bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection of Galectin‐Binding Ligands from Synthetic Glycopeptide Libraries
Authors: Kovalová Anna , Prouza Vít , Zavřel Martin , Hájek Miroslav , Dzijak Rastislav , Magdolenová Alžbeta , Pohl Radek , Voburka Zdeněk , Parkan Kamil , Vrabel Milan 
Published: November 2023

AbstractGalectins, a class of carbohydrate‐binding proteins, play a crucial role in various physiological and disease processes. Therefore, the identification of ligands that efficiently bind these proteins could potentially lead to the development of new therapeutic compounds. In this study, we present a method that involves screening synthetic click glycopeptide libraries to identify lectin‐binding ligands with low micromolar affinity. Our methodology, initially optimized using Concanavalin A, was subsequently applied to identify binders for the therapeutically relevant galectin 1. Binding affinities were assessed using various methods and showed that the selected glycopeptides exhibited enhanced binding potency to the target lectins compared to the starting sugar moieties. This approach offers an alternative means of discovering galectin‐binding ligands as well as other carbohydrate‐binding proteins, which are considered important therapeutic targets.
Function of proprotein convertase subtilisin/kexin type 9 and its role in central nervous system diseases: An update on clinical evidence
Authors: Zhu Xiao‐Bin , Xu Yao‐Yao , Li Liu‐Cheng , Sun Jia‐Bin , Wang Yu‐Zhen , Chen Jie , Wang Chen , Zhang Su , Jin Liang‐Yan 
Published: November 2023

AbstractProprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low‐density lipoprotein cholesterol (LDL‐C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL‐C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.
Lead exposure and student outcomes: A study of Flint schools
Authors: Sauve‐Syed Jessica 
Published: November 2023

AbstractThis paper estimates the impacts of cumulative lead exposure on the short‐run discipline and academic achievement of elementary school students. An exogenous, heterogeneous shock of lead‐in‐water levels within classrooms at Flint Community Schools provides the treatment variation used to focus on the understudied, short‐run effects of lead on older children. At the mean level of classroom lead exposure disciplinary actions increased by 8 actions per grade within each school, and the share of students proficient in both math and reading declined. These results may help explain observed disparities in both behavior and academic achievement for underprivileged groups.
Miracles in medicine: A narrative inquiry exploring extraordinary events in pediatrics
Authors: Huynh Geraldine , Rashid Marghalara , Foulds Jessica L. 
Published: November 2023

AbstractBackground and AimsWhether miracles are seen as a source of conflict between healthcare teams and families, a foolish or even harmful belief, or a hindrance to system‐wide improvements and scientific inquiry, miracles within medicine have long been questioned. We were interested in the perspectives of pediatricians on miracles and how that has informed their care of patients. We also sought to explore the intersection and relationship between the medical sciences, faith, and how we view miracles.MethodsUsing narrative inquiry as a research methodology, we had conversations and explored the experiences of physicians who work directly within pediatric clinical care. We used purposeful sampling by emailing several pediatricians whom we felt might have been interested in the project and may have had experiences with perceived medical miracles. All conversations were conducted over Zoom and recorded.ResultsWe conducted one to three conversations with each participant. During our analysis, we identified two threads. First, participants described miracles mostly as favorable and fortuitous events that invoked a sense of wonder due to contextual factors such as geography, access to resources, time in history but also previous experiences and the expectations of the clinician. Second, there is a complex dynamic within and between the medical sciences and the faith commitments of clinicians and families, especially when facing life‐limiting or end‐of‐life illness.ConclusionsThe stories that our participants told not only informed their past experiences and how they remembered them but also their present and future experiences. Exploring the topic of medical miracles allowed us to better understand the social discourses that shape our perceptions of miracles, death, and the role of the physician. These stories offer us hope and possibility in a time when we as a medical community may have lost our sense of wonder and the ability to notice miracles.
Mandatory CSR disclosure, institutional ownership and firm value: Evidence from China
Authors: Shah Syed Zulfiqar Ali , Akbar Saeed , Zhu Xiaoyun 
Published: November 2023

AbstractThis study aims to contribute to the relevant accounting, corporate governance, and corporate social responsibility (CSR) literature by examining the value relevance of mandatory CSR disclosures in China. Using a difference‐in‐differences (DID) research design and a sample based on propensity score matching (PSM) over the period from 2003 to 2020, our findings suggest that mandatory CSR disclosures are negatively associated with firm' values. We also find that firms with a high level of institutional ownership and leverage experience a relatively lower drop in firms' values as a result of the mandatory CSR disclosures. These findings remain robust to alternative sampling design, use of market to book value as an alternative measure of firms' market‐based performance, and a parallel test to validate our DID analysis. Our findings have useful implications for managers, regulators, policy makers and other stakeholders.
Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long‐term dietary administration
Authors: Mondal Shirsha , Basu Soumyadeep , Ghosh Songita , Guria Suktara , Mukherjee Sutapa 
Published: November 2023

AbstractThe incidence of metabolic diseases is increasing alarmingly in recent times. Parallel to nutritional excess and sedentary lifestyle, the random usage of several endocrine disrupting chemicals including plasticizers is reported to be closely associated with metabolic diseases. Diethyl phthalate (DEP) is a widely used plasticizer in a host of consumer and daily care products. Adipose tissue plays a central role in energy storage and whole‐body metabolism. The impairment of adipose function is critically implicated in the pathogenesis of insulin resistance, diabetes, and related metabolic diseases. Recently, exposure to certain phthalate esters has been linked to the development of obesity and diabetes, although there are contradictions and the mechanisms are not clearly understood. In an effort to ascertain the metabolic consequences of chronic phthalate exposure and the underlying mechanism, the present study was designed to examine the effects of long‐term dietary consumption of DEP in adipocytes. DEP‐treated mice were hyperglycemic but nonobese; their body weight initially increased which subsequently was reduced compared to control. DEP exposure at lower levels impaired adipogenesis by downregulating the key transcription factor, peroxisome proliferator‐activated receptor γ and its downstream insulin‐sensitizing adipokine, adiponectin, thereby severely compromising adipocyte function. The activation of master regulator nuclear factor κB led to rise in proinflammatory cytokines. We found that DEP triggered intrinsic apoptotic pathways through activated cytochrome c‐Apaf1‐caspase 9‐caspase 3 axis in adipocytes. Taken together, our data revealed that chronic administration of dietary DEP could unleash adverse metabolic outcomes by initiating oxidative stress, inflammation, and apoptosis in the adipocytes, thus leading to adipose tissue dysfunction.
Forsythoside B alleviates osteoarthritis through the HMGB1/TLR4/NF‐κB and Keap1/Nrf2/HO‐1 pathways
Authors: Li Shujuan , Li Yan , Hou Li , Tang Li , Gao Fang 
Published: November 2023

AbstractOsteoarthritis (OA) is a joint pain and dysfunction syndrome resulting from severe joint degeneration. Inflammation and degeneration of the articular cartilage are two main features of OA and have tight interactions during OA progression. Conventional treatment with nonsteroidal anti‐inflammatory drugs has been widely utilized clinically, whereas the side effects have restricted their application. Forsythoside B has been found with anti‐inflammatory effects and antiapoptosis in inflammatory diseases, whereas in OA it remains poorly understood. Interleukin (IL)−1β (10 ng/mL) was taken to induce an OA cell model on HC‐A chondrocytes and an OA rat model was constructed for in vivo experiments. Forsythoside B was adopted to treat HC‐A chondrocytes and OA rats. As shown by the data, Forsythoside B hampered IL‐1β‐elicited rat chondrocyte apoptosis, oxidative stress, and facilitated proliferation. The profiles of inflammatory factors, NOD‐like receptor family pyrin domain containing 3 inflammasomes, Kelch‐like epichlorohydrin‐associated protein‐1 (Keap1), and nuclear factor‐κB (NF‐κB) phosphorylation were suppressed by Forsythoside B, whereas the nuclear factor E2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) levels were promoted. Further, Forsythoside B mitigated cartilage damage and degeneration. Moreover, the oxidative stress and inflammation mediators in the cartilage tissue of OA rats were remarkably abated. Collectively, Forsythoside B hinders the NF‐κB and Keap1/Nrf2/HO‐1 pathways to curb IL‐1β‐elicited OA rat oxidative stress and inflammation both in vivo and ex vivo, ameliorating OA development. All over, this study provides an underlying strategy for treating OA, which might help the clinical treatment of OA patients.
Bioinformatics insights into CENP‐T and CENP‐W protein‐protein interaction disruptive amino acid substitution in the CENP‐T‐W complex
Authors: Mohanty Suryakanta , Bhadane Rajendra , Kumar Shashank 
Published: November 2023

AbstractKinetochores are multi‐protein assemblies present at the centromere of the human chromosome and play a crucial role in cellular mitosis. The CENP‐T and CENP‐W chains form a heterodimer, which is an integral part of the inner kinetochore, interacting with the linker DNA on one side and the outer kinetochore on the other. Additionally, the CENP‐T‐W dimer interacts with other regulatory proteins involved in forming inner kinetochores. The specific roles of different amino acids in the CENP‐W at the protein‐protein interaction (PPI) interface during the CENP‐T‐W dimer formation remain incompletely understood. Since cell division goes awry in diseases like cancer, this CENP‐T‐W partnership is a potential target for new drugs that could restore healthy cell division. We employed molecular docking, binding free energy calculations, and molecular dynamics (MD) simulations to investigate the disruptive effects of amino acids substitutions in the CENP‐W chain on CENP‐T‐W dimer formation. By conducting a molecular docking study and analysing hydrogen bonding interactions, we identified key residues in CENP‐W (ASN‐46, ARG‐53, LEU‐83, SER‐86, ARG‐87, and GLY‐88) for further investigation. Through site‐directed mutagenesis and subsequent binding free energy calculations, we refined the selection of mutant. We chose four mutants (N46K, R53K, L83K, and R87E) of CENP‐W to assess their comparative potential in forming CENP‐T‐W dimer. Our analysis from 250 ns long revealed that the substitution of LEU83 and ARG53 residues in CENP‐W with the LYS significantly disrupts the formation of CENP‐T‐W dimer. In conclusion, LEU83 and ARG53 play a critical role in CENP‐T and CENP‐W dimerization which is ultimately required for cellular mitosis. Our findings not only deepen our understanding of cell division but also hint at exciting drug‐target possibilities.
Discovery of a series of silicon‐based ferrimagnets in CrMnSin (n = 4–20) clusters
Authors: Wang Kai , Zhang Ying , Wang Chaoyong , Zhao Jun , Liu Le , Chen Jiaye , Wang Yarui 
Published: November 2023

AbstractHerein, the structural evolution, electronic and magnetic properties of silicon clusters with two different dopants, CrMnSin (n = 4–20) clusters were investigated at density functional theory (DFT) level. Small‐sized CrMnSin (n = 4–9) clusters tend to adopt bipyramid‐based geometries, while clusters with sizes n = 10 and 11 prefer to opening cage‐like structures. For sizes n = 12 to 14, the half‐encapsulated structures gradually transform into closed‐cage Cr@Sin structures, with the Mn atom exposed outside. Starting from size 15, both the Cr and Mn atoms are completely encapsulated by silicon atoms. Meanwhile, the Cr and Mn atoms in smaller‐sized CrMnSin (n = 4–7) clusters tend to be separated, while they prefer to stay together for larger sizes. Cr atom always acts as electron donor, but not for Mn atom. From the average binding energies, one can conclude that it is easier to form larger size clusters. Smaller and larger sized CrMnSin (n = 4–9 and 19–20) clusters prefer to exhibit ferromagnetic Cr–Mn coupling, while sizes n = 10–18 always exhibit ferrimagnetic state. To our knowledge, the CrMnSin clusters is the first kind of neutral transition‐metal doped semiconductor clusters that show ferrimagnetic state within a wide size range.
OCT4 regulates WNT/β‐catenin signaling and prevents mesoendoderm differentiation by repressing EOMES in porcine pluripotent stem cells
Authors: Xu Tian , Su Peng , Wu Linhui , Li Delong , Qin Wei , Li Qiao , Zhou Jilong , Miao Yi‐Liang 
Published: November 2023

AbstractThe regulatory network between signaling pathways and transcription factors (TFs) is crucial for the maintenance of pluripotent stem cells. However, little is known about how the key TF OCT4 coordinates signaling pathways to regulate self‐renewal and lineage differentiation of porcine pluripotent stem cells (pPSCs). Here, we explored the function of OCT4 in pPSCs by transcriptome and chromatin accessibility analysis. The TFs motif enrichment analysis revealed that, following OCT4 knockdown, the regions of increased chromatin accessibility were enriched with EOMES, GATA6, and FOXA1, indicating that pPSCs differentiated toward the mesoendoderm (ME) lineage. Besides, pPSCs rapidly differentiated into ME when the WNT/β‐catenin inhibitor XAV939 was removed. However, the ME differentiation of pPSCs caused by OCT4 knockdown did not rely on the activation of WNT/β‐catenin signaling because the target gene of WNT/β‐catenin signaling, AXIN2 was not upregulated after OCT4 knockdown, despite significant upregulation of WLS and some WNT ligands. Importantly, OCT4 is directly bound to the promoter and enhancers of EOMES and repressed its transcription. Overexpression of EOMES was sufficient to induce ME differentiation in the presence of XAV939. These results demonstrate that OCT4 can regulate WNT/β‐catenin signaling and prevent ME differentiation of pPSCs by repressing EOMES transcription.
NDP52 SUMOylation contributes to low‐dose X‐rays‐induced cardiac hypertrophy through PINK1/Parkin‐mediated mitophagy via MUL1/SUMO2 signalling
Authors: Gao Anbo , Wang Mengjie , Tang Xing , Shi Gangqing , Hou Kai , Fang Jinren , Zhou Linlin , Zhou Hong , Jiang Weimin , Li Yukun , Ouyang Fan 
Published: November 2023

AbstractRadiation‐induced heart damage caused by low‐dose X‐rays has a significant impact on tumour patients' prognosis, with cardiac hypertrophy being the most severe noncarcinogenic adverse effect. Our previous study demonstrated that mitophagy activation promoted cardiac hypertrophy, but the underlying mechanisms remained unclear. In the present study, PARL‐IN‐1 enhanced excessive hypertrophy of cardiomyocytes and exacerbated mitochondrial damage. Isobaric tags for relative and absolute quantification‐based quantitative proteomics identified NDP52 as a crucial target mediating cardiac hypertrophy induced by low‐dose X‐rays. SUMOylation proteomics revealed that the SUMO E3 ligase MUL1 facilitated NDP52 SUMOylation through SUMO2. Co‐IP coupled with LC–MS/MS identified a critical lysine residue at position 262 of NDP52 as the key site for SUMO2‐mediated SUMOylation of NDP52. The point mutation plasmid NDP52K262R inhibited mitophagy under MUL1 overexpression, as evidenced by inhibition of LC3 interaction with NDP52, PINK1 and LAMP2A. A mitochondrial dissociation study revealed that NDP52K262R inhibited PINK1 targeting to endosomes early endosomal marker (EEA1), late/lysosome endosomal marker (LAMP2A) and recycling endosomal marker (RAB11), and laser confocal microscopy confirmed that NDP52K262R impaired the recruitment of mitochondria to the autophagic pathway through EEA1/RAB11 and ATG3, ATG5, ATG16L1 and STX17, but did not affect mitochondrial delivery to lysosomes via LAMP2A for degradation. In conclusion, our findings suggest that MUL1‐mediated SUMOylation of NDP52 plays a crucial role in regulating mitophagy in the context of low‐dose X‐ray‐induced cardiac hypertrophy. Two hundred sixty‐second lysine of NDP52 is identified as a key SUMOylation site for low‐dose X‐ray promoting mitophagy activation and cardiac hypertrophy. Collectively, this study provides novel implications for the development of therapeutic strategies aimed at preventing the progression of cardiac hypertrophy induced by low‐dose X‐rays.
Apoptosis antagonizing transcription factor‐mediated liver damage and inflammation to cancer: Therapeutic intervention by curcumin in experimental metabolic dysfunction associated steatohepatitis‐hepatocellular carcinoma
Authors: Srinivas Akshatha N. , Suresh Diwakar , Chidambaram Saravana B. , Santhekadur Prasanna K. , Kumar Divya P. 
Published: November 2023

AbstractIn tandem with the expanding obesity pandemic, the prevalence of metabolic dysfunction associated steatohepatitis (MASH, formerly known as NASH)‐ driven hepatocellular carcinoma (HCC) is predicted to rise globally, creating a significant need for therapeutic interventions. We previously identified the upregulation of apoptosis antagonizing transcription factor (AATF), which is implicated in facilitating the progression from MASH to HCC. The objective of this study was to examine whether the intervention of curcumin could alleviate AATF‐mediated MASH, inhibit tumor growth, and elucidate the underlying mechanism. A preclinical murine model mimicking human MASH‐HCC was employed, subjecting mice to either a chow diet normal water (CDNW) or western diet sugar water (WDSW) along with very low dose of carbon tetrachloride (CCl4‐ 0.2 μL/g, weekly). Mice receiving curcumin (CUR) alongside WDSW/CCl4 exhibited significant improvements, including reduced liver enzymes, dyslipidemia, steatosis, inflammation, and hepatocellular ballooning. Curcumin treatment also suppressed hepatic expression of inflammatory, fibrogenic, and oncogenic markers. Of note, there was a significant reduction in the expression of AATF upon curcumin treatment in WDSW/CCl4 mice and human HCC cells. In contrast, curcumin upregulated Kruppel‐like factor 4 (KLF4) in MASH liver and HCC cells, which is known to downregulate sp1 (specificity protein‐1) expression. Thus, curcumin treatment effectively inhibited the progression of MASH to HCC by downregulating the expression of AATF via the KLF4‐Sp1 signaling pathway. These preclinical findings establish a novel molecular connection between curcumin and AATF in reducing hepatocarcinogenesis, and provide a strong rationale for the development of curcumin as a viable treatment for MASH‐HCC in humans.
Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus
Authors: Nakamura Shintaro , Miyachi Yasutaka , Shinjo Akihito , Yokomizo Hisashi , Takahashi Masatomo , Nakatani Kohta , Izumi Yoshihiro , Otsuka Hiroko , Sato Naoichi , Sakamoto Ryuichi , Miyazawa Takashi , Bamba Takeshi , Ogawa Yoshihiro 
Published: November 2023

AbstractBackgroundDiabetes is associated with an increased risk of deleterious changes in muscle mass and function or sarcopenia, leading to physical inactivity and worsening glycaemic control. Given the negative energy balance during sodium–glucose cotransporter‐2 (SGLT2) inhibition, whether SGLT2 inhibitors affect skeletal muscle mass and function is a matter of concern. However, how SGLT2 inhibition affects the skeletal muscle function in patients with diabetes remains insufficiently explored. We aimed to explore the effects of canagliflozin (CANA), an SGLT2 inhibitor, on skeletal muscles in genetically diabetic db/db mice focusing on the differential responses of oxidative and glycolytic muscles.MethodsDb/db mice were treated with CANA for 4 weeks. We measured running distance and handgrip strength to assess skeletal muscle function during CANA treatment. At the end of the experiment, we performed a targeted metabolome analysis of the skeletal muscles.ResultsCANA treatment improved the reduced endurance capacity, as revealed by running distance in db/db mice (414.9 ± 52.8 vs. 88.7 ± 22.7 m, P < 0.05). Targeted metabolome analysis revealed that 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranosyl 5′‐monophosphate (AICARP), a naturally occurring AMP‐activated protein kinase (AMPK) activator, increased in the oxidative soleus muscle (P < 0.05), but not in the glycolytic extensor digitorum longus muscle (P = 0.4376), with increased levels of AMPK phosphorylation (P < 0.01).ConclusionsThis study highlights the potential role of the AICARP/AMPK pathway in oxidative rather than glycolytic skeletal muscles during SGLT2 inhibition, providing novel insights into the mechanism by which SGLT2 inhibitors improve endurance capacity in patients with type 2 diabetes.
Vaccine escape challenges virus prevention: The example of two vaccine‐preventable oncogenic viruses
Authors: Qu Wenjie , Sui Long , Li Yanyun 
Published: November 2023

AbstractOver the years, the pace of developing vaccines for HBV and HPV has never stopped. After more than 30 years of application, the HBV vaccine has reduced 80% of hepatocellular carcinoma (HCC). However, vaccine escape variants occur under selective pressure induced by widespread vaccination and antiviral therapy, which results in fulminant infection and horizontal transmission. Several mechanisms have been studied to explain HBV vaccine escape, including vaccine escape mutations (VEMs) in the major hydrophilic region, which leads to a decrease in the binding ability to neutralize antibodies and is the primary escape mechanism, protein conformational and N‐linked glycosylation sites changes caused by VEMs, differences in genotype distribution, gene recombination, and some temporarily unknown reasons. However, effective solutions are still being explored. The HPV vaccine has also been proven to prevent 70%–90% of cervical cancer worldwide. Cases of HPV infection after being vaccinated have been observed in clinical practice. However, few researchers have paid attention to the mechanism of HPV vaccine escape. Thus, we reviewed the literature on vaccine escape of both HBV and HPV to discuss the mechanism of the virus escaping from vaccine protection and possible solutions to this problem. We analyzed the gap between studies of HPV and HBV and made prospects for further research in HPV vaccine escape.