bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCN5 suppresses injury-induced vascular restenosis by inhibiting smooth muscle cell proliferation and facilitating endothelial repair via thymosin β4 and Cd9 pathway
Authors: Zhang Qi , Li Hongda , Zhuang Tao , Xu Lehua , Wu Wenrun , Pi Jingjiang , Zhu Pengxiong , Geng Liang , Duan Yunhao , Xu Jianfei , Yue Jinnan , Liu Xiuxiang , He Chenlong , Chen Xiaoli , Ruan Chengchao , Zhuang Shougang , Liu Zhongmin , Wang Yilong , Zhang Lin , Liu Jie , Zhang Yuzhen 
Published: December 2024

Abstract

Background and Aims
Members of the CCN matricellular protein family are crucial in various biological processes. This study aimed to characterize vascular cell-specific effects of CCN5 on neointimal formation and its role in preventing in-stent restenosis (ISR) after percutaneous coronary intervention (PCI).

Methods
Stent-implanted porcine coronary artery RNA-seq and mouse injury-induced femoral artery neointima single-cell RNA sequencing were performed. Plasma CCN5 levels were measured by enzyme-linked immunosorbent assay. Endothelial cell (EC)- and vascular smooth muscle cell (VSMC)-specific CCN5 loss-of-function and gain-of-function mice were generated. Mass spectrometry and co-immunoprecipitation were conducted to identify CCN5 interacting proteins. Additionally, CCN5 recombinant protein (CCN5rp)-coated stents were deployed to evaluate its anti-ISR effects in a porcine model.

Results
Plasma CCN5 levels were significantly reduced and correlated closely with the degree of restenosis in ISR patients. CCN5 expression was significantly decreased in VSMCs of stent-implanted porcine coronary segments and injured mouse femoral arteries, especially in synthetic VSMCs. In contrast, elevated CCN5 expression was observed in regenerating ECs of injured vessels. Endothelial cell- and VSMC-specific CCN5 deletion mice exhibited exacerbation of injury-induced neointimal hyperplasia, while CCN5 gain-of-function alleviated neointimal formation. Mechanistic studies identified thymosin β4 (Tβ4) as a CCN5 interacting protein in ECs and EC-CCN5 promoted injury repair through Tβ4 cleavage product Ac-SDKP. Also, CCN5rp promoted EC repair to suppress neointimal hyperplasia via interaction with Cd9 extracellular domain. Moreover, implantation with CCN5rp-coated stent significantly increased stent strut coverage with ECs, which suppressed neointimal formation and ultimately alleviated ISR.

Conclusions
CCN5 exerts a dual protective effect on ISR by inhibiting VSMC proliferation and facilitating EC repair. CCN5rp-coated stent might be promising in the prevention of ISR after PCI.
Study on the metastatic mechanism of LINC00115 in adenocarcinoma of the Esophagogastric junction
Authors: Zhao Xia , Zhang Haifeng , Liu Yangyang , Li Li , Wei Haitao 
Published: December 2024

Abstract
Adenocarcinoma of the esophagogastric junction (AEG) is a common and deadly cancer, and an in-depth investigation of its molecular mechanisms of metastasis is crucial for discovering new therapeutic targets. This study explores the role of the long non-coding RNA (lncRNA) LINC00115 in AEG metastasis and its underlying mechanisms. Through the analysis of 108 pairs of AEG cancer tissues and matched adjacent tissues, we found a significant upregulation of LINC00115 in AEG tissues, closely associated with TNM staging and lymph node metastasis. Utilizing cell counting kit-8 (CCK-8) assays, colony formation experiments, wound healing assays, flow cytometry for apoptosis and cell cycle analysis, and Transwell assays, we have confirmed that LINC00115 significantly promotes proliferation, migration, and invasion of AEG cells in vitro. Animal experiments further validate the role of LINC00115 in promoting tumor growth and metastasis in vivo. Additionally, our nuclear-cytoplasmic fractionation experiments and RNA fluorescence in situ hybridization (FISH) reveal that LINC00115, along with its interacting protein KH-Type splicing regulatory protein (KHSRP), predominantly localizes to the cell nucleus. By conducting RNA pull-down assays and mass spectrometry (MS) analysis, we have identified a direct interaction between LINC00115 and KHSRP protein and further determined their binding sites through catRAPID and ENCORI databases. This study provides evidence of LINC00115 as a novel biomarker and potential therapeutic target for AEG and offers a fresh perspective on understanding the molecular mechanisms of AEG metastasis.
New Insights into the Pathogenesis of Intestinal Fibrosis in Inflammatory Bowel Diseases: Focusing on Intestinal Smooth Muscle Cells
Authors: Kalafateli Maria , Tourkochristou Evanthia , Tsounis Efthymios P , Aggeletopoulou Ioanna , Triantos Christos 
Published: December 2024

Abstract
Strictures in inflammatory bowel disease, especially Crohn’s disease (CD), are characterized by increased intestinal wall thickness, which, according to recent accumulating data, is mainly attributed to the expansion of the intestinal smooth muscle layers and to a lesser extent to collagen deposition. In this review, we will discuss the role of intestinal smooth muscle cells (SMCs) as crucial orchestrators of stricture formation. Activated SMCs can synthesize extracellular matrix (ECM), thus contributing to intestinal fibrosis, as well as growth factors and cytokines that can further enhance ECM production, stimulate other surrounding mesenchymal and immune cells, and increase SMC proliferation via paracrine or autocrine signaling. There is also evidence that, in stricturing CD, a phenotypic modulation of SMC toward a myofibroblast-like synthetic phenotype takes place. Moreover, the molecular mechanisms and signaling pathways that regulate SMC hyperplasia/hypertrophy will be extensively reviewed. The understanding of the cellular network and the molecular background behind stricture formation is essential for the design of effective anti-fibrotic strategies, and SMCs might be a promising therapeutic target in the future.
Antibody Levels From High-Throughput Variant-Specific SARS-CoV-2 Anti-Spike Immunoglobulin G and Angiotensin-Converting Enzyme 2 Neutralization Assays Correlate With COVID-19 Infection Risk in a Large Population
Authors: Jacobs Marni B , Clark Alex E , Goldhaber Nicole H , Valentine Holly D , Rivera Andrea , Ngo Toan , Barber Tom , Holmes Jacqueline , Manfredi Brittany , Garretson Aaron F , Bray William , Knight Rob , Longhurst Christopher A , Carlin Aaron F , De Hoff Peter , Laurent Louise C 
Published: December 2024

Abstract

Background
SARS-CoV-2 antibody levels have been proposed as a correlate of protection from infection. Yet, large-scale prospective studies of cost-effective scalable antibody measures as predictors of infection under real-world conditions are limited. We examined whether antibody levels measured by high-throughput variant-specific SARS-CoV-2 anti-spike immunoglobulin G (IgG) and angiotensin-converting enzyme 2 (ACE2) neutralization assays correlate with cell-based neutralizing antibody measurements and whether they can serve as a reasonable correlate of protection from SARS-CoV-2 infection.

Methods
We conducted a large institutional cohort study between January 2022 and March 2023. Participants (N = 2513) provided dried blood spot (DBS) samples for assessment of anti-spike IgG and ACE2 inhibition levels through high-throughput assays. Comparison with authentic cell-based SARS-CoV-2 neutralizing antibody assays was conducted with serum samples (n = 105). Associations between antibody levels and risk of infection were evaluated.

Results
Correlation between serum and DBS sampling and between cell-based neutralizing and high-throughput antibody binding assays was high for anti-spike IgG and ACE2 neutralization, though the degree of correlation varied by variant. Longitudinal evaluation suggested that DBS-based IgG and ACE2 inhibition levels were anticorrelated with infection risk, with higher sensitivity noted for ACE2 inhibition and variant-matched measures. IgG and ACE2 inhibition levels decreased over time, with more durable responses observed in participants whose most recent priming event was infection vs vaccination.

Conclusions
Findings suggest that variant-specific SARS-CoV-2 antibody levels may be a useful correlate of protection for infection, which has important implications for vaccination recommendations and evaluating infection risk. High-throughput assays measured via DBS may have utility in timing of boosters at the population or individual level.
Novel approach using automated target enrichment enables culture-independent accurate whole-genome sequencing of Neisseria gonorrhoeae directly from clinical urogenital and extragenital specimens
Authors: Golparian Daniel , Rapp Ellionor , Hasmats Johanna , Unemo Magnus 
Published: December 2024

Abstract

Objectives
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is compromising gonorrhoea treatment, and enhanced N. gonorrhoeae AMR and genome-based epidemiological surveillance is imperative. Molecular tests are replacing N. gonorrhoeae culture internationally, excluding possibilities to perform WGS. We describe and evaluate a novel approach using a custom SureSelectXTHS Target-Enrichment probe panel automated on the Magnis NGS Prep System and Illumina sequencing to generate accurate N. gonorrhoeae genomes directly from clinical urogenital and extragenital specimens.

Methods
One hundred thirteen clinical N. gonorrhoeae-positive APTIMA Combo 2 (AC2) specimens (with 89 linked N. gonorrhoeae isolates) were included. DNA was extracted using QIAsymphony DSP Virus/Pathogen kit. Amplisens multiplex RT–PCR assay (AM-PCR) identified 105 (92.9%) of the AC2 specimens as N. gonorrhoeae positive, which were further examined. Sequence libraries for AC2 specimens were prepared on the Magnis NGS Prep System using the Magnis SureSelectXTHS Reagent kit for Illumina paired-end platforms. Paired-end sequencing was performed on Illumina platforms.

Results
Seventy-four of the 105 (70.5%) AC2 samples remained N. gonorrhoeae positive with a cycle threshold &lt;20 in the AM-PCR and subjected to SureSelectXTHS target enrichment and subsequently Illumina WGS. Seventy-two (97.3%) of all target-enriched specimens were successfully genome-sequenced. All linked AC2 specimens and N. gonorrhoeae isolates from the same anatomical site had identical AMR determinants and molecular epidemiological sequence types.

Conclusions
We show that custom SureSelectXTHS target enrichment automated on the Magnis NGS Prep System, followed by Illumina sequencing, enables culture-independent genome-based surveillance of N. gonorrhoeae AMR and molecular epidemiology. This novel methodological advancement provides an efficient and accurate WGS of N. gonorrhoeae directly from clinical urogenital and extragenital NAAT specimens.
Genetics of recombination rate variation within and between species
Authors: Payseur Bret A 
Published: December 2024

Abstract
Recombination diversifies the genomes of offspring, influences the evolutionary dynamics of populations, and ensures that chromosomes segregate properly during meiosis. Individuals recombine at different rates, but observed levels of variation in recombination rate remain mostly unexplained. Genetic dissection of differences in recombination rate within and between species provides a powerful framework for understanding how this trait evolves. In this Perspective, I amalgamate published findings from genetic studies of variation in the genome-wide number of crossovers within and between species, and I use exploratory analyses to identify preliminary patterns. The narrow-sense heritability of crossover count is consistently low, indicating limited resemblance among relatives and predicting a weak response to short-term selection. Variants associated with crossover number within populations span the range of minor allele frequency (MAF). The size of the additive effect of recombination-associated variants, along with a negative correlation between this effect and MAF, raises the prospect that mutations inducing phenotypic shifts larger than a few crossovers are deleterious, though the contributions of methodological biases to these patterns deserve investigation. Quantitative trait loci that contribute to differences between populations or species alter crossover number in both directions, a pattern inconsistent with selection toward a constant optimum for this trait. Building on this characterization of genetic variation in crossover number within and between species, I describe fruitful avenues for future research. Better integrating recombination rate into quantitative genetics will reveal the balance of evolutionary forces responsible for genetic variation in this trait that shapes inheritance.
A chromosome-level genome of the giant vinegaroon Mastigoproctus giganteus exhibits the signature of pre-Silurian whole genome duplication
Authors: Kulkarni Siddharth S , Klementz Benjamin C , Sharma Prashant P 
Published: December 2024

Abstract
Within the arachnids, chromosome-level genome assemblies have greatly accelerated the understanding of gene family evolution and developmental genomics in key groups, such as spiders (Araneae), mites and ticks (Acariformes and Parasitiformes). Among other poorly studied arachnid orders that lack genome assemblies altogether are members of the clade Pedipalpi, which is comprised of three orders that form the sister group of spiders and diverged over 400 Mya. We close this gap by generating the first chromosome-level assembly from a single specimen of the vinegaroon Mastigoproctus giganteus (Uropygi). We show that this highly complete genome retains plesiomorphic conditions for many gene families that have undergone lineage-specific derivations within the more diverse spiders. Consistent with the phylogenetic position of Uropygi, macrosynteny in the M. giganteus genome substantiates the signature of an ancient whole genome duplication.
Role of radiation emergency medicine: historical view—a perspective on the past, present, and future
Authors: Akashi Makoto 
Published: December 2024

Abstract
The more science progresses, the more life and society change. Medicine also changes with the times and the culture. This is also true for radiation emergency medicine, which includes dose-assessment leading to diagnosis, treatment, medical follow-up and prognosis of persons who have developed acute injury or illness due to radioactive contamination or radiation exposure. Before the report of X-rays by Roentgen, there was evidence that X-rays had been emitted from the electrically excited Crookes tube and that skin injury had been caused by the X-rays. Thus, the history of radiation and its exposure started before Roentgen. During the early stage of radiation use, people were simply exposed to radiation but were unaware of any danger. Radioactive materials were found soon after Roentgen’s report, and contamination with these materials occurred. Together with the development of science and technology, sophisticated radiation devices were produced, and the use and application of radiation became much enhanced. New radionuclides were found one after another, leading to identification of different qualities of radiation. Development of nuclear physics allowed people to artificially produce radionuclides and to construct a nuclear reactor. After World War II, nuclear power plants were constructed, and related facilities such as nuclear fuel processing, reprocessing and spent fuel storage facilities were built. If radiation accidents or events occur at such facilities, radiation exposure with thermal or chemical burns could occur. Together with the expansion of globalism in the world and division in the society, there are now increasing concerns regarding the malicious usage of radiation by radiological dispersal devices (RDDs) including a dirty bomb. Upon detonation of RDDs, blast and thermal injuries with radiation exposure could be caused. In the present society, the natures of exposure to radiation and contamination with radioactive materials have become much more complicated. Not even mentioning the atomic bomb, the detonation of RDDs also necessitates scenarios of medical responses to complicated injuries and the involvement of numbers of people. This article looks back at the history of radiation and addresses the medical responses to radiation injuries that change with the times.
Estimating prevalence of opiate and crack cocaine use and injecting in England using mixed-effects capture–recapture models
Authors: Djennad Abdelmajid , Harris Ross J , Presanis Anne M , Jahr Stefan , Charlett Andre , De Angelis Daniela 
Published: December 2024

Abstract
Multiple social and health problems are associated with opiate and crack cocaine use and injecting, but the prevalence of these behaviours is unknown. We linked three sources of administrative data on individuals engaging in opiate and/or crack cocaine use (OCU) community treatment; arrests, prison, or probation; and drug-related deaths. We used probabilistic linkage to increase the number of matching records and capture-recapture analysis to estimate the unknown number of individuals not observed in any source. We fitted random effects models to data stratified by source, local authority (LA) area, age, sex, drug type, and injecting. Two-way interactions between sources and explanatory variables were included as fixed effects. We included random effects at the LA level, with random intercepts and random coefficients. The total count of opiate and/ or crack cocaine use in the financial year 2018/19 was estimated at 336,531 [95% confidence interval (CI): 311,932-360,845], corresponding to 9.44 (95% CI: 8.75-10.12) per 1,000 population in England. Three-quarters were men, and the estimate of people currently injecting drugs was 67,715 (95% CI: 64,769-70,526). Our study used random effects models to borrow strength across local authorities and produce robust prevalence estimates of OCU for England
Unveiling the virulence mechanism of Leptosphaeria maculans in the Brassica napus interaction: the key role of sirodesmin PL in the induction of cell death
Authors: Pombo Marina A , Rosli Hernan G , Maiale Santiago , Elliott Candace , Stieben Micaela E , Romero Fernando M , Garriz Andrés , Ruiz Oscar A , Idnurm Alexander , Rossi Franco R 
Published: December 2024

Abstract
Leptosphaeria maculans is the causal agent of blackleg disease in Brassica napus, leading to substantial yield losses. Sirodesmin PL, the principal toxin produced by L. maculans, has been implicated in the infection process in plants. However, the precise molecular and physiological mechanisms governing its effects remain elusive. This study investigates the changes induced by sirodesmin PL at the transcriptomic, physiological, and morphological levels in B. napus cotyledons. Sirodesmin PL treatment up-regulated genes associated with plant defense processes, including response to chitin, sulfur compound biosynthesis, toxin metabolism, oxidative stress response, and jasmonic acid/ethylene synthesis and signaling. Validation of these transcriptomic changes is evidenced by several typical defense response processes, such as the accumulation of reactive oxygen species (ROS) and callose deposition. Concomitantly, oxidized sirodesmin PL induced concentration- and exposure duration-dependent cell death. This cellular death is likely to be attributed to diminished activity of PSII and reduced number of chloroplasts per cell. In agreement, a down-regulation of genes associated with the photosynthesis process is observed following sirodesmin PL treatment. Thus, it is plausible that L. maculans exploits sirodesmin PL as a virulence factor to instigate cell death in B. napus during its necrotrophic stage, favoring the infection process.
The homeodomain leucine zipper protein RhHB22 promotes petal senescence by repressing ascorbic acid biosynthesis in rose
Authors: Li Ping , Qiu Yuexuan , Wang Rui , Zhang Bingjie , Ma Yanxing , Sun Xiaoming , Gao Junping , Jiang Yunhe 
Published: December 2024

Abstract
Premature petal senescence dramatically reduces flower quality and value. Ethylene and reactive oxygen species (ROS) are key players in accelerating rose petal senescence, but the molecular mechanism by which ethylene antagonizes ROS scavenging is not well understood. Here, we showed that ethylene reduces ascorbic acid (AsA) production, leading to the accumulation of ROS and hastening petal senescence. Ethylene treatment suppressed the expression of GDP-l-galactose phosphorylase 1 (RhGGP1), encoding the rate-controlling enzyme in AsA biosynthesis. A HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP) II transcription factor, RhHB22, directly bound to the promoter of RhGGP1 and inhibited its transcription. RhHB22 is induced by ethylene, and silencing of RhHB22 increased RhGGP1 expression and AsA production, resulting in reduced H2O2 accumulation and delayed petal senescence. Additionally, the delayed petal senescence symptoms of RhHB22-silenced plants were suppressed by silencing RhGGP1. Moreover, the expression of RhGGP1, which is suppressed by ethylene in wild-type petals, was significantly compromised in RhHB22-silenced petals. These findings uncover the transcriptional regulatory mechanism by which ethylene promotes ROS accumulation and petal senescence by inhibiting AsA biosynthesis, enhance our understanding of ethylene-induced petal senescence, and provide novel insights for improving the longevity of cut flowers.
Use of a small molecule microarray screen to identify inhibitors of the catalytic RNA subunit of Methanobrevibacter smithii RNase P
Authors: Sidharthan Vaishnavi , Sibley Christopher D , Dunne-Dombrink Kara , Yang Mo , Zahurancik Walter J , Balaratnam Sumirtha , Wilburn Damien B , Schneekloth John S , Gopalan Venkat 
Published: December 2024

Abstract
Despite interest in developing therapeutics that leverage binding pockets in structured RNAs—whose dysregulation leads to diseases—such drug discovery efforts are limited. Here, we have used a small molecule microarray (SMM) screen to find inhibitors of a large ribozyme: the Methanobrevibacter smithii RNase P RNA (Msm RPR, ∼300 nt). The ribonucleoprotein form of RNase P, which catalyzes the 5′-maturation of precursor tRNAs, is a suitable drug target as it is essential, structurally diverse across life domains, and present in low copy. From an SMM screen of 7,300 compounds followed by selectivity profiling, we identified 48 hits that bound specifically to the Msm RPR—the catalytic subunit in Msm (archaeal) RNase P. When we tested these hits in precursor-tRNA cleavage assays, we discovered that the drug-like M1, a diaryl-piperidine, inhibits Msm RPR (KI, 17 ± 1 μM) but not a structurally related archaeal RPR, and binds to Msm RPR with a KD(app) of 8 ± 3 μM. Structure–activity relationship analyses performed with synthesized analogs pinpointed groups in M1 that are important for its ability to inhibit Msm RPR. Overall, the SMM method offers prospects for advancing RNA druggability by identifying new privileged scaffolds/chemotypes that bind large, structured RNAs.