bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic intermittent hypobaric hypoxia ameliorates osteoporosis after spinal cord injury through balancing osteoblast and osteoclast activities in rats
Authors: Zhang Li , Yin Yingchao , Guo Jialiang , Jin Lin , Hou Zhiyong 
Published: May 2023

IntroductionAs a common complication of spinal cord injury (SCI), most SCI patients suffer from osteoporosis. In our previous study, chronic intermittent hypobaric hypoxia (CIHH) could promote bone fracture healing. We speculated that it may act a role in the progression of osteoporosis. The current study purposed to explore the role of CIHH in the osteoporosis triggered by SCI in rats.MethodsA SCI-induced SCI model was established by completed transection at T9-T10 spinal cord of Wistar rats. One week after SCI, the rats were conducted to CIHH treatment (PB = 404 mmHg, Po2 = 84 mmHg) 6 hours a day for continuously 7 weeks.ResultsThe results of X-radiography and Micro-CT assessment demonstrated that compared with sham rats, the areal bone mineral density (BMD), bone volume to tissue volume, volumetric BMD, trabecular thickness, trabecular number, and trabecular connectivity were decreased. Trabecular bone pattern factor, trabecular separation, as well as structure model index were increased at the distal femur and proximal tibia of SCI rats, which were effectively reversed by CIHH treatment. Histomorphometry showed that CIHH treatment increased bone formation of SCI rats, as evidenced by the increased osteoid formation, the decreased number and surface of TRAP-positive osteoclasts. Furthermore, ELISA and real time PCR results showed that the osteoblastogenesis-related biomarkers, such as procollagen type 1 N-terminal propeptide, osteocalcin in serum, as well as ALP and OPG mRNAs in bone tissue were decreased, while the osteoclastogenesis-related biomarkers, including scleorostin in serum and RANKL and TRAP mRNAs in bone tissue were increased in SCI rats. Importantly, the deviations of aforementioned biomarkers were improved by CIHH treatment. Mechanically, the protective effects of CIHH might be at least partly mediated by hypoxia-inducible factor-1 alpha (HIF-1α) signaling pathway.ConclusionThe present study testified that CIHH treatment ameliorates osteoporosis after SCI by balancing osteoblast and osteoclast activities in rats.
Tibial plateau fracture and RNA sequencing with osteogenesis imperfecta: a case report
Authors: Chen Yixiao , Li Guoqing , Wei Liangchen , Weng Jian , Liu Su , Gu Mingxi , Liu Pei , Zhu Yuanchao , Xiong Ao , Zeng Hui , Yu Fei 
Published: May 2023

Osteogenesis imperfecta (OI) is a hereditary skeletal dysplasia with an incidence of approximately 1:15,000 to 20,000. OI is usually caused by the mutation of COL1A1 and COL1A2, which would encode the α-chain of type I collagen. OI is clinically characterized by decreased bone mass, increased risk of bone fragility, blue sclerae, and dentinogenesis.Case presentationA 29-year-old male patient was diagnosed with right tibial plateau fracture caused by slight violence. Physical examination revealed the following: height, 140 cm; weight, 70 kg; body mass index (BMI), 35.71 kg/m2; blue sclera and barrel chest were observed. X-ray examination showed left convex deformity of the thoracic vertebrae with reduced thoracic volume. Laboratory examinations revealed a decrease in both vitamin D and blood calcium levels. Bone mineral density (BMD) was lower than the normal range. After the preoperative preparation was completed, the open reduction and internal fixation of the right tibial plateau fracture were performed. Meanwhile, whole blood samples of this OI patient and the normal control were collected for RNA transcriptome sequencing. The RNA sequence analysis revealed that there were 513 differentially expressed genes (DEGs) between this OI patient and the normal control. KEGG-enriched signaling pathways were significantly enriched in extracellular matrix (ECM)–receptor interactions.ConclusionIn this case, DEGs between this OI patient and the normal control were identified by RNA transcriptome sequencing. Moreover, the possible pathogenesis of OI was also explored, which may provide new evidence for the treatment of OI.
Machine learning-based signature of necrosis-associated lncRNAs for prognostic and immunotherapy response prediction in cutaneous melanoma and tumor immune landscape characterization
Authors: Cui Zhiwei , Liang Zhen , Song Binyu , Zhu Yuhan , Chen Guo , Gu Yanan , Liang Baoyan , Ma Jungang , Song Baoqiang 
Published: May 2023

BackgroundCutaneous melanoma (CM) is one of the malignant tumors with a relative high lethality. Necroptosis is a novel programmed cell death that participates in anti-tumor immunity and tumor prognosis. Necroptosis has been found to play an important role in tumors like CM. However, the necroptosis-associated lncRNAs’ potential prognostic value in CM has not been identified.MethodsThe RNA sequencing data collected from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) was utilized to identify differentially expressed genes in CM. By using the univariate Cox regression analysis and machine learning LASSO algorithm, a prognostic risk model had been built depending on 5 necroptosis-associated lncRNAs and was verified by internal validation. The performance of this prognostic model was assessed by the receiver operating characteristic curves. A nomogram was constructed and verified by calibration. Furthermore, we also performed sub-group K-M analysis to explore the 5 lncRNAs’ expression in different clinical stages. Function enrichment had been analyzed by GSEA and ssGSEA. In addition, qRT-PCR was performed to verify the five lncRNAs’ expression level in CM cell line (A2058 and A375) and normal keratinocyte cell line (HaCaT).ResultsWe constructed a prognostic model based on five necroptosis-associated lncRNAs (AC245041.1, LINC00665, AC018553.1, LINC01871, and AC107464.3) and divided patients into high-risk group and low-risk group depending on risk scores. A predictive nomogram had been built to be a prognostic indicator to clinical factors. Functional enrichment analysis showed that immune functions had more relationship and immune checkpoints were more activated in low-risk group than that in high-risk group. Thus, the low-risk group would have a more sensitive response to immunotherapy.ConclusionThis risk score signature could be used to divide CM patients into low- and high-risk groups, and facilitate treatment strategy decision making that immunotherapy is more suitable for those in low-risk group, providing a new sight for CM prognostic evaluation.
Design of AUVs based on 3D coils positioning and distributed base station control for nuclear spent fuel pools
Authors: Shen Shijun , Chen Jiaoyuan , Wang Chaofan , Wang Chenyang , Gong Dawei 
Published: May 2023

An underwater magnetic induction positioning and communication system and an energy-efficient distributed control algorithm for underwater base stations are proposed in this paper. The positioning and communication system consists of a number of base stations and an Autonomous Underwater Vehicle (AUV) equipped with three-axis source coils respectively. The AUV receives this signal and based on its amplitude and phase information is able to locate the AUV and communicate with the base station. Due to the short positioning distance of magnetic induction positioning technology, a large number of base stations need to be installed underwater, which puts high demands on the control of the base stations. In this paper, an energy-efficient distributed control algorithm for underwater base stations is proposed to enable the AUV to meet the operational requirements while minimizing the total energy consumption of the base station. According to the simulation results, the design solves the problem that traditional underwater positioning and communication equipment cannot work stably for long periods of time in a high radiated environment, with a positioning error of no more than 10 cm within a preset operating range, and the algorithm proposed in this paper is able to reduce energy wastage by about 20%.
Comprehensive assessment of climate extremes in high-resolution CMIP6 projections for Ethiopia
Authors: Rettie Fasil M. , Gayler Sebastian , Weber Tobias K. D. , Tesfaye Kindie , Streck Thilo 
Published: May 2023

Climate extremes have more far-reaching and devastating effects than the mean climate shift, particularly on the most vulnerable societies. Ethiopia, with its low economic adaptive capacity, has been experiencing recurrent climate extremes for an extended period, leading to devastating impacts and acute food shortages affecting millions of people. In face of ongoing climate change, the frequency and intensity of climate extreme events are expected to increase further in the foreseeable future. This study provides an overview of projected changes in climate extremes indices based on downscaled high-resolution (i.e., 10 × 10 km 2) daily climate data derived from global climate models (GCMs). The magnitude and spatial patterns of trends in the projected climate extreme indices were explored under a range of emission scenarios called Shared Socioeconomic Pathways (SSPs). The performance of the GCMs to reproduce the observed climate extreme trends in the base period (1983–2012) was evaluated, the changes in the climate projections (2020–2100) were assessed and the associated uncertainties were quantified. Overall, results show largely significant and spatially consistent trends in the projected temperature-derived extreme indices with acceptable model performance in the base period. The projected changes are dominated by the uncertainties in the GCMs at the beginning of the projection period while by the end of the century proportional uncertainties arise both from the GCMs and SSPs. The results for precipitation-related extreme indices are heterogeneous in terms of spatial distribution, magnitude, and statistical significance coverage. Unlike the temperature-related indices, the uncertainty from internal climate variability constitutes a considerable proportion of the total uncertainty in the projected trends. Our work provides a comprehensive insight into the projected changes in climate extremes at relatively high spatial resolution and the related sources of projection uncertainties.
In utero arsenic exposure and early childhood motor development in the New Hampshire Birth Cohort Study
Authors: Butler Erin E. , Karagas Margaret R. , Demidenko Eugene , Bellinger David C. , Korrick Susan A. 
Published: May 2023

IntroductionHigh-level prenatal and childhood arsenic (As) exposure characteristic of several regions in Asia (e.g., Bangladesh), may impact motor function. However, the relationship between lower-level arsenic exposure (characteristic of other regions) and motor development is largely unstudied, despite the potential for deficient motor skills in childhood to have adverse long-term consequences. Thus, we sought to investigate the association between prenatal As exposure and motor function among 395 children in the New Hampshire Birth Cohort Study, a rural cohort from northern New England.MethodsPrenatal exposure was estimated by measuring maternal urine speciated As at 24–28 weeks of gestation using high-performance liquid chromatography (HPLC) inductively coupled plasma mass spectrometry (ICP-MS) and summing inorganic As, monomethylarsonic acid, and dimethylarsinic acid to obtain total urinary As (tAs). Motor function was assessed with the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition (BOT-2) at a mean (SD) age of 5.5 (0.4) years.ResultsChildren who completed this exam were largely reported as white race (97%), born to married mothers (86%) with a college degree or higher (67%). The median (IQR) gestational urine tAs concentration was 4.0 (5.0) µg/L. Mean (SD) BOT-2 scores were 48.6 (8.4) for overall motor proficiency and 48.2 (9.6) for fine manual control [standard score = 50 (10)], and were 16.3 (5.1) for fine motor integration and 12.5 (4.1) for fine motor precision [standard score = 15 (5)]. We found evidence of a non-linear dose response relationship and used a change-point model to assess the association of tAs with overall motor proficiency and indices of fine motor integration, fine motor precision, and their composite, fine manual control, adjusted for age and sex. In models adjusted for potential confounders, each doubling of urine tAs decreased overall motor proficiency by –3.3 points (95% CI: –6.1, –0.4) for tAs concentrations greater than the change point of 9.5 µg/L and decreased fine motor integration by –4.3 points (95% CI: –8.0, –0.6) for tAs concentrations greater than the change point of 17.0 µg/L.DiscussionIn summary, we found that levels of prenatal As exposure above an empirically-derived threshold (i.e., the change point) were associated with decrements in childhood motor development in a US population.
Genetic diagnosis of fetal microcephaly at a single tertiary center in China
Authors: Wang You , Fu Fang , Lei Tingying , Zhen Li , Deng Qiong , Zhou Hang , Ma Chunling , Cheng Ken , Huang Ruibin , Li Ru , Yu Qiuxia , Li Lushan , Han Jin , Yang Xin , Li Dongzhi , Liao Can 
Published: May 2023

Background: Microcephaly is common in patients with neuropsychiatric problems, and it is usually closely related to genetic causes. However, studies on chromosomal abnormalities and single-gene disorders associated with fetal microcephaly are limited.Objective: We investigated the cytogenetic and monogenic risks of fetal microcephaly and evaluated their pregnancy outcomes.Methods: We performed a clinical evaluation, high-resolution chromosomal microarray analysis (CMA), and trio exome sequencing (ES) on 224 fetuses with prenatal microcephaly and closely followed the pregnancy outcome and prognosis.Results: Among 224 cases of prenatal fetal microcephaly, the diagnosis rate was 3.74% (7/187) for CMA and 19.14% (31/162) for trio-ES. Exome sequencing identified 31 pathogenic or likely pathogenic (P/LP) single nucleotide variants (SNVs) in 25 genes associated with fetal structural abnormalities in 37 microcephaly fetuses; 19 (61.29%) of which occurred de novo. Variants of unknown significance (VUS) was found in 33/162 (20.3%) fetuses. The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3. The live birth rate of fetal microcephaly in the syndromic microcephaly group was significantly higher than that in the primary microcephaly group [62.9% (117/186) vs 31.56% (12/38), p = 0.000].Conclusion: We conducted a prenatal study by conducting CMA and ES for the genetic analysis of fetal microcephaly cases. CMA and ES had a high diagnostic rate for the genetic causes of fetal microcephaly cases. In this study, we also identified 14 novel variants, which expanded the disease spectrum of microcephaly-related genes.
Identification of the lncRNA–miRNA‒mRNA regulatory network for middle cerebral artery occlusion-induced ischemic stroke
Authors: Shi Guixin , He Dong , Xiao Hua , Liu Yu’e , Liu Chuanyong , Cao Fang 
Published: May 2023

Stroke known as a neurological disease has significant rates of disability and mortality. Middle cerebral artery occlusion (MCAO) models in rodents is crucial in stroke research to mimic human stroke. Building the mRNA and non-conding RNA network is essential for preventing MCAO-induced ischemic stroke occurrence. Herein, genome-wide mRNA, miRNA, and lncRNA expression profiles among the MCAO group at 3 h, 6 h, and 12 h after surgery and controls using high-throughput RNA sequencing. We detected differentially expressed mRNAs (DE-mRNAs), miRNAs (DE-miRNAs), and lncRNAs (DE-lncRNAs) between the MCAO and control groups. In addition, biological functional analyses were conducted, including GO/KEGG enrichment analysis, and protein-protein interaction analysis (PPI). GO analysis indicated that the DE-mRNAs were mainly enriched in several important biological processes as lipopolysaccharide, inflammatory response, and response to biotic stimulus. The PPI network analysis revealed that the 12 DE-mRNA target proteins showed more than 30° with other proteins, and the top three proteins with the highest node degree were Alb, IL-6, and TNF. In the DE-mRNAs, we found the mRNA of Gp6 and Elane interacting with two miRNAs (novel_miR_879 and novel_miR_528) and two lncRNAs (MSTRG.348134.3 and MSTRG.258402.19). As a result of this study, a new perspective can be gained into the molecular pathophysiology leading to the formation of MCAO. The mRNA-miRNA‒lncRNA regulatory networks play an important role in MCAO-induced ischemic stroke pathogenesis and could be applied to the treatment and prevention of ischemic stroke in the future.
A rapid and efficient platform for antiviral crRNA screening using CRISPR-Cas13a-based nucleic acid detection
Authors: Yang Lan , Zhang Youcui , Yi Wenyanbo , Dong Xue , Niu Mengwei , Song Yingjie , Han Yao , Li Hao , Sun Yansong 
Published: May 2023

IntroductionRapid and high-throughput screening of antiviral clustered regularly interspaced short palindromic repeat (CRISPR) RNAs (crRNAs) is urgently required for the CRISPR-Cas13a antiviral system. Based on the same principle, we established an efficient screening platform for antiviral crRNA through CRISPR-Cas13a nucleic acid detection.MethodIn this study, crRNAs targeting PA, PB1, NP, and PB2 of the influenza A virus (H1N1) were screened using CRISPR-Cas13a nucleic acid detection, and their antiviral effects were confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The RNA secondary structures were predicted by bioinformatics methods.ResultsThe results showed that crRNAs screened by CRISPR-Cas13a nucleic acid detection could effectively inhibit viral RNA in mammalian cells. Besides, we found that this platform for antiviral crRNA screening was more accurate than RNA secondary structure prediction. In addition, we validated the feasibility of the platform by screening crRNAs targeting NS of the influenza A virus (H1N1).DiscussionThis study provides a new approach for screening antiviral crRNAs and contributes to the rapid advancement of the CRISPR-Cas13a antiviral system.
Exploiting endocytosis for transfection of mRNA for cytoplasmatic delivery using cationic gold nanoparticles
Authors: Gustà Muriel F. , Edel Michael J. , Salazar Vivian A. , Alvarez-Palomo Belén , Juan Manel , Broggini Massimo , Damia Giovanna , Bigini Paolo , Corbelli Alessandro , Fiordaliso Fabio , Barbul Alexander , Korenstein Rafi , Bastús Neus G. , Puntes Víctor 
Published: May 2023

IntroductionGene therapy holds promise to cure various diseases at the fundamental level. For that, efficient carriers are needed for successful gene delivery. Synthetic ‘non-viral’ vectors, as cationic polymers, are quickly gaining popularity as efficient vectors for transmitting genes. However, they suffer from high toxicity associated with the permeation and poration of the cell membrane. This toxic aspect can be eliminated by nanoconjugation. Still, results suggest that optimising the oligonucleotide complexation, ultimately determined by the size and charge of the nanovector, is not the only barrier to efficient gene delivery.MethodsWe herein develop a comprehensive nanovector catalogue comprising different sizes of Au NPs functionalized with two different cationic molecules and further loaded with mRNA for its delivery inside the cell.Results and DiscussionTested nanovectors showed safe and sustained transfection efficiencies over 7 days, where 50 nm Au NPs displayed the highest transfection rates. Remarkably, protein expression was increased when nanovector transfection was performed combined with chloroquine. Cytotoxicity and risk assessment demonstrated that nanovectors are safe, ascribed to lesser cellular damage due to their internalization and delivery via endocytosis. Obtained results may pave the way to design advanced and efficient gene therapies for safely transferring oligonucleotides.
Single-cell landscape dissecting the transcription and heterogeneity of innate lymphoid cells in ischemic heart
Authors: Jiang Shijiu , Zheng Yuqi , Lv Bingjie , He Shaolin , Yang Wenling , Wang Boyuan , Zhou Jin , Liu Shangwei , Li Dazhu , Lin Jibin 
Published: May 2023

BackgroundUntil now, few articles have revealed the potential roles of innate lymphoid cells (ILCs) in cardiovascular diseases. However, the infiltration of ILC subsets in ischemic myocardium, the roles of ILC subsets in myocardial infarction (MI) and myocardial ischemia-reperfusion injury (MIRI) and the related cellular and molecular mechanisms have not been described with a sufficient level of detail.MethodIn the current study, 8-week-old male C57BL/6J mice were divided into three groups: MI, MIRI and sham group. Single-cell sequencing technology was used to perform dimensionality reduction clustering of ILC to analyze the ILC subset landscape at a single-cell resolution, and finally flow cytometry was used to confirm the existence of the new ILC subsets in different disease groups.ResultsFive ILC subsets were found, including ILC1, ILC2a, ILC2b, ILCdc and ILCt. It is worth noting that ILCdc, ILC2b and ILCt were identified as new ILC subclusters in the heart. The cellular landscapes of ILCs were revealed and signal pathways were predicted. Furthermore, pseudotime trajectory analysis exhibited different ILC statuses and traced related gene expression in normal and ischemic conditions. In addition, we established a ligand–receptor–transcription factor–target gene regulatory network to disclose cell communications among ILC clusters. Moreover, we further revealed the transcriptional features of the ILCdc and ILC2a subsets. Finally, the existence of ILCdc was confirmed by flow cytometry.ConclusionCollectively, by characterizing the spectrums of ILC subclusters, our results provide a new blueprint for understanding ILC subclusters’ roles in myocardial ischemia diseases and further potential treatment targets.