bluuebunny/crossref_metadata_2025_split huggingface dataset:
A BSL-2 compliant mouse model of SARS-CoV-2 infection for efficient and convenient antiviral evaluation
Authors: Chen Zinuo , Cui Qinghua , Ran Yan , Achi Jazmin Galvan , Chen Zhaoyu , Rong Lijun , Du Ruikun 
Published: June 2024

ABSTRACT

Animal models of authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require operation in biosafety level 3 (BSL-3) containment. In the present study, we established a mouse model employing a single-cycle infectious virus replicon particle (VRP) system of SARS-CoV-2 that can be safely handled in BSL-2 laboratories. The VRP [ΔS-VRP(G)-Luc] contains a SARS-CoV-2 genome in which the spike gene was replaced by a firefly luciferase (Fluc) reporter gene (Rep-Luci), and incorporates the vesicular stomatitis virus glycoprotein on the surface. Intranasal inoculation of ΔS-VRP(G)-Luc can successfully transduce the Rep-Luci genome into mouse lungs, initiating self-replication of Rep-Luci and, accordingly, inducing acute lung injury mimicking the authentic SARS-CoV-2 pathology. In addition, the reporter Fluc expression can be monitored using a bioluminescence imaging approach, allowing a rapid and convenient determination of viral replication in ΔS-VRP(G)-Luc-infected mouse lungs. Upon treatment with an approved anti-SARS-CoV-2 drug, VV116, the viral replication in infected mouse lungs was significantly reduced, suggesting that the animal model is feasible for antiviral evaluation. In summary, we have developed a BSL-2-compliant mouse model of SARS-CoV-2 infection, providing an advanced approach to study aspects of the viral pathogenesis, viral-host interactions, as well as the efficacy of antiviral therapeutics in the future.

IMPORTANCE
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and pathogenic in humans; thus, research on authentic SARS-CoV-2 has been restricted to biosafety level 3 (BSL-3) laboratories. However, due to the scarcity of BSL-3 facilities and trained personnel, the participation of a broad scientific community in SARS-CoV-2 research had been greatly limited, hindering the advancement of our understanding on the basic virology as well as the urgently necessitated drug development. Previously, our colleagues Jin et al. had generated a SARS-CoV-2 replicon by replacing the essential spike gene in the viral genome with a Fluc reporter (Rep-Luci), which can be safely operated under BSL-2 conditions. By incorporating the Rep-Luci into viral replicon particles carrying vesicular stomatitis virus glycoprotein on their surface, and via intranasal inoculation, we successfully transduced the Rep-Luci into mouse lungs, developing a mouse model mimicking SARS-CoV-2 infection. Our model can serve as a useful platform for SARS-CoV-2 pathological studies and antiviral evaluation under BSL2 containment.
Alterations in gut microbiota and inflammatory cytokines after administration of antibiotics in mice
Authors: Gao Wang , Liu Xingyu , Zhang Shuobo , Wang Jingxia , Qiu Bo , Shao Junhua , Huang Weixin , Huang Yilun , Yao Mingfei , Tang Ling-Ling 
Published: June 2024

ABSTRACT

Antibiotics are widely used to treat bacterial infection and reduce the mortality rate, while antibiotic overuse can cause gut microbiota dysbiosis. The impact of antibiotics on gut microbiota is not fully understood. In our study, four commonly used antibiotics (ceftazidime, cefoperazone-sulbactam, imipenem-cilastatin, and moxifloxacin) were given subcutaneously to mice, and their impacts on the gut microbiota composition and serum cytokine levels were evaluated through 16S rRNA analysis and a multiplex immunoassay. Antibiotic treatment markedly reduced gut microbiota diversity and changed gut microbiota composition. Antibiotic treatment significantly increased and decreased the abundance of Firmicutes and Bacteroidota, respectively. The antibiotic treatments increased the abundance of opportunistic pathogens such as
Enterococcus
and decreased that of
Lachnospiraceae
and
Muribaculaceae
. For moxifloxacin, the significantly high abundance of
Enterococcus
and
Klebsiella
was observed after 14 and 21 days of treatment. However, a relatively low abundance of opportunistic pathogens was found after 14 days of imipenem-cilastatin treatment. Additionally, the serum levels of various pro-inflammatory cytokines, such as IL-1β, IL-12 (p70), and IL-17, significantly increased after 21 days of antibiotic treatments. Overall, these results provide a guide for rational use of antibiotics in clinical settings: short-term use of moxifloxacin is recommended with regard to gut microbiota health, and the 14-day use of imipenem-cilastatin may have a less severe impact than other antibiotics.

IMPORTANCE
Antibiotic treatments are directly associated with changes in gut microbiota and are effective against both pathogens and beneficial bacteria. Gut microbiota dysbiosis induced by antibiotic treatment could increase the risk of some diseases. Therefore, an adequate understanding of gut microbiota changes after antibiotic use is crucial. In this study, we investigated the effects of continuous treatment with antibiotics on gut microbiota, serum cytokines, and intestinal inflammatory response. Our results suggest that short-term use of moxifloxacin is recommended, and the 14-day use of imipenem-cilastatin may have a less severe effect on gut microbiota health than cefoperazone-sulbactam. These results provide useful guidance on the rational use of antibiotics with regard to gut microbiota health.
Exploring the economic toxicity experiences and coping styles of patients with colorectal cancer fistula in Jiangsu province, China: a qualitative study
Authors: Zhao Weijing , Xu Qin , Zhou Xia , Liu Chunmei , Ding Lingyu 
Published: June 2024

ObjectivesIn recent years, economic toxicity has significantly affected the physical and mental health as well as the quality of life of patients with colorectal cancer. However, this issue has not garnered adequate attention from healthcare professionals. This study aims to investigate the experiences of economic toxicity and coping strategies among patients with colorectal cancer fistula. The findings are intended to inform the development of suitable and effective intervention programmes to address economic toxicity within this patient population.DesignA descriptive phenomenological approach was employed in this qualitative research, using a semistructured method for data collection and analysis of interview data. Traditional content analysis methods were applied, encompassing coding, categorisation and theme distillation. Data analysis continued until thematic saturation was achieved, with no new themes emerging.SettingNanjing Medical University Lianyungang Clinical Medical College.ParticipantsA total of 21 patients with colorectal cancer fistula were selected as interview subjects through purposive sampling. The selection took place from May 2022 to May 2023, involving patients during their stay at a tertiary hospital in Lianyungang city, Jiangsu province, China.ResultsIn total, three pieces and eight subthemes were distilled: subjective feelings (worries about treatment costs, concerns about uncertainty about the future, worries about daily life), coping styles (coping alone, unwillingness to help, prepurchased insurance, dealing with illness, giving up treatment, inability to afford costs) and needs and aspirations (need for health policies, need for social support).ConclusionsPatients with colorectal cancer fistulae experience economic toxicity, leading to significant impairment in both physical and mental health. Despite employing various coping strategies, healthcare professionals must prioritise addressing the economic toxicity issue in patients. Implementing rational and effective interventions can greatly assist patients in effectively managing economic toxicity.
Cohort profile: the ‘Biomarkers of heterogeneity in type 1 diabetes’ study—a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands
Authors: Aanstoot Henk-Jan , Varkevisser Rita D M , Mul Dick , Dekker Pim , Birnie Erwin , Boesten Lianne S M , Brugts Michael P , van Dijk Peter R , Duijvestijn Petronella H L M , Dutta Sanjoy , Fransman Christine , Gonera Rob K , Hoogenberg Klaas , Kooy Adriaan , Latres Esther , Loves Sandra , Nefs Giesje , Sas Theo , Vollenbrock Charlotte E , Vosjan-Noeverman Marleen J , de Vries-Velraeds Martine M C , Veeze Henk J , Wolffenbuttel Bruce H R , van der Klauw Melanie M 
Published: June 2024

PurposeThe ‘Biomarkers of heterogeneity in type 1 diabetes’ study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D).ParticipantsData and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected.Findings to dateStimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia.Future plansResearch groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function.Trial registration numberNCT04977635.
Defoliation level interacts with tree species and soil richness to determine volume increment reduction and recovery from simulated spruce budworm attack
Authors: MacLean David A. , Collier Joe , MacKinnon Wayne E. , Porter Kevin B. 
Published: June 2024

Defoliation and tree species determine growth during spruce budworm outbreaks, with site showing inconsistent effects. We determined effects of artificial defoliation treatments (0%, 50%, 100%, 100%+bud) for 3 years on volume increment of 240 balsam fir, black spruce, and white spruce trees, initially 7–10 years old and 2.3–4.1 m tall, on four soil drainage/richness classes. Current annual increment was significantly affected by species × site and site × defoliation interactions, with DBH as covariate. Specific volume increment (SVI) was significantly affected by a species × site × defoliation treatment interaction. Combining species and sites, volume reductions after 3 years were 21%–28%, 43%–51%, and 55%–66% for 50% defoliation, 100% defoliation, and 100%+bud. SVI was negatively, linearly related to cumulative defoliation. Marginal r2 and conditional r2 showed that 64% of variance of SVI was explained by site, species, cumulative defoliation, and DBH, but 90% was explained by fixed and random variables. After 3 years of defoliation, SVI of white spruce was 21%–23% greater than balsam fir and black spruce, and SVI on rich was 55%–79% greater than on poor sites. Cumulative defoliation was a good predictor of growth, and soil richness had a stronger effect on growth after defoliation than in previous studies.
The acute effects of dietary nitrate supplementation on postmenopausal endothelial resistance to ischemia reperfusion injury: a randomized, placebo-controlled, double blind, crossover clinical trial
Authors: Delgado Spicuzza Jocelyn M. , Gosalia Jigar , Studinski Matthew , Armando Chenée , Alipour Elmira , Kim-Shapiro Daniel B. , Flanagan Michael , Somani Yasina B. , Proctor David N. 
Published: June 2024

Postmenopausal cardiovascular health is a critical determinant of longevity. Consumption of beetroot juice (BR) and other nitrate-rich foods is a safe, effective non-pharmaceutical intervention to increase systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate (NO3 −)–nitrite (NO2 −)–nitric oxide (NO) pathway. We hypothesized that a single dose of nitrate-rich beetroot juice (BRnitrate 600 mg NO3 −/140 mL, BRplacebo ∼ 0 mg/140 mL) would improve resting endothelial function and resistance to ischemia–reperfusion (IR) injury to a greater extent in early-postmenopausal (1–6 years following their final menstrual period (FMP), n = 12) compared to late-postmenopausal (6+ years after FMP, n = 12) women. Analyses with general linear models revealed a significant ( p < 0.05) time*treatment interaction effect for brachial artery adjusted flow-mediated dilation (FMD). Pairwise comparisons revealed that adjusted FMD was significantly lower following IR-injury in comparison to all other time points with BRplacebo (early FMD 2.51 ± 1.18%, late FMD 1.30 ± 1.10, p < 0.001) and was lower than post-IR with BRnitrate (early FMD 3.84 ± 1.21%, late FMD 3.21 ± 1.13%, p = 0.014). A single dose of BRnitrate significantly increased resting macrovascular function in the late postmenopausal group only ( p = 0.005). Considering the postmenopausal stage-dependent variations in endothelial responsiveness to dietary nitrate, we predict differing mechanisms underpin macrovascular protection against IR injury.
Ab initio description of monopole resonances in light- and medium-mass nuclei
Authors: Porro A. , Duguet T. , Ebran J.-P. , Frosini M. , Roth R. , Somà V. 
Published: June 2024

AbstractGiant resonances (GRs) are a striking manifestation of collective motions in atomic nuclei. The present paper is the second in a series of four dedicated to the use of the projected generator coordinate method (PGCM) for the ab initio determination of the isoscalar giant monopole resonance (GMR) in closed- and open-shell mid-mass nuclei. While the first paper was dedicated to quantifying various uncertainty sources, the present paper focuses on the first applications to three doubly-open shell nuclei, namely $$^{46}\hbox {Ti}$$

46

Ti

, $$^{28}\hbox {Si}$$

28

Si

and $$^{24}\hbox {Mg}$$

24

Mg

. In particular, the goal is to investigate, starting from chiral effective field theory nuclear interactions, (i) the coupling of the GMR with the giant quadrupole resonance (GQR) in intrinsically-deformed nuclei, (ii) the possible impact of shape coexistence and shape mixing on the GMR, (iii) the GMR based on shape isomers and (iv) the impact of anharmonic effects on the monopole response. The latter is studied by comparing PGCM results to those obtained via the quasi-particle random phase approximation (QRPA), the traditional many-body approach to giant resonances, performed in a consistent setting. Eventually, PGCM results for sd-shell nuclei are in good agreement with experimental data, which is attributed to the capacity of the PGCM to capture the important fragmentation of the monopole response in light, intrinsically-deformed systems. Still, the comparison to data in $$^{28}\hbox {Si}$$

28

Si

and $$^{24}\hbox {Mg}$$

24

Mg

illustrates the challenge (and the potential benefit) of extracting unambiguous experimental information.
RUVBL1/2 Blockade Targets YTHDF1 Activity to Suppress m6A-Dependent Oncogenic Translation and Colorectal Tumorigenesis
Authors: Chen Danyu , Ji Fenfen , Zhou Qiming , Cheung Henley , Pan Yasi , Lau Harry C.-H. , Liang Cong , Yang Zhenjie , Huang Pingmei , Wei Qinyao , Cheung Alvin H.-K. , Kang Wei , Chen Huarong , Yu Jun , Wong Chi Chun 
Published: June 2024

Abstract
The N6-methyladenosine (m6A) RNA-binding protein YTHDF1 is frequently overexpressed in colorectal cancer and drives chemotherapeutic resistance. To systematically identify druggable targets in colorectal cancer with high expression of YTHDF1, this study used a CRISPR/Cas9 screening strategy that revealed RUVBL1 and RUVBL2 as putative targets. RUVBL1/2 were overexpressed in primary colorectal cancer samples and represented independent predictors of poor patient prognosis. Functionally, loss of RUVBL1/2 preferentially impaired the growth of YTHDF1-high colorectal cancer cells, patient-derived primary colorectal cancer organoids, and subcutaneous xenografts. Mechanistically, YTHFD1 and RUVBL1/2 formed a positive feedforward circuit to accelerate oncogenic translation. YTHDF1 bound to m6A-modified RUVBL1/2 mRNA to promote translation initiation and protein expression. Coimmunoprecipitation and mass spectrometry identified that RUVBL1/2 reciprocally interacted with YTHDF1 at 40S translation initiation complexes. Consequently, RUVBL1/2 depletion stalled YTHDF1-driven oncogenic translation and nascent protein biosynthesis, leading to proliferative arrest and apoptosis. Ribosome sequencing revealed that RUVBL1/2 loss impaired the activation of MAPK, RAS, and PI3K-AKT signaling induced by YTHDF1. Finally, the blockade of RUVBL1/2 by the pharmacological inhibitor CB6644 or vesicle-like nanoparticle-encapsulated siRNAs preferentially arrested the growth of YTHDF1-expressing colorectal cancer in vitro and in vivo. Our findings show that RUVBL1/2 are potential prognostic markers and druggable targets that regulate protein translation in YTHDF1-high colorectal cancer.
Significance: RUVBL1/2 inhibition is a therapeutic strategy to abrogate YTHDF1-driven oncogenic translation and overcome m6A dysregulation in colorectal cancer.
Proteomic Profiling of Serum Extracellular Vesicles Identifies Diagnostic Signatures and Therapeutic Targets in Breast Cancer
Authors: Xu Ganfei , Huang Rui , Wumaier Reziya , Lyu Jiacheng , Huang Minjing , Zhang Yaya , Chen Qingjian , Liu Wenting , Tao Mengyu , Li Junjian , Tao Zhonghua , Yu Bo , Xu Erxiang , Wang Lingfeng , Yu Guoying , Gires Olivier , Zhou Lei , Zhu Wei , Ding Chen , Wang Hongxia 
Published: June 2024

Abstract
Analysis of extracellular vesicles (EV) is a promising noninvasive liquid biopsy approach for breast cancer detection, prognosis, and therapeutic monitoring. A comprehensive understanding of the characteristics and proteomic composition of breast cancer–specific EVs from human samples is required to realize the potential of this strategy. In this study, we applied a mass spectrometry–based, data-independent acquisition proteomic approach to characterize human serum EVs derived from patients with breast cancer (n = 126) and healthy donors (n = 70) in a discovery cohort and validated the findings in five independent cohorts. Examination of the EV proteomes enabled the construction of specific EV protein classifiers for diagnosing breast cancer and distinguishing patients with metastatic disease. Of note, TALDO1 was found to be an EV biomarker of distant metastasis of breast cancer. In vitro and in vivo analysis confirmed the role of TALDO1 in stimulating breast cancer invasion and metastasis. Finally, high-throughput molecular docking and virtual screening of a library consisting of 271,380 small molecules identified a potent TALDO1 allosteric inhibitor, AO-022, which could inhibit breast cancer migration in vitro and tumor progression in vivo. Together, this work elucidates the proteomic alterations in the serum EVs of breast cancer patients to guide the development of improved diagnosis, monitoring, and treatment strategies.
Significance: Characterization of the proteomic composition of circulating extracellar vesicles in breast cancer patients identifies signatures for diagnosing primary and metastatic tumors and reveals tumor-promoting cargo that can be targeted to improve outcomes.
Identification of Therapy-Induced Clonal Evolution and Resistance Pathways in Minimal Residual Clones in Multiple Myeloma through Single-Cell Sequencing
Authors: Cui Jian , Li Xiaoyun , Deng Shuhui , Du Chenxing , Fan Huishou , Yan Wenqiang , Xu Jingyu , Li Xiaoqing , Yu Tengteng , Zhang Shuaishuai , Lv Rui , Sui Weiwei , Hao Mu , Du Xin , Xu Yan , Yi Shuhua , Zou Dehui , Cheng Tao , Qiu Lugui , Gao Xin , An Gang 
Published: June 2024

Abstract

Purpose:
In multiple myeloma (MM), therapy-induced clonal evolution is associated with treatment resistance and is one of the most important hindrances toward a cure for MM. To further understand the molecular mechanisms controlling the clonal evolution of MM, we applied single-cell RNA sequencing (scRNA-seq) to paired diagnostic and posttreatment bone marrow (BM) samples.

Experimental Design:
scRNA-seq was performed on 38 BM samples from patients with monoclonal gammopathy of undetermined significance (n = 1), MM patients at diagnosis (n = 19), MM posttreatment (n = 17), and one healthy donor (HD). The single-cell transcriptome data of malignant plasma cells (PC) and the surrounding immune microenvironment were analyzed.

Results:
Profiling by scRNA-seq data revealed three primary trajectories of transcriptional evolution after treatment: clonal elimination in patients with undetectable minimal residual disease (MRD−) and clonal stabilization and clonal selection in detectable MRD (MRD+) patients. We noted a metabolic shift toward fatty acid oxidation in cycling-resistant PCs, whereas selective PCs favored the NF-κB pathway. Intriguingly, when comparing the genetic and transcriptional dynamics, we found a significant correlation between genetic and nongenetic factors in driving the clonal evolution. Furthermore, we identified variations in cellular interactions between malignant PCs and the tumor microenvironment. Selective PCs showed the most robust cellular interactions with the tumor microenvironment.

Conclusions:
These data suggest that MM cells could rapidly adapt to induction treatment through transcriptional adaptation, metabolic adaptation, and specialized immune evasion. Targeting therapy-induced resistance mechanisms may help to avert refractory disease in MM.