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Porcine circovirus (PCV) is one of the smallest known DNA viruses in mammals. At present, PCVs are divided into three species, PCV1, PCV2, and PCV3. PCV1 and PCV2 were found in the 1970s and the 1990s, respectively, whereas PCV3 was discovered recently in 2016. PCV1 does not cause diseases in pigs. However, PCV3, similar to PCV2, is reported to be associated with several swine diseases, including porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure. PCVs are very common in domestic pigs as well as wild boars. However, PCVs have been occasionally isolated from non-porcine animals, including ruminants (such as cattle, goats, wild chamois, and roe deers), rodents (such as NMRI mice, BALB/c mice, Black C57 mice, ICR mice, Mus musculus , and Rattus rattus ), canines (such as dogs, minks, foxes, and raccoon dogs), insects (such as flies, mosquitoes, and ticks), and shellfish. Moreover, PCVs are frequently reported in biological products, including human vaccines, animal vaccines, porcine-derived commercial pepsin products, and many cell lines. PCVs are also abundant in the environment, including water samples and air samples. Interestingly, PCV1 and/or PCV2 antibody or antigen has also been detected in sera, stool samples and respiratory swab samples of human, revealing zoonotic potential of PCVs. Thus, PCVs inhabit many types of reservoirs. In this review, we summarize the reservoirs of PCVs, and this information would be helpful in understanding the natural circulating status and possible cross-species transmission of PCVs., (Copyright © 2019 Zhai, Lu, Wei, Lv, Wen, Zhai, Chen, Sun and Xi.)

Background: Laparoscopic pancreatectomy (LP) is increasingly performed with several institutional series and comparative studies reported. We have applied LP to a variety of pancreatic resections since 2004. This article is to report results of 15-year practice of 605 LPs for pancreatic and periampullary diseases. Methods: Patients with benign or malignant diseases in the pancreas and periampullary region, who underwent LP from June 2004 to June 2018, were retrospectively reviewed. The demographics and indications, and intraoperative and perioperative outcomes were evaluated. Results: A total of 605 consecutive LPs were analyzed, including 237 (39.2%) distal pancreatectomy with splenectomy (DPS), 116 (19.2%) spleen-preserving distal pancreatectomy (SPDP), 30 (5.0%) enucleation (EN), 30 (5.0%) central pancreatectomy (CP), 186 (30.7%) pancreatoduodenectomy (PD), and 6 (1.0%) pancreatoduodenectomy with total pancreatectomy (PDTP). The most common pathologic finding was pancreatic ductal adenocarcinomas (146, 24.1%). Conversion to open procedure was required in 22 patients (3.6%) (12 with PD, 8 with DPS, 1 with CP, and 1 with PDTP). The mean operative time was 241.5 ± 105.5 minutes (range 50-550 minutes) for the entire population and 367.1 ± 61.8 minutes (range 230-550 minutes) for PD. Clinically significant pancreatic fistula (ISGPF grade B and C) rate was 12.4% for the entire cohort and 16.1% for PD. Rate of Clavien-Dindo III-V complications was 17.4% for the entire cohort and 23.7% for PD. Ninety-day mortality was observed only in the cohort of patients undergoing PD ( n  = 4). Conclusions: The LP procedure appears to be technically safe and feasible, with an acceptable rate of morbidity when performed at our experienced, high-volume center. However, PD has less favorable outcomes and needs further evaluation.

The modulation of VDR signaling is important in regulating tumor-related signal transduction and protecting from microorganismal infection. In this study we discovered by luciferase reporter assay that several fused bicyclic derivatives of 1H-pyrrolo[1,2-c]imidazol-1-one with the assistance of calcitriol result in up to three-fold increases of VDR promoter activity. Preliminary SAR results from 20 compounds disclose that ideal VDR signaling regulators of these compounds are built up by the optimal combination of multiple factors. Western blot analysis indicates that compounds of ZD-3, ZD-4 and ZD-5 not only significantly upregulate p62 and LC3-II but also elevate the ratio of LC3-II/LC3-I, which possibly leads to activated autophagy. All of five compounds also significantly downregulate p65 and upregulate p-p65 and ZD-3 is the most active one to NF-κB signaling, suggesting a possible induction of apoptosis through the regulation of NF-κB signal transduction mediated by VDR signaling. Compounds of ZD-3, ZD-4 and ZD-5 significantly counteract the interference by VDR shRNA, in which ZD-3 gets the highest compensation of VDR expression and the highest ratio of LC3-II/LC3-I, indicating that ZD-3 very likely activates VDR-mediated autophagy. Taken together, these 1H-pyrrolo[1,2-c]imidazol-1-one derivatives can modulate VDR signaling, possibly resulting in the regulation of some signal pathways to induce autophagy and apoptosis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The increasing antimicrobial resistance in manure-amended soil can potentially enter food chain, representing an important vehicle for antibiotic resistance genes (ARGs) transmission into human microbiome. However, the pathways for transmission of ARGs from soil to plant remain unclear. Here, we explored the impacts of poultry and cattle manure application on the patterns of resistome in soil and lettuce microbiome including rhizosphere, root endosphere, leaf endosphere and phyllosphere, to identify the potential transmission routes of ARGs in the soil-plant system. After 90 days of cultivation, a total of 144 ARGs were detected in all samples using high-throughput quantitative PCR. Rhizosphere soil samples harbored the most diverse ARGs compared with other components of lettuce. Cattle manure application increased the abundance of ARGs in root endophyte, while poultry manure application increased ARGs in rhizosphere, root endophyte and phyllosphere, suggesting that poultry manure may have a stronger impact on lettuce resistomes. The ARG profiles were significantly correlated with the bacterial community, and the enrichment of soil and plant resistomes was strongly affected by the bacterial taxa including Solibacteres, Chloroflexi, Acidobacteria, Gemm-1 and Gemmatimonadetes, as revealed by the network analyses. Moreover, the overlaps of ARGs between lettuce tissues and soil were identified, which indicated that plant and environmental resistomes are interconnected. Our findings provide insights into the transmission routes of ARGs from manured soil to vegetables, and highlight the potential risks of plant resistome migration to the human food chain., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Memristors, which feature small sizes, fast speeds, low power, CMOS compatibility and nonvolatile modulation of device resistance, are promising candidates for next-generation data storage and in-memory computing paradigms. Compared to the binary logics enabled by memristor devices, ternary logics with larger information-carrying capacity can provide higher computation efficiency with simple operation schemes, reduced circuit complexity and smaller chip areas. In this study, we report the fabrication of memristor devices based on nano-columnar crystalline ZnO thin films; they show symmetric and reliable multi-level resistive switching characteristics over three hundred cycles, which benefits the implementation of univariate ternary logic operations. Experimental results demonstrate that a three-valued logic complete set can be realized by the univariate operations of the present ZnO memristor device, and a ternary multiplier unit circuit is designed for potential applications. The present methodology can be beneficial for constructing future high-performance computation architectures., Competing Interests: The authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

The importance of diet in regulating the gut microbiome of globally distributed and functionally important soil generalist invertebrates such as collembolans remain poorly understood. Here, we studied a model collembolan (Folsomia candida) and found that diet (bacteria, plant litters, yeast, mixed food) is a critical factor in regulating the microbial diversity and community composition of this important soil organism. Collembolans fed with litter exhibited the lowest bacterial diversity and were dominated by Ochrobactrum. Conversely, collembolans fed with mixed diets resulted in the highest bacterial diversity. Our findings further suggest that microbial communities associated with different diets are linked to different levels of collembolan fitness. For example, the relative abundance of the genera of unclassified Thermogemmatisporaceae, Brevibacillus, and Novosphingobium were positively correlated with growth of the collembolans. Together, our work provides evidence that diet is a major force controlling the gut microbiome of collembolans, and is a good environmental predictor for collembolan growth, with implications for ecosystem functioning in terrestrial environments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Minimally invasive pancreatoduodenectomy (MIPD) is being increasingly performed as an alternative to open pancreatoduodenectomy (OPD) in selected patients. Our study aimed to present a meta-analysis of the high-quality studies conducted that compared MIPD to OPD performed for pancreatic head and periampullary diseases., Methods: A systematic review of the available literature was performed to identify those studies conducted that compared MIPD to OPD. Here, all randomized controlled trials identified were included, while the selection of high-quality, nonrandomized comparative studies were based on a validated tool (i.e., Methodological Index for Nonrandomized Studies). Intraoperative outcomes, postoperative recovery, oncologic clearance, and postoperative complications were also evaluated., Results: Sixteen studies matched the selection criteria, including a total of 3168 patients (32.1% MIPD, 67.9% OPD). The pooled data showed that MIPD was associated with a longer operative time (weighted mean difference [WMD] = 80.89 minutes, 95% confidence interval [CI]: 39.74-122.05, P < .01), less blood loss (WMD = -227.62 mL, 95% CI: -305.48 to -149.75, P < .01), shorter hospital stay (WMD = -4.68 days, 95% CI: -5.52 to -3.84, P < .01), and an increase in retrieved lymph nodes (WMD = 1.85, 95% CI: 1.33-2.37, P < .01). Furthermore, the overall morbidity was significantly lower in the MIPD group (OR = 0.67, 95% CI: 0.54-0.82, P < .01), as were total postoperative pancreatic fistula (POPF) (OR = 0.79, 95% CI: 0.63-0.99, P = .04), delayed gastric emptying (DGE) (OR = 0.71, 95% CI: 0.52-0.96, P = .02), and wound infection (OR = 0.56, 95% CI: 0.39-0.79, P < .01). However, there were no statistically significant differences observed in major complications, clinically significant POPFs, reoperation rate, and mortality., Conclusion: Our study suggests that MIPD is a safe alternative to OPD, as it is associated with less blood loss and better postoperative recovery in terms of the overall postoperative complications as well as POPF, DGE, and wound infection. Methodologic high-quality comparative studies are required for further evaluation.

Objective: To observe the effect of collecting and retransfusing autologous platelet rich plasma (aPRP) on the amount of allogeneic blood usage in total arch replacement (Sun's surgery) and the outcomes 30 days after surgery., Design: A prospective, randomized trial., Setting: A tertiary university hospital specialized in cardiovascular diseases., Participants: The study comprised 120 patients undergoing Sun's surgery for Stanford type A acute aortic dissection., Interventions: aPRP was harvested before incision and was re-transfused after heparin neutralization for patients in the treatment group., Measurements and Main Results: There was no significant difference in preoperative demographic data between the 2 study groups. Intraoperative transfusions of erythrocyte (p = 0.009), plasma (p = 0.017), cryoprecipitate (p = 0.002), and platelets (p < 0.001) in the treatment group were reduced significantly. In addition, less blood loss was observed in the treatment group (p = 0.002). The durations of postoperative mechanical ventilation (p = 0.029) and hospitalization (p = 0.002) of the treatment group were significantly shorter. There were no statistically significant differences in the length of intensive care unit stay, the incidence of complications, and mortality 30 days after surgery., Conclusion: In total arch replacement (Sun's surgery), collecting and retransfusing aPRP reduced intraoperative transfusions of erythrocyte, plasma, and cryoprecipitate and decreased the duration of postoperative mechanical ventilation and hospitalization. This technique had no significant effect on the incidence of complications and mortality 30 days postoperatively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We present a facile strategy for fabricating a new type of one-dimensional (1D) carbon nanomaterial named carbon nanobranches (CNBs) covered with botryoidal carbon dots (CDs) by direct pyrolysis of a green precursor (starch). The resultant CNBs display both photoluminescence and electrical conductivity and can be assembled into chemical sensors and energy-storage devices. In terms of their bright photoluminescence, CNBs with a fabulous crystalline structure are utilized as fluorescent probes to sensitively and selectively detect Co 2+ with a very low detection limit of 2.85 nM and a wide linear concentration range from 10 nM to 1 mM. Moreover, an efficient micro-supercapacitor (micro-SC) is constructed based on conductive CNB fibers produced via a customized microfluidic spinning technique. The micro-SCs exhibit a large specific capacitance of 201.4 mF cm -2 , an energy density of 4.5 μW h cm -2 and high cycling stability, and can successfully power 19 light-emitting diodes (LEDs). The main purpose of this paper is to offer a perspective into simplifying the connecting of research and industry by starting from green carbon-based materials., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Rabies is a zoonotic infectious disease caused by lyssavirus and characterized by central nervous system symptoms. The fatality rate of rabies is almost 100%. About 59 000 cases die of rabies worldwide every year, mainly in Asia and Africa. China is an epidemic country of rabies. Grade II and III exposures are the main types of rabies exposures in China. Standardized post-exposure prophylaxis (PEP) can prevent rabies almost 100%. Human Rabies Vaccine Technical Working Group, National Immunization Advisory Committee and invited experts reached an expert consensus on PEP by referring to the World Health Organization's position paper on rabies vaccine in 2018 and related research progress in recent.

Morindae Officinalis Radix (MOR), the dried root of Morinda officinalis F.C. How (Rubiaceae), is a popular food supplement in southeastern China for bone protection, andrological, and gynecological healthcare. In clinical use, 3-4 year old MOR is commonly used and the xylem is sometimes removed. However, there is no scientific rationale for these practices so far. In this study, metabolomics and glycomics were integrated using multiple chromatographic and mass spectrometric techniques coupled with multivariate statistical analysis to investigate the qualitative and quantitative variations of secondary metabolome and glycome in different growth years (1-7 years) and tissues (xylem and cortex) of MOR. The results showed that various types of bioactive components reached a maximum between 3 and 4 years of growth and that the xylem contained more potentially toxic constituents but less bioactive components than the cortex. This study provides the chemical basis for the common practice of using 3-4 year old MOR with the xylem removed.

Background: Although recent reports have suggested the advantages of laparoscopic distal pancreatectomy (LDP), the potential benefits of this approach in elderly patients remain unclear. The aim of this study was to clarify the value of LDP in the elderly, in whom co-morbid diseases were generally more common., Methods: Seventy elderly patients (≥ 70 years) and 264 non-elderly patients (40-69 years) who underwent LDP, and 48 elderly patients (≥ 70 years) who underwent open distal pancreatectomy (ODP) between May 2005 and May 2018 were studied. Demographics, intraoperative, and postoperative outcomes were compared., Results: Comorbidity was more common in elderly patients than in non-elderly patients who underwent LDP (57.1 vs. 38.3%, p < 0.01). The intraoperative factors, postoperative complication rate, and length of hospital stay were comparable in these two groups. Elderly patients who underwent LDP had a significantly shorter operative time (185.5 vs. 208.0 min, p = 0.02), less blood loss (191.0 vs. 291.8 mL, p < 0.01), and reduced length of postoperative hospital stay (11.4 vs. 15.1 days, p < 0.01) than elderly patients who had ODP. The overall complication rate tended to be lower in LDP group than that in ODP group (20.0 vs. 33.3%, p = 0.07)., Conclusion: LDP performed on the elderly is safe and feasible, leading to short-term outcomes similar to those of non-elderly patients. LDP could be an alternative to ODP in elderly patients, providing a lower rate of morbidity and favorable postoperative recovery and outcomes.

Growing evidences have demonstrated that heavy metal contamination can promote the proliferation of antibiotic resistance genes (ARGs) via co-selection. However, effects of nano-metal-materials on the occurrence and level of ARGs in the soil and plant, have not been fully explored. To gain insights into this impact, we conducted a pot experiment by adding nano‑silver particles (AgNPs) as a stimuli and Ag ion (AgNO 3 ) and tetracycline as a comparison. By using high throughput quantitative PCR, our results indicated that application of AgNPs (~20 nm and ~50 nm) at a concentration of 100 ppm resulted in no significant changes in the abundance of ARGs in either soil or phyllosphere (P > 0.05). Nevertheless, the overall pattern of resistome, especially in soil, was shifted following AgNPs application, with a significance increase in the relative abundance of efflux pumps genes, which is an important mechanism for co-selection of ARGs by heavy metals. By comparison, Ag ion at an equivalent Ag mass of AgNPs markedly increased ARGs abundance and shifted ARGs profile in soil, indicating that free Ag ion had a stronger impact on ARGs than AgNPs. These findings provide new insights in assessing the risks of manufactured nanomaterials accumulated in the environment., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study aims to evaluate the diagnostic accuracy and clinical application value of multi-slice spiral CT (MSCT) enhanced scans combined with multiplanar reformations (MPRs) images compared with postoperative pathological results in preoperative T staging of rectal cancer.One hundred sixty-eight consecutive patients with rectal cancer were admitted in our hospital between January 2013 and October 2018. Conventional MSCT plain scans, multi-phase dynamic contrast-enhanced scans, and MPRs were performed in all patients before surgical operation. The preoperative T staging of the rectal cancer lesions was evaluated using MSCT enhanced scans combined with MPRs, which was verified by postoperative pathological results. The diagnostic accuracy of MSCT enhanced scans combined with MPRs in evaluating T staging of the rectal cancer lesions were analyzed by χ test and Kappa test.Compared with postoperative pathology, T staging using MSCT enhanced scans combined with MPRs had overall accuracy of 85.7%. Consistency between MSCT enhanced scans combined with MPRs and postoperative pathological staging was effective for T staging (Kappa = 0.658, χ = 4.200, P = .122).Conventional MSCT enhanced scans combined with MPRs are simple and feasible. It is consistent with the pathological diagnosis of evaluating T staging in the rectal cancer lesions. It can provide reliable imaging evidence for the preoperative evaluation of primary rectal cancer, especially in patients with magnetic resonance imaging (MRI) contraindications, or in grass-roots hospitals due to lack of MRI equipment.

Growing evidence points to the pivotal role of the environmental factors in influencing the transmission of antibiotic resistance genes (ARGs) and the propagation of resistant human pathogens. However, our understanding of the ecological and evolutionary environmental factors that contribute to development and dissemination of antibiotic resistance is lacking. Here, we profiled a wide variety of ARGs using the high-throughput quantitative PCR analysis in 61 soil samples collected from ocean and river beaches, which are hotspots for human activities and platforms for potential transmission of environmental ARGs to human pathogens. We identified the dominant abiotic and biotic factors influencing the diversity, abundance and composition of ARGs in these ecosystems. A total of 110 ARGs conferring resistance to eight major categories of antibiotics were detected. The core resistome was mainly affiliated into β-lactam and multidrug resistance, accounting for 66.9% of the total abundance of ARGs. The oprJ gene conferring resistance to multidrug was the most widespread ARG subtype detected in all the samples. The relative abundances of total ARGs and core resistome were significantly correlated with salinity-related properties including electrical conductivity and concentrations of sodium and chloride. Random forest analysis and structural equation modelling revealed that salinity was the most important factor modulating the distribution patterns of beach soil ARGs after accounting for multiple drivers. These findings suggest that beach soil is a rich reservoir of ARGs and that salinity is a predominant factor shaping the distribution patterns of soil resistome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Microorganisms associated with plants may alter the traits of the human microbiome important for human health, but this alteration has largely been overlooked. The plant microbiome is an interface between plants and the environment, and provides many ecosystem functions such as improving nutrient uptake and protecting against biotic and abiotic stress. The plant microbiome also represents a major pathway by which humans are exposed to microbes and genes consumed with food, such as pathogenic bacteria, antibiotic-resistant bacteria, and antibiotic-resistance genes. In this review we highlight the main findings on the composition and function of the plant microbiome, and underline the potential of plant microbiomes in the dissemination of antibiotic resistance via food consumption or direct contact., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Antibiotic resistance genes (ARGs) have emerged as a global health concern. A large volume of work has already been devoted to ARGs in aquatic ecosystems. However, ARG dispersal patterns in air remain to be largely unknown despite of its greater role in transmission. This work aims to investigate time-resolved airborne spread of ARGs and their corresponding subtype bacterial carriers in highly polluted air. Time-resolved air samples (20 m 3 each with three samples) were collected using a high volume sampler (1 m 3 /min) every 4 h continuously (both day and night) during low (14-93 μg/m 3 ) and high PM 2.5 (36-205 μg/m 3 ) pollution times (over 6 days with a total of 69 air samples) in Beijing. All air samples were subjected to 16S rRNA sequence analysis for 39 ARG subtypes. Pure culturable bacterial isolates from Beijing and Shijiazhuang were Sanger sequenced for species identification and also subjected to high throughput ARG subtype detection. ARG and its subtype relative abundances in the air were observed to differ greatly (up to 3 folds for abundance) both day and night, and the blaTEM gene was found to lead the ARG abundance. For an early morning time, the multi-drug resistant NDM-1 gene was detected up to 30% of total ARG abundance in highly polluted air. Identified as a major NDM-1 and vanB gene carrier, Bacillus halotolerans were also shown to disseminate more ARG subtypes. On another front, tnpA and intI1 were shown to vary greatly in abundance, while the sul3 gene was found widespread among the culturable Bacillus isolates in the air. Principal component analysis (PCA) showed different gene co-occurrence networks for different PM 2.5 pollution episodes, e.g., tnpA and intI1 for gene transfer and integration, respectively, were found more abundant for the high PM 2.5 pollution episode. This study highlights a serious yet previously unidentified public health threat from time-resolved airborne spread of ARGs. Further work is urgently warranted to track the sources of ARGs for their optimized control during high PM 2.5 pollution episodes., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

As a novel alkaloid, trolline is a potential methionine aminopeptidase Ⅱ inhibitor. However, up to now, no informations about the quantification of trolline were available in biosamples. In this study, a simple, specific and sensitive analytical method based on UHPLC-MS/MS method has been established and validated for determination of trolline in rat plasma and tissues after intravenous administration. Sample preparation was carried out by a simple liquid-liquid extraction and carbamazepine was used as internal standard (I.S.). Chromatographic separation was achieved by using a Waters BEH C 18 column and involving the optimized mobile phase of 0.1% formic acid aqueous solution and acetonitrile with gradient elution flow of 0.20 ml/min. Trolline and I.S. were detected by multiple reaction monitoring (MRM) modes with positive electrospray ionization and transitions at m/z 220.0→136.8 for trolline and m/z 237.0→193.9 for carbamazepine (I.S.). Good linearity was ranged from 10.0 ng/ml to 4000 ng/ml for trolline both in plasma and various tissues. The lower limit of quantification (LLOQ) was 10 ng/ml in all samples. The intra- and inter-day precision (RSD%) were below 11.3% and the accuracy (RE%) was ranged from -10.2% to 12.3%. The validated method was successfully applied to the pharmacokinetics and tissue distribution study of trolline after intravenous administration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Osteoblast differentiation, defined as the process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, is directly linked to multiple myeloma (MM) bone disease. Wnt and bone morphogenetic protein (BMP) are proved to be implicated in the pathological or defective osteoblast differentiation process. This study aims to test the involvement of Wnt, bone morphogenetic proteins (BMP) pathways, and empty spiracles homeobox 2 (EMX2) in osteoblast differentiation and MM development. Initially, differentially expressed genes in bone marrow mesenchymal stem cells (MSCs) from MM patients and healthy donors were identified using microarray-based gene expression profiling. The functional role of Wnt and BMP in MM was determined. Next, we focused on the co-operative effects of Wnt and BMP on calcium deposition, alkaline phosphatase (ALP) activity, the number of mineralized nodules, and osteocalcin (OCN) content in MSCs. The expression patterns of Wnt and BMP pathway-related genes, EMX2 and osteoblast differentiation-related factors were determined to assess their effects on osteoblast differentiation. Furthermore, regulation of Wnt and BMP in ectopic osteogenesis was also investigated in vivo. An integrated genomic screen suggested that Wnt and BMP regularly co-operate to regulate EMX2 and affect MM. EMX2 was downregulated in MSCs. The activated Wnt and BMP resulted in more calcium salt deposits, mineralized nodules, and a noted increased in ALP activity and OCN content by upregulating EMX2, leading to induced differentiation of MSCs into osteoblasts. Collectively, this study demonstrated that Wnt and BMP pathways could co-operatively stimulate differentiation of MSCs into osteoblasts and inhibit MM progression, representing potential targets for MM treatment., (© 2018 Wiley Periodicals, Inc.)

Liming is a common agronomic practice used for alleviating soil acidification to improve plant growth. However, it is still unclear how liming can affect the gut microbiota composition of soil fauna, and subsequently the nutrient cycling and litter decomposition mediated by soil fauna. In the present study the effect of liming on the gut microbiota of two types of soil fauna, Folsomia candida, and Enchytraeus crypticus was investigated by using 16S rRNA gene high-throughput sequencing. The results revealed that there are differences between the gut microbial communities of the two types of soil fauna as well as between the gut microbiome of the soil fauna and the surrounding soil. Enterobacteriaceae and Bacillaceae were the predominant families in the gut microbiota of E. crypticus, while Rickettsiaceae and Moraxellaceae were the predominant families in the gut microbiota of F. candida. Liming affected the gut microbiota of E. crypticus at both the taxonomical and core microbiota level. The gut microbiota of F. candida was not affected by liming. Structural equation models suggest that 97% of the variation in the E. crypticus gut microbiota could be explained by liming-induced changes in soil properties and the soil microbial community. The indirect effects of liming, caused by a shift in the soil microbial community, contributed more in reshaping the gut microbiota of E. crypticus than the direct effects of the changed soil properties did. These findings suggest that the effects of liming on the gut microbiota composition in soil fauna are species-specific and are likely dependent on the response of the host to changes in soil properties and the soil microbial community., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Near infrared spectroscopy(NIRS) was used for rapid quantitative analysis of saponins in Pien Tze Huang troches and powders. The near infrared spectra of Pien Tze Huang were collected,and the contents of notoginsenoside R1,ginsenoside Rg1 and ginsenoside Rb1 in Pien Tze Huang were determined by high performance liquid chromatography(HPLC) as the reference values. Then the near infrared spectra of the samples were associated with the reference values to establish the quantitative analysis models by using partial least squares(PLS) method. Finally,the models were verified by unknown samples. The results showed that root mean square error of cross-validation(RMSECV) of R1,Rg1,Rb1 and the total content was 0.095 1,0.555,0.414,0.960 mg·g-1 for the troches models,0.085 6,0.443,0.405,0.913 mg·g-1 for the powders models. After external validations,root mean square error of prediction(RMSEP) of R1,Rg1,Rb1 and the total content was 0.111,0.274,0.276,0.807 mg·g-1 for the troches models,0. 059 2,0. 322,0. 327,0. 705 mg·g-1 for the powders models. The averages of relative standard deviation between the predicted values and the chemical measured values were all less than 2.0%. According to the results of paired-t tests at the level of α = 0.05,there were no significant differences between the predicted values and the measured values. The established quantitative analysis models can be used to predict the contents of saponins in Pien Tze Huang accurately and the proposed method is simple,fast,non-destructive and environmentally friendly for the rapid detection and quality control of saponins in Pien Tze Huang.

The Mawangdui tomb No.1 cadaver, a female corpse from the Western Han Dynasty, was unearthed in 1972. Forensic examination at the time of discovery indicated fairly remarkable presence of bodily constituents at the anatomical, histological, and molecular levels. The cadaver was preserved in a formalin-based fixative afterward, and maintained in the Hunan Museum. To better protect this rare human corpse, a reappraisal of the status of preservation was carried out using noninvasive approaches, including X-ray radiography, gross anatomical examination, and histological, microbiological, and molecular analyses of sampled tissues. The cadaver remained essentially intact from a gross anatomical perspective, with radiography of the skeletal system and arterial contrast filling appeared comparable with the original documentation. The light microscopic features of the skin, cartilage, and skeletal muscle remained detectable, as were the stratified ultrastructure of the collagen and muscle fibers. The levels of nitrogen and amino acidic elements appeared elevated in the cadaver and liver preservation fixatives, with a higher calcium and phosphate concentration in the former. These findings suggest that there existed a certain degree of macromolecule degradation and bone decalcification in the cadaver, likely irrelevant to biological decomposition. The reappraisal also led to the implementation of stronger scientific measures to better protect the cadaver through a renovated Museum-University coadministrative management agreement.

Metastasis is a major cause of death in patients with breast cancer. In the process of cancer development, epithelial-mesenchymal transition (EMT) is crucial to promoting the invasion and migration of tumor cells. In a previous study, the role of resveratrol in migration and metastasis was investigated in MDA-MB-231 (MDA231) human breast cancer cells and a xenograft-bearing mouse model. Additionally, the related mechanism was explored. In the present study, in vitro Transwell assays showed that resveratrol can inhibit the migration of transforming growth factor (TGF)-β1-induced MDA231 cells in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) showed that resveratrol can reduce the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Immunofluorescence was performed to confirm the expression of EMT-related markers. Immunofluorescence assays confirmed that resveratrol changed the expression of the EMT-related markers E-cadherin and vimentin. Western blot analysis demonstrated that resveratrol decreased the expression levels of MMP-2, MMP-9, Fibronectin, α-SMA, P-PI3K, P-AKT, Smad2, Smad3, P-Smad2, P-Smad3, vimentin, Snail1, and Slug, as well as increased the expression levels of E-cadherin in MDA231 cells. In vivo, resveratrol inhibited lung metastasis in a mouse model bearing MDA231 human breast cancer xenografts without marked changes in body weight or liver and kidney function. These results indicate that resveratrol inhibits the migration of MDA231 cells by reversing TGF-β1-induced EMT and inhibits the lung metastasis of MDA231 human breast cancer in a xenograft-bearing mouse model., Competing Interests: The author(s) confirm that this article content has no conflict of interest.

To investigate the mechanism of a Bushen-Jianpi decoction (BSJPD) in liver cancer (LC) treatment, we analyzed clinical therapy data, conducted network pharmacology analysis, and performed pharmacological experimental verification in vitro and in vivo . The univariate analysis of clinical therapy showed that the BSJPD was protective factor ( p < 0.05). The network pharmacology analysis showed that 9 compounds were important nodes of BSJPD-LC therapy network. In experimental verification, the rate of apoptosis increased in the liver tumors of mice treated with the BSJPD ( p < 0.05); drug serum with 20 % BSJPD inhibited cell viability ( p < 0.05) and reduced the expression of PI3K, the Bcl-xL/BAD ratio, and the levels of p53 and p-Akt in HepG2 cells. Moreover, licochalcone A, alisol B, and hederagenin inhibited cell viability ( p < 0.05), induced cell apoptosis ( p < 0.01), reduced p-Akt levels, and increased cleaved-CASP3 ( p < 0.05) and p53 expression levels in HepG2 cells. These data suggest that the BSJPD prolongs the survival of LC patients and induces apoptosis and that it may be associated with the regulation of PI3K, Akt, p53, CASP3, and Bcl-xL/BAD expression.

Antibiotic resistance genes (ARGs), prevalent across multiple environmental media, threaten human health worldwide and are considered emerging environmental contaminants. Earthworm gut, a niche for bacteria to survive, represents a potential reservoir for ARGs in soil. However, the compositions of ARGs in the earthworm gut microbiota remain elusive, especially under field conditions. In this study, we applied high-throughput quantitative PCR to profile the ARGs in the gut microbiota of earthworms after chronic exposure to fertilizers. To elucidate the factors that impact the ARGs composition, the bacterial community of gut microbiota, mobile genetic elements (MGEs), soil (nutrients, heavy metals, and antibiotics) and the properties of gut content (pH and nutrients) were analyzed. A total of 98 subtypes among 9 major types of ARGs, and 3 different MGEs were detected in the gut microbiota of earthworms. Organic fertilizer (sewage sludge and chicken manure) application significantly increased the diversity and abundance of ARGs. Of the 1123 identified operational taxonomic units (OTUs) at 97% similarity cutoff, most of them were assigned to Firmicutes (55.5%) and Proteobacteria (33.6%) in earthworm gut microbiota. Long-term organic fertilization slightly changed the microbiota composition, but did not impact the diversity. Partial redundancy analysis (pRDA) revealed that bacterial community, combined with environmental factors (soil and gut content properties) and MGEs, explained 72% of the variations of ARGs in the earthworm gut. Furthermore, the co-occurrence pattern between ARGs and MGEs indicated that horizontal gene transfer via MGEs may occur in the earthworm gut. These findings improve the current understanding of the dynamics of soil fauna-associated ARGs and the gut microbiota of earthworms may be an underappreciated hotspot for ARGs in the environment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Microbial symbiosis is essential for the normal development and growth of hosts. Past attention has mostly been paid to its effects on plants and vertebrates. The effects of environmental pressures such as antibiotics on the microbiome of soil fauna remain largely elusive. We used bacterial 16S rRNA gene high-throughput sequencing to examine the response of microbiome of soil invertebrate Enchytraeus crypticus to oral tetracycline exposure. After two-week exposure, tetracycline-free oat was used as food to monitor the restoration of E. crypticus microbiome. The results showed that Proteobacteria, Actinobacteria and Planctomycetes were the three dominant phyla in all samples, Rhizobiaceae and Kaistia were the most abundant family and genus in all samples, respectively. After 14 days tetracycline exposure, Planctomycetes declined dramatically from 33.05% to 3.28% (P = 0.016), but Actinobacteria elevated substantially from 2.47% to 23.65% (P = 0.004). The alpha-diversity of microbial community increased significantly after tetracycline exposure compared to the control (P = 0.014). Terminating tetracycline exposure led to the recovery of E. crypticus microbiome back to the background level within 14 days. Our results suggest that while tetracycline can disturb the microbiome in E. crypticus significantly, the effects of the antibiotic on E. crypticus microbiome may not be permanent but reversibly diminish after stopping exposure for a period of time. The results may contribute to extending our understanding of the effect of antibiotics on microbiome of soil invertebrates. CAPSULE: The microbiome of E. crypticus exposed to tetracycline is perturbed and reversibly restored after terminating the exposure., (Copyright © 2018. Published by Elsevier B.V.)

Plasmid conjugation is one of the dominant mechanisms of horizontal gene transfer, playing a noticeable role in the rapid spread of antibiotic resistance genes (ARGs). Broad host range plasmids are known to transfer to diverse bacteria in extracted soil bacterial communities when evaluated by filter mating incubation. However, the persistence and dissemination of broad range plasmid in natural soil has not been well studied. In this study, Pseudomonas putida with a conjugative antibiotic resistance plasmid RP4 was inoculated into a soil microcosm, the fate and persistence of P. putida and RP4 were monitored by quantitative PCR. The concentrations of P. putida and RP4 both rapidly decreased within 15-day incubation. P. putida then decayed at a significantly lower rate during subsequent incubation, however, no further decay of RP4 was observed, resulting in an elevated RP4/ P. putida ratio (up to 10) after 75-day incubation, which implied potential transfer of RP4 to soil microbiota. We further sorted RP4 recipient bacteria from the soil microcosms by fluorescence-activated cell sorting. Spread of RP4 increased during 75-day microcosm operation and was estimated at around 10 -4 transconjugants per recipient at the end of incubation. Analysis of 16S rRNA gene sequences of transconjugants showed that host bacteria of RP4 were affiliated to more than 15 phyla, with increased diversity and shift in the composition of host bacteria. Proteobacteria was the most dominant phylum in the transconjugant pools. Transient transfer of RP4 to some host bacteria was observed. These results emphasize the prolonged persistence of P. putida and RP4 in natural soil microcosms, and highlight the potential risks of increased spread potential of plasmid and broader range of host bacteria in disseminating ARGs in soil.

Schizophrenia is a complex psychiatric disorder with high genetic heterogeneity, however, the contribution of rare mutations to the disease etiology remains to be further elucidated. We herein performed exome sequencing in a Han Chinese schizophrenia family and identified a missense mutation (c.6724C>T, p.R2242C) in the teneurin transmembrane protein 4 ( TENM4 ) gene in the SCZD2 locus, a region previously linked to schizophrenia at 11q14-21. The mutation was confirmed to co-segregate with the schizophrenia phenotype in the family. Subsequent investigation of TENM4 exons 31, 32, and 33 adjacent to the p.R2242C mutation revealed two additional missense mutations in 120 sporadic schizophrenic patients. Residues mutated in these mutations, which are predicted to be deleterious to protein function, were highly conserved among vertebrates. These rare mutations were not detected in 1000 Genomes, NHLBI Exome Sequencing Project databases, or our in-house 1136 non-schizophrenic control exomes. Analysis of RNA-Seq data showed that TENM4 is expressed in the brain with high abundance and specificity. In line with the important role of TENM4 in central nervous system development, our findings suggested that increased rare variants in TENM4 could be associated with schizophrenia, and thus TENM4 could be a novel candidate gene for schizophrenia in the SCZD2 locus.

The "4 per mil" initiative recognizes the pivotal role of soil in carbon resequestration. The need for evidence to substantiate the influence of agricultural practices on chemical nature of soil carbon and microbial biodiversity has become a priority. However, owing to the molecular complexity of soil dissolved organic matter (DOM), specific linkages to microbial biodiversity have eluded researchers. Here, we characterized the chemodiversity of soil DOM, assessed the variation of soil bacterial community composition (BCC), and identified specific linkages between DOM traits and BCC. Sustained organic carbon amendment significantly ( P < 0.05) increased total organic matter reservoirs, resulted in higher chemodiversity of DOM and emergence of recalcitrant moieties (H/C < 1.5). In the meantime, sustained organic carbon amendment shaped the BCC to a more eutrophic state while long-term chemical fertilization directed the BCC toward an oligotrophic state. Meanwhile, higher connectivity and complexity were observed in organic carbon amendment by DOM-BCC network analysis, indicating that soil microbes tended to have more interaction with DOM molecules after organic matter inputs. These results highlight the potential for organic carbon amendments to not only build soil carbon stocks and increase their resilience but also mediate the functional state of soil bacterial communities.

Environmental estrogens are capable of interfering with the spermatogenesis and fertility of fish. However in natural waters, these chemicals are more likely to occur as a combination rather than a single stressor. Whether and how the mixture of xenoestrogens with environmental relevant concentrations may affect fish spermatogenesis remains largely unknown. In this study, male zebrafish adults were administered to 17alpha-ethinylestradiol (EE2) and a mixture of xenoestrogens (Mix (E2, EE2, DES, 4-t-OP, 4-NP and BPA)), with the estrogenic potency equivalent to EE2. After a 60-day exposures, elevated mRNA levels of vitellogenin 1 (vtg1) and estrogen receptor 1 (esr1) in the liver of fish in both treated groups were observed. Moreover, the plasma level of E2 declined significantly in the Mix group and the ratio of 11-KT/E2 was significantly elevated in both treated groups. Consistently, the mRNA level of P450 side-chain cleavage (scc) in the EE2 group and ovarian type aromatase (cyp19a1a) in the Mix group was significantly suppressed. In addition, decreased gonadosomatic index and sperm count in the fish of Mix group were present. Furthermore, increased number of the proliferating germ cells (such as spermatogonia and spermatocytes) was observed in the fish of both groups, suggesting a stimulated germ cell proliferation and meiosis. Accordingly, both exposures significantly up-regulated the mRNA levels of genes in mitosis (cyclinb1) and meiosis (cyp26a1 in EE2 group, aldh1a2, cyp26a1, sycp3 and spo11 in Mix). In addition, decreased number of spermatozoa and increased number of TUNEL-positive signals were present in the testis of fish in the Mix group, indicating an enhanced apoptosis. Further analyses demonstrated the significant elevated expressions of tnfrsf1a and the ratio of tnfrsf1a/tnfrsf1b in the Mix group, suggesting an elevated apoptosis in the testis of fish in the Mix group via extrinsic pathway. The present study greatly extends our understanding of the underlying mechanisms of the reproductive toxicity of xenoestrogens on fish., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Numerous studies have investigated the composition and diversity of antibiotic resistance genes (ARGs) in multiple environments but the pattern of ARGs in field-collected soil fauna remains poorly understood. In the present study soil collembolans were collected from six sites with three different land use types (parkway land, park land, and arable land) and 285 ARGs and 10 mobile genetic elements (MGEs) in the microbiome of these "wild" collembolans were quantified by high-throughput quantitative PCR. A total of 76 unique ARGs and 5 MGEs were detected. There were significant differences between collection sites in the antibiotic resistome in the collembolans. Land use significantly altered the distribution patterns of collembolan ARGs. Thirty shared ARGs and three shared MGEs were identified. The co-occurrences of shared resistomes were largely random, and more positive relationships were found in the coassociation network. Partial redundancy analysis confirms that the changes in bacterial communities explained 27.77% of the variation in ARGs. These findings suggest that resistance genes are pervasive in the microbiome associated with the field collembolan and the activity of the collembolans may contribute to the spread and dissemination of resistance genes in the environment, an aspect of ARGs that has until now been largely overlooked.

Phyllosphere contains various microorganisms that may harbor diverse antibiotic resistance genes (ARGs). However, we know little about the composition of antibiotic resistome and the factors influencing the diversity and abundance of ARGs in the phyllosphere. In this study, 16S rRNA gene amplicon sequencing and high-throughput quantitative PCR approaches were employed to investigate the effects of long-term (over 10 years) organic fertilization on the phyllosphere bacterial communities and antibiotic resistome. Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes dominated in the phyllosphere bacterial communities. Long-term application of sewage sludge and chicken manure altered the phyllosphere bacterial community composition, with a remarkable decrease in bacterial alpha-diversity. A total of 124 unique ARGs were detected in the phyllosphere. The application of sewage sludge and chicken manure significantly increased the abundance of ARGs, with a maximum 2638-fold enrichment. Variation partitioning analysis (VPA) together with network analysis indicated that the profile of ARGs is strongly correlated with bacterial community compositions. These results improve the knowledge about the diversity of plant-associated antibiotic resistome and factors influencing the profile of ARGs in the phyllosphere., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: To retrospectively evaluate the safety and feasibility of a new modified laparoscopic Sugarbaker repair in patients with parastomal hernias., Methods: A retrospective study was performed to analyze eight patients who underwent parastomal hernia repair between June 2016 and January 2018. All of these patients received modified laparoscopic Sugarbaker hernia repair treatment. This modified technique included an innovative three-point anchoring and complete suturing technique to fix the mesh. All procedures were performed by a skilled hernia surgeon. Demographic data and perioperative outcomes were collected to evaluate the safety and efficacy of this modified technique., Results: Of these eight patients, two had concomitant incisional hernias. All the hernias were repaired by the modified laparoscopic Sugarbaker technique with no conversion to laparotomy. Three patients had in-situ reconstruction of intestinal stoma. The median mesh size was 300 cm 2 , and the mean operative time was 205.6 min. The mean postoperative hospitalization time was 10.4 d, with a median pain score of 1 (visual analog scale method) at postoperative day 1. Two patients developed postoperative complications. One patient had a pocket of effusion surrounding the biologic mesh, and one patient experienced an infection around the reconstructed stoma. Both patients recovered after conservative management. There was no recurrence during the follow-up period (6-22 mo, average 13 mo)., Conclusion: The modified laparoscopic Sugarbaker repair could fix the mesh reliably with mild postoperative pain and a low recurrence rate. The technique is safe and feasible for parastomal hernias., Competing Interests: Conflict-of-interest statement: All the authors declare no conflicts of interest related to this article.

Gut microbiota contribute to host health. Numerous recent studies have focused on the survival and reproduction of nontarget soil animals exposed to the toxicity of silver nanoparticles (AgNPs) but changes in the gut microbiota due to nanoparticle toxicity are largely unknown. Here, we examine some effects of AgNPs and silver nitrate (ionic Ag) on the gut microbiota of the common soil collembolan Folsomia candida using Illumina sequencing and concomitant changes in antibiotic resistance genes (ARGs) of the gut microbiota using high-throughput quantitative PCR. A large number of Ag accumulated in Ag-exposed individuals after 28 days and ionic Ag significantly inhibited the reproduction of the collembolan (by 19.3%). Exposure to AgNPs disturbed the composition of the collembolan gut bacterial community, resulting in dysbiosis of the gut microbiota. However, the dominant microbiota was shared among different treatments. In addition, AgNPs exposure did indeed reduce the incidence of ARGs in the collembolan gut microbiota. A weak relationship was identified between gut bacterial communities and ARG profiles. These results extend our knowledge regarding the role of the gut microbiota in assessing the soil ecotoxicology of AgNPs.

To characterize ticks in cattle from Guangdong Province and Guangxi Zhuang Nationality Autonomous Region, Southern China, 783 cattle in four localities were examined. Among them, 232 (29.63%) cattle were positive for tick infection. A total of 503 ticks collected in these cattle were further investigated. Two Rhipicephalus species, namely R. microplus and R. sanguineus, were firstly identified by morphological features. Thereinto, R. microplus is the prevalent species in cattle in southern China, with high prevalent in summer and autumn annually. Mixed infection of R. microplus and R. sanguineus was just found in yellow cattle. To further confirm the morphological identification of these cattle-origin ticks, a phylogeographic analysis inferred from the sequences of the ribosomal internal transcribed spacer-2 (ITS-2) was performed, and R. microplus and R. sanguineus were identified. However, the morphological taxonomy of R. microplus has been challenged in recent years. The mitochondrial cytochrome c oxidase subunit 1 (cox1) marker was then used to provide higher resolution of R. mircoplus complex. The re-constructed cox1 phylogenetic tree further identified these R. mircoplus tick samples as R. microplus Clade A. These findings illustrated the prevalence and characterization of cattle-origin ticks in Southern China for the first time, and provided base-line information for further control of tick and tick-borne disease in these areas., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Despite its emerging significant public health concern, the presence of antibiotic resistance genes (ARGs) in urban air has not received significant attention. Here, we profiled relative abundances (as a fraction, normalized by 16S rRNA gene) of 30 ARG subtypes resistant to seven common classes of antibiotics, which are quinolones, β-lactams, macrolides, tetracyclines, sulfonamides, aminoglycosides, and vancomycins, in ambient total particulate matter (PM) using a novel protocol across 19 world cities. In addition, their longitudinal changes in PM 2.5 samples in Xi'an, China as an example were also studied. Geographically, the ARGs were detected to vary by nearly 100-fold in their abundances, for example, from 0.07 (Bandung, Indonesia) to 5.6 (San Francisco, USA). The β-lactam resistance gene blaTEM was found to be most abundant, seconded by quinolone resistance gene qepA; and their corresponding relative abundances have increased by 178% and 26%, respectively, from 2004 to 2014 in Xi'an. Independent of cities, gene network analysis indicates that airborne ARGs were differentially contributed by bacterial taxa. Results here reveal that urban air is being polluted by ARGs, and different cities are challenged with varying health risks associated with airborne ARG exposure. This work highlights the threat of urban airborne transmission of ARGs and the need of redefining our current air quality standards in terms with public health.

The present working hypothesis is that the Cu-induced changes in lipid metabolism may be mediated by miRNAs. Here, we describe the miRNA profile of the liver tissues of yellow catfish exposed to waterborne Cu, based on larger-scale sequencing of small RNA libraries. We identified a total of 172 distinct miRNAs. Among these miRNAs, compared to the control, mRNA expression levels of 16 miRNAs (miR-203a, 205, 1788-3p, 375, 31, 196a, 203b-3p, 2187-5p, 196d, 459-3p, 153a and miR-725, and two novel-miRNAs: chr4-1432, chr-7684) were down-regulated, and mRNA levels of miR-212 and chr20-5274 were up-regulated in Cu-exposed group. The functions of their target genes mainly involved ether lipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism and α-linolenic acid metabolism. Cu exposure inhibited the expression of miR-205, whose predicted target genes were enriched in the pathway of lipid metabolism, including fas , lxrα , ddit3 , lamp2 , casp3a and baxa . These potential target genes were further verified by Dual-luciferase reporter gene assay. Using primary hepatocytes of yellow catfish, Cu incubation down-regulated miR-205 expression, and increased TG contents and FAS activity. LXR antagonist effectively ameliorate the Cu-induced change of TG content and FAS activity. These data suggest that down-regulation of the miRNA-205 may be an important step in Cu-induced changes in lipid metabolism in yellow catfish.

Objective: To investigate the characteristics and predictors for anastomotic leakage after oesophagectomy for oesophageal carcinoma from the perspective of anastomotic level., Design: Retrospective cohort study., Settings: A single tertiary medical centre in China., Participants: From January 2010 to December 2016, all patients with oesophageal cancer of the distal oesophagus or gastro-oesophageal junction undergoing elective oesophagectomy with a curative intent for oesophageal carcinoma with intrathoracic oesophagogastric anastomosis (IOA) versus cervical oesophagogastric anastomosis (COA) were included. We investigated anastomotic level and perioperative confounding factors as potential risk factors for postoperative leakage by univariate and multivariate logistic regression., Primary Outcome Measures: The primary outcome was the odds of anastomotic leakage by different confounding factors. Secondary outcome was the association of IOA versus COA with other postoperative outcomes., Results: Of 458 patients included, 126 underwent cervical anastomosis and 332 underwent intrathoracic anastomosis. Anastomotic leakage developed in 55 patients (12.0%), with no statistical differences between COA and IOA (16.6% vs 10.2%; p=0.058). Multivariable analysis identified active diabetes mellitus (OR 2.001, p=0.047), surgical procedure (open: reference; minimally invasive: OR 1.770, p=0.049) and anastomotic method (semimechanical: reference; stapled: OR 1.821; handsewn: OR 2.271, p=0.048) rather than anastomotic level (IOA: reference; COA: OR 1.622, p=0.110) were independent predictors of leakage., Conclusions: Surgical and anastomotic techniques rather than the level of anastomotic site were independent predictors of postoperative anastomotic leakage in patients undergoing oesophageal cancer surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Myeloma severely threatens public health, and molecular targeting treatment becomes the future perspective. Dual specificity phosphatases (DSUP) protein has multiple functions including modulating cell proliferation, differentiation, aging, and apoptosis. Whether DUSP can regulate myeloma cell is unclear. This study thus aimed to investigate the effect of DUSP on myeloma cell line RPMI8226 cell aging and provide evidence for the clinical treatment of myeloma., Materials and Methods: H2O2-induced aging model of myeloma cell line RPMI8226 was generated. DUSP over-expression plasmid or specific siRNA was transfected by liposome. Western blot was used to detect the expression of DUSP in RPMI8226 cells. Cell aging condition was evaluated by β-galactosidase assay. Aging proteins P53 and P16 expression levels, the activation of TLR4 signal pathway were tested by immunoblotting. TLR4 signal pathway was then suppressed by Verteporfin for testing RPMI8226 cell aging., Results: Growing levels of DUSP, aging proteins P53 and P16, with inhibition of TLR4 signal pathway were found in the H2O2-induced aging model of myeloma cell line RPMI8226. Transfection of DUSP over-expression plasmid or siRNA potentiated or inhibited the aging of RPMI8226 cells induced by H2O2 and suppressed or enhanced TLR4 signal pathway, respectively. Verteporfin, an inhibitor of TLR4, increased the level of P53 and aging of RPMI8226 cells., Conclusions: DUSP facilitates H2O2-induced aging of myeloma cell line RPMI8226 and suppresses TLR4 expression, which provides academic basis for clinical intervention.

Objective: To understand the etiology, clinical prognosis and risk factors of adult community-acquired acute bacterial meningitis (ABM) and provide the evidence for clinical diagnosis and treatment., Methods: We performed a retrospective study of 181 clinically diagnosed hospitalized patients with community-acquired adult ABM from Jan.2010 to Jan.2018. The patients were categorized as non-elderly (16≤age<65 years old, n =156 ) and elderly (age≥65 years old, n =25) group. The etiology, clinical features, prognosis and risk factors of the two groups were compared., Results: Sixty-four of 181 patients (35.4%) had pathogens detected. The most common pathogens were Streptococcus pneumoniae (17.9%), Listeria monocytogenes (13.4%) and Klebsiella pneumoniae (10.5%). The mortality of the elderly group was higher than that of the non-elderly group ( P <0.05). Univariate analysis showed that there was a significant difference between the elderly group and the non-elderly group in the incidence of hypertension, hypokalemia, pulmonary infection, ear-nose-throat ( ENT) infection, cerebrospinal fluid (CSF) protein concentration, head CT abnormalities and mortality. Logistic regression analysis showed that pulmonary infection and temperature ≥38.5 ℃ were independent risk factors for poor prognosis in the non-elderly group. CSF pressure ≥200 mmH 2 O was a independent risk factors for poor prognosis in the elderly group., Conclusion: The pathogens that cause acute bacterial meningitis in adult community are mainly Streptococcus pneumoniae, Listeria monocytogenes and Klebsiella pneumoniae. Pulmonary infection and temperature ≥38.5 ℃ are independent risk factors of poor prognosis in the non-elderly patients, as CSF pressure ≥200 mmH 2 O a independent risk factor in the elderly patients., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Porcine reproductive and respiratory syndrome virus (PRRSV) is considered an important economic pathogen for the international swine industry. At present, both PRRSV-1 and PRRSV-2 have been confirmed to be co-circulating in China. However, there is little available information about the prevalence or distribution of PRRSV-1 in Guangdong province, southern China. In this study, we performed molecular detection of PRRSV-1 in 750 samples collected from 50 farms in 15 major pig farming regions in this province. After RT-PCR testing, 64% (32/50) of farms were confirmed as PRRSV-1-positive. Surprisingly, PRRSV-1 was circulating on at least one pig farm in all 15 regions; of the 750 samples, 186 samples (24.8%) were positive for PRRSV-1. Furthermore, 15 representative PRRSV-1 ORF5 sequences (606 bp) (n = 1 per region) were obtained from those PRRSV-1-positive regions. Sequence alignment analysis indicated that they shared 81.8% ~ 100% nucleotide and 81.2% ~ 100% amino acid similarity with each other. Although all current PRRSV-1 sequences were divided into pandemic subtype 1, most of them had unique glycoprotein-5 amino acid sequences that are significantly different from other known PRRSV-1 isolates. To conclude, the present findings revealed wide geographical distribution of PRRSV-1 in Guangdong province, southern China. This study further extends the epidemiological significance of PRRSV-1 in China.

Aim: To describe the clinical features of congenital double elevator palsy (CDEP) and to evaluate various surgical outcomes between the standard Knapp and augmented Knapp procedures, based on improvements in primary eye position and ocular motility., Methods: Twenty-two patients with CDEP at Shanghai Children's Hospital were enrolled from July 2014 to January 2018. The forced duction test (FDT) was negative in 21 patients, aged 8mo to 12y (mean 5.4y). Patients were divided into two treatment groups: 16 patients underwent the standard Knapp procedure (group A), with or without horizontal squint procedure; and 5 patients underwent the augmented Knapp procedure (Foster procedure; group B). One patient underwent inferior rectus recession in the affected eye and superior rectus recession in the sound eye because of a positive FDT. The pre- and postoperative vertical deviations in the primary position and ocular motility were compared in the two groups., Results: Twenty-one eyes of the 22 patients (95%) were aligned within 10 prism diopters (PD), and all patients (100%) reached ≥25% elevation improvement after surgery. The average corrected vertical deviation in group B was statistically better than that of group A. For group A, the vertical deviation in the primary position decreased from 24.75Δ±8.35Δ to 4.56Δ±8.07Δ after surgery, for an improvement of 23.06Δ±6.51Δ ( P <0.05). In group B, the decrease was from 35.00Δ±5.00Δ (range 30Δ-40Δ) to 1.00Δ±2.24Δ, for an improvement of 34.00Δ±4.18Δ ( P <0.05). There were significant differences between the pre- and postoperative elevation in each group (group A, P <0.05; group B, P <0.05). The average scale of improved elevation in group B (1.80±0.45) was not significantly better than that of group A (1.69±0.87; Z =-0.732, P =0.548). The average follow-up periods lasted 21mo in group A and 18mo in group B., Conclusion: For vertical deviations <30Δ, the standard Knapp procedure can be chosen. For deviations greater than 30Δ-40Δ, the Foster procedure should be chosen. Because of our early interference, the inferior rectus (IR) muscle did not show mechanical restriction. Monocular elevation deficiency (MED) should be diagnosed early so that complications will be reduced and the procedure will be easier for the surgeon.

Wastewater treatment plants (WWTPs) contain diverse antibiotic resistance genes (ARGs), and thus are considered as a major pathway for the dissemination of these genes into the environments. However, comprehensive evaluations of ARGs dynamic during wastewater treatment process lack extensive investigations on a broad spectrum of ARGs. Here, we investigated the dynamics of ARGs and bacterial community structures in 114 samples from eleven Chinese WWTPs using high-throughput quantitative PCR and 16S rRNA-based Illumina sequencing analysis. Significant shift of ARGs profiles was observed and wastewater treatment process could significantly reduce the abundance and diversity of ARGs, with the removal of ARGs concentration by 1-2 orders of magnitude. Whereas, a considerable number of ARGs were detected and enriched in effluents compared with influents. In particular, seven ARGs mainly conferring resistance to beta-lactams and aminoglycosides and three mobile genetic elements persisted in all WWTPs samples after wastewater treatment. ARGs profiles varied with wastewater treatment processes, seasons and regions. This study tracked the footprint of ARGs during wastewater treatment process, which would support the assessment on the spread of ARGs from WWTPs and provide data for identifying management options to improve ARG mitigation in WWTPs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Struvite recovered from wastewater is promising for recycling phosphorus into soil as fertilizers. However, struvite application may prompt the proliferation of antibiotic resistance in soil and plant. This study examined the impacts of struvite application and biochar amendment on integrons abundance and gene cassette contexts in rhizosphere soil and phyllosphere using quantitative PCR and clone library analysis. Microcosm experiments revealed that class 1 integron was the most prevalent in all samples, with higher concentration and higher relative abundance in rhizosphere than those in phyllosphere. The majority of resistance gene cassettes were associated with genes encoding resistance to aminoglycosides, beta-lactams and chloramphenicols. Struvite application significantly increased the genetic diversity of antibiotic resistance gene cassettes in both rhizosphere and phyllosphere. However, biochar amendment attenuated the increasing effect of struvite application exerting on the class 1 integron antibiotic resistance gene cassette pool in phyllosphere. These findings highlighted human activities to be the source of integron gene cassette pool and raised the possibility of using biochar amendment as an alternative mean for mitigating antibiotic resistance in environments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Unfortunately, after publication of this article [1], it was noticed that the accession numbers for the study were missing. The correct numbers are PRJNA438554, SRP148953.

Background: As a disease of hematopoietic stem cell, chronic myeloid leukemia (CML) possesses unique biological and clinical features. However, the biologic mechanism underlying its development remains poorly understood. Thus, the objective of the present study is to discuss the effect of cytidine deaminase (CDA) gene silencing on the apoptosis and proliferation of CML K562 cells., Methods: CDA mRNA expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzymatic activity of CDA was measured by a nuclide liquid scintillation method. RT-qPCR and Western blot analysis were used to detect CDA mRNA and protein expression. Cell proliferation, apoptosis and cell cycle were measured by CCK-8 assay and flow cytometry. The expression of proteins relevant to cell proliferation, apoptosis and cell cycle was measured by Western blot analysis. Tumor xenografts were implanted in nude mice to verify the effect of CDA silencing on tumor growth in vivo., Results: CML and AL patients showed increased mRNA expression and enzymatic activity of CDA. Compared with the blank group, the mRNA and protein expression of CDA in the shRNA-1 and shRNA-2 groups decreased significantly. As a result, the proliferation of K562 cells was inhibited after CDA silencing and the cells were mainly arrested in S and G2 phases, while the apoptosis rate of these cells was increased. In addition, CDA gene silencing in K562 cells led to down-regulated p-ERK1/2, t-AKT, p-AKT and BCL-2 expression and up-regulated expression of P21, Bax, cleaved caspase-3/total caspase-3 and cleaved PARP/total PARP. Finally, CDA gene silencing inhibited tumor growth., Conclusion: Our study demonstrated that CDA gene silencing could inhibit CML cell proliferation and induce cell apoptosis. Therefore, CDA gene silencing may become an effective target for the treatment of leukemia.

Tributyltin (TBT), an organotin acting as aromatase (Cyp19a1) inhibitor, has been found to disrupt gametogenesis and reproductive behaviors in several fish species. However, few studies addressing the mechanisms underlying the impaired gametogenesis and reproduction have been reported. In this study, female adults of zebrafish (Danio rerio) were continuously exposed to two nominal concentrations of TBT (100 and 500 ng/L, actual concentrations: 90.8 ± 1.3 ng/L and 470.3 ± 2.7 ng/L, respectively) for 28 days. After exposures, TBT decreased the total egg number, reduced the hatchability and elevated the mortality of the larvae. Decreased gonadosomatic index (GSI) and altered percentages of follicles in different developmental stages (increased early-stage follicles and reduced mid/late-stage follicles) were also observed in the ovary of TBT-treated fish. TBT also lowered the plasma level of 17β-estradiol and suppressed the expressions of cyp19a1a in the ovary. In treated fish, up-regulated expressions of aldhla2, sycp3 and dmc1 were present in the ovary, indicating an enhanced level of meiosis. The mRNA level of vtg1 was dramatically suppressed in the liver of TBT-treated fish, suggesting an insufficient synthesis of Vtg protein, consistent with the decreased percentage of mid/late-stage follicles in the ovaries. Moreover, TBT significantly suppressed the reproductive behaviors of the female fish (duration of both sexes simultaneously in spawning area, the frequency of meeting and the visit in spawning area) and down-regulated the mRNA levels of genes involved in the regulation of reproductive behaviors (cyp19a1b, gnrh-3 and kiss 2) in the brain. In addition, TBT significantly suppressed the expressions of serotonin-related genes, such as tph2 (encoding serotonin synthase), pet1 (marker of serotonin neuron) and kiss 1 (the modulator of serotonin synthesis), suggesting that TBT might disrupt the non-reproductive behaviors of zebrafish. The present study demonstrated that TBT may impair the reproductive success of zebrafish females probably through disrupting oogenesis, disturbing reproductive behaviors and altering serotonin synthesis. The present study greatly extends our understanding on the reproductive toxicity of TBT on fish., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The optimal therapeutic strategy in UICC stage T3 hepatocellular carcinoma (HCC) patients that maximizes both safety and long-term outcome has not yet been determined. Our aim was to compare clinical outcomes following hepatic resection (HR) versus transarterial chemoembolization (TACE) for stage T3 HCC., Methods: From 2005 to 2013, 1179 patients with T3 HCC who underwent HR or TACE were divided into two groups, HR group (n = 280) or TACE group (n = 899). The clinical outcomes were compared before and after propensity score matching., Results: The propensity model matched 244 patients in each group for further analyses. After matching, medium overall survival (OS), 1, 3, and 5-year OS rates in TACE group were 11.8 (95%CI, 9.9-13.7) months, 49.6, 16.5, and 8.4%, respectively; which in HR group were 17.8 (95% CI, 14.8-20.8) months, 63.1, 33.3, and 26.4%, respectively; (log rank = 19.908, P < 0.01). Patients in HR group were more likely to develop pleural effusion, compared with those in TACE group (0.4% vs. 5.3%, P = 0.01). However, no significant differences in other adverse events (AEs) were found between two groups. Similar results were also demonstrated prior to the matched analysis. Multivariate analysis indicated that prothrombin time (PT), tumor size, tumor numbers, UICC staging status, and initial treatment were independent prognostic factors., Conclusions: Our study revealed that TACE was an option for UICC T3 HCC patients. However, HR seemed to be safe and yield a survival benefit compared with TACE, especially for patients with a good underlying liver function.

Liver fibrosis is a consequence of chronic liver disease that can progress to liver cirrhosis or even hepatocarcinoma. Fuzheng Huayu (FZHY), a Chinese herbal formula, has been shown to exert anti-fibrotic effects. To better understand the molecular mechanisms underlying the anti-fibrotic effects of FZHY, we analyzed transcriptomic and proteomic combination profiles in CCl 4 -induced liver fibrosis in rats, which were treated with extracted FZHY powder (0.35 g·kg -1 ·d -1 , ig) for 3 weeks. We showed that FZHY administration significantly improved liver function, alleviated hepatic inflammatory and fibrotic changes, and decreased the hydroxyproline content in the livers of CCl 4 -treated rats. When their liver tissues were examined using microarray and iTRAQ, we found 255 differentially expressed genes (fold change ≥1.5, P<0.05) and 499 differentially expressed proteins (fold change ≥1.2, P<0.05) in the FZHY and model groups. Functional annotation with DAVID (The Database for Annotation, Visualization and Integrated Discovery) showed that 15 enriched gene ontology terms, including drug metabolic process, response to extracellular stimulus, response to vitamins, arachidonic acid metabolic process, response to wounding, and oxidation reduction might be involved in the anti-fibrotic effects of FZHY; whereas KEGG pathway analysis revealed that eight enriched pathways, including arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450, and drug metabolism might also be involved. Moreover, the protein-protein interaction network demonstrated that 10 core genes/proteins overlapped, with Ugt2a3, Cyp2b1 and Cyp3a18 in retinol metabolism pathway overlapped to a higher degree. Compared to the model rats, the livers of FZHY-treated rats had significantly higher mRNA and protein expression levels of Ugt2a3, Cyp2b1 and Cyp3a18. Furthermore, the concentration of retinoic acid was significantly higher in the FZHY-treated rats compared with the model rats. The results suggest that the anti-fibrotic effects of FZHY emerge through multiple targets, multiple functions, and multiple pathways, including FZHY-regulated retinol metabolism, xenobiotic metabolism by cytochrome P450, and drug metabolism through up-regulated Ugt2a3, Cyp2b1, and Cyp3a18. These genes may play important anti-fibrotic roles in FZHY-treated rats.