bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorimetric aptasensor coupled with a deep-learning-powered smartphone app for programmed death ligand-1 expressing extracellular vesicles
Authors: Khan Adeel , Khan Haroon , He Nongyue , Li Zhiyang , Alyahya Heba Khalil , Bin Jardan Yousef A.
Published: January 2025

Lung cancer is a devastating public health threat and a leading cause of cancer-related deaths. Therefore, it is imperative to develop sophisticated techniques for the non-invasive detection of lung cancer. Extracellular vesicles expressing programmed death ligand-1 (PD-L1) markers (PD-L1@EVs) in the blood are reported to be indicative of lung cancer and response to immunotherapy. Our approach is the development of a colorimetric aptasensor by combining the rapid capturing efficiency of (Fe3O4)-SiO2-TiO2 for EV isolation with PD-L1 aptamer-triggered enzyme-linked hybridization chain reaction (HCR) for signal amplification. The numerous HRPs catalyze their substrate dopamine (colorless) into polydopamine (blackish brown). Change in chromaticity directly correlates with the concentration of PD-L1@EVs in the sample. The colorimetric aptasensor was able to detect PD-L1@EVs at concentrations as low as 3.6×102 EVs/mL with a wide linear range from 103 to 1010 EVs/mL with high specificity and successfully detected lung cancer patients’ serum from healthy volunteers’ serum. To transform the qualitative colorimetric approach into a quantitative operation, we developed an intelligent convolutional neural network (CNN)-powered quantitative analyzer for chromaticity in the form of a smartphone app named ExoP, thereby achieving the intelligent analysis of chromaticity with minimal user intervention or additional hardware attachments for the sensitive and specific quantification of PD-L1@EVs. This combined approach offers a simple, sensitive, and specific tool for lung cancer detection using PD-L1@EVs. The addition of a CNN-powered smartphone app further eliminates the need for specialized equipment, making the colorimetric aptasensor more accessible for low-resource settings.
Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus
Authors: Zhao Jindong , Fang Zhaohui
Published: January 2025

Introduction

Type 2 diabetes mellitus (T2DM) is a disease that involves autoimmunity. However, how immune cells function in the peripheral blood remains unclear. Exploring T2DM biomarkers via single-cell RNA sequencing (scRNA-seq) could provide new insights into the underlying molecular mechanisms.

Methods

The clinical trial registration number is ChiCTR2100049613. In this study, we included three healthy participants and three T2DM patients. The observed clinical indicators included weight and fasting blood glucose (FBG), glycosylated haemoglobin A1c (HbA1c) and fasting insulin levels. Direct separation and purification of peripheral blood mononuclear cells (PBMCs) were performed via the Ficoll density gradient centrifugation method. Immune cell types were identified via scRNA-seq. The differentially expressed genes, biological functions, cell cycle dynamics, and correlations between blood glucose indicators and genes in different cell types were analysed.

Results

There were differences between the healthy and T2DM groups in terms of FBG and HbA1c (p<0.05 or p<0.01). We profiled 13,591 cells and 3188 marker genes from PBMCs. B cells, T cells, monocytes, and NK cells were grouped into 4 subclusters from PBMCs. CD4+ T cells are mainly in the memory activation stage, and CD8+ T cells are effectors. Monocytes include mainly CD14+ monocytes and FCGR3A+ monocytes. There were 119 differentially expressed genes in T cells and 175 differentially expressed genes in monocytes. Gene set enrichment analysis revealed that the marker genes were enriched in HALLMARK_ INTERFERON_GAMMA_RESPONSE and HALLMARK_TNFA_SIGNALING_VIA_ NFKB. Moreover, TNFRSF1A was identified as the core gene involved in network interactions in T cells.

Discussion

Our study provides a transcriptional map of immune cells from PBMCs and provides a framework for understanding the immune status and potential immune mechanisms of T2DM patients via scRNA-seq.

Clinical trial registration

http://www.chictr.org.cn, identifier ChiCTR2100049613.
The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in women
Authors: Hu Xinjun , Li Shasha , Huang Renliang , Fu Ziwei , Ma Chenyu , Cheng Zheng , Hu Hongjun , Zhou Qiaomiao , Petersen Frank , Yu Xinhua , Zheng Junfeng
Published: January 2025

Introduction

The neutrophil cytosolic factor 1 (NCF1) rs201802880 polymorphism is a missense mutation resulting in an amino acid substitution from arginine to histidine at position 90, which impairs the function of NADPH oxidase. This casual variant confers an increased risk for multiple autoimmune disorders, including primary Sjögren’s syndrome and systemic lupus erythematosus. Given the high prevalence of this autoimmune disease risk variant in East Asia, we hypothesized that it may confer an evolutionary advantage by providing protection against infectious diseases.

Methods

To test this hypothesis, we investigated whether the NCF1 rs201802880 variant offers a protective effect against tuberculosis (TB), a historically significant and deadly infectious disease. Our study included 490 healthy controls and 492 TB patients who were genotyped for the NCF1 rs201802880 polymorphism.

Results

Our results showed that the NCF1 rs201802880 AA genotype was associated with a reduced risk of TB in women (OR= 0.25, 95% CI: 0.09-0.68, p=0.0023). Additionally, healthy individuals with the NCF1 rs201802880 AA genotype had significantly lower circulating white blood cell (5.56 ± 1.78 vs 6.43 ± 1.59, p=0.003) and neutrophil (3.23 ± 1.20 vs 3.74 ± 1.23, p = 0.02) counts compared to those with the GG or GA genotypes, with this difference being more pronounced in women than in men.

Conclusion

This study demonstrates that the autoimmune disease-causal NCF1 variant is associated with a protective effect against TB infection.
Sintilimab for the treatment of lung adenocarcinoma-induced immune-related hypophysitis: a case report
Authors: Wang Ming-xing , Liu Ai-xin , Sun Qing-ming , Dong Wan-hui
Published: January 2025

Immune checkpoint inhibitors (ICIs) are extensively utilized in the treatment of oncological patients, and the immune-related adverse reactions they induce merit close monitoring. This report describes a case of a lung cancer patient who, after receiving chemotherapy in combination with the programmed death-1 (PD-1) inhibitor sintilimab, presented with systemic fatigue, alterations in mental and behavioral patterns, somnolence, and symptoms of diabetes insipidus, leading to a diagnosis of grade 4 immune-related hypophysitis. The patient experienced symptomatic relief following pulse therapy with dexamethasone sodium phosphate injections (30mg every 12 hours), and was subsequently treated with prednisone acetate tablets (30 mg/day), which were gradually reduced to a physiological replacement dose. The treatment with sintilimab was discontinued, and the patient’s symptoms gradually improved, with normalization of urine output.
Path planning for unmanned surface vehicles in anchorage areas based on the risk-aware path optimization algorithm
Authors: Wang Hongbo , Mao Shuaiwei , Mou Xiaoguang , Zhang Jinfeng , Li Ronghui
Published: January 2025

In dense anchorage areas, the challenge of navigation for Unmanned Surface Vehicles (USVs) is particularly pronounced, especially regarding path safety and economy. A Risk-Aware Path Optimization Algorithm (RAPO) is proposed to enhance the safety and efficiency of USV navigating in anchorage areas. The algorithm incorporates risk assessment based on the A* algorithm to generate an optimized path and employs a Dual-Phase Smoothing Strategy to ensure path smoothness. First, the anchorage area is spatially separated using a Voronoi polygon, the RAPO algorithm includes a grid risk function, derived from the ship domain and Gaussian influence function, in the path evaluation criteria, directing USV to successfully bypass high-risk areas and as a result. Then the DPSS is used to decrease path turning points and boost path continuity, which in turn improves path economy. Simulation results demonstrate that this method significantly reduces the path length and the number of turning points, enhancing USV navigation safety in anchorage areas.
Seasonal variation of underwater sound propagation in the Beibu Gulf
Authors: Zeng Feihong , Xie Lingling , Li Mingming , Li Qiang , Liu Simeng
Published: January 2025

Variations in the underwater sound speed significantly influence sound propagation in the ocean, thereby impacting both underwater navigation systems and a substantial portion of marine organisms reliant on sound. This study utilizes cruise data from the Beibu Gulf during the summer and winter of 2023–2024 to explore the seasonal variations in temperature and salinity affecting the sound speed distribution and characteristics of sound propagation. Results indicate significant differences in the sound speed on either side of the 30-m isobath in the Beibu Gulf, with pronounced changes corresponding to seasonal temperature and salinity variations. In summer, the sound speed in the Beibu Gulf exhibits a north-high–south-low pattern. In areas shallower than 30 m, the sonocline is predominantly positive or absent, whereas, in deeper areas, it is mainly negative. During winter, there is a south-high–north-low pattern in sound speed across the Beibu Gulf, with pronounced sound speed extremes in areas shallower than 30 m. Sound propagation simulations based on the Beibu Gulf sound-speed field reveal that sounds at the 100-Hz frequency propagate significantly farther and cover larger areas in depths less than 30 m compared to deeper areas. In summer, this phenomenon is more pronounced than in winter due to the presence of positive sonoclines. The results have significant implications for target detection, underwater acoustic communication, and the protection of aquatic animals that rely on underwater sound for survival in the Beibu Gulf.
A study on the codon usage bias of arenavirus common genes
Authors: Thomas Pablo Daniel , Ferrer María Florencia , Lozano Mauricio J. , Gómez Ricardo Martín
Published: January 2025

Introduction

The Arenaviridae family consists of the genera Mammarenavirus, Reptarenavirus, Hartmanivirus, Antennavirus and Innmovirus. The codon usage bias between the different genera has not yet been studied comparatively.

Methods

We retrieved the arenavirus genome sequences from public databases and used bioinformatics tools to compare the codon usage bias between the different genera for the GPC, NP and L proteins, common to all arenaviruses.

Results and discussion

Hartmaniviruses show a larger codon usage bias, which can be partially explained by mutational bias. Patterns of relative use of synonymous codons were maintained within genera, with individual genera differing in their preference for the third nucleotide position in synonymous codons. Of the three proteins examined, the ARN polymerase L protein exhibited a slightly stronger codon usage bias, but overall, the patterns were repeated between genera for the three proteins examined. Our results suggest that codon usage pattern bias in arenaviruses is influenced by selection pressure and to a lesser extent by mutational selection.
Soil microbial community and influencing factors of different vegetation restoration types in a typical agricultural pastoral ecotone
Authors: Huang Pei , Shi Hanyu , Jiang Lina , Zhu Duoping , Zhou Zefeng , Hou Zhenhong , Ma Xingyu
Published: January 2025

Microbial network complexity is an important indicator for assessing the effectiveness of vegetation restoration. However, the response of the microbial network complexity of bacteria and fungi to different vegetation restoration types is unclear. Therefore, in this study, we selected four vegetation restoration types (Pinus sylvestris var. mongholica, Larix principis- rupprechtii, Populus tomentosa, and Ulmus pumila), while selected the nature grassland as a control, in the Zhangjiakou Tunken Forest Farm, which is a typical agricultural pastoral ecotone in northern China, to investigate the response of soil microbial diversity and network complexity to different vegetation restoration types. Our result showed that the bacterial Shannon and Chao indices of P. sylvestris var. mongholica were significantly 7.77 and 22.39% higher than those of grassland in the 20–40 cm soil layer, respectively. The fungal Chao indices of U. pumila were significantly 85.70 and 146.86% higher than those of grassland in the 20–40 cm and 40–60 cm soil layer, respectively. Compared to natural grassland, soil microbial networks became more complex in plantation forests restoration types (P. sylvestris var. mongholica, L. principis- rupprechtii, P. tomentosa, and U. pumila). Microbial network complexity increased with soil carbon and nitrogen. P. tomentosa is suitable for planting in the agricultural pastoral ecotone of Zhangjiakou, because of its high soil carbon, nitrogen and microbial network complexity. Bacterial community composition was found to be closely related to soil organic carbon (SOC), total nitrogen (TN), while that of fungi was closely related to SOC, clay and silt content. This improvement in microbial complexity enhances the ecological service function of the agricultural pastoral ecotone. These findings offer theoretical basis and technical support for the vegetation restoration of ecologically fragile areas in agricultural pastoral ecotone.
Biology, genetics, and ecology of the cosmopolitan ectomycorrhizal ascomycete Cenococcum geophilum
Authors: Wang Huayong , Kohler Annegret , Martin Francis M.
Published: January 2025

The ascomycete Cenococcum geophilum is a cosmopolitan and ecologically significant ectomycorrhizal (ECM) fungus that forms symbiotic associations with diverse host plants worldwide. As the only known ECM species within the large class Dothideomycetes, C. geophilum exhibits several characteristics that distinguish it from other ECM fungi. This fungus significantly contributes to ecosystem stability and development as an early colonizer of primary forest succession. The capacity of this symbiont to rapidly colonize disturbed or newly formed environments promotes the development of conditions that support the growth of other plant species, thus playing a crucial role in the ecological progression and restoration of ecosystems. Several C. geophilum isolates are known to enhance the drought resistance of host plants, a trait that is becoming increasingly important in the context of climate change and frequent drought events. In this review, we examined genetic studies that have assessed the phylogenetic structure of C. geophilum populations and identified the genes associated with adaptation to environmental stress and symbiosis. The high genetic diversity of C. geophilum is particularly noteworthy, considering its putative asexual reproductive mode. Population genomic analyses have suggested that C. geophilum is not a single species but rather a species complex comprising multiple cryptic lineages. This genetic variability may contribute to its adaptability and extensive distribution across habitats from circumpolar to tropical biomes. These lineages exhibit potential host preferences, suggesting a degree of specialization within the complex. The nuclear genome of C. geophilum has been sequenced, providing valuable insights into the symbiont genetic traits. Notably, this genome encodes a large set of repeated sequences and effector-like small secreted proteins. Transcriptomics has been used to identify candidate genes related to symbiosis and adaptation to environmental stress. Additionally, we briefly discuss how C. geophilum offers potential for sustainable forestry practices by improving resilience to stress.
Linking machine learning and biophysical structural features in drug discovery
Authors: Ahmadi Armin , Gupta Shivangi , Menon Vineetha , Baudry Jerome
Published: January 2025

Introduction

Machine learning methods were applied to analyze pharmacophore features derived from four protein-binding sites, aiming to identify key features associated with ligand-specific protein conformations.

Methods

Using molecular dynamics simulations, we generated an ensemble of protein conformations to capture the dynamic nature of their binding sites. By leveraging pharmacophore descriptors, the AI/ML framework prioritized features uniquely associated with ligand-selected conformations, enabling a mechanism-driven understanding of binding interactions. This novel approach integrates biophysical insights with machine learning, focusing on pharmacophoric properties such as charge, hydrogen bonding, hydrophobicity, and aromaticity.

Results

Results showed significant enrichment of true positive ligands—improving database enrichment by up to 54-fold compared to random selection—demonstrating the robustness of this approach across diverse proteins.

Conclusion

Unlike conventional structure-based or ligand-based screening methods, this work emphasizes the role of specific protein conformations in driving ligand binding, making the process highly interpretable and actionable for drug discovery. The key innovation lies in identifying pharmacophore features tied to conformations selected by ligands, offering a predictive framework for optimizing drug candidates. This study illustrates the potential of combining ML and pharmacophoric analysis to develop intuitive and mechanism-driven tools for lead optimization and rational drug design.
Opioidergic tuning of social attachment: reciprocal relationship between social deprivation and opioid abuse
Authors: Galiza Soares Julia A. , Sutley-Koury Samantha N. , Pomrenze Matthew B. , Tucciarone Jason M.
Published: January 2025

Individuals misusing opioids often report heightened feelings of loneliness and decreased ability to maintain social connections. This disruption in social functioning further promotes addiction, creating a cycle in which increasing isolation drives drug use. Social factors also appear to impact susceptibility and progression of opioid dependence. In particular, increasing evidence suggests that poor early social bond formation and social environments may increase the risk of opioid abuse later in life. The brain opioid theory of social attachment suggests that endogenous opioids are key to forming and sustaining social bonds. Growing literature describes the opioid system as a powerful modulator of social separation distress and attachment formation in rodents and primates. In this framework, disruptions in opioidergic signaling due to opioid abuse may mediate social reward processing and behavior. While changes in endogenous opioid peptides and receptors have been reported in these early-life adversity models, the underlying mechanisms remain poorly understood. This review addresses the apparent bidirectional causal relationship between social deprivation and opioid addiction susceptibility, investigating the role of opioid transmission in attachment bond formation and prosocial behavior. We propose that early social deprivation disrupts the neurobiological substrates associated with opioid transmission, leading to deficits in social attachment and reinforcing addictive behaviors. By examining the literature, we discuss potential overlapping neural pathways between social isolation and opioid addiction, focusing on major reward-aversion substrates known to respond to opioids.
Functional characterization of endocytic signals in the SynDIG/PRRT family members SynDIG1 and SynDIG4 in heterologous cells and neurons
Authors: Speca David J. , He Chun-Wei , Meyer Christina M. , Scott Erin C. , Díaz Elva
Published: January 2025

The transmembrane protein Synapse Differentiation Induced Gene 4 (SynDIG4), also known as Proline-rich transmembrane protein 1 (PRRT1), is an AMPA-type glutamate receptor (AMPAR) auxiliary factor that is necessary for maintaining extra-synaptic pools of GluA1. Loss of SynDIG4, and the subsequent decrease in extra-synaptic GluA1, has been found to significantly impact synaptic plasticity in the hippocampus. However, how SynDIG4 establishes and maintains these pools is unclear. Previous studies suggested that endocytic machinery is important for maintaining a pool of mobile surface AMPARs, and that proteins associated with such cellular machinery are critical for proper protein trafficking and internalization. Given that SynDIG4 co-localizes with GluA1 in early and recycling endosomes in cultured hippocampal neurons, we sought to identify the sorting signals that target SynDIG4 to endosomes to further elucidate the role of SynDIG4 in GluA1 trafficking. In this study, we report that SynDIG4 possesses a YxxΦ sorting motif, 178-YVPV-181, responsible for binding to the AP-2 complex cargo-sorting subunit μ2. This motif appears critical for proper SynDIG4 internalization, as SynDIG4 mutant 178-AVPA-181, which disrupts binding to μ2, induces aberrant SynDIG4 accumulation at the plasma-membrane of heterologous cells and primary rat hippocampal neurons. We also show that SynDIG4 mutants lacking an endocytic signal co-localize with GluA1 but less so with GluA2 on the surface of heterologous cells. Furthermore, we show that another family member, SynDIG1, is enriched in the trans-Golgi network (TGN) and can traffic between the TGN and plasma membrane. We have identified a non-canonical μ2 binding sequence in SynDIG1 that induces aberrant accumulation at the plasma membrane of heterologous cells and primary rat hippocampal neurons, suggesting a conserved role for μ2-mediated endocytosis within the SynDIG family. These results provide important insight into the mechanisms by which SynDIG proteins are targeted to endosomal compartments as a step in understanding SynDIG-mediated regulation of AMPAR trafficking.
Proof of concept of fully automated adaptive workflow for head and neck radiotherapy treatments with a conventional linear accelerator
Authors: Muti Gaia , Felisi Marco M. J. , Monti Angelo F. , Carsana Chiara , Pellegrini Roberto , Salmeri Edoardo , Palazzi Mauro , Colombo Paola E.
Published: January 2025

Introduction

The objective of this study is to evaluate the performance of an automatic workflow for head-and-neck (H&N) radiotherapy using a multi-atlas based auto-contouring software and an a-priori multicriteria plan optimization algorithm and implement an adaptive online approach with CBCT images. Two different modalities are investigated, the fluence-to-position (FTP) and the adapt-to-shape (ATS) approach.

Materials and methods

Nine patients are used for the multi-atlas database. The organs at risk (OARs) of the H&N district and five additional structures (air, fat, tissue, bone and patient’s exterior) subsequently used for the creation of the synthetic CT are auto-contoured with the Elekta ADMIRE® software. The mCycle algorithm is used for the a-priori multicriteria plan calculation. A total of twenty H&N patients are selected for this step. The automatic plans are compared to manual VMAT plans by assessing differences in planning time, dose delivered to targets and OARs, and calculating the plan quality indexes (PQIs). Two patients are chosen for the retrospective CBCT adaptive online feasibility analysis. To assess the differences for the two adaptive modalities, the clinical goals for targets and OARs and the number of passed constraints are explored. An analysis of the timing for the different steps is carried out to assess its clinical applicability.

Result

The dice of the five HU layer structures range between 0.66 and 0.99. The mCycle auto-planning significantly reduces planning time, from 2 hours to 10 minutes. The radiotherapist deems all plans clinically acceptable, and in the majority of cases the automatic plan is the preference choice. The automatic plans enhance OARs sparing and preserve a good target coverage, this is also confirmed by the PQIs result. Comparing FTP and ATS modes in adaptive radiotherapy, ATS exhibits superior outcomes, mostly in the target coverage. In the FTP techniques target coverage is inadequate and statistically different from the accepted values. In the ATS the results align with the initial approved values. Using the ATS mode the planning time takes around 14 minutes and approximately 20 minutes for the entire treatment.

Conclusion

This study contributes to the advancement of automatic and adaptive radiotherapy, demonstrating the potential of an automated workflow in H&N treatments.
Trazodone effectiveness in depression: impacts of trazodone extended release vs SSRIs on the health status and quality of life of patients with major depressive disorder
Authors: Siwek Marcin , Chrobak Adrian Andrzej , Krupa Anna Julia , Gorostowicz Aleksandra , Juryk Andrzej , Dudek Dominika
Published: January 2025

Introduction

Early research on the pharmacotherapy for major depressive disorder (MDD) has largely focused on symptomatic improvements, whereas this focus has shifted to functioning and quality of life in recent years. Studies have confirmed that antidepressants generally improve the functional outcomes in MDD, but very few works have compared the efficacies of specific drugs. The present work aims to compare the impacts of trazodone once-a-day extended-release (XR) vs selective serotonin reuptake inhibitors (SSRIs) on the health status and quality of life in MDD.

Methods

Data were gathered from 180 subjects through a naturalistic observation study of trazodone effectiveness in depression (TED) and analyzed. The TED study participants received trazodone XR of SSRIs in flexible doses for 12 weeks. The health status and health-related quality of life (HRQoL) were evaluated using the EQ-5D-5L tool at baseline as well as 2, 4, 8, and 12 weeks.

Results

At baseline, the subjects treated with trazodone XR vs SSRIs presented similar health status profiles and HRQoL values with respect to the mobility, self-care, and anxiety/depression dimensions along with lower scores for the usual activities, pain/discomfort, overall HRQoL, and health status. Both trazodone XR and SSRIs improved the health status and HRQoL of the MDD patients at all subsequent timepoints. Compared to SSRIs, trazodone XR provided greater improvements in terms of the self-care, usual activities, pain/discomfort, and anxiety/depression measures and more often improved participant overall health status and HRQoL. More participants reported mixed changes in their health status and HRQoL in the SSRI group than the trazodone XR group.

Discussion

Health status and HRQoL improved in both treatment arms, with preferable scores in trazodone XR vs. SSRIs group.
A post-marketing pharmacovigilance study of triazole antifungals: adverse event data mining and analysis based on the FDA adverse event reporting system database
Authors: Tian Yalan , Jin Min , Ning Hong
Published: January 2025

Background

To explore and analyze post-marketing adverse drug event (ADE) signals for voriconazole, posaconazole, and isavuconazole, and to compare the safety differences among the three drugs, aiming to provide insights for rational clinical use.

Methods

Using the Open Vigil 2.1 online tool, extract adverse drug event (ADE) report data for voriconazole, posaconazole, and isavuconazole from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from the time the drugs were marketed up to the third quarter of 2023. Employ the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods for data mining. Filter out ADE signals detected by both the ROR and PRR methods, and categorize these ADE signals by System Organ Class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA 26.0).

Results

A total of 8,898 ADE reports with voriconazole as the primary suspect drug were retrieved, 1,948 for posaconazole, and 944 for isavuconazole. From the basic analysis of the adverse event reports, male patients (50.31%) outnumber female patients (32.11%). In terms of age, the majority of patients are over 45 years old (52.72%). The reports primarily come from the United States, Japan, France, China, and other countries. A total of 607 ADE signals were identified, with 402 for voriconazole, 159 for posaconazole, and 46 for isavuconazole. Voriconazole ADEs primarily involved the following SOCs: Investigations (9.45%), Eye Disorders (8.46%), and Nervous System Disorders (7.21%); Posaconazole ADEs primarily involved the following SOCs: Investigations (13.84%), General Disorders and Administration Site Conditions (11.95%), and Nervous System Disorders (6.29%); Isavuconazole ADEs primarily involved the following SOCs: General Disorders and Administration Site Conditions (15.22%), Hepatobiliary Disorders (10.87%), and Blood and Lymphatic System Disorders (10.87%).

Conclusion

Voriconazole, posaconazole, and isavuconazole all potentially pose safety risks related to hepatobiliary disorders and cardiac disorders. Additionally, voriconazole carries a higher safety risk for eye disorders and nervous system disorders. Newly discovered ADE signals not mentioned in the drug package inserts include voriconazole-induced rhabdomyolysis, posaconazole-induced peripheral neuropathy, and isavuconazole-induced visual impairment and mental confusion. These findings are significant for guiding rational clinical use of these medications.
hERG activators exhibit antitumor effects in breast cancer through calcineurin and β-catenin-mediated signaling pathways
Authors: Yu Yan , Zhu Chengchun , Wang Xiao , Shi Ying , Gao Yiping , Yu Zhiyi
Published: January 2025

Background

Breast cancer remains a leading cause of mortality among women worldwide, with existing therapeutic options often accompanied by significant side effects and a persistent risk of disease recurrence. This highlights the need for novel drug candidates with new mechanisms of action by targeting alternative signaling pathways. While hERG channel is notoriously regarded as an off-target due to drug-induced cardiotoxicity, its therapeutic potential as a drug target remains largely unexplored.

Methods

This study investigated the role of hERG in breast cancer progression and its impact on patient survival. The anti-proliferative, anti-migratory, anti-invasive and pro-apoptotic effects of hERG activators were evaluated using the Cell Counting Kit-8, wound healing assay, transwell assay and cell apoptosis assay, respectively. Western blotting, Ca2+ imaging and immunofluorescence assays were employed to study their antitumor mechanisms of actions.

Results

We identified two novel hERG activators, SDUY429 and SDUY436, which effectively inhibited the proliferation and migration of MDA-MB-231 and MCF-7 cells. In addition, SDUY436 demonstrated significant anti-invasive and pro-apoptotic effects in MDA-MB-231 cells. Mechanistically, the anti-proliferative activity of hERG activators were mediated through calcineurin activation via enhanced calcium ion influx, which facilitated the nuclear translocation of nuclear factor of activated T cells (NFAT) and upregulated p21Waf/Cip expression. Furthermore, both SDUY429 and SDUY436 remarkably suppressed the migration and invasion of MDA-MB-231 cells by downregulating the protein kinase B (AKT)/glycogen synthase kinase-3 beta (GSK3β)/β-catenin signaling pathway. The observed reduction in phospho-AKT-Ser473 (pAKTS473) expression resulted in the decreased levels of phospho-GSK3β-Ser9 (pGSK3βS9), thereby limiting the nuclear localization of β-catenin, which led to the inhibition of cell migration and invasion. Notably, combining SDUY429 or SDUY436 with the AKT inhibitor MK-2206 produced synergistic anti-proliferative effects.

Conclusion

These findings suggest that hERG activators hold promise as new potential therapeutic agents for the treatment of breast cancer, paving the way for future investigations into their clinical applications.
Transcriptional survey of the light-induced anthocyanin pathway in non-GM purple tomatoes
Authors: Gonzali Silvia , Menconi Jacopo , Perata Pierdomenico
Published: January 2025

Anthocyanins are polyphenolic compounds with antioxidant capacity, free radical scavenging power, and signaling activities in animal pathogenesis-associated pathways, thus playing an important role as nutraceuticals. Tomato fruits do not usually contain anthocyanins because their biosynthesis is switched off in these organs, but anthocyanin-enriched purple tomatoes have been produced in recent years. The varieties obtained by breeding express a functional copy of the R2R3-MYB transcription factor AN2-like, necessary to start the biosynthetic pathway, and do not produce a functional MYB-ATV repressor. The combination of these traits allows the accumulation of anthocyanins in tomatoes, strengthened under specific environmental factors such as high light intensity or low temperatures. Light starts anthocyanin synthesis and gradually extends its distribution on the fruit exocarp. The analyses carried out in the present study indicate that anthocyanin biosynthesis triggered by light is under HY5 control. However, the process is not active in mesocarp for the absence of the bHLH factor AN1, necessary to produce the MBW complex inducing the late enzymes of the biosynthetic pathway, as a consequence of insufficient expression of the R2R3-MYB gene AN2-like. This occurs since light cannot be perceived in the tissues underneath the skin because of the solar shield produced by the anthocyanins accumulated in the exocarp and for the activation of regulatory loops controlling HY5 levels. This is shown by the expression of genes involved in the production of photoreceptors and in the light signaling chain operating upstream of the anthocyanin pathway and responsible for its activation.
Characterization of rectus femoris lesions in knee osteoarthritis at different stages and the effect of ultrasound-guided acupotomy
Authors: Yu Wen-Ying , Liu Jing , Lin Ze-Hao , Liu Hong , Zhang Liang-Zhi , Feng Xiang-Long , Xiu Zhong-Biao
Published: January 2025

Introduction

Chronic injury to the rectus femoris muscle induces and exacerbates the progression of knee osteoarthritis (KOA). However, the lesion characteristics of the rectus femoris muscle in KOA at different stages have not been fully characterized. The aim of this study was to analyze the pattern of lesion characteristics of the rectus femoris muscle at different stages of KOA and to investigate the mechanism by which ultrasound-guided acupotomy operations can prevent and control KOA.

Methods

Early, middle, and late-stage rabbit KOA models were constructed using the modified Videman method. Ultrasonography was used to record the elastic modulus and cross-sectional area of the rectus femoris muscle, and morphology was used to observe the ultramicroscopic changes in the rectus femoris muscle and assess the degree of fibrosis. Additionally, ultrasound-guided acupotomy operations were performed on the rabbit model of late-stage KOA, and alterations in the key molecular markers of rectus femoris fibrosis were determined using Western Blot and qPCR methods.

Results

As the disease progressed, the elastic modulus of the rectus femoris muscle in KOA rabbits gradually increased, the cross-sectional area gradually decreased, and the degree of fibrosis increased. In contrast, the degree of fibrosis in the rectus femoris muscle improved after ultrasound-guided acupotomy intervention.

Conclusion

These findings highlight the gradual increase in the modulus of elasticity, the gradual decrease in cross-sectional area, and the increased fibrosis of the rectus femoris muscle in KOA rabbits as the disease progressed. Ultrasoundguided acupotomy operations have been shown to have a protective effect on KOA cartilage and to delay the progression of KOA by ameliorating pathological changes in the rectus femoris muscle. The mechanism may involve reducing chronic injury to the rectus femoris muscle and protecting joint homeostasis by attenuating the degree of rectus femoris fibrosis.
Salt tolerance evaluation and key salt-tolerant traits at germination stage of upland cotton
Authors: An Mengjie , Huang Xinhui , Long Yilei , Wang Yin , Tan Yanping , Qin Zhen , Ai Xiantao , Wang Yan
Published: January 2025

Cotton is an important cash crop with a certain salt tolerance, but its germination stage is very susceptible to the damage of salt stress, causing significant yield loss. However, few studies have evaluated the cotton salt tolerance and selected salt tolerance traits at germination stage. Therefore, in this study, 16 cotton samples with geographical representation were randomly selected from 308 cotton germplasms to determine the optimal 200 mmol·L-1 NaCl in cotton germination experiments. On this basis, the salt tolerance of 308 upland cotton varieties and the growth, ion distribution and transport of highly salt-tolerant and non salt-tolerant cotton germplasms were analyzed. The results showed that the 308 germplasms were classified into five classes through cluster analysis, i.e, (1) highly salt-tolerant germplasms (HST, 49), (2) salt-tolerant germplasms (ST, 169), (3) moderately salt-tolerant class (MST,43), (4) lowly salt-tolerant germplasms (LST, 16), and (5) non-salt-tolerant germplasms (NST, 31). By calculating the salt tolerance index (STI) of various cotton germination and growth parameters and principal component analysis, combined with the correlation analysis and linear regression between mean membership function value (MFV) and STI, the key indexes of cotton germination and growth under salt stress, including total fresh weight, shoot fresh weight, and shoot length, were determined. In addition, three salt tolerance evaluation models constructed with different variables (6 variables in Model 1; 3 variables in Model 2; 1 variable in Model 3) found that the total fresh weight was the most reliable trait for the salt tolerance evaluation. In practical application, the variable selection for modelling could be adjusted based on the experimental workload. The comparison of the K+, Na+, and Ca2+ contents between HST and NST found that the higher the salt tolerance of cotton germplasms, the lower the Na+ content in the root system. Besides, the ion ratios and ion selective transport coefficients (ST) was found to be significantly positively correlated with the salt tolerance of cotton. This study will provide a basis for evaluating and breeding salt-tolerant cotton germplasms.
Deep application of controlled-release urea increases the yield and saponin content of Panax notoginseng by regulating soil nitrate distribution
Authors: Su Yun-xia , Zhao Ping , Jia Li-jie , Cao Yuan-feng , Liu Guan-ze , Chen Jun-wen , Yang Sheng-chao , Zhou Yan-li , Long Guang-qiang
Published: January 2025

Introduction

The deep application of controlled-release urea (CRU) offers potential advantages for crops with extended growth periods. However, its effects on P. notoginseng yield and quality, a medicinal plant with a prolonged nutrient acquisition duration, remain unclear.

Methods

In this study, we conducted a two-year field plot experiment to investigate the effect of CRU on P. notoginseng with three placement depths (0, 6, and 12 cm denoted as R0, R6, and R12, respectively) at an application dosage of 250 kg N ha-1 with biochar addition (R6B) and 20% N reduction (R6R) based on the R6, with conventional fertilization (250 kg N ha-1, common urea) serving as the control (CK).

Results

Our results indicated that yields increased by 27.1–37.6% with R0, R6, R12, and R6B, while remaining stable with R6R compared to CK. Simultaneously, the total saponin content in the roots of R6, R6B, and R6R was improved by 14.3–38.1%, compared to CK. The distribution depth of soil NO3⁻-N and plant roots increased with the depth of CRU application, with a high overlap in time and space, indicating P. notoginseng N uptake peaked when CRU was applied at a depth of 6 cm (R6). Structural equation modeling indicated that soil NO3⁻-N supply in specific microareas directly affected the N uptake and increased total saponin content by increasing root length and surface area, thus boosting yield.

Conclusion

This study identifies that the deep application of CRU at a depth of 6 cm has the potential to enhance both yield and quality of P. notoginseng and highlights that the spatial-temporal matching of soil NO₃⁻-N and plant roots was the key to applying CRU to ensure high yield and quality.
Evolutionary analysis of DELLA proteins in sweet potato and related species reveals their roles in development and stress responses
Authors: Zuo Zhidan , Zhao Haoqiang , Fan Yue , Zhu Yixuan , Song Wenpeng , Zhai Hong , He Shaozhen , Zhang Huan , Zhao Ning , Liu Qingchang , Gao Shaopei
Published: January 2025

DELLA proteins act as master negative regulators in the gibberellin signaling pathway, which controls numerous aspects of plant growth and development. Despite the pivotal role of DELLA proteins, a comprehensive genome-wide analysis of the DELLA gene family in sweet potato (Ipomoea batatas) and its related species has yet to be conducted. Here, we performed a comparative analysis of this gene family among six Ipomoea species, including Ipomoea batatas, Ipomoea trifida, Ipomoea triloba, Ipomoea nil, Ipomoea cairica, and Ipomoea aquatica. Among the six Ipomoea species, only I. nil contains five DELLA genes, while the remaining species have three DELLA genes each. The DELLA genes were categorized into three distinct subgroups based on the phylogenetic topology in selected Ipomoea species. Comparative analysis of gene structure and protein motifs revealed that members within the same phylogenetic group exhibit comparable exon/intron and motif organization. The cis-regulatory elements of the DELLA gene in selected Ipomoea species contain unique promoter elements, indicating the presence of species-specific regulatory mechanisms. A multitude of shared cis-regulatory elements related to stress responses were identified in the DELLA gene promoters. Furthermore, a syntenic analysis indicates two groups of syntenic DELLA genes have undergone several rearrangements. The results of the duplication analysis indicated that dispersed duplications contribute to the expansion of the DELLA genes. Moreover, the DELLA genes in sweet potato display an expression pattern that tends to control the growth and development of either the aerial or below-ground parts, and they are responsive to a range of hormones and abiotic stresses. Thus, these findings provide insights into the evolutionary history of DELLA genes within the genus Ipomoea and the functions of sweet potato DELLA genes.
Does the therapeutic alliance process explain the results of the Egokitzen post-divorce intervention program?
Authors: Alvarez Irati , Herrero Marta , Martínez-Pampliega Ana
Published: January 2025

Objective

The objective of this study was to explain the relationship between therapeutic alliance and the changes observed in the parents’ psychological symptomatology after participation in the Egokitzen program, analyzing the mediating role of emotion regulation.

Methods

The study involved 117 divorced parents and 40 therapists.

Results

It has been observed that the early development and maintenance of the therapeutic alliance influence the parents’ psychological symptomatology after the intervention, through emotion regulation.

Conclusion

The study reinforce the role of the therapeutic alliance as a determining factor in the success of group interventions. This effect has turned out to be indirect through emotion regulation, highlighting the importance of emotional management.
Students’ cross-domain mindset profiles and academic achievement in Finnish lower-secondary education
Authors: Laurell Jenni , Puusepp Ita , Hakkarainen Kai , Tirri Kirsi
Published: January 2025

Introduction

This study uses a person-centered approach to explore Finnish lower-secondary school students’ (N = 1106) mindsets across intelligence, giftedness, and creativity. It further investigates the relationship between mindsets profiles, school achievement in various subjects, and gender differences, aiming to address the domain-specificity of the three ability domains.

Methods

A self-reported questionnaire was used to measure students’ mindsets, with latent profile analysis (LPA) identifying distinct profiles. School achievement was assessed through academic grades in core and arts subjects, while gender differences in profile membership were examined via logistic regression.

Results

Four mindset profiles emerged: Growth, Fixed, Mixed, and Opposing. Most students exhibited consistent “general” mindsets across domains, except those in the Opposing profile, who combined a growth mindset for intelligence and creativity with a fixed mindset for giftedness. Students in the Opposing profile outperformed others in mathematics and foreign languages, while those in the Growth profile excelled across other subjects. The Fixed profile was linked to the lowest achievement, except in reading, foreign languages, and music, where Mixed and Fixed profiles performed similarly. Girls were more likely to belong to the Growth profile, while boys dominated the Fixed and Opposing profiles.

Discussion

The findings highlight the cross-domain nature of mindsets but reveal unique domain-specific variations, particularly for giftedness. These differences influenced academic outcomes, underscoring the nuanced role of mindsets in student achievement. Gender disparities in mindset profiles align with observed differences in school performance.

Conclusion

By identifying distinct mindset profiles, this study emphasizes the complexity of students’ beliefs and possible educational implications. Future research should explore qualitative aspects of mindset formation across ability-related constructs, its broader motivational frameworks, and their relation to students’ academic outcomes.
The efficacy of telemedicine interventions on quality of life and depression in individuals with spinal cord injury: a systematic review and meta-analysis
Authors: Tan YinHu , Liang Xue , Ming Wei , Xing HuiMin , Liang Yan , Wang Yang , Onodu Emmanuel Onyebuchi
Published: January 2025

Objective

The purpose of this systematic review and meta-analysis is to examine the impact of telemedicine interventions on the quality of life (QoL) and depression in individuals with spinal cord injury (SCI).

Methods

A literature search was conducted in four electronic databases (PubMed, Web of Science, EMBASE, and the Cochrane Library) from their inception to February 1, 2024. Two authors independently screened the studies and extracted the data. Cochrane’s bias risk tool for randomized controlled trials was used to examine the methodological quality of the included studies. A meta-analysis was conducted using Review Manager (version 5.4) to synthesize the results of the included studies.

Results

A total of 10 trials with 728 participants were included in the review. The results of the meta-analysis showed that telemedicine interventions significantly improved QoL [Standardized Mean Difference (SMD)=0.72, 95% Confidence Interval (CI) (0.11, 1.32), P=0.02] and reduced depression scores [SMD=-0.18, 95% CI (-0.31, -0.05), P=0.006].

Conclusions

Telemedicine interventions are a feasible method to support people with SCI, and can mitigate depression and enhance quality of life. In the future, studies should involve larger sample sizes and extended follow-up periods to validate these findings and to identify the most effective telemedicine interventions for improving the overall health outcomes of individuals with SCI.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024508702.