phylogenetic tree demonstrated that Vitis vinifera × Vitis labrusca 'Shenhua' is different from the other 16 varieties., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Two-dimensional Cd-MOF/Tb 3+ (Cd-MOF = [Cd (μ-2,3-pdc) (H 2 O) 3 ] n (2,3-pdc = 2,3-pyridine dicarboxylic acid)) fluorescent nanosheets with the thickness of 1.4 nm were successfully synthesized by a simple solution route with subsequent ultrasonic exfoliation at room temperature. It was found that as-obtained Cd-MOF/Tb 3+ ultrathin nanosheets could be homogeneously dispersed in aqueous system to form a sol with excellent stability. Also, the fluorescence intensity of nanosheets remarkably increased to almost 12 times higher than that of Cd-MOF/Tb 3+ microsheets before exfoliation. Further investigations uncovered that the above strong fluorescence of Cd-MOF/Tb 3+ nanosheets could be highly sensitively quenched by Cefixime antibiotic in aqueous solution without interference from other antibiotics, amino acids and pesticides. Hence, the as-obtained ultrathin Cd-MOF/Tb 3+ nanosheets could be prepared as a highly selective and sensitive fluorescence probe for the detection of Cefixime in aqueous system. Compared with the bulk Cd-MOF/Tb 3+ sensor, the Cd-MOF/Tb 3+ ultrathin nanosheets sensor exhibited a far lower detection limit down to 26.7 nM for CFX. Also, the as-obtained nanosheets sensor presented satisfactory recovery ranging from 98.07% to 103.01% and acceptable repeatability (RSD < 6.29%, n = 6) for the detection of CFX in domestic water. Furthermore, the sensing mechanism studies revealed that the high selection of the present fluorescent probe for detection of CFX should be attributed to the cooperation of the photoinduced electron transfer and the inner filter effect., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is one of the common complex neurodegenerative diseases and characterized by abnormal metabolic brain networks. Fibroblast growth factor 21 (FGF21), an endocrine hormone that belongs to the fibroblast growth factor superfamily, plays an extensive role in the regulation of metabolism. However, our understandings of the specific function and mechanisms of FGF21 on PD are still quite limited. Here we aimed to elucidate the actions and the underlying mechanisms of FGF21 on dopaminergic neurodegeneration using cellular and animal models of parkinsonism. To investigate the effects of FGF21 on dopaminergic neurodegeneration in vivo and in vitro, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine models of PD were utilized, and animals were treated with recombinant FGF21 protein or FGF21 gene delivered via an adeno-associated virus. In the present study, systemic and continuous intracerebroventricular recombinant FGF21 protein administration to mice both prevented behavioral deficits, protected dopaminergic neurons against degeneration, and ameliorated α-synuclein pathology in PD models; and in vivo gene delivery of FGF21 improved PD-like symptoms and pathologies suggesting a potential implication of FGF21 in gene therapy for PD. In vitro evidence confirmed FGF21 mediated neuroprotective benefits against PD pathologies. Further, our data suggested that enhanced autophagy was involved in the FGF21 neuroprotection in PD models, and silent information regulator 2 homolog 1 may play a crucial role in molecular mechanisms underlying anti-PD activities of FGF21., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Nitrate plays an important role in grapevines vegetative and reproductive development. However, how grapevines uptake, translocate and utilize nitrate and the molecular mechanism still remains to be investigated., Results: In this study, we report the functional characterization of VvNPF6.5, a member of nitrate transporter 1/peptide transporter family (NRT1/PTR/NPF) in Vitis vinifera. Subcellular localization in Arabidopsis protoplasts indicated that VvNPF6.5 is plasma membrane localized. Quantitative RT-PCR analysis indicated that VvNPF6.5 is expressed predominantly in roots and stems and its expression is rapidly induced by nitrate. Functional characterization using cRNA-injected Xenopus laevis oocytes showed that VvNPF6.5 uptake nitrate in a pH dependent way and function as a dual-affinity nitrate transporter involved in both high- and low-affinity nitrate uptake. Further ectopic expression of VvNPF6.5 in Arabidopsis resulted in more 15 NO 3 - accumulation in shoots and roots and significantly improved nitrogen use efficiency (NUE). Moreover, VvNPF6.5 might participate in the nitrate signaling by positively regulating the expression of primary nitrate response genes., Conclusion: Our results suggested that VvNPF6.5 encodes a pH-dependent, dual-affinity nitrate transporter. VvNPF6.5 regulates nitrate uptake and allocation in grapevines and is involved in primary nitrate response.

Sulfur trioxide (SO 3 ) is a crucial compound for atmospheric sulfuric acid (H 2 SO 4 ) formation, acid rain formation, and other atmospheric physicochemical processes. During the daytime, SO 3 is mainly produced from the photo-oxidation of SO 2 by OH radicals. However, the sources of SO 3 during the early morning and night, when OH radicals are scarce, are not fully understood. We report results from two field measurements in urban Beijing during winter and summer 2019, using a nitrate-CI-APi-LTOF (chemical ionization-atmospheric pressure interface-long-time-of-flight) mass spectrometer to detect atmospheric SO 3 and H 2 SO 4 . Our results show the level of SO 3 was higher during the winter than during the summer, with high SO 3 levels observed especially during the early morning (∼05:00 to ∼08:30) and night (∼18:00 to ∼05:00 the next day). On the basis of analysis of SO 2 , NO x , black carbon, traffic flow, and atmospheric ions, we suggest SO 3 could be formed from the catalytic oxidation of SO 2 on the surface of traffic-related black carbon. This previously unidentified SO 3 source results in significant H 2 SO 4 formation in the early morning and thus promotes sub-2.5 nm particle formation. These findings will help in understanding urban SO 3 and formulating policies to mitigate secondary particle formation in Chinese megacities., Competing Interests: The authors declare no competing financial interest.

It is long known that dihydroperoxidation of aliphatic aldehydes is extremely difficult and normally stops halfway at the hydroxyhydroperoxide stage. This strange phenomenon now has been explored, and a highly effective protocol for conversion of aliphatic aldehydes into gem -dihydroperoxides has been developed. Silyl protection of primary gem -dihydroperoxides, which is also a challenge due to unexpected based-induced decomposition, was achieved using 2,6-lutidine as the base. The silyl-protected gem -dihydroperoxides were then examined in a peroxycarbenium [3 + 2] cycloaddition reaction with alkenes for the first time. Aromatic substrates normally reacted smoothly, affording the expected 1,2-dioxolanes smoothly. Aliphatic aldehydes generally failed to yield 1,2-dioxolane. In all cases, unexpected formation of either a chlorohydrin or a 1,2-dichloride (with Cl atoms derived from TiCl 4 ) depending on the alkene employed was observed, which displays some so far unknown facets of the cycloaddition and helped to gain many mechanistic insights.

Hybrid nanocomposites based on UiO-66-NH 2 and carboxyl-functionalized carbon nanotubes were developed in this study via different synthetic pathways. Combining them through interfacial in situ growth was beneficial for the better dispersity of UiO-66-NH 2 in the CNTs@UiO-66-NH 2 composite than physically mixing CNTs/UiO-66-NH 2 and chemically bonded CNTs-CONH-UiO-66. Coordination between carboxyl groups of CNTs and zirconium ions resulted in the interfacial growth of UiO-66-NH 2 on CNTs. Adsorption experiments showed that CNTs@UiO-66-NH 2 exhibited the highest adsorption efficiency towards methyl orange (MO). The adsorption capacity of CNTs@UiO-66-NH 2 was up to 392 mg g -1 , which was 77.45% and 201.5% higher than those of CNTs-CONH-UiO-66 and CNTs/UiO-66-NH 2 respectively. Moreover, CNTs@UiO-66-NH 2 could selectively adsorb MO from the MO/MB mixture.

A new photo-electrochemical sensor based on MIL-101(Cr) MOF/carbon black (CB) is fabricated and characterized. By using differential pulse voltammetry, dopamine (DA) can be effectively detected using a photo-electrochemical MIL-101(Cr)/CB sensor under visible light. The CB acts as the electron bridge to combine with the large specific surface area and photo-catalytic feature of MOF, which contribute to the improvements of sensitivity of DA detection. The concentration of the catalyst, pH value, accumulation potential, and accumulation time were also optimized. Furthermore, the electrochemical performances of MIL-101(Cr)/CB sensor was investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scan rate, electrochemically active surface area (ECSA), and amperometric responses. A detection limit of 0.38 nM (LOD = 3 s b /S, s b  = 0.028) and a working range of 1 nM to 2.22 μM has been achieved. The MIL-101(Cr)/CB sensor exhibits excellent reproducibility, stability, and selectivity and also has satisfactory recovery rate for the analysis of real samples including calf serum and human urine. Graphical abstract.

Numerous evidence has revealed that single-nucleotide polymorphisms (SNPs) are associated with liver cancer risk. To assess whether the MIR17HG polymorphisms are associated with the liver cancer risk in the Chinese Han population, we performed a case-control (432 liver cancer patients and 430 healthy controls) study. Genotyping of four variants of MIR17HG was performed with the Agena MassARRAY platform. We used χ2 test to compare the distribution of SNPs allele and genotypes frequencies of cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the association under genetic models. The results indicated that the rs7318578 was significantly associated with increased the risk of liver cancer in the allele (OR = 1.45, 95% CI: 1.18-1.77, P=3.04E-04), recessive (OR = 3.69, 95% CI: 2.45-5.56, P=4.52E-10) and additive model (OR = 1.35, 95% CI: 1.13-1.62, P=0.001). Moreover, we found that individuals with the genotype CC of rs7318578 presented with an increased risk of liver cancer (OR = 3.03, 95% CI: 1.98-4.65, P=3.83E-07); however, the CA genotype of rs7318578 significantly decreased the risk of liver cancer (OR = 0.61, 95% CI: 0.45-0.83, P=0.001, compared with those with the AA genotype. Our findings indicated that MIR17HG polymorphism (rs7318578) contributes to liver cancer susceptibility to the Chinese Han population. Further studies with larger samples are required to confirm the results, as well as functional studies to determine the role of this SNP in miRNA expression or molecular pathways., (© 2020 The Author(s).)

Objective: To explore the mechanism of a false-negative result from karyotyping of chorionic villi cells for a trisomy 13 fetus featuring multiple malformations., Methods: For a fetus with multiple malformations by ultrasonography and a 46,XY karyotype by chorionic villi analysis, amniocytes were further analyzed with quantitative fluorescence PCR (QF-PCR), G-banded karyotyping and chromosomal microarray analysis (CMA). Meanwhile, non-invasive prenatal testing (NIPT) was conducted on peripheral blood sample from the pregnant woman to determine the chromosomal composition of cytotrophoblast. After induction of labor, common aneuploidies in placenta and fetal tissue were also analyzed by QF-PCR., Results: QF-PCR, chromosomal karyotyping and CMA analysis of the amniocytes all suggested complete trisomy 13 (47,XY,+13) in the fetus. NIPT also suggested existence of fetal trisomy 13. QF-PCR analysis of the placenta and fetal tissues revealed that cells derived from the maternal surface and right side of fetal surface harbored mosaic trisomy 13, while those derived from other sites of fetal surface of the placenta, umbilical cord, amniotic membrane and fetal muscle tissue harbored trisomy 13., Conclusion: Karyotyping of long-term cultured chorionic villus sample may give rise to false negative results due to placental mosaicism. To ensure accurate prenatal diagnosis, discordance between karyotyping of chorionic villi cells, fetal ultrasound and NIPT result should be verified by amniocentesis or cordocentesis and application of multiple cytogenetic and molecular techniques.

A range of allylic alcohols are shown to readily react with ethereal H 2 O 2 in the presence of catalytic amounts of Na 2 MoO 4 -gly or MoO 2 (acac) 2 , affording the C═C trans hydroxylation-hydroperoxylation products in good yields with high regio- and stereoselectivity. Use of enantiomers of cyclic substrates resulted in corresponding enantiopure diol- tert -hydroperoxides. The possibility of further conversion of the diol- tert -hydroperoxides into triols or linear building blocks with an isolated tert -peroxy group containing a quaternary center is also exemplified.

Background: As a global pandemic, COVID-19 has aroused great concern in the last few months and a growing number of related researches have been published. Therefore, a bibliometric analysis of these publications may provide a direction of hot topics and future research trends., Methods: The global literatures about COVID-19 published between 2019 and 2020 were scanned in the Web of Science collection database. "COVID-19" "Novel Coronavirus" "2019-nCoV" and "SARS-CoV-2" were used as the keywords to reach the relevant publications. VOSviewer was applied to perform the bibliometric analysis of these articles., Results: Totally 3,626 publications on the topic of COVID-19 were identified and "COVID-19" with a total link strength of 2,649 appeared as the most frequent keyword, which had a strong link to "pneumonia" and "epidemiology". The mean citation count of the top 100 most cited articles was 96 (range, 26-883). Most of them were descriptive studies and concentrated on the clinical features. The highest-ranking journal was British medical journal with 211 publications and the most cited journal was Lancet with 2,485 citation counts. Eleven articles written by Christian Drosten from Berlin Institute of Virology have been cited for 389 times and 40 articles from Chinese Academy of Sciences have been cited for 1,597 times which are the most cited author and organization. The number of collaborators with China is 44 and the total link strength is 487. The main partners of China are USA, England and Germany. The published literatures have focused on three topics: disease management, clinical features and pathogenesis., Conclusions: The current growth trends predict a large increase in the number of global publications on COVID-19. China made the most outstanding contribution within this important field. Disease treatment, spike protein and vaccine may be hotspots in the future., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4235). YY serves as an unpaid section editor of Annals of Translational Medicine from Oct 2019 to Sep 2020. The other authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Background: Liver cancer is one of the most common cancers in the world. The primary aim of this research was to discover the correlation between single nucleotide polymorphisms (SNPs) of the MIR155HG and liver cancer risk., Methods: The selected SNPs in MIR155HG were genotyped utilizing the Agena MassARRAY platform. We evaluated the correlation between MIR155HG polymorphisms and Liver cancer by genetic model analysis, stratification analysis and haplotype analysis. Relative risk of Liver cancer was shown based on odds ratios (ORs) and 95% confidence intervals (95% CIs)., Results: Our results uncovered that rs12482371 and rs1893650 in the MIR155HG were associated with protection against Liver cancer. And the rs928883 was related to increase risk of Liver cancer. Furthermore, apart from rs77218221, other selected SNPs formed two LD blocks, and haplotype "GATAG" in block 2 elevated individual liver cancer risk., Conclusions: MIR155HG gene polymorphism may be correlated to Liver cancer susceptibility in Han Chinese population, particularly in males and aged ≤55 years.

A novel fluorescent Zn(II)-based metal-organic framework (Zn-MOF), [Zn 2 (oba) 4 (4,4'-bpy) 2 ] n , was successfully synthesized through a simple solvothermal route at 130 °C for 48 h, employing Zn(NO 3 ) 2 ·6H 2 O, 4,4'-Oxybis(benzoic acid) (oba) and 4,4'-Bipyridine (4,4'-bpy) as the initial reactants, dimethylacetamide (DMA) as the reaction medium. The as-obtained Zn-MOF was characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectrum (FTIR), Thermogravimetric analysis (TGA) and elemental analysis. The fluorescence tests showed that the as-obtained Zn-MOF emit a strong violet light centered at 445 nm under the excitation of 323 nm UV light. Intriguingly, the above strong violet emission could be highly selectively quenched by aromatic nitrophenols or antibiotic metronidazole (MET) in aqueous systems with fairly low detection limits. Other substituted phenols and antibiotics, as well as some cations, anions, amino acids and small organic molecules hardly affected the violet emission of the as-obtained Zn-MOF, indicating that this novel Zn-MOF could be prepared as a selective fluorescent probe for detections of aromatic nitrophenols and MET antibiotic in water solutions., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There is growing evidence that microcystin-LR (MC-LR) is a new endocrine disruptor, whereas the impacts of persistent exposure to MC-LR on the hypothalamic-pituitary-interrenal (HPI) axis and health hazards thereafter have not been investigated. In this work, adult male zebrafish ( Danio rerio ) were immersed into MC-LR solutions at concentrations of 0, 1, 5 and 25 μg/L for 30 d, respectively. The results showed that persistent MC-LR exposure caused an extensive upregulation of HPI-axis genes but an inhibition of brain nuclear receptors ( gr and mr ), which finally increased serum cortisol levels. Furthermore, the decreased expression of hepatic gr might partly be responsible for the strong inhibition on the expression of downstream genes involved in glucose metabolic enzymes, including gluconeogenesis-related genes ( pepck , fbp1a , g6pca ), glycogenolysis-related gene ( pyg ), glycolysis-related genes ( gk , pfk1b , pk ) and glycogenesis-related gene ( gys2 ). These findings are in accordance with the decline in serum glucose, indicating that long-term MC-LR exposure caused a lower production of glucose relative to glucose lysis. Our above results firstly establish the link between persistent MC-LR exposure and impaired glucose metabolism, suggesting that long-term MC-LR-mediated stress might threaten fish's health.

Cluster thinning and girdling are common and simple practices applied to improve berry quality in table grape cultivation. However, there is limited information about the accumulation and biosynthesis of the entire aromatic profile under cluster thinning and girdling, notably in table grapes. This research investigated the influences of cluster thinning and girdling (alone or in combination) on aroma profiles, particularly the changes in biosynthesis and accumulation of Muscat-flavored related compounds from véraison to harvest in 'Jumeigui' grape. Cluster thinning and girdling (alone or in combination) significantly increased the concentrations of total soluble solids (TSS) and key aromatic compounds at harvest, with higher concentrations of both under cluster thinning than girdling. Berry weight and titratable acidity (TA) were unaffected by cluster thinning, girdling, or in combination at harvest. Linalool, the most abundant and active odorant related to Muscat flavor, accumulated in 28.6% and 20.2% higher concentrations from cluster thinning than control and girdling at maturity, respectively. Furthermore, higher DXS3 transcript abundance in cluster thinning groups might contribute to the increased accumulation of terpenes and linalool in 'Jumeigui' grape. The results will contribute to further understand the mechanism of source/sink ratio modulation on aroma accumulation and better apply cluster thinning and girdling for grape production.

Two-dimensional (2D) Co-based MOF-on-MOF heterojunction nanostructures with improved electrocatalytic activity were successfully constructed via a mild two-step solution route, employing Co 2+ ions as the center atoms, and 1,4-benzenedicarboxylate (BDC) and 4,4'-biphenyldicarboxylate (BPDC) as ligands. The as-obtained heterojunction nanostructures were characterized by field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) surface area analysis, thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) technologies. Electrochemical measurements showed that as-prepared Co-BPDC/Co-BDC heterojunction nanostructures presented markedly enhanced OER electrocatalytic activity, compared with single Co-BPDC, Co-BDC, and/or their physical mixture. Also, the Co-BPDC/Co-BDC-3 heterojunction prepared after treatment for 3 h exhibited the strongest catalytic activity. To reach the current density j geo = 10 mA cm -2 , the Co-BPDC/Co-BDC-3 heterojunction-modified glassy carbon electrode required an overpotential of 335 mV in 1 M KOH, which was reduced by 57 and 93 mV, compared to the electrodes modified by Co-BDC and Co-BPDC, respectively. Simultaneously, the heterojunction catalyst also displayed better long-term stability. The improvement of the above performances should be attributed to the increased structure stability, BET surface area, ECSA, and electron transfer ability of the heterojunction.

Objective: In order to evaluate the reliability and feasibility of pueraria reference extractive substance (RES) used in biological sample, the pharmacokinetics of 3'‑hydroxy puerarin (3'-HP), puerarin, 3'‑methoxy puerarin (3'-MP), and daidzein-8- C -apiosyl-(1-6)-glucoside (DAG) in beagle plasma following oral administration of Yufeng Ningxin Tablet were quantitated., Methods: A reliable and sensitive high-performance liquid chromatography-tandem triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method developed with chromatographic separation was operated on a Merck C 18 column, and acetonitrile-5 mmol/L ammonium was used as mobile phase in gradient elution. The plasma samples were deproteinized by acetone, detected by triple quadrupole mass spectrometry with an electrospray ionization interface, and quantified using selected ion monitoring mode. The pharmacokinetic parameters were calculated by Winnonlin 4.1., Results: The calibration curves of the reference extractive substance and standard substance methods were linear over the ranges 0.0417-11.3309 µg/mL and 0.0394-10.0000 µg/mL. The intra-day and inter-day precision of the two methods at three concentrations were less than 13.63%, and the average recoveries of 3'-HP, puerarin, 3'-MP, and DAG were more than 70.67%. The RSD of the mean plasma concentrations of the analytes calculated by the two methods was less than 5%, and cos (ϑ) = =1.000. Among the analytes, puerarin showed the highest blood concentration [(940 ± 185) ng/mL] and the longest retention time [(5 ± 1) h] in the dog's bodies., Conclusion: Pueraria reference extractive substance can be seen as an alternative to the standard substance to overcome the scarcity of standard substance for the analysis of biological samples., Competing Interests: The authors declare no conflict of interest., (© 2019 Tianjin Press of Chinese Herbal Medicines. Published by Elsevier B.V.)

Hollow α-Co(OH) 2 and Cl-doped α-Co(OH) 2 nano-dodecahedrons were successfully synthesized via a ZIF-67-assisted template route in the absence/presence of NaCl. The reactions were carried out in a Teflon-lined stainless-steel autoclave at 40 °C for 4 h, employing dodecahedral ZIF-67 and hexamethylenetetramine (HMT) as the reactants. The as-obtained hollow nano-dodecahedrons were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), X-ray photoelectron energy, EDS mapping and N 2 sorption-desorption technologies. Electrochemical measurements showed that both α-Co(OH) 2 and Cl-doped α-Co(OH) 2 hollow nano-dodecahedrons displayed excellent catalytic activities for the oxygen evolution reaction (OER) and Cl-doped α-Co(OH) 2 hollow ones possessed stronger electrocatalytic performances. To deliver a current density of 10 mA cm -2 , Cl-doped α-Co(OH) 2 hollow nano-dodecahedrons required a low overpotential of 298 mV, which is smaller than most reported α-Co(OH) 2 catalysts. Also, the as-obtained hollow catalyst still had excellent OER cycling stability and durability. After 1000 CV cycles, the overpotential merely slightly increased. Continuously catalyzing at the current density of 10 mA cm -2 for 40 h, the voltage only increased ∼2.5%.

Nitrate radical (NO 3 ) and dinitrogen pentoxide (N 2 O 5 ) play crucial roles in the nocturnal atmosphere. To quantify their impacts, we deployed a thermal-dissociation chemical ionization mass spectrometry (TD-CIMS), to measure their concentration, as well as ClNO 2 at a coastal background site in the southern of China during the late autumn of 2012. Moderate levels of NO 3 , N 2 O 5 and high concentration of ClNO 2 were observed during the study period, indicating active NO x -O 3 chemistry in the region. Distinct features of NO 3 , N 2 O 5 and ClNO 2 mixing ratios were observed in different airmasses. Further analysis revealed that the N 2 O 5 heterogeneous reaction was the dominant loss of N 2 O 5 and NO 3 , which showed higher loss rate compared to that in other coastal sites. Especially, the N 2 O 5 loss rates could reach up to 0.0139 s -1 when airmasses went across the sea. The fast heterogeneous loss of N 2 O 5 led to rapid NO x loss which could be comparable to the daytime process through NO 2 oxidization by OH, and on the other hand, to rapid nitrate aerosol formation. In summary, our results revealed that the N 2 O 5 hydrolysis could play significant roles in regulating the air quality by reducing NO x but forming nitrate aerosols., (Copyright © 2019. Published by Elsevier B.V.)

Background: Leflunomide (LEF) is a first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA). However, there are still a few nonresponders. It is logical to suggest that employing combinations including LEF that produce synergistic effects in terms of pharmacological activity is a promising strategy to improve clinical outcomes., Methods: We propose a novel approach for predicting LEF combinations through investigating the potential effects of drug targets on the disease signaling network. We first constructed an RA signaling network with disease-associated driver genes. Thousands of available FDA-approved and investigational compounds were then selected based on a drug-RA network, which was generated using an algorithm model named synergistic score that combines chemical structure, functional prediction and target pathway. We then validated our predicted combination in a prospective clinical trial., Results: Ligustrazine (LIG), a key component of the Chinese herb Chuanxiong and an approved drug in China, ranked first according to synergistic score. In the clinical trial, after 48 weeks, the American College of Rheumatology (ACR) 20 response rate was significantly lower ( P  < 0.05) in the LEF group [58.8% (45.4%, 72.3%)] than in the LEF + LIG group [78.7% (68.5%, 89.0%)]. Consistently, the erosion score was lower in patients treated with LEF + LIG than in those treated with LEF (0.34 ± 0.20 vs 1.12 ± 0.30, P  < 0.05)., Conclusions: Our algorithm combines structure and target pathways into one model that predicted that the combination of LEF and LIG can reduce joint inflammation and attenuate bone erosion in RA patients. To our knowledge, this study is the first to apply this paradigm to evaluate drug combination hypotheses., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Aims: The purpose of this prospective, single-center study was to measure the value of Krebs von den Lungen-6 (KL-6), a kind of transmembrane mucoprotein, in diagnosing interstitial lung disease (ILD) and in assessing the severity of ILD., Methods: We enrolled 184 patients and 30 healthy controls. Ninety-eight patients were diagnosed with ILD, 47 with pneumonia, 19 with non-small cell lung cancer without ILD (NSCLC/non-ILD) and 20 with other lung diseases. Serum KL-6 levels, CT scores of high-resolution computerised tomography (HRCT) and pulmonary function in ILD patients were assessed., Results: The mean value of serum KL-6 in patients with ILD, pneumonia, NSCLC/non-ILD, other lung diseases and healthy controls were 1000.67±882.73U/ml, 234.11±91.02U/ml, 269.95±149.23U/ml, 234.85±83.51U/ml and 189.03±55.50U/ml, respectively. Serum KL-6 levels of patients with ILD were significantly higher than that of other groups (P<0.000). The level of serum KL-6 in patients with pneumonia, NSCLC/non-ILD and other lung diseases was also statistically higher than healthy controls (P<0.05). When the cut-off value was 312U/ml, the sensitivity and specificity of KL-6 for the diagnosis of ILD was 84.7% and 85.3% respectively (AUC: 0.936, 95% CI: 0.906-0.965). The serum KL-6 levels in patients with ILD were significantly positively correlated with the CT scores (r=0.539, P=0.000) and negatively correlated with DLCO (r=-0.513, P=0.000)., Conclusion: Serum KL-6 might be useful in the diagnosis of ILD, especially in the hard-to-diagnose cases, with high sensitivity and specificity. Furthermore, KL-6 might be a valuable marker for evaluation of ILD severity., (Copyright © 2018 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Ketones, ketals, and epoxides were converted into corresponding hydroperoxides in high yields by reaction with ethereal H 2 O 2 in the presence of a catalytic amount of MoO 2 (acac) 2 with distinct (to date unattainable) chemoselectivity.

The various post-translational modifications (PTMs) of plant proteins have important regulatory roles in development. We therefore examined various modified proteins from strawberry stigmata and found that succinylation of lysine residues was the most abundant type of modification. We then subjected proteins from strawberry stigmata to an efficient enrichment method for succinylated peptides and identified 200 uniquely succinylated lysines (Suks) in 116 proteins. A bioinformatics analysis revealed that these proteins are involved in important biological processes, including stress responses, vesicular transport, and energy metabolism. Proteomics, combined with immunoprecipitation and immunoblotting, revealed an obvious increase in succinylation of the assembly polypeptide 2 (AP2) and clathrin from 0.5 to 2 h after pollination, suggesting that succinylation is involved in the recognition of pollen-stigma signaling substances and vesicular transport. These results suggest that AP2/clathrin-mediated vesicular transport processes are regulated by lysine succinylation during pollen recognition.

A major fraction of atmospheric aerosol particles, which affect both air quality and climate, form from gaseous precursors in the atmosphere. Highly oxygenated organic molecules (HOMs), formed by oxidation of biogenic volatile organic compounds, are known to participate in particle formation and growth. However, it is not well understood how they interact with atmospheric pollutants, such as nitrogen oxides (NO x ) and sulfur oxides (SO x ) from fossil fuel combustion, as well as ammonia (NH 3 ) from livestock and fertilizers. Here, we show how NO x suppresses particle formation, while HOMs, sulfuric acid, and NH 3 have a synergistic enhancing effect on particle formation. We postulate a novel mechanism, involving HOMs, sulfuric acid, and ammonia, which is able to closely reproduce observations of particle formation and growth in daytime boreal forest and similar environments. The findings elucidate the complex interactions between biogenic and anthropogenic vapors in the atmospheric aerosol system.

Previous studies have suggested that increased opioid receptor κ1 (OPRK1) and opioid receptor δ1 (OPRD1) methylation levels are involved in Alzheimer's disease (AD). In the present study, the methylation levels of two opioid receptor genes, opioid receptor µ1 (OPRM1) and opioid related nociceptin receptor 1 (OPRL1), were analyzed for their association with AD. Gene methylation levels were measured using bisulfite pyrosequencing in DNA samples derived from blood samples of 51 AD patients and 63 controls. The results indicated that there were significantly elevated promoter methylation levels of OPRM1 and OPRL1 in AD (OPRM1: P=0.007; OPRL1: P=2.987x10‑6). Dual‑luciferase reporter gene assays demonstrated that the promoter fragments of these two genes were able to promote gene expression (OPRM1: Fold‑change=2.616, P=0.003; OPRL1: Fold change=11.395, P=0.007). In addition, receiver operating characteristic analyses further indicated that a methylation panel of four opioid receptor genes (area under the curve=0.848, sensitivity=0.723, and specificity=0.879) performed well in the prediction of AD. These results suggested that opioid receptor genes may be used as potential methylation biomarkers for the diagnosis of AD.

Nucleation and growth of aerosol particles from atmospheric vapors constitutes a major source of global cloud condensation nuclei (CCN). The fraction of newly formed particles that reaches CCN sizes is highly sensitive to particle growth rates, especially for particle sizes <10 nm, where coagulation losses to larger aerosol particles are greatest. Recent results show that some oxidation products from biogenic volatile organic compounds are major contributors to particle formation and initial growth. However, whether oxidized organics contribute to particle growth over the broad span of tropospheric temperatures remains an open question, and quantitative mass balance for organic growth has yet to be demonstrated at any temperature. Here, in experiments performed under atmospheric conditions in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN), we show that rapid growth of organic particles occurs over the range from [Formula: see text]C to [Formula: see text]C. The lower extent of autoxidation at reduced temperatures is compensated by the decreased volatility of all oxidized molecules. This is confirmed by particle-phase composition measurements, showing enhanced uptake of relatively less oxygenated products at cold temperatures. We can reproduce the measured growth rates using an aerosol growth model based entirely on the experimentally measured gas-phase spectra of oxidized organic molecules obtained from two complementary mass spectrometers. We show that the growth rates are sensitive to particle curvature, explaining widespread atmospheric observations that particle growth rates increase in the single-digit-nanometer size range. Our results demonstrate that organic vapors can contribute to particle growth over a wide range of tropospheric temperatures from molecular cluster sizes onward., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Objective: To detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them., Methods: The 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies., Results: Biallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions (c.851del4, c.1092&#95;1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A (p.Y24X)), one duplication mutation (c.1638&#95;1660dup), one insertion (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c.851del4 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated., Conclusion: Analysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.

It remains a crucial challenge to achieve efficient cellular uptake and intracellular drug release in tumor cells for the nanoscale drug delivery systems. Herein, acid-degradable nanogels were prepared by cross-linking methacrylated soy protein with an acid-labile ortho ester cross-linker (NG1), and then modified with lactobionic acid (LA) to give tumor-targeted nanogels (NG2). Both NG1 and NG2 displayed excellent stability in neutral environment, while showed pH-triggered degradation behaviors under mildly acidic conditions resulting from the breakage of ortho ester bonds. Doxorubicin (DOX) was successfully loaded into nanogels, which exhibited an accelerated release at low pH. In vitro cell studies demonstrated that LA-modified nanogels could effectively improve cellular internalization, show higher cytotoxicity and apoptosis toward asialoglycoprotein receptor (ASGPR) over-expressed HepG2 cells. In vivo antitumor experimentproved that LA modification could significantly enhance the tumor-targeting ability of nanogels and increase DOX concentration in tumor site, leading to better therapeutic efficacy. Histological analysis further demonstrated that soy protein-based nanogels did not cause any damage to normal organs. Overall, these pH-sensitive and tumor-targeting soy protein-based nanogels can be potential drug carriers for efficient tumor treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We have established an induced pluripotent stem (iPS) cell line using urine-derived cells from a 27-year-old male patient with retinitis pigmentosa associated with point mutations in the USH2A gene. Feeder-free culture conditions and the integration-free CytoTune™-iPS 2.0 Sendai Reprogramming Kit were used., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

A substantial fraction of aerosols, which affect air quality and climate, is formed from gaseous precursors. Highly oxygenated organic molecules (HOMs) are essential to grow the newly formed particles and have been evidenced to initiate ion-induced nucleation in chamber experiments in the absence of sulfuric acid. We investigate this phenomenon in the real atmosphere using an extensive set of state-of-the-art ion and mass spectrometers deployed in a boreal forest environment. We show that within a few hours around sunset, HOMs resulting from the oxidation of monoterpenes are capable of forming and growing ion clusters even under low sulfuric acid levels. In these conditions, we hypothesize that the lack of photochemistry and essential vapors prevents the organic clusters from growing past 6 nm. However, this phenomenon might have been a major source of particles in the preindustrial atmosphere and might also contribute to particle formation in the future and consequently affect the climate.

Atmospheric oxidizing capacity (AOC), dominated by the hydroxyl radical (OH), is an important index of the self-cleaning capacity of atmosphere and plays a vital role in the tropospheric chemistry. To better understand the key processes governing the chemistry of rural atmosphere of southern China, we analyzed the oxidation capacity and radical chemistry at a regional background site in Hong Kong from 23 August to 22 December 2012, which covered the summer, autumn and winter seasons. A chemical box model built on the latest Master Chemical Mechanism (v3.3) was used to elucidate the OH reactivity and sources of RO X radicals (RO X =OH+HO 2 +RO 2 ). The AOC showed a clear seasonal pattern with stronger intensity in late summer compared to autumn and winter. Reactions with NO 2 (30%) and oxygenated volatile organic compounds (OVOCs) (31%) together dominated the OH loss in summer, while reactions with CO (38% in autumn and 39% in winter) and OVOCs (34% in autumn and 25% in winter) made larger contributions in autumn and winter. Photolysis of O 3 (36%-47%) presented the major RO X source during all three seasons. The second largest ROx source was HONO photolysis (25%) in summer compared to HCHO photolysis in autumn (20%) and winter (21%). Besides, photolysis of other OVOCs was another important primary source of ROx radicals with average contributions of 14%, 13% and 20% for the summer, autumn and winter cases, respectively. Overall, the present study evaluates the oxidizing capacity of the rural atmosphere of South China and elucidates the varying characteristics of photochemical processes in different air masses., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A new type of pH-triggered hyaluronic acid nanogel system (HA-NGs) was successfully developed for tumor-targeted delivery of drugs. HA-NGs were obtained by copolymerization between methacrylate HA and a new cross-linker containing ortho ester groups in an aqueous solution. The therapeutic drug (DOX) was loaded into the HA-NGs (DOX@HA-NGs) and exhibited appropriate loading of about 17.3% with a size of around 200nm. Such new pH-triggered HA-NGs are found to be highly desirable for targeted cancer therapy because it could significantly minimize the amount of premature drug release in neutral pH, and also provide a sufficient amount of drug to effectively kill the cancer cells caused by the degradation of ortho ester groups at acid pH values. Results from the cellular uptake and cytotoxicity of DOX@HA-NGs performed in two-dimensional (2D) cell culture demonstrated that DOX@HA-NGs exhibit excellent tumor homing and higher cytotoxicity. Importantly, the penetration and inhibition against three-dimensional (3D) tumor spheroids demonstrated that DOX@HA-NGs could fully penetrate into HepG2 tumor spheroids, thus leading to higher inhibition. So, such new tumor-targeting DOX@HA-NGs prepared via ortho ester linkages will exhibit excellent stability in a neutral environment, pH-triggered drug release, as well as enhanced penetration and destruction against 3D tumor spheroids, thereby making targeted cancer therapy possible., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Clinical practice guidelines (CPGs) for Chinese medicine (CM) are being developed to assist doctors with appropriate decisions concerning CM care. To date, there has been little investigation on the perspectives of those to whom the guidelines are directed., Methods: A self-administered questionnaire was sent to 4503 doctors in 28 provinces of China in the latter half of 2012. Questions were organized around the topics of knowledge, application, practice changes, beliefs and outcomes of implementation. Basic classificatory data on specialties and years of qualification were also collected., Results: Replies were received from 4495 CM doctors (99.82%). Of these, 85.56% of CM doctors reported being familiar with CPG recommendations, but the overall adherence rate was only 50.39%. The length of time practicing CM may influence the rate of adherence, since 709 doctors (51.90%) with less than 5 years of experience reported never having followed CPGs. Doctors in nine specialties showed a modest degree of homogeneity in their attitudes towards CM diagnosis and treatment, which were generally positive. Most doctors regarded CPG-recommended therapies as safe (92%), economic (84%), and effective (76%). Approximately four-fifths of those questioned selected 'acceptable' (60.84%) and 'acceptable after revision' (19.23%) regarding their comprehensive assessment of the CPGs., Conclusions: An encouraging result from this survey is that the majority of CM doctors support the concept of CPGs for the practice of CM. However, the results of this survey also suggest that improving the adherence of CM doctors to the guidelines remains a major challenge to improving the practice standards for CM.

This work describes an acid-degradable and tumor-targeted nanogels prepared by the copolymerization between lactobionic acid-modified methacrylated carboxymethyl chitosan and acid-labile methacrylated orthoester-based monomers. The size distribution and micromorphology of the prepared nanogels were observed by dynamic light scattering, transmission electron microscopy and scanning electron microscopy. The stability of nanogels in various environments was then investigated. Doxorubicin as a model drug was successfully encapsulated into nanogels. In vitro cellular uptake and MTT results indicate that the tumor-targeting and pH-sensitive nanogels display higher cellular internalization and cytotoxicity than non-target nanogels and free DOX. The improved penetration and growth inhibition against 3-D multicellular spheroids further demonstrate that the dual-functional nanogels may be a potential nano-carrier for drug delivery in cancer therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)