bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental capture of miRNA targetomes: disease-specific 3′UTR library-based miRNA targetomics for Parkinson’s disease
Authors: Hart Martin , Kern Fabian , Fecher-Trost Claudia , Krammes Lena , Aparicio Ernesto , Engel Annika , Hirsch Pascal , Wagner Viktoria , Keller Verena , Schmartz Georges Pierre , Rheinheimer Stefanie , Diener Caroline , Fischer Ulrike , Mayer Jens , Meyer Markus R. , Flockerzi Veit , Keller Andreas , Meese Eckart
Published: April 2024

The identification of targetomes remains a challenge given the pleiotropic effect of miRNAs, the limited effects of miRNAs on individual targets, and the sheer number of estimated miRNA–target gene interactions (MTIs), which is around 44,571,700. Currently, targetome identification for single miRNAs relies on computational evidence and functional studies covering smaller numbers of targets. To ensure that the targetome analysis could be experimentally verified by functional assays, we employed a systematic approach and explored the targetomes of four miRNAs (miR-129-5p, miR-129-1-3p, miR-133b, and miR-873-5p) by analyzing 410 predicted target genes, both of which were previously associated with Parkinson’s disease (PD). After performing 13,536 transfections, we validated 442 of the 705 putative MTIs (62,7%) through dual luciferase reporter assays. These analyses increased the number of validated MTIs by at least 2.1-fold for miR-133b and by a maximum of 24.3-fold for miR-873-5p. Our study contributes to the experimental capture of miRNA targetomes by addressing i) the ratio of experimentally verified MTIs to predicted MTIs, ii) the sizes of disease-related miRNA targetomes, and iii) the density of MTI networks. A web service to support the analyses on the MTI level is available online (https://ccb-web.cs.uni-saarland.de/utr-seremato), and all the data have been added to the miRATBase database (https://ccb-web.cs.uni-saarland.de/miratbase).
Transmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles
Authors: Kang Hyunji , Lee C. Justin
Published: April 2024

A transmembrane (TMEM) protein with an unknown function is a type of membrane-spanning protein expressed in the plasma membrane or the membranes of intracellular organelles. Recently, several TMEM proteins have been identified as functional ion channels. The structures and functions of these proteins have been extensively studied over the last two decades, starting with TMEM16A (ANO1). In this review, we provide a summary of the electrophysiological properties of known TMEM proteins that function as ion channels, such as TMEM175 (KEL), TMEM206 (PAC), TMEM38 (TRIC), TMEM87A (GolpHCat), TMEM120A (TACAN), TMEM63 (OSCA), TMEM150C (Tentonin3), and TMEM43 (Gapjinc). Additionally, we examine the unique structural features of these channels compared to those of other well-known ion channels. Furthermore, we discuss the diverse physiological roles of these proteins in lysosomal/endosomal/Golgi pH regulation, intracellular Ca2+ regulation, spatial memory, cell migration, adipocyte differentiation, and mechanical pain, as well as their pathophysiological roles in Parkinson’s disease, cancer, osteogenesis imperfecta, infantile hypomyelination, cardiomyopathy, and auditory neuropathy spectrum disorder. This review highlights the potential for the discovery of novel ion channels within the TMEM protein family and the development of new therapeutic targets for related channelopathies.
The pathogenic mechanism of syndactyly type V identified in a Hoxd13Q50R knock-in mice
Authors: Wang Han , Chen Xiumin , Meng Xiaolu , Cao Yixuan , Han Shirui , Liu Keqiang , Zhao Ximeng , Zhao Xiuli , Zhang Xue
Published: April 2024

Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifth metacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) of HOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlying pathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed to generate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly and partial syndactyly between digits 2–4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in homozygotes. Focusing on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limb development, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud at E10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibited notable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involved in various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopic expression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both the anterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascade ultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations in homozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may be responsible for the manifestation of human SDTY5.
FOXP3 promote the progression of glioblastoma via inhibiting ferroptosis mediated by linc00857/miR-1290/GPX4 axis
Authors: Cao Wenpeng , He Ya , Lan Jinzhi , Luo Shipeng , Sun Baofei , Xiao Chaolun , Yu Wenfeng , Zeng Zhirui , Lei Shan
Published: April 2024

The oncogenic properties of members belonging to the forkhead box (FOX) family have been extensively documented in different types of cancers. In this study, our objective was to investigate the impact of FOXP3 on glioblastoma multiforme (GBM) cells. By conducting a screen using a small hairpin RNA (shRNA) library, we discovered a significant association between FOXP3 and ferroptosis in GBM cells. Furthermore, we observed elevated levels of FOXP3 in both GBM tissues and cell lines, which correlated with a poorer prognosis. FOXP3 was found to promote the proliferation of GBM cells by inhibiting cell ferroptosis in vitro and in vivo. Mechanistically, FOXP3 not only directly upregulated the transcription of GPX4, but also attenuated the degradation of GPX4 mRNA through the linc00857/miR-1290 axis, thereby suppressing ferroptosis and promoting proliferation. Additionally, the FOXP3 inhibitor epirubicin exhibited the ability to impede proliferation and induce ferroptosis in GBM cells both in vitro and in vivo. In summary, our study provided evidences that FOXP3 facilitates the progression of glioblastoma by inhibiting ferroptosis via the linc00857/miR-1290/GPX4 axis, highlighting FOXP3 as a potential therapeutic target for GBM.
A novel long non-coding RNA SLNCR1 promotes proliferation, migration, and invasion of melanoma via transcriptionally regulating SOX5
Authors: Cong Lele , Zhao Qing , Sun Hongyan , Zhou Zilong , Hu Yue , Li Chunyi , Hao Miao , Cong Xianling
Published: April 2024

Steroid receptor RNA activator (SRA)-like non-coding RNA (SLNCR1) has been implicated in various tumorigenic processes, but the precise regulatory role in melanoma progression remains uncertain. We performed a comprehensive analysis to investigate the prognostic value of SLNCR1 expression in patients with melanoma by TCGA database and melanoma tissue samples via the Kaplan–Meier method. Subsequently, we conducted qRT-PCR and Fluorescence in Situ Hybridization (FISH) assays to identify SLNCR1 expression levels and localization in tissues and cells, respectively. Loss-of-function assays utilizing shRNAs vectors were used to investigate the potential impact of SLNCR1. Our data showed that SLNCR1 is significantly up-regulated in human malignant melanoma tissues and cell lines and functions as an oncogene. Silencing of SLNCR1 suppressed melanoma cell proliferation, migration, invasion, and inhibited tumorigenesis in a mouse xenograft model. Additionally, we employed bioinformatic predictive analysis, combined with dual-luciferase reporter analysis and functional rescue assays, to elucidate the mechanistic target of the SLNCR1/SOX5 axis in melanoma. Mechanistically, we discovered that SLNCR1 promotes EMT of human melanoma by targeting SOX5, as downregulation of SLNCR1 expression leads to a decrease in SOX5 protein levels and inhibits melanoma tumorigenesis. Our research offers promising insights for more precise diagnosis and treatment of human melanoma.
p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response
Authors: Serra François , Nieto-Aliseda Andrea , Fanlo-Escudero Lucía , Rovirosa Llorenç , Cabrera-Pasadas Mónica , Lazarenkov Aleksey , Urmeneta Blanca , Alcalde-Merino Alvaro , Nola Emanuele M. , Okorokov Andrei L. , Fraser Peter , Graupera Mariona , Castillo Sandra D. , Sardina Jose L. , Valencia Alfonso , Javierre Biola M.
Published: April 2024

Activation of the p53 tumor suppressor triggers a transcriptional program to control cellular response to stress. However, the molecular mechanisms by which p53 controls gene transcription are not completely understood. Here, we uncover the critical role of spatio-temporal genome architecture in this process. We demonstrate that p53 drives direct and indirect changes in genome compartments, topologically associating domains, and DNA loops prior to one hour of its activation, which escort the p53 transcriptional program. Focusing on p53-bound enhancers, we report 340 genes directly regulated by p53 over a median distance of 116 kb, with 74% of these genes not previously identified. Finally, we showcase that p53 controls transcription of distal genes through newly formed and pre-existing enhancer-promoter loops in a cohesin dependent manner. Collectively, our findings demonstrate a previously unappreciated architectural role of p53 as regulator at distinct topological layers and provide a reliable set of new p53 direct target genes that may help designs of cancer therapies.
The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation
Authors: Tang Xiuxiao , Zeng Pengguihang , Liu Kezhi , Qing Li , Sun Yifei , Liu Xinyi , Lu Lizi , Wei Chao , Wang Jia , Jiang Shaoshuai , Sun Jun , Chang Wakam , Yu Haopeng , Chen Hebing , Zhou Jiaguo , Xu Chengfang , Fan Lili , Miao Yi-Liang , Ding Junjun
Published: April 2024

CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.
Comparison studies identify mesenchymal stromal cells with potent regenerative activity in osteoarthritis treatment
Authors: Chu Hongshang , Zhang Shaoyang , Zhang Zhenlin , Yue Hua , Liu Huijuan , Li Baojie , Yin Feng
Published: April 2024

Osteoarthritis affects 15% of people over 65 years of age. It is characterized by articular cartilage degradation and inflammation, leading to joint pain and disability. Osteoarthritis is incurable and the patients may eventually need joint replacement. An emerging treatment is mesenchymal stromal cells (MSCs), with over two hundred clinical trials being registered. However, the outcomes of these trials have fallen short of the expectation, due to heterogeneity of MSCs and uncertain mechanisms of action. It is generally believed that MSCs exert their function mainly by secreting immunomodulatory and trophic factors. Here we used knee osteoarthritis mouse model to assess the therapeutic effects of MSCs isolated from the white adipose or dermal adipose tissue of Prrx1-Cre; R26tdTomato mice and Dermo1-Cre; R26tdTomato mice. We found that the Prrx1-lineage MSCs from the white adipose tissues showed the greatest in vitro differentiation potentials among the four MSC groups and single cell profiling showed that the Prrx1-lineage MSCs contained more stem cells than the Dermo1 counterpart. Only the Prrx1-lineage cells isolated from white adipose tissues showed long-term therapeutic effectiveness on early-stage osteoarthritis models. Mechanistically, Prrx1-lineage MSCs differentiated into Col2+ chondrocytes and replaced the damage cartilage, activated Col1 expressing in resident chondrocytes, and inhibited synovial inflammation. Transcriptome analysis showed that the articular chondrocytes derived from injected MSCs expressed immunomodulatory cytokines, trophic factors, and chondrocyte-specific genes. Our study identified a MSC population genetically marked by Prrx1 that has great multipotentiality and can differentiate into chondrocytes to replace the damaged cartilage.
Tailored alumina nanocomposite membranes featuring MIL-125-NH2 metal-organic frameworks for oily wastewater treatment
Authors: Baig Umair , Waheed Abdul , Yogarathinam Lukka Thuyavan , Aljundi Isam H.
Published: April 2024

Ceramic membranes offer significant potential for addressing challenging and harsh wastewater streams such as produced water (PW) and surfactant-stabilized oil/water (O/W) emulsions. This study focuses on developing a stable and a uniformly structured active layer solely composed of MIL-125-NH2 MOF on a ceramic Alumina support. A stable covalent bonding approach was employed using interfacial polymerization, with isophthaloyl chloride (IPC) acting as the organic crosslinker during interfacial polymerization reaction. Three distinct MIL-125-NH2 decorated membranes M50, M75, and M100 were prepared by using varying MOF concentrations. Surface wettability analysis of the membranes indicated that the MIL-125-NH2 MOF active layer displayed super-hydrophilic characteristics in the air (water contact angle = 0°) and super-oleophobic characteristics underwater (oil contact angle = 161.5°). In oil separation experiments, all the MIL-125-NH2 deposited membranes displayed >99% oil rejection. Among the fabricated membranes, M50 demonstrated the highest water flux of 2100 Lm−2 h−1 under a transmembrane pressure of 2 bar. The MIL-125-NH2 MOF deposited membranes also showed stable performance under longer-run filtration. This study would be a simple and effective method of decorating MOFs as an active layer on ceramic support for efficient O/W emulsion separation and desalination applications.
Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL
Authors: Ding Lianggong , Huwyler Florian , Long Fen , Yang Wu , Binz Jonas , Wernlé Kendra , Pfister Matthias , Klug Manuel , Balaz Miroslav , Ukropcova Barbara , Ukropec Jozef , Wu Chunyan , Wang Tongtong , Gao Min , Clavien Pierre-Alain , Dutkowski Philipp , Tibbitt Mark W. , Wolfrum Christian
Published: April 2024

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7FBXW8 in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P–CUL7FBXW8–ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.
Weak anvil cloud area feedback suggested by physical and observational constraints
Authors: McKim Brett , Bony Sandrine , Dufresne Jean-Louis
Published: April 2024

Changes in anvil clouds with warming remain a leading source of uncertainty in estimating Earth’s climate sensitivity. Here we develop a feedback analysis that decomposes changes in anvil clouds and creates testable hypotheses for refining their proposed uncertainty ranges with observations and theory. To carry out this storyline approach, we derive a simple but quantitative expression for the anvil area feedback, which is shown to depend on the present-day measurable cloud radiative effects and the fractional change in anvil area with warming. Satellite observations suggest an anvil cloud radiative effect of about ±1 W m−2, which requires the fractional change in anvil area to be about 50% K−1 in magnitude to produce a feedback equal to the current best estimate of its lower bound. We use quantitative theory and observations to show that the change in anvil area is closer to about −4% K−1. This constrains the area feedback and leads to our revised estimate of 0.02 ± 0.07 W m−2 K−1, which is many times weaker and more constrained than the overall anvil cloud feedback. In comparison, we show the anvil cloud albedo feedback to be much less constrained, both theoretically and observationally, which poses an obstacle for bounding Earth’s climate sensitivity.
Enhanced gorilla troops optimizer powered by marine predator algorithm: global optimization and engineering design
Authors: Hassan Mohamed H. , Kamel Salah , Mohamed Ali Wagdy
Published: April 2024

This study presents an advanced metaheuristic approach termed the Enhanced Gorilla Troops Optimizer (EGTO), which builds upon the Marine Predators Algorithm (MPA) to enhance the search capabilities of the Gorilla Troops Optimizer (GTO). Like numerous other metaheuristic algorithms, the GTO encounters difficulties in preserving convergence accuracy and stability, notably when tackling intricate and adaptable optimization problems, especially when compared to more advanced optimization techniques. Addressing these challenges and aiming for improved performance, this paper proposes the EGTO, integrating high and low-velocity ratios inspired by the MPA. The EGTO technique effectively balances exploration and exploitation phases, achieving impressive results by utilizing fewer parameters and operations. Evaluation on a diverse array of benchmark functions, comprising 23 established functions and ten complex ones from the CEC2019 benchmark, highlights its performance. Comparative analysis against established optimization techniques reveals EGTO's superiority, consistently outperforming its counterparts such as tuna swarm optimization, grey wolf optimizer, gradient based optimizer, artificial rabbits optimization algorithm, pelican optimization algorithm, Runge Kutta optimization algorithm (RUN), and original GTO algorithms across various test functions. Furthermore, EGTO's efficacy extends to addressing seven challenging engineering design problems, encompassing three-bar truss design, compression spring design, pressure vessel design, cantilever beam design, welded beam design, speed reducer design, and gear train design. The results showcase EGTO's robust convergence rate, its adeptness in locating local/global optima, and its supremacy over alternative methodologies explored.
Utilizing ultra-early continuous physiologic data to develop automated measures of clinical severity in a traumatic brain injury population
Authors: Yang Shiming , Hu Peter , Kalpakis Konstantinos , Burdette Bradford , Chen Hegang , Parikh Gunjan , Felix Ryan , Podell Jamie , Badjatia Neeraj
Published: April 2024

Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009–2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3–8), 223 (3.7%) moderate TBI (GCS 9–12), and 5913 (88.5%) mild TBI (GCS 13–15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation.
Adaptive neighborhood rough set model for hybrid data processing: a case study on Parkinson’s disease behavioral analysis
Authors: Raza Imran , Jamal Muhammad Hasan , Qureshi Rizwan , Shahid Abdul Karim , Vistorte Angel Olider Rojas , Samad Md Abdus , Ashraf Imran
Published: April 2024

Extracting knowledge from hybrid data, comprising both categorical and numerical data, poses significant challenges due to the inherent difficulty in preserving information and practical meanings during the conversion process. To address this challenge, hybrid data processing methods, combining complementary rough sets, have emerged as a promising approach for handling uncertainty. However, selecting an appropriate model and effectively utilizing it in data mining requires a thorough qualitative and quantitative comparison of existing hybrid data processing models. This research aims to contribute to the analysis of hybrid data processing models based on neighborhood rough sets by investigating the inherent relationships among these models. We propose a generic neighborhood rough set-based hybrid model specifically designed for processing hybrid data, thereby enhancing the efficacy of the data mining process without resorting to discretization and avoiding information loss or practical meaning degradation in datasets. The proposed scheme dynamically adapts the threshold value for the neighborhood approximation space according to the characteristics of the given datasets, ensuring optimal performance without sacrificing accuracy. To evaluate the effectiveness of the proposed scheme, we develop a testbed tailored for Parkinson’s patients, a domain where hybrid data processing is particularly relevant. The experimental results demonstrate that the proposed scheme consistently outperforms existing schemes in adaptively handling both numerical and categorical data, achieving an impressive accuracy of 95% on the Parkinson’s dataset. Overall, this research contributes to advancing hybrid data processing techniques by providing a robust and adaptive solution that addresses the challenges associated with handling hybrid data, particularly in the context of Parkinson’s disease analysis.
Reliability and validity of a graphical computerized adaptive test Longshi scale for rapid assessment of activities of daily living in stroke survivors
Authors: Zhou Jing , Zha Fubing , Liu Fang , Wan Li , Zhou Mingchao , Long Jianjun , Chen Miaoling , Xue Kaiwen , Wang Yulong
Published: April 2024

Stroke survivors frequently experience difficulties in daily activities, such as bathing, feeding, and mobility. This study aimed to evaluate the reliability and validity of a computer-adaptive test-Longshi scale (CAT-LS) for assessing activities of daily living (ADL) in stroke survivors. This cross-sectional study collected data using an electronic application. The ADL function of stroke survivors in rehabilitation departments of hospitals was assessed using both the CAT-LS and BI. Correlations between the CAT-LS and Barthel index (BI) and concurrent validity were evaluated using Pearson’s correlation test and multiple linear regression. Interrater reliability was evaluated using the intraclass correlation coefficient based on a two-way random effect. The internal consistency of the CAT-LS was assessed using Cronbach’s coefficient (α) and corrected item-total correlations. Overall, 103 medical institutions in China were used in this study. In total, 7151 patients with stroke were included in this study. The CAT-LS classified patients into three ADL groups (bedridden, domestic, and community) with significantly different BI scores (P < 0.05). The CAT-LS results obtained using the decision-tree scoring model were consistent with the scores for each BI item. A strong correlation was observed between CAT-LS and BI (Pearson’s r: 0.6–0.894, P < 0.001). The CAT-LS demonstrated good internal consistency (Cronbach’s α, 0.803–0.894) and interrater reliability (ICC, 0.928–0.979). CAT-LS is time-efficient and requires < 1 min to administer. The CAT-LS is a reliable and valid tool for assessing ADL function in stroke survivors and can provide rapid and accurate assessments that reduce the burden on healthcare professionals. Further validation of this tool in other populations and settings is necessary.

Study registration number: No.: ChiCTR2000034067;http://www.chictr.org.cn/showproj.aspx?proj=54770.
Mechanism of muscle atrophy in a normal-weight rat model of type 2 diabetes established by using a soft-pellet diet
Authors: Akieda-Asai Sayaka , Ma Hao , Han Wanxin , Nagata Junko , Yamaguchi Fumitake , Date Yukari
Published: April 2024

Dietary factors such as food texture affect feeding behavior and energy metabolism, potentially causing obesity and type 2 diabetes. We previously found that rats fed soft pellets (SPs) were neither hyperphagic nor overweight but demonstrated glucose intolerance, insulin resistance, and hyperplasia of pancreatic β-cells. In the present study, we investigated the mechanism of muscle atrophy in rats that had been fed SPs on a 3-h time-restricted feeding schedule for 24 weeks. As expected, the SP rats were normal weight; however, they developed insulin resistance, glucose intolerance, and fat accumulation. In addition, skeletal muscles of SP rats were histologically atrophic and demonstrated disrupted insulin signaling. Furthermore, we learned that the muscle atrophy of the SP rats developed via the IL-6–STAT3–SOCS3 and ubiquitin–proteasome pathways. Our data show that the dietary habit of consuming soft foods can lead to not only glucose intolerance or insulin resistance but also muscle atrophy.
Effect of different buried depth on the disintegration characteristic of red-bed soft rock and the evolution model of disintegration breakage under cyclic drying-wetting
Authors: Zhang Jun , Guo Yang , Huang Kai , Cui Wei , Ke Zhaibang , Chen Xiaochuang , Yue Tengsheng , Gao Kun
Published: April 2024

The disintegration of red-bed soft rock exhibits a strong correlation with various geological disasters. However, the investigation into the evolutionary mechanisms underlying disintegration breakage has not yet received extensive exploration. In order to comprehensively examine the disintegration characteristics of red-bed soft rock, the slake durability tests were conducted to red-bed soft rocks of varying burial depths. Subsequently, an investigation was carried out to examine the disintegration characteristics and the evolution of disintegration parameters, including the coefficient of uniformity (Cu), coefficient of curvature (Cc), disintegration rate (DRE), disintegration ratio (Dr), and fractal dimension (D), throughout the disintegration process. Finally, employing the energy dissipation theory, an energy dissipation model was developed to predicate the disintegration process of samples at various burial depths. The findings demonstrate a decrease in the abundance of large particles and a concurrent increase in the abundance of small particles as the number of drying-wetting cycles increases. Furthermore, as the number of drying-wetting cycles increases, a significant alteration is observed in the content of particles larger than 10 mm, whereas the content of particles smaller than 10 mm undergoes only minor changes. The disintegration parameters, including the curvature coefficient, non-uniformity coefficient, disintegration rate, and fractal dimension, exhibit a positive correlation with the number of drying-wetting cycles. Conversely, the disintegration index demonstrates a decreasing trend with the increasing number of cycles. Nevertheless, as the burial depth increases, a notable trend emerges in the disintegration process, characterized by a gradual increase in the content of large particles alongside a progressive decrease in the content of small particles. Concurrently, the curvature coefficient, non-uniformity coefficient, disintegration rate, and fractal dimension exhibit a gradual decline, while the durability index experiences a gradual increase. In addition, based on the principle of energy dissipation, it is revealed that the surface energy increment of red-bed soft rock increases with the increase of the number of drying-wetting cycles, but decreases with the increase of burial depth. Ultimately, by leveraging the outcomes of energy dissipation analyses, a theoretical model is constructed to elucidate the correlation between surface energy and both the number of drying-wetting cycles and burial depth. This model serves as a theoretical reference for predicting the disintegration behavior of samples, offering valuable insights for future research endeavors.
Permeation of photochemically-generated gaseous chlorine dioxide on Mars as a significant factor in destroying subsurface organic compounds
Authors: Newmark Jacob , Kounaves Samuel P.
Published: April 2024

It has been shown that ultraviolet (UV) irradiation is responsible for the destruction of organic compounds on the surface of Mars. When combined with the photochemically-driven production of oxychlorines (ClOx) it can generate highly reactive species that can alter or destroy organic compounds. However, it has been assumed that since UV only penetrates the top few millimeters of the martian regolith, reactive ClOx oxidants are only produced on the surface. Of all the oxychlorine intermediates produced, gaseous chlorine dioxide [ClO2(g)] is of particular interest, being a highly reactive gas with the ability to oxidize organic compounds. Here we report on a set of experiments under Mars ambient conditions showing the production and permeation of ClO2(g) and its reaction with alanine as a test compound. Contrary to the accepted paradigm that UV irradiation on Mars only interacts with a thin layer of surface regolith, our results show that photochemically-generated ClO2(g) can permeate below the surface, depositing ClOx species (mainly Cl− and $${\text{ClO}}_{3}^{ - }$$

ClO

3

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) and destroying organic compounds. With varying levels of humidity and abundant chloride and oxychlorines on Mars, our findings show that permeation of ClO2(g) must be considered as a significant contributing factor in altering, fragmenting, or potentially destroying buried organic compounds on Mars.
Surface defect detection of hot rolled steel based on multi-scale feature fusion and attention mechanism residual block
Authors: Zhang Hongkai , Li Suqiang , Miao Qiqi , Fang Ruidi , Xue Song , Hu Qianchuan , Hu Jie , Chan Sixian
Published: April 2024

To improve the precision of defect categorization and localization in images, this paper proposes an approach for detecting surface defects in hot-rolled steel strips. The approach uses an improved YOLOv5 network model to overcome the issues of inadequate feature extraction capacity and suboptimal feature integration when identifying surface defects on steel strips. The proposed method achieves higher detection accuracy and localization precision, making it more competitive and applicable in real production. Firstly, the multi-scale feature fusion (MSF) strategy is utilized to fuse shallow and deep features effectively and enrich detailed information relevant to target defects. Secondly, the CSPLayer Res2Attention block (CRA block) residual module is introduced to reduce the loss of defect information during hierarchical transmission, thereby enhancing the extraction of fine-grained features and improving the perception of details and global features. Finally, the experimental results indicate that the mAP on the NEU-DET and GC10-DET datasets approaches 78.5% and 67.3%, respectively, which is 4.9% and 2.1% higher than that of the baseline. Meanwhile, it has higher precision and more precise localization capabilities than other methods. Furthermore, it also achieves 59.2% mAP on the APDDD dataset, indicating its potential for growth in further domains.
CircGPC3 promotes hepatocellular carcinoma progression and metastasis by sponging miR-578 and regulating RAB7A/PSME3 expression
Authors: Ju Linling , Luo Yunfeng , Cui Xiaohui , Zhang Hao , Chen Lin , Yao Min
Published: April 2024

CircRNAs are a class of highly stable noncoding RNAs that play an important role in the progression of many diseases, especially cancer. In this study, high-throughput sequencing was used to screen for abnormally expressed circRNAs, and we found that circGPC3 was overexpressed in HCC tissues. However, the underlying mechanism of circGPC3 in the development and metastasis of hepatocellular carcinoma (HCC) remains unknown. In our study, we found that circGPC3 was significantly upregulated in HCC tissues and cells and that its overexpression was positively correlated with overall survival, TNM stage and lymph node metastasis. In vivo and in vitro experiments showed that circGPC3 knockdown repressed HCC cell migration, invasion and proliferation and promoted apoptosis. Mechanistically, circGPC3 promoted HCC proliferation and metastasis through the miR-578/RAB7A/PSME3 axis. Our results demonstrate that circGPC3 contributes to the progression of HCC and provides an intervention target for HCC.
Spatial-temporal graph neural ODE networks for skeleton-based action recognition
Authors: Pan Longji , Lu Jianguang , Tang Xianghong
Published: April 2024

In the field of skeleton-based action recognition, accurately recognizing human actions is crucial for applications such as virtual reality and motion analysis. However, this task faces challenges such intraindividual action differences and long-term temporal dependencies. To address these challenges, we propose an innovative model called spatial-temporal graph neural ordinary differential equations (STG-NODE). First, in the data preprocessing stage, the dynamic time warping (DTW) algorithm is used to normalize and calculate 3D skeleton data to facilitate the derivation of customized adjacency matrices for improving the influence of intraindividual action differences. Secondly, a custom ordinary differential equation (ODE) integrator is applied based on the initial conditions of the temporal features, producing a solution function that simulates the dynamic evolution trend of the events of interest. Finally, the outstanding ODE solver is used to numerically solve the time features based on the solution function to increase the influence of long-term dependencies on the recognition accuracy of the model and provide it with a more powerful temporal modeling ability. Through extensive experiments conducted on the NTU RGB+D 60 and Kinetics Skeleton 400 benchmark datasets, we demonstrate the superior performance of STG-NODE in the action recognition domain. The success of the STG-NODE model also provides new ideas and methods for the future development of the action recognition field.
Clumped isotopes reveal relationship between mussel growth and river discharge
Authors: Brewer Melanie A. , Grossman Ethan L. , Randklev Charles R.
Published: April 2024

Freshwater mussels preserve valuable information about hydrology, climate, and population dynamics, but developing seasonal chronologies can be problematic. Using clumped isotope thermometry, we produced high-resolution reconstructions of modern and historic (~ 1900) temperatures and δ18Owater from mussel shells collected from an impounded river, the Brazos in Texas, before and after damming. We also performed high-resolution growth band analyses to investigate relationships between mussel growth rate, rainfall, and seasonal temperature. Reconstructed δ18Owater and temperature vary little between the modern (3R5) and historic shell (H3R). However, a positive relationship between reconstructed δ18Owater and growth rate in H3R indicates that aside from diminished growth in winter, precipitation and flow rate are the strongest controls on mussel growth in both modern and pre-dam times. Overall, our results demonstrate (1) the impact, both positive and negative, of environmental factors such as flow alteration and temperature on mussel growth and (2) the potential for clumped isotopes in freshwater mussels as a paleohydrology and paleoclimate proxies in terrestrial environments.
Exercise effect on pain is associated with negative and positive affective components: A large-scale internet-based cross-sectional study in Japan
Authors: Wakaizumi Kenta , Shinohara Yuta , Kawate Morihiko , Matsudaira Ko , Oka Hiroyuki , Yamada Keiko , Jabakhanji Rami , Baliki Marwan N.
Published: April 2024

Pain is a global health problem that leads to sedentary behavior and tends to cause negative emotion. In contrast, exercise is widely recommended for a health promotion, while pain often worsens with physical activity. Although exercise therapy is often prescribed to people with pain, the mechanisms of exercise effect on pain remains unclear. In this study, we tried to identify a universal association factor between regular exercise and pain intensity utilizing a cross-sectional web-based survey involving 52,353 adult participants from a large national study conducted in Japan. Using principal component analysis, we uncovered a mediation model of exercise effect on pain through psychological components. Analyses were performed in half of the population with pain (n = 20,330) and validated in the other half (n = 20,330), and showed that high-frequency exercise had a significant association with reduction in pain intensity. We also found Negative Affect and Vigor, two psychological components, are fully associating the exercise effect on pain (indirect effect =  − 0.032, p < 0.001; association proportion = 0.99) with a dose-dependent response corresponding to the frequency of exercise. These findings were successfully validated (indirect effect of high-frequency exercise =  − 0.028, p < 0.001; association proportion = 0.85). Moreover, these findings were also identified in subpopulation analyses of people with low back, neck, knee pain, and the tendency of the exercise effect on pain was increased with older people. In conclusion, the effect of exercise on pain is associated with psychological components and these association effects increased in parallel with the frequency of exercise habit regardless pain location.
Diversity analysis of sea anemone peptide toxins in different tissues of Heteractis crispa based on transcriptomics
Authors: Guo Qiqi , Fu Jinxing , Yuan Lin , Liao Yanling , Li Ming , Li Xinzhong , Yi Bo , Zhang Junqing , Gao Bingmiao
Published: April 2024

Peptide toxins found in sea anemones venom have diverse properties that make them important research subjects in the fields of pharmacology, neuroscience and biotechnology. This study used high-throughput sequencing technology to systematically analyze the venom components of the tentacles, column, and mesenterial filaments of sea anemone Heteractis crispa, revealing the diversity and complexity of sea anemone toxins in different tissues. A total of 1049 transcripts were identified and categorized into 60 families, of which 91.0% were proteins and 9.0% were peptides. Of those 1049 transcripts, 416, 291, and 307 putative proteins and peptide precursors were identified from tentacles, column, and mesenterial filaments respectively, while 428 were identified when the datasets were combined. Of these putative toxin sequences, 42 were detected in all three tissues, including 33 proteins and 9 peptides, with the majority of peptides being ShKT domain, β-defensin, and Kunitz-type. In addition, this study applied bioinformatics approaches to predict the family classification, 3D structures, and functional annotation of these representative peptides, as well as the evolutionary relationships between peptides, laying the foundation for the next step of peptide pharmacological activity research.
The miR-183/96/182 cluster regulates sensory innervation, resident myeloid cells and functions of the cornea through cell type-specific target genes
Authors: Gupta Naman , Somayajulu Mallika , Gurdziel Katherine , LoGrasso Giovanni , Aziz Haidy , Rosati Rita , McClellan Sharon , Pitchaikannu Ahalya , Santra Manoranjan , Shukkur Muhammed Farooq Abdul , Stemmer Paul , Hazlett Linda D. , Xu Shunbin
Published: April 2024

The conserved miR-183/96/182 cluster (miR-183C) is expressed in both corneal resident myeloid cells (CRMCs) and sensory nerves (CSN) and modulates corneal immune/inflammatory responses. To uncover cell type-specific roles of miR-183C in CRMC and CSN and their contributions to corneal physiology, myeloid-specific miR-183C conditional knockout (MS-CKO), and sensory nerve-specific CKO (SNS-CKO) mice were produced and characterized in comparison to the conventional miR-183C KO. Immunofluorescence and confocal microscopy of flatmount corneas, corneal sensitivity, and tear volume assays were performed in young adult naïve mice; 3′ RNA sequencing (Seq) and proteomics in the trigeminal ganglion (TG), cornea and CRMCs. Our results showed that, similar to conventional KO mice, the numbers of CRMCs were increased in both MS-CKO and SNS-CKO vs age- and sex-matched WT control littermates, suggesting intrinsic and extrinsic regulations of miR-183C on CRMCs. The number of CRMCs was increased in male vs female MS-CKO mice, suggesting sex-dependent regulation of miR-183C on CRMCs. In the miR-183C KO and SNS-CKO, but not the MS-CKO mice, CSN density was decreased in the epithelial layer of the cornea, but not the stromal layer. Functionally, corneal sensitivity and basal tear volume were reduced in the KO and SNS-CKO, but not the MS-CKO mice. Tear volume in males is consistently higher than female WT mice. Bioinformatic analyses of the transcriptomes revealed a series of cell-type specific target genes of miR-183C in TG sensory neurons and CRMCs. Our data elucidate that miR-183C imposes intrinsic and extrinsic regulation on the establishment and function of CSN and CRMCs by cell-specific target genes. miR-183C modulates corneal sensitivity and tear production through its regulation of corneal sensory innervation.
Multilevel thresholding with divergence measure and improved particle swarm optimization algorithm for crack image segmentation
Authors: Nie Fangyan , Liu Mengzhu , Zhang Pingfeng
Published: April 2024

Crack formation is a common phenomenon in engineering structures, which can cause serious damage to the safety and health of these structures. An important method of ensuring the safety and health of engineered structures is the prompt detection of cracks. Image threshold segmentation based on machine vision is a crucial technology for crack detection. Threshold segmentation can separate the crack area from the background, providing convenience for more accurate measurement and evaluation of the crack condition and location. The segmentation of cracks in complex scenes is a challenging task, and this goal can be achieved by means of multilevel thresholding. The arithmetic-geometric divergence combines the advantages of the arithmetic mean and the geometric mean in probability measures, enabling a more precise capture of the local features of an image in image processing. In this paper, a multilevel thresholding method for crack image segmentation based on the minimum arithmetic-geometric divergence is proposed. To address the issue of time complexity in multilevel thresholding, an enhanced particle swarm optimization algorithm with local stochastic perturbation is proposed. In crack detection, the thresholding criterion function based on the minimum arithmetic-geometric divergence can adaptively determine the thresholds according to the distribution characteristics of pixel values in the image. The proposed enhanced particle swarm optimization algorithm can increase the diversity of candidate solutions and enhance the global convergence performance of the algorithm. The proposed method for crack image segmentation is compared with seven state-of-the-art multilevel thresholding methods based on several metrics, including RMSE, PSNR, SSIM, FSIM, and computation time. The experimental results show that the proposed method outperforms several competing methods in terms of these metrics.