bluuebunny/crossref_metadata_2025 huggingface dataset:
ARHGAP25: a novel player in the Pathomechanism of allergic contact hypersensitivity
Authors: Czárán Domonkos , Sasvári Péter , Lőrincz Kende , Ella Krisztina , Gellén Virág , Csépányi-Kömi Roland
Published: February 2025

Objective

Contact hypersensitivity (CHS), or allergic contact dermatitis (ACD), is an inflammatory skin disorder characterized by an exaggerated allergic reaction to specific haptens. During this delayed-type allergic reaction, the first contact with the allergen initiates the sensitization phase, forming memory T cells. Upon repeated contact with the hapten, the elicitation phase develops, activating mostly macrophages, cytotoxic T cells, and neutrophilic granulocytes. Our group previously demonstrated that the leukocyte-specific GTPase-activating protein ARHGAP25 regulates phagocyte effector functions and is crucial in the pathomechanism of autoantibody-induced arthritis. Here, we investigate its role in the pathogenesis of the more complex inflammatory process of contact hypersensitivity.

Methods

For sensitization, the abdomens of wild-type and ARHGAP25 deficient (KO) mice on a C57BL/6 background, as well as bone marrow chimeric mice, were coated with 3% TNCB (2-chloro-1,3,5-trinitrobenzene) or acetone in the control group. After five days, ears were treated with 1% TNCB for elicitation. Swelling of the ears caused by edema formation was evaluated by measuring the ear thickness. Afterward, ears were harvested, and histological analysis, investigation of leukocyte infiltration, cytokine production, and changes in relevant signaling pathways were carried out. ARHGAP25 expression at the mRNA and protein levels was measured using murine ear and human skin samples.

Results

ARHGAP25 expression increased in human patients suffering from contact dermatitis and in contact hypersensitivity induced in mice. Our data suggest that ARHGAP25 expression is infinitesimal in keratinocytes. In the CHS mouse model, the absence of ARHGAP25 mitigated the severity of inflammation in a leukocyte-dependent manner by reducing the infiltration of phagocytes and cytotoxic T cells. ARHGAP25 altered cytokine composition in the sensitization and elicitation phase of the disease. However, this protein did not affect T cell homing and activation in the sensitization phase.

Conclusion

Our findings suggest that ARHGAP25 is essential in developing contact hypersensitivity by modulating the cytokine environment and leukocyte infiltration. Based on these findings, we propose ARHGAP25 as a promising candidate for future therapeutic approaches and a potential ACD biomarker.
Multi-centered clinical validation demonstrating superior precision in lupus diagnosis: T cell autoantibodies and TC4d outperform conventional lupus erythematosus biomarkers
Authors: Kyttaris Vasileios , Wallace Daniel J. , Khosroshahi Arezou , Concoff Andrew , Wilson Nicole , Liu Chau Ching , Manzi Susan , Ahearn Joseph , Taghavi Sepehr , Warsi Touba , Park Stanley , Schleif Christine , Partain Brittany D. , O’Malley Tyler
Published: February 2025

Introduction

T Cell autoantibodies, TIgG and TIgM, as well as the T Cell-bound complement protein fragment C4d (TC4d) are novel diagnostic biomarkers that have demonstrated high specificity and sensitivity for SLE. The present study aims to characterize the clinical performance characteristics of the emergent T Cell biomarkers in a multi-center clinical validation cohort.

Methods

A cohort of 400 adult patients enrolled across 3 academic and 2 community-based autoimmune rheumatic centers, comprised of 105 SLE patients, 173 patients with autoimmune rheumatic diseases (ARD), 83 apparently healthy volunteers (AHV) and 39 other (non-autoimmune) disease (OD) controls were tested for TC4d, TIgG, TIgM and an extensive autoantibody profile. Diagnostic specificity was assessed against the ARD, AHV and OD groups, individually. Semi-quantitative flow cytometry analysis included TIgG and TIgM autoantibodies, cell-bound complement activation products (CB-CAPs), TC4d, erythrocyte-bound C4d (EC4d) and B lymphocyte-bound C4d (BC4d). Conventional autoantibodies and soluble complement proteins, C3 and C4, were assessed by ELISA and immunoturbidimetry, respectively.

Results

ROC analysis distinguishing ANA-positive (ANA+) SLE (N = 91) from ARD, TIgG, BC4d and TC4d demonstrated AUC values 0.81, 0.80 and 0.79, respectively, outperforming anti-dsDNA (0.72), C3 (0.69), TIgM (0.67), C4 (0.66) and anti-Smith (0.61). A similar ranking of discriminatory power was observed in ROC analysis distinguishing ANA+ SLE vs. OD as well as ANA+ SLE vs. AHV. At 95% diagnostic specificity for SLE vs. AHV, the sensitivity (95% CI) of TC4d, TIgG and TIgM for SLE was 58.1% (48.1 – 67.7%), 31.4% (22.7 – 41.2%) and 29.5% (21.0 – 39.2%), respectively. The T Cell SLE biomarkers uniquely identified 19% (20/105) of SLE patients who were otherwise negative (serologically inactive) for conventional SLE autoantibodies and had normal serum complement levels. Among the serologically inactive SLE subset, the T Cell SLE biomarkers collectively identified 53% of subjects.

Conclusions

The novel SLE biomarkers TC4d, TIgG and TIgM consistently outperform conventional markers across multiple cohorts. Their integration enhances diagnostic sensitivity, especially in SLE-specific autoantibody negative patients with normal complement levels. When coupled with conventional biomarkers, these novel tests may enable earlier and more accurate SLE detection, leading to more timely diagnosis and treatment.
Prospect of extracellular vesicles in tumor immunotherapy
Authors: Xia Wenbo , Tan Yunhan , Liu Yongen , Xie Na , Zhu Huili
Published: February 2025

Extracellular vesicles (EVs), as cell-derived small vesicles, facilitate intercellular communication within the tumor microenvironment (TME) by transporting biomolecules. EVs from different sources have varied contents, demonstrating differentiated functions that can either promote or inhibit cancer progression. Thus, regulating the formation, secretion, and intake of EVs becomes a new strategy for cancer intervention. Advancements in EV isolation techniques have spurred interest in EV-based therapies, particularly for tumor immunotherapy. This review explores the multifaceted functions of EVs from various sources in tumor immunotherapy, highlighting their potential in cancer vaccines and adoptive cell therapy. Furthermore, we explore the potential of EVs as nanoparticle delivery systems in tumor immunotherapy. Finally, we discuss the current state of EVs in clinical settings and future directions, aiming to provide crucial information to advance the development and clinical application of EVs for cancer treatment.
Phase 2 study of chidamide in combination with CAG and venetoclax-azacitidine in older patients with newly diagnosed acute myeloid leukemia
Authors: Liu Qingyang , Yang Jingjing , Lv Lei , Zhang Xiawei , Li Meng , Xu Lingmin , Huang Sai , Jing Yu , Dou Liping
Published: February 2025

Introduction

Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. DNA methyltransferases (DNMTs) and histone-deacetylases (HDACs) are key regulators of gene expression in cells and have been investigated as important therapeutic targets. However, their effects remains unclear as induction therapy for AML.

Methods

Previously untreated AML patients aged 60 years and over (N=40) were enrolled into this single arm, open-label, phase 2 study to evaluate the clinical efficacy and safety of chidamide combined with CAG and venetoclax-azacitidine (referred to as CACAG-VEN) in elderly AML patients (ClinicalTrials.gov:NCT05659992). All patients received induction treatment with aclarubicin (10 mg/m2/d on days 1, 3, and 5), azacitidine (75 mg/m2 on days 1–7), cytarabine (75 mg/m2 bid on days 1–5), chidamide (30 mg, twice/week for 2 weeks), and venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg on days 3–14). Granulocyte colony-stimulating factor 5 mg/kg/day was administered.

Results

Theoverall response rate was 97.5%, with a composite complete response (CRc) rate of 85.0% after one cycle of CACAG-VEN. Patients with adverse risk according to the ELN guidelines had CRc rates of 81.3%. No patients experienced early death within 30 days of therapy initiation. Grade 3 - 4 non-hematological adverse events included febrile neutropenia in 15 (37.5%) of 40 patients, pneumonia in three (7.5%), sepsis in two (5.0%) and blood bilirubin increase in one (2.5%). The 12-month overall survival rate was 73.4% (95% CI: 55.9–84.8%). The median time to recovery was 15.0 (IQR 10.0-19.5) days for platelets ≥ 20000/mL and 13.0 (IQR 10.5-17.0) days for an absolute neutrophil count ≥ 1000 cells/mL after induction therapy.

Discussion

In conclusion, chidamide in combination with CAG and venetoclaxazacitidine was effective and well tolerated in elderly patients with AML.

Clinical trial registration

https://www.clinicaltrials.gov/, identifier NCT05659992.
Integrated ecological quality assessment of the sea area adjacent to the Yellow River estuary under multiple pollutants
Authors: Li Wen , Ye Jinqing , Gao Xin , Zhang Yunlei , Li Ying , Li Hongjun
Published: February 2025

Estuaries are increasingly threatened by pollutants derived from human activities, which severely impair their water quality, biodiversity, and ecological functions. Therefore, within this context, it is essential to conduct comprehensive and scientifically rigorous assessments of estuarine ecological quality. Taking the Yellow River estuary as a case study, a composite index was here developed to evaluate the impacts of eutrophication and heavy metal pollution on estuarine ecological quality. The Trix eutrophication index and potential ecological risk index revealed significant risks of eutrophication and heavy metal pollution. Redundancy analysis identified that nutrients (NO2-N and NO3-N) and heavy metals (Cd, Hg, and Cr) were the primary pollutants affecting the composition of dominant macrofauna. Threshold Indicator Taxa Analysis was used to identify indicator species for these pollutants and, based on them, bioindicators capable of reflecting eutrophication and heavy metal pollution levels were then determined. A composite index integrating these bioindicators with other biotic indexes was constructed for comprehensive ecological quality assessment. The results showed that the ecological quality of the estuary was good, with values being even lower in the nearshore area. Structural equation modeling confirmed that estuarine ecological quality was significantly influenced, both directly and indirectly, by multiple pollutants, validating the effectiveness of the composite index as an analytical tool. We argue that integrating bioindicators of major pollutants with other benthic indexes into the developed composite index allows to effectively assess the effects of multiple pollutants on estuarine ecological quality and provide valuable insights for ecosystem management.
The role of digital health in respiratory diseases management: a narrative review of recent literature
Authors: Althobiani Malik A. , Russell Anne-Marie , Jacob Joseph , Ranjan Yatharth , Ahmad Rami , Folarin Amos A. , Hurst John R. , Porter Joanna C.
Published: February 2025

This review provides a detailed overview of how digital health can be utilized in the management of Interstitial Lung Disease (ILD), and Chronic Obstructive Pulmonary Disease (COPD). ILD encompasses a diverse range of lung disorders characterized by inflammation and scarring of lung tissue, leading to restrictive lung physiology and impaired gas exchange, with symptoms including progressive dyspnoea, cough, and hypoxia. COPD which ranks as the third leading cause of death globally, is characterized by chronic lung inflammation causing irreversible airflow obstruction, recurrent exacerbations. While recent advances in digital health have shown promise, predicting disease progression in patients with ILD and exacerbation in patients with COPD remains challenging. This review explores the role of digital health in managing ILD and COPD, particularly focusing on telehealth and digital health technologies. Telehealth, defined broadly as the use of electronic information and telecommunications technologies in healthcare, has become increasingly relevant, especially during the COVID-19 pandemic. This review examines the role of digital health technologies in the management of ILD and COPD, with particular focus on telemedicine, and digital health tools. Remote monitoring technologies, including home spirometry and wearable devices, have demonstrated feasibility in managing respiratory diseases. However, challenges such as evidence, data reliability, varying adherence, education, and the high costs of data collection and lack of qualified clinicians present barriers for many national health systems.
Internal in-frame translation generates Cas11b, which is important for effective interference in an archaeal CRISPR-Cas system
Authors: Sailer A-L. , Brendel J. , Chernev A. , König S. , Bischler T. , Gräfenhan T. , Urlaub H. , Gophna U. , Marchfelder A.
Published: February 2025

CRISPR-Cas is a sophisticated defence system used by bacteria and archaea to fend off invaders. CRISPR-Cas systems vary in their Cas protein composition and have therefore been divided into different classes and types. Type I systems of bacteria have been shown to contain the small protein Cas11 as part of the interference complex known as Cascade. Here we show for the first time that an archaeal CRISPR-Cas type I-B system also contains a homolog of Cas11. The Cas11b protein, encoded by the cas8b gene in Haloferax volcanii, represents the first known case of an internal in-frame translation of an archaeal protein. Translation initiation at an internal methionine of the cas8b open reading frame results in synthesis of Cas11b. Cas11b is required for an effective CRISPR-Cas interference reaction, and in its absence fewer Cascade complexes are formed. Comparison of transcriptomes from wild type and a Cas11b-less strain shows that the depletion of Cas11b also results in differential transcript abundance of many genes, presumably affecting their regulation. Taken together, Cas11b is important for the defence reaction of the type I-B CRISPR-Cas system and seems to play an additional cellular role.
High prevalence of carbapenem-resistant Pseudomonas aeruginosa and identification of a novel VIM-type metallo-β-lactamase, VIM-92, in clinical isolates from northern China
Authors: Zhao Linbo , Pu Jiekun , Liu Yunning , Cai Heng , Han Meijuan , Yu Yunsong , Tang Jianhua
Published: February 2025

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has become a serious global health concern due to the limited treatment options. The primary resistance mechanism in CRPA involves the production of metallo-β-lactamases (MBLs), making MBL-producing P. aeruginosa a significant component of CRPA cases. To understand the prevalence of CRPA in hospitals in northern China, we conducted a preliminary screening and identification of CRPA in 143 clinical isolates of P. aeruginosa collected from various departments of a tertiary hospital between 2021 and 2023, analyzing CRPA resistance trends in certain regions of northern China during this period. We identified 71 CRPA isolates that exhibited high carbapenem resistance and phylogenetic tree analysis revealed that ST244 CRPA isolates had widely spread across various departments of the same hospital over three consecutive years. We also identified two VIM-producing isolates, PJK40 and PJK43, both of which carried the same novel VIM-type metallo-β-lactamase, VIM-92, encoded by a newly identified gene, blaVIM-92, closely related to blaVIM-24. blaVIM-92 was embedded in class 1 integrons within the Tn1403 transposon. The blaVIM-92-carrying plasmid, pPJK40, was found to resemble the pJB37 megaplasmid. The expression of VIM-92 and VIM-24 in DH5α and PAO1 revealed similar effects of the MICs of β-lactams, except for aztreonam. The high prevalence of CRPA in clinical settings, and the identification of VIM-92, highlights the urgent need for ongoing surveillance of CRPA and emerging MBL variants in P. aeruginosa.
TRP channels and breast cancer: the role of TRPs in the pathophysiological development
Authors: Zhang Yu , Yi Yanfeng , Shu Yinghao , Ru Xiaochen , He Shuaibing
Published: February 2025

TRP channels play important roles in regulating various physiological and pathological processes, including the progression of cancer. Several TRP channels mediate tumour development. This review focuses on the role of TRP channels in the development of breast cancer, including their involvement in proliferation, apoptosis, autophagy, metastasis, and angiogenesis. TRP channels are associated with breast carcinogenesis and their role as potential therapeutic targets and prognostic biomarkers is under investigation. This review summarizes the reported effects of inhibiting or agonizing various TRP channel in breast cancer cells. Although there are relatively mature protocols for the treatment of breast cancer, its treatment is not currently a breakthrough, and therapies targeting TRP channels may be a developable strategy for it.
Effects of intermittent theta burst stimulation on upper limb motor recovery in early stroke patients: an fNIRS study
Authors: Liu Menghui , Wan Chunxiao , Wang Chunyan , Li Xinyi
Published: February 2025

Objective

To explore the recovery of upper limb motor function and the changes in cortical functional connectivity in patients with early subcortical small infarcts accompanied by severe upper limb motor dysfunction (PESSUM) after intermittent theta burst stimulation (iTBS) via functional near-infrared spectroscopy (fNIRS) and to explore the related mechanisms.

Methods

We enrolled 56 subcortical ischemic stroke patients with FMA-UE ≤28 and randomly assigned them to receive either genuine (TG, n = 29) or sham (CG, n = 23) iTBS plus standard rehabilitation over 8 days. fNIRS was used to monitor cerebral HbO, HbD, and HbT concentrations, and RSFC changes were analyzed. The FMA-UE and MBI scores were used to evaluate upper limb motor function and daily activities. Intergroup comparisons were conducted using independent samples t tests, whereas intragroup comparisons were performed using paired samples t tests or Mann–Whitney U tests. The trend of the RSFC changes was analyzed via repeated-measures Analysis of Variance (ANOVA).

Results

Both groups showed significant improvements in FMA-UE and MBI scores postintervention (p < 0.001). The TG had higher MBI scores than the CG (p = 0.005). fNIRS revealed accelerated cyclical changes in cortical activity in the TG.

Conclusion

iTBS significantly improved motor function and daily living ability in stroke patients, supporting a role for iTBS in promoting neural repair by accelerating cortical recovery cycles. This study provides evidence that iTBS is an effective rehabilitation strategy poststroke.

Clinical trial registration

https://www.chictr.org.cn/showproj.html?proj=169674, ChiCTR2200060955.
Persistent homology for MCI classification: a comparative analysis between graph and Vietoris-Rips filtrations
Authors: Bhattacharya Debanjali , Kaur Rajneet , Aithal Ninad , Sinha Neelam , Gregor Issac Thomas
Published: February 2025

Introduction

Mild cognitive impairment (MCI), often linked to early neurodegeneration, is associated with subtle disruptions in brain connectivity. In this paper, the applicability of persistent homology, a cutting-edge topological data analysis technique is explored for classifying MCI subtypes.

Method

The study examines brain network topology derived from fMRI time series data. In this regard, we investigate two methods for computing persistent homology: (1) Vietoris-Rips filtration, which leverages point clouds generated from fMRI time series to capture dynamic and global changes in brain connectivity, and (2) graph filtration, which examines connectivity matrices based on static pairwise correlations. The obtained persistent topological features are quantified using Wasserstein distance, which enables a detailed comparison of brain network structures.

Result

Our findings show that Vietoris-Rips filtration significantly outperforms graph filtration in brain network analysis. Specifically, it achieves a maximum accuracy of 85.7% in the Default Mode Network, for classifying MCI using in-house dataset.

Discussion

This study highlights the superior ability of Vietoris-Rips filtration to capture intricate brain network patterns, offering a robust tool for early diagnosis and precise classification of MCI subtypes.
Electrically evoked mismatch negativity from speech stimuli as an objective measure of cochlear implant performance
Authors: Zhang Lichun , Stauga Pattric , Mißler David , Ehrt Karsten , Großmann Wilma , Mlynski Robert , Schmidt Florian Herrmann
Published: February 2025

Introduction

Cochlear implant (CI) success is often assessed using subjective tests like word recognition scores (WRS). However, these tests are unsuitable for children, non-native speakers, and individuals with cognitive impairments. Mismatch negativity (MMN), an objective measure of cortical auditory processing, offers a promising alternative for evaluating speech perception. This study aimed to assess speech perception in CI patients using MMN and examine its correlation with WRS.

Methods

The study included 23 ears from CI users fitted for at least six months. Speech stimuli were presented via direct audio input to the CI processor at 70 dB nHL using an MMN paradigm. The syllables ‘ba’ (standard) and ‘da’ (deviant) served as stimuli. MMN amplitude and latency were analyzed, and their correlation with WRS was examined.

Results

A significant correlation was observed between WRS and MMN responses. CI users with lower WRS scores exhibited reduced MMN amplitudes and prolonged latencies compared to those with higher scores, indicating impaired cortical speech processing.

Discussion

These findings suggest that speech-induced MMN could serve as an objective tool for assessing speech perception in CI users. MMN provides valuable insights for optimizing CI fitting, particularly for patients unable to undergo subjective testing. Integrating MMN into clinical practice could improve speech perception outcomes and enhance the quality of life for CI users.
Impact of Ligilactobacillus salivarius Li01 on benzo[a]pyrene-induced colitis, based on host-microbiome interactions in Mongolian gerbils
Authors: Huang Yilun , Yang Can , Fu Bingmeng , Guo Honggang , Chen Yunxiang , Xu Dengfeng
Published: February 2025

Background

Probiotics supplementations have been regarded as an effective strategy for colitis treatment. However, the effect of Ligilactobacillus salivarius Li01 on benzo[a]pyrene (BaP)-induced colitis in Mongolian gerbils remains unclear. In this study, we leverage a BaP-induced model of colitis that exhibits significant remission following Ligilactobacillus salivarius Li01 intervention, to conduct an animal experiment that integrates histopathological assessment, inflammatory cytokines, 16S rRNA sequencing, targeted metabolomic profiling to investigate the relationship between Ligilactobacillus salivarius Li01, gut microbiota, and colitis.

Results

We demonstrated that the improvements in colon histopathological assessment and inflammatory cytokines by Ligilactobacillus salivarius Li01 supplementation are accompanied by alterations in gut microbiota structure marked by increased abundance of strains with probiotic potential belonging to Bifidobacterium and Eubacterium_coprostanoligenes. Targeted metabolomic profiling analysis showed that Ligilactobacillus salivarius Li01 supplementation increases the concentration of acetic, propionic, butyric, and valeric acid. Correlation analysis showed that the alteration in the indicators associated with colitis is closely correlated to the changed microbial taxa and short-chain fatty acids (SCFAs).

Conclusion

These data highlighted that Ligilactobacillus salivarius Li01 supplementation ameliorated the BaP-induced colitis, probably via modulating the structure of gut microbiota and promoting the production of SCFAs. Our findings provide preliminary evidence for a possible therapeutic strategy for the treatment of colitis based on host-microbiome interactions.
Enteral nutritional support for an elderly critically ill patient with gastroesophageal reflux disease and situs inversus totalis: a case report
Authors: Chen Yuanyuan , Ma MengLin , Huang Xiaoqing , Wan Jia , Huang Haiyan
Published: February 2025

Herein, we present a case of serious protein-energy malnutrition in an elderly critically ill patient with situs inversus totalis. It was difficult to implement enteral nutrition in this patient for more than 2 months of hospitalisation in another hospital, and we applied electromagnetic navigation guidance to implement enteral nutrition after successful placement of nasojejunal tubes. We reviewed the management of enteral nutrition support.
Beta-blocker administration within 24 hours after admission to the intensive care unit and mortality in critical heart failure patients: a retrospective analysis from the MIMIC-IV database
Authors: Xie Linfeng , Chen Jing , Li Yuanzhu , Liu Gang , Shen Jian , Li Xiang , Yang Yuan , Chen Yintao , Luo Suxin , Huang Bi
Published: February 2025

Background

It remains poorly understood whether early use of beta-blockers could provide a survival advantage in patients with critical heart failure (HF) .

Methods

This retrospective study was conducted using the American Medical Information Mart for Intensive Care (MIMIC)-IV database. Study participants were critical HF patients who were divided into two groups: within 24-hour use of beta-blockers group and no use of beta-blockers group. The primary study endpoints were 7-day, 30-day, and 360-day all-cause mortality.

Results

Out of the 10,184 patients diagnosed with critical HF, after propensity score match (PSM), 7352 patients were recruited and were divided into within 24-h use of beta-blockers group (n = 3676) and no beta blockers group (n = 3676). The 7-day, 30-day, and 360-day all-cause mortality were significantly higher in the no beta blockers group (7-day: 10.3% vs 5.5%; 30-day: 21.4% vs 15.7%; 360-day: 40.0% vs 35.3%; all p < 0.001). Kaplan–Meier analyses showed that the cumulative incidence of 7-day, 30-day, and 360-day all-cause mortality were significantly higher in the no beta blockers group (all log-rank p < 0.001). After PSM, Cox proportional hazards analyses revealed that beta blockers administration within 24 h of admission to intensive care unit (ICU) was independently associated with decreased 7-day (HR = 0.52 95%CI: 0.44, 0.62, p < 0.001), 30-day (HR = 0.70 95%CI: 0.63, 0.78, p < 0.001), and 360-day (HR = 0.83 95%CI: 0.77, 0.89, p < 0.001) all-cause mortality.

Conclusion

Administration of beta blockers within 24 h after admission to ICU was associated with reduced risk of mortality in critical HF patients. However, prospective randomized controlled trials are needed to confirm our findings due to the retrospective nature of the present study and the limitations of the MIMIC-IV database itself.
A combinatorial screening protocol for identifying novel and highly potent dual-target inhibitor of BRD4 and STAT3 for kidney cancer therapy
Authors: Zhang Shizhu , Wu Nan , Geng Yifei , Guan Lixia , Niu Miao-Miao , Li Jindong , Zhu Lusha
Published: February 2025

Concurrent inhibition of bromodomain-containing protein 4 (BRD4) and signal transductor and activator of transcription 3 (STAT3) could potentially be an effective strategy against renal cell carcinoma (RCC). Here, we successfully identified five dual-targeted BRD4/STAT3 inhibitors (BSTs 1–5) using a combinatorial screening protocol. Particularly, BST-4 was the most potent inhibitor simultaneously targeting BRD4 (IC50 = 2.45 ± 0.11 nM) and STAT3 (IC50 = 8.07 ± 0.51 nM). MD simulation indicated that BST-4 stably bound to the active sites of BRD4 and STAT3. The cytotoxicity assays exhibited that BST-4 had a significant antiproliferative activity against RCC cell lines, especially CAKI-2 cells (IC50 = 0.76 ± 0.05 μM). Moreover, in vivo experiments revealed that BST-4 more effectively inhibited the growth of xenograft tumors compared with positive controls RVX-208 and CJ-1383. Overall, these data indicated that BST-4 could be a promising candidate compound for RCC therapy.
Visualization techniques for the gyrokinetic tokamak simulation code
Authors: Feibush Eliot , Ethier Stephane , Yan Jason , Yao Alexander
Published: February 2025

Gyrokinetic simulations of plasma microturbulence in tokamaks are challenging to visualize because the compute grid follows the magnetic field lines that spiral around the torus. We have overcome this challenge by developing three new approaches that improve visualization of gyrokinetics. Our techniques work directly with the topology of magnetic flux surfaces where the simulation stores variables in concentric rings on poloidal planes (vertical cross sections of the torus). Our visualization preview step triangulates each consecutive pair of rings to display the data on a poloidal plane. The second visualization technique follows spiral field lines around the torus and constructs polygons to visualize a flux surface. Third, the poloidal triangles are connected between planes to form prisms that compose a 3-D model of the entire torus. The visualization workflow produces detailed geometry that matches the high resolution, irregular compute grid for every time step. The surface and solid models are displayed in scientific visualization programs to effectively explore and communicate the results, including fluctuation of electron density, ion temperature, and electrostatic potential. Highly detailed renderings verify plasma behavior along magnetic field lines over time.
Genome-wide analysis of OPR family genes in Vitis vinifera and the role of VvOPR1 in copper, zinc tolerance
Authors: You Shuang-Hong , Chen Yuan-Ping , Shi Wen-Jing , Li Xue , Wu Zheng , Yao Quan-Hong
Published: February 2025

12-oxo-phytodienoic acid reductase (OPR) is one of the key enzymes in the octadecanoid pathway, and it controls the last step of jasmonic acid (JA) biosynthesis. Although multiple isoforms and functions of OPRs have been identified in various plants, no OPR genes have been identified, and their possible roles in grapevine development and defense mechanisms remain unknown. In this study, nine VvOPR genes were identified from grapevine genome and classified into two subfamilies. Systematic analyses of the physical and chemical properties, the expression and structure of the VvOPR genes, promoter elements, and chromosome locations were performed via bioinformatics and molecular biology methods. In addition, we described the characterization of the OPRI gene VvOPR1, which was synthesized via a PCR-based two-step DNA synthesis quantification reverse-transcription (PTDS) method. VvOPR1 expression is tissue-specific and induced by various stresses. The overexpression of VvOPR1 in Arabidopsis and rice (OT) significantly increased tolerance to Cu, Zn stress, and Cu, Zn stress-induced restriction of the germination rate, root/shoot length and fresh weight was significantly alleviated in OT. In OT, VvOPR1 enhanced the photosynthetic capacity, promoted ABA synthesis and the ABA-dependent stress response pathway, improved the antioxidation capacity by increasing the activities of ROS scavengers and the expression level of the related genes, while enhancing the accumulation of proline, AsA, GSH and reducing MDA and H2O2 levels. Moreover, VvOPR1 reduced Cu2+, Zn2+ accumulation and translocation. Together, we first systematically characterized the grapevine OPR gene family and reported that VvOPR1 responded to Cu, Zn stress in an ABA-dependent manner, and was quite independent of JA synthesis and signaling. All of the above results provide an important research basis and theoretical basis for further revealing the functions of VvOPR in grapevines in the future.
Integrated transcriptome and metabolome analyses reveals the mechanisms of function loss of Lr29 leaf rust resistance gene at high temperatures in wheat
Authors: Wang Liwen , Yu Yang , Li Hang , Lu Mingzhu , Cao Shubo , Li Ziqi , Song Haoyuan , Purnhauser Laszlo , Li Jinlong , Wu Jiajie
Published: February 2025

Leaf rust (LR) is one of the most common diseases of wheat. The resistance gene Lr29 provides wide resistance to LR, but loses its function under high temperatures. Despite the importance of this gene, the mechanism of resistance is unclear. In this study we investigated the resistance mechanism of the Lr29 gene to LR at the seedling stage, as well as the reasons behind the loss of gene function at high temperatures by using integrated transcriptome and metabolome analyses. Results suggests that the pathways of reactive oxygen species (ROS), which could be due to expression of genes including LOX (lipoxygenase), APX (ascorbate peroxidase) and GST (glutathione S-transferase), play a key role in the resistance of Lr29 to LR, furthermore flavonoids, such as epicatechin, cosmosiin, apiin, vitexin and rutin, were identified as the key metabolites linked to Lr29 resistance. We also found that, at high temperatures, Lr29 downregulated the genes and metabolites associated with glycolysis and the tricarboxylic acid (TCA) cycle, while genes and metabolites related to the shikimic acid pathway were upregulated. This study might provide a valuable theoretical foundation for the cloning of the Lr29 gene, the analysis of its disease resistance mechanism, and the understanding of how temperature affects gene function.
When helping hurts: validating a measure of compulsive helping and exploring potential correlates
Authors: Workman Katey , Padilla-Walker Laura M. , Reschke Peter J. , Rogers Adam A.
Published: February 2025

Introduction

This cross-sectional study proposes and validates a new measure of compulsive helping: helping which harms the helper.

Methods

Emerging Adults (N = 438; Mage = 20.29, SD = 1.04, 51.71% Female) reported on compulsive helping. Confirmatory factor analysis was used to assess construct validity, while bivariate correlations were used to assess convergent and discriminant validity.

Results

Confirmatory factor analysis suggested convergent validity with all 10 items loading onto a single factor, with factor loadings above 0.44. Model fit was acceptable. Convergent validity was demonstrated such that compulsive helping was positively correlated with prosocial behavior and anxiety. Discriminant validity was demonstrated such that compulsive helping was negatively associated with self-regulation.

Conclusion

This new concept and measure of compulsive helping is a first step toward defining the limits of the adaptiveness of prosocial behavior. Though not frequent, it appears helping which is harmful is not uncommon. Future research should employ qualitative means and consider the multidimensionality of prosocial behavior.
How does internet use affect the sense of gain in older adults? A moderated mediation model
Authors: Yang Yi , Ni Ying
Published: February 2025

In the context of the digital era, Internet use is of major significance for enhancing the sense of gain among elderly people and enabling them to share in the development dividend of the digital society. Based on CGSS 2021 (N = 2,929), this study explores the impact of Internet use on the sense of gain in the elderly, and a moderated mediation model was constructed to explore the mediating role of perceived social justice and the potential moderating role of social status. The results showed that (1) Internet use in general significantly enhanced elderly’s sense of gain. Among this group, economic sense of gain (ESG) was significantly enhanced, political sense of gain (PSG) was positively affected but not significantly, while security sense of gain (SSG) was negatively affected. (2) A sense of social equity plays a mediating role in the impact of Internet use on the sense of gain among older adults. (3) Social status does not play a moderating role in the latter half of the path of the mediation model. Meanwhile, heterogeneity analysis revealed that Internet use positively and significantly affects the sense of gain among elderly people with low household incomes, high levels of literacy, an urban household registration, and a spouse. The research conclusion of this article provides strong empirical support for solving the problem of digital integration among the elderly and effectively enhancing their sense of achievement.
Study on the impact of rural public sports facilities and instructors on residents’ participation in sports activities in China
Authors: Guo Xiujin , Yang Xiangjun , Mao Sujie
Published: February 2025

Objective

This study aims to explore how rural public sports facilities and their instructors influence the participation of rural residents in sports activities under the background of China’s rural revitalization strategy. The goal is to provide strategies for the effective use and management of rural sports facilities, thereby encouraging rural residents to actively participate in sports activities, improve their quality of life, and support comprehensive rural revitalization.

Methods

A cross-sectional study design was used, employing a stratified sampling method to distribute questionnaires to 5,000 residents in the eastern, central, western, and southern regions of China. Data analysis was conducted using R4.1.3 software. The main research indicators included the funding sources of sports facilities and the composition of social sports instructors, while residents’ basic characteristics were considered secondary indicators for correlation, regression, and cross-analysis.

Results

Analysis of 3,956 valid questionnaires revealed that increasing age led to a decrease in the frequency of sports activities (−0.098), while higher education levels increased activity frequency (0.097). Facilities provided by county sports bureaus significantly promoted participation in sports activities (B = 0.320, p < 0.001). Facilities donated by villagers or township enterprises and the sports lottery fund also effectively increased participation (B = 0.219, p < 0.001; B = 0.159, p = 0.011). Sports facility instructors, particularly urban residents and retirees, significantly positively impacted activity time, while the absence of instructors reduced residents’ participation in sports activities (B = −0.445, p < 0.001).

Conclusion

Age and education level are negatively correlated with sports activity participation, while the source of public sports facilities, especially those provided by county sports bureaus, the sports lottery fund, and village committees, significantly enhance participation. The presence of social sports instructors significantly increases the time and frequency of residents’ sports activities. Policymakers need to focus on the construction and management of public sports facilities, develop and utilize diversified funding sources, and enhance the role of sports facility instructors. By providing professional guidance and organizing diverse sports activities, rural residents’ enthusiasm for participation can be effectively stimulated.
Parental smoking is associated with adolescent loneliness: evidence from 71 low- and middle-income countries
Authors: Xie Jintang , Yang Hui , Zhao Min , Magnussen Costan G. , Xi Bo
Published: February 2025

Introduction

The association between parental smoking and adolescent mental health is not well understood. We aimed to examine the association between parental smoking and adolescent loneliness using global data collected from the Global School-based Student Health Survey (GSHS) between 2009 and 2019.

Methods

A total of 187,552 adolescents aged 12–15 years in 71 low- and middle-income countries (LMIC) from the GSHS with cross-sectional design were included in this study. Loneliness was defined as feeling lonely sometimes or more frequently in the past 12 months. Parental smoking, reported by the adolescent, was defined as the use of any form of tobacco by the father and/or mother. Logistic regression models were used to examine the odds ratio (OR) of adolescent loneliness according to parental smoking status.

Results

Compared with neither parent smoking, parental smoking was associated with adolescent loneliness (father only: OR = 1.18, 95% CI = 1.10–1.26; mother only: OR = 1.39, 95% CI = 1.15–1.67; both: OR = 1.65, 95% CI = 1.41–1.93) after adjustment for potential covariates. Subgroup analyses stratified by sex, age, and WHO region showed similar results (except not in the African and Western Pacific regions).

Discussion

Parental smoking is associated with loneliness in adolescents from LMIC. Our finding expands the well-known physical damage of parental smoking in adolescents to the psychological damage. Strict policies and strategies should be established to encourage smoking cessation for parents who are current smokers.
The variability in hydrocarbon ions (CnH−) of polymers detected by ToF-SIMS: principal component analysis on carbon density and cross-linking degree
Authors: Nie Heng-Yong
Published: February 2025

Negative hydrocarbon ions, CnH− (n = 1–10), are ubiquitous in time-of-flight secondary ion mass spectrometry, but their utility may have been overlooked. Recently, however, it has been demonstrated that the ion intensity ratio between C6H− and C4H−, denoted as ρ, can differentiate the chemical structures of polymers such as polyethylene, polypropylene, polyisoprene and polystyrene, as well as depth profile the cross-linking degree of poly (methyl methacrylate). It was found that ρ increases with the carbon density of polymers. Principal component analysis (PCA), a dimensionality reduction technique, can reveal hidden data structures through exploring the relationships among the CnH− intensities for the four polymers. Assisted by the biplot approach, PCA is key to uncovering hidden data structures, from which characteristic ions may be identifiable and their relationships classifiable. The four polymers were classified by their carbon densities, which dictate the variability of CnH− intensities and are captured by the first principal component (PC1). It also became clear that PC1 is correlated with ρ. This data-driven analytical approach is imperative when differentiating chemicals with similar structures, especially when diagnostic ions are lacking. We demonstrate the usefulness of this approach by examining poly (methyl methacrylate) with different degrees of cross-linking.
Application of chlorous acid water for disinfection of surgical site in dairy cows
Authors: Ichii Osamu , Nakamura Teppei , Hiraishi Masaya , Namba Takashi , Rubel Md. Zahir Uddin , Umeyama Takuya , Asai Megumi
Published: February 2025

Disinfection is crucial for preventing surgical site infections. Recently, the effectiveness of sanitizers using chlorous acid (HClO2) under conditions rich in organic matter has been reported, and chlorous acid water (CAW) has been approved as a food additive. This study evaluated the potential of CAW as a new presurgical disinfectant for cattle. The experiments were performed on the paralumbar fossa of cattle in Sapporo during March (winter to spring) and August (summer). Colony-forming units (CFUs) of standard plate count bacteria (SPCB), Enterococcus faecalis (EF), Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus spp. (SP) were analyzed as indicators of bacterial load. SPCB and SP were abundantly detected, exceeding 6 log10 CFU/100 g on clipped hair and 6 log10 CFU/100 cm2 on the skin immediately after clipping, with no significant seasonal differences. The bacterial load on the skin was evaluated at three time points: after clipping, cleansing, and disinfection. Clipping and cleansing with liquid soap were common procedures, following this, either the standard disinfection protocol using 7.5% iodine scrub for 1 min, 10% povidone-iodine for 5 min, and 70% alcohol for 5 min (SPA), or a modified protocol using CAW with contact times of 15, 10, or 5 min (CAW15, CAW10, CAW5) were performed separately. The cleansing procedure significantly reduced the SPCB, EF, and SP on the skin after clipping, and all disinfection methods significantly decreased the SP after cleansing. Draping significantly enhanced the disinfection efficiency of the SPA, CAW10, and CAW5 protocols. The CAW procedure did not alter skin histology in the paralumbar fossa or udder compared to 10% povidone-iodine or 70% alcohol. Our data suggest that the disinfection method using CAW is useful and comparable to routine disinfection methods and might reduce the time required for presurgical disinfection in farm fields.
Calibration of DEM Polyhedron Model for Wheat Seed Based on Angle of Repose Test and Semi-Resolved CFD-DEM Coupling Simulation
Authors: Wang Longbao , Yang Hanyu , Wang Zhinan , Wang Qingjie , Lu Caiyun , Wang Chao , He Jin
Published: February 2025

The shape of particles is a critical determinant that significantly influences the accuracy of discrete element simulations. To reduce the discrepancies between the discrete element model of wheat seeds and the actual particle shapes, and to enhance the accuracy of Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) coupling simulations in gas–solid two-phase flow studies, We employed laser scanning and inverse modeling techniques to develop a three-dimensional (3D) reconstruction of the wheat seed. Subsequently, we employed Rocky DEM simulation software to develop a polyhedron model and an Angle of Repose (AOR) test model. The interval range of material parameters was determined through a series of physical experiments and subsequently employed to delineate the high and low levels of parameters for the simulation tests. The simulation parameters were calibrated using data from AOR simulation tests. The Plackett–Burman test, Steepest-Ascent test, and Box–Behnken test were conducted sequentially to determine the optimal parameter configuration. A test bench for wheat gas-assisted seeding was constructed, and a semi-resolved CFD-DEM coupling simulation model was developed to perform comparative analysis. The results demonstrated that the optimal parameters were as follows: the static friction coefficient of wheat seed was 0.15, the dynamic friction coefficient of wheat seed was 0.11694, and the dynamic friction coefficient between wheat seed and resin was 0.0797. In this scenario, the relative error of AOR was 2.3% and the maximum relative error of ejection velocity observed was 4.1%. The reliability of the polyhedron model and its calibration parameters was rigorously validated, thereby providing a robust reference for studies on gas–solid two-phase flows.