bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of carotenoid supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials
Authors: Behzadi Mehrdad , Akbarzadeh Marzieh , Mohammadi Sartang Mohsen , Rabiee Mohammadreza , Bideshki Mohammad Vesal 
Published: December 2023

Abstract

Context
Hypertension (HTN) is regarded as a serious public health issue throughout the world. High blood pressure (BP) may be improved by carotenoid supplementation; however, randomized controlled trials (RCTs) provide conflicting evidence.

Objective
The aim of this study was to evaluate the effects of carotenoid supplementation on BP in RCTs by systematically review and meta-analysis.

Data Sources
A comprehensive literature search was performed in the Scopus, PubMed, and Web of Science databases until October 2023, with no limitation on the date or language of publication.

Data Extraction
Studies that evaluated the net effects of carotenoids in the form of supplements on BP in adults were selected. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated on the basis of a fixed or random-effects model. Sensitivity analysis, meta-regression, publication bias, and heterogeneity were assessed using standard methods. Cochrane quality assessments were used to evaluate the included studies' bias risks. Evidence certainty was calculated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework).

Data Analysis
Reports on a total of 19 RCTs involving 1151 participants were included in this review. Carotenoid supplementation significantly reduced the systolic BP (SBP) (WMD, –2.492 mmHg; 95%CI, –4.52, –0.47; P = 0.016) and diastolic BP (DBP) (WMD, –1.60 mmHg; 95%CI, –2.73, –0.47; P = 0.005). Greater effects were observed in Asian participants, those aged &gt;50 years, nonhealthy participants, and participants with a baseline SBP ≥130 mmHg and DBP ≥80 mmHg, at dose &gt;10 mg. Dose–response analysis showed that carotenoid supplementation decreased SBP and DBP levels at doses of, respectively, 0–25 and 0–20 mg/d. Evidence for all SBP, DBP, and heart rate values was high quality.

Conclusions
Carotenoid supplementation had a beneficial effect on BP parameters, especially in nonhealthy study participants with high BP baseline levels.

PROSPERO registration no
CRD42023402740.
What is a real black hole?
Authors: Sugawara Hirotaka 
Published: December 2023

Abstract
Four dimensional Einstein equation with non-vanishing energy momentum tensor is solved to give a solution where the event horizon of a celestial body is outside of the body, which corresponds to a black hole by definition. There is no singularity at the center of the object unlike the case of Schwarzschild solution. We do not have the gravitational collapse. We do not have the gravitational collapse thus avoiding the Penrose-Hawking singularity theorems. The main feature of our black hole solution is that it has the horizon inside the black hole in addition to the usual outside horizon. This inner horizon singularity is not removable by a coordinate transformation because the determinant of metric tensor is singular at this point but there is no singularity neither in the density nor in the pressure indicating there is no gravitational collapse.
Recent progress in functional metal–organic frameworks for bio-medical application
Authors: Chai Wenwen , Chen Xiaochen , Liu Jing , Zhang Liyan , Liu Chunyu , Li Li , Honiball John Robert , Pan Haobo , Cui Xu , Wang Deping 
Published: December 2023

Abstract
Metal–organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.
Transcriptomic features of systemic lupus erythematosus patients in flare and changes during acute in-hospital treatment
Authors: Liu Zhongyi , Shao Li , Hou Fei , Li Weiyang , Wang Yong-Fei , Feng Hong , Wang Frank Qingyun , Lei Yao , Zheng Lichuan , Liang Rui , Li Jian , Guo Xianghua , Zhang Lili , Zhang Yanfang , Yang Jing , Qin Xiao , Wei Wei , Yang Xingtian , Dang Xiao , Ma Wen , She Chun Hing , Kong Qingsheng , Yang Jing , Ban Bo , Lau Yu Lung , Song Qin , Yang Wanling 
Published: December 2023

Abstract

Objectives
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies.

Methods
RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analysed and scored to elucidate the transcriptomic changes during treatment.

Results
Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts.

Conclusions
In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.
Alpine Extremophytes in Evolutionary Turmoil: Complex Diversification Patterns and Demographic Responses of a Halophilic Grass in a Central Asian Biodiversity Hotspot
Authors: Wróbel Anna , Klichowska Ewelina , Nowak Arkadiusz , Nobis Marcin 
Published: December 2023

Abstract
Diversification and demographic responses are key processes shaping species evolutionary history. Yet we still lack a full understanding of ecological mechanisms that shape genetic diversity at different spatial scales upon rapid environmental changes. In this study, we examined genetic differentiation in an extremophilic grass Puccinellia pamirica and factors affecting its population dynamics among the occupied hypersaline alpine wetlands on the arid Pamir Plateau in Central Asia. Using genomic data, we found evidence of fine-scale population structure and gene flow among the localities established across the high-elevation plateau as well as fingerprints of historical demographic expansion. We showed that an increase in the effective population size could coincide with the Last Glacial Period, which was followed by the species demographic decline during the Holocene. Geographic distance plays a vital role in shaping the spatial genetic structure of P. pamirica alongside with isolation-by-environment and habitat fragmentation. Our results highlight a complex history of divergence and gene flow in this species-poor alpine region during the Late Quaternary. We demonstrate that regional climate specificity and a shortage of nonclimate data largely impede predictions of future range changes of the alpine extremophile using ecological niche modeling. This study emphasizes the importance of fine-scale environmental heterogeneity for population dynamics and species distribution shifts.
Dietary of different forms of Humulus scandens on growth performance and intestinal bacterial communities in piglets
Authors: Hao Lihong , Wang Cheng , Wang Huaizhong , Zhou Meng , Wang Yong , Hu Hongmei 
Published: December 2023

Abstract
The present study was aimed at elucidating the effects of feeding different forms of Humulus scandens (Hu) on performance and bacterial communities in piglets. A total of 160 piglets were divided into four groups: (1) a control (CG, basal diet); (2) a basal diet with Hu pulp (HS), basal diet + Hu pulp; (3) a basal diet with Hu juice (HSJ), basal diet + Hu juice; and (4) a basal diet with Hu residue (HSR), basal diet + Hu residue. Results showed that HS, HSJ, and HSR supplementation led to rich average daily gain (ADG) and poor feed conversion ratio (FCR) during 28 to 70 d of age, increased 120 d body weight (BW), average daily feed intake (ADFI) and ADG and decreased FCR during 71 to 120 d of age. Three experiment groups presented greater (P &lt; 0.05) IgA, IgG, and IgM and lower (P &lt; 0.05) glucose, and blood urea nitrogen. The content of diamine oxidase significantly decreased (P &lt; 0.05) in HS group. The crude protein and crude fiber digestibility were improved (P &lt; 0.05) in HS group and the Ca digestibility was increased (P &lt; 0.05) in HS and HSJ groups. HSR supplementation improved the abundance of Firmicutes and decreased the abundance of Bacteroidetes. Hu supplementation with different forms increased the proportion of Lactobacillus in cecum content. These results indicated that supplemental feeding of Hu with different forms improved serum immunity, nutrient digestibility, and bacterial communities in piglets, promoting growth and development, which may be regarded as a reference for developing novel feed resources for piglets.
20(S)-Ginsenoside Rh1 alleviates sevoflurane-induced ototoxicity by reducing oxidative stress levels
Authors: Lin Jin , Gang Li , Wen Li , Zi He Ying , Xia Shen 
Published: December 2023

Context
Sevoflurane is an inhalational anesthetic widely used in pediatric surgery. However, animal studies have shown that multiple sevoflurane exposures during the neonatal period led to ototoxicity. 20(S)-Ginsenoside Rh1, a ginsenoside extract, protects against cisplatin-induced ototoxicity by scavenging free radicals.

Objective
This study aimed to assess the effects of Rh1 on sevoflurane-induced ototoxicity.

Materials and methods
Neonatal cochlear explants and House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were cultured and randomly divided into three groups: the control group, the sevoflurane group and the Rh1 pretreatment group. We pretreated cochlear explants or HEI-OC1 cells with 100 μM Rh1 2 hours before performing sevoflurane exposure. Immunofluorescence was used to detect hair cells and spiral ganglion neurons. Cell Counting Kit-8 assay was used to determine cell viability. Annexin V-fluorescein isothiocyanate and propidium iodide were used to evaluate apoptosis. CellROX-Green and MitoSOX-Red probes were used to measure the amount of reactive oxygen species (ROS). Tetramethylrhodamine methyl ester labeling was used to examine mitochondrial membrane potential.

Results
Rh1 attenuated spiral ganglion neuron nerve fibers and synapses degeneration in cochlear explants after sevoflurane exposure. Rh1 significantly increased the viability of HEI-OC1 cells, reduced reactive oxygen species accumulation in HEI-OC1 cells, and prevented mitochondrial damage in HEI-OC1 cells after sevoflurane exposure.

Discussion and conclusion
These findings suggest that Rh1 is a promising drug for preventing sevoflurane-induced ototoxicity.
The tumour suppressor Fat1 is dispensable for normal murine hematopoiesis
Authors: Zhang Qing , Li Meng Ke , Hu Xin Yuan , Wang Ying Ying , Zhao Pan Pan , Cheng Lin Na , Yu Rong Hua , Zhang Xu Dong , Chen Song , Zhu Zun Min , de Bock Charles E. , Thorne Rick F. 
Published: December 2023

AbstractLoss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vavi-Cre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hemopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine haematopoiesis.
Mechanism of action of Buqing Granule against Diabetic retinopathy based on network pharmacology and animal experiments
Authors: Yang Yifan , Yuan Ling , Li Xiangyang , Liu Qian , Jiang Wenjie , Jiao Taiqiang , Li Jiaqing , Ye Mengyi , Niu Yang , Nan Yi 
Published: December 2023

ABSTRACTObjectiveFor this study, network pharmacology and animal experiments were used together to get a better idea of how BQKL works at the molecular level to treat DR.MethodsIn this study, we obtained the relevant action target information of BQKL from the TCMSP and also combined the GeneCards, OMIM, TTD, and PharmGKB databases with the GEO database to obtain the relevant target information of DR. The intersection of these targets was determined using a Venn diagram to identify the target of action for the treatment of DR with BQKL. The target proteins of BQKL for DR were then uploaded to the String database. The resultant data were imported into Cytoscape 3.9.0 to construct PPI networks and identify key targets of action. The DAVID database was used to do a GO and KEGG pathway enrichment analysis of target genes for treating DR with BQKL. Molecular docking was performed to validate the core action targets with the core compounds of BQKL. In addition, we induced DR production in rats by a high-fat, high-sugar diet and intraperitoneal injection of STZ and validated the results obtained from the network pharmacological analysis by changes in body weight and blood glucose, serum levels of biochemical markers, HE staining, immunohistochemistry, qRT-PCR, and Western blot experiments in rats.ResultsIn this study, quercetin, kaempferol, β-sitosterol, lignanserin, and stigmasterol were identified as the key components, TP53, AKT1, JUN, CASPASE3, MAPK3, and MAPK1 as the key targets, and PI3K-Akt, AGE-RAGE, and MAPK signaling pathways as the main pathways involved. The results of animal experiments showed that BQKL could not only effectively reduce the degree of blood glucose, blood lipids, and oxidative damage in diabetic rats but also slow down the development process of DR. At the same time, it can significantly up-regulate the expression of AKT1, MAPK1, and MAPK3 and down-regulate the expression of CASPASE3, c-JUN, and TP53 in retinal tissue.ConclusionBQKL ameliorates oxidative stress, apoptosis, and inflammation due to hyperglycemia-related stress by regulating key targets of CASPASE3, AKT1, c-JUN, TP53, MAPK1, and MAPK3, thereby delaying the onset and progression of DR.
“I found out about Zika virus after she was born.” Women’s experiences of risk communication during the Zika virus epidemic in Brazil, Colombia, and Puerto Rico
Authors: Miranda María Consuelo , Sánchez Claudia Hormiga , Souto Ester Paiva , Pérez Edna Acosta , Matta Gustavo Corrêa , Daza Marcela , Gama Gabriela Lopes , Pimentel Camila , Mercado Marcela , Niño Angélica María Amado , Leegstra Luz Marina , Marbán Castro Elena , Manders Olivia C. , Maxwell Lauren 
Published: December 2023

AbstractIntroductionProviding accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis of the infection and the associated risk. The 2015-17 Zika virus epidemic overwhelmingly affected women in countries with limited access to safe abortion. Understanding women’s perspectives on risk communication during pregnancy in the context of an emerging pathogen can help inform risk communication in response to future outbreaks that affect fetal or child development.MethodsWe conducted a cross-sectional qualitative interview study with 73 women from 7 locations in Brazil, Colombia, and Puerto Rico to understand women’s experiences of ZIKV test and outcome-related communication during the ZIKV pandemic. We used thematic analysis to analyze the in-depth interviews.FindingsParticipants in Brazil and Colombia reported that the healthcare system’s lack of preparation and organization in communicating ZIKV test results and associated adverse outcomes led to their feeling abandoned and alone in confronting the challenges of a ZIKV-affected pregnancy. In contrast, participants in Puerto Rico reported that the regular testing schedules and clear, well-planned communication between the care team and between providers and pregnant women helped them to feel they could prepare for a ZIKV-affected pregnancy.ConclusionCommunication of the risk associated with an emerging pathogen suspected to affect pregnancy and developmental outcomes is a fraught issue. Public health authorities and healthcare providers should work together in the interpandemic period to understand families’ preferences for risk communication during pregnancy in the presence of uncertainty and develop a community-informed plan for risk communication.
Activated PI3Kδ specifically perturbs mouse Treg homeostasis and function leading to immune dysregulation
Authors: Singh Akhilesh K. , Qureshah Fahd Al , Drow Travis , Hou Baidong , Rawlings David J 
Published: December 2023

AbstractFoxp3+regulatory T cells (Treg) are required for maintaining immune tolerance and preventing systemic autoimmunity. PI3Kδ is required for normal Treg development and function. However, the impacts of dysregulated PI3Kδ signaling on Treg function remain incompletely understood. Here, we used a conditional mouse model of activated PI3Kδ syndrome (APDS) to investigate the role of altered PI3Kδ signaling specifically within the Treg compartment. Aged mice expressing a PIK3CD gain-of-function mutation (aPIK3CD) specifically within the Treg compartment exhibited weight loss and evidence for chronic inflammation as demonstrated by increased memory/effector CD4+and CD8+T cells with enhanced IFN-γ secretion, spontaneous germinal center responses and production of broad-spectrum autoantibodies. Intriguingly, aPIK3CD facilitated Treg precursor development within the thymus and an increase in peripheral Treg numbers. Peripheral Treg, however, exhibited an altered phenotype including increased PD1 expression and reduced competitive fitness. Consistent with these findings, Treg specific-aPIK3CD mice mounted an elevated humoral response following immunization with a T-cell dependent antigen, that correlated with a decrease in follicular Treg. Taken together, these findings demonstrate that an optimal threshold of PI3Kδ activity is critical for Treg homeostasis and function, suggesting that PI3Kδ signaling in Treg might be therapeutically targeted to either augment or inhibit immune responses.
Simple syntactic rules through rapid synaptic changes
Authors: Sun Lin , Manohar Sanjay G 
Published: December 2023

AbstractSyntax is a central organizing component of human language but few models explain how it may be implemented in neurons. We combined two rapid synaptic rules to demonstrate how neurons can implement a simple grammar without accounting for the hierarchical property of syntax. Words bind to syntactic roles (e.g. “dog” as subject or object) and the roles obey ordering rules (e.g. subject → verb → object), guided by predefined syntactic knowledge. We find that, like humans, the model recalls sentences better than shuffled word-lists, and when given the permitted role orderings, and a set of words, the model can select a grammatical ordering and serialize the words to form a sentence influenced by the priming effect (e.g. producing a sentence in the passive voice after input of a different sentence also in the passive voice). The model also supports languages reliant on affixes, rather than word order, to define grammatical roles, exhibits syntactic priming and demonstrates typical patterns of aphasia when damaged. Crucially, it achieves these using an intuitive representation where words fill roles, allowing structured cognition.
Virus-encoded glycosyltransferases hypermodify DNA with diverse glycans
Authors: Pyle Jesse D. , Lund Sean R. , O’Toole Katherine H. , Saleh Lana 
Published: December 2023

ABSTRACTEnzymatic modification of DNA nucleobases can coordinate gene expression, protection from nucleases, or mutagenesis. We recently discovered a new clade of phage-specific cytosine methyltransferase (MT) and 5-methylpyrimidine dioxygenase (5mYOX,e.g.,TET) enzymes that produce 5-hydroxymethylcytosine (5hmC) as a precursor for additional post-replicative enzymatic hypermodifications on viral genomes. Here, we identify phage MT- and 5mYOX-dependent glycosyltransferase (GT) enzymes that catalyze linkage of diverse glycans directly onto 5hmC reactive nucleobase substrates. Using targeted bioinformatic mining of the phage metavirome databases, we discovered thousands of new biosynthetic gene clusters (BGCs) containing enzymes with predicted roles in cytosine sugar hypermodification. We developed a pathway reassembly platform for high-throughput functional screening of GT-containing BGCs, relying on the endogenousE. colimetabolome as a substrate pool. We successfully reconstituted a subset of phage BGCs and isolated novel and highly diverse sugar modifications appended to 5hmC, including mono-, di-, or tri-saccharide moieties comprised of hexose, N-acetylhexosamine or heptose sugars. Structural predictions and sugar product analyses suggest that phage GTs are related to host lipopolysaccharide, teichoic acid, and other small molecule biosynthesis enzymes and have been repurposed for DNA substrates. An expanded metagenomic search revealed hypermodification BGCs within gene neighborhoods containing phage structural proteins and putative genome defense systems. These findings enrich our knowledge of secondary modifications on DNA and the origins of corresponding sugar writer enzymes. Post-replicative cytosine hypermodification by virus-encoded GTs is discussed in the context of genome defense, DNA partitioning and virion assembly, and host-pathogen co-evolution.