bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA sequencing reveals the local cell landscape in mouse epididymal initial segment during aging
Authors: Zhuang Jintao , Li Xiangping , Yao Jiahui , Sun Xiangzhou , Liu Jiumin , Nie Hua , Hu Yang , Tu Xiangan , Liu Huang , Qin Weibing , Xie Yun 
Published: May 2023

AbstractBackgroundMorphological and functional alterations in aging reproductive organs result in decreased male fertility. The epididymis functions as the transition region for post-testicular sperm maturation. And we have previously demonstrated that the epididymal initial segment (IS), a region of the reproductive tract essential for sperm maturation and capacitation, undergoes considerable histological changes and chronic immune activation in mice during aging. However, the local aging-associated cellular and molecular changes in the aged epididymal IS are poorly understood.ResultsWe conducted single-cell RNA sequencing analysis on the epididymal IS of young (3-month-old) and old (21-month-old) mice. In total, 10,027 cells from the epididymal IS tissues of young and old mice were obtained and annotated. The cell composition, including the expansion of a principal cell subtype andMs4a4bHiMs4a6bHiT cells, changed with age. Aged principal cells displayed multiple functional gene expression changes associated with acrosome reaction and sperm maturation, suggesting an asynchronous process of sperm activation and maturation during epididymal transit. Meanwhile, aging-related altered pathways in immune cells, especially the “cell chemotaxis” inCx3cr1Hiepididymal dendritic cells (eDCs), were identified. The monocyte-specific expression of chemokineCcl8increased with age in eDCs. And the aged epididymal IS showed increased inflammatory cell infiltration and cytokine secretion. Furthermore, cell–cell communication analysis indicated that age increased inflammatory signaling in the epididymal IS.ConclusionContrary to the general pattern of lower immune responses in the male proximal genital tract, we revealed an inflammaging status in mouse epididymal initial segment. These findings will allow future studies to enable the delay of male reproductive aging via immune regulation.
Age, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody
Authors: Faresjö Rebecca , Sehlin Dag , Syvänen Stina 
Published: May 2023

Abstract
Background
Transferrin receptor 1 (TfR1) mediated brain delivery of antibodies could become important for increasing the efficacy of emerging immunotherapies in Alzheimer's disease (AD). However, age, dose, binding to TfR1 on blood cells, and pathology could influence the TfR1-mediated transcytosis of TfR1-binders across the blood–brain barrier (BBB). The aim of the study was, therefore, to investigate the impact of these factors on the brain delivery of a bispecific TfR1-transported Aβ-antibody, mAb3D6-scFv8D3, in comparison with the conventional antibody mAb3D6.

Methods
Young (3–5 months) and aged (17–20 months) WT and tg-ArcSwe mice (AD model) were injected with 125I-labeled mAb3D6-scFv8D3 or mAb3D6. Three different doses were used in the study, 0.05 mg/kg (low dose), 1 mg/kg (high dose), and 10 mg/kg (therapeutic dose), with equimolar doses for mAb3D6. The dose-corrected antibody concentrations in whole blood, blood cells, plasma, spleen, and brain were evaluated at 2 h post-administration. Furthermore, isolated brains were studied by autoradiography, nuclear track emulsion, and capillary depletion to investigate the intrabrain distribution of the antibodies, while binding to blood cells was studied in vitro using blood isolated from young and aged mice.

Results
The aged WT and tg-ArcSwe mice showed significantly lower brain concentrations of TfR-binding [125I]mAb3D6-scFv8D3 and higher concentrations in the blood cell fraction compared to young mice. For [125I]mAb3D6, no significant differences in blood or brain delivery were observed between young and aged mice or between genotypes. A low dose of [125I]mAb3D6-scFv8D3 was associated with increased relative parenchymal delivery, as well as increased blood cell distribution. Brain concentrations and relative parenchymal distribution of [125I]mAb3D6-scFv8D6 did not differ between tg-ArcSwe and WT mice at this early time point but were considerably increased compared to those observed for [125I]mAb3D6.

Conclusion
Age-dependent differences in blood and brain concentrations were observed for the bispecific antibody mAb3D6-scFv8D3 but not for the conventional Aβ antibody mAb3D6, indicating an age-related effect on TfR1-mediated brain delivery. The lowest dose of [125I]mAb3D6-scFv8D3 was associated with higher relative BBB penetration but, at the same time, a higher distribution to blood cells. Overall, Aβ-pathology did not influence the early brain distribution of the bispecific antibody. In summary, age and bispecific antibody dose were important factors determining brain delivery, while genotype was not.
Intra-articular injection of bone marrow aspirate concentrate (BMAC) or adipose-derived stem cells (ADSCs) for knee osteoarthritis: a prospective comparative clinical trial
Authors: Pintore Andrea , Notarfrancesco Donato , Zara Arnaldo , Oliviero Antonio , Migliorini Filippo , Oliva Francesco , Maffulli Nicola 
Published: May 2023

Abstract
Background
We determined whether autologous mesenchymal stem cells (MSCs) injections provide clinical and functional improvements in knee osteoarthritis (KOA) patients, and whether the results differ between autologous bone marrow cells (BMAC) and adipose-derived stromal cells (ADSCs).

Methods
Between January 2021 and April 2022, 51 patients undergoing intra-articular injection of BMAC and 51 patients undergoing intra-articular injection of ADSCs were prospectively recruited. The Kellgren and Lawrence (K–L) classification was used to grade the severity of osteoarthritis. Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), and visual analog scale (VAS) were collected for all 102 patients in the previous week before the procedures, and at the one and 6 months from injection.

Results
Knee KOOS scores, knee OKS scores, and VAS pain scores changed in similar ways in the two treatment groups. Both treatment groups demonstrated significant improvement pre-procedure to post-procedure in knee KOOS scores (p < 0.0001), knee OKS scores (p < 0.0001), and VAS pain scores (p < 0.0001). Patients with K–L grade 2 showed better functional and clinical outcomes than patients with K–L grades 3 and 4 (p < 0.0001).

Conclusion
Both intra-articular BMAC and ADSC injections significantly improved pain and functional outcomes at 6-month follow-up in patients with KOA. The difference between BMAC and ADCSs groups as tissue sources of MSCs was not statistically significant in terms of clinical and functional outcomes.
Exploring the effect of Yinzhihuang granules on alcoholic liver disease based on pharmacodynamics, network pharmacology and molecular docking
Authors: Tan Yingying , Zhang Fanqin , Fan Xiaotian , Lu Shan , Liu Yingying , Wu Zhishan , Huang Zhihong , Wu Chao , Cheng Guoliang , Li Bing , Huang Jiaqi , Stalin Antony , Zhou Wei , Wu Jiarui 
Published: May 2023

Abstract
Background
Yinzhihuang granules (YZHG) is a commonly used Chinese patent medicine for the treatment of liver disease. However, the mechanism of YZHG in alcoholic liver disease (ALD) is still unclear.

Methods
This study combined liquid chromatography-mass spectrometry technology, pharmacodynamics, network pharmacology and molecular docking methods to evaluate the potential mechanism of YZHG in the treatment of ALD.

Results
A total of 25 compounds including 4-hydroxyacetophenone, scoparone, geniposide, quercetin, baicalin, baicalein, chlorogenic acid and caffeic acid in YZHG were identified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The pharmacodynamic investigations indicated that YZHG could improve liver function and the degree of liver tissue lesions, and reduce liver inflammation and oxidative stress in ALD mice. Network pharmacology analysis showed that YZHG treated ALD mainly by regulating inflammation-related signaling pathways such as the PI3K-Akt signaling pathway. The results of the PPI network and molecular docking showed that the targets of SRC, HSP90AA1, STAT3, EGFR and AKT1 could be the key targets of YZHG in the treatment of ALD.

Conclusion
This study explored the potential compounds, potential targets and signaling pathways of YZHG in the treatment of ALD, which is helpful to clarify the efficacy and mechanism of YZHG and provide new insights for the clinical application of YZHG.
Parent-adolescent informant discrepancy on the Strengths and Difficulties Questionnaire in the UK Millennium Cohort Study
Authors: Booth Charlotte , Moreno-Agostino Dario , Fitzsimons Emla 
Published: May 2023

Abstract
Background
Developmental researchers often use a multi-informant approach to measure adolescent behaviour and adjustment, but informant discrepancies are common. In general population samples, it is often found that parents report more positive and less negative outcomes than adolescents themselves. This study aimed to investigate factors associated with informant discrepancy, including adolescent sex, and parental level of psychological distress and education.

Methods
Informant discrepancy on the Strengths and Difficulties Questionnaire was investigated using a Latent Difference Score (LDS) approach, which estimates the true difference between parent and adolescent reports in a structural equation model. The sample were parent-adolescent dyads from the seventh wave of the UK Millennium Cohort Study (N = 6947, 49.3% female, aged 17 years).

Results
Parents reported lower levels of difficulties (emotion symptoms, peer problems, conduct problems), and higher levels of pro-social behaviour than adolescents themselves. Conditional effects were found, as discrepancy was greater amongst parent-daughter dyads for emotion and peer problems, and greater amongst parent-son dyads for conduct problems and pro-social behaviour. Parent-adolescent discrepancy was also greater generally if parents had a lower level of psychological distress or a higher level of education.

Conclusions
In a large general population sample from the UK, it was found that adolescents tended to report more negative and less positive outcomes than parents reported about them. Conditional effects were found at the parent and adolescent level suggesting that specific informant biases are likely to impact the measurement of adolescent behaviour and adjustment across reporters.
Beneficial effects of luseogliflozin on lipid profile and liver function in patients with type 2 diabetes mellitus (BLUE trial): a single-center, single-arm, open-label prospective study
Authors: Hajika Yuriko , Kawaguchi Yuji , Hamazaki Kenji , Kumeda Yasuro 
Published: May 2023

Abstract
Background
Arteriosclerosis and non-alcoholic fatty liver disease are major complications of diabetes mellitus. Hyperglycemia, insulin resistance, obesity, and metabolic syndrome are associated with the progression of these complications. Sodium-glucose transporter 2 inhibitors such as luseogliflozin are oral hypoglycemic agents that reduce glucose levels, induce loss of weight or body fat, and improve liver function. However, the effects of these agents on lipid profiles are unclear. Therefore, this study aimed to investigate these effects and their relationship with arteriosclerosis and non-alcoholic fatty liver disease.

Methods
This single-center, single-arm, open-labeled prospective study enrolled 25 outpatients with type 2 diabetes mellitus who visited Minami Osaka Hospital. Laboratory tests and body measurements were performed at weeks 0 and 24. Luseogliflozin was started at 2.5 mg/day after breakfast, and data from weeks 0 and 24 were evaluated. There were no changes in the doses of other antidiabetic and dyslipidemia drugs a month prior to or during the study.

Results
The patients showed significant reductions in the levels of triglycerides, remnant-like particle cholesterol, and triglyceride/high-density lipoprotein cholesterol ratio, along with significant increases in the levels of high-density lipoprotein cholesterol and apolipoprotein A-1. Alanine aminotransferase, γ-glutamyl transpeptidase, and the fatty liver index were significantly reduced.

Conclusions
Luseogliflozin-induced changes in the lipid profile were related to the suppression or improvement of arteriosclerosis and liver function, respectively. Patients who received this drug also showed improvements in the levels of liver enzymes and reductions in the fatty liver index. Earlier use of luseogliflozin might prevent diabetic complications.
Trial registration This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000043595) on April 6th, 2021
Severe lumbar pain in an adolescent due to idiopathic vena cava thrombosis: a case report
Authors: Gevers Anthony , Dessart Patricia , Vanmarsenille Jean-Marie , Vande Berg Bruno , Yildiz Halil , Hatem Samar M. 
Published: May 2023

Abstract
Background
Lumbar back pain in an adolescent is generally musculoskeletal, that is, due to a muscle strain or scoliosis. This case describes a young individual without any previous health issues who rapidly developed a life-threatening condition, though initially presenting with “only” back pain.

Case presentation
A 16-year-old Caucasian male patient was admitted twice to the emergency department with debilitating lumbar pain without neurological or vascular symptoms. Imagery showed an extensive thrombosis of the inferior vena cava. No external cause, structural abnormality, or any systemic disease were found that predisposed the patient to this highly unusual vaso-occlusive incident.

Conclusion
Thrombosis of the inferior vena cava is a rare but life-threatening entity. It is underrecognized and associated with serious short- and long-term morbidity and mortality. Increased awareness is essential because deep vein thrombosis in children seems to cause atypical symptoms, such as spinal pain or the absence of edema of the lower limbs, as in the present case.
Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
Authors: Baldassarro Vito Antonio , Perut Francesca , Cescatti Maura , Pinto Valentina , Fazio Nicola , Alastra Giuseppe , Parziale Valentina , Bassotti Alessandra , Fernandez Mercedes , Giardino Luciana , Baldini Nicola , Calzà Laura 
Published: May 2023

Abstract
Background
Greater knowledge of mesenchymal stromal cell (MSC)-based therapies is driving the research into their secretome, identified as the main element responsible for their therapeutic effects. The aim of this study is to characterize the individual variability of the secretome of adipose tissue-derived MSCs (adMSCs) with regard to potential therapeutical applications in neurology.

Methods
adMSCs were isolated from the intact adipose tissue of ten subjects undergoing abdominal plastic surgery or reduction mammoplasty. Two commercial lines were also included. We analyzed the expansion rate, production, and secretion of growth factors of interest for neurological applications (VEGF-A, BDNF, PDGF-AA and AA/BB, HGF, NGF, FGF-21, GDNF, IGF-I, IGF-II, EGF and FGF-2). To correlate these characteristics with the biological effects on the cellular targets, we used individual media conditioned with adMSCs from the various donors on primary cultures of neurons/astrocytes and oligodendrocyte precursor cells (OPCs) exposed to noxious stimuli (oxygen–glucose deprivation, OGD) to evaluate their protective and promyelinating properties, using MSC medium as a control group.

Results
The MSC secretome showed significant individual variability within the considered population with regard to PDGF-AA, PDGF-AB/BB, VEGF-A and BDNF. None of the MSC-derived supernatants affected neuron viability in normoxia, while substantial protection by high BDNF-containing conditioned MSC medium was observed in neuronal cultures exposed to OGD conditions. In OPC cultures, the MSC-derived supernatants protected cells from OGD-induced cell death, also increasing the differentiation in mature oligodendrocytes. Neuroprotection showed a positive correlation with VEGF-A, BDNF and PDGF-AA concentrations in the culture supernatants, and an inverse correlation with HGF, while OPC differentiation following OGD was positively correlated to PDGF-AA concentration.

Conclusions
Despite the limited number of adMSC donors, this study showed significant individual variability in the biological properties of interest for neurological applications for adMSC secretome, an under-researched aspect which may represent an important step in the translation of MSC-derived acellular products to clinical practice. We also showed the potential protection capability of MSC conditioned medium on neuronal and oligodendroglial lineages exposed to oxygen–glucose deprivation. These effects are directly correlated to the concentration of specific growth factors, and indicate that the remyelination should be included as a primary target in MSC-based therapies.
ISG15 suppresses ovulation and female fertility by ISGylating ADAMTS1
Authors: Chen Yaru , Zhou Jiawei , Wu Shang , Wang Lei , Chen Gaogui , Chen Dake , Peng Xianwen , Miao Yi-Liang , Mei Shuqi , Li Fenge 
Published: May 2023

Abstract
Background
ISGylation is a post-translational protein modification that regulates many life activities, including immunomodulation, antiviral responses, and embryo implantation. The exact contribution of ISGylation to folliculogenesis remains largely undefined.

Results
Here, Isg15 knockout in mice causes hyperfertility along with sensitive ovarian responses to gonadotropin, such as increases in cumulus expansion and ovulation rate. Moreover, ISG15 represses the expression of ovulation-related genes in an ISGylation-dependent manner. Mechanistically, ISG15 binds to ADAMTS1 via the ISG15-conjugating system (UBA7, UBE2L6, and HERC6), ISGylating ADAMTS1 at the binding sites Lys309, Lys593, Lys597, and Lys602, resulting in ADAMTS1 degradation via a 20S proteasome-dependent pathway.

Conclusion
Taken together, the present study demonstrates that covalent ISG15 conjugation produces a novel regulatory axis of ISG15-ADAMTS1 that enhances the degradation of ADAMTS1, thereby compromising ovulation and female fertility.
Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Authors: Semikasev Eugen , Ahlemeyer Barbara , Acker Till , Schänzer Anne , Baumgart-Vogt Eveline 
Published: May 2023

AbstractPeroxisomes are eukaryotic organelles that rapidly change in number depending on the metabolic requirement of distinct cell types and tissues. In the brain, these organelles are essential for neuronal migration and myelination during development and their dysfunction is associated with age-related neurodegenerative diseases. Except for one study analysing ABCD3-positive peroxisomes in neurons of the frontal neocortex of Alzheimer disease (AD) patients, no data on other brain regions or peroxisomal proteins are available. In the present morphometric study, we quantified peroxisomes labelled with PEX14, a metabolism-independent peroxisome marker, in 13 different brain areas of 8 patients each either with low, intermediate or high AD neuropathological changes compared to 10 control patients. Classification of patient samples was based on the official ABC score. During AD-stage progression, the peroxisome density decreased in the area entorhinalis, parietal/occipital neocortex and cerebellum, it increased and in later AD-stage patients decreased in the subiculum and hippocampal CA3 region, frontal neocortex and pontine gray and it remained unchanged in the gyrus dentatus, temporal neocortex, striatum and inferior olive. Moreover, we investigated the density of catalase-positive peroxisomes in a subset of patients (> 80 years), focussing on regions with significant alterations of PEX14-positive peroxisomes. In hippocampal neurons, only one third of all peroxisomes contained detectable levels of catalase exhibiting constant density at all AD stages. Whereas the density of all peroxisomes in neocortical neurons was only half of the one of the hippocampus, two thirds of them were catalase-positive exhibiting increased levels at higher ABC scores. In conclusion, we observed spatiotemporal differences in the response of peroxisomes to different stages of AD-associated pathologies.
Graphical Abstract
A potential immunotherapeutic and prognostic biomarker for multiple tumors including glioma: SHOX2
Authors: Wu Xiaocong , Chen Hui , You Chao , Peng Zongjun 
Published: May 2023

AbstractBackgroundShort stature homeobox 2 (SHOX2) is significant gene in the development and progression of multiple types of tumors. Nonetheless, the biological role of SHOX2 within pan-cancer datasets has not been investigated. Thus, comprehensive bioinformatics analyses of pan-cancer datasets were conducted to explore how SHOX2 regulates tumorigenesis.MethodsA variety of tumor datasets and online analytical tools, including SangerBox, TIMER2, LinkedOmic, GEPIA2 and cBioPortal, were applied to explore SHOX2 expression in various tumors. To ascertain the connections between SHOX2 expression and genetic alterations, SHOX2-related genes and tumor immunity, the pan-cancer datasets were examined. In vitro assays were applied to verify the biological functions of SHOX2 in glioma cells via CCK-8, wound healing, Transwell and colony formation assays.ResultsAnalyses found that SHOX2 was overexpressed in multiple cancer types. SHOX2 expression level was significantly correlated with isocitrate dehydrogenase (IDH), 1p/19q, O6-methylguanine DNA methyltransferase (MGMT) status and new types of glioma patients. High mRNA expression levels of SHOX2 were associated with a poor prognosis in multiple tumor patients. KEGG enrichment analysis showed that SHOX2-related genes were associated with cell cycle and DNA damage repair. Genetic alterations of SHOX2 were identified in multiple types of cancers, including duplications and deep mutations. Immune analysis showed that SHOX2 was closely correlated with the tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen and neoantigens and immune checkpoint (ICP) in a variety of tumors and could influence the immunotherapy sensitivity of cancers. CCK-8, wound healing, Transwell and colony formation experiments showed that SHOX2 knockdown inhibited glioma cell proliferation, migration, invasion and colony formation abilities.ConclusionSHOX2 was overexpressed in multiple cancer types in TCGA cohort. SHOX2 knockdown inhibited glioma cell proliferation, migration and colony formation ability. Our study showed that SHOX2 may be an immunotherapeutic and promising prognostic biomarker in certain types of tumors.