bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging-related aneuploidy is associated with mitochondrial imbalance and failure of spindle assembly
Authors: Zhang Fa-Li , Li Wei-Dong , Zhu Ke-Xin , Zhou Xu , Li Lan , Lee Tin-Lap , Shen Wei 
Published: July 2023

AbstractDespite aging is closely linked to increased aneuploidy in the oocytes, the mechanism of how aging affects aneuploidy remains largely elusive. Here, we applied single-cell parallel methylation and transcriptome sequencing (scM&T-seq) data from the aging mouse oocyte model to decode the genomic landscape of oocyte aging. We found a decline in oocyte quality in aging mice, as manifested by a significantly lower rate of first polar body exclusion (P < 0.05), and dramatically increasing aneuploidy rate (P < 0.01). Simultaneously, scM&T data suggested that a large number of differential expression genes (DEGs) and differential methylation regions (DMRs) were obtained. Next, we identified strong association of spindle assembly and mitochondrial transmembrane transport during oocyte aging. Moreover, we verified the DEGs related to spindle assembly (such as Naip1, Aspm, Racgap1, Zfp207) by real-time quantitative PCR (RT-qPCR) and checked the mitochondrial dysfunction by JC-1 staining. Pearson correlation analysis found that receptors for mitochondrial function were strongly positively correlated with abnormal spindle assembly (P < 0.05). In conclusion, these results suggested that the mitochondrial dysfunction and abnormal spindle assembly of aging oocytes ultimately may lead to increased oocyte aneuploidy.
Potential diagnostic biomarkers: 6 cuproptosis- and ferroptosis-related genes linking immune infiltration in acute myocardial infarction
Authors: Miao Mengdan , Cao Shanhu , Tian Yifei , Liu Da , Chen Lixia , Chai Qiaoying , Wei Mei , Sun Shaoguang , Wang Le , Xin Shuanli , Liu Gang , Zheng Mingqi 
Published: July 2023

AbstractThe current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment.
ATPase activity of DFCP1 controls selective autophagy
Authors: Nähse Viola , Raiborg Camilla , Tan Kia Wee , Mørk Sissel , Torgersen Maria Lyngaas , Wenzel Eva Maria , Nager Mireia , Salo Veijo T. , Johansen Terje , Ikonen Elina , Schink Kay Oliver , Stenmark Harald 
Published: July 2023

AbstractCellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction. Here, we demonstrate that DFCP1 is an ATPase that is activated by membrane binding and dimerizes in an ATP-dependent fashion. Whereas depletion of DFCP1 has a minor effect on bulk autophagic flux, DFCP1 is required to maintain the autophagic flux of p62 under both fed and starved conditions, and this is dependent on its ability to bind and hydrolyse ATP. While DFCP1 mutants defective in ATP binding or hydrolysis localize to forming omegasomes, these omegasomes fail to constrict properly in a size-dependent manner. Consequently, the release of nascent autophagosomes from large omegasomes is markedly delayed. While knockout of DFCP1 does not affect bulk autophagy, it inhibits selective autophagy, including aggrephagy, mitophagy and micronucleophagy. We conclude that DFCP1 mediates ATPase-driven constriction of large omegasomes to release autophagosomes for selective autophagy.
Weakly coordinated Li ion in single-ion-conductor-based composite enabling low electrolyte content Li-metal batteries
Authors: Kwon Hyeokjin , Choi Hyun-Ji , Jang Jung-kyu , Lee Jinhong , Jung Jinkwan , Lee Wonjun , Roh Youngil , Baek Jaewon , Shin Dong Jae , Lee Ju-Hyuk , Choi Nam-Soon , Meng Ying Shirley , Kim Hee-Tak 
Published: July 2023

AbstractThe pulverization of lithium metal electrodes during cycling recently has been suppressed through various techniques, but the issue of irreversible consumption of the electrolyte remains a critical challenge, hindering the progress of energy-dense lithium metal batteries. Here, we design a single-ion-conductor-based composite layer on the lithium metal electrode, which significantly reduces the liquid electrolyte loss via adjusting the solvation environment of moving Li+ in the layer. A Li||Ni0.5Mn0.3Co0.2O2 pouch cell with a thin lithium metal (N/P of 2.15), high loading cathode (21.5 mg cm−2), and carbonate electrolyte achieves 400 cycles at the electrolyte to capacity ratio of 2.15 g Ah−1 (2.44 g Ah−1 including mass of composite layer) or 100 cycles at 1.28 g Ah−1 (1.57 g Ah−1 including mass of composite layer) under a stack pressure of 280 kPa (0.2 C charge with a constant voltage charge at 4.3 V to 0.05 C and 1.0 C discharge within a voltage window of 4.3 V to 3.0 V). The rational design of the single-ion-conductor-based composite layer demonstrated in this work provides a way forward for constructing energy-dense rechargeable lithium metal batteries with minimal electrolyte content.
Glycopeptide database search and de novo sequencing with PEAKS GlycanFinder enable highly sensitive glycoproteomics
Authors: Sun Weiping , Zhang Qianqiu , Zhang Xiyue , Tran Ngoc Hieu , Ziaur Rahman M. , Chen Zheng , Peng Chao , Ma Jun , Li Ming , Xin Lei , Shan Baozhen 
Published: July 2023

AbstractHere we present GlycanFinder, a database search and de novo sequencing tool for the analysis of intact glycopeptides from mass spectrometry data. GlycanFinder integrates peptide-based and glycan-based search strategies to address the challenge of complex fragmentation of glycopeptides. A deep learning model is designed to capture glycan tree structures and their fragment ions for de novo sequencing of glycans that do not exist in the database. We performed extensive analyses to validate the false discovery rates (FDRs) at both peptide and glycan levels and to evaluate GlycanFinder based on comprehensive benchmarks from previous community-based studies. Our results show that GlycanFinder achieved comparable performance to other leading glycoproteomics softwares in terms of both FDR control and the number of identifications. Moreover, GlycanFinder was also able to identify glycopeptides not found in existing databases. Finally, we conducted a mass spectrometry experiment for antibody N-linked glycosylation profiling that could distinguish isomeric peptides and glycans in four immunoglobulin G subclasses, which had been a challenging problem to previous studies.
A cytochrome P450 CYP87A4 imparts sterol side-chain cleavage in digoxin biosynthesis
Authors: Carroll Emily , Ravi Gopal Baradwaj , Raghavan Indu , Mukherjee Minakshi , Wang Zhen Q. 
Published: July 2023

AbstractDigoxin extracted from the foxglove plant is a widely prescribed natural product for treating heart failure. It is listed as an essential medicine by the World Health Organization. However, how the foxglove plant synthesizes digoxin is mostly unknown, especially the cytochrome P450 sterol side chain cleaving enzyme (P450scc), which catalyzes the first and rate-limiting step. Here we identify the long-speculated foxglove P450sccthrough differential transcriptomic analysis. This enzyme converts cholesterol and campesterol to pregnenolone, suggesting that digoxin biosynthesis starts from both sterols, unlike previously reported. Phylogenetic analysis indicates that this enzyme arises from a duplicated cytochrome P450CYP87Agene and is distinct from the well-characterized mammalian P450scc. Protein structural analysis reveals two amino acids in the active site critical for the foxglove P450scc’s sterol cleavage ability. Identifying the foxglove P450sccis a crucial step toward completely elucidating digoxin biosynthesis and expanding the therapeutic applications of digoxin analogs in future work.
Molecular basis and design principles of switchable front-rear polarity and directional migration in Myxococcus xanthus
Authors: Carreira Luís António Menezes , Szadkowski Dobromir , Lometto Stefano , Hochberg Georg. K. A. , Søgaard-Andersen Lotte 
Published: July 2023

AbstractDuring cell migration, front-rear polarity is spatiotemporally regulated; however, the underlying design of regulatory interactions varies. In rod-shaped Myxococcus xanthus cells, a spatial toggle switch dynamically regulates front-rear polarity. The polarity module establishes front-rear polarity by guaranteeing front pole-localization of the small GTPase MglA. Conversely, the Frz chemosensory system, by acting on the polarity module, causes polarity inversions. MglA localization depends on the RomR/RomX GEF and MglB/RomY GAP complexes that localize asymmetrically to the poles by unknown mechanisms. Here, we show that RomR and the MglB and MglC roadblock domain proteins generate a positive feedback by forming a RomR/MglC/MglB complex, thereby establishing the rear pole with high GAP activity that is non-permissive to MglA. MglA at the front engages in negative feedback that breaks the RomR/MglC/MglB positive feedback allosterically, thus ensuring low GAP activity at this pole. These findings unravel the design principles of a system for switchable front-rear polarity.
The structural pathology for hypophosphatasia caused by malfunctional tissue non-specific alkaline phosphatase
Authors: Yu Yating , Rong Kewei , Yao Deqiang , Zhang Qing , Cao Xiankun , Rao Bing , Xia Ying , Lu Yi , Shen Yafeng , Yao Ying , Xu Hongtao , Ma Peixiang , Cao Yu , Qin An 
Published: July 2023

AbstractHypophosphatasia (HPP) is a metabolic bone disease that manifests as developmental abnormalities in bone and dental tissues. HPP patients exhibit hypo-mineralization and osteopenia due to the deficiency or malfunction of tissue non-specific alkaline phosphatase (TNAP), which catalyzes the hydrolysis of phosphate-containing molecules outside the cells, promoting the deposition of hydroxyapatite in the extracellular matrix. Despite the identification of hundreds of pathogenic TNAP mutations, the detailed molecular pathology of HPP remains unclear. Here, to address this issue, we determine the crystal structures of human TNAP at near-atomic resolution and map the major pathogenic mutations onto the structure. Our study reveals an unexpected octameric architecture for TNAP, which is generated by the tetramerization of dimeric TNAPs, potentially stabilizing the TNAPs in the extracellular environments. Moreover, we use cryo-electron microscopy to demonstrate that the TNAP agonist antibody (JTALP001) forms a stable complex with TNAP by binding to the octameric interface. The administration of JTALP001 enhances osteoblast mineralization and promoted recombinant TNAP-rescued mineralization in TNAP knockout osteoblasts. Our findings elucidate the structural pathology of HPP and highlight the therapeutic potential of the TNAP agonist antibody for osteoblast-associated bone disorders.
Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFβ pathways promote diabetic wound healing
Authors: Niu Hong , Guan Ya , Zhong Ting , Ma Liang , Zayed Mohamed , Guan Jianjun 
Published: July 2023

AbstractVarious therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFβ receptor II inhibitor (PTβR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTβR2I inhibits the TGFβ1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTβR2I does not interfere with the TGFβ1/Smad2/3 pathway that is required to regulate myofibroblasts, a critical cell type for wound healing. The hydrogel’s ability to scavenge ROS in diabetic wounds further decreases inflammation. Single-dose application of the wound dressing significantly accelerates wound healing with complete wound closure after 14 days. Overall, using wound dressings capable of adaptively modulating TGFβ pathways provides a new strategy for diabetic wound treatment.
Spatial association of surface water quality and human cancer in China
Authors: Wang Zixing , Gu Wentao , Guo Xiaobo , Xue Fang , Zhao Jing , Han Wei , Li Hairong , Chen Wangyue , Hu Yaoda , Yang Cuihong , Zhang Luwen , Wu Peng , Chen Yali , Zhao Yujie , Du Jin , Jiang Jingmei 
Published: July 2023

AbstractLittle is known about the association between surface water quality and cancer incidence, especially in China. Drinking water quality has been linked to the incidence of several cancers in individual-level studies. However, few studies have attempted to examine multiple pollutants and multiple cancers at population level. This study used water monitoring and population-level cancer data from across China to examine spatial associations between water pollutants and types of cancer. We found a “dose–response” relationship between the number of pollutants present at high levels and cancer incidence. These results provide evidence of a nationwide spatial association between water quality and cancer in China. The precise relationship varies with cancers and pollutants. However, the overall consistency of the “dose–response” relationship suggests that surface water quality is an important factor in cancer incidence. Our findings highlight new issues such as the changing effects when different pollutants co-exist and an increasing number of new cancer cases partially attributable to poor water quality. Our work also points to some ways to deal with these challenges.
Extension and update of multiscale monthly household carbon footprint in Japan from 2011 to 2022
Authors: Huang Liqiao , Montagna Sebastian , Wu Yi , Chen Zhiheng , Tanaka Kenji , Yoshida Yoshikuni , Long Yin 
Published: July 2023

AbstractHousehold consumption significantly contributes to greenhouse gas emissions as it is the largest component of final demand in the national accounting system. Nevertheless, there is an apparent lack of comprehensive and consistent datasets detailing emissions from household consumption. Here, we expand and update Japan’s multiscale monthly household carbon footprint from January 2011 to September 2022, combining data from government statistics and surveys. We constructed a dataset comprising 37,692 direct and 4,852,845 indirect emission records, covering households at the national, regional, and prefectural city levels. The dataset provides critical spatiotemporal information that allows for revealing carbon emission patterns, pinpointing primary sources of emissions, and discerning regional variances. Moreover, the inclusion of micro-scale carbon footprint data enables the identification of specific consumption habits, thereby regulating individual consumption behavior to achieve a low-carbon society.
Cellular immunity reflects the persistent symptoms among COVID-19 recovered patients in Japan
Authors: Miyata Yoshiharu , Suzuki Kohjin , Nagano Tatsuya , Iida Keiji , Hasegawa Takehiro , Uga Hitoshi , Matsuoka Hiroshi 
Published: July 2023

AbstractCoronavirus disease (COVID-19) often causes persistent symptoms long after infection, referred to as “long COVID” or post-acute COVID-19 syndrome (PACS). This phenomenon has been studied primarily concerning B-cell immunity, while the involvement of T-cell immunity is still unclear. This retrospective study aimed to examine the relationship among the number of symptoms, cytokine levels, and the Enzyme-linked immunosorbent spot (ELISPOT) assay data in patients with COVID-19. To examine inflammatory conditions, plasma interleukin (IL)-6, IL-10, IL-18, chemokine ligand 9 (CXCL9), chemokine ligand 3 (CCL3), and vascular endothelial growth factor (VEGF) levels were analyzed using plasma obtained from COVID-19 recovery patients and healthy controls (HC). These levels were significantly higher in the COVID-19 group than those in the HC group. ELISPOT assays were performed to investigate the correlation between COVID-19 persistent symptoms and T-cell immunity. Cluster analysis of ELISPOT categorized COVID-19 recovery patients in the ELISPOT-high and -low groups, based on the values of S1, S2, and N. The number of persistent symptoms was significantly higher in the ELISPOT-low group than those in the ELISPOT-high group. Thus, T cell immunity is critical for the rapid elimination of COVID-19 persistent symptoms, and its measurement immediately after COVID-19 recovery might predict long-term COVID-19 or PACS.
VDR alleviates endothelial cell injury in arteriovenous fistula through inhibition of P66Shc-mediated mitochondrial ROS
Authors: Han Ya-chun , Liu Yu-ting , Zhang Hao , Xu Yong , Liu Jun , Chen Hong , Song Na , Qin Dong-lu , Yang Shikun 
Published: July 2023

AbstractTo investigate the effects and mechanism of Vitamin D receptor (VDR) signaling on arteriovenous fistula (AVF) endothelial cell injury. Venous tissues of AVF stenosis patients were collected and analyzed, vascular morphology, reactive oxygen species (ROS), and the expression of VDR, P66Shc, fibronectin (FN), collagen-1 (Col-1) were detected. In addition, human umbilical vein endothelial cells (HUVECs) was used in in vitro studies. HUVECs was incubated with transforming growth factor-beta (TGF-β, 50 ng/ml). Aditionally, paricalcitol, VDR overexpression plasmid and Pin1 inhibitor Juglone were used to investigate the regulatory mechanism of VDR in mitochondrial ROS. The parameters of ROS (e.g. MitoSox) and the expression of FN, Col-1 were tested. Moreover, the mitochondrial translocation of P66Shc was analyzed. The expression of VDR was obviously decreased in the venous tissues of AVF stenosis patients. On the contrary, the expression of P66Shc, P-P66Shc, FN, Col-1 and 8-OHdG were increased significantly in the venous tissues of AVF stenosis patients (P < 0.05). In line with this, the level of mitochondrial ROS and the expression of P66Shc, P-P66Shc, FN, Col-1 increased obviously in HUVECs cells under TGF-β condition. Both VDR over-expression plasmid and Pin1 inhibitor Juglone could alleviate TGF-β induced endothelial injury. Mechanistically, VDR overexpression plasmid and Juglone could inhibit the expression of Pin1, and then restrain P66Shc mitochondrial translocation, eventually reduce the level of mitochondrial ROS. Our research indicated that activation of VDR could alleviate venous endothelial cell dysfunction through inhibiting Pin1-mediated mitochondrial translocation of P66Shc and consequently reducing mitochondrial ROS. It suggested that VDR signaling might be an effective target for AVF stenosis treatment.
Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway
Authors: Farrag Eman A. E. , Hammad Maha O. , Safwat Sally M. , Hamed Shereen , Hellal Doaa 
Published: July 2023

AbstractDiabetes mellitus is a common metabolic disorder. About two-thirds of diabetic patients develop diabetic cardiomyopathy (DCM), which becomes a challenging issue as it severely threatens the patient’s life. Hyperglycemia and the resulting advanced glycated end products (AGE) and their receptor (RAGE)/High Mobility Group Box-1 (HMGB-1) molecular pathway are thought to be key players. Recently, artemisinin (ART) has gained more attention owing to its potent biological activities beyond its antimalarial effect. Herein, we aim to evaluate the effect of ART on DCM and the possible underlying mechanisms. Twenty-four male Sprague–Dawley rats were divided into: control, ART, type 2 diabetic and type 2 diabetic treated with ART groups. At the end of the research, the ECG was recorded, then the heart weight to body weight (HW/BW) ratio, fasting blood glucose, serum insulin and HOMA-IR were evaluated. Cardiac biomarkers (CK-MB and LDH), oxidative stress markers, IL-1β, AGE, RAGE and HMGB-1 expression were also measured. The heart specimens were stained for H&E as well as Masson’s trichrome. DCM induced disturbances in all studied parameters; contrary to this, ART improved these insults. Our study concluded that ART could improve DCM through modulation of the AGE-RAGE/HMGB-1 signaling pathway, with subsequent impacts on oxidative stress, inflammation and fibrosis. ART could therefore be a promising therapy for the management of DCM.
Optimization of laser dosimetry based on patient-specific anatomical models for the ablation of pancreatic ductal adenocarcinoma tumor
Authors: Namakshenas Pouya , Di Matteo Francesco Maria , Bianchi Leonardo , Faiella Eliodoro , Stigliano Serena , Quero Giuseppe , Saccomandi Paola 
Published: July 2023

AbstractLaser-induced thermotherapy has shown promising potential for the treatment of unresectable primary pancreatic ductal adenocarcinoma tumors. Nevertheless, heterogeneous tumor environment and complex thermal interaction phenomena that are established under hyperthermic conditions can lead to under/over estimation of laser thermotherapy efficacy. Using numerical modeling, this paper presents an optimized laser setting for Nd:YAG laser delivered by a bare optical fiber (300 µm in diameter) at 1064 nm working in continuous mode within a power range of 2–10 W. For the thermal analysis, patient-specific 3D models were used, consisting of tumors in different portions of the pancreas. The optimized laser power and time for ablating the tumor completely and producing thermal toxic effects on the possible residual tumor cells beyond the tumor margins were found to be 5 W for 550 s, 7 W for 550 s, and 8 W for 550 s for the pancreatic tail, body, and head tumors, respectively. Based on the results, during the laser irradiation at the optimized doses, thermal injury was not evident either in the 15 mm lateral distances from the optical fiber or in the nearby healthy organs. The present computational-based predictions are also in line with the previous ex vivo and in vivo studies, hence, they can assist in the estimation of the therapeutic outcome of laser ablation for pancreatic neoplasms prior to clinical trials.