bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-restricted feeding improves metabolic syndrome by activating thermogenesis in brown adipose tissue and reducing inflammatory markers
Authors: Gong Yueling , Zhang Honghui , Feng Jiang , Ying Li , Ji Mengmeng , Wei Shiyin , Ma Qiming 
Published: January 2025

BackgroundObesity and metabolic syndrome (MetS) have become increasingly significant global health issues. Time-restricted feeding (TRF), as a novel dietary intervention, has garnered attention in recent years. However, there is limited research focusing on the effects of TRF on energy expenditure and systemic low-grade inflammation. This study aims to investigate the impact of TRF on weight management, glucose metabolism, insulin resistance, and lipid metabolism in male C57BL/6J mice, particularly in the context of metabolic disorders induced by a high-fat diet (HFD).MethodsC57BL/6J mice were divided into two groups: a normal diet (ND) group and a high-fat diet (HFD) group. The study duration was 12 weeks. Key parameters observed included body weight, glucose tolerance (via glucose tolerance tests), insulin resistance (HOMA-IR), and insulin secretion under glucose stimulation. Additionally, liver tissue was subjected to Oil Red O staining to assess lipid accumulation, and white and brown adipose tissues were stained with hematoxylin and eosin (HE) to evaluate adipocyte size. The expression of hepatic lipogenesis-related genes (Srebp-c, Chrebp, Fasn, and Acc1) and thermogenic genes in brown adipose tissue (UCP1 and PGC-1α) were also measured. Furthermore, temperature changes in the interscapular brown adipose tissue (BAT) were monitored.ResultsIn the ND group: TRF improved insulin resistance and reduced circulating levels of the pro-inflammatory cytokine IL-6, with a slight reduction in body weight.In the HFD group: TRF significantly mitigated weight gain, improved glucose tolerance and insulin resistance, and enhanced insulin secretion under glucose stimulation. Additionally, TRF reduced hepatic steatosis by downregulating the expression of lipogenesis-related genes in the liver. TRF also increased thermogenesis by upregulating the expression of thermogenic genes (UCP1 and PGC-1α) in BAT, while lowering serum levels of pro-inflammatory cytokines IL-6 and TNF-α, though IL-1β levels remained unchanged.ConclusionThis study demonstrates that TRF can activate thermogenesis in brown adipose tissue and reduce inflammation maker, leading to an improvement in hepatic steatosis and a reduction in white adipose tissue accumulation. These findings suggest that TRF may be a promising intervention for mitigating metabolic disturbances associated with obesity and metabolic syndrome. The study provides mechanistic insights into the beneficial effects of TRF, highlighting its potential in modulating lipid metabolism and exerting anti-inflammatory effects.
Evaluation of B cell related markers and autoantibodies in rheumatoid arthritis patients treated with abatacept
Authors: Wang Ting , Giltiay Natalia V. , Lood Christian , Wang Ning , Han Bobby Kwanghoon 
Published: January 2025

ObjectivesTo investigate whether biomarkers related to B cell activation and autoantibody production are associated with the response to abatacept in rheumatoid arthritis (RA) patients.MethodsTwenty-five patients with RA were enrolled in this study. Responders (n=10) to abatacept were subjects who achieved ACR50 response at week 24. Serum levels of soluble biomarkers were measured with ProcartaPlex by Luminex or ELISA. Peripheral blood mononuclear cells were isolated and analysed for T cell and B cell subsets by flow cytometry. Patients were genotyped for human leukocyte antigen (HLA)-DRB1 shared epitope (SE) alleles. Baseline levels and longitudinal changes of markers were assessed between responders and nonresponders.ResultsBaseline levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies (p=0.01), IgM rheumatoid factor (RF) (p=0.02), CXC chemokine ligand 13 (CXCL13, p=0.02), sCD23 (p&lt;0.05), as well as frequencies of CD19+CD11c+IgD-CD27- B cells (p=0.04), were higher in responders than nonresponders. Among them, anti-CCP and frequencies of CD19+CD11c+IgD-CD27- B cells were independently associated with response to abatacept. The presence of two alleles of SE was associated with responders (p=0.04). Patients with 2 alleles of SE had higher levels of anti-CCP (p=0.02) and IgM RF (p=0.04) compared to patients with 0 or 1 allele. Further, IgM RF and CXCL13 levels decreased only in responders (p=0.02 and 0.004 respectively, at week 24), while anti-CCP levels did not decrease significantly in either responders or nonresponders.ConclusionMarkers of B cell activation including anti-CCP and frequencies of CD19+CD11c+IgD-CD27- B cells in RA were associated with response to abatacept. IgM RF and CXCL13 decreased only in responders and could be potentially used as pharmacodynamic markers.
Comprehensive single-cell pan-cancer atlas unveils IFI30+ macrophages as key modulators of intra-tumoral immune dynamics
Authors: Jiang Lihe , Wang Peili , Hou Yixuan , Chen Jingying , Li Hua 
Published: January 2025

BackgroundThe convergence of macrophage-targeted strategies with immune checkpoint blockade therapies defines a pivotal avenue in contemporary tumor therapy. Identifying robust genetic regulators in this context is imperative.MethodsThis study elucidates IFI30's role in enhancing Major Histocompatibility Complex II (MHC-II) restriction antigen processing. Despite its recognition in cancer immunotherapy, IFI30 remains a nascent focus. Our approach involves a multi-omics analysis of IFI30 tumor immunological profile in the macrophage-mediated Tumor Microenvironment (TME), spanning various cancers and bolstered by rigorous co-culture laboratory work.ResultsIFI30 predominantly localizes in monocyte/macrophage populations, correlating strongly with immune cell infiltration. Substantiated by single-cell analysis, IFI30 exhibits significant functional enrichment in immune-related pathways. Co-expression with immune-related genes, including MHC elements and immune checkpoints, further validates its relevance.ConclusionOur study positions IFI30 as a promising immunotherapeutic target. Pan-cancer analyses and glioblastoma multiforme (GBM) investigations collectively underscore IFI30's potential as a TME modulator, particularly in its interaction with M2-macrophages. IFI30 emerges as a prospective intervention point in the immunotherapeutic landscape.
Exhaustion of CD8pos central memory regulatory T cell differentiation is involved in renal allograft rejection
Authors: Kälble Florian , Leonhard Jonas , Zeier Martin , Zivanovic Oliver , Schaier Matthias , Steinborn Andrea 
Published: January 2025

BackgroundThe role of regulatory CD8pos T cells (CD8pos Tregs) and cytotoxic CD8pos responder T cells (CD8pos Tresps) in maintaining stable graft function in kidney transplant recipients (KTR) remains largely unclear. The pathogenesis of graft deterioration in case of rejection involves the exhaustive differentiation of both CD8pos T cell subsets, but the causal mechanisms have not yet been identified.MethodsIn this study, we separately investigated the differentiation of CD8posTregs/Tresps in 134 stable KTR with no evidence of renal graft rejection, in 41 KTR diagnosed with biopsy-confirmed rejection at enrolment and in 5 patients who were unremarkable at enrolment, but developed rejection within three years of enrolment. We were investigating whether changed differentiation of CCR7posCD45RAposCD31pos recent thymic emigrant (RTE) cells via CD45RAnegCD31pos memory (CD31pos memory) cells (pathway 1), via direct proliferation (pathway 2), or via CCR7posCD45RA+CD31neg resting mature naïve (MN) cells (pathway 3) into CD45RAnegCD31neg memory (CD31neg memory) cells affects the CD8pos Treg/Tresp ratio or identifies a CD8pos Treg/Tresp subset that predicts or confirms renal allograft rejection.ResultsWe found that RTE Treg differentiation via pathway 1 was age-independently increased in KTR, who developed graft rejection during the follow-up period, leading to abundant MN Treg and central memory Treg (CM Treg) production and favoring a strongly increased CD8pos Treg/Tresp ratio. In KTR with biopsy-confirmed rejection at the time of enrolment, an increased differentiation of RTE Tregs into CCR7negCD45RAposCD31neg terminally differentiated effector memory (CD31neg TEMRA Tregs) and CD31pos memory Tregs was observed. CD31neg memory Treg production was maintained by alternative differentiation of resting MN Tregs, resulting in increased effector memory Treg (EM Treg) production, while the CD8pos Treg/Treg ratio was unaffected. An altered differentiation of CD8pos Tresps was not observed, shifting the Treg/Tresp ratio in favor of Tregs.ConclusionsOur results show that exhaustive CD8pos Treg differentiation into CM Tregs may lead to future rejection, with a shift towards EM Treg production and an accumulation of CD31neg TEMRA Tregs in KTR with current rejection.
Ochratoxin A induces immunotoxicity by targeting Annexin A1 mediated neutrophil apoptosis in zebrafish
Authors: Zheng Yihong , Liu Yinuo , Tian Jin , Liu Shuhong , Ma Gaowei , Xie Yupeng , Zheng Chenhua , Wu Zekai 
Published: January 2025

IntroductionOchratoxin A (OTA) is a toxic secondary metabolite produced by Aspergillus and Penicillium species, posing a significant threat to global food safety. Previous studies have demonstrated the diverse toxic effects of OTA, including hepatotoxicity, nephrotoxicity, and carcinogenicity. However, limited understanding exists regarding its immunotoxicity and the underlying mechanisms, particularly in relation to innate immunity.MethodsZebrafish embryos were exposed to varying concentrations of OTA to assess its impact on embryonic development, innate immune cell formation, and immune response. Transcriptome sequencing analysis was performed to identify changes in gene expression. Additionally, the potential therapeutic effect of aesculetin was evaluated.ResultsOur results demonstrated that exposure to OTA inhibited embryonic development and induced malformations in a concentration-dependent manner. Additionally, OTA exposure led to a significant reduction in the number of neutrophils and macrophages, indicating compromised formation of innate immune cells. Furthermore, OTA exposure hampered the immune response during zebrafish fin regeneration, as evidenced by the diminished migration of neutrophils and macrophages to the wound area. Transcriptome sequencing analysis identified significant up-regulation of the anxa1a and anxa1d-mediated apoptosis signaling pathway in neutrophils following OTA treatment. Notably, administration of aesculetin, known for its anti-apoptosis activity, effectively attenuated the immunotoxic effects induced by OTA.DiscussionThese findings provide valuable insights into the immunotoxicity of OTA while highlight the potential therapeutic strategy using aesculetin for mitigating immune dysfunction caused by OTA.
T-cell immune status in patients with acute exacerbation of chronic obstructive pulmonary disease: a case-control study
Authors: Xiong Xiao-feng , Zhu Min , Wu Hong-xia , Wu Zuo-hong , Fan Li-li , Cheng De-yun 
Published: January 2025

IntroductionImmune inflammatory response plays an important role in chronic obstructive pulmonary disease (COPD). However, the cellular immune status of patients with COPD at different phases is unclear. Herein, we aim to investigate the distribution and functional status of T cell subsets in different phases of COPD (acute exacerbation of COPD [AECOPD] and stable COPD [SCOPD]).MethodsThis is an observational case-control study undertaken in West China Hospital. The distribution of T cell subsets in peripheral blood of AECOPD, SCOPD, and healthy controls (HCs) was measured using multi-color flow cytometry, and the functional status was analyzed by additional staining of activation markers.ResultsA total of 43 HCs, 43 SCOPD patients, and 64 AECOPD patients were evaluated. The total number and percentage of lymphocytes and the CD4+/CD8+ T cells ratio were significantly lower in AECOPD patients when compared to HCs. HLA-DR expression in CD3+, CD4+, CD8+, CD8+ TCR aβ, and CD4+ TCR aβ T cells was upregulated in the AECOPD group. Similarly, the expressions of HLA-DR, CD57, and PD-1 were higher in T cell subsets in the AECOPD group. Compared with the SCOPD and HC groups, the AECOPD had a significantly lower proportion of CD4+CD27+CD28+ T cells, but opposite results were found for CD4+CD27-CD28- T cells. In addition, the proportion of CD4+CD39+ T cells and CD4+CD25+FoxP3+ T cells was significantly higher in the AECOPD and SCOPD groups when compared to the HC group (P &lt; 0.05).DiscussionThe distribution of nearly half the T cell subsets in AECOPD patients was significantly different from that in SCOPD patients and HCs. AECOPD patients may have cellular immune suppression, immune dysfunction, abnormal activation, and higher senescence depletion of T cells.
Prophylactic phage administration provides a time window for delayed treatment of vancomycin-resistant Enterococcus faecalis in a murine bacteremia model
Authors: Wang Wei-Xiao , Yu Jiao-Yang , Chen Xiu-Zhen , Fu Shi-Yong , Li Hui , Yi Peng-Cheng , Ren Yun-Yao , Gu Shuang-Lin , Gao Jing-Han , Fan Jing , Sun Yan-Mei , Feng Jie , Wang Shi-Wei , Chen Wei 
Published: January 2025

IntroductionVancomycin-resistant Enterococcus faecalis (VRE) poses a significant challenge in clinical settings due to its resistance to multiple antibiotics. Phage therapy offers a promising alternative to address this resistance crisis. However, critical gaps remain regarding optimal dosing, therapeutic design, and treatment timing for phage therapy targeting VRE-induced bacteremia.MethodsThe biological and genomic characteristics of a novel lytic phage specific to VRE were investigated. Its in vitro bactericidal and antibiofilm activities were evaluated, along with its synergy with antimicrobial agents. In vitro safety and protective efficacy were assessed using a mouse bacteremia model. The impact of phage therapy on gut microbiota was examined through 16S rDNA gene sequencing.ResultsWe isolated and characterized a novel lytic phage, vB_EfaS-1017, specific to vancomycin-resistant E. faecalis. This phage features a circular, double-stranded DNA genome (40,766 bp), sharing 91.19% identity and 79% coverage with Enterococcus phage vB_EfaS_SRH2. vB_EfaS-1017 exhibited robust bactericidal and antibiofilm activity in vitro and demonstrated synergy with levofloxacin. Safety assessments confirmed its non-toxicity to mammalian cells and lack of hemolytic activity. In a mouse bacteremia model, phage treatment alone rescued 60% of infected mice, while combining phage with levofloxacin increased survival to 80%. Prophylactic administration of phage 24 hours prior to infection failed to prevent mortality. However, a combination of prophylactic phage administration and delayed treatment rescued 60% of mice, compared to 100% mortality in the delayed treatment alone group. Additionally, phage therapy helped maintain or restore gut microbiota balance.DiscussionThese findings underscore the potential of phage-antibiotic combinations as a superior therapeutic strategy against VRE infections. The observed synergy between phages and antibiotics highlights a promising approach to overcoming bacterial resistance and improving clinical outcomes. Furthermore, prophylactic phage administration may provide a critical time window for effective delayed treatment. Further preclinical research is essential to refine phage therapy protocols for clinical application.
Systematic review of multidrug-resistant Klebsiella pneumoniae in the Arabian Peninsula: molecular epidemiology and resistance patterns
Authors: Idrees Enaam K. , Aldriwesh Marwh G. , Alkhulaifi Manal M. , Alghoribi Majed F. 
Published: January 2025

BackgroundThe rapid emergence of multidrug-resistant Klebsiella pneumoniae (MDR K. pneumoniae) is a major public health and economic burden worldwide. Various resistance mechanisms complicate treatment, leading to increased morbidity and mortality. Despite numerous studies conducted in Gulf Health Council (GHC) countries, the molecular epidemiology of MDR K. pneumoniae remains not clearly defined. This systematic review aims to analyze the emergence of antimicrobial resistance genes in MDR K. pneumoniae across GHC countries.MethodsA systematic search was conducted using PubMed, ScienceDirect, and OpenMD for articles published up to March 15, 2023. The search strategy focused on the bacterial name, drug-resistance genotypes, and GHC countries. The review followed PRISMA guidelines, with two independent reviewers assessing the risk of bias using NIH Study Quality Assessment tools.ResultsThe primary search yielded 1,663 studies, of which 67 met the inclusion criteria. Saudi Arabia contributed the most studies, with 41 (61.1%), followed by Kuwait with 7 (10.4%), and the UAE with 6 (9%) studies. Oman and Qatar each contributed 4 studies (6%), and Bahrain contributed three studies (4.5%). The remaining 4 studies (4.4%) were from multiple GHC countries. The studies exhibited considerable heterogeneity in detection methods, target genes, and resistance mechanisms. Notably, only one environmental study was conducted in the UAE, and one community-based study in Kuwait, while the remaining studies focused on clinical samples. Various resistance mechanisms and patterns were observed between countries and across different years within the same country. The review highlighted the widespread prevalence of ESBL genes, particularly blaTEM and blaCTX-M-15, and the emergence of carbapenemase genes such as blaOXA-48 and blaNDM-1 and blaKPC-2. Additionally, colistin resistance through the mcr-1 gene and mgrB mutations was reported in Saudi Arabia and the UAE, posing a significant public health challenge.ConclusionData from GHC countries shows significant gaps, particularly in community and environmental and molecular epidemiology studies. Limited molecular and genome-based investigations hinder comprehensive AMR surveillance. Implementing standardized methodologies and fostering molecular and genome-based AMR surveillance programs at both national and regional levels within the GHC are essential for effectively combating the spread of MDR K. pneumoniae and improving public health outcomes in the region.
Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis
Authors: Yun Jin-Seung , Shin Eunkyung , Lee Young-Ran , Lee Jung-Ah , Lee Hyeokjin , Kim Jong-Seok , Shin Sung Jae , Ha Sang-Jun , Lee Sang-Won , Kim Dokeun , Yoo Jung-Sik , Jeong Hye-Sook 
Published: January 2025

IntroductionThe inadequate efficacy of the Bacillus Calmette–Guérin (BCG) vaccine against adult pulmonary tuberculosis (TB) necessitates the development of new and effective vaccines. Human adenovirus serotype 5 (Ad5), which induces T-cell response, is a widely used viral vector. In this study, we aimed to evaluate the efficacy of a multi-antigenic recombinant Ad5 vectored vaccine and determine the optimal immunization route for enhanced immune response against Mycobacterium tuberculosis.MethodsWe constructed a multi-antigenic recombinant Ad5 vectored vaccine expressing four antigens (Ag85B-ESAT6-MPT64-Rv2660c) of M. tuberculosis (rAd-TB4), immunized with rAd-TB4 (5 × 107 infectious virus units/mouse) twice at an interval of 4 weeks starting at 10 weeks after BCG priming, and evaluated its boosting efficacy in a BCG-primed mouse model, and determined the optimal immunization route.ResultsCompared with the BCG-only (2 × 105 colony forming units/mouse), subcutaneous injection of rAd-TB4 (1 × 107 infectious virus units/mL; two doses) elicited a T-cell response and cytokine production in lung lymphocytes and splenocytes. rAd-TB4 immunization significantly reduced bacterial loads and inflamed lung areas compared to BCG immunization (p &lt; 0.01) and protected against the H37Rv challenge performed at 17 weeks of BCG priming. RNA sequencing of the whole blood of rAd-TB4-vaccinated mice collected pre- and, 1 and 4 weeks post-infection, identified differentially expressed genes associated with immune and inflammatory responses, especially those in the Wnt signaling pathway.ConclusionOur results indicate that rAd-TB4 immunization enhances the immune response to the vaccine boosting antigens in BCG-primed mice, making it a potential adult pulmonary TB vaccine candidate.
NavBLIP: a visual-language model for enhancing unmanned aerial vehicles navigation and object detection
Authors: Li Ye , Yang Li , Yang Meifang , Yan Fei , Liu Tonghua , Guo Chensi , Chen Rufeng 
Published: January 2025

IntroductionIn recent years, Unmanned Aerial Vehicles (UAVs) have increasingly been deployed in various applications such as autonomous navigation, surveillance, and object detection. Traditional methods for UAV navigation and object detection have often relied on either handcrafted features or unimodal deep learning approaches. While these methods have seen some success, they frequently encounter limitations in dynamic environments, where robustness and computational efficiency become critical for real-time performance. Additionally, these methods often fail to effectively integrate multimodal inputs, which restricts their adaptability and generalization capabilities when facing complex and diverse scenarios.MethodsTo address these challenges, we introduce NavBLIP, a novel visual-language model specifically designed to enhance UAV navigation and object detection by utilizing multimodal data. NavBLIP incorporates transfer learning techniques along with a Nuisance-Invariant Multimodal Feature Extraction (NIMFE) module. The NIMFE module plays a key role in disentangling relevant features from intricate visual and environmental inputs, allowing UAVs to swiftly adapt to new environments and improve object detection accuracy. Furthermore, NavBLIP employs a multimodal control strategy that dynamically selects context-specific features to optimize real-time performance, ensuring efficiency in high-stakes operations.Results and discussionExtensive experiments on benchmark datasets such as RefCOCO, CC12M, and Openlmages reveal that NavBLIP outperforms existing state-of-the-art models in terms of accuracy, recall, and computational efficiency. Additionally, our ablation study emphasizes the significance of the NIMFE and transfer learning components in boosting the model's performance, underscoring NavBLIP's potential for real-time UAV applications where adaptability and computational efficiency are paramount.