bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mi-2β-targeted inhibition induces immunotherapy response in melanoma
Authors: Zhu Bo , Wang Zhengyu , Yao Licheng , Lin Xingyu , Zhang Jie , Li Xin , Hagman James , Shao Jingwei , Tran Phuc , Cao Meng , Zhang Jianming , Goding Colin , Liao Xuebin , Li Hong-yu , Cao Peng , Miao Xiao , Cui Rutao 
Published: December 2020

Abstract
Recent development of some new immune checkpoint inhibitors has been particularly successfully in melanoma, but the majority of melanoma patients exhibit resistance. Understanding and targeting the potential underlying mechanism/targets, especially the tumor-intrinsic modulators to convert resistant melanomas to immunotherapy sensitivity will potentially provide a significant improvement in patient outcome. Here, Mi-2β, a chromatin remodeling enzyme was identified as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response. Loss of Mi-2β rescued the immune response to immunotherapy in vivo. Mechanistically, targeting Mi-2β induced the adaptive immune response by transcriptionally enhancing expression of a set of IFN-γ-responsive genes including CXCL9, CXCL10 and IRF1. Finally, we developed a Mi-2β-targeted inhibitor Z36-MP5, which specifically and effectively induced a response to immune checkpoint blockades in otherwise resistant melanomas. Our work provides a new insight into the epigenetic regulation in adaptive immune response, and highlights a viable strategy to improve immunotherapies in melanoma.
Use of Benzodiazepines in Patients With Bipolar Disorder
Authors: Martin Marta Zubia , Mesa Susana Alberich , Peña Maria Purificación López , Martínez Iñaki Zorrilla , Pascual Juan Pablo Chart , Pinto Ana Maria González 
Published: December 2020

Abstract
BackgroundBenzodiazepines (BZDs) are widely used in patients with bipolar disorder. The aim of this study was to determine chronic use of BZDs in patients with a first bipolar episode and the association between its use and cognition.MethodsA prospective longitudinal study was conducted in a cohort of 63 patients under 40 years old with a first manic or mixed episode. The percentage of patients taking BZDs in the baseline sample was evaluated at 6 months and for the next 3 years. Cognitive functioning was compared between patients with chronic BDZ use and those who did not use them. A linear regression model adjusted for potential confounding variables such as age and education level were used.ResultsJust over half the sample (55.6%; n = 35) took BZD at the start of the study. At 6 months, this percentage decreased to 34.9% (n = 22) and to 14.3% (n = 9) at 3 years of follow-up. Patients who took BZD chronically had worse outcomes in overall attention. These differences remained significant when controlled for the variables age and education level (B -0.462, p = 0.046, 95% CI: - 0.914 - 0.009).ConclusionsChronic administration of BZD occurs in a small percentage of bipolar patients at disease onset, and is associated with decreased attention. These side effects should be followed up.
Two-Dimensional Frank-Kasper Z Phase with One Unit-Cell Thickness
Authors: Hongbo Xie , Bai Junyuan , Ren Haiyan , Li Shanshan , Pan Hucheng , Ren Yuping , Qin Gaowu 
Published: December 2020

Abstract
Z phase is one of the three basic units by which the Frank-Kasper phases are generally assembled. Compared to the other two basic units, i.e., A15 and C15 structures, the Z phase structure is rarely experimentally observed because of a relatively large volume ratio among the constituents to inhibit its formation. Moreover, the discovered Z structures are generally the three-dimensional (3D) ordered Gibbs bulk phases to conform to their thermodynamic stability. Herein, we confirmed the existence of a metastable two-dimensional (2D) Frank-Kasper Z phase with one unit-cell height in the crystallography in a model Mg-Sm-Zn system, by using aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) combined with density functional theory (DFT) calculations. This finding is important for understanding the relationship between the traditional crystal structures and the quasicrystals, and it is also expected to provide a new insight to understand the clustering and stacking behavior of atoms in condensed matters.
Conserved and None-Conserved Functions of the Rice Homologs of the Arabidopsis Trichome Initiation-Regulating MBW Complex Proteins
Authors: Zheng Kaijie , Wang Xutong , Wang Yating , Wang Shucai 
Published: December 2020

Abstract
Background: Trichome initiation in Arabidopsis is regulated by a MYB-bHLH-WD40 (MBW) transcriptional activator complex formed by the R2R3 MYB transcription factor GLABRA1 (GL1), MYB23 or MYB82, the bHLH transcription factor GLABRA3 (GL3), ENHANCER OF GLABRA3 (EGL3) or TRANSPARENT TESTA8 (TT8), and the WD40-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1). However, the functions of the rice homologs of the MBW complex proteins remained uncharacterized. Results: Based on amino acid sequence identity and similarity, and protein interaction prediction, we identified OsGL1s, OsGL3s and OsTTG1s as rice homologs of the MBW complex proteins. By using protoplast transfection, we show that OsGL1D, OsGL1E, OsGL3B and OsTTG1A were predominantly localized in the nucleus, OsGL3B functions as a transcriptional activator and is able to interact with GL1 and TTG1. By using yeast two hybridization and protoplast transfection assays, we show that OsGL3B is able to interact with OsGL1E and OsTTG1A, and OsGL1E and OsTTG1A are also able to interact with GL3. On the other hand, we found that OsGL1D functions as a transcription activator, and it can interact with GL3 but not OsGL3B. These results suggest that rice homologs of the Arabidopsis MBW complex proteins are able to form MBW complexes, but may have conserved and none-conserved functions. Furthermore, we found that expression of OsTTG1A in the ttg1 mutant restored the phenotypes including alternations in trichome and root hair formation, seed color, mucilage production and anthocyanin biosynthesis, indicating that OsTTG1A and TTG1 may have similar functions. Conclusion: These results aid in our understanding of the mechanism of trichome initiation in rice.
WITHDRAWN: Transcriptome and targeted metabolome reveal the regulation network of Lilium davidii var. unicolor during dormancy release
Authors: Fan Xinyue , Yang Yue , Li Min , Fu Linlan , Zang Yuqing , Wang Chunxia , Hao Tianyou , Sun Hongmei 
Published: December 2020

Abstract
Background：Regulation and control of bulb dormancy are critical for ensuring annual production and high-level cultivation of lily. Application of low temperatures is the most effective method for breaking lily bulb dormancy, but the molecular regulatory mechanism underlying this response is unclear. Results：Herein, targeted metabolome and transcriptome analyses were performed with buds of Lilium davidii var. unicolor bulbs stored for 0, 50 and 100 days at 4°C. Dormancy release mainly depended on the accumulation of GA4 and GA7, which are synthesized by the "non13-hydroxylation" pathway, rather than GA3, and ABA was degraded in the process. The contents of nonbioactive GA9, GA15 and GA24, the precursors of GA4 synthesis, increased with bulb dormancy release. Altogether, 113,252 unique transcripts were de novo assembled through high-throughput transcriptome sequences, and 639 genes were continuously differentially expressed. Enrichment analysis showed that the carbohydrate metabolism and hormone metabolism pathways play major roles in dormancy release. Energy sources during carbohydrate metabolism mainly depend on glycolysis and the PPP pathway rather than on the TCA cycle. Association analysis of the transcriptome and target metabolome showed that genes related to ABA, GA, starch and sucrose metabolism and some TF families, such as MYB, WRKY, NAC and TCP, involved in dormancy release were highly correlated with the target metabolome. Coexpression analysis further confirmed that ABI5, PYL8, PYL4 and PP2C, vital ABA signaling elements, regulated GA3ox and GA20ox in the GA4 biosynthesis pathway. The TFs WRKY32, WRKY71, MYB, DAM14, NAC8, ICE1, bHLH93 and TCP15 also participated in the ABA/GA4 regulatory network, and ICE1 may be the key factor linking temperature signals and hormone metabolism. Conclusions：These results will help to reveal the bulb dormancy molecular mechanism and to develop new strategies for high-quality bulb production.
USF2 Knockdown Downregulates THBS1 to Inhibit the TGF-β Signaling Pathway and Reduce Pyroptosis in Sepsis-Induced Acute Kidney Injury
Authors: Sun Jian , Wang Yang , Niu Lei , Tang Lujia , Pan Shuming 
Published: December 2020

Abstract
BackgroundAcute kidney injury (AKI) is a serious complication of sepsis. This study was performed to explore the mechanism that THBS1 mediated pyroptosis by regulating TGF-β signaling pathway in sepsis-induced AKI.MethodsGene expression microarray related to sepsis-induced AKI was obtained from the GEO database, and the mechanism in sepsis-induced AKI was predicted by bioinformatics analysis. qRT-PCR and ELISA were performed to detect expressions of THBS1, TNF-α, IL-1β, and IL-18 in sepsis-induced AKI patients and healthy volunteers. Mouse model of sepsis-induced AKI was established, with serum creatinine, urea nitrogen, 24-h urine output measured, and renal tissue lesions observed by HE staining. Cell model of sepsis-induced AKI was cultured in vitro, with expressions of TNF-α, IL-1β, and IL-18, pyroptosis, Caspase-1 and GSDMD-N, and activation of TGF-β pathway detected. The upstream transcription factor USF2 was knocked down in cells to explore it effect on sepsis-induced AKI.ResultsTHBS1 was highly expressed in patients with sepsis-induced AKI. Silencing THBS1 protected mice against sepsis-induced AKI, and significantly decreased the expressions of NLRP3, Caspase-1, GSDMD-N, IL-1β, and IL-18, increased cell viability, and decreased LDH activity, partially reversing changes in cell morphology. Mechanistically, USF2 promoted oxidative stress response by transcriptionally activating THBS1 to activate TGF-β/NLRP3/Caspase-1 signaling pathway and stimulate pyroptosis, and finally exacerbated sepsis-induced AKI.ConclusionsUSF2 knockdown downregulates THBS1 to inhibit TGF-β signaling pathway and reduce pyroptosis and further to ameliorate sepsis-induced AKI.
Community Health Worker Knowledge , Attitudes, and Practices Towards Epilepsy in Mozambique
Authors: Cumbe Vasco Francisco Japissane , Greene M. Claire , Fumo Afonso Mazine Tiago , Fumo Hélder , Mabunda Dirceu , Gouveia Maria Lídia Chaúque , Oquendo Maria A. , Duarte Cristiane S. , Sidat Mohsin , Mari Jair de Jesus , Wainberg Milton L. 
Published: December 2020

Abstract
Background: Epilepsy is the most common neurological disease in the world, affecting 50 million people, with the majority living in low- and middle-income countries (LMICs). A major focus of epilepsy treatment in LMICs has focused on task-sharing identification and epilepsy care by community health workers (CHWs). The present study aimed to assess the KAPs of CHWs towards epilepsy in Sofala province, Mozambique. Methods: One hundred and thirty five CHWs completed a questionnaire that included socio-demographic characteristics and 44-items divided in six subscales pertaining to KAPs towards epilepsy (QKAP-EPI) in nine districts of Sofala Province, Mozambique. The internal consistency and factor structure were examined to evaluate the reliability and construct validity of the QKAP-EPI, respectively. To examine correlates of KAPs toward epilepsy we evaluated the association between sociodemographic variables and QKAP-EPI subscales using linear regression models. Results: CHWs demonstrated adequate knowledge regarding epilepsy for medical treatment details (Mean=1.63, SD=0.28) and epilepsy safety/risks (Mean=1.62, SD=0.59). However, CHWs reported low levels of knowledge related to the causes of epilepsy, espousing stigmatizing attitudes, as well as cultural treatment, which is the perception in different cultures of how epilepsy should be treated. Knowledge about how to manage epilepsy during crisis varied across the different types of emergency care practices. Heterogeneity in the level of knowledge regarding epilepsy was observed among CHWs in the different districts of Sofala Province and when using different local names of epilepsy (Dzumba, Nzwiti).Conclusion: CHWs knowledge of medical treatment and epilepsy safety/risks were adequate. However, information on the causes of epilepsy, stigmatizing attitudes, cultural treatment, and some aspects of epileptic crisis response were low. These areas of poor knowledge should be the focus of educating CHWs in increasing their ability to provide quality care for patients with epilepsy in LMICs.
Antimicrobial Usage in Cattle and Poultry Production in Dar Es Salaam, Tanzania: Pattern and Quantity
Authors: Azabo Rogers , Mshana Stephen , Matee Mecky , Kimera Sharadhuli I 
Published: December 2020

Abstract
Background: Antimicrobials are extensively used in cattle and poultry production in Tanzania. However, there is dearth of information on its quantitative use. A questionnaire-based cross-sectional study was conducted from August to September 2019 in randomly selected poultry and small-scale dairy farms, in three districts of Dar es Salaam City eastern, Tanzania, to assess the practice and quantify antimicrobial use. Descriptive and statistical analyses were performed at a confidence interval of 95%. The ratio of Used Daily Dose (UDD) and Defined Daily Dose (DDD) were used to determine whether the antimicrobial was overdosed or under dosed. Results: A total of 51 poultry and 65 small-scale dairy farms were involved in the study. The route of antimicrobial administration was 98% orally via drinking water and 2% in feeds for poultry and for small-scale dairy farms, all through parenteral route. Seventeen types of antimicrobials comprising seven classes were recorded in poultry farms while nine belonging to six classes in the small dairy farms. Majority of the farms (poultry, 87.7% and small-scale dairy, 84.3%) used antimicrobials for therapeutic purposes. About 41% of the poultry and one third (34%) of the dairy farmers’ were not compliant to the drug withdrawal periods. Beta-lactams, fluoroquinolones, sulphonamides, tetracyclines and macrolides were the commonly used antimicrobials on these farms. Trimethoprim and tylosin were under dosed whereas colistin, sulfadiazine, sulfamerazine, flumequin and sulfadimidine were over dosed in the poultry farms and only tylosin over dosed in small dairy farms. The majority (58.6%) of farmers had adequate level of practices regarding antimicrobial use in cattle and poultry production. This was associated with the age and level of education of the cattle and poultry farmers. Conclusion: The study revealed a high and widespread misuse of antimicrobials of different types and classes in both poultry and small-scale dairy farming in Dar es Salaam, Tanzania. This result gives insight into the antimicrobial use practices and its quantification. The information obtained can guide and promote prudent use of antimicrobials among the farmers by developing mitigate strategies that reduce antimicrobial resistance risk potentials.
Volatile Constituents Analysis and Antimicrobial Activity of Two Subspecies Ballota nigra L. From Iran
Authors: Bidgoli Reza Dehghani 
Published: December 2020

Abstract
Background Ballota nigra L. is a perennial herb of the Lamiaceae family and it's native to the Mediterranean region and central Asia, also it can found throughout Europe. during this research, the volatile oil composition and antimicrobial activity of the methanol extract from flowering aerial parts of two subspecies of B. nigra (B. nigra ssp. foetida and B. nigra ssp. anatolica) were evaluated. Plant extraction was prepared by the maceration method and the antibacterial activity of methanolic extracts against 12 microorganisms was investigated by disc diffusion and minimal inhibitory concentration (MIC) methods.Results: GC/MS analysis of the volatile oil confirms the presence of 25 constituents in B. nigra ssp. foetida and 27 constituents in B. nigra ssp. anatolica. the most constituents in these two subspecies were α- Terpineol, Eicosane, Hexadecanoic acid, Longipinene epoxide, and Ethyl linoleate, which had slight differences within the amount of total volatile oil. within the antibacterial and MIC tests, indicated that methanolic extract of two subspecies Ballota nigra L. had acceptable antibacterial activity and therefore the B. nigra ssp. anatolica had more antibacterial activity in compression to B. nigra ssp. foetida.Conclusion: Today the tendency of natural products due to antioxidant and antimicrobial properties is increasing, and plants are the main source of these safe materials. During this respect, our study is often considered because of the first report on the volatile oil composition and antimicrobial activity of methanol extract of various subspecies of .B. nigra.
Rickettsiae in Red Fox (Vulpes Vulpes), Marbled Polecat (Vormela Peregusna) and Their Ticks in Northwestern China
Authors: Liu Gang , Zhao Shanshan , Tan Wenbo , Hornok Sándor , Yuan Wumei , Mi Ligu , Wang Suwen , Liu Zhiqiang , Zhang Yanyan , Hazihan Wurelihazi , Gu Xinli , Wang Yuanzhi 
Published: December 2020

Abstract
BackgroundPreviously, twelve Rickettsia species were found in ticks, fleas, sheep keds (Melophagus ovinus), bats (common pipistrelle: Pipistrellus pipistrellus) and a tick-bitten patient in Xinjiang Uygur Autonomous Region (XUAR), northwestern China. Here we aimed to molecularly detect rickettsial agents in red fox (Vulpes vulpes), marbled polecat (Vormela peregusna) and their ticks.MethodsDuring 2018-2019, 12 red foxes, 1 marbled polecat and their ticks were sampled in two counties and a city of Xinjiang Uygur Autonomous Region (northwestern China). The heart, liver, spleen, lung and kidney of these 13 carnivores were dissected, followed by DNA extraction. Hard ticks were identified both morphologically and molecularly. All samples were examined for the presence of rickettsiae by amplifying four genetic markers.ResultsA total of 26 adult ticks and 28 nymphs (38 Ixodes canisuga, nine Ixodes kaiseri, six Haemaphysalis erinacei and one Dermacentor marginatus) were collected from red foxes, and four H. erinacei ticks were removed from a marbled polecat. Analysis of cytochrome c oxidase subunit I (COI) gene sequences indicated that 2-32 nucleotides differed between I. canisuga, I. kaiseri and H. erinacei from northwestern China and Europe. Rickettsia raoultii was detected in three red foxes, Candidatus Rickettsia barbariae in a red fox, Rickettsia sibirica in a red fox and a marbled polecat, and R. raoultii in two tick species (I. canisuga and D. marginatus).Conclusions﻿To the best of our knowledge, I. canisuga and I. kaiseri have not been previously reported from red foxes in China. The DNA of R. sibirica and R. raoultii was detected for the first time in organs of red foxes, and R. sibirica in organs of marbled polecat. This is also the first molecular evidence for the presence of R. raoultii in I. canisuga. Our findings add to the range of tick-borne pathogens in wildlife species and associated ticks in China.
Evaluation and Selection of Suitable qRT-PCR Reference Genes for Light Responses in Tea Plant (Camellia Sinensis)
Authors: Wang Jiaxin , Tang Qianhui , Sun Kang , Zeng Liang , Wu Zhijun 
Published: December 2020

Abstract
Background: Tea plant (Camellia sinensis) is an important woody economic crop used for processing leaf-type beverages. Tea has been proved to be beneficial to human health because it is rich in tea polyphenols and other active ingredients. Numerous studies have shown that light is a necessary environmental condition to control the growth and metabolism of C. sinensis. Gene expression experiments are always performed to explore the transcriptional regulation mechanism of plants widely based on the technique of quantitative real time polymerase chain reaction (qRT-PCR). The screening and application of reference genes are necessary for the normalization of gene expression under specific conditions. However, the reference genes for systematic analysis of light-induced transcription mechanisms are still not available in C. sinensis.Results: In this research, we identified actin family genes that are always used as reference genes with high frequency and without distinction for various expression experiments in C. sinensis. Six pairs of distinctive primers (corresponding to CsACT1, CsACT2, CsACT(3-4), CsACT(5-6), CsACT(7-8), and CsACT(9-10) genes) were designed to evaluate their expression stability in response to light quality (LQ), light intensity (LI), and photoperiod (PD). Simultaneously, six other family members (CsUBC1, CsCLATHRIN1, CsGAPDH, CsTBP, CsTIP41, and CseIF-4α) of C. sinensis commonly used as reference genes were also investigated. The stability rankings of gene expression were calculated by the statistical algorithms of geNorm, BestKeeper, NormFinder, and RefFinder softwares. Conclusions: CsACT(5-6), CsTIP41, and CsACT(3-4) were the most stable genes for light quality (LQ), light intensity (LI), and photoperiod (PD) treatments, respectively. This study provides a basis for the selection of reference genes for future research on the transcription mechanism of light response in C. sinensis. Moreover, the analysis of actin family members of C. sinensis will help to understand the individual transcription mechanism of housekeeping family.
Gender-specific Predictive Ability for the Risk of Hypertension Incidence Related to Baseline Level or Trajectories of Adiposity Indices: Cohort Study of Functional Community in Beijing Urban from 2015 to 2019 year
Authors: LU Ya-ke , DONG Jing , SUN Yue , HU Li-kun , LIU Yu-hong , Chu Xi , Yan Yu-xiang 
Published: December 2020

Abstract
Background: Early prevention of hypertension is important for global cardiovascular disease morbidity and mortality. The current study aims to exploit better predictor for hypertension incidence related to baseline level or trajectories of adiposity indices, as well as the gender-specific effect.Methods: 6085 subjects from a functional community cohort in urban Beijing participated in our study. Restricted cubic splines were used to estimated nonlinear associations of BMI and WHtR as continuous variable with risk of hypertension. Stepwise logistic regression model was performed to estimate the RRs of adiposity indices and metabolic status, adjusted for covariates. Nomogram models and receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of BMI trajectory groups and WHtR trajectory groups. Further, all analysis were performed by gender.Results: The risk of hypertension incidence was significant related to BMI trajectory groups (persistent overweight: RR=1.99, 95%CI: 1.57-2.52; persistent obese: RR=3.07, 95%CI: 2.40-3.93; persistent the highest: RR=4.55, 95%CI: 3.37-6.14) and WHtR trajectory groups (persistent medium: RR=2.90, 95%CI: 2.23-3.77; persistent high: RR=4.48, 95%CI: 3.41-5.89; increasing to higher: RR=7.77, 95%CI:5.48-11.0). In total population, BMI trajectories and WHtR trajectories showed similar ability to predict the risk of hypertension incidence with AUC 0.713 and 0.720, respectively. After stratified by gender, BMI trajectories showed higher power in female than male butsimilar in WHtR trajectories (BMI trajectories: 0.762 vs. 0.662; WHtR trajectories: 0.769 vs. 0.663). Conclusions: BMI and WHtR trajectories have higher predictive power for hypertension incidence compared to baseline data. Women are more vulnerable to obese and abnormal MS than man.