bluuebunny/crossref_metadata_2025_split huggingface dataset:
VD3/VDR attenuates bisphenol A–induced impairment in mouse Leydig cells via regulation of autophagy
Authors: Wang Ling , Zhuang Jianan , Xue Zhen , Lu Hongzhao , Zeng Wenxian , Zhang Tao 
Published: May 2024

AbstractBisphenol A (BPA) is an endocrine disruptor with reproductive toxicity. Further, 1,25‐dihydroxyvitamin D3 (VD3) plays an important role in male reproduction by binding vitamin D receptor (VDR) and mediating the pleiotropic biological actions that include spermatogenesis. However, whether VD3/VDR regulates the effect of BPA on Leydig cells (LCs) injury remains unknown. This study aimed to explore the effects of VD on BPA‐induced cytotoxicity in mouse LCs. Hereby, LCs treated with BPA, VD3, or both were subjected to the assays of cell apoptosis, proliferation, autophagy, and levels of target proteins. This study unveiled that cell viability was dose‐dependently reduced after exposure to BPA. BPA treatment significantly inhibited LC proliferation, induced apoptosis, and also downregulated VDR expression. By jointly analyzing transcriptome data and Comparative Toxicogenomics Database (CTD) data, autophagy signaling pathways related to testicular development and male reproduction were screened out. Therefore, the autophagy phenomenon of cells was further detected. The results showed that BPA treatment could activate cell autophagy, Vdr−/− inhibits cell autophagy, and active VD3 does not have a significant effect on the autophagy of normal LCs. After VD3 and BPA were used in combination, the autophagy of cells was further enhanced, and VD3 could alleviate BPA‐induced damage of LCs. In conclusion, this study found that supplementing VD3 could eliminate the inhibition of BPA on VDR expression, further enhance LCs autophagy effect, and alleviate the inhibition of LCs proliferation and induction of apoptosis by BPA, playing a protective role in cells. The research results will provide valuable strategies to alleviate BPA‐induced reproductive toxicity.
How to count bird calls? Vocal activity indices may provide different insights into bird abundance and behaviour depending on species traits
Authors: Hutschenreiter Anja , Andresen Ellen , Briseño‐Jaramillo Margarita , Torres‐Araneda Alejandra , Pinel‐Ramos Eduardo , Baier Jacqueline , Aureli Filippo 
Published: May 2024

Abstract

Passive acoustic monitoring (PAM) has become an important tool for surveying birds, and there is a growing demand for approaches to obtain abundance and behavioural information from PAM recordings. Changes in bird populations have been assessed by counting recorded calls and calculating the vocal activity rate (VAR, i.e. the number of calls per recording time). However, bird calls could be counted in various ways and depending on species traits, these call counts could give us different insights on bird abundance, vocal behaviour and/or habitat use.

Our study had two goals: (1) to present and evaluate two new indices based on call counts, the detection rate (DR, i.e. the number of 1‐min recordings in which the presence of a target vocalization is detected) and the maximum count per minute (MAX, i.e. the maximum number of calls found in a 1‐min recording); and (2) to present a conceptual framework showing how the interpretations of VAR, DR and MAX could depend on the index and on species traits.

For three Neotropical bird species with distinct traits, we calculated VAR, DR and MAX based on PAM data from 25 sites in the Yucatan Peninsula (Mexico) that varied in their degree of anthropogenic habitat disturbance. We found moderate to high correlations between the indices and higher temporal variability in VAR compared to DR and MAX. We also found different effect sizes of habitat disturbance on the three species and indices.

We suggest that DR might be a more reliable index of relative abundance than VAR for species whose calling behaviour exhibits a high cue rate and that MAX may be suitable for estimating family or flock size in gregarious birds. Our findings show the potential usefulness of developing new indices based on call counts to generate ecological hypotheses and assess changes in bird abundance and behaviour.
Oxidative stress‐related cellular aging causes dysfunction of the Kv3.1/KCNC1 channel reverted by melatonin
Authors: Spinelli Sara , Remigante Alessia , Liuni Raffaella , Mantegna Gianluca , Legname Giuseppe , Marino Angela , Morabito Rossana , Dossena Silvia 
Published: May 2024

AbstractThe voltage‐gated Kv3.1/KCNC1 channel is abundantly expressed in fast‐spiking principal neurons and GABAergic inhibitory interneurons throughout the ascending auditory pathway and in various brain regions. Inactivating mutations in the KCNC1 gene lead to forms of epilepsy and a decline in the expression of the Kv3.1 channel is involved in age‐related hearing loss. As oxidative stress plays a fundamental role in the pathogenesis of epilepsy and age‐related hearing loss, we hypothesized that an oxidative insult might affect the function of this channel. To verify this hypothesis, the activity and expression of endogenous and ectopic Kv3.1 were measured in models of oxidative stress‐related aging represented by cell lines exposed to 100 mM d‐galactose. In these models, intracellular reactive oxygen species, thiobarbituric acid reactive substances, sulfhydryl groups of cellular proteins, and the activity of catalase and superoxide dismutase were dysregulated, while the current density of Kv3.1 was significantly reduced. Importantly, the antioxidant melatonin reverted all these effects. The reduction of function of Kv3.1 was not determined by direct oxidation of amino acid side chains of the protein channel or reduction of transcript or total protein levels but was linked to reduced trafficking to the cell surface associated with Src phosphorylation as well as metabolic and endoplasmic reticulum stress. The data presented here specify Kv3.1 as a novel target of oxidative stress and suggest that Kv3.1 dysfunction might contribute to age‐related hearing loss and increased prevalence of epilepsy during aging. The pharmacological use of the antioxidant melatonin can be protective in this setting.
Aging amplifies a gut microbiota immunogenic signature linked to heightened inflammation
Authors: Caetano‐Silva Maria Elisa , Shrestha Akriti , Duff Audrey F. , Kontic Danica , Brewster Patricia C. , Kasperek Mikaela C. , Lin Chia‐Hao , Wainwright Derek A. , Hernandez‐Saavedra Diego , Woods Jeffrey A. , Bailey Michael T. , Buford Thomas W. , Allen Jacob M. 
Published: May 2024

AbstractAging is associated with low‐grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low‐grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial‐induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)‐binding protein (LBP) and colonic calprotectin. Ex vivo immunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll‐like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonic Il6, Tnf, and Tlr4) and endotoxemia (circulating LBP) in young germ‐free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging‐induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad‐spectrum antibiotic challenge (Abx), with sustained elevation in Escherichia (Proteobacteria) and altered TLR5 immunogenicity 7 days post‐Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age‐associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations.
Non‐pituitary growth hormone enables colon cell senescence evasion
Authors: Chesnokova Vera , Zonis Svetlana , Apaydin Tugce , Barrett Robert , Melmed Shlomo 
Published: May 2024

AbstractDNA damage‐induced senescence is initially sustained by p53. Senescent cells produce a senescence‐associated secretory phenotype (SASP) that impacts the aging microenvironment, often promoting cell transformation. Employing normal non‐tumorous human colon cells (hNCC) derived from surgical biopsies and three‐dimensional human intestinal organoids, we show that local non‐pituitary growth hormone (npGH) induced in senescent cells is a SASP component acting to suppress p53. npGH autocrine/paracrine suppression of p53 results in senescence evasion and cell‐cycle reentry, as evidenced by increased Ki67 and BrdU incorporation. Post‐senescent cells exhibit activated epithelial‐to‐mesenchymal transition (EMT), and increased cell motility. Nu/J mice harboring GH‐secreting HCT116 xenografts with resultant high GH levels and injected intrasplenic with post‐senescent hNCC developed fourfold more metastases than did mice harboring control xenografts, suggesting that paracrine npGH enables post‐senescent cell transformation. By contrast, senescent cells with suppressed npGH exhibit downregulated Ki67 and decreased soft agar colony formation. Mechanisms underlying these observations include npGH induction by the SASP chemokine CXCL1, which attracts immune effectors to eliminate senescent cells; GH, in turn, suppresses CXCL1, likely by inhibiting phospho‐NFκB, resulting in SASP cytokine downregulation. Consistent with these findings, GH‐receptor knockout mice exhibited increased colon phospho‐NFκB and CXCL1, while GH excess decreased colon CXCL1. The results elucidate mechanisms for local hormonal regulation of microenvironmental changes in DNA‐damaged non‐tumorous epithelial cells and portray a heretofore unappreciated GH action favoring age‐associated epithelial cell transformation.
Current trends in the role of neuroinflammation & α‐synuclein in alcohol use disorder: A systematic quantitative literature review
Authors: James Brandon C. , Cox Amanda J. , Lewohl Joanne M. 
Published: May 2024

AbstractThe neurodegenerative effects alcohol use disorder (AUD) have been well characterized and are likely due to the long‐term effects of alcohol on the brain. The molecular events that underlie regional neuronal loss are a focus of current research. Chronic inflammation in the central nervous system, termed neuroinflammation, contributes to the progressive loss of neurons in the brain. Using data from genome‐wide association studies and genetic and gene expression data, α‐synuclein was identified as a gene of interest for AUD almost 10 years ago. Despite this and the well‐recognized role of α‐synuclein in mediating neuroinflammation in other neurodegenerative diseases, its role in alcohol‐induced brain damage and AUD is yet to be elucidated. This systematic literature review quantifies and analyzes relationships between AUD, α‐synuclein, and neuroinflammation. The review identified fewer studies focused on the role in AUD of α‐synuclein (30) than on neuroinflammation (177), with published studies heavily centered on the myeloid differentiation primary response 88 (MyD88)‐dependent toll‐like receptor 4 (TLR4) pathway. The systematic review revealed that no original literature investigates the roles of α‐synuclein and neuroinflammation in AUD and that there are significantly fewer published articles on the role of α‐synuclein in AUD than in other neuroinflammatory conditions. Studies of the role of neuroinflammation in AUD are largely centered on the TLR4 signaling cascade, followed by TLR2 and TLR3, and soluble cytokines such as IL‐10, IL‐1β, and TNF‐α. Key research themes identified in other neurodegenerative disorders provide new insights for further investigation in AUD.
Phenotypic heterogeneity of mycosis fungoides cells leads to the difficulties in determining tumour origin
Authors: Jin Sha , Zhao Yige , Wang Shiwen , Wang Panpan , Tang Chenyu , Zhu Mengyan , Wang Ping 
Published: May 2024

AbstractMycosis fungoides (MF) is a low‐grade malignant cutaneous T‐cell lymphoma that originates from memory T cells. It typically follows a unique and relatively indolent disease course. MF is used to be characterized by a tissue‐resident memory T cell (TRM) phenotype, although recent molecular research has revealed its complexity, casting doubt on the cell of origin and the TRM‐MF paradigm. Recent clonal heterogeneity studies suggest that MF may originate from immature early precursor T cells. During development, the tumour microenvironment (TME) influences tumour cell phenotype. The exact origin and development trajectory of MF remains elusive. Clarifying the origin of MF cells is vital for accurate diagnosis and effective treatment.
Letter: Intestinal permeability accounting for ongoing gastrointestinal symptoms following endoscopic remission in IBD
Authors: Leong Rupert W. , Jairath Vipul , Ma Christopher 
Published: May 2024

LINKED CONTENTThis article is linked to Aliu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17988 and https://doi.org/10.1111/apt.18031.
Cognitive impairment among patients with chronic immune thrombocytopenia
Authors: Kuter David J. , Khan Umer , Maruff Paul , Daak Ahmed 
Published: May 2024

SummaryImmune thrombocytopenia (ITP) is an autoimmune disease typically associated with severely depleted platelet counts. However, additional symptoms (e.g. increased fatigue and memory/concentration difficulties) can profoundly impact patients' quality of life. The nature and severity of cognitive impairment in ITP, and potential association with patient/disease characteristics were evaluated in 49 adults with relapsed/refractory ITP. The Cogstate Brief Battery quantitatively assessed psychomotor function (DET), attention (IDN), visual learning (OCL) and working memory (ONB) individually, as well as DET/IDN and OCL/ONB composites. Clinically important cognitive impairment (defined as z‐score ≤ −1) for ≥2 individual tests was observed in 29 patients (59%). Impairment was highest for IDN (67% of patients), followed by DET (53%), ONB (39%) and OCL (16%). A higher magnitude of impairment was observed for the DET/IDN composite (mean z‐score −1.54; 95% CI, −1.94 to −1.13) than OCL/ONB (mean z‐score −0.21; 95% CI, −0.49 to 0.07). The severity of cognitive impairment was comparable to mild traumatic brain injury and associated with increasing age and fatigue but unrelated to platelet count or corticosteroid use. Overall, these results warrant a clinical need to further consider the potential of cognitive dysfunction in assessing ITP patients.
Associations between parental socioeconomic status and mental health in Chinese children: the mediating roles of parenting practices
Authors: Sun Xiaoyue , Yuan Yiqing 
Published: May 2024

BackgroundThe significance of socioeconomic status (SES) in child mental health is well‐established in Western populations; however, there is little evidence on this topic in Chinese populations. The possibility that Chinese families with different SES elicit different parenting practices that cause positive or negative child mental health outcomes warrants further investigation.MethodsThis study examined the associations of SES, parenting practices, and child mental health among 1401 Chinese school children and their parents residing in Shanghai. SES was measured by a composed index of parental education levels, occupations, and household incomes. The Alabama parenting questionnaire (APQ; child version) and the strengths and difficulties questionnaire (SDQ; parent version) were used to assess parenting practices and child mental health. We also explored the underlying mechanisms between parental SES and the mental health of children by testing different parenting practices as mediators of the relationships.ResultsThe results showed that a higher SES is positively associated with better mental health in children. Positive involvement and deficient monitoring can mediate the relationship between SES and child mental health outcomes. Negative discipline did not significantly mediate the above relationship.ConclusionsThe results highlight the significance of positive involvement and sufficient monitoring in promoting children's mental health and provide evidence for designing effective programs to improve parenting skills.
Diagnostic discordance among histopathological reviewers of melanocytic lesions
Authors: Hosler Gregory A. , Goldberg Matthew S. , Estrada Sarah I. , O'Neil Brendan , Amin Sapna M. , Plaza Jose A. 
Published: May 2024

AbstractBackgroundHistopathological examination is adequate for the diagnosis of most cutaneous melanocytic neoplasms. However, there is a subset that is either difficult to definitively diagnose or would have diagnostic disagreement upon review by multiple dermatopathologists if a more exhaustive review was performed.MethodsMelanocytic lesions underwent an independent, blinded diagnostic histopathological review of hematoxylin and eosin‐stained sections. Each lesion was reviewed by three to six dermatopathologists and categorized as benign, malignant, or unknown malignant potential (UMP). Diagnoses were grouped as concordant (all the same designation); opposing (received benign and malignant designations); majority (single designation with the highest number of diagnoses, no benign/malignant opposing designations); and non‐definitive (equal number of non‐opposing designations [i.e., benign/UMP or malignant/UMP]). Lesions with equivocal designations (concordant or majority UMP, opposing, majority, and non‐definitive) were utilized in a patient treatment model of projected surgical treatment discrepancies.ResultsIn total, 3317 cases were reviewed, and 23.8% of lesions received equivocal diagnoses. Of these, 7.3% were majority benign, 4.8% were majority malignant, 2.7% were majority UMP, 0.5% were concordant UMP, 6.9% were opposing, and 1.6% were non‐definitive. Patient treatment models of those with equivocal lesions (n = 788) revealed a potential of overall surgical treatment variations ranging from 18% to 72%, with the highest variation amongst lesions with opposing, non‐definitive, or majority UMP (40%–72%) diagnoses.ConclusionHistopathologic review in this large cohort demonstrated substantial diagnostic variation, with 23.8% of cases receiving equivocal diagnoses. We identified diagnostic ambiguity even in lesions where a definitive diagnosis was previously rendered by a single real‐world dermatopathologist. The combined clinical impact of diagnostic discordance or a final diagnosis of UMP is highlighted by high diagnosis‐dependent treatment variation in the patient treatment model, which could be underreported in a real‐world setting, where review by more than one to two dermatopathologists is relatively rare.
Drivers and spatial patterns of avian defaunation in tropical forests
Authors: Ferreiro‐Arias Iago , Santini Luca , Sagar H. S. Sathya Chandra , Richard‐Hansen Cécile , Guilbert Eric , Forget Pierre‐Michel , van Kuijk Marijke , Scabin Andressa B. , Peres Carlos A. , Revilla Eloy , Benítez‐López Ana 
Published: May 2024

AbstractAimWildlife overexploitation, either for food consumption or for the pet trade, is one of the main threats to bird species in tropical forests. Yet, the spatial distribution and intensity of harvesting pressure on tropical birds remain challenging to quantify. Here, we identify the drivers of hunting‐induced declines in bird abundance and quantify the magnitude and the spatial extent of avian defaunation at a pantropical scale.LocationPantropical.MethodsWe compiled 2968 abundance estimates in hunted and non‐hunted sites across the tropics spanning 518 bird species. Using a Bayesian modelling framework, we fitted species' abundance response ratios to a set of drivers of hunting pressure and species traits. Subsequently, we applied our model to quantify the spatial patterns of avian defaunation across tropical forests and to assess avian defaunation across biogeographic realms, and for species captured for the pet trade or for food consumption.ResultsBody mass and its interactions with hunter accessibility and proximity to urban markets were the most important drivers of hunting‐induced bird abundance declines. We estimated a mean abundance reduction of 12% across the tropics for all species, and that 43% of the extent of tropical forests harbour defaunated avian communities. Large‐bodied species and the Indomalayan realm displayed the greatest abundance declines. Further, moderate to high levels of defaunation extended over 24% of the pantropical forest area, with distinct spatial patterns for species captured for the pet trade (Brazil, China and Indonesia) and for food consumption (SE Asia and West Africa).Main ConclusionsOur study emphasizes the role of hunter accessibility and the proximity to urban markets as major drivers of bird abundance declines due to hunting and trapping. We further identified hotspots where overexploitation has detrimental effects on tropical birds, encompassing local extinction events, thus underscoring the urgent need for conservation efforts to address unsustainable exploitation for both subsistence and trade.
Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough
Authors: Rishabh  , Rohilla Manni , Bansal Seema , Bansal Nitin , Chauhan Samrat , Sharma Sheenam , Goyal Navjyoti , Gupta Sumeet 
Published: May 2024

AbstractIn females, Alzheimer's disease (AD) incidences increases as compared to males due to estrogen deficiency after menopause. Estrogen therapy is the mainstay therapy for menopause and associated complications. Estrogen, a hormone with multifaceted physiological functions, has been implicated in AD pathophysiology. Estrogen plays a crucial role in amyloid precursor protein (APP) processing and overall neuronal health by regulating various factors such as brain‐derived neurotrophic factor (BDNF), intracellular calcium signalling, death domain‐associated protein (Daxx) translocation, glutamatergic excitotoxicity, Voltage‐Dependent Anion Channel, Insulin‐Like Growth Factor 1 Receptor, estrogen‐metabolising enzymes and apolipoprotein E (ApoE) protein polymorphisms. All these factors impact the physiology of postmenopausal women. Estrogen replacement therapies play an important treatment strategy to prevent AD after menopause. However, use of these therapies may lead to increased risks of breast cancer, venous thromboembolism and cardiovascular disease. Various therapeutic approaches have been used to mitigate the effects of estrogen on AD. These include hormone replacement therapy, Selective Estrogen Receptor Modulators (SERMs), Estrogen Receptor Beta (ERβ)‐Selective Agonists, Transdermal Estrogen Delivery, Localised Estrogen Delivery, Combination Therapies, Estrogen Metabolism Modulation and Alternative Estrogenic Compounds like genistein from soy, a notable phytoestrogen from plant sources. However, mechanism via which these approaches modulate AD in postmenopausal women has not been explained earlier thoroughly. Present review will enlighten all the molecular mechanisms of estrogen and estrogen replacement therapies in AD. Along‐with this, the association between estrogen, estrogen‐metabolising enzymes and ApoE protein polymorphisms will also be discussed in postmenopausal AD.