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Ting-Yu Lin,1,2 Chun-Yu Lo,1,2 Po-Jui Chang,1,2 Yu-Lun Lo,1,2 Chung-Shu Lee,1– 3 Chih-Hao Chang,1– 3 Chih-Teng Yu,1,2 Jonathan Huai Yao,1 Shu-Min Lin1,2 1Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Pulmonary and Critical Care Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, TaiwanCorrespondence: Shu-Min Lin, Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa N. Road, Taipei, Taiwan, Fax + 886 33272474, Email smlin100@gmail.comBackground: The immunological features of eosinophils in early-onset asthma (EOA) differ from those in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA.Methods: Eosinophils obtained from well-controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was further analyzed.Results: The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function.Conclusion: This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.Graphical Abstract: Keywords: late-onset asthma, early-onset asthma, eosinophils, messenger RNA

Yan Yang,1 Jing-Hao Yao,1 Qian-Yu Du,1 Yong-Chun Zhou,2 Ting-Jing Yao,3 Qiong Wu,4 Jing Liu,1 Yu-Rong Ou41Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 2Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 3Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 4Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of ChinaBackground: Oxaliplatin (OXA)-based chemotherapy is critical in the management of advanced hepatocellular carcinoma (HCC); however, acquired drug resistance has largely restricted its clinical efficacy. This study aims to explore the key mechanisms and regulatory factors determining chemosensitivity in HCC.Methods: We developed OXA-resistant (OR) HCC cells and used multiple methods, including real-time RT-PCR, Western blot, immunofluorescence, transwell invasion assay, wound-healing assay, MTT assay, gene transfection, and immunohistochemistry to achieve our goals.Results: We found that OR HCC cells showed a typical epithelial–mesenchymal transition (EMT) phenotype. Meanwhile, the expression of Cx32, a major member of the liver connexin (Cx) family, was lowly expressed in OR HCC cells. Downregulation of Cx32 in parental HCC cells led to EMT induction and thereby reduced OXA cytotoxicity, while Cx32 upregulation in OR HCC cells could reverse the EMT phenotype and partially restore chemosensitivity to OXA. Finally, in human HCC tissue samples, Cx32 was positively correlated with the expression of the EMT marker E-cadherin and negatively correlated with the expression of Vimentin.Conclusion: Our findings demonstrated that downregulation of Cx32 may be an important determinant for HCC cells to acquire EMT-related acquired drug resistance to OXA, and targeting Cx32 could be a novel strategy to overcome OXA resistance in HCC.Keywords: hepatocellular carcinoma, oxaliplatin chemoresistance, connexin32, epithelial-mesenchymal transition

Contents mi RNAs are small non-coding regulatory RNAs that play key roles in diverse biological processes. In this study, we used the Solexa sequencing technique to profile mi RNAs in breeder cock testes to illustrate their functions. A total of 663 co-expressed mi RNAs and 3,180 co-expressed pi RNAs were detected in three libraries. Based on Mir-X™ mi RNA qRT- PCR, three mi RNAs representing low, medium and high expression levels according to the sequencing results were selected randomly to validate the mi RNAs' expression profiles. Results suggested that the mi RNA expression profiles data could represent actual mi RNA expression levels. Moreover, target genes prediction of the co-expressed mi RNAs and further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed, which revealed that some candidate mi RNAs were involved in the regulation of the spermatogenesis process, spermatozoa function and testicular metabolism. In conclusion, we provided a useful resource for further elucidation of the mi RNAs' regulatory role in spermatogenesis, contributing to a preliminary database for functional and molecular mechanistic studies in testicular metabolism, spermatogenesis and other testes functions. [ABSTRACT FROM AUTHOR]

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring's PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

Objective: Through the analysis of five cases of occupational heat illness caused by high temperature, we expounded the pathogenesis and summarized the clinical characteristics of heat cramp and heat exhaustion of the newly revised diagnostic criteria for occupational heat illness (GBZ41-2019), in order to prevent the occurrence of occupational heat illness to put forward controllable countermeasures. Methods: According to the occupational history, clinical diagnosis and treatment and the other relevant data submitted by five patients, the diagnosis process was analyzed and summarized. Results: Five patients developed symptoms from July to August in summer, belonging to high-temperature operation. They improved by timely treatment. The symptoms, signs and laboratory tests of the five patients were different, but they were diagnosed as occupational heat illness. Conclusion: Employers should pay attention to the high temperature protection and cooling work, and strengthen the labor protection. If patients with heat cramp and heat exhaustion were timely treated, they could basically recover. Occupational disease diagnosticians should seriously study the new diagnostic criteria of occupational disease and constantly improve their diagnostic ability.

High growth rates and body weight are important traits of young dairy goats that can shorten generation intervals, improve animal performance, and increase economic benefits. In the present study, ninety-nine, 6-month-old, female goats were fed with the same diet and kept under the same management condition. The ten goats with highest average daily gain (ADG, HADG, 135.27 ± 4.59 g/d) and ten goats with lowest ADG (LADG, 87.74 ± 3.13 g/d) were selected to identify the key serum metabolites associated with ADG, and to investigate the relationships of serum metabolome profiles with digestive tract microbiota. The results showed that a total of 125 serum metabolites were significantly different between HADG and LADG. Of these, 43 serum metabolites were significantly higher levels in HADG, including D-ornithine, l-glutamine, L-histidine, carnosine, LysoPC (16:1(9Z)/0:0), DCTP and hydroxylysine, while, 82 serum metabolites were significantly higher levels in LADG, including P-salicylic acid and deoxycholic acid 3-glucuronide. Pathway analysis indicated that these different metabolites were mainly involved in amino acid and lipid metabolism. Furthermore, Spearman's rank correlation analysis revealed that these differential serum metabolites were correlated with ADG and ADG-related bacteria. Notably, serum hydroxylysine and L-histidine could be used as biomarkers for distinguishing HADG and LADG goats, with an accuracy of >92.0%. SIGNIFICANCE: Our study confirms that individual microbiota and metabolic differences contribute to the variations of growth rate in young goats. Some serum metabolites may be useful in improving the growth performance of young goats, which provides directions for developing further nutritional regulation in the goat industry to achieve healthy feeding and efficiency enhancement., Competing Interests: Declaration of Competing Interest The authors declare that there are no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Silicosis is a progressive pulmonary fibrosis disease caused by long-term inhalation of a large amount of free crystalline silica, which seriously threatens the health of relevant workers and causes a huge amount of disease burden. The pathogenesis of silicosis is complex and unclear, it has been reported that long non coding RNA (lncRNA) plays an important role in the pathogenesis of silicosis. In order to improve the understanding of the disease and provide directions for the prevention and treatment of silicosis, this article reviewed the mechanism of lncRNA in the pathogenesis and disease progression of silicosis.

Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows. This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expression of the main genes involved in gluconeogenesis in calf hepatocytes and elucidate the associated mechanisms. Calf hepatocytes were obtained from 5 healthy calves (1 d old; 30 to 40 kg) and exposed to 0-, 1-, 2.5-, or 5-mM sodium propionate (NaP), which is known to promote the expression of genes involved in the gluconeogenesis pathway, including fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase. With regard to the underlying mechanism, propionate promoted the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, hepatocyte nuclear factor 4, and forkhead box O1 (transcription factors that regulate the expression of hepatic gluconeogenic genes) by promoting mammalian target of rapamycin complex 1 (mTORC1), but inhibiting mTORC2 activity ( P  < 0.01). We also established a model of palmitic acid (PA)-induced hepatic injury in calf hepatocytes and found that PA could inhibit the gluconeogenic capacity of calf hepatocytes by suppressing the expression of gluconeogenic genes, inhibiting mTORC1, and promoting the activity of mTORC2 ( P  < 0.01). In contrast, NaP provided protection to calf hepatocytes by counteracting the inhibitory effect of PA on the gluconeogenic capacity of calf hepatocytes ( P  < 0.05). Collectively, these findings indicate that NaP enhances the gluconeogenic capacity of calf hepatocytes by regulating the mTOR pathway activity. Thus, in addition to improving the glucose production potential, propionate may have therapeutic potential for the treatment of hepatic injury in dairy cows., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

In the absence of adequate treatment, effective bone regeneration remains a great challenge. Exploring hydrogels with properties of excellent bioactivity, stability, non-immunogenicity, and commercialization is an important step to develop hydrogel-based bone regeneration materials. In this study, we engineered a self-assembled chelating peptide hydrogel loaded with an osteogenic metal ion cluster extracted from the processed pyritum decoction, including Fe 2+ , Cu 2+ , Zn 2+ , Mn 2+ , Mg 2+ , and Ca 2+ ions, named processed pyritum hydrogel (PPH). We demonstrated that as a reservoir of beneficial metal ion clusters in bone regeneration, PPH has been shown to regulate a variety of genes in the process of bone regeneration. These genes are mainly involved in extracellular matrix synthesis, cell adhesion and migration, cytokine expression, antimicrobial and inflammation. Therefore, PPH accelerated the progress of various bone healing stages, and shortened the bone healing cycle by 4 weeks. Our investigation outcomes showed that the engineered metal ion cluster hydrogel is a novel, simple, and commercializable bone-regenerating hydrogel with potential clinical use., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Background: Despite evidence of adverse health consequences of inadequate restorative sleep for older adults, assessment of sleep quantity, quality, and use of sleep aids is not routinely done. We aimed to characterize sleep problems, sleep risks, and advice received about sleep in a community-dwelling older adult population, overall and in subgroups with health conditions and functional difficulties., Methods: This cross-sectional study used weighted self-report data for 5074 Kaiser Permanente Northern California members aged 65-79y who responded to a 2017 or 2020 Member Health Survey. We estimated usual amount of sleep (&lt; 6, 6 to &lt; 7, ≥7 hours) and prevalence of sleep problems (frequent insomnia, frequent daytime fatigue, poor quality sleep, and potential sleep apnea (OSA) symptoms (frequent very loud snoring, apnea episodes)) for older adults overall, by self-rated health, and in subgroups reporting hypertension, diabetes, heart disease, frequent problems with balance/walking, and frequent memory problems. We also estimated percentages who regularly used sleep aids and had discussed sleep adequacy with a healthcare professional in the past year., Results: Approximately 30% of older adults usually got less than the recommended ≥7 hours sleep per day, and 9% experienced frequent daytime fatigue, 13% frequent insomnia, 18% frequent insomnia/poor quality sleep, and 8% potential OSA symptoms. Prevalence of frequent insomnia was higher among women than men (16% vs. 11%). Higher percentages of those in fair/poor health and those with frequent balance/walking and memory problems reported sleeping &lt; 6 hours per day and having all four types of sleep problems. Nearly 20% of all older adults (22% of women vs. 17% of men) and 45% of those with frequent insomnia (no sex difference) reported regular sleep aid use. Only 10% of older adults reported discussing sleep with a healthcare professional whereas &gt; 20% reported discussing diet and exercise., Conclusions: Large percentages of older adults experience sleep problems or get less sleep than recommended for optimal sleep health. Older patients should routinely be assessed on multiple components of sleep health (sleep hygiene, quantity, quality, problems, and sleep aid use) and educated about sleep hygiene and the importance of getting adequate restorative sleep for their overall health and wellbeing., (© 2022. The Author(s).)

Background: Smoking behavior is influenced by multiple genes, including the bitter taste gene TAS2R38. It has been reported that the correlation between TAS2R38 and smoking behavior has ethnicity-based differences. However, the TAS2R38 status in Chinese smokers is still unclear., Objective: This study aims to investigate the possible relationship between genetic variations in TAS2R38 (A49P, V262A and I296V) and smoking behaviors in the Han Chinese population., Methods: The haplotype analyses were performed and smoking behavior questionnaire was completed by 1271 individuals. Genetic association analyses for smoking behavior were analyzed using chi-square test. Further, for investigating the molecular mechanism of TAS2R38 variants effect on smoking behavior, we conducted TAS2R38-PAV and TAS2R38-AVI expression plasmids and tested the cellular calcium assay by cigarette smoke compounds stimulus in HEK293., Results: Significant associations of genetic variants within TAS2R38 were identified with smoking behavior. We found a higher PAV/PAV frequency than AVI/AVI in moderate and high nicotine dependence (FTND ≥ 4; X 2  = 4.611, 1 df, p = 0.032) and strong cigarette smoke flavor intensity preference (X 2  = 4.5383, 1 df, p = 0.033) in participants. Furthermore, in the in vitro cellular calcium assay, total particle matter (TPM), N-formylnornicotine and cotinine, existing in cigarette smoke, activated TAS2R38-PAV but not TAS2R38-AVI-transfected cells., Conclusion: Our data highlights that genetic variations in TAS2R38 are related to smoking behavior, especially nicotine dependence and cigarette smoke flavor intensity preference. Our findings may encourage further consideration of the taste process to identify individuals susceptible to nicotine dependence, particularly Han Chinese smokers., (© 2022. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Background: N1-methyladenosine (m1A) is a reversible post-transcriptional modification in mRNA, which has been proved to play critical roles in various biological processes through interaction with different m1A regulators. There are several m1A regulators existing in the human genome, including YTHDF1-3 and YTHDC1., Methods: Several techniques have been developed to identify the substrates of m1A regulators, but their binding specificity and biological functions are not yet fully understood due to the limitations of wet-lab approaches. Here, we submitted the framework m1ARegpred (m1A regulators substrate prediction), which is based on machine learning and the combination of sequence-derived and genome-derived features., Results: Our framework achieved area under the receiver operating characteristic (AUROC) scores of 0.92 in the full transcript model and 0.857 in the mature mRNA model, showing an improvement compared to the existing sequence-derived methods. In addition, motif search and gene ontology enrichment analysis were performed to explore the biological functions of each m1A regulator., Conclusions: Our work may facilitate the discovery of m1A regulators substrates of interest, and thereby provide new opportunities to understand their roles in human bodies., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Cow milk consumption (CMC) and alterations of gut bacterial composition are proposed to be closely related to human health and disease. Our research aims to investigate the changes in human gut microbial composition in Chinese peri-/postmenopausal women with different CMC habits. A total of 517 subjects were recruited and questionnaires about their CMC status were collected; 394 subjects were included in the final analyses. Fecal samples were used for studying gut bacterial composition. All the subjects were divided into a control group ( n = 248 ) and a CMC group ( n = 146 ) according to their CMC status. Non-parametric tests and LEfSe at different taxonomic levels were used to reveal differentially abundant taxa and functional categories across different CMC groups. Relative abundance (RA) of one phylum ( p&#95;Actinobacteria ), three genera ( g&#95;Bifidobacterium , g&#95;Anaerostipes , and g&#95;Bacteroides ), and 28 species diversified significantly across groups. Specifically, taxa g&#95;Anaerostipes ( p < 0.01 ), g&#95;Bacteroides ( p < 0.05 ), s&#95;Anaerostipes&#95;hadrus ( p < 0.01 ), and s&#95;Bifidobacterium&#95;pseudocatenulatum ( p < 0.01 ) were positively correlated with CMC levels, but p&#95;Actinobacteria ( p < 0.01 ) and g&#95;Bifidobacterium ( p < 0.01 ) were negatively associated with CMC levels. KEGG module analysis revealed 48 gut microbiome functional modules significantly ( p < 0.05 ) associated with CMC, including Vibrio cholerae pathogenicity signature, cholera toxins ( p = 9.52e-04 ), and cephamycin C biosynthesis module ( p = 0.0057 ), among others. In conclusion, CMC was associated with changes in gut microbiome patterns including beta diversity and richness of some gut microbiota. The alterations of certain bacteria including g&#95;Anaerostipes and s&#95;Bifidobacterium&#95;pseudocatenulatum in the CMC group should be important for human health. This study further supports the biological value of habitual cow milk consumption., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Yao, Lin, Lv, Jiang, Wang, Shen, Xiao, Xu, Xu, Cheng, Shen, Qiu, Luo, Zhao, Yan, Deng and Zhang.)

We hypothesised that adding a combination of fibrolytic and amylolytic enzymes to the diet of early-lactation dairy cows would improve rumen enzyme activity and bacterial diversity, promote energy metabolism, and benefit milk production in cows. Twenty multiparous early-lactation (90 ± 5 d) Holstein cows with similar body conditions were randomly allocated to control (CON, n = 10) and experimental (EXP, n = 10) groups in a completely randomised single-factor design. The CON was fed only a basal total mixed ration diet, and the diet of the EXP was supplemented with a combination of fibrolytic and amylolytic enzymes at 70 g/cow/d (cellulase 3 500 CU/g, xylanase 2 000 XU/g, β-glucanase 17 500 GU/g, and amylase 37 000 AU/g). The experiment lasted 28 days, with 21 days for adaptation and 7 days for sampling. Enzyme addition increased the activity levels of α-amylase and xylanase, and the ammonia-N concentration (P < 0.05) tended to increase the activity of β-glucanase (P = 0.08) in rumen fluid. However, there was no significant difference in the rumen bacterial richness and diversity, phylum (richness > 0.1%) or genus (richness > 1%) composition between the CON and EXP groups (P > 0.05). A tendency of difference was found between CON and EXP (R = 0.22, P = 0.098) in principal component analysis. Ten genera showed different abundances across the CON and EXP groups (linear discriminant analysis effect size, linear discriminant analysis > 2). EXP increased the ratio of albumin to globulin and the concentrations of total cholesterol and low-density lipoprotein cholesterol (P < 0.05) and tended to increase triglycerides (P = 0.09) in blood. Milk yield, 3.5% fat-corrected milk yield and energy-corrected milk yield increased with enzyme supplementation (P < 0.05). The production levels of milk fat and lactose increased, but the percentage of solids, not fat and protein, decreased in EXP (P < 0.05). Although the DM intake was not affected, the feed efficiency tended to increase (P = 0.07) in EXP. In conclusion, dietary supplementation with a mixture of fibrolytic and amylolytic enzymes on multiparous early-lactation dairy cows increased α-amylase and xylanase activity levels in rumen fluid, enhanced milk performance and tended to improve the feed efficiency in cows., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: In this study, we aimed to examine the efficacy of micro ribonucleic acid (miRNA)-23a-5p in gouty arthritis and to investigate its possible mechanism., Materials and Methods: Gouty arthritis in rat was established by intraarticular injection of 0.2 mL monosodium urate crystal (20 mg/mL) inside knee joint cavity. THP-1 cell was induced using lipopolysaccharides (LPS) for in vitro model., Results: Serum miRNA-23a-5p expression levels were increased in rats of gouty arthritis. However, overexpression of miRNA-23a-5p promoted inflammation and induced myeloid differential protein-88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway by induction toll-like receptor-2 (TLR2) in vitro . The inhibition of TLR2 attenuated the pro-inflammation effects of miRNA-23a-5p in inflammation in in vitro model of gouty arthritis., Conclusion: Our findings demonstrate that miRNA-23a-5p is a biomarker for gouty arthritis and promotes inflammation in rats of gouty arthritis via MyD88/NF-κB pathway by targeting TLR2., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2022, Turkish League Against Rheumatism.)

The bioconversion of coal at ambient conditions is a promising technology for coal processing. However, there are few examples of the optimization of processes for industrial-scale use. In this work, the optimization of process parameters affecting lignite bioconversion by an isolated fungus WF8 using an artificial neural network (ANN) combined with a genetic algorithm (GA) was carried out for modeling of humic acids (HAs) yield and parameters. Kinetic models were used to understand the release characteristics of HAs from the bioconversion of lignite. The results of the present work indicate that the optimal process parameters (OPP) are 29 °C, initial pH of 7, 180 rpm, 0.6 mmol·L -1 of CuSO 4 , 0.4 mmol L -1 of MnSO 4 , and 6.4 μmol·L -1 of veratryl alcohol (VA). The predicted experimental data obtained by ANN is similar to the actual and the significant correlation coefficient value (R 2 ) of 0.99 indicates that ANN has good predictability. The actual yield of HAs are 5.17 mg·mL -1 . During bioconversion, the fungus WF8 could loosen and attack the structure of lignite. The release of HAs produced by bioconversion of lignite under the OPP via diffusion and swelling is fit to zero-order model independent on concentration. This provides support for the industrial bioconversion of lignite., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Essential oils(EOs) from Chinese medicinals, which can be used as adjuvants and exert certain therapeutic effect, are directly used in Chinese medicine formulas. Conventional research strategy for EOs from Chinese medicinals is to compare the efficacy of the prescriptions before and after the addition of EOs, and the penetration-enhancing mechanisms of EOs remain unclear. In modern research on EOs from Chinese medicinals, the method for studying chemical penetration enhancers is often used, which fails to reflect the overall efficacy of EOs. This study clarified the property regularity of EOs from Chinese medicinals as transdermal penetration enhancers, and thereby proposed a research model which integrated the medicinal and adjuvant properties of EOs from Chinese medicinals via &quot;component-delivery-effect&quot; characterization route. The core concept is that constituents of EOs from Chinese medicinals and their delivery process play a key role in their external application. This research model is expected to serve as a reference for further research on EOs from Chinese medicinals for transdermal application.

Background: IL-18 is known as an interferon-inducing factor that belongs to the IL-1 family, and is synthesized as an inactive precursor protein., Objective: The present study aims to investigate the expression of IL-18, IL-18R, R and IL-18 binding protein (BP) mRNA in various types of human pituitary tumors, such as adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH)-producing adenomas and non-function adenomas., Methods: Pituitary adenoma tissues were obtained during the surgery of 41 patients: nine patients had ACTH-producing pituitary adenomas, nine patients had GH-producing pituitary adenomas, five patients had TSH-producing pituitary adenomas, seven patients had PRL-producing pituitary adenomas, and 11 patients had non-functioning adenomas. The mRNA expression levels of IL-18, IL-18BP, IL-18R and IL-18R were quantified using real-time quantitative PCR., Results: The mRNA expression of IL-18 was significantly higher in ACTH-, GH- and PRL-producing adenomas, when compared to non-function tumors. Similarly, a significantly higher mRNA expression of IL-18BP and IL-18R was observed in ACTH-, GH- and PRL-producing adenomas, when compared with non-functional adenomas. In contrast, no upregulation of IL-18R mRNA was observed in any of the pituitary adenomas., Conclusions: The mRNA levels of IL-18, IL-18BP and IL-18R are significantly elevated in clinical pituitary tumors, such as ACTH-, GH- and PRL-producing adenomas, when compared to non-functional adenomas. These present results suggest the possibility that IL-18 may be involved in the pathogenesis of pituitary adenoma.

Development of acquired resistance to lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor, severely limits the duration of clinical response in advanced HER2-driven breast cancer patients. Although the compensatory activation of the PI3K/Akt survival signal has been proposed to cause acquired lapatinib resistance, comprehensive molecular mechanisms remain required to develop more efficient strategies to circumvent this therapeutic difficulty. In this study, we found that suppression of HER2 by lapatinib still led to Akt inactivation and elevation of FOX3a protein levels, but failed to induce the expression of their downstream pro-apoptotic effector p27 kip1 , a cyclin-dependent kinase inhibitor. Elevation of miR-221 was found to contribute to the development of acquired lapatinib resistance by targeting p27 kip1 expression. Furthermore, upregulation of miR-221 was mediated by the lapatinib-induced Src family tyrosine kinase and subsequent NF-κB activation. The reversal of miR-221 upregulation and p27 kip1 downregulation by a Src inhibitor, dasatinib, can overcome lapatinib resistance. Our study not only identified miRNA-221 as a pivotal factor conferring the acquired resistance of HER2-positive breast cancer cells to lapatinib through negatively regulating p27 kip1 expression, but also suggested Src inhibition as a potential strategy to overcome lapatinib resistance., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: To determine whether the teaching method of seminars combined with case-based learning (CBL) is superior to the traditional lecture-based learning (LBL) for teaching cancer pain in medical oncology internship., Methods: Sixty medical and nursing interns in the medical oncology department of our hospital were selected between January 2019 and December 2020. Thirty students received traditional LBL instruction as the control group, and 30 students received combined seminars and CBL instruction as the observation group. The teaching evaluation and assessment was performed by theoretical and practical examinations and questionnaires., Results: In the after-class examination, case analysis, clinical practice and overall scores of the observation group were higher than those of the control group (all p < 0.001). Theoretical knowledge scores did not differ significantly between the two groups ( p = 0.470). In the questionnaire regarding attitudes towards opioid use, the observation group had better perceptions of using opioids than the control group (all p < 0.01). In the meantime, students in the observation group outperformed the control group in four aspects: self-learning ( p < 0.001), analytical and problem-solving ( p < 0.001), clinical thinking ( p = 0.001), and clinical practice ( p = 0.002) abilities all improved, while stimulating learning interest ( p = 0.184) and enhancing theoretical knowledge mastery ( p = 0.221) were not significantly different from those of the control group. Overall, students in the observation group were more satisfied with the teaching, teaching methods and teacher performances than the control group (all p < 0.001)., Conclusion: Compared to the LBL, the combination of seminars and CBL is a more effective teaching method for cancer pain management, which is worth further study., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Yang et al.)

COVID-19 is an important public health issue of great concern at home and abroad, and it is still in the state of global pandemic. During the normalization stage of prevention and control of the epidemic of COVID-19, China effectively controlled the outbreak and spread of the epidemic by adopting the strategy of "import of external prevention and rebound of internal prevention", and effectively reduced the occurrence of death cases. The social economy recovered quickly, and various measures were highly recognized by the public, and the positive trend of the epidemic continued to consolidate. At present, although the spread of the local epidemic has been basically stopped, the international epidemic continues to rise rapidly, and the pressure of "imported prevention and control" in China continues to increase. Considering the characteristics of the normalization of epidemic prevention and control and the particularity of the virus, the connotation of the normalization of epidemic prevention and control should be understood scientifically. The prevention and control goal of the epidemic in the normalization stage should be to maximize early detection, early treatment and early disposal, and resolutely prevent the continuous spread of the epidemic in communities, that is, to prevent the infection as much as possible, and resolutely prevent the rebound (sustained spread in communities), rather than "zero infection". The prevention and control policy of "timely detection, rapid disposal, precise management and control, and effective treatment" has been implemented in various localities, and a series of effective and regular experience in prevention and control has been formed in the practice of prevention and control. Winter and spring are the key periods for the prevention and control of the epidemic. We should continue to work together to prevent and control the epidemic, fulfill the responsibilities of all parties, and prevent and control the epidemic in a scientific and effective way.

The caecum is the primary site where microbial fermentation and acidosis occurred. The supplementation of starter feed and alfalfa hay has the potential to influence caecal microbiota and then affect caecal fermentation. This study aims to investigate the effect of starter feed and alfalfa hay supplementation on caecal microbiota, immune homeostasis, and growth of preweaning yaks. Twenty 30-day-old male yak calves were randomly assigned to four groups, which separately fed with milk replacer (CON group), milk replacer with alfalfa hay (A group), milk replacer with starter feed (S group), and milk replacer with starter feed plus alfalfa hay (SA group) throughout the trial. Growth performance and plasma physiological and biochemical indicators were measured every 30 days. Calves were sacrificed at 120 days of age. The caecal contents were collected for measuring pH and contents of volatile fatty acids (VFAs) and lipopolysaccharide (LPS) and for characterizing caecal microbiota. The results indicated that individual or simultaneous supplementation with alfalfa hay and starter feed all significantly increased the BW, body height, body length, and chest girth of yak calves. However, supplementation with starter feed significantly increased plasma cortisol, nitric oxide, tumor necrosis factor-α, and interferon-γ concentrations and the ratio of aspartate aminotransferase to alanine aminotransferase of yak calves when compared with the control and alfalfa hay feeding groups, while the co-supplementation of starter feed and alfalfa hay could significantly decrease these inflammation-related indices when compared with the starter feeding group. Sequencing of the 16S rRNA gene showed that starter feed and alfalfa hay separately stimulated the proliferation of starch-decomposing and cellulose- or hemicellulose-decomposing bacteria. This also significantly increased the levels of acetate, propionate, butyrate, valerate, isobutyrate, and isovalerate in the caecal contents. Furthermore, compared with the S and CON groups, the significantly increased genera of Desulfobulbus, Olsenella, Pseudoflavonifractor, and Stomatobaculum in the SA and A groups were beneficial to the immune homeostasis, and the significantly decreased Blautia, Clostridium IV, Bacteroides, Eubacterium, Clostridium XVIII, and Mogibacterium in the SA and A groups were related to the reduced caecal lactate and LPS contents, the decreased inflammatory reaction, and the improved healthy hepatic condition of yak calves. In conclusion, milk replacer supplemented with alfalfa hay and starter feed is recommended during preweaning to improve yak calf health and growth because this regimen promotes the growth and maintains the immune homeostasis of yak calves., (Copyright © 2020. Published by Elsevier B.V.)

Busulfan-induced testicular injury mouse models are commonly used for experiments on spermatogonial stem cell transplantation, treatments for azoospermia due to spermatogenic failure and preserving male fertility after chemotherapy. Here, we investigated the value of testicular quantitative ultrasound for evaluating spermatogenic function in this model. In this study, testicular ultrasound was performed on mice from day 0 to 126 after busulfan treatment (n = 48), and quantitative data, including the testicular volume, mean pixel intensity and pixel uniformity, were analysed. The results revealed that from day 0 to 36, the testicular volume was positively associated with the testicle-to-body weight ratio (r = .92). On day 63, the pixel uniformity, which remained stable from day 0 to 36, declined significantly compared with that on day 36 (p < .01). On day 126, when the whole progression of spermatogenesis could be observed in most tubules, the mean pixel intensity also returned to normal (p > .05). In conclusion, testicular quantitative ultrasound could be used as a noninvasive and accurate monitoring method for evaluating spermatogenic function in busulfan-induced testicular injury mouse models., (© 2020 Wiley-VCH GmbH.)

Agglomerated ZnMn₂O₄ nanoparticles with average particle sizes of 90-130 nm are synthesized by a facile chemical co-precipitation method. It is found that the consumption of precipitant ammonia has an important impact on the morphology and lithium storage property of the prepared ZnMn₂O₄ nanomaterials. With increasing ammonia consumption (molar ratios of Zn 2+ to the precipitant ammonia of 1:10, 1:15, 1:20 and 1:25, respectively), the particle size of the prepared ZnMn₂O₄ nanomaterials becomes smaller, the porous morphology formed by the primary nanoparticles agglomeration becomes more obvious, and the lithium storage performance is improved. When Zn 2+ /ammonia mole ratio is 1:25, the prepared ZnMn₂O₄ material presents a reversible capacity of 780 mAh g -1 after 200 cycles at a current density of 0.5 A g -1 . At a very high current density of 5 A g -1 , the sample still retains a reversible capacity of 250 mAh g -1 . This superior lithium storage performance of the sample is associated with its porous structure, which benefits the penetration of the electrolyte and enhances the electrochemical reaction activity of the active materials in the electrode. These results suggest that agglomerated ZnMn₂O₄ nanoparticles prepared by chemical coprecipitation method have potential as anode electroactive materials for next-generation lithium-ion batteries.

Purpose: To evaluate diagnostic and predictive values of the serum vascular endothelial growth factor-A (VEGF-A) level and systemic immune-inflammation index (SII) in small cell lung cancer (SCLC) patients. Methods: From January 2018 to April 2020, we prospectively enrolled 59 untreated SCLC patients in the study group and 50 non-neoplastic patients in the control group. Blood samples were collected at baseline, after the first two cycles of chemotherapy and at progression in the study group and at entry in the control group. Serum VEGF-A was measured by chemiluminescence, SII was calculated based on complete blood count results, and the relationship between the VEGF-A/SII and clinicopathological characteristics, chemotherapeutic efficacy and progression-free survival (PFS) of SCLC patients was analyzed. Results: Baseline serum VEGF-A was significantly higher in SCLC patients than in non-neoplastic patients ( P< 0.001), while baseline SII was not ( P= 0.114). There was no correlation between baseline VEGF-A and SII in SCLC patients ( P= 0.123); however, there was a significant correlation between baseline VEGF-A and disease stage and central nervous system (CNS) metastasis ( P= 0.021 and P= 0.012, respectively), as well as between baseline SII and disease stage and liver metastasis ( P= 0.026 and P= 0.018, respectively). Serum VEGF-A was significantly lower than the pretreatment level after 2 cycles of treatment ( P= 0.049) but was not different at progression ( P= 0.247). Baseline VEGF-A was correlated with the treatment response of first-line chemotherapy ( P= 0.001), while baseline SII was not ( P= 0.392). Kaplan-Meier survival analysis suggested that the PFS of first-line chemotherapy was significantly longer in the low-VEGF-A group at baseline than the high-VEGF-A group (11.37 vs. 6.17 months, P< 0.001). There was a trend toward longer PFS of first-line chemotherapy in the low-SII group at baseline than the high-SII group, but the difference was not significant (12.10 vs. 9.10 months, P> 0.050). Univariate and multivariate Cox regression analyses suggested that baseline VEGF-A (HR: 3.443, 95% CI: 1.330-8.908, P= 0.011) was an independent prognostic factor for PFS in SCLC patients. Conclusions: Baseline serum VEGF-A and SII are associated with important clinicopathological characteristics of SCLC patients. VEGF-A, but not SII, has the ability of diagnosis and predicting first-line chemotherapeutic efficacy and prognosis in SCLC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: To analyze the clinical and molecular characteristics, as well as pathologic diagnosis and treatment of lung tumors that spread to the breast in 22 Chinese patients., Materials and Methods: A systematic literature search of PubMed, Embase, ScienceDirect, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database and Wanfang Databases was conducted to identify the related studies published before March 31, 2020. A case of a 64-year-old man who underwent pneumonectomy and who was eventually diagnosed with a breast lump 5 years after surgery at our hospital, was also included in the present study. We analyzed the clinical and immunohistochemical characteristics from these case reports., Results: The analysis totally incorporates 21 case reports and our own case, covering 22 subjects. Among all cases we found 11 adenocarcinomas, 7 small-cell carcinomas, and 4 squamous carcinomas. In addition, most of metastatic breast masses were located below or near the nipple, rather than in the outer quadrant. The results of immunohistochemistry mostly showed triple negative breast cancers., Conclusion: A lung cancer patient with a breast tumor should suggest the possibility of metastasis. It is extremely difficult to distinguish secondary breast cancer from primary simply through medical observation and pathologic testing. Additional immunohistochemical examinations are necessary to avoid delays in diagnosis and treatment., Competing Interests: None., (IJCEP Copyright © 2020.)

Objective: To investigate the gene mutation occurved in AML patients with 29 kinds of fusion genes and 51 kinds of tumor gene., Methods: Next-generation sequencing (NGS) was used to detected the 49 kinds of targeted gene. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutation were detected by DNA-based PCR and Sanger sequencing. Twenty-nine kinds of fusion genes were dected by multiplex nested RT-PCR., Results: The total gene mutation rate was 91% (109/121) in all the 121 patients. On average, 2.1 mutated genes per patient were identified, among these 121 patients, coexistence of ≥ 3 mutations was frequent (34.7%). The most commonly mutated genes were NRAS (23.96%, n=29), followed by NPM1 (14.04%, n=17), CEBPA double mutations (14.04%, n=17), KRAS (11.57%, n=14)，FLT3-ITD (10.74%, n=13), CSF3R (10.74%, n=13), TET2 (9.92%, n=12) and IDH1 (9.1%, n=11). Overall, fusion genes were detected in 47 (37.3%) patients, including AML/ETO (n=12), CBFβ/MYH11 (n=11), PML/RARa (n=12), MLL rearranagement realated mutation MLL-X (n=10). TLS/ERG (n=1) and DEK/CAN (n=1) in an order of decreasing frequency. Patients with normal karyotype (NK)- AML exhibited more mutations in CEBPA, NPM1, TET2, RUNX1 and IDH1, comparing with abnormal karyotype patients. KRAS mutation in abnormal kayotype patients was significantly higher than that in normal kayotype patients (P=0.014). TP53 mutations were predominantly associated with complex cytogenetics (P=0.199). KRAS mutations were more frequent in core binding factor (CBF) acute myeloid leukemia (AML) and 11q23/MLL rearrangement leukemia, compared with NK-AML (P=0.006 and 0.003, respectively). KIT mutations predominated in CBF-AML (P=0.006). JAK2V617F mutations were detected in two patients and co-occurred with AML-ETO fusions., Conclusion: At least one mutation is observed in more than 90% patients. On average, more than 2 mutated genes per patient are identified. Some gene mutations are associated with gene rearrangement.

In the present work, the effects of different energy substrates and nickel ions (Ni 2+ ) and cadmium ions (Cd 2+ ) on the growth of Acidithiobacillus ferrooxidans (A. ferrooxidans) were investigated. Ferrous sulphate (FeSO 4 ) was the optimum energy substrate for A. ferrooxidans growth, among the selected substrates. When cultured together with FeSO 4 and sulphur (S), A. ferrooxidans first oxidised the ferrous ions (Fe 2+ ), and the S was utilised as the concentration of Fe 2+ decreased. After adapting to culture with Ni 2+ and Cd 2+ , A. ferrooxidans presented good tolerance to both ions, with the maximum concentration reaching 4.11 g/L Ni 2+ and 1.69 g/L Cd 2+ . A preliminary simulation of industrial application was also performed on used Ni-Cd batteries. With bioleaching, the highest concentrations of Cd 2+ and Ni 2+ were 3003 mg/L at day 8 and 1863 mg/L at day 14, respectively.

Background: Intestinal ischemia reperfusion (I/R) occurs in various diseases, such as trauma and intestinal transplantation. Excessive reactive oxygen species (ROS) accumulation and subsequent apoptotic cell death in intestinal epithelia are important causes of I/R injury. PTEN-induced putative kinase 1 (PINK1) and phosphorylation of dynamin-related protein 1 (DRP1) are critical regulators of ROS and apoptosis. However, the correlation of PINK1 and DRP1 and their function in intestinal I/R injury have not been investigated. Thus, examining the PINK1/DRP1 pathway may help to identify a protective strategy and improve the patient prognosis., Aim: To clarify the mechanism of the PINK1/DRP1 pathway in intestinal I/R injury., Methods: Male C57BL/6 mice were used to generate an intestinal I/R model via superior mesenteric artery occlusion followed by reperfusion. Chiu's score was used to evaluate intestinal mucosa damage. The mitochondrial fission inhibitor mdivi-1 was administered by intraperitoneal injection. Caco-2 cells were incubated in vitro in hypoxia/reoxygenation conditions. Small interfering RNAs and overexpression plasmids were transfected to regulate PINK1 expression. The protein expression levels of PINK1, DRP1, p-DRP1 and cleaved caspase 3 were measured by Western blotting. Cell viability was evaluated using a Cell Counting Kit-8 assay and cell apoptosis was analyzed by TUNEL staining. Mitochondrial fission and ROS were tested by MitoTracker and MitoSOX respectively., Results: Intestinal I/R and Caco-2 cell hypoxia/reoxygenation decreased the expression of PINK1 and p-DRP1 Ser637. Pretreatment with mdivi-1 inhibited mitochondrial fission, ROS generation, and apoptosis and ameliorated cell injury in intestinal I/R. Upon PINK1 knockdown or overexpression in vitro , we found that p-DRP1 Ser637 expression and DRP1 recruitment to the mitochondria were associated with PINK1. Furthermore, we verified the physical combination of PINK1 and p-DRP1 Ser637., Conclusion: PINK1 is correlated with mitochondrial fission and apoptosis by regulating DRP1 phosphorylation in intestinal I/R. These results suggest that the PINK1/DRP1 pathway is involved in intestinal I/R injury, and provide a new approach for prevention and treatment., Competing Interests: Conflict-of-interest statement: All the authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Milk is a dynamic source of nutrients and bioactive factors, varying with the nutrition status of the cattle. We partly replaced alfalfa hay with whole cotton seed and soybean hull (non-forage fiber source, NFFS) in the feed formula of treated cows and evaluated the effects on milk extracellular vesicles (EVs). The NFFS supplement did not affect the shape of milk EVs observed using a transmission electron microscope. Nanoparticle tracking analysis revealed that the EV concentration increased significantly in treated cows (P = 0.019), with the peak diameter unaffected by the treatment. The EV-RNA concentration and small RNA content, particularly rRNAs and tRNAs, significantly increased in the treated cows (P < 0.05). The other small RNAs, i.e. miRNAs, cis-regulatory elements, snRNAs, and other Rfam RNAs showed no significant difference between the two groups. Totally 276 milk EV-miRNAs were identified. Thirteen miRNAs, accounting for 76%, in the highly expressed top 20, were immune-related. In addition, 9 differently expressed miRNAs (4 up-regulated and 5 down-regulated) were identified (P < 0.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the differently expressed miRNAs were related to the citrate cycle, fat digestion and absorption process, taurine and hypo-taurine metabolism, and glycosphingolipid biosynthesis. This study documents the milk nutrition assessment from macromolecules, especially EVs.

A STRN-ALK fusion protein has been recently identified as a potential therapeutic target in multiple cancers; however, the role of STRN alone in regulating the biological function of hepatocellular carcinoma (HCC) remains unclear. In this study, we firstly detected an overexpression of STRN in HCC tissues compared to that in adjacent nontumour (ANT) tissues through IHC analysis, and the expression level of this protein was positively correlated with lymph node metastasis and TNM stage. In vitro , high expression of STRN was also confirmed in different HCC cell lines, and regulation of STRN expression in Huh7 cells did not significantly affect tumour cell proliferation or apoptosis but was positively correlated with tumour cell invasion and migration capacities. Moreover, both the knockdown and overexpression of STRN in Huh7 cells can lead to cell morphological changes that are accompanied with an alteration of epithelial-mesenchymal transition (EMT) molecular markers E-cadherin and Vimentin. Finally, STRN was further proved to be negatively related to E-cadherin expression but positively related to Vimentin expression in human HCC tissue samples. Taken together, STRN is upregulated in HCC and acts as a tumour promoter regulating cell invasion and migration through facilitating the EMT process., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Qian-yu Du et al.)

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg -1 . In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg -1 ) on day 36 or a dose of 40 mg kg -1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg -1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg -1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity., Competing Interests: None

Background: The aim of this study is to explore the efficacy and safety of ulinastatin for the treatment of patients with severe acute pancreatitis (SAP)., Methods: We will search randomized controlled trials which assess the efficacy and safety of ulinastatin for patients with SAP from the electronic databases of Cochrane Library, MEDILINE, EMBASE, CINAHL, PsycINFO, Scopus, CBM, Wangfang, VIP, and CNKI. All electronic databases will be searched from inception to the present with no limitations of language and publication status. Two researchers will carry out study selection, data extraction, and study quality assessment independently. Another researcher will help to resolve any disagreements between 2 researchers., Results: The outcomes include overall mortality, time of hospital stay, complications of systematic or local infection, multiple organ deficiency syndrome, health related quality of life (as measured as the 36-Item Short Form Health Survey), and adverse events related to nutrition., Conclusion: This study will provide evidence to evaluate the efficacy and safety of ulinastatin in the treatment of patients with SAP., Systematic Review Registration: PROSPERO CRD42019149566.

Starch digestion in the small intestines of the dairy cow is low, to a large extent, due to a shortage of syntheses of α-amylase. One strategy to improve the situation is to enhance the synthesis of α-amylase. The mammalian target of rapamycin (mTOR) signalling pathway, which acts as a central regulator of protein synthesis, can be activated by leucine. Our objectives were to investigate the effects of leucine on the mTOR signalling pathway and to define the associations between these signalling activities and the synthesis of pancreatic enzymes using an in vitro model of cultured Holstein dairy calf pancreatic tissue. The pancreatic tissue was incubated in culture medium containing l-leucine for 3 h, and samples were collected hourly, with the control being included but not containing l-leucine. The leucine supplementation increased α-amylase and trypsin activities and the messenger RNA expression of their coding genes (P <0.05), and it enhanced the mTOR synthesis and the phosphorylation of mTOR, ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 (P <0.05). In addition, rapamycin inhibited the mTOR signal pathway factors during leucine treatment. In sum, the leucine regulates α-amylase and trypsin synthesis in dairy calves through the regulation of the mTOR signal pathways.

Background: Intestinal ischemia reperfusion (I/R) injury is a serious but common pathophysiological process of many diseases, resulting in a high mortality rate in clinical practice. Ubiquitin-specific protease 22 (USP22) acts as regulator of cell cycle progression, proliferation, and tumor invasion. Depleted USP22 expression has been reported to contribute to arrested cell cycle and disrupted generation of differentiated cell types in crypts and villi. However, the role of USP22 in intestinal damage recovery has not been investigated. Therefore, elucidation of the underlying mechanism of USP22 in intestinal I/R injury may help to improve the tissue repair and patient prognosis in clinical practice., Aim: To investigate the role of USP22 in intestinal cell proliferation and regeneration after intestinal I/R injury., Methods: An animal model of intestinal I/R injury was generated in male Sprague-Dawley rats by occlusion of the superior mesenteric artery followed by reperfusion. Chiu's scoring system was used to grade the damage to the intestinal mucosa. An in vitro model was developed by incubating rat intestinal epithelial IEC-6 cells in hypoxia/reoxygenation conditions in order to simulate I/R in vivo . siRNA and overexpression plasmid were used to regulate the expression of USP22. USP22, Cyclin D1, and proliferating cell nuclear antigen (PCNA) expression levels were measured by Western blot analysis and immunohistochemistry staining. Cell survival (viability) and cell cycle were evaluated using the Cell Counting Kit-8 and flow cytometry, respectively., Results: USP22 expression was positively correlated with the expression levels of PCNA and Cyclin D1 both in vivo and in vitro , which confirmed that USP22 was involved in cell proliferation and intestinal regeneration after intestinal I/R injury. Decreased levels of Cyclin D1 and cell cycle arrest were observed in the USP22 knockdown group ( P < 0.05), while opposite results were observed in the USP22 overexpression group ( P < 0.05). In addition, increased expression of USP22 was related to improved intestinal pathology or IEC-6 cell viability after I/R or hypoxia/reoxygenation. These results suggested that USP22 may exert a protective effect on intestinal I/R injury by regulating cell proliferation and facilitating tissue regeneration., Conclusion: USP22 is correlated with promoting intestinal cell proliferation and accelerating intestinal tissue regeneration after intestinal I/R injury and may serve as a potential target for therapeutic development for tissue repair during intestinal I/R injury., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.

Our previous study found that 2-aryl-1-cyano-1,2,3,4-tetrahydroisoquinolines (CATHIQs) have excellent anti-cancer activity and obvious apoptosis induction phenomenon. As our continuing research, this study further explored their underlying molecular mechanism of apoptosis induction in cancer cells. Flow cytometry analysis showed that the NB4 cells treated by 1-cyano-2-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline or the MKN-45 cells treated by 1-cyano-2-(4-trifluoromethylphenyl)-1,2,3,4-tetrahydroisoquinoline for 48 h were at early stage of apoptosis, and the cell cycle arrest was only slightly affected. Apoptosis rates of the cells significantly increase with the treatment concentration of the compounds. The compounds could significantly decrease the activities of SOD, raise the MDA level and promote the LDH leakage, suggesting that the excessive formation of ROS should be involved in the cell apoptosis. Western blot analysis showed that the compounds improved both Bax/Bcl-2 ratio and cleavages of procaspase-3, promoted efflux of cytochrome c to cytosol and phosphorylation of p38 and JNK, and attenuated phosphorylations of Akt and ERK. Together, inhibitions of PI3K/Akt and ERK and activation of p38 mediated the compounds-induced apoptosis through modulating the mitochondrial pathway and/or ROS production., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To compare the penetration-enhancing effect of cinnamon oil and its main components (cinnamaldehyde) on ibuprofen and their self-percutaneous absorption behavior in vitro. Firstly, cinnamon oil was extracted by steam distillation, then the compositions were analyzed by gas chromatography mass spectrometry (GC-MS) and the cinnamaldehyde content in cinnamon oil was determined by high performance liquid chromatography (HPLC). With azone as positive control, ibuprofen as model drug, cinnamon oil and cinnamaldehyde as penetration enhancers (PE) were prepared and administered to the SD rat's abdominal skin. The penetration-enhancing effects of cinnamon oil and cinnamaldehyde and their own transdermal absorption properties were compared. The results showed that yield of cinnamon oil was (3.55±0.36)% ( n =3), and the cinnamaldehyde content in cinnamon oil was (73.48±0.21)% ( n =3). As compared with blank group, the enhancing rate (ER) of cinnamon oil, cinnamaldehyde, and azone was 3.56, 1.13, 2.47 respectively. The cumulative penetration rate of cinnamaldehyde in cinnamon oil and cinnamaldehyde monomer in 24 h was (63.30±0.98)%, (51.03±3.34)% ( n =4) respectively. The penetration-enhancing effect of cinnamon oil was significantly better than that of cinnamaldehyde, indicating the existence of muti-component synergy. The penetration rate of cinnamaldehyde in cinnamon oil was higher than that of cinnamaldehyde monomer, suggesting that a "pull effect" may be present., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Bacillus cereus strain Jdm1 was isolated and tested for activity as a biocontrol agent to suppress Meloidogyne incognita . Petri dish test results indicated that Jdm1 culture supernatant significantly inhibited the second-stage juvenile (J2) activity and egg hatching, and also decreased the number of galls on tomato roots in the pot test. Control efficiency reached 43%, with improved growth compared to control plants. In field tests, control efficacies were greater than 50% 30 day post-inoculation, before decreasing. Furthermore, when avermectins were included to manage M. incognita , the yield of tomatoes was increased significantly. The effect of Jdm1 on the bacterial community in the tomato rhizosphere soil was monitored using PCR-denaturing gradient gel electrophoresis (PCR-DGGE) on field plants. DGGE band patterns and principal component analysis showed that application of Jdm1 did not permanently imperil the bacterial community, which recovered soon after inoculation, despite being impacted initially. The plant growth stage had a much greater influence on the bacterial community in tomato rhizosphere soil., Competing Interests: Compliance with ethical standardsThe authors have declared that no competing interests exist.

A Gram-staining-negative, aerobic, motile and rod-shaped bacterium, designated strain X1-8 T , was isolated from rhizosphere soil of Nicotiana tabacum L. collected from the tobacco produce base located in Kunming, south-west PR China. Cells showed oxidase-negative and catalase-positive reactions and were motile by means of peritrichous flagella. Growth occurred at 25-40 °C and pH 6.0-8.0 with optimal growth at 30-35 °C, pH 7.0. The major respiratory lipoquinone was Q-10. C16 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) were identified as major cellular fatty acids. The profile of polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, sphingoglycolipid, phosphatidylcholine and one unidentified glycolipid. The major polyamine was sym-homospermidine. The genomic DNA G+C content was 66.5 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that X1-8 T should be affiliated to the genus Sphingomonasand formed a clade with most closely related species Sphingomonas changbaiensisNBRC 104936 T . The results of 16S rRNA gene sequences similarity analysis indicated that X1-8 T had the highest similarity with S. changbaiensisNBRC 104936 T (98.4 %) and lower than 96.0 % with other species of the genus Sphingomonas. DNA-DNA hybridization data indicated that X1-8 T represented a novel genomic species of the genus Sphingomonas. The characteristics determined in the polyphasic taxonomic study indicated that X1-8 T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas tabacisoli sp. nov. (type strain X1-8 T =KCTC 62032 T =CGMCC 1.16275 T ) is proposed.