bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chestnut tannin extract modulates growth performance and fatty acid composition in finishing Tan lambs by regulating blood antioxidant capacity, rumen fermentation, and biohydrogenation
Authors: Gao Changpeng , Qi Mingjiang , Zhou Yuxiang 
Published: January 2024

AbstractTannins as plant extracts have emerged as promising and potential alternatives for antibiotics in modern livestock cultivation systems. This study investigates the effect of dietary chestnut tannin extract (CTE) in finishing Tan lambs. Twenty-seven male Tan lambs were randomly divided into three groups: (1) control group (CON; basal diet); (2) low-dose CTE group (LCTE; basal diet + 2 g/kg CTE, dry matter [DM] basis); (3) high-dose CTE group (HCTE; basal diet + 4 g/kg CTE, DM basis). The HCTE group exhibited markedly higher average daily gain (ADG) and DM intake than CON (P < 0.01). The ruminal total volatile fatty acid concentration increased linearly with increasing CTE supplementation (P < 0.01), while the opposite trend was observed for butyrate molar proportion (P < 0.01). Upon increasing CTE dosage, plasma glucose, high-density lipoprotein cholesterol, glutathione peroxidase, and superoxide dismutase content increased linearly (P < 0.05), whereas low-density lipoprotein cholesterol and urea nitrogen decreased linearly or quadratically (P < 0.05), respectively. A linear increase was also observed in ruminal t6 C18:1 and t9, c12 C18:2 proportions (P < 0.01), and plasma C18:2n-6 and n-6 polyunsaturated fatty acids proportions with increased CTE supplementation (P < 0.01). In the longissimus dorsi muscle, the atherogenic index decreased linearly (P < 0.05), while c11 C18:1 and C20:5n-3 increased linearly (P < 0.05). Moreover, c9, t11 conjugated linoleic acids proportion increased in subcutaneous fat with CTE supplementation (P < 0.01). In conclusion, Dietary CTE enhances the ADG of finishing Tan lambs in a dose-dependent manner, modulates plasma metabolites and antioxidant capacity, and improves rumen fermentation and body fatty acid composition. These results provide a reference for the rational application of CTE in ruminant production.
Identification of a new gene signature for prognostic evaluation in cervical cancer: based on cuproptosis-associated angiogenesis and multi-omics analysis
Authors: Kang Jiawen , Jiang Jingwen , Xiang Xiaoqing , Zhang Yong , Tang Jie , Li Lesai 
Published: January 2024

AbstractPatients with recurrent or metastatic cervical cancer are in urgent need of novel prognosis assessment or treatment approaches. In this study, a novel prognostic gene signature was discovered by utilizing cuproptosis-related angiogenesis (CuRA) gene scores obtained through weighted gene co-expression network analysis (WGCNA) of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. To enhance its reliability, the gene signature was refined by integrating supplementary clinical variables and subjected to cross-validation. Meanwhile, the activation of the VEGF pathway was inferred from an analysis of cell-to-cell communication, based on the expression of ligands and receptors in cell transcriptomic datasets. High-CuRA patients had less infiltration of CD8 + T cells and reduced expression of most of immune checkpoint genes, which indicated greater difficulty in immunotherapy. Lower IC50 values of imatinib, pazopanib, and sorafenib in the high-CuRA group revealed the potential value of these drugs. Finally, we verified an independent prognostic gene SFT2D1 was highly expressed in cervical cancer and positively correlated with the microvascular density. Knockdown of SFT2D1 significantly inhibited ability of the proliferation, migration, and invasive in cervical cancer cells. CuRA gene signature provided valuable insights into the prediction of prognosis and immune microenvironment of cervical cancer, which could help develop new strategies for individualized precision therapy for cervical cancer patients.
DNA mismatch repair system regulates the expression of PD-L1 through DNMTs in cervical cancer
Authors: Guo Fan , Lu Ruijiao , Kong Weina , Anwar Miyessar , Feng Yangchun 
Published: January 2024

Abstract
Background
Cervical cancer (CC) is a potential clinical application of PD-1/PD-L1 inhibitor. We aimed to study the mechanism of DNA mismatch repair (MMR) system regulating the expression of PD-L1 in CC through DNA methyltransferase (DNMTs).

Methods
We collected pathological specimens from 118 cases of CC to analyze the relationship between PD-L1 expression and DNMTs in different MMR states. RNA interference (RNAi) technique was used to simulate the formation of CC cell line with MMR deficiency (dMMR) state, and subcutaneous tumor formation experiment was carried out in nude mice to verify the relationship between PD-L1 expression and DNMTs in MMR state.

Results
The PD-L1 positive rate in 118 cases of CC was 58.47%, while the microsatellite instability (MSI) status accounted for 5.93%. There was a significant difference in the expression of PD-L1 between patients within the dMMR and MMR proficient (pMMR) groups (χ2 = 21.405, P < 0.001). Subcutaneous inoculation after infection of Siha cells led to successful tumorigenesis in nude mice, accompanied by a significant increase in the level of PD-L1 expression in the mouse tumors, while the expression level of MLH1 and MSH2 protein decreased significantly. We also found that PD-L1 expression was closely related to the expression of DNMTs.

Conclusion
PD-L1 is universal expressed on the surface of CC cells, dMMR status enhances the expression of PD-L1 on the surface of CC cells, dMMR states of CC are related to the demethylation status of the PD-L1 gene promoter region.
Advancement in nanomaterials for environmental pollutants remediation: a systematic review on bibliometrics analysis, material types, synthesis pathways, and related mechanisms
Authors: Asghar Nosheen , Hussain Alamdar , Nguyen Duc Anh , Ali Salar , Hussain Ishtiaque , Junejo Aurangzeb , Ali Attarad 
Published: January 2024

AbstractEnvironmental pollution is a major issue that requires effective solutions. Nanomaterials (NMs) have emerged as promising candidates for pollution remediation due to their unique properties. This review paper provides a systematic analysis of the potential of NMs for environmental pollution remediation compared to conventional techniques. It elaborates on several aspects, including conventional and advanced techniques for removing pollutants, classification of NMs (organic, inorganic, and composite base). The efficiency of NMs in remediation of pollutants depends on their dispersion and retention, with each type of NM having different advantages and disadvantages. Various synthesis pathways for NMs, including traditional synthesis (chemical and physical) and biological synthesis pathways, mechanisms of reaction for pollutants removal using NMs, such as adsorption, filtration, disinfection, photocatalysis, and oxidation, also are evaluated. Additionally, this review presents suggestions for future investigation strategies to improve the efficacy of NMs in environmental remediation. The research so far provides strong evidence that NMs could effectively remove contaminants and may be valuable assets for various industrial purposes. However, further research and development are necessary to fully realize this potential, such as exploring new synthesis pathways and improving the dispersion and retention of NMs in the environment. Furthermore, there is a need to compare the efficacy of different types of NMs for remediating specific pollutants. Overall, this review highlights the immense potential of NMs for mitigating environmental pollutants and calls for more research in this direction.
Graphical Abstract
Claudin-18.2 mediated interaction of gastric Cancer cells and Cancer-associated fibroblasts drives tumor progression
Authors: Liu Shengde , Zhang Zizhen , Jiang Lei , Zhang Miao , Zhang Cheng , Shen Lin 
Published: January 2024

Abstract
Background
Claudin-18.2 (CLDN18.2) has emerged as an alluring therapeutic target against gastrointestinal tumors in recent years. However, a thorough understanding of its regulatory mechanism in gastric cancer remains elusive.

Methods
We presented a comprehensive study comprising 185 gastric cancer patients, which included 112 cases with high CLDN18.2 expression and 73 cases with low CLDN18.2 expression as determined by immunohistochemistry. After overdressed CLDN18.2 in AGS and NUGC4 cell lines, we elucidated the functions of CLDN18.2 in connecting gastric cancer cells and cancer-associated fibroblasts (CAFs) through an in vitro adhesion models and in vivo lung colonization models. The molecular mechanism underlying CLDN18.2-mediated interaction between gastric cancer cells and CAFs was identified through RNA sequencing and protein-proximity labeling techniques in vivo.

Results
In our own cohort, a correlation was observed between high levels of CLDN18.2 expression and advanced cancer stage, poor prognosis, and heightened infiltration of CAFs. We elucidated a pivotal role of CLDN18.2 in mediating adhesion between gastric cancer cells and CAFs, which leads to the adhesion of cancer cells to stroma tissue and facilitates the clustering of cancer cells and CAFs into embolus, enhancing gastric cancer’s metastatic progression and the risk of embolic death. Mechanistically, it was discovered that CAFs can activate adhesion and metastasis-related signaling pathways in CLDN18.2-positive gastric cancer cells. Furthermore, using an in vivo protein-proximity labeling approach, we identified S100 calcium binding protein A4 (S100A4) as a distinctive marker of CAFs that interacts with CLDN18.2 to enhance gastric cancer progression.

Conclusions
Our findings illuminated the role of the CLDN18.2-mediated interaction between cancer cells and CAFs in promoting gastric cancer progression and embolism, thereby providing insight into potential therapeutic avenues for CLDN18.2 positive cancers.
Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis
Authors: Liu Xin Tracy , Huang Yu , Liu Da , Jiang Yingxin Celia , Zhao Min , Chung Long Hoa , Han Xingxing Daisy , Zhao Yinan , Chen Jinbiao , Coleman Paul , Ting Ka Ka , Tran Collin , Su Yingying , Dennis Claude Vincent , Bhatnagar Atul , Liu Ken , Don Anthony Simon , Vadas Mathew Alexander , Gorrell Mark Douglas , Zhang Shubiao , Murray Michael , Kavurma Mary Meltem , McCaughan Geoffrey William , Gamble Jennifer Ruth , Qi Yanfei 
Published: January 2024

Abstract
Background
Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice. Therefore, the development of PF-543, a highly selective SphK1 inhibitor, opens a new avenue for HCC treatment. However, the anti-cancer efficacy of PF-543 has not yet been investigated in primary cancer models in vivo, thereby limiting its further translation.

Methods
Building upon the identification of the active form of SphK1 as a viable therapeutic target in human HCC specimens, we assessed the capacity of PF-543 in suppressing tumor progression using a diethylnitrosamine-induced mouse model of primary HCC. We further delineated its underlying mechanisms in both HCC and endothelial cells. Key findings were validated in Sphk1 knockout mice and lentiviral-mediated SphK1 knockdown cells.

Results
SphK1 activity was found to be elevated in human HCC tissues. Administration of PF-543 effectively abrogated hepatic SphK1 activity and significantly suppressed HCC progression in diethylnitrosamine-treated mice. The primary mechanism of action was through the inhibition of tumor neovascularization, as PF-543 disrupted endothelial cell angiogenesis even in a pro-angiogenic milieu. Mechanistically, PF-543 induced proteasomal degradation of the critical glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, thus restricting the energy supply essential for tumor angiogenesis. These effects of PF-543 could be reversed upon S1P supplementation in an S1P receptor-dependent manner.

Conclusions
This study provides the first in vivo evidence supporting the potential of PF-543 as an effective anti-HCC agent. It also uncovers previously undescribed links between the pro-cancer, pro-angiogenic and pro-glycolytic roles of the SphK1/S1P/S1P receptor axis. Importantly, unlike conventional anti-HCC drugs that target individual pro-angiogenic drivers, PF-543 impairs the PFKFB3-dictated glycolytic energy engine that fuels tumor angiogenesis, representing a novel and potentially safer therapeutic strategy for HCC.
The effects of reproductive variables on child mortality in Ethiopia: evidence from demographic and health surveys from 2000 to 2016
Authors: Debere Hailu Refera , Adjiwanou Visseho 
Published: January 2024

Abstract
Background
Child mortality is a crucial indicator reflecting a country's health and socioeconomic status. Despite significant global improvements in reducing early childhood deaths, Southern Asia and sub-Saharan Africa still bear the highest burden of newborn mortality. Ethiopia is one of five countries that account for half of new-born deaths worldwide.

Methods
This study examined the relationship between specific reproductive factors and under-five mortality in Ethiopia. A discrete-time survival model was applied to analyze data collected from four Ethiopian Demographic and Health Surveys (EDHS) conducted between 2000 and 2016. The study focused on investigating the individual and combined effects of three factors: preceding birth interval, maternal age at childbirth, and birth order, on child mortality.

Results
The study found that lengthening the preceding birth interval to 18–23, 24–35, 36–47, or 48+ months reduced the risk of under-five deaths by 30%, 46%, 56%, and 60% respectively, compared to very short birth intervals (less than 18 months). Giving birth between the ages 20–34 and 35+ reduced the risk by 34% and 8% respectively, compared to giving birth below the age of 20. The risk of under-five death was higher for a 7th-born child by 17% compared to a 2nd or 3rd-born child. The combined effect analysis showed that higher birth order at a young maternal age increased the risk. In comparison, lower birth order in older maternal age groups was associated with higher risk. Lastly, very short birth intervals posed a greater risk for children with higher birth orders.

Conclusion
Not only does one reproductive health variable negatively affect child survival, but their combination has the strongest effect. It is therefore recommended that policies in Ethiopia should address short birth intervals, young age of childbearing, and order of birth through an integrated strategy.
Impact of ACE I gene insertion/deletion, A-240T polymorphisms and the renin–angiotensin–aldosterone system on COVID-19 disease
Authors: Zobel Christian M. , Kuhn Hartmut , Schreiner Maximilian , Wenzel Werner , Wendtland Jasper , Goekeri Cengiz , Scheit Lorenz , Oltmanns Klaas , Rauschning Dominic , Grossegesse Marica , Hofmann Natalie , Wirtz Hubert , Spethmann Sebastian ,   BwKrhs-Covid-Research-Group, Baumgarten Ullrich , Wageloehner Tobias , Neumann Nino , Mueller Annette , Mueller Rico , Krueger Jan Philip , Borchert Alena , Weinreich Felix , Keidel Franziska , Koch Maria , Schüßler Meike 
Published: January 2024

Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin–angiotensin–aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19.

Methods
Our preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19.

Results
Our study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels.

Conclusions
Although there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response.
Clinical trial registration: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020.
HTLV-1 reverse transcriptase homology model provides structural basis for sensitivity to existing nucleoside/nucleotide reverse transcriptase inhibitors
Authors: Tardiota Nicolas , Jaberolansar Noushin , Lackenby Julia A. , Chappell Keith J. , O’Donnell Jake S. 
Published: January 2024

AbstractThe human T-lymphotropic virus type 1 (HTLV-1) infects millions of people globally and is endemic to various resource-limited regions. Infections persist for life and are associated with increased susceptibility to opportunistic infections and severe diseases including adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy-tropical spastic paraparesis. No HTLV-1-specific anti-retrovirals have been developed and it is unclear whether existing anti-retrovirals developed for treatment of human immunodeficiency virus (HIV) have efficacy against HTLV-1. To understand the structural basis for therapeutic binding, homology modelling and machine learning were used to develop a structural model of the HTLV-1 reverse transcriptase. With this, molecular docking experiments using a panel of FDA-approved inhibitors of viral reverse transcriptases to assess their capacity for binding, and in turn, inhibition. Importantly, nucleoside/nucleotide reverse transcriptase inhibitor but not non-nucleoside reverse transcriptase inhibitors were predicted to bind the HTLV-1 reverse transcriptase, with similar affinity to HIV-1 reverse transcriptase. By strengthening the rationale for clinical testing of therapies such as tenofovir alafenamide, zidovudine, lamivudine, and azvudine for treatment of HTLV-1, this study has demonstrated the power of in silico structural biology approaches in drug design and therapeutic testing.
Neuronal and glial vulnerability of the suprachiasmatic nucleus in tauopathies: evidence from human studies and animal models
Authors: Son Gowoon , Neylan Thomas C. , Grinberg Lea T. 
Published: January 2024

AbstractTauopathies, a group of neurodegenerative diseases that includes Alzheimer’s disease, commonly lead to disturbances in sleep-wake patterns and circadian rhythm disorders. The circadian rhythm, a recurring 24-hour cycle governing human biological activity, is regulated by the hypothalamic suprachiasmatic nucleus (SCN) and endogenous transcriptional-translational feedback loops. Surprisingly, little attention has been given to investigating tauopathy-driven neuropathology in the SCN and the repercussions of SCN and circadian gene dysfunction in the human brain affected by tauopathies. This review aims to provide an overview of the current literature on the vulnerability of the SCN in tauopathies in humans. Emphasis is placed on elucidating the neuronal and glial changes contributing to the widespread disruption of the molecular circadian clock. Furthermore, this review identifies areas of knowledge requiring further investigation.
Granulomatous myocarditis arising from intravesical Bacillus Calmette–Guérin therapy leading to death diagnosed by postmortem examination: a case report
Authors: Geetha Saroja D. , Chavarria Hector D. , Abdelwahed Mohammed , Kataria Nidhi , Bijol Vanesa , Das Kasturi 
Published: January 2024

Abstract
Background
Intravesical Bacillus Calmette–Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach.

Case presentation
We present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus.

Conclusion
Granulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.