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Yan HF, Zheng CL, Li Z, et al. Cancer Manag Res. 2019;11:3237-3251. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Concerns were raised about the integrity of the data in the article following the author’s request to make a correction. It was found images from several figures within the article had been duplicated. Specifically, The image for Figure 2C, Migration, SNU216, Si1 has been duplicated with the image for Figure 2C, Invasion, SNU216, Si1. The western blot bands for Figure 2B, SNU216, GAPDH, have been duplicated with the image for Figure 4B, BGC823, GAPDH. The image for Figure S3D, Collagen, 30 minutes, OE, has been duplicated with the image for Figure S3D, Collagen, 60 minutes, NC. When approached for an explanation, the authors were cooperative and provided original data for their study. However, the provided data did not satisfactorily explain how the duplication of these images occurred and was unable to alleviate the journal’s concerns regarding the validity of the findings. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors do not agree with the retraction. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Hongfei Yan,1,2,* Chunlei Zheng,1,2,* Zhi Li,1,2 Bowen Bao,1,2 Bowen Yang,1,2 Kezuo Hou,1,2 Xiujuan Qu,1,2 Jiawen Xiao,3 Xiaofang Che,1,2 Yunpeng Liu1,2 1Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China; 2Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang 110001, China; 3Department of Medical Oncology, Shenyang Fifth People Hospital, Tiexi District, Shenyang 110001, China *These authors contributed equally to this work Purpose: This study aimed to investigate the effect of NPTX1 on the prognosis of gastric cancer (GC), as well as the metastatic process in GC. Materials and methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the association between NPTX1 expression and prognosis in GC. Quantitative real-time polymerase chain reaction and Western blots were applied to examine the expression of NPTX1 in GC cell lines and expression of genes in downstream pathways. The role of NPTX1 on the migration, invasion, adhesion, and proliferation of GC cell lines was investigated with the transwell assay, the adhesion assay, and the MTT assay. Immunofluorescence staining was used to observe the effect of NPTX1 knockdown on the morphology of cells. Results: According to the review of TCGA and GEO databases of GC, we found that the expression of NPTX1 increased in cancer tissues and high NPTX1 expression was correlated with poor overall survival, which was associated with lymph node stage in clinicopathologic parameters. Knockdown of NPTX1 attenuated the migration, invasion, and adhesion abilities of GC cells. According to gene set enrichment analysis, NPTX1 was found to be positively related to integrin and focal adhesion (FA). Additionally, NPTX1 knockdown decreased the expression of integrin α1 and integrin α7, followed by deregulation of the expression of p-Src, p-Akt, p-Erk, MMP2, and MMP7, as well as inhibiting the formation of FA complexes and decreasing the length of pseudopods in GC cells. Conclusion: Our study provides strong evidence that NPTX1 plays a crucial role in promoting metastasis and acts as a prognostic indicator in GC. Keywords: gastric cancer, NPTX1,metastasis, integrin

Li Qun Jiang,1 Ting Yu Wang,1 Thomas J Webster,2 Hua-Jian Duan,1 Jing Ying Qiu,1 Zi Ming Zhao,1 Xiao Xing Yin,1,* Chun Li Zheng3,* 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Biodegradable nanomaterials have been widely used in numerous medical fields. To further improve such efforts, this study focused on the intracellular disposition of chitosan nanoparticles (CsNPs) in macrophages, a primary cell of the mononuclear phagocyte system (MPS). Such interactions with the MPS determine the nanoparticle retention time in the body and consequently play a significant role in their own clinical safety. In this study, various dye-labeled CsNPs (about 250 nm) were prepared, and a murine macrophage cell line (RAW 264.7) was selected as a model macrophage. The results showed two mechanisms of macrophage incorporation of CsNPs, ie, a clathrin-mediated endocytosis pathway (the primary) and phagocytosis. Following internalization, the particles partly dissociated in the cells, indicating cellular digestion of the nanoparticles. It was proved that, after intracellular uptake, a large proportion of CsNPs were exocytosed within 24 h; this excretion induced a decrease in fluorescence intensity in cells by 69%, with the remaining particles possessing difficulty being cleared. Exocytosis could be inhibited by both wortmannin and vacuolin-1, indicating that CsNP uptake was mediated by lysosomal and multivesicular body pathways, and after exocytosis, the reuptake of CsNPs by neighboring cells was verified by further experiments. This study, thus, elucidated the fate of CsNPs in macrophages as well as identified cellular disposition mechanisms, providing the basis for how CsNPs are recognized by the MPS; such information is crucial to numerous medical applications of CsNPs. Keywords: exocytosis, uptake, intercellular transport, chitosan nanoparticles, macrophages

Minhui Hu,1 Chunlan Zheng,1 Feng Gao2 1Department of Internal Medicine – Section 5, Wuhan Pulmonary Hospital (Wuhan Tuberculosis Control Institute), 2Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Abstract: Antituberculosis (anti-TB) treatment may be affected by both diabetes and hypoglycemic agents in patients with these 2 comorbidities. However, data supporting this conclusion relate only to standard anti-TB therapies. Sirturo® (bedaquiline) and Deltyba® (delamanid), novel drugs for multidrug-resistant tuberculosis (MDR-TB), are recommended for diabetes patients when another effective treatment regimen cannot be provided. Currently, there are no clinical data related to the use of these agents in diabetes patients. Possible alterations in the pharmacokinetics of these novel drugs induced by changes in subcutaneous adipose blood flow, gastric emptying, or nephropathy in diabetes patients, and possible drug–drug interactions with hypoglycemic agents, are of special interest, since the efficacy of bedaquiline and delamanid is concentration dependent. Moreover, it is of fundamental importance to avoid possible additive or synergistic effects of adverse drug reactions in this already vulnerable patient group. We reviewed clinical particularities related to the use of bedaquiline and delamanid in patients with type 1 and 2 diabetes mellitus (DM), as well as pharmacological aspects of the concurrent use of these agents with oral and injectable hypoglycemic agents. Bedaquiline shares liver metabolic pathways with several oral hypoglycemic agents, whereas delamanid may compete with several oral hypoglycemic agents and insulin analogs at protein-binding sites. Special concern exists regarding the use of bedaquiline and delamanid in diabetes patients aged >65 years and patients with severe renal or hepatic impairment or electrolyte disturbances. Concurrent use of bedaquiline and delamanid with insulin analogs, and other hypoglycemic agents that prolong the heart rate-corrected QT interval, such as sulfonylureas and glinides, may enhance this adverse reaction. Hepatic-related adverse reactions may develop more frequently when these drugs are combined with thiazolidinediones and acarbose. Data from Phase III and postmarketing studies are needed to elucidate the effect of DM and hypoglycemic agents on bedaquiline and delamanid effects in MDR-TB patients. Keywords: bedaquiline, delamanid, oral hypoglycemic agents, insulin analogs, pharmacokinetics

Peng Zhao,1,2 Jiansheng Li,1,2 Ya Li,1,2 Yange Tian,1,2 Yonghua Wang,2,3 Chunli Zheng3 1Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, 2Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, 3Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, People’s Republic of China Background: The Chinese herbal Bufei Jianpi formula (BJF) provides an effective treatment option for chronic obstructive pulmonary disease (COPD). However, the systems-level mechanism underlying the clinical effects of BJF on COPD remains unknown. Methods: In this study, a systems pharmacology model based on absorption filtering, network targeting, and systems analyses was applied specifically to clarify the active compounds and therapeutic mechanisms of BJF. Then, a rat model of cigarette smoke- and bacterial infection-induced COPD was used to investigate the therapeutic mechanisms of BJF on COPD and its comorbidity. Results: The pharmacological system successfully identified 145 bioactive ingredients from BJF and revealed 175 potential targets. There was a significant target overlap between the herbal constituents of BJF. These results suggested that each herb of BJF connected with similar multitargets, indicating potential synergistic effects among them. The integrated target–disease network showed that BJF probably was efficient for the treatment of not only respiratory tract diseases but also other diseases, such as nervous system and cardiovascular diseases. The possible mechanisms of action of BJF were related to activation of inflammatory response, immune responses, and matrix metalloproteinases, among others. Furthermore, we demonstrated that BJF treatment could effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo. Conclusion: This study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD. Keywords: chronic obstructive pulmonary disease, Bufei Jianpi formula, systems pharma­cology

Dongxi Xiang,1 Yang Zheng,2 Wei Duan,1 Xiujing Li,3 Jianjian Yin,3 Sarah Shigdar,1 Michael Liam O’Connor,1 Manju Marappan,1 Xiaojuan Zhao,4 Yingqiu Miao,3 Bin Xiang,5 Conglong Zheng31School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia; 2Department of Pharmacology, Osaka University, Osaka, Japan; 3Department of Biology, Medical College, Dalian University, Liaoning, People’s Republic of China; 4Department of Gynaecology and Obstetrics, Qingdao Central Hospital, Shandong, People’s Republic of China; 5Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Liaoning, People’s Republic of ChinaAbstract: Silver nanoparticles (AgNPs) have attracted much attention as antimicrobial agents and have demonstrated efficient inhibitory activity against various viruses, including human immunodeficiency virus, hepatitis B virus, and Tacaribe virus. In this study, we investigated if AgNPs could have antiviral and preventive effects in A/Human/Hubei/3/2005 (H3N2) influenza virus infection. Madin-Darby canine kidney cells infected with AgNP-treated H3N2 influenza virus showed better viability (P

Aeromonas salmonicida is the typical pathogen causing furunculosis, reported widely in salmonids. Because of multiple serotypes, the control of A. salmonicida-caused disease has increasingly received much attention. Recently, A. salmonicida infection was reported in non-salmonid fish species. Here, a pathogenic A. salmonicida, named as As-s, was isolated from cultured snakehead (Channa argus) in a local fish farm in Shandong, China. As-s displayed clear hemolysis, amylase, and positive catalase activities, and grew at a wide range of temperatures (10-37 °C) and pH values (5.5-8.5). As-s was highly sensitive to cefuroxime sodium, ceftriaxone, ceftazidime, piperacillin, and cefoperazone and also apparently sensitive to chloramphenicol, erythromycin, and 25% cinnamaldehyde. The Virulence array protein gene cloning' results suggested that As-s has this gene compared with the other two vapA-containing strains, despite a close relationship of these strains via phylogenetic analysis. Severe ulcers on skin, muscle, and abnormal liver, and hemorrhage in pectoral/ventral fins and anal region were observed, and exophthalmos were also noticed in infected juvenile snakehead, as well as necrosis and infiltration of blood cells emerged in the internal organs using pathological section. In addition, As-s caused high mortality in snakehead, consistently with its immune gene response. This study reports the first isolation of vapA-absent A. salmonicida in snakehead., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Microbially induced carbonate precipitation (MICP) has been used to cure rare earth slags (RES) containing radionuclides (e.g. Th and U) and heavy metals with favorable results. However, the role of microbial extracellular polymeric substances (EPS) in MICP curing RES remains unclear. In this study, the EPS of Lysinibacillus sphaericus K-1 was extracted for the experiments of adsorption, inducing calcium carbonate (CaCO 3 ) precipitation and curing of RES. The role of EPS in in MICP curing RES and stabilizing radionuclides and heavy metals was analyzed by evaluating the concentration and morphological distribution of radionuclides and heavy metals, and the compressive strength of the cured body. The results indicate that the adsorption efficiencies of EPS for Th (IV), U (VI), Cu 2+ , Pb 2+ , Zn 2+ , and Cd 2+ were 44.83%, 45.83%, 53.7%, 61.3%, 42.1%, and 77.85%, respectively. The addition of EPS solution resulted in the formation of nanoscale spherical particles on the microorganism surface, which could act as an accumulating skeleton to facilitate the formation of CaCO 3 . After adding 20 mL of EPS solution during the curing process (Treat group), the maximum unconfined compressive strength (UCS) of the cured body reached 1.922 MPa, which was 12.13% higher than the CK group. The contents of exchangeable Th (IV) and U (VI) in the cured bodies of the Treat group decreased by 3.35% and 4.93%, respectively, compared with the CK group. Therefore, EPS enhances the effect of MICP curing RES and reduces the potential environmental problems that may be caused by radionuclides and heavy metals during the long-term sequestration of RES., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In light of the important biological activities and widespread applications of organic disulfides, dithiocarbamates, xanthates, thiocarbamates and thiocarbonates, the continual persuit of efficient methods for their synthesis remains crucial. Traditionally, the preparation of such compounds heavily relied on intricate multi-step syntheses and the use of highly prefunctionalized starting materials. Over the past two decades, the direct sulfuration of C-H bonds has evolved into a straightforward, atom- and step-economical method for the preparation of organosulfur compounds. This review aims to provide an up-to-date discussion on direct C-H disulfuration, dithiocarbamation, xanthylation, thiocarbamation and thiocarbonation, with a special focus on describing scopes and mechanistic aspects. Moreover, the synthetic limitations and applications of some of these methodologies, along with the key unsolved challenges to be addressed in the future are also discussed. The majority of examples covered in this review are accomplished via metal-free, photochemical or electrochemical approaches, which are in alignment with the overraching objectives of green and sustainable chemistry. This comprehensive review aims to consolidate recent advancements, providing valuable insights into the dynamic landscape of efficient and sustainable synthetic strategies for these crucial classes of organosulfur compounds., (© 2024 Wiley-VCH GmbH.)

Organochalcogen compounds are prevalent in numerous natural products, pharmaceuticals, agrochemicals, polymers, biological molecules and synthetic intermediates. Direct chalcogenation of C-H bonds has evolved as a step- and atom-economical method for the synthesis of chalcogen-bearing compounds. Nevertheless, direct C-H chalcogenation severely lags behind C-C, C-N and C-O bond formations. Moreover, compared with the C-H monochalcogenation, reports of selective mono-/dichalcogenation and exclusive dichalcogenation of C-H bonds are relatively scarce. The past decade has witnessed significant advancements in selective mono-/dichalcogenation and exclusive dichalcogenation of various C(sp 2 )-H and C(sp 3 )-H bonds via transition-metal-catalyzed/mediated, photocatalytic, electrochemical or metal-free approaches. In light of the significance of both mono- and dichalcogen-containing compounds in various fields of chemical science and the critical issue of chemoselectivity in organic synthesis, the present review systematically summarizes the advances in these research fields, with a special focus on elucidating scopes and mechanistic aspects. Moreover, the synthetic limitations, applications of some of these processes, the current challenges and our own perspectives on these highly active research fields are also discussed. Based on the substrate types and C-H bonds being chalcogenated, the present review is organized into four sections: (1) transition-metal-catalyzed/mediated chelation-assisted selective C-H mono-/dichalcogenation or exclusive dichalcogenation of (hetero)arenes; (2) directing group-free selective C-H mono-/dichalcogenation or exclusive dichalcogenation of electron-rich (hetero)arenes; (3) C(sp 3 )-H dichalcogenation; (4) dichalcogenation of both C(sp 2 )-H and C(sp 3 )-H bonds. We believe the present review will serve as an invaluable resource for future innovations and drug discovery.

The advantages of microbial induced carbonate precipitation (MICP) as bio-cementation technology for tailings-solidification are under extensive investigation. In order to improve performance of bio-cementation, many strengthening materials were applied to the bio-cementation of tailings. Steel slag (SS) is a kind of industrial solid waste, its chemical composition and mineral composition are similar to cement, and it has a certain application prospect as an auxiliary cementing material. In this study, the properties and mechanism of SS strengthening MICP cementation of cyanide tailings (CT) were investigated. The results showed that Sporosarcina pasteurii growth is not inhibited by SS, and Sporosarcina pasteurii can promote the hydration reaction of SS, providing a suitable alkaline environment and Ca 2+ , promoting the production of more CaCO 3 in the MICP process. When 200 mL of CT leachate was added 1.4 g SS (200-400 mesh), the adsorption of Cu, Pb, Zn, Cd, total cyanide (T-CN), and free cyanide (F-CN) reached 48.05%, 44.28%, 36.25%, 16.67%, 79.05%, and 67.20%, respectively. The maximum unconfined compressive strength（UCS） of the cemented body (with 5%, 150 mesh SS) was 1.97 MPa, which was 3.396 times as high as that without SS. The cemented body with the addition of SS (5%, 150 mesh) contained more carbonate bound Cu (2.75%), Pb (4.89%), Zn (5.37%), and Cd (5.75%), and less exchangeable Cu (3.65%), Pb (6.85%), Zn (2.27%), and Cd (4.42%) than that without SS. In summary, the addition of SS improved the UCS of cemented bodies and the stability of heavy metals and cyanide, reduced the environmental risks existing in the process of CT storage. Meanwhile, it also provides new ideas for resource utilization of industrial solid waste SS and improvement of mine filling materials., 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 © 2023 Elsevier Ltd. All rights reserved.)

In this study, sRNA libraries and mRNA libraries of HFs of FMD were constructed and sequenced using an Illumina HiSeq 2500, and the expression profiles of miRNAs and genes in the HFs of FMD were obtained at the anagen and catagen stages. In total, 565 differentially expressed unigenes (DEGs) were identified, 90 of which were upregulated and 475 of which were downregulated. In the BP category of GO enrichment, the DEGs were enriched in the processes related to HF development and differentiation, including the hair cycle regulation and processes, HF development, skin epidermis development, regulation of HF development, skin development, the Wnt signaling pathway, and the BMP signaling pathway. Through KEGG analysis it was found that DEGs were significantly enriched in pathways associated with HF development and growth. A total of 186 differentially expressed miRNAs (DEmiRNAs) were screened ( p < 0.05) in the HFs of FMD at the anagen stage vs. the catagen stage, 33 of which were upregulated and 153 of which were downregulated. Through DEmiRNA-mRNA association analysis, we found DEmiRNAs and target genes that mainly play regulatory roles in HF development and growth. The enrichment analysis of DEmiRNA target genes revealed similarities with the enrichment results of DEGs associated with HF development. Notably, both sets of genes were enriched in key pathways such as the Notch signaling pathway, melanogenesis, the cAMP signaling pathway, and cGMP-PKG. To validate our findings, we selected 11 DEGs and 11 DEmiRNAs for experimental verification using RT-qPCR. The results of the experimental validation were consistent with the RNA-Seq results.

Cyanide extraction dominates the gold smelting industry, which leads to the generation of large amounts of cyanide-containing wastewater. In this study, Aneurinibacillus tyrosinisolvens strain named JK-1 was used for cyanide wastewater biodegradation. First, we tested the performance of JK-1 in degrading cyanide under different conditions. Then, we screened metabolic compounds and pathways associated with cyanide degradation by JK-1. Finally, we explored the potential JK-1-mediated cyanide degradation pathway. Our results showed that the optimal pH and temperature for cyanide biodegradation were 7.0 and 30 °C, respectively; under these conditions, a degradation rate of >98% was achieved within 48 h. Untargeted metabolomics results showed that increased cyanide concentration decreased the abundance of metabolic compounds by 71.1% but upregulated 32 metabolic pathways. The Kyoto Encyclopedia of Genes and Genomes enrichment results revealed significant changes in amino acid metabolism pathways during cyanide degradation by JK-1, including cyanoamino acid metabolism, β-alanine metabolism, and glutamate metabolism. Differential metabolic compounds included acetyl-CoA, l-asparagine, l-glutamic acid, l-phenylalanine, and l-glutamine. These results confirmed that cyanide degradation by JK-1 occurs through amino acid assimilation. This study provides new insights into the mechanism of cyanide biodegradation, which can be applied in the treatment of cyanide wastewater or tailings., 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 © 2023. Published by Elsevier Ltd.)

Conventional compost sludge has a long fermentation period and is not nutrient rich. Potassium-rich mining waste was used as an additive for aerobic composting of activated sludge to make a new sludge product. The effects of different feeding ratios of potassium-rich mining waste and activated sludge on the physicochemical properties and thermophilic bacterial community structure during aerobic composting were investigated. The results showed that potassium-rich waste minerals contribute to the increase in mineral element contents; although the addition of potassium-rich waste minerals affected the peak temperature and duration of composting, the more sufficient oxygen content promoted the growth of thermophilic bacteria and thus shortened the overall composting period. Considering the requirements of composting temperature, it is recommended that the addition of potassium-rich waste minerals is less than or equal to 20%., (© 2023. The Author(s).)

Although biochar has been widely used in the remediation of heavy metal pollution in acidic and neutral soils, less attention has been paid to whether biochar will alter its structural properties and the ability to retain heavy metals after different degrees of aging in alkaline soils. In this study, two artificial accelerated aging methods (freeze-thaw cycle and dry-wet cycle) and a short-term natural aging method were used to simulate the aging process of biochar prepared from corn stalk. We investigated the changes in the soil pH and bioavailability, total content, and transformation of Cd 2+ before and after aging treatments. Biochar was separated from the soil for characterization to explore the effect of aging on the passivation of Cd 2+ by biochar in the alkaline soil of the mining area. The results showed that adding biochar to alkaline soil in the Bayan Obo mining area had no significant liming effect, and pH decreased after the freeze-thaw and dry-wet accelerated aging treatments. Compared with that in the control, the CaCl 2 -extractable contents of Cd 2+ decreased by 19.32%-30.67%, and the total contents of Cd 2+ decreased by 5.02%-7.18%. Aging did not significantly change the transformation of Cd 2+ but reduced the distribution of acid-soluble and reducible fractions, indicating that biochar could immobilize Cd 2+ for a long time after aging, which was related to the increase in oxygen-containing functional groups and the pore structure of biochar. These results are important for evaluating its long-term application prospects in the mining environment.

Many studies reported that long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) metastasis and tumorigenesis. However, the underlying mechanisms of lncRNAs in GC remain unexplored to a great extent. LINC01537 expression level was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Its biological roles in GC were then investigated using functional experiments. In order to investigate the underlying mechanism of LINC01537 in GC, RNA pull-down, RNA immunoprecipitation, and ubiquitination assays were performed. LINC01537 was significantly overexpressed in GC tissues and associated with a poor prognosis. Functional experimental results revealed that LINC01537 promoted the proliferation, invasion, and migration of GC cells. The animal experiments revealed that LINC01537 promoted tumorigenesis and metastasis in vivo. Mechanistically, LINC01537 stabilizes RIPK4 by reducing the binding of RIPK4 to TRIM25 and reducing its ubiquitination degradation, thereby promoting the expression of the NF-κB signaling pathway. According to our findings, the LINC01537-RIPK4-NF-κB axis promoted GC metastasis and tumorigenesis.

The unreasonable use of antibiotics and the transmission of antibiotic resistance genes (ARGs) induced by antibiotics have led to a large number of ARGs entered the water environment, which seriously threatened human health and environmental safety. The estuarine aquatic environment connects with inland rivers and sea and is frequently influenced by human activities. This study aims to reveal the occurrences and abundances of ARGs and bacterial community composition by high-throughput quantitative PCR including 296 primers and high-throughput sequencing in the tide rising and ebbing of surface water in the Yongjiang Estuary, China. The results showed that there were a large number of ARGs and mobile genetic elements (MGEs) detected in the rising tide and ebb tide water bodies. The numbers of detected ARGs in each sample at rising and ebb tide ranged from 16 to 77 and 61 to 88, respectively, and the absolute abundance ranges were 1.69 × 10 4 -1.69 × 10 9 copies/L and 3.18 × 10 3 -2.57 × 10 9 copies/L, respectively. Obvious tidal distribution characteristics of ARGs were showed. Most of ARGs conferred resistance to multidrug, aminoglycosides and sulfanilamides. Proteobacteria, Actinobacteria and Bacteroidetes were the dominantly bacterial phylum in the Yongjiang Estuary. Network analysis results indicated that multi-genera were identified as possible ARGs hosts, and they carried more than two types of ARGs genes. Partial least squares path modeling further revealed that MGEs and bacterial community composition were the most important driving factors. The results of the study can provide the corresponding scientific basis for the diffusion and control of ARGs in estuaries., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mucosal-associated Invariant T (MAIT) cells are an innate-like T cell subset that recognize a broad array of microbial pathogens, including respiratory pathogens. Here we investigate the transcriptional profile of MAIT cells localized to the human lung, and postulate that MAIT cells may play a role in maintaining homeostasis at this mucosal barrier. Using the MR1/5-OP-RU tetramer, we identified MAIT cells and non-MAIT CD8 + T cells in lung tissue not suitable for transplant from human donors. We used RNA-sequencing of MAIT cells compared to non-MAIT CD8 + T cells to define the transcriptome of MAIT cells in the human lung. We show that, as a population, lung MAIT cells are polycytotoxic, secrete the directly antimicrobial molecule IL-26, express genes associated with persistence, and selectively express cytokine and chemokine- related molecules distinct from other lung-resident CD8 + T cells, such as interferon-γ- and IL-12- receptors. These data highlight MAIT cells' predisposition to rapid pro-inflammatory cytokine responsiveness and antimicrobial mechanisms in human lung tissue, concordant with findings of blood-derived counterparts, and support a function for MAIT cells as early sensors in the defense of respiratory barrier function., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Southern Taihang Mountain area is an important part of the key ecological regions along the Yellow River in China. Understanding the climate change trend in this area is of significance for the maintenance of ecological security and the planning and decision-making of major ecological projects in the Yellow River Basin. Taking Jiyuan City in southern Taihang Mountain area as the research area, we analyzed the climate change trend in Jiyuan based on the meteorological data from 1980 to 2019. The results showed that climate in Jiyuan tended to be warmer and wetter during the study period. The change rates of temperature and precipitation were 0.48 ℃·(10 a) -1 and 14.21 mm·(10 a) -1 , respectively. The rise of temperature in spring and summer was higher than that in autumn and winter. Climate was warmer and drier in spring, while warmer and wetter in the other three seasons. Potential evapotranspiration and aridity index showed increasing and decreasing trends, with the average value of 748 mm and 1.36, respectively. The first and last days ≥10 ℃ were about 3 days in advance and 1 day in delay every 10 years. The change rate of effective accumulated temperature ≥10 ℃, duration days ≥10 ℃ and high temperature days were 116.57 ℃·(10 a) -1 , 4 d·(10 a) -1 , and 5 d·(10 a) -1 , respectively. The 1990s was the driest decade in Jiyuan during the study period, with strongest increases of temperature. Half of the years showed the characteristics of semi-arid climate in that decade. From 2010 to 2019, the trend of climate warming and wetting in Jiyuan had accelerated significantly, which was the warmest and wettest decade. In recent 10 years, duration days ≥10 ℃ and the effective accumulated temperature increased by about 28 days and 389.36 ℃, respectively. The frequency and intensity of high temperature weather also increased significantly in this decade.

Objective: To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells., Methods: Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot., Results: KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01)., Conclusion: KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G 1 phase arrest in gastric cancer cells., (© 2020. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent years, more and more countries are focusing on the control of mining sites and the surrounding ecological environment, and the new environmental concept of green mines has been proposed. By investigating the ecological background of a mine site, pollution and ecological imbalances in the mine can be predicted, managed or transformed. This study investigated the effects of rare earth elements on plant growth in the Baotou Bayan Obo Rare Earth Mine and evaluated soil contamination and subsequent remediation through the measured plant height. Using linear regression, BP(Back Propagation) neural networks, GA-BP(Genetic Algorithm- Back Propagation) neural networks, ELM(Extreme Learning Machine) and GA-ELM(Genetic Algorithm- Extreme Learning Machine) model prediction instruments, the different rare earth solution concentrations were set as input values and the heights of Artemisia desertorum, which as the model plant, were set as output values in the prediction. The results showed that the linear regression predicted the standard error of single La(III), Ce(III) solution and compound La(III) + Ce(III) solution for Artemisia desertorum growth stress was on the high side, 7.02%- 8.92%; the efficiency range of each group of models under BP neural network, GA-BP neural network and ELM neural network were 1.15%- 2.53%, 0.85%- 1.28%, 1.76%- 3.53%; while the efficiency range under GA-ELM neural network was 0.59%- 0.68%, with average error values and predicted values close to the true values. Among them, the MAPE of GA-ELM neural network are significantly lower than other models, and the error decreases with increasing concentration of the compound solution. So GA-ELM neural network can be used as an efficient, fast and reasonable optimal model for predicting the growth stress of Artemisia desertorum in Bayan Obo mining area. The experimental results can provide a theoretical basis for assessing the risk of soil rare earth contamination in the area, evaluating the expectation of later remediation, and provide a degree of new ideas for the construction of green mines., (Copyright © 2022. Published by Elsevier Inc.)

Brackish water resource is widely distributed in the North China Plain, which has not been effectively utilized. Using brackish water for irrigation can alleviate water resource conflict in the well-irrigated area and solve the problem of groundwater over-exploitation of the North China Plain. A long-term experiment (since 2006) was conducted to investigate the effects of brackish water irrigation on the quality and yield of winter wheat in the North China Plain. There were five salinity degrees of irrigation water, i.e. 1, 2, 4, 6, and 8 g·L -1 , respectively. The results showed that higher salinity degree of irrigation water (4-8 g·L -1 ) significantly increased water absorption, development time, sedimentation, wet gluten content, and protein content, but decreased the stabilization time, flour yield, and gluten index. There was no significant difference between the treatments of 1 g·L -1 and 2 g·L -1 on grain yield and yield components, but the treatment of 2 g·L -1 significantly improved grain quality, including water absorption, development time, sedimentation, wet gluten, and protein content. Higher salinity degree of irrigation water (4-8 g·L -1 ) treatments significantly decreased spike number (44.0%-60.7%) and grain yield (35.6%-64.7%), compared with 1 g·L -1 treatment. Results of principal component analysis showed that 2 g·L -1 treatment had the best overall effect with no significant decrease in grain yield and quality of grain. This study could provide theoretical basis and technical support for use of brackish water in the North China Plain.

It is of great importance to explore the effects of saline-water furrow irrigation on soil water-stable aggregates for safe and efficient utilization of saline water resources. We conducted a long-term cotton experiment with six levels of saline-water furrow irrigation (1, 2, 4, 6, 8, 10 g·L -1 ) since 2006 and analyzed the variations of soil salinity and water-stable aggregates in the 10th and 15th years under saline irrigation. The results showed that soil salinity in the 0-30 cm layer at the ditch increased with increasing salinity level of irrigation water. There were significant differences between the 6, 8, 10 g·L -1 and 1 g·L -1 treatments. Soil salinity in each treatment increased gradually with increasing soil depth. Saline-water furrow irrigation tended to reduce the stability of soil water-stable aggregates. When the salinity level of the irrigation water was ≥6 g·L -1 , the mass fraction of macroaggregates (&gt;0.25 mm), the mean weight diameter and geometric mean diameter of water-stable aggregates significantly decreased. In contrast, the fractal dimension and mean weight specific surface area increased significantly. The stability of soil water-stable aggregates decreased with soil depth in all treatments. Under the condition of saline-water furrow irrigation for several years, there was no accumulation of soil salinity and instability of water-stable aggregates in the 0-30 cm soil layer at the ditch with each passing year. With the irrigation scheduling of this study, saline-water furrow irrigation with salinity ≤4 g·L -1 did not affect soil salinity and water-stable aggregate stability of cotton field in this area.

Objective: To study the effects on extravascular lung water of lung protective ventilation strategy applying on piglets with acute respiratory distress syndrome (ARDS) induced by paraquat (PQ) under pulse indicating continuous cardiac output (PiCCO) monitoring. Methods: The piglets models with ARDS induced by PQ were established in June 2020 and all of them were received mechanical ventilation and divided into three groups according to tidal volume (V(T)) : small V(T) group (6 ml/kg) , middle V(T) group (10 ml/kg) and large V(T) group (15 ml/kg) , there were 5 piglets in each group. The positive end expiratory pressure (PEEP) were all setup on 10 cmH(2)O. The indexes such as arterial blood gas analysis, oxygenation index (OI) , extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were monitored at time of before the model was established (baseline) , time of the model was established (t(0)) and 2 h (t(2)) , 4 h (t(4)) , 6 h (t(6)) after mechanical ventilation. Lung tissue were punctured at time of baseline, t(0) and t(6) to be stained by Hematoxylin-eosin (HE) staining and pulmonary pathology were observed under light microscopy. Results: The heart rate (HR) , mean arterial pressure (MAP) and partial pressure of carbon dioxide (PaCO(2)) of all groups were higher than the base value while the pH values, partial pressure of oxygen (PaO(2)) and OI were lower than the base value when the models were established ( P <0.05) . After mechanical ventilation, the HR and MAP values of all groups at t(2), t(4) and t(6) were lower than t(0) while the PaCO(2) of t(4) and t(6) were all higher than t(0), the differences were statistically significant ( P <0.05) . The PaO(2) and OI of all groups showed a trend of rising at first and then decreasing after mechanical ventilation. The MAP, PaO(2), PaCO(2) and OI of the middle V(T) group and large V(T) group were apparently lower than that of the small V(T) group at t(2), t(4) and t(6) ( P <0.05) . The ELWI and PVPI at t(0) of all groups were higher than that of baseline ( P <0.05) . The ELWI of the small V(T) group at t(6) were lower than t(0) of the same group and t(6) of the middle V(T) group and large V(T) group ( P <0.05) . HE staining showed congestion and edema of alveolar tissue, swelling of capillaries, exudation of red blood cells and widening of alveolar septum in piglets after successful modeling. And further widening of alveolar septum and rupture of alveolar septum could be seen in the lung tissues of each group at t(6), and the injury was the slightest in the small V(T) group. Conclusion: The lung protective ventilation strategy can alleviate the extravascular lung water and ARDS induced by PQ and improve oxygenation.

More and more studies have indicated an association between immune infiltration in lung cancer and clinical outcomes. Matrix metalloproteinase 14 (MMP14) has been reported to be dysregulated in many types of tumors and involved in the development and progression of tumors. However, its contribution to cancer immunity was rarely reported. In the study, we found that MMP14 expression was distinctly upregulated in lung cancer specimens compared with nontumor lung specimens. High MMP14 expression predicted a poor prognosis of lung squamous cell carcinoma (LUSC) patients. Increased MMP14 expressions were observed to be positively related to high immune infiltration levels in most of the immune cells. A pathway enrichment analysis of 32 MMP14-associated immunomodulators indicated the involvement of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Based on MMP14-associated immunomodulators, we applied multivariate assays to construct multiple-gene risk prediction signatures. We observed that risk scores were independently associated with overall survival. These data highlighted that MMP14 was involved in tumor immunity, indicating that MMP14 could serve as a novel prognostic biomarker and therapeutic target for lung cancer. Our data suggest that the four genes identified in this study may serve as valuable biomarkers of lung cancer patient outcomes., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Chun-long Zheng et al.)

Objectives: To analyze the trends of HIV/syphilis/HSV-2 seropositive rate and explore the related factors with HSV-2 infection to provide the basis for adjusting STD intervention strategies and formulating prevention and control measures among MSM in Shenzhen., Methods: Time-location sampling was conducted among MSM in Shenzhen in 2012, 2014, 2016, and 2018. Data on demographics, sexual behaviors and the laboratory test results of HIV, syphilis, HSV-2 were collected. The χ2 trend test was used to analyze the trends of HIV/syphilis/HSV-2 seropositive rate. The binary logistic regression model was used to explore the factors associated with HSV-2 infection., Results: The seropositive rate of HIV fell significantly from 15.9% in 2012 to 8.7% in 2018 (Ptrend = 0.003), syphilis seropositive rate was significantly decreased from 20.4% in 2012 to 14.8% in 2018 (Ptrend = 0.025), HSV-2 seropositive rate had no significant change (16.7% in 2012 to 14.0% in 2018; Ptrend = 0.617). In principal component logistic regression analysis showed that FAC1&#95;1 (X1 = Ever had sex with female, X2 = Gender of first sexual partner, X3 = Marital status, X4 = Age group), FAC2&#95;1 (X5 = Education, X6 = Monthly income (RMB), X7 = Frequency of condom use in anal sex with men in the past 6 months), and FAC4&#95;1 (X9 = History of STDs) were significantly associated with HSV-2 infection., Conclusions: The seropositive rates of HIV and syphilis have dropped significantly but are still high. HSV-2 seropositive rate had no significant change and maintained a high level. It is necessary to continue strengthening HIV and syphilis interventions among MSM in Shenzhen. HSV-2 detection and intervention are urgently required for MSM, which might be another effective biological strategy further to control the HIV epidemic among MSM in Shenzhen., Competing Interests: The authors have declared that no competing interests exist.

Previous studies have shown that an effective damage detection method for model rats from macro individual to micro cellular, was applied to assess the groundwater quality from rare earth metals tailings seepage. To determine whether it is universal method for measuring the toxicological damage caused by contaminated water around other mining areas to organisms at the organ-tissue-cell-chromosome-gene level. In this study, a rare earth mining area in North China was used as research base. Firstly, the core pollution factors in surface water and groundwater from five different sites were analyzed. Then, the degree of toxicological damage to Sprague-Dawley (SD) rats caused by contaminated water were systematically assessed using biological methods. Finally, the possible molecular mechanism of toxicological damage was further discussed. The synthesis results showed that the main pollution factors were some metal elements (Mn, Zn, Co, Ni) and rare earth elements (Sc, Nb, La, Ce, Pr, Dy and Y), which might cause significant DNA genetic damage to SD rats. Further, differential gene expression profile showed that DNA damage-inducible genes (Gadd45g and Ddit4), immunity-related genes (Mpo, Slpi and Elane) and two cancer-related genes (Mmp8 and Ltf) were used as a new prognostic and predictive biomarker for biosafety assessment. Therefore, this study provides a possible molecular mechanism for the toxicological damage, and also it provides a universal method to scientifically and effectively evaluate the water pollution risk for other mining areas., 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.)

The Bayan Obo deposit is the largest light rare earth ore deposit in the world, which releases rare earth elements (REEs) to the surrounding environment through long-term mining processes. To inform restoration plans, it is necessary to investigate the concentration, spatial distribution, pollution level, and ecological risk of REEs. Sample analyses showed that the average total concentration of REEs in this area is 6064.95 mg·kg -1 , which was higher than the background levels of control soils (207.44 mg·kg -1 ), Inner Mongolia (150.95 mg·kg -1 ), and China (184.72 mg·kg -1 ). Light REEs (LREEs) accounted for 83%-99% of the detected REE, and Ce was the dominant element. Areas with high REE concentrations were mainly located near the source bed, and the distribution was extremely inhomogeneous, being greatly affected by external interference. Chondrite normalized REE patterns of different functional areas were similar and normalized curves inclined to the right, indicating district fractionation between the LREE and heavy REEs (HREEs). Significant negative Eu anomalies and positive Ce anomalies were observed in the soils based on δ Ce and δ Eu values. La/Yb, La/Sm, and Gd/Yb ratios all indicated that the soils were LREE-enriched, whereas the LREEs were more fractionated than the HREE. Four methods were employed to evaluate the pollution and ecological risk of the detected soil REEs. The average values of Ce, Nd, Pr, and La reached heavily contaminated levels based the geo-accumulation index ( I geo ). The modified degree of contamination method showed that the average m C d values of REEs in different functional areas ranged from 7.14 to 31.38. The tailings pond had a high level of pollution, residential and industrial areas had a very high pollution level, and the mining area and waste dump showed extremely high levels of pollution. Based on the pollution load index, the tailings pond is moderately polluted while all other functional areas are severely polluted. The potential ecological risk index values ranged from 120.99 to 6376.46, with REEs in soils posing high strong risk, very strong risk, strong risk, moderate risk, and low risk in 33%, 16%, 12%, 30%, and 9% of the sampling sites, respectively. Based on these findings, measures for controlling current pollution and potential ecological risks from REE in the soils of the Bayan Obo mining region are urgently needed.

We used statistical approach by coupling redundancy analysis with linear regression analysis, which is useful to understand potential sources of antibiotics in the tide rising and ebbing of surface water in the Yongjiang Estuary, China. This study aimed to investigate the relationship between 29 antibiotics at five sites over four seasons and 13 environmental parameters during the tide rising and ebbing durations. The results found that dissolved organic carbon (DOC), salinity, temperature and chlorophyll a (Chla) were the main factors to impact antibiotics. The concentrations of macrolides were increasing with DOC, suggesting DOC may influence the adsorption capacity of antibiotics. The concentrations of tetracyclines had significant correlation with temperature and Chla during the tide rising period. This study demonstrated a method of exploring the relationship between the concentrations of antibiotics and environmental parameters, which is beneficial to future antibiotics research in estuaries., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Forest musk deer ( Moschus berezovskii , FMD) is an endangered artiodactyl species, male FMD produce musk. We have sequenced the whole genome of FMD, completed the genomic assembly and annotation, and performed bioinformatic analyses. Our results showed that microsatellites (SSRs) displayed nonrandomly distribution in genomic regions, and SSR abundances were much higher in the intronic and intergenic regions compared to other genomic regions. Tri- and hexanucleotide perfect (P) SSRs predominated in coding regions (CDSs), whereas, tetra- and pentanucleotide P-SSRs were less abundant. Trifold P-SSRs had more GC-contents in the 5'-untranslated regions (5'UTRs) and CDSs than other genomic regions, whereas mononucleotide P-SSRs had the least GC-contents. The repeat copy numbers (RCN) of the same mono- to hexanucleotide P-SSRs had different distributions in different genomic regions. The RCN of trinucleotide P-SSRs had increased significantly in the CDSs compared to the transposable elements (TEs), intronic and intergenic regions. The analysis of coefficient of variability (CV) of P-SSRs showed that the RCN of mononucleotide P-SSRs had relative higher variation in different genomic regions, followed by the CV pattern of RCN: dinucleotide P-SSRs > trinucleotide P-SSRs > tetranucleotide P-SSRs > pentanucleotide P-SSRs > hexanucleotide P-SSRs. The CV variations of RCN of the same mono- to hexanucleotide P-SSRs were relative higher in the intron and intergenic regions, followed by that in the TEs, and the relative lower was in the 5'UTR, CDSs and 3'UTRs. 58 novel polymorphic SSR loci were detected based on genotyping DNA from 36 captive FMD and 22 SSR markers finally showed polymorphism, stability, and repetition.

Objective: To investigate the expression of miR-130a in human colon cancer patients and its specific mechanism of regulating the biological function of colon cancer cells., Patients and Methods: Cancer tissues, paracancerous tissues, and serum samples of 40 colon cancer patients who underwent surgery in The Second Affiliated Hospital of Qiqihar Medical University from May 2018 to March 2019 were collected, and 40 healthy volunteers who received physical examination in The Second Affiliated Hospital of Qiqihar Medical University were collected. Real Time-quantitative Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of miR-130a. Human colon cancer cell was divided into miR-130a mimic group, miR-130a inhibitor group, mimic NC (negative control), and inhibitor NC group. QRT-PCR was used to detect the expression of miR-130a, and MTT assay, colony formation assay, cell scratch assay, transwell assay were performed to detect cell viability, proliferation, migration, and invasion ability., Results: Compared with adjacent tissues, the expression of miR-130a was significantly increased in colon cancer tissues (p=0.0125); the expression of miR-130a in transfected miR-130a mimic group was higher than that in NC group, but the expression in transfected miR-130a inhibitor group was significantly lower than that in NC group; overexpression of miR-130a significantly increased cell viability, proliferation, migration, and invasion of colon cancer cells, while knockdown of miR-130a significantly inhibited colon cancer cell biological activity; target prediction, qRT-PCR, and Western blot assays showed that miR-130a participated in the development and progression of colon cancer by targeting inhibition of PTEN expression., Conclusions: The expression of miR-130a in serum and cancer tissues of colon cancer patients is significantly increased, and it can regulate the biological function of colon cancer cells by inhibiting the expression of target gene PTEN. Knockdown of miR-130a may be used as a new clinical treatment for colon cancer.

Background: Genome-wide profiling to examine brain transcriptional features associated with excessive ethanol (EtOH) consumption has been applied to a variety of species including rodents, nonhuman primates (NHPs), and humans. However, these data were obtained from cross-sectional samples which are particularly vulnerable to individual variation when obtained from small outbred populations typical of human and NHP studies. In the current study, a novel within-subject design was used to examine the effects of voluntary EtOH consumption on prefrontal cortex (PFC) gene expression in a NHP model., Methods: Two cohorts of cynomolgus macaques (n = 23) underwent a schedule-induced polydipsia procedure to establish EtOH self-administration followed by 6 months of daily open access to EtOH (4% w/v) and water. Individual daily EtOH intakes ranged from an average of 0.7 to 3.7 g/kg/d. Dorsal lateral PFC area 46 (A46) brain biopsies were collected in EtOH-naïve and control monkeys; contralateral A46 biopsies were collected from the same monkeys following the 6 months of fluid consumption. Gene expression changes were assessed using RNA-Seq paired analysis, which allowed for correction of individual baseline differences in gene expression., Results: A total of 675 genes were significantly down-regulated following EtOH consumption; these were functionally enriched for immune response, cell adhesion, plasma membrane, and extracellular matrix. A total of 567 genes that were up-regulated following EtOH consumption were enriched in microRNA target sites and included target sites associated with Toll-like receptor pathways. The differentially expressed genes were also significantly enriched in transcription factor binding sites., Conclusions: The data presented here are the first to use a longitudinal biopsy strategy to examine how chronic EtOH consumption affects gene expression in the primate PFC. Prominent effects were seen in both cell adhesion and neuroimmune pathways; the latter contained both pro- and antiinflammatory genes. The data also indicate that changes in miRNAs and transcription factors may be important epigenetic regulators of EtOH consumption., (© 2019 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals, Inc. on behalf of Research Society on Alcoholism.)

Three female workers in a golf club production company in Guangzhou were diagnosed with occupational chronic mild benzene poisoning. Two of the female workers were assessed as Grade 7 disabilities. One female worker showed the symptoms of the decline of whole blood cells for unknown reasons in the later stages of the medical period. The final assessment was a Class 5 disability. The problems in this work ability appraisal include: the injury condition of the patient who has not been stable during the work ability appraisal, and the contradiction between the disability grade and the occupational disease diagnosis conclusion. In order to avoid similar situations, the following recommendations are recommended: after the worker's injury situation is relatively stable, the assessment will be conducted, the employer will actively exercise the right to review and appraisal, and the diagnosis of occupational diseases will be included in the evaluation criteria for disability grade.

Hepatitis B virus (HBV) core protein (HBc) serves pivotal roles in the viral life cycle, particularly serving as the basic unit for capsid assembly, and is closely associated with HBV genome replication and progeny virion production. Previous studies have demonstrated that HBc has at least two functional interfaces; two HBc monomers form a homodimer via an intradimer interface, and then 90 or 120 homodimers form an icosahedral capsid via a dimer‑dimer interface. In the present study, the role of the HBc dimer‑dimer interface in HBV replication was investigated. A panel of residues located at the dimer‑dimer interface were identified based on the crystal structure of HBc. Native gel electrophoresis and western blotting revealed that, despite mutations in the dimer‑dimer interface, HBc formed a capsid‑like structure, whereas mutations at amino acid residues 23‑39 completely disrupted capsid assembly. Using denaturing gel electrophoresis, Southern and Northern blotting, and quantitative polymerase chain reaction, it was demonstrated that none of the mutations in the dimer‑dimer interface supported pregenomic RNA encapsidation or DNA replication. In addition, these mutants interacted with the wild-type (WT) HBc monomer and inhibited WT genome replication and virion production in a dose‑dependent manner. However, the quantity of covalently closed circular DNA in the nucleus was not affected. The present study highlighted the importance of the HBc dimer‑dimer interface for normal capsid function and demonstrated that the HBc dimer‑dimer interface may be a novel antiviral target.

This review summarizes the proceedings of a symposium presented at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference held in Volterra, Italy on May 9-12, 2017. Psychiatric diseases, including alcohol-use disorders (AUDs), are influenced through complex interactions of genes, neurobiological pathways, and environmental influences. A better understanding of the common neurobiological mechanisms underlying an AUD necessitates an integrative approach, involving a systematic assessment of diverse species and phenotype measures. As part of the World Congress on Stress and Alcoholism, this symposium provided a detailed account of current strategies to identify mechanisms underlying the development and progression of AUDs. Dr. Sean Farris discussed the integration and organization of transcriptome and postmortem human brain data to identify brain regional- and cell type-specific differences related to excessive alcohol consumption that are conserved across species. Dr. Brien Riley presented the results of a genome-wide association study of DSM-IV alcohol dependence; although replication of genetic associations with alcohol phenotypes in humans remains challenging, model organism studies show that COL6A3, KLF12, and RYR3 affect behavioral responses to ethanol, and provide substantial evidence for their role in human alcohol-related traits. Dr. Rob Williams expanded upon the systematic characterization of extensive genetic-genomic resources for quantifying and clarifying phenotypes across species that are relevant to precision medicine in human disease. The symposium concluded with Dr. Robert Hitzemann's description of transcriptome studies in a mouse model selectively bred for high alcohol ("binge-like") consumption and a non-human primate model of long-term alcohol consumption. Together, the different components of this session provided an overview of systems-based approaches that are pioneering the experimental prioritization and validation of novel genes and gene networks linked with a range of behavioral phenotypes associated with stress and AUDs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Antibiotics are used to fight diseases in humans and farm animals. Their residues, however, can enter aquatic environments and affect the resistance of non-target microbial strains, and the prevalence of antibiotic resistance genes (ARGs) potentially poses negative impacts on human health. In order to better understand how the studies of antibiotics have been conducted, we analyzed the publications on antibiotics in aquatic systems for the period of 1945-2017. We applied a bibliometric analysis method by coupling cluster analysis and network analysis. Results indicated that early research on antibiotics in water was mostly performed in America and Europe, while, in recent years, publications for the same subject were dominated by China and the USA. The majority of the articles were published in journal Chemosphere and the most representative subject categories of the seven sections were "Environmental science and ecology," "Chemistry," "Engineering," "Biochemistry and molecular biology," "Water resources," "Agriculture," and "Pharmacology and pharmacy." The most studied class of antibiotics was tetracyclines in wastewater. Antibiotic resistance, ARGs, Escherichia coli, and some mechanistic studies such as adsorption, toxicity, degradation, and kinetics were common topics in this field. ARGs present a major public health concern and much attention should be directed at the problems with antibiotics in the future studies of water.

This is the first description of the relationship between chronic ethanol self-administration and the brain transcriptome in a non-human primate (rhesus macaque). Thirty-one male animals self-administered ethanol on a daily basis for over 12 months. Gene transcription was quantified with RNA-Seq in the central nucleus of the amygdala (CeA) and cortical Area 32. We constructed coexpression and cosplicing networks, and we identified areas of preservation and areas of differentiation between regions and network types. Correlations between intake and transcription included largely distinct gene sets and annotation categories across brain regions and between expression and splicing; positive and negative correlations were also associated with distinct annotation groups. Membrane, synaptic and splicing annotation categories were over-represented in the modules (gene clusters) enriched in positive correlations (CeA); our cosplicing analysis further identified the genes affected only at the exon inclusion level. In the CeA coexpression network, we identified Rab6b, Cdk18 and Igsf21 among the intake-correlated hubs, while in the Area 32, we identified a distinct hub set that included Ppp3r1 and Myeov2. Overall, the data illustrate that excessive ethanol self-administration is associated with broad expression and splicing mechanisms that involve membrane and synapse genes., (© 2017 Society for the Study of Addiction.)

Aluminum (Al) is ubiquitous and toxic to microbes. High Al 3+ concentration and low pH are two key factors responsible for Al toxicity, but our present results contradict this idea. Here, an Al-tolerant yeast strain Rhodotorula taiwanensis RS1 was incubated in glucose media containing Al with a continuous pH gradient from pH 3.1-4.2. The cells became more sensitive to Al and accumulated more Al when pH increased. Calculations using an electrostatic model Speciation Gouy Chapman Stern indicated that, the increased Al sensitivity of cells was associated with AlOH 2+ and Al(OH) 2 + rather than Al 3+ . The alcian blue (a positively charged dye) adsorption and zeta potential determination of cell surface indicated that, higher pH than 3.1 increased the negative charge and Al adsorption at the cell surface. Taken together, the enhanced sensitivity of R. taiwanensis RS1 to Al from pH 3.1-4.2 was associated with increased hydroxy-Al and cell-surface negativity.

Trastuzumab has been widely applied as a treatment for human epidermal growth factor 2 (HER2)-overexpressing breast cancer. However, the therapeutic efficacy of trastuzumab is limited. Flap endonuclease 1 (FEN1) is a multifunctional endonuclease that has a crucial role in DNA recombination and repair. Inhibition of FEN1 is associated with the reversal of anticancer drug resistance. However, it is unclear whether FEN1 is involved in trastuzumab resistance. In the present study, it was demonstrated that trastuzumab increases the expression of FEN1, and FEN1 knockdown significantly enhanced the sensitivity of BT474 cells to trastuzumab (P<0.05). It was also revealed that trastuzumab induced HER receptor activation, increased binding with FEN1 and estrogen receptor α (ERα), and upregulated ERα-target gene transcription (P<0.05). Upon silencing of FEN1 expression with siRNA, activation of HER receptor and FEN1 binding to ERα were decreased, and trastuzumab-induced ERα target gene upregulation was partially ameliorated (P<0.05). These results suggest that FEN1 may mediate trastuzumab resistance via inducing HER receptor activation and enhancing ERα-target gene transcription. The findings of the present study indicate a novel role of FEN1 in trastuzumab resistance, suggesting that targeting FEN1 may enhance the efficiency of trastuzumab as a treatment for HER2-positive breast cancer.

Relationship between nighttime snack and human health conditions remains unclear. In this paper, we analyzed the association of frequency of nighttime snacking with obesity, hyperlipidemia and hyperglycemia using a Chinese teacher cohort. The Chinese teacher study contains 22,176 of the general adult population operated on in 2015. Information of nighttime snacking frequency was acquired by questionnaire. Overweight and obesity outcome were assessed by body mass index (BMI), and hypertension; hyperlipidemia and hyperglycemia were self-reported. Associations between nighttime snacking consumption and outcomes were performed with multivariat regression and further stratification analyses. We found a significant association (OR 2.11, 95% CI 1.24, 3.62;P for trend<0.001) between most frequent nighttime snacking and hyperglycemia. A remarkable association was also observed between most frequent consumption of nighttime snack and obesity (OR 3.10, 95% CI 1.63, 5.89; Pfor trend<0.001). The present results provide epidemiological evidence that consumption of nighttime snack was associated with obesity and hyperglycemia in Chinese adult teachers. However, the underlying mechanisms still need further investigation..

Previous studies on changes in murine brain gene expression associated with the selection for ethanol preference have used F 2 intercross or heterogeneous stock (HS) founders, derived from standard laboratory strains. However, these populations represent only a small proportion of the genetic variance available in Mus musculus. To investigate a wider range of genetic diversity, we selected mice for ethanol preference using an HS derived from the eight strains of the collaborative cross. These HS mice were selectively bred (four generations) for high and low ethanol preference. The nucleus accumbens shell of naive S 4 mice was interrogated using RNA sequencing (RNA-Seq). Gene networks were constructed using the weighted gene coexpression network analysis assessing both coexpression and cosplicing. Selection targeted one of the network coexpression modules (greenyellow) that was significantly enriched in genes associated with receptor signaling activity including Chrna7, Grin2a, Htr2a and Oprd1. Connectivity in the module as measured by changes in the hub nodes was significantly reduced in the low preference line. Of particular interest was the observation that selection had marked effects on a large number of cell adhesion molecules, including cadherins and protocadherins. In addition, the coexpression data showed that selection had marked effects on long non-coding RNA hub nodes. Analysis of the cosplicing network data showed a significant effect of selection on a large cluster of Ras GTPase-binding genes including Cdkl5, Cyfip1, Ndrg1, Sod1 and Stxbp5. These data in part support the earlier observation that preference is linked to Ras/Mapk pathways., (© 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Sensing bitter tastes is crucial for most animals because it can prevent them from ingesting harmful food. This process is mainly mediated by the bitter taste receptors (T2R) that are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires. Marked variation in repertoire size has been noted among species. However, research on T2Rs is still limited and the mechanisms underlying the evolution of vertebrate T2Rs remain poorly understood. In the present study, we analyzed the structure and features of the protein encoded by the forest musk deer (Moschus berezovskii) T2R16 and submitted the gene sequence to NCBI GenBank. The results showed that the full coding DNA sequence (CDS) of musk deer T2R16 (GenBank accession No. KP677279) was 906 bp, encoding 301 amino acids, which contained ATG start codon and TGA stop codon, with a calculated molecular weight of 35.03 kDa and an isoelectric point of 9.56. The T2R16 protein receptor had seven conserved transmembrane regions. Hydrophobicity analysis showed that most amino acid residues in T2R16 protein were hydrophobic, and the grand average of hydrophobicity (GRAVY) was 0.657. Phylogenetic analysis based on this gene revealed that forest musk deer had the closest association with sheep (Ovis aries), as compared to cow (Bos taurus), Tursiops truncatus, and other species, whereas it was genetically farthest from humans (Homo sapiens). We hope these results would complement the existing data on T2R16 and encourage further research in this respect.

Forest musk deer is one of the large-scale farming musk deer animals with the largest population at the same time. The male musk deer can secrete valuable medicines, which has high medicinal and economic value. Due to the loss of habitat and indiscriminate hunting, the numbers of wild population specie and the distribution have been drastically reduced. Therefore, in-depth understanding of the molecular genetics progress of forest musk deer will pave a way for musk deer protection and breeding. In this review, the progress associated with the molecular marker, genetic classification, artificial breeding, musk secretion and disease in past decades were reviewed, in order to provide a theoretical basis for subsequent molecular genetic researches in forest musk deer.