Search

Cultivated strawberry (Fragaria × ananassa) is a popular, economically important fruit. The ripening of the receptacle (pseudocarp), the main edible part, depends on endogenously produced abscisic acid (ABA) and is suppressed by the high level of auxin produced from achenes (true fruit) during early development. However, the mechanism whereby auxin regulates receptacle ripening through inhibiting ABA biosynthesis remains unclear. Here, we identified AUXIN RESPONSE FACTOR 2 (FaARF2), which showed decreased expression with reduced auxin content in the receptacle, leading to increased ABA levels and accelerated ripening. Dual-luciferase, yeast one-hybrid, and electrophoretic mobility shift assays demonstrated that FaARF2 could bind to the AuxRE element in the promoter of 9-CIS-EPOXYCAROT-ENOID DIOXYGENASE 1 (FaNCED1), a key ABA biosynthetic gene, to suppress its transcriptional activity. Transiently overexpressing FaARF2 in the receptacles decreased FaNCED1 expression and ABA levels, resulting in inhibition of receptacle ripening and of development of quality attributes, such as pigmentation, aroma, and sweetness. This inhibition caused by overexpressing FaARF2 was partially recovered by the injection of exogenous ABA; conversely, transient silencing of FaARF2 using RNA interference produced the opposite results. The negative targeting of FaNCED1 by FaARF2 is a key link between auxin-ABA interactions and regulation of strawberry ripening., Competing Interests: Conflict of interest statement. The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Recently, renewable bio-based materials have received more and more attention due to environmental issues such as global warming and ecosystem destruction. In the present work, a series of isosorbide-based bioelastomers poly(isosorbide carbonate-co-butanediol aliphatic esters)s (PICBAs) are synthesized by a facile and economical two-step melt polycondensation. Due to the slightly self-crosslinking reaction of isosorbide, PICBAs exhibit excellent tensile strength and self-healing ability, the mechanical properties of PICBAs can recover over 95% after 48 h under room temperature. In addition, PICBAs can stick different substances, such as glass, rubber, plastic, and stones, and show better adhesive performance than 3M commercially available double-sided tape. Consequently, isosorbide-based bioelastomers PICBAs are of great potential to be used as environmentally friendly pressure-sensitive adhesives (PSA) in the future., (© 2024 Wiley‐VCH GmbH.)

Background: The most popular traditional Chinese exercise (TCE) techniques include Tai Chi, Yijinjing, Baduanjin, Wuqinxi, and Qigong. Exercise is advised as a primary treatment for knee osteoarthritis (KOA) according to clinical standards. According to several studies, TCE may be an effective way to help people with KOA manage their pain, stiffness, and physical function. Which TCE therapy is the most effective and whose particular usefulness is still debatable. The network meta-analysis (NMA) method is used in this study to evaluate and compare the effects of various TCE therapies on KOA patients., Methods: We will search PubMed, Embase, Scopus, Cochrane Library, Web of Science, the China National Knowledge Infrastructure, Wanfang, the Chinese Scientific Journal Database (VIP), and the China Biology Medical Literature Database (CBM) for randomized controlled trials reporting TCE therapy for KOA patients published before October 25, 2023. The Stata 16.0 program will compare the effectiveness of various TCE therapies on KOA patients using conventional pairwise and NMA., Results: The final 29 studies included 15 articles on Tai Chi, 7 articles on Baduanjin, 4 articles on Wuqinxi, and 3 articles on Yijinjing. Tai Chi was first for the effect sizes of VAS scores, WOMAC pain scores, and WOMAC available scores, while Baduanjin was ranked top for WOMAC stiffness scores. Research should continue to be conducted on the effect of Qigong on KOA intervention., Conclusions: This NMA will help determine the best TCE treatment for KOA and offer evidence-based bias for clinical decision-making., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Baicalein, showing higher bioavailability and stronger pharmacological activity, can be obtained via a β-glucuronidase (GUS)-catalyzed transformation of baicalein 7-O-β-D-glucuronide (baicalin). Recently, we have found that the fermentation broth of Lacticaseibacillus rhamnosus HP-B1083 can efficiently convert baicalin to baicalein. In this study, the L. rhamnosus HP-B1083-derived enzyme involved in baicalin biotransformation was identified and characterized. First, the LruidA gene, encoding the responsible enzyme, was cloned and sequenced. Sequence analysis revealed that the deduced enzyme (designated as LrUidA) belonged to the glycosyl hydrolase family 2. The recombinant LrUidA was expressed and purified for characterization. LrUidA had a molecular weight of 70 kDa, with an optimal temperature of 50 °C and pH 4.5. Although LrUidA was susceptible to temperature, it possessed a relative pH stability. Its Michaelis-Menten constant, maximum reaction velocity and catalytic constant values were 9.710 mM, 13.08 mM/min/mg, and 14.95 s -1 , respectively. Site-directed mutagenesis experiment results demonstrated that the enzyme reaction uses side chains of E509 and E415 to hydrolyze the glycosidic bond of baicalin and involves three negatively charged residues, E450, D451, and D452, respectively. Surprisingly, biotransformation was performed under optimized reaction conditions by incubating the purified enzyme with 0.1 % baicalin for 4 h, resulting in a considerable conversion ratio of 99 %. Altogether, our findings provide insights into the properties of L. rhamnosus HP-B1083-derived enzyme and expand our understanding regarding using GUS for the industrial production of baicalein., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Shao-Yang Hou reports financial support was provided by Shandong natural resources fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26 . However, the positive regulators of ANKRD26 are still unknown., Aim: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription., Methods: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26 . Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26 . Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients., Results: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26 . Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26 . Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26 . In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients., Conclusion: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the value of detection of epidermal growth factor receptor (EGFR) gene amplification in peripheral blood rare cells in the assessment of benign and malignant pulmonary nodules. Methods: A total of 262 patients with pulmonary nodules were selected as the retrospectively study subjects from the Second Affiliated Hospital of Army Military Medical University and Peking Union Medical College Hospital from July 2022 to August 2023. There were 98 males and 164 females, with the age range from 16 to 79 (52.1±12.1) years. The EGFR gene amplification testing was performed on the rare cells enriched from patients' peripheral blood, and the clinical manifestations, CT imaging features, histopathological and/or pathological cytological confirmed results of patients were collected. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of the method of detection of EGFR gene amplification in peripheral blood rare cells, and its diagnostic efficacy was evaluated. Results: Among the 262 patients, 143 were malignant pulmonary nodules and 119 were benign pulmonary nodules. The differences between malignant pulmonary nodules and benign pulmonary nodules in nodule diameter and nodule density were statistically significant (both P <0.001), while the differences in age, gender and nodule number were not statistically significant (all P >0.05). The number [ M ( Q 1 , Q 3 )] of EGFR gene amplification positive rare cells in patients with malignant pulmonary nodule was 8 (6, 11), which was higher than that in patients with benign pulmonary nodule [2 (1, 4), P <0.001]. The ROC curve results showed that when the optimal cut-off value was 5 (that was, the number of EGFR gene amplification positive rare cells was>5), the area under the curve (AUC) of the detection of EGFR gene amplification in peripheral blood rare cells for discrimination of benign and malignant pulmonary lesions was 0.816 (95% CI : 0.761-0.870), with a sensitivity of 83.2%, a specificity of 80.7%, and an accuracy of 82.1%. Based on the analysis of the diameter of the nodules, the AUC for distinguishing between benign and malignant pulmonary nodules with diameter 5-9 mm and 10-30 mm was 0.797 (95% CI : 0.707-0.887) and 0.809 (95% CI : 0.669-0.949), respectively, with sensitivity, specificity and accuracy reached 75% or above. Based on the analysis of nodule density, the AUC for distinguishing between benign and malignant solid nodule and subsolid nodule was 0.845 (95% CI : 0.751-0.939) and 0.790 (95% CI : 0.701-0.880), respectively, with sensitivity, specificity and accuracy reached 75% or above. Based on the analysis of nodule number, the AUC for distinguishing between benign and malignant solitary pulmonary nodule and multiple pulmonary nodule was 0.830 (95% CI : 0.696-0.965) and 0.817 (95% CI : 0.758-0.877), respectively, with sensitivity, specificity and accuracy reached 80% or above. Conclusion: The detection of EGFR gene amplification in peripheral blood rare cells contributes to the evaluation of benign and malignant pulmonary nodules, and can be used in the auxiliary diagnosis of benign and malignant pulmonary nodules.

Purpose: This study aims to test the effectiveness of brief mindfulness for anxiety-provoked adverse events during ultrasound-guided fine needle aspiration biopsy (FNAB)., Results: A total of 439 patients were randomized to two groups. The ratio of anxiety in all patients with TN before FNAB was 25.3%, which was correlated with the intraoperative stress index. The FNAB-related adverse events in the control group were significantly higher than in the intervention group (65.0% vs. 17.3%; odds ratio [OR], 0.11 [95%CI, 0.56-0.74]; P < 0.001), especially for emotional stress (61.5% vs. 15.5%, odds ratio [OR], 0.12 [95%CI, 0.53-0.70]; P < 0.001) and patient's noncooperation (12.0% vs. 1.8%, odds ratio [OR], 0.14 [95%CI, 0.06-0.18]; P = 0.002). The stress index in control group were significantly higher than in the intervention group (87.82 [range, 27-99] vs 83.48 [range, 31-95]; P < 0.001)., Conclusions: Brief mindfulness decreased anxiety-provoked adverse events and stress index in patients with thyroid nodules during FNAB., Competing Interests: Declaration of competing interest All authors declare that no conflict of interest in this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide as well as a significant cause of mortality. The conventional treatment could cause serious side effects and induce drug resistance, recurrence and metastasis of cancers. Hence, specific targeting of cancer cells without affecting the normal tissues is currently an urgent necessity in cancer therapy. The emerging of peptide-drug conjugates (PDC) is regarded as a promising approach to address malignant tumors. LWJ-M30, a conjugate of DM1 and B6 peptide, targeted transferrin receptors (TfRs) on the surface of the CRC cells, showing a powerful anti-cancer effect. LWJ-M30 significantly inhibited the HCT116 cells proliferation and migration in vitro . LWJ-M30 also dramatically decreased the level of polymeric tubulin, while the disruption of microtubules caused the cell cycle to be arrested in the G2/M phase. LWJ-M30 induced the HCT116 cells apoptosis both in vivo and in vitro . The results in vivo demonstrated that LWJ-M30 could inhibit the HCT116 growth without affecting the mouse body weight. Taking these results together, our data indicated that LWJ-M30 could improve the therapeutic effects of DM1 while reducing the systemic toxicity in normal tissues., 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., (This journal is © The Royal Society of Chemistry.)

The Tibetan Plateau is the third pole of the world, with an essential role in regulating Northern Hemisphere climate. Previous studies showed that atmospheric aerosols over the Tibetan Plateau are influenced by biomass burning (BB) products from South and Southeast Asia. In fact, open biomass burning (OBB) is also an important form of BB in Southeast Asian countries, causing serious springtime air pollution yearly. However, there are still scientific gaps in the contribution of OBB to surrounding regional aerosols, especially on the Tibetan Plateau. In order to quantify this contribution, we collected samples of fine particulate matter and derived the concentrations of major water soluble ion, water soluble organic carbon (WSOC), and total carbon (TC) and total nitrogen (TN) as well as the dual isotopic compositions of carbon and nitrogen (δ 13 C and δ 15 N) during March-June on the southeastern Tibetan Plateau. δ 13 C and δ 15 N showed no significant difference (p > 0.05) between the OBB and non-OBB periods. Furthermore, both δ 13 C and δ 15 N (-25.7 ± 0.7 ‰ and 8.0 ± 3.6 ‰) values calculated during the whole sampling period were similar to the BB value, indicating that the primary source of TC and TN in aerosols was BB, whether OBB or non-OBB burning periods. TC and TN concentrations during the OBB period (6.5 ± 2.9 μg m -3 and 1.2 ± 0.4 μg m -3 , respectively) were significantly higher than during the non-OBB period (4.1 ± 1.7 μg m -3 , with p = 0.014, and 0.7 ± 0.3 μg m -3 , with p = 0.013, respectively). Active fire data and surface smoke concentrations further indicated that BB emissions from Southeast Asia were higher during the OBB period. This suggests that OBB-related high BB emissions significantly enhanced atmospheric aerosols concentrations on the southeastern Tibetan Plateau., 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 B.V. All rights reserved.)

Objective: The consequences and impact of violent behavior in schizophrenia are often serious, and identification of risk factors is of great importance to achieve early identification and effective management., Methods: This follow-up study sampled adult patients with schizophrenia in primary mental health care in a rural area of southern China, in which 491 participants completed a comprehensive questionnaire at baseline and the 2-year follow-up. Sociodemographic, clinical and psychological assessment data were collected from all participants. Paired sample T- Tests and the McNemar Test were performed to examine changes over the follow-up period. Generalized Estimating Equations (GEE) were used to analyze the risk factors for violent behavior., Results: The results showed that about two in five community-dwelling patients with schizophrenia reported violent behavior in the past year. At follow-up, participants were significantly less employed, had more times of hospitalization, more psychotropic medication, and severer depressive symptoms, but had better health-related quality of life than at baseline. Use of clozapine and better insight into medication decreased the possibility of violent behavior, while more severe positive symptoms, insomnia, as well as use of second-generation antipsychotics other than clozapine, antidepressants and mood stabilizers increased the possibility of violent behavior., Conclusions: Risk evaluation, prevention and management of violence in patients with schizophrenia are demanded in primary mental health care., 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 © 2023 Huang, Wang, Chen, Xiao, Wang, Wang, He, Migliorini, Harvey and Hou.)

Influenza virus infection in pregnant women may put the fetus at higher risk; however, to date, there has been no detailed research about the expression of influenza virus receptors in the human placenta. We employed the lectin staining technique, which is a classic influenza virus receptor research method for studying the distribution of viral receptors in the human placenta. In addition, we examined the susceptibility of the human placenta to H1N1/09, by detecting viral proteins and RNA at different time points post-infection. We found that the human placenta expressed both avian and human influenza A virus receptors (α-2, 3-linked sialic acid and α-2, 6-linked sialic acid). In addition, H1N1/09 did not only infect the human placenta, but also replicated and was released into the culture media. We concluded that the human placenta is susceptible to the 2009 influenza A virus (H1N1/09) infection, and that particular attention should be paid to shielding pregnant women from infection during influenza season.

Objective: Quality of life (QoL) has been always an important way to evaluate the outcomes of schizophrenia, but there have been few previous longitudinal studies and few in middle-income countries. This study aimed to explore the QoL in Chinese patients with schizophrenia treated in primary mental health care and the risk factors of QoL over time., Methods: Patients with schizophrenia treated in primary mental health care in rural/regional areas in Luoding, Guangdong, PR China, were evaluated with an extended questionnaire including the Chinese version of the World Health Organization Quality of Life (WHOQOL-BREF) at baseline and 2-year follow-up. Bivariate and multivariate analyses were conducted including Generalized Estimated Equation analyses (GEE)., Results: Four hundred and ninety-one patients with schizophrenia in primary care completed the 2-year follow up evaluation. The QoL physical, environmental, and social relationships domains showed improvement after the 2-year period, but the psychological domain did not. GEE results showed that earlier age of onset, older age, being employed, being unmarried, the thicker waist circumference, less use of clozapine or other SGAs, fewer hospitalizations, more frequent insomnia, more severe depressive and negative symptoms as well as worse treatment insight were independently associated with poor QoL in patients with schizophrenia., Conclusion: According to our results, to improve the quality of life of patients with schizophrenia in primary care, we should pay more attention to the treatment of depression, negative and insomnia symptoms of schizophrenia, the choice and dosage of antipsychotic medication and improvement in the treatment compliance. The combined use of educational and behavioral strategies may improve treatment adherence., 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 He, Migliorini, Huang, Wang, Zhou, Chen, Xiao, Wang, Wang, Harvey and Hou.)

Aims: We aimed to determine whether lymphocyte activation gene 3 (LAG-3), also known as CD223, is associated with microvessel density (MVD) in primary hepatocellular carcinoma (HCC), as well as their clinical significance in predicting survival., Materials and Methods: One hundred and twenty-seven patients were enrolled in the study. Samples were obtained on resection at the Department of Hepatobiliary Surgery of the Qingdao Municipal Hospital from June 2014 to June 2016. Immunohistochemistry was used to determine vessel density and LAG-3 abundance. Statistical analyses were performed to test for correlation of LAG-3 density and other clinicopathological variables with overall survival (OS)., Results: High LAG-3 abundance was significantly correlated with increased MVD in primary HCC (P < 0.05). The χ 2 test revealed a significant association of LAG-3 with preoperative AFP level, tumor diameter, N stage, and the presence of HBV infection (P < 0.05). Patients with high LAG-3 expression had shorter OS compared to those with low LAG-3 expression (P < 0.05). The Cox proportional hazards model showed that both higher LAG-3 and MVD density, age, the number of tumors, preoperative AFP level, tissue differentiation, Child-Pugh grade, and lymph node metastasis correlated with survival., Conclusions: High expression of LAG-3 is associated with angiogenesis and poor prognosis in HCC patients. With the deepening of research, LAG-3 is likely to become a novel biomarker for clinical diagnosis and prognosis and can even be a therapeutic target of HCC., Competing Interests: None

COVID-19 has brought a significant impact to the global health system, and also opportunities and challenges to epidemiological researches. Theoretical epidemiological models can simulate the process of epidemic in scenarios under different conditions. Therefore, modeling researches can analyze the epidemical trend of COVID-19, predict epidemical risks, and evaluate effects of different control measures and vaccine policies. Theoretical epidemiological modeling researches provide scientific advice for the prevention and control of infectious diseases, and play a crucial role in containing COVID-19 over the past year. In this study, we review the theoretical epidemiological modeling researches on COVID-19 and summarize the role of theoretical epidemiological models in the prevention and control of COVID-19, in order to provide reference for the combination of mathematical modeling and epidemic control.

The first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib significantly improved the therapeutic effect in non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, the EGFR T790M mutation occurs and results in acquired resistance. Consequently, mutant selective third-generation EGFR TKIs represented by AZD9291 (Osimertinib) have been developed to offer more effective therapeutic treatment, but the clinical application is limited by the acquired resistance and the high costs. A series of 5-chloropyrimidine-2,4-diamine derivatives were synthesized and screened for in vitro antitumor activity on H1975 and A431 cells. XHL11 showed the strongest antineoplastic activity. Compared to AZD9291, XHL11 suppressed cellular proliferation and colony formation and induced apoptosis in H1975 cells with EGFR L858R/T790M mutation. In addition, XHL11 caused expression changes in EGFR and apoptosis-related pathways. Moreover, oral administration of XHL11 suppressed tumor progression in vivo in a H1975 subcutaneous xenograft model. These data demonstrated that XHL11 might be developed as a promising EGFR TKI for the therapeutic use of NSCLC patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Soluble sugars play key roles in plant growth, development, and adaption to the environment. Characterizing sugar content profiling of plant tissues promotes our understanding of the mechanisms underlying these plant processes. Several technologies have been developed to quantitate soluble sugar content in plant tissues; however, it is difficult with only minute quantities of plant tissues available. Here, we provide a detailed protocol for gas chromatography mass spectrometry (GC-MS)-based soluble sugar profiling of rice tissues that offers a good balance of sensitivity and reliability, and is considerably more sensitive and accurate than other reported methods. We summarize all the steps from sample collection and soluble sugar extraction to derivatization procedures of the soluble extracted sugars, instrumentation settings, and data analysis., Competing Interests: Competing interestsThe authors declare no conflicts of interest., (Copyright © 2021 The Authors; exclusive licensee Bio-protocol LLC.)

Objective: In the context of COVID-19 pandemic, the epidemic severities, non-pharmaceutical intervention intensities, individual behavior patterns and vaccination coverage vary with countries in the world. China has experienced a long period without indigenous cases, unfortunately, multi local outbreaks caused by imported cases and other factors have been reported, posing great challenges to COVID-19 prevention and control in China. Thus it is necessary to explore the mechanisms of the re-emerged COVID-19 epidemics and their differences. Methods: Based on susceptible exposed infectious recovered (SEIR) epidemic dynamics model, we developed a set of novel evolution equations which can describe the dynamic processes of integrated influence of interventions, vaccination coverage and individual behavior changes on the re-emergency of COVID-19 epidemic. We developed methods to calculate the optimal intervention intensity and vaccination rate at which the size of susceptible population can be reduced to less than threshold for the re-emergency of COVID-19 epidemic. Results: If strong interventions or super interventions are lifted too early, even a small cause can lead to the re-emergence of COVID-19 epidemic at different degrees. Moreover, the stronger the early control measures lifted are, the more severe the epidemic is. The individual behavior changes for the susceptibility to the epidemic and the enhancement or lifting of prevention and control measures are key factors to influence the incidence the multi outbreaks of COVID-19. The optimist early intervention measures and timely optimization of vaccination can not only prevent the re-emergency of COVID-19 epidemic, but also effectively lower the peak of the first wave of the epidemic and delay its arrival. Conclusion: The study revealed that factors for the re-emergence of COVID-19 epidemics included the intensity and lifting of interventions, the change of individual behavior to the response of the epidemic, external incentives and the transmissibility of COVID-19.

On infection, plant-parasitic nematodes establish feeding sites in roots from which they take up carbohydrates among other nutrients. Knowledge on how carbohydrates are supplied to the nematodes' feeding sites is limited. Here, gene expression analyses showed that RNA levels of OsSWEET11 to OsSWEET15 were extremely low in both Meloidogyne graminicola (Mg)-caused galls and noninoculated roots. All the rice sucrose transporter genes, OsSUT1 to OsSUT5, were either down-regulated in Mg-caused galls compared with noninoculated rice roots or had very low transcript abundance. OsSUT1 was the only gene up-regulated in galls, at 14 days postinoculation (dpi), after being highly down-regulated at 3 and 7 dpi. OsSUT4 was down-regulated at 3 dpi. No noticeable OsSUTs promoter activities were detected in Mg-caused galls of pOsSUT1 to -5::GUS rice lines. Loading experiments with carboxyfluorescein diacetate (CFDA) demonstrated that symplastic connections exist between phloem and Mg-caused giant cells (GCs). According to data from OsGNS5- and OsGSL2-overexpressing rice plants that had decreased and increased callose deposition, respectively, callose negatively affected Mg parasitism and sucrose supply to Mg-caused GCs. Our results suggest that plasmodesmata-mediated sucrose transport plays a pivotal role in sucrose supply from rice root phloem to Mg-caused GCs, and OsSWEET11 to -15 and OsSUTs are not major players in it, although further functional analysis is needed for OsSUT1 and OsSUT4., (© 2021 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Checkpoint blockade therapy has shown significant therapeutic benefits and resulted in durable responses in patients with various tumors. However, accumulating evidence has demonstrated that 4-29% of all patients with cancers with various histologies may suffer from tumor flare following such therapy. This novel tumor response pattern, termed hyperprogression, is a potentially deleterious side effect of checkpoint blockade therapy that accelerates disease progression in a subset of patients. In this review, we describe possible immune checkpoint blockade biomarkers and the epidemiology, different definitions, and predictors of hyperprogression based on the research findings and further present the available evidence supporting pathophysiological hypotheses that might explain hyperprogression during checkpoint blockade therapy. We also compare hyperprogression and pseudoprogression. Finally, we discuss areas requiring further study., (© 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: The coronavirus disease 2019 (COVID-19) outbreak has seriously endangered the health and lives of Chinese people. In this study, we predicted the COVID-19 epidemic trend and estimated the efficacy of several intervention strategies in the mainland of China., Methods: According to the COVID-19 epidemic status, we constructed a compartmental model. Based on reported data from the National Health Commission of People's Republic of China during January 10-February 17, 2020, we estimated the model parameters. We then predicted the epidemic trend and transmission risk of COVID-19. Using a sensitivity analysis method, we estimated the efficacy of several intervention strategies., Results: The cumulative number of confirmed cases in the mainland of China will be 86 763 (95% CI: 86 067-87 460) on May 2, 2020. Up until March 15, 2020, the case fatality rate increased to 6.42% (95% CI: 6.16-6.68%). On February 23, 2020, the existing confirmed cases reached its peak, with 60 890 cases (95% CI: 60 350-61 431). On January 23, 2020, the effective reproduction number was 2.620 (95% CI: 2.567-2.676) and had dropped below 1.0 since February 5, 2020. Due to governmental intervention, the total number of confirmed cases was reduced by 99.85% on May 2, 2020. Had the isolation been relaxed from February 24, 2020, there might have been a second peak of infection. However, relaxing the isolation after March 16, 2020 greatly reduced the number of existing confirmed cases and deaths. The total number of confirmed cases and deaths would increase by 8.72 and 9.44%, respectively, due to a 1-day delayed diagnosis in non-isolated infected patients. Moreover, if the coverage of close contact tracing was increased to 100%, the cumulative number of confirmed cases would be decreased by 88.26% on May 2, 2020., Conclusions: The quarantine measures adopted by the Chinese government since January 23, 2020 were necessary and effective. Postponing the relaxation of isolation, early diagnosis, patient isolation, broad close-contact tracing, and strict monitoring of infected persons could effectively control the COVID-19 epidemic. April 1, 2020 would be a reasonable date to lift quarantine in Hubei and Wuhan.

Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.

Aim: The aim of this study was to screen potential lotus plant endophytic bacterial isolate for effective inhibition against lotus rot causing fungal pathogen Fusarium oxysporum., Methods and Results: In this study, endophytic bacteria were isolated from lotus tissues and tested for antagonistic activities against the pathogenic fungus F. oxysporum. Among the putative endophytic Bacillus strains identified, suspensions of the strain B-36 showed the highest inhibition rate against F. oxysporum growth. Pot assays indicated that B-36 was effective in controlling F. oxysporum-inducing lotus rot. However, the control efficiency varied with the inoculation method and concentration, where injection of 800 μl B-36 suspension per plant (2 × 10 8  CFU per ml) into stems showed the highest control efficiencies of 77·1 and 60·0% for pre-inoculation and post-inoculation. In addition, the colonizing population levels (CPLs) of B-36 on lotus also varied with the inoculation method and concentration, with the highest CPLs, that is, 3·05 and 2·83 log(CFU per gram), being observed on lotus leaves and stems respectively for stem injection of 200 μl per plant. Moreover B-36 showed no noticeable effects on lotus seed germination rate or seedling growth. Finally, B-36 was characterized as Bacillus velezensis based on its morphology, Gram-positive characteristics, as well as its 16S rDNA and gyrB sequences., Conclusion: The isolate B-36 can be applied as a biocontrol agent against F. oxysporum-inducing lotus rot., Significance of Impact of the Study: The soil-borne fungus F. oxysporum causes lotus rot and severe yield loss, and currently available control methods are very limited. Here we identify a new promising biocontrol agent against lotus rot caused by F. oxysporum., (© 2019 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.)

Background: Radiation induces rapid bone loss and enhances bone resorption and adipogenesis, leading to an increased risk of bone fracture. There is still a lack of effective preventive or therapeutic method for irradiation-induced bone injury. Receptor activator of nuclear factor κB ligand (RANKL) provides the crucial signal to induce osteoclast differentiation and plays an important role in bone resorption. However, the mechanisms of radiation-induced osteoporosis are not fully understood., Aim: To investigate the role of CR6-interacting factor-1 (Crif1) in osteoclastogenesis after radiation and its possible mechanism., Methods: C57BL/6 mice were exposed to Co-60 gamma rays and received 5 Gy of whole-body sublethal irradiation at a rate of 0.69 Gy/min. For in vitro study, mouse bone marrow mesenchymal stem/stromal cells (BM-MSCs) were irradiated with Co-60 at a single dose of 9 Gy. For osteoclast induction, monocyte-macrophage RAW264.7 cells were cocultured with mouse BM-MSCs for 7 d. ClusPro and InterProSurf were used to investigate the interaction interface in Crif1 and protein kinase cyclic adenosine monophosphate (cAMP)-activited catalytic subunit alpha complex. Virtual screening using 462608 compounds from the Life Chemicals database around His120 of Crif1 was carried out using the program Autodock&#95;vina. A tetrazolium salt (WST-8) assay was carried out to study the toxicity of compounds to different cells, including human BM-MSCs, mouse BM-MSCs, and Vero cells., Results: Crif1 expression increased in bone marrow cells after radiation in mice. Overexpression of Crif1 in mouse BM-MSCs and radiation exposure could increase RANKL secretion and promote osteoclastogenesis in vitro . Deletion of Crif1 in BM-MSCs could reduce both adipogenesis and RANKL expression, resulting in the inhibition of osteoclastogenesis. Deletion of Crif1 in RAW264.7 cells did not affect the receptor activator of nuclear factor κB expression or osteoclast differentiation. Following treatment with protein kinase A (PKA) agonist (forskolin) and inhibitor (H-89) in mouse BM-MSCs, Crif1 induced RANKL secretion via the cAMP/PKA pathway. Moreover, we identified the Crif1-protein kinase cyclic adenosine monophosphate-activited catalytic subunit alpha interaction interface by in silico studies and shortlisted interface inhibitors through virtual screening on Crif1. Five compounds dramatically suppressed RANKL secretion and adipogenesis by inhibiting the cAMP/PKA pathway., Conclusion: Crif1 promotes RANKL expression via the cAMP/PKA pathway, which induces osteoclastogenesis by binding to receptor activator of nuclear factor κB on monocytes-macrophages in the mouse model. These results suggest a role for Crif1 in modulating osteoclastogenesis and provide insights into potential therapeutic strategies targeting the balance between osteogenesis and adipogenesis for radiation-induced bone injury., Competing Interests: Conflict-of-interest statement: The authors report no conflicts of interest in this work., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The 2019 novel coronavirus disease (COVID-19) is running rampantly in China and is swiftly spreading to other countries in the world, which causes a great concern on the global public health. The absence of specific therapeutic treatment or effective vaccine against COVID-19 call for other avenues of the prevention and control measures. Media reporting is thought to be effective to curb the spreading of an emergency disease in the early stage. Cross-correlation analysis based on our collected data demonstrated a strong correlation between media data and the infection case data. Thus we proposed a deterministic dynamical model to examine the interaction of the disease progression and the media reports and to investigate the effectiveness of media reporting on mitigating the spread of COVID-19. The basic reproduction number was estimated as 5.3167 through parameterization of the model with the number of cumulative confirmed cases, the number of cumulative deaths and the daily number of media items. Sensitivity analysis suggested that, during the early phase of the COVID-19 outbreak, enhancing the response rate of the media reporting to the severity of COVID-19, and enhancing the response rate of the public awareness to the media reports, both can bring forward the peak time and reduce the peak size of the infection significantly. These findings suggested that besides improving the medical levels, media coverage can be considered as an effective way to mitigate the disease spreading during the initial stage of an outbreak.

Background: To date no study has compared more specifically the psychotropic medication treatment patterns for patients with schizophrenia living in community between rural and urban areas. This study examined the rural-urban differences of the use of psychotropic drugs among community-dwelling individuals with schizophrenia in China., Method: Data on 993 community-dwelling patients with schizophrenia (n = 479 in rural area and n = 514 urban area) were collected by interviews during 2013-2014, and 2015-2016 according to the diagnosis of DSM-IV or ICD-10. Data on patients' socio-demographic and clinical characteristics, prescriptions of psychotropic drugs were collected using a standardized protocol and data acquisition procedure., Results: Multivariate analyses revealed that in comparison with the rural counterparts, the patients from the urban area were significantly more frequently prescribed antipsychotic polypharmacy, clozapine, and benzodiazepines, but the patients from the rural area had more frequently prescribed anticholinergics., Conclusions: Substantial variations in psychotropic medication treatment patterns for patients with schizophrenia living in community were found between rural and urban areas in China. Common use of antipsychotic polypharmacy, clozapine and benzodiazepines in urban area, and anticholinergics in rural area need to be further addressed.

In this paper, we considered a mathematical model describing the nonlinear susceptibles-guided vaccination and isolation strategies, incorporating the continuously saturated treatment. In this strategy, we find that the disease-free periodic solution can always exist, and consequently the control reproduction number can be defined through analyzing the stability of the disease-free periodic solution. Also, we discussed the existence and stability of the positive order-1 periodic solution from two points of view. Initially, we investigated the transcritical and pitchfork bifurcation of the Poincaré map with respect to key parameters, and proved the existence of a stable or an unstable positive order-1 periodic solution near the disease-free periodic solution. For another aspect, by studying the properties of the Poincaré map, we verified the existence of the positive order-1 periodic solution in a large range of the control parameters, especially, we verified the co-existence of finite or infinite countable different positive order-1 periodic solutions. Furthermore, numerical simulations show that the unstable order-1 periodic solution can co-exist with the stable order-1, or order-2, or order-3 periodic solution. The finding implies that the nonlinear susceptibles-triggered feedback control strategy can induce much rich dynamics, which suggests us to carefully choose key parameters to ensure the stability of the disease-free periodic solution, indicating that infectious diseases die out.

Dengue and Zika viruses belong to the same Flavivirus family and usually cocirculate within the same area. Both the viruses can be transmitted by a common mosquito species Aedes aegypti. However, non-vector-borne transmission of Zika virus, such as sexual transmission and vertical transmission, has been reported in recent studies. In this study, we develop a dengue-Zika coinfection model with a particular focus on the impact of Zika sexual transmission to the transmission dynamics of both dengue and Zika. Our sensitivity analysis shows that Zika sexual transmission has a significant influence on the Zika basic reproduction number. Consequently, Zika sexual transmission can lead Zika to be endemic within an area where vector-borne transmission only cannot. Theoretically, we prove that the disease-free equilibrium for dengue only model is always globally stable if the dengue basic reproduction number is less than 1. However, our cascade analysis and numerical simulations show that increasing the sexual transmission coefficient of Zika can also result in the persistence of dengue even though the dengue basic reproduction number is less than 1, due to the cocirculation of dengue and Zika and the antibody-dependent enhancement of Zika infection for dengue infection. Our numerical analyses also show that the endemic levels of Zika increase as the Zika sexual transmission probability increases.

In this paper, we propose an SIS-type reaction-diffusion equations, which contains both direct transmission and indirect transmission via free-living and spatially diffusive bacteria/virus in the contaminated environment, motivated by the dynamics of hospital infections. We establish the basic reproduction number R ₀ which can act as threshold level to determine whether the disease persists or not. In particular, if R ₀<1 then ="" the ="" disease-free ="" equilibrium ="" is ="" globally ="" asymptotically ="" stable ="" whereas ="". For the spatially homogeneous system, we investigate the traveling wave solutions and obtain that there exists a critical wave speed, below which there has no traveling waves, above which the traveling wave solutions may exist for small diffusion coefficient by the geometric singular perturbation method. The finding implies that great spatial transmission leads to an increase in new infection, while large diffusion of bacteria/virus results in the new infection decline for spatially heterogeneous environment.

Background: Refractory and relapsed multiple myeloma (RRMM) remains a clinical challenge. We compared the progression-free survival (PFS) of RRMM patients treated with lenalidomide and low dose dexamethasone plus elotuzumab or carfilzomib (ELD vs. CLD), using reconstructed individual patient data (IPD) based on two published trials reports., Methods: We extracted data of study-level characteristics from original trial reports. We evaluated the comparability between the two treatment groups in terms of baseline status. Digitization of PFS Kaplan-Meier curves, reconstruction of IPD data, and subsequent survival analysis were performed. Distribution of progression and death events over time was visualized as histograms and corresponding kernel density lines, and Kaplan-Meier survival curves were plotted. Hazard ratio (HR) and corresponding 95% confidence interval (95% CI) were calculated., Results: Significant difference in race and disease stage distribution was found (P < 0.0001). Higher proportion of white patients and patients with advanced disease in the carfilzomib group was identified. Survival analysis revealed better PFS in the carfilzomib group (elotuzumab group vs. carfilzomib group: HR = 1.36, 95% CI = [1.11-1.67])., Conclusion: The CLD regimen may result in better PFS as compared with the ELD regimen in RRMM patients.

The pancreas of vertebrates is separately derived from both the dorsal and ventral endodermal domains. However, the difference between these two programs has been unclear. Here, using a pancreatic determination gene, Pdx1 , driven GFP transgenic mouse strain, we identified Pdx1-GFP highly expressing cells (Pdx1 high ) and Pdx1-GFP lowly expressing cells (Pdx1 low ) in both embryonic dorsal Pdx1-expressing region (DPR) and ventral Pdx1-expressing region (VPR). We analyzed the transcriptomes of single Pdx1 low and Pdx1 high cells from the DPR and VPR. In the VPR, Pdx1 low cells have an intermediate progenitor identity and can generate hepatoblasts, extrahepatobiliary cells, and Pdx1 high pancreatic progenitor cells. In the DPR, Pdx1 high cells are directly specified as pancreatic progenitors, whereas Pdx1 low cells are precocious endocrine cells. Therefore, our study defines distinct road maps for dorsal and ventral pancreatic progenitor specification. The findings provide guidance for optimization of current β-cell induction protocols by following the in vivo dorsal pancreatic specification program., (© 2018 The Authors.)

Objective: To date, no study has specifically compared antipsychotic-free patients with schizophrenia living in the community between rural and urban areas. This study examined the rural-urban differences among antipsychotic-free community-dwelling individuals with schizophrenia in China., Methods: Data on 1,365 community-dwelling patients with schizophrenia (n = 742 in a rural area and n = 623 in an urban area) with diagnoses according to DSM-IV or ICD-10 were collected by interviews during 2013-2014 and 2015-2016. Data on patients' sociodemographic and clinical characteristics, prescriptions of psychotropic drugs, and antipsychotic treatment status were recorded using a standardized protocol and data collection procedure., Results: The prevalence of antipsychotic-free status in the total sample (N = 1,365) was 27.3%; the proportion of antipsychotic-free patients was significantly lower (17.5%) in the urban area (17.5%) than in the rural area (35.4%; χ² = 55.03, P < .001). Binary logistic regression analysis revealed that antipsychotic-free patients, whether from the urban area or the rural area, were older (P = .001, odds ratio [OR] = 0.95 in urban; P = .006, OR = 0.97 in rural) and had poorer attitude toward medication treatment (P < .001, OR = 1.21 in urban; P < .001, OR = 1.31 in rural). Antipsychotic-free patients from the urban area also had fewer admissions, lower education level, and greater likelihood of living by themselves. Antipsychotic-free patients from the rural area also had worse insight into the disease, fewer anxiety symptoms, more prominent positive symptoms, and lower body mass index and were more likely to be women., Conclusions: Antipsychotic-free status was more common in community-dwelling patients with schizophrenia in the rural area than in the urban area. Older age and poorer attitude toward medication treatment were common features of antipsychotic-free patients. There were correspondingly different risk factors for antipsychotic-free status between rural and urban areas. Building a positive medication treatment attitude is an important strategy for establishing medication adherence in older, community-dwelling patients with schizophrenia., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Quantifying carbon sequestration in paddy soil is necessary to understand the effect of agricultural practices on carbon cycles. The objective of this study was to assess the effect of organic fertilizer addition (MF) on the soil respiration and net ecosystem carbon dioxide (CO 2 ) absorption of paddy fields under water-saving irrigation (CI) in the Taihu Lake Region of China during the 2014 and 2015 rice-growing seasons. Compared with the traditional fertilizer and water management (FC), the joint regulation of CI and MF (CM) significantly increased the rice yields and irrigation water use efficiencies of paddy fields by 4.02~5.08 and 83.54~109.97% (p < 0.05). The effects of organic fertilizer addition on soil respiration and net ecosystem CO 2 absorption rates showed inter-annual differences. CM paddy fields showed a higher soil respiration and net CO 2 absorption rates during some periods of the rice growth stage in the first year and during most periods of the rice growth stage in the second year. These fields also had significantly higher total CO 2 emission through soil respiration (total R soil ) and total net CO 2 absorption compared with FC paddy fields (p < 0.05). The total R soil and net ecosystem CO 2 absorption of CM paddy fields were 67.39~91.55 and 129.41~113.75 mol m -2 , which were 27.66~135.52 and 12.96~31.66% higher than those of FC paddy fields. The interaction between water and fertilizer management had significant effects on total net ecosystem CO 2 absorption. The frequent alternate wet-dry cycles of CI paddy fields increased the soil respiration and reduced the net CO 2 absorption. Organic fertilizer promoted the soil respiration of paddy soil but also increased its net CO 2 absorption and organic carbon content. Therefore, the joint regulation of water-saving irrigation and organic fertilizer is an effective measure for maintaining yield, increasing irrigation water use efficiency, mitigating CO 2 emission, and promoting paddy soil fertility.

Human behaviour plays an important role in the spread of emerging infectious diseases, and understanding the influence of behaviour changes on epidemics can be key to improving control efforts. However, how the dynamics of individual behaviour changes affects the development of emerging infectious disease is a key public health issue. To develop different formula for individual behaviour change and introduce how to embed it into a dynamic model of infectious diseases, we choose A/H1N1 and Ebola as typical examples, combined with the epidemic reported cases and media related news reports. Thus, the logistic model with the health belief model is used to determine behaviour decisions through the health belief model constructs. Furthermore, we propose 4 candidate infectious disease models without and with individual behaviour change and use approximate Bayesian computation based on sequential Monte Carlo method for model selection. The main results indicate that the classical compartment model without behaviour change and the model with average rate of behaviour change depicted by an exponential function could fit the observed data best. The results provide a new way on how to choose an infectious disease model to predict the disease prevalence trend or to evaluate the influence of intervention measures on disease control. However, sensitivity analyses indicate that the accumulated number of hospital notifications and deaths could be largely reduced as the rate of behaviour change increases. Therefore, in terms of mitigating emerging infectious diseases, both media publicity focused on how to guide people's behaviour change and positive responses of individuals are critical., (Copyright © 2017 John Wiley & Sons, Ltd.)

A novel disease characterized by small brown-black spots (1 to 2 mm in diameter) on tender tea leaves (Camellia sinensis) has been observed in many regions of Hubei Province, China, which severely affects the yield and quality of tea. Tea leaf samples with typical symptoms were collected from three major tea-cultivation regions of Hubei, and were subjected to pathogen isolation for etiological analysis. As a result, 34 Pestalotiopsis isolates were obtained from 20 samples, and they were identified as Pestalotiopsis theae (14 isolates), P. camelliae (12), and P. clavispora (8), determined by morphologies and phylogenetic analysis based on internal transcribed spacer, and partial β-tubulin and translation elongation factor 1-alpha genes. Pathogenicity tests on detached tea leaves showed that no matter what mycelial discs or conidium suspensions were used, inoculation of the Pestalotiopsis fungi could result in small brown-black spots (1 to 2 mm in diameter) on wounded leaves, similar to those observed in the field in the sizes and colors. It also revealed that only P. theae had pathogenicity on unwounded tea leaves, and P. theae and P. clavispora showed significantly higher virulence than P. camelliae. Inoculation test with conidium suspension on intact tea leaves in the field further confirmed that P. theae as the pathogen of brown-black spots. Reisolation of the pathogens from diseased leaves confirmed that the symptom was caused by the inoculation of Pestalotiopsis fungi. The P. theae isolates responsible for brown-black spots were also compared with those for tea gray blight disease in growth rate, pathogenicity, and molecular characteristics in parallel. To our knowledge, this is the first report that the Pestalotiopsis fungi cause brown-black spot disease on tender tea leaves. The results provide important implications for the prevention and management of this economically important disease.

Background: The safety and efficacy of different drugs in treatment of gestational diabetes mellitus (GDM) patients who could not maintain normal glucose level only through diet and exercise remains to be debated. We performed this network meta-analysis (NAM) to compare and rank different antidiabetic drugs in glucose level control and pregnancy outcomes in GDM patients., Methods: We searched PubMed, Cochrane Library, Web of Science, and Embase up to December 31, 2016. Randomized controlled trials (RCTs) related to different drugs in the treatment of GDM patients were enrolled. We extracted the relevant information and assessed the risk of bias with the Cochrane risk of bias tool. We did pair-wise meta-analyses using the fixed-effects model or random-effects model and then adopted random-effects NAM combining both direct and indirect evidence within a Bayesian framework, to calculate the odds ratio (OR) or standardized mean difference (SMD) and to draw a surface under the cumulative ranking curve of the neonatal and maternal outcomes of different treatments in GDM patients., Results: Thirty-two randomized controlled trials (RCTs) were included in this NAM, including 6 kinds of treatments (metformin, metformin plus insulin, insulin, glyburide, acarbose, and placebo). The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177). In terms of the incidence of admission to the NICU, insulin had higher incidence compared with glyburide (OR, 1.844). As for the incidence of neonatal hypoglycemia, metformin had lower incidence than insulin and glyburide (OR, 0.6331 and 0.3898), and insulin was lower than glyburide (OR, 0.6236). For mean birth weight, metformin plus insulin was lower than insulin (SMD, -0.5806), glyburide (SMD, -0.7388), and placebo (SMD, -0.6649). Besides, metformin was observed to have lower birth weight than glyburide (SMD, 0.2591). As for weight gain, metformin and metformin plus insulin were lower than insulin (SMD, -0.9166, -1.53). Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight. Besides, insulin had the highest incidence of NICU admission, acarbose had the lowest risk of neonatal hypoglycemia., Conclusion: Our study concluded that metformin is fastest in glucose control, with a more favorable pregnancy outcomes-would be a better option, but its rate of glucose control is the lowest.However, glyburide is the optimumtreatment regarding the rate of glucose control, but withmore adverse outcomes. This NAMbased on 32 RCTs will strongly help to guide further development of management for GDM patients, clinicians should carefully balance the risk-benefit profile of different treatments according to various situations.

We obtained a strain of Bacillus subtilis, which we named Czk1, from the aerial roots of rubber trees. This bacterial isolate exhibits strong antagonistic activity against Ganoderma pseudoferreum, Phellinus noxius, Helicobasidium compactum, Rigidoporus lignosus, Sphaerostilbe repens, and Colletotrichum gloeosporioides. Our earlier research has shown that the antagonistic activity of a fermentation supernatant Czk1 isolate produces a complex mixture of lipopeptides. In this study, we used methanol to extract crude lipopeptides, purified them using a Sephadex G-25 column, cloned the lipopeptide genes, and analyzed purified fractions by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) to identify the lipopeptides from B. subtilis strain Czk1. The cloned lipopeptide genes included those that encode the enzymes lpa, ituD, sfp, and fenB. The crude lipopeptides were purified and found in five fractions. Further analysis revealed that five fractions of the purified composition contained members of the surfactin, iturin, fengycin, and bacillomycin families of antibiotics. This suggests that these lipopeptides from strain Czk1 have potential as plant disease biocontrol agents.

Metformin has garnered considerable interest as a chemo-preventive and chemo-therapeutic agent given the increased risk of liver cancer among diabetic patients. This work was performed to illustrate the association between metformin use and survival of diabetic liver cancer patients. We conducted a comprehensive literature search of PubMed, Web of Science, Embase, BIOSIS Previews, Cochrane Library from inception to 12 May 2016. Meta-analyses were performed using Stata (version 12.0), with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) as effect measures. Eleven cohort studies involving 3452 liver cancer patients fulfilled the inclusion criteria. Meta-analyses showed that metformin use was associated with better survival (HR = 0.59; 95% CI, 0.42-0.83; p = 0.002) of liver cancer patients, and the beneficial effect persisted (HR = 0.64; 95% CI, 0.42-0.97; p = 0.035) when the population was restricted to diabetic liver cancer patients. After adjusting for age, etiology, index of tumor severity and treatment of liver cancer, the association between metformin use and better survival of liver cancer patients was stable, pooled HR ranged from 0.47 to 0.57. The results indicated that metformin use improved survival of diabetic liver cancer patients. However, the results should be interpreted with caution given the possibility of residual confounding. Further prospective studies are still needed to confirm the prognostic benefit of metformin use.

Previous study has indicated that exposure to anesthesia in early development leads to neuro-apoptosis and is followed by long-term cognitive dysfunction. Given that larger numbers of pregnant women currently receive anesthesia during the first trimester, we wanted to mimic this process in vitro using mouse embryonic stem cells (mESCs) and to explore how different anesthetics affect the self-renewal of mESCs. In the present study, mESCs were exposed to dexmedetomidine, fentanyl, or remifentanil at clinical concentrations for 48 h. The mESCs were then analyzed for cell proliferation and apoptosis. Furthermore, we used flow cytometry to analyze the cell cycle and quantitative real-time polymerase chain reaction to detect the gene expression during the cell cycle as well as the relevant stemness markers. We found that prolonged anesthesia with dexmedetomidine or fentanyl significantly inhibited mESC proliferation, with fewer cell numbers as well as decreased expression of cyclin B and cyclin E mRNA compared to that in the control group; meanwhile, p21 and RB2 gene expression was increased. Additionally, increases or decreases in the proportion of cells in the G1 and S phases, respectively, were observed in the dexmedetomidine- and fentanyl-treated groups. These anesthetics also repressed the gene expression of mESC stemness makers such as Oct4 and Sox2. However, remifentanil seemed to have no significant influence on the self-renewal of mESCs. These results demonstrated that prolonged anesthesia with dexmedetomidine or fentanyl, but not remifentanil, inhibited mESC proliferation by blocking the G1 to S transition, and repressed the maintenance of mESC stemness.

Calcification of end plate chondrocytes is a major cause of intervertebral disc (IVD) degeneration. However, the underlying molecular mechanism of end plate chondrocyte calcification is still unclear. The aim of this study was to clarify whether autophagy in end plate chondrocytes could protect the calcification of end plate chondrocytes. Previous studies showed that intermittent cyclic mechanical tension (ICMT) contributes to the calcification of end plate chondrocytes in vitro. While autophagy serves as a cell survival mechanism, the relationship of autophagy and induced end plate chondrocyte calcification by mechanical tension in vitro is unknown. Thus, we investigated autophagy, the expression of the autophagy genes, Beclin-1 and LC3, and rat end plate chondrocyte calcification by ICMT. The viability of end plate chondrocytes was examined using the LIVE/DEAD viability/cytotoxicity kit. The reverse transcription-polymerase chain reaction and western blotting were used to detect the expression of Beclin-1; LC3; type I, II and X collagen; aggrecan; and Sox-9 genes. Immunofluorescent and fluorescent microscopy showed decreased autophagy in the 10- and 20-day groups loaded with ICMT. Additionally, Alizarin red and alkaline phosphatase staining detected the palpable calcification of end plate chondrocytes after ICMT treatment. We found that increased autophagy induced by short-term ICMT treatment was accompanied by an insignificant calcification of end plate chondrocytes. To the contrary, the suppressive autophagy inhibited by long-term ICMT was accompanied by a more significant calcification. The process of calcification induced by ICMT was partially resisted by increased autophagy activity induced by rapamycin, implicating that autophagy may prevent end plate chondrocyte calcification., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To investigate the risk factors for depressive disorders in manufacturing workers and to provide a basis for developing health promotion measures at workplace., Methods: A questionnaire survey was performed in 8085 front-line production workers from 33 manufacturing enterprises in Nanhai District of Foshan, Guangdong Province, China. The questionnaire contained a survey of demographic characteristics, the Safety Climate Scale, the Center for Epidemiological Studies Depression Scale, etc. The multilevel logistic regression analysis was applied to investigate the risk factors for depressive disorders in workers., Results: A total of 6260 workers completed the survey; their mean age was 31.1 ± 8.6 years, and 53.2% of them were males. The multilevel logistic regression analysis showed that after adjustment for sociodemographic factors such as age, sex, and martial status, more depressive disorders were reported in the enterprises with higher score of "production safety training" than in those with lower score (OR = 1.46, 95%CI = 1.07 ∼ 1.97); fewer depressive disorders were reported in the enterprises with higher score of "colleagues concerned about production safety" than in those with lower score (OR = 0.08, 95%CI = 0.03 ∼ 0.26); the relationships of "safety warnings and precautions" and "managers concerned about production safety" with workers' depressive disorders were not statistically significant (OR = 0.78, 95%CI = 0.48 ∼ 1.28; OR = 1.08, 95%CI = 0.68 ∼ 1.72)., Conclusion: Depressive disorders in manufacturing workers are related to the safety climate at workplace, which indicates that a good safety climate at workplace should be created to prevent and control depressive disorders in workers.

LC-MS/MS is a promising analytical platform for the quantification of recombinant therapeutic proteins in biological fluids for pharmacokinetic (PK) studies. Herein, an absolute quantification method based on LC-MS/MS technique was developed to quantify endostar, which is modified from the recombinant human endostatin by adding a nine-amino acid sequence (MGGSHHHHH) at the N-terminal. A reproducible three-step analytical procedure was adopted: (1) Ni(2+) Sepharose was used to selectively extract endostar; (2) the signature peptide "TEAPSATGQASSLLGGR" (m/z 802.3(2+)-651.8(2+)) of endostar and a synthetic peptide "TEAPSATGQVSSLLGGR" (m/z 816.9(2+)-666.4(2+)) as internal standard (IS) were selected and analyzed in the multiple reaction monitoring (MRM) mode; (3) the proposed method was validated and applied to the pharmacokinetic study of endostar. The lower limit of quantification (LLOQ) for quantifying endostar was 50 ng/ml and this method is linear over 50-10,000 ng/ml. The accuracy was between 85% and 115%, and the intra-batch and inter-batch analytic precision and accuracy were below 15%. This LC-MS/MS approach was validated for the application to the pharmacokinetic study of endostar in rats., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The gene HtNB confers non-lesion resistance to the fungal pathogen Exserohilum turcicum in maize. To map this gene, we developed two F₂ populations, P111 (resistant line) x HuangZao 4 (susceptible line) and P111 x B73 (susceptible). HtNB was located on chromosome 8.07 bin, flanked by MAC216826-4 and umc2218 at distances of 3.3 and 3.4 cM, respectively. HtNB appears to be a new gene responsible for resistance to northern corn leaf blight. Functions of the genes in the region between umc1384 and umc2218 were predicted. In addition, several genes were found to be related to disease resistance, such as the genes encoding Ser/Thr protein kinase and protein-like leaf senescence.

Objective: To evaluate the associations of perception of safety atmosphere at workplace, occupational safety attitude and behaviors with occupational unintentional injury among manufacturing workers., Methods: A cross-sectional study was performed and a self-administered questionnaire was used to inquire socio-demographic characteristics, perceived safety atmosphere, occupational safety attitudes, occupational safety behaviors and occupational unintentional injuries among 10585 manufacturing workers selected from 46 enterprises in Guangdong. Structural equation modeling was applied to assess the relationship of the perception of safety atmosphere at workplace, occupational safety attitude, and occupational safety behaviors with occupational unintentional injury., Results: Among 24 pathways supposed in structural equation model, 20 pathways (except for the attitude toward occupational safety, the attitude toward managers' support, the work posture and individual protection) were significantly related to the occupational unintentional injuries. The further analysis indicated that the perceived safety atmosphere might impact the occupational unintentional injuries by the attitude toward occupational safety and occupational safety behaviors., Conclusion: Workers' perception of safety atmosphere indirectly influenced on occupational unintentional injuries through occupational safety attitudes and occupational safety behaviors.

A new eremophilane sesquiterpene was isolated from the roots of Senecio nemorensis. Its structure was established as 10alpha-hydroxy-6beta-propionyloxy-1-oxoeremophila-7(11),8-dieno-12,8-lactone on the basis of spectral analysis.

A bacterial strain BW003, which could utilize quinoline as sole carbon, nitrogen and energy source, was isolated from the activated sludge in a coking wastewater treatment plant. According to the 16S rRNA gene sequence analysis, the strain was identified as Pseudomonas sp. Biodegradation experiments showed that the strain could degrade 192-911 mg/L of quinoline efficiently within 3-8 h, and the removal rates of quinoline were ranged from 96% to 98%. The optimum conditions for the degradation were 30 degrees C and pH 8. Metabolic products analysis revealed that at least 43% quinoline was first transformed into 2-hydroxyquinoline, 0.69% 2-hydroxyquinoline was then transformed into 2,8-dihydroxyquinoline, and subsequently into 8-hydroxycoumarin in the process of biodegradation. Additionally, at least 48% of nitrogen in quinoline was transformed into NH3-N directly and external carbon source could promote the nitrogen transformation, demonstrating that the quinoline and its metabolic products could be eliminated if controlling proper C/N ratio.