bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analyses of the single-cell ATAC-seq and RNA-seq reveal the epigenetic landscape of human ovarian aging
Authors: Xu Yunzhao , Chen Jinling , Gu Shuting , Liu Yuanlin , Ni Huihua , Huang Yan , Gao Sainan , Sheng Nan , Zhang Xiaojing , He Xin , Zhou Songlin , Ge Wenliang 
Published: January 2022

Abstract
Studying the molecular mechanisms of ovarian aging is crucial for understanding the age-related fertility issues in females. Recently, a single-cell transcriptomic roadmap of ovarian aging based on non-human primates revealed the molecular signatures of the oocytes at different developmental stages. Herein, we present the first epigenetic landscape of human ovarian aging, through an integrated analysis of the single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) and single-cell RNA-seq. We depicted the transcriptional profiles and chromatin accessibility of the ovarian tissues isolated from old (n=4) and young (n=2) donors. The unsupervised clustering of data revealed seven distinct cell populations in the ovarian tissues and six subtypes of oocytes, which could be distinguished by age difference. Further analysis of the scATAC-seq data from the young and old oocytes revealed that the interaction between the Notch signaling pathway and AP-1 family transcription factors may crucially determine oocyte aging. Finally, a machine-learning algorithm was applied to calculate the optimal model based on the single-cell dataset for predicting oocyte aging, which exhibited excellent accuracy with a cross-validated area under the receiver operating characteristics score of 0.99. In summary, this study provides a comprehensive understanding of human ovarian aging at both the transcriptomic and epigenetic levels, based on an integrated analysis of large-scale single-cell datasets. We believe our results will shed light on the discovery of potential therapeutic targets or diagnostic markers for age-related ovarian disorders.
The Functionality of Health Facility Governing Committees and Their Associated Factors in Selected Primary Health Facilities Implementing Direct Health Facility Financing in Tanzania
Authors: Kesale Anosisye , Mahonge Christopher , Muhanga Mikidadi 
Published: January 2022

Abstract
Background: Decentralization has dominated the agenda for the reforms of the organization of service delivery in Lower and Middle-Income Countries (LMICs). Decentralization faces a formidable challenge of fiscal decentralization in primary healthcare facilities. Of now, LMICs are implementing fiscal decentralization reforms to empower health facilities and their Health Facility Governing Committees (HFGCs). Given the paucity of the impact of fiscal decentralization, this study was conducted to assess the functionality of HFGCs and their associative factors in primary health care facilities implementing fiscal decentralization through Direct Health Facility Financing (DHFF) in Tanzania.Methods: A cross-sectional design was employed to gather both qualitative and quantitative data. The study was conducted in 32 selected primary health facilities implementing DHFF in Tanzania. Probability and nonprobability sampling procedures were employed, in which a multistage sampling procedure was used to select 280 respondents. Data were collected through a structured questionnaire, in-depth interviews and focus group discussions. Descriptive analysis was employed to determine the functionality of HFGCs and binary logistic regression was employed to determine associated factors for the functionality of HFGC. Qualitative analysis was done through thematic analysis.Result: HFGC functionality under DHFF has been found to be good by 78.57%. Specifically, HFGCs have been found to have good functionality in mobilizing communities to join Community Health Funds 87.14%, participating in the procurement process 85%, discussing community health challenges 81.43% and planning and budgeting 80%. The functionality of HFGCs has been found to be associated with the planning and budgeting aspects p-value of 0.0011, procurement aspects p-value 0.0331, availability of information reports p-value 0.0007 and Contesting for HFGC position p-value 0.0187.Conclusion: The study has revealed that fiscal decentralization through DHFF significantly improves the functionality of HFGCs. Therefore, the study recommends more effort be put into facilitating the availability of finances to the health facilities.
Electroredox Carbene Organocatalysis with iodine cocatalyst
Authors: Zhou Peng , Li Wenchang , Lan Jianyong , Zhu Tingshun 
Published: January 2022

Abstract
Oxidative carbene organocatalysis, inspired from Vitamin B1 catalyzed oxidative activation from pyruvate to acetyl coenzyme A, have been developed as a versatile synthetic method. To date, the α-, β-, γ-, δ- and carbonyl carbons of (unsaturated)aldehydes have been successfully activated via oxidative N-heterocyclic carbene (NHC) organocatalysis. In comparison with chemical redox or photoredox methods, electroredox methods, although widely used in mechanistic study, were much less studied in NHC catalyzed organic synthesis. Herein, an electroredox NHC organocatalysis system with iodine cocatalyst was developed. With the help of non-uniform distribution of electrolysis system, NHC and iodine, which was normally not compatible in chemical reaction, cooperated well in the electrochemical system. This cocatalyst system provided general solutions for electrochemical single-electron-transfer (SET) oxidation of Breslow intermediate towards versatile transformations. Radical clock experiment and cyclic voltammetry results suggested an anodic radical coupling pathway.
Selective skeletal editing of polycyclic arenes using organophotoredox dearomative functionalization
Authors: Wang Wei , Ji Peng , Davies Cassondra , Gao Feng , Chen Jing , Meng Xiang , Houk Kendall , Chen Shuming 
Published: January 2022

Abstract
Reactions that lead to destruction of aromatic ring systems often require harsh conditions and, thus, take place with poor selectivities. Selective partial dearomatization of fused arenes is even more challenging but it can be a strategic approach to creating versatile, complex polycyclic frameworks. Herein we describe a general organophotoredox approach for the chemo- and regioselective dearomatization of structurally diverse polycyclic aromatics, including quinolines, isoquinolines, quinoxalines, naphthalenes, anthracenes and phenanthrenes. The success of the new method for chemoselective oxidative rupture of aromatic moieties relies on precise manipulation of the electronic nature of the fused polycyclic arenes. Experimental and computational results show that the key to overcoming the intrinsic thermodynamic and kinetic unfavorability of the dearomatization process is an ultimate hydrogen atom transfer (HAT) step, which enables dearomatization to predominate over the otherwise favorable aromatization pathway. We show that this strategy can be applied to rapid synthesis of biologically valued targets and late-stage skeletal remodeling en route to complex structures.
Antimicrobial And Synergistic Activity of The Drug Association of Allium Sativum And Antibiotics Against Group B Streptococcus
Authors: Lima Sônia Maria Rolim Rosa , Gamberini Maria Thereza , Rodrigues Domingos Sávio , Junior Pedro Ismael Silva , Torres Kátia Andrea de Menezes 
Published: January 2022

Abstract
Maternal colonization by Group B Streptococcus during pregnancy increases the risk of neonatal infection due to vertical transmission from mother to fetus before or during labor. The aims of this study were to evaluate the antimicrobial activity of SP80 (obtained from RGE) and its synergism associated with the antibiotic against strains of Streptococcus agalactiae. Biomonitoring of SP80 disclosed antimicrobial activity only in fractions F18, F19, F20 and F42. The broth microdilution was used to determine the antimicrobial activity of SP80 and fractions from SP80 and to establish the MIC of SP80 (2.40 mg/mL). By using the disk diffusion method, fifty-five clinical isolates of S. agalactiae and 1 ATCC were tested against the association of SP80 with antibiotic penicillin G and ampicillin, respectively, for synergistic assessment. The association of SP80 with penicillin G showed that the mean of the inhibition halos decreased, but it was not significant, with p<0.07. In contrast, the association of SP80 with ampicillin caused the mean inhibition halos to increase with a p<0.001, a significant result. SP80 has antimicrobial activity against S. agalactiae Gram-positive bacteria, and the association with the antibiotic ampicillin showed a synergistic effect, which did not occur when in association with penicillin G.
Lipases and carboxylesterases are involved in interspecific pheromone differences between two moth species
Authors: de Fouchier Arthur , Fruitet Elise , Lievers Rik , Kuperus Peter , Emerson Jennifer , Gould Fred , Heckel David , Groot Astrid 
Published: January 2022

Abstract
Moth sex pheromones are a classical model for studying sexual selection. Females produce a species-specific pheromone blend that attracts males. Revealing the enzymes involved in the interspecific variation in blend composition is key for understanding the evolution of these sexual communication systems. The nature of the enzymes involved in the variation of acetate esters, which are prominent compounds in moth pheromone blends, remains unclear. We identified enzymes involved in acetate metabolism in two closely related species: Heliothis (Chloridea) subflexa and H. (C.) virescens, which differ in production of acetate esters. Through comparative transcriptomic analyses and CRISPR/Cas9 knockouts, we showed that two lipases and two esterases induce lower levels of acetate esters in female pheromones. To place our findings in an evolutionary context, we explored the molecular evolution of related lipases and esterases in Lepidoptera. Together, our results show that lipases and carboxylesterases are unexpectedly involved in tuning Lepidoptera pheromones composition.
Remodeling Articular Immune Homeostasis with an Efferocytosis-inspired Nanoimitator Mitigates Rheumatoid Arthritis
Authors: Jiang Xinyi , Zhang Shengchang , Chai Qihao , Tang Chunwei , Li Ziyang , Man Zhentao , Chen Chen , Zhang Jing , Liu Ying , Sun Peng , Zhang Rui , Yang Zhenmei , Han Maosen , Wang Yan , Wei Xia , Li Jun , Li Wei , Abdalla Mohnad , Yu Gongchang , Shi Bin 
Published: January 2022

Abstract
Massive intra-articular infiltration of the pro-inflammatory macrophages is a prominent feature of rheumatoid arthritis (RA) lesions, which are thought to underlie articular immune dysfunction, severe synovitis and ultimate joint erosion. Here we report an efferocytosis-inspired nanoimitator (EINI) for in situ targeted reprogramming of the synovial inflammatory macrophages (SIMs) and thus thwarting their autoimmune attack and reinstating articular immune homeostasis, which mitigates RA. The EINI consisted of a drug-based core with an oxidative stress-responsive phosphatidylserine (PtdSer) corona and a shell of P-selectin-blocking motif, low molecular weight heparin (LMWH). When systemically administrated, the LMWH on the EINI first bound to P-selectin overexpressed on endothelium in subsynovial capillaries, which functioned as an antagonist disrupting neutrophils synovial trafficking. Due to the high dysregulation of the synovial microvasculature, the EINI subsequently enriched in joint synovium where the shell was exfoliated upon the reactive oxygen species stimulation, and PtdSer corona was then exposed. In an efferocytosis-like manner, the PtdSer-coroneted core was in turn phagocytosed by SIMs, which synergistically terminated the SIMs-initiated pathological cascades and serially reconstructed the intra-articular immune homeostasis, conferring a chondroprotection effect. These findings demonstrate that SIMs can be precisely remodeled via the efferocytosis-mimetic strategy, which holds great potential for RA treatment.
The Protective Effect of Kirenol in Osteoarthritis: an in Vitro and in Vivo Study
Authors: Hu Wei , Mao Chao , Sheng Weibin 
Published: January 2022

Abstract
Background: Osteoarthritis (OA) is a chronic degenerative disease, its main characteristic involves articular cartilage destruction and inflammation response, absent of effective medical treatment. Our current research aimed to explore anti-inflammatory effect of kirenol, a diterpenoid natural product compound, in the development of OA and its potential molecular mechanism through in vitro and in vivo study.Methods: In vitro, chondrocytes were pretreated with kirenol for 2 h before IL-1β stimulation. Production of NO, PGE2, TNF-α, IL-6, aggrecan, collagen-II, MMP13and ADAMTS5 were evaluated by the Griess reaction and ELISAs. The mRNA (aggrecan and collagen-II) and protein expression (COX-2, iNOS, P65, IκB, PI3K, AKT) were measured by qRT-PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and P65. The in vivo effect of kirenol was evaluated in mice OA models induced by destabilization of the medial meniscus (DMM).Results: We found that kirenol inhibited IL-1β-induced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, ADAMTS-5. Besides, kirenol remarkably decreased IL-1β-induced degradation of aggrecan and collagen-II. Furthermore, kirenol significantly inhibited IL-1β-induced phosphorylation of PI3K/Akt and NF-κB signaling. In vivo, the cartilage in kirenol-treated mice exhibited less cartilage degradation and lower OARSI scores.Conclusions: Taken together, the results of this study provide potent evidence that kirenol could be utilized as a potentially therapeutic agent in prevention and treatment of OA.
Greater Reduction of Blood Pressure with Exercise Intervention Than Standard Care After Recent Ischaemic Atroke: A Randomized Clinical Trial
Authors: Francis-Emmanuel Patrice , Boyne Michael , Ryan Alice , Hafer-Macko Charlene , Macko Richard , Osmond Clive , Lawrence-Wright Marilyn , Green Curtis , Nelson Gail , Forrester Terrence 
Published: January 2022

Abstract
Context and Objectives: Ischaemic stroke (IS) causes disability and uses massive public health resources. Cumulative disability from recurrence may be reduced with cardiometabolic risk reduction strategies e.g., lowering blood pressure (BP). We hypothesized that intensive exercise plus best available care in adults with recent IS improves fitness, glucose metabolism, muscle protein synthesis in paretic limbs compared to controls. BP changes were compared between intervention (INT) and controls (CON). Research Design and Setting: A randomised, interventional clinical trial conducted in Jamaican adults subjects: We investigate 103 adults with recent IS and residual weakness. Forty-nine subjects (24 women: mean age 61.5; 25 men: mean age 63.8) received task-oriented exercise training (TEXT) plus best available care. Fifty-four subjects (23 women: mean age 60.2; 31 men: mean age 61.3) received best care, including exercise advice. Measurements: We measured baseline, 3-month and 6-month BP. Results: After recent IS, TEXT plus best available care reduced systolic BP by 21 mmHg and diastolic by 12 mmHg compared to controls, independent of medication adherence, body composition; stroke severity. Men in the TEXT group had increased lean mass (P < 0.007), VO2 max (P = 0.03); 6-minute walk distance (P = 0.003). Leg press on paretic (P = 0.004) and non-paretic (P < 0.001) increased with TEXT vs CON over 6 months, in both sexes (P-values for sex difference > 0.2). Time-to-chair-rise decreased in both sexes who received intervention vs controls (P <0.04) Conclusions: TEXT results in significant blood pressure reduction in adults with recent ischaemic stroke and residual weakness when compared with best available medical care only.
Bone Health in Children With Risk Factors for Low Bone Mass
Authors: Magallares Berta , Cerda Dacia , Betancourt Jocelyn , Fraga Gloria , Quesada-Masachs Estefanía , Lopez-Corbetó Mireia , Torrent Montserrat , Marin Ana , Herrera Silvia , Gich Ignasi , Boronat Susana , Zilberman Samuel , Casademont Jordi , Corominas Hector , Malouf Jorge 
Published: January 2022

Abstract
Purpose: To describe clinical and biological characteristics of pediatric patients with at least one risk factor (RF) for low bone mass for chronological age (LBMca)/childhood osteoporosis (cOP) and to assess its influence on bone mineral density (BMD).Methods: Patients between 2 and 20 years of age with at least 1 RF were recruited. Daily calcium intake, number of previous fractures and other RFs and their distribution among different groups were assessed. Spine and whole body DXA and vertebral morphometry were performed.Results: 103 patients were included. Mean age was 9.8 years old. 52.4% were female. Of the RFs, 84.5% presented insufficient calcium intake, 38.8% were receiving or had received corticosteroids, 31.1% were receiving other treatments with osteotoxic potential, 13.6% led a sedentary lifestyle, 12.6% presented history of fractures, and up to 8.1% had hypovitaminosis D. 38% of the cohort had 2 RFs, 31% had 3 RFs, 15% had 4 RFs, and 12% associated 5 or more RFs. 10.5% met LBMca criteria and 4.8% met cOP criteria. 73% of vertebral BMD was justified by age and hypovitaminosis D (positive effect), and male sex and Hispanic ethnicity (negative effect). 82% of total body less head BMD was justified by age (positive effect), and Hispanic ethnicity and sedentary lifestyle (negative effect).Conclusions: Pediatric populations with risk of LBM/cOP have 2 or more risk factors. Up to 10.5% of children with RFs present LBM and 4.8% have an unknown cOP. RFs related to changes in BMD are age, sex, sedentary lifestyle, ethnicity, and hypovitaminosis D.
Identification of a Key Glioblastoma Candidate Gene, FUBP3, Based on Weighted Gene Co-expression Network Analysis
Authors: Li Jianmin , Zhang Zhao , Guo Ke , Wu Shuhua , Guo Chong , Zhang Xinfan , Wang Zi 
Published: January 2022

Abstract
Background: Glioblastoma multiforme (GBM) is the most common aggressive malignant brain tumor. However, the molecular mechanism of glioblastoma formation is still poorly understood. To identify candidate genes that may be connected to glioma growth and development, weighted gene co-expression network analysis (WGCNA) was performed to construct a gene co-expression network between gene sets and clinical characteristics. We also explored the function of the key candidate gene.Methods: Two GBM datasets were selected from GEO Datasets. The R language was used to identify differentially expressed genes. WGCNA was used to construct a gene co-expression network in the GEO glioblastoma samples. A custom Venn diagram website was used to find the intersecting genes. The GEPIA website was used for survival analysis to determine the significant gene, FUBP3. OS,DSS, and PFI analyses, based on the UCSC Cancer Genomics Browser, were performed to verify the significance of FUBP3. Immunohistochemistry was performed to evaluate the expression of FUBP3 in glioblastoma and adjacent normal tissue. KEGG and GO enrichment analyses were used to reveal possible functions of FUBP3. Microenvironment analysis was used to explore the relationship between FUBP3 and immune infiltration. Immunohistochemistry was performed to verify the results of the microenvironment analysis.Results: GSE70231 and GSE108474 were selected from GEO Datasets, then 715 and 694 differentially expressed genes (DEGs) from GSE70231 and GSE108474, respectively, were identified. We then performed weighted gene co-expression network analysis (WGCNA) and identified the most downregulated gene modules of GSE70231 and GSE108474, and 659 and 3915 module genes from GSE70231 and GSE108474, respectively, were selected. Five intersection genes (FUBP3, DAD1, CLIC1, ABR, and DNM1) were calculated by Venn diagram. FUBP3 was then identified as the only significant gene by survival analysis using the GEPIA website. OS, DSS, and PFI analyses verified the significance of FUBP3. Immunohistochemical analysis revealed FUBP3 expression in GBM and adjacent normal tissue. KEGG and GO analyses uncovered the possible function of FUBP3 in GBM. Tumor microenvironment analysis showed that FUBP3 may be connected to immune infiltration, and immunohistochemistry identified a positive correlation between immune cells (CD4+ T cells, CD8+ T cells, and macrophages) and FUBP3.Conclusion: FUBP3 is associated with immune surveillance in GBM, indicating that it has a great impact on GBM development and progression. Therefore, interventions involving FUBP3 and its regulatory pathway may be a new approach for GBM treatment.
Fungal xenosiderophores from mycobiota and diet promote Salmonella colonization of the inflamed gut
Authors: Santus William , Rana Amisha , Devlin Jason , Kiernan Kaitlyn , Jacob Carol , Tjokrosurjo Joshua , Underhill David , Behnsen Judith 
Published: January 2022

Abstract
The fungal gut microbiota (mycobiota) has been implicated in diseases that disturb gut homeostasis. However, little is known about functional relationships between bacteria and fungi in the gut during infectious colitis. We investigated the role of fungal metabolites during infection with the intestinal pathogen Salmonella enterica serovar Typhimurium. We found that in the gut lumen, both the mycobiota and fungi present in the diet can be a source of siderophores, small molecules that scavenge iron from the host. The ability to use fungal siderophores, such as ferrichrome and coprogen, conferred a competitive growth advantage to Salmonella strains expressing the fungal siderophore receptors FhuA or FhuE in vitro and in a mouse model. Our study highlights the role of inter-kingdom cross-feeding between fungi and Salmonella, and elucidates a new function for the gut mycobiota, revealing the importance of these under-studied members of the gut ecosystem during bacterial infection.
Preconditioning Prefrontal Connectivity Using Transcranial Direct Current Stimulation and Transcranial Magnetic Stimulation
Authors: Alkhasli Isabel , Mottaghy Felix M. , Binkofski Ferdinand , Sakreida Katrin 
Published: January 2022

Abstract
Transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been shown to modulate functional connectivity. Their specific effects seem to be dependent on the pre-existing neuronal state. We aimed to precondition frontal networks using tDCS and subsequently stimulate the left dorsolateral prefrontal cortex (lDLPFC) using TMS. Thirty healthy participants underwent either excitatory, inhibitory or sham tDCS for 10 min, as well as an excitatory intermittent theta burst (iTBS) protocol (600 pulses in 190 s, 20 x 2 s trains), applied over the lDLPFC at 90% of the individual resting motor threshold. Functional connectivity was measured in three task-free, 10-min-long baseline resting state fMRI sessions, immediately before and after tDCS, as well as after iTBS. Connectivity analyses between stimulation site and all other brain voxels, contrasting the interaction effect between the experimental tDCS groups (excitatory vs inhibitory) and the repeated measure (post tDCS vs. post TMS), revealed significantly affected voxels bilaterally in the anterior cingulate and paracingulate gyri, the caudate nuclei, the insula and operculum cortices, as well as the Heschl’s gyrus. ROI-to-ROI analyses additionally showed temporo-parietal-striatal and temporo-parietal-fronto-cingulate differences between the anodal and cathodal group post tDCS, as well as striatal-temporo-parietal anodal-cathodal differences and frontostriatal cathodal-sham group differences post TMS. Excitatory iTBS to a tDCS-inhibited lDLPFC yielded stronger functional connectivity to various areas, as compared to excitatory iTBS to a tDCS-enhanced prefrontal cortex. Results demonstrate complex, whole-brain stimulation effects, most-likely facilitated by cortical homeostatic control mechanisms, as well as the feasibility of using tDCS to modulate TMS effects.