bluuebunny/crossref_metadata_2025 huggingface dataset:
Noise-immune zeroing neural dynamics for dynamic signal source localization system and robotic applications in the presence of noise
Authors: Zhao Yuxin , Wu Jiahao , Zheng Mianjie
Published: February 2025

Time angle of arrival (AoA) and time difference of arrival (TDOA) are two widely used methods for solving dynamic signal source localization (DSSL) problems, where the position of a moving target is determined by measuring the angle and time difference of the signal's arrival, respectively. In robotic manipulator applications, accurate and real-time joint information is crucial for tasks such as trajectory tracking and visual servoing. However, signal propagation and acquisition are susceptible to noise interference, which poses challenges for real-time systems. To address this issue, a noise-immune zeroing neural dynamics (NIZND) model is proposed. The NIZND model is a brain-inspired algorithm that incorporates an integral term and an activation function into the traditional zeroing neural dynamics (ZND) model, designed to effectively mitigate noise interference during localization tasks. Theoretical analysis confirms that the proposed NIZND model exhibits global convergence and high precision under noisy conditions. Simulation experiments demonstrate the robustness and effectiveness of the NIZND model in comparison to traditional DSSL-solving schemes and in a trajectory tracking scheme for robotic manipulators. The NIZND model offers a promising solution to the challenge of accurate localization in noisy environments, ensuring both high precision and effective noise suppression. The experimental results highlight its superiority in real-time applications where noise interference is prevalent.
Inflammation and endothelial gene polymorphism are associated with ischemic stroke
Authors: Chen Wanli , Li Jie , Zhou Jintao , Yi Xingyang , Chen Hong
Published: February 2025

Aim

Evaluate the correlation between ischemic stroke and genetic variations related to inflammation and endothelial function.

Methods

This was a multicenter cross-sectional research conducted in southwestern China. Residents aged ≥40 years voluntarily join in the face-to-face survey in 8 communities. 2,377 participants were at high risk of stroke, of which 429 had a previous history of ischemic stroke. We selected the 429 ischemic stroke patients as the research subjects, and adopted a 1:1 matching method to select 429 healthy people with a 2-year age difference and the same gender and hypertension as the control group. We detected genotypes of 19 variants in 10 genes related to inflammation and endothelial function. Analyze gene–gene interaction through generalized multifactor dimensionality reduction (GMDR).

Results

Analysis found no statistically significant differences in age, gender, hypertension, BMI, and smoking history between ischemic stroke patients and healthy control group. Compared with the healthy group, ischemic stroke group has a higher proportion of diabetes, heart disease, dyslipidemia, stroke family history, and a higher proportion of lack of exercise. HABP2 rs7923349, NOS2A rs8081248, HABP2 rs932650 were related to stroke in univariate analysis. GMDR analysis showed significant gene–gene interactions between HABP2 rs7923349, HABP2 rs932650. After adjusting for covariates, high-risk interaction genotypes between these two variants were independently associated with higher stroke risk (OR, 3.578, 95% CI: 2.618–4.890, p < 0.001).

Conclusion

This study found that specific variations in genes related to inflammation and endothelial function are associated with ischemic stroke. The high-risk interactive genotypes among HABP2 rs7923349, HABP2 rs932650 distinctly increased the risk of ischemic stroke.
Analyzing the correlation between acute ischemic stroke and triglyceride-glucose index based on ordered logistic regression
Authors: He Liu , Li Rong , Wang Lei , Zhu Xi , Zhou Qiang , Yang Zhiyong , Liu Hua
Published: February 2025

Objective

To investigate the association between insulin resistance, measured by the triglyceride-glucose (TyG) index, and clinical outcomes in patients with acute ischemic stroke who underwent intravenous thrombolysis with alteplase.

Methods

This retrospective study included 165 patients with acute ischemic stroke treated with intravenous alteplase. Insulin resistance was evaluated using the TyG index, and its relationship with the modified Rankin Scale (mRS) scores was analyzed. The analysis was conducted using R software (version R 4.1.3) to evaluate the correlation between the TyG index and functional outcomes at 14, 30, and 90 days post-stroke.

Results

The study found that each unit increase in the TyG index significantly raised the risk of poor functional outcomes at 14 days (OR 9.86; 95% CI: 3.32–32.21; P < 0.001), 30 days (OR 5.82; 95% CI: 2.08–17.45; P = 0.001), and 90 days (OR 9.79; 95% CI: 3.33–31.66; P < 0.001) following a stroke. Higher TyG index values were associated with worse neurological outcomes. Although male gender, older age, and smoking were also linked to poorer outcomes, these associations did not reach statistical significance.

Conclusion

The findings suggest that a higher TyG index, indicating greater insulin resistance, is associated with worse neurological outcomes in stroke patients. Early intervention targeting insulin resistance may improve clinical outcomes in ischemic stroke patients, and further research is needed to explore additional factors affecting neurological recovery.
A pooled analysis of the side effects of non-invasive Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)
Authors: Giraudier Manon , Ventura-Bort Carlos , Szeska Christoph , Weymar Mathias
Published: February 2025

Introduction

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising technique for modulating vagal afferent fibers non-invasively and has shown therapeutic potential in neurological, cognitive, and affective disorders. While previous research highlights its efficacy, the safety profile of taVNS has been less extensively examined.

Methods

This study therefore aimed to systematically investigate side effects of taVNS in a large pooled dataset consisting of n = 488 participants, utilizing a standardized questionnaire to assess ten reported side effects. Analyses included effects of stimulation type (interval vs. continuous), stimulation duration, stimulation intensity and participant characteristics (age and gender) as potential modulators.

Results

The findings support the safety of taVNS, with minimal and mild side effects reported across participants (M = 1.86, SD = 1.36). Although participants receiving sham stimulation were 32.4% less likely to report unpleasant feelings compared to participants receiving taVNS, this effect was driven primarily by low-end ratings (specifically, a rating of 1, indicating not at all when experiencing the corresponding side effect), thus suggesting limited clinical relevance. Interval stimulation notably reduced the likelihood of some side effects, particularly for neck pain, dizziness and unpleasant feelings, suggesting potential for optimizing taVNS protocols. Stimulation intensity and duration showed few statistically significant, but clinically minimal (i.e., very small) effects.

Conclusion

Overall, these findings demonstrate a favorable safety profile of taVNS, with mostly mild and transient effects, supporting its use as a suitable non-invasive tool in both research and clinical applications.
Identifying natural inhibitors against FUS protein in dementia through machine learning, molecular docking, and dynamics simulation
Authors: Li Darwin
Published: February 2025

Dementia, a complex and debilitating spectrum of neurodegenerative diseases, presents a profound challenge in the quest for effective treatments. The FUS protein is well at the center of this problem, as it is frequently dysregulated in the various disorders. We chose a route of computational work that involves targeting natural inhibitors of the FUS protein, offering a novel treatment strategy. We first reviewed the FUS protein's framework; early forecasting models using the AlphaFold2 and SwissModel algorithms indicated a loop-rich protein—a structure component correlating with flexibility. However, these models showed limitations, as reflected by inadequate ERRAT and Verify3D scores. Seeking enhanced accuracy, we turned to the I-TASSER suite, which delivered a refined structural model affirmed by robust validation metrics. With a reliable model in hand, our study utilized machine learning techniques, particularly the Random Forest algorithm, to navigate through a vast dataset of phytochemicals. This led to the identification of nimbinin, dehydroxymethylflazine, and several other compounds as potential FUS inhibitors. Notably, dehydroxymethylflazine and cleroindicin C identified during molecular docking analyses—facilitated by AutoDock Vina—for their high binding affinities and stability in interaction with the FUS protein, as corroborated by extensive molecular dynamics simulations. Originating from medicinal plants, these compounds are not only structurally compatible with the target protein but also adhere to pharmacokinetic profiles suitable for drug development, including optimal molecular weight and LogP values conducive to blood-brain barrier penetration. This computational exploration paves the way for subsequent experimental validation and highlights the potential of these natural compounds as innovative agents in the treatment of dementia.
Multiple patterns of EEG parameters and their role in the prediction of patients with prolonged disorders of consciousness
Authors: Li Hui , Dong Linghui , Su Wenlong , Liu Ying , Tang Zhiqing , Liao Xingxing , Long Junzi , Zhang Xiaonian , Sun Xinting , Zhang Hao
Published: February 2025

Introduction

Prognostication in patients with prolonged disorders of consciousness (pDoC) remains a challenging task. Electroencephalography (EEG) is a neurophysiological method that provides objective information for evaluating overall brain function. In this study, we aim to investigate the multiple features of pDoC using EEG and evaluate the prognostic values of these indicators.

Methods

We analyzed the EEG features: (i) spectral power; (ii) microstates; and (iii) mismatch negativity (MMN) and P3a of healthy controls, patients in minimally conscious state (MCS), and unresponsive wakefulness syndrome (UWS). Patients were followed up for 6 months. A combination of machine learning and SHapley Additive exPlanations (SHAP) were used to develop predictive model and interpret the results.

Results

The results indicated significant abnormalities in low-frequency spectral power, microstate parameters, and amplitudes of MMN and P3a in MCS and UWS. A predictive model constructed using support vector machine achieved an area under the curve (AUC) of 0.95, with the top 10 SHAP values being associated with transition probability (TP) from state C to F, time coverage of state E, TP from state D to F and D to F, mean duration of state A, TP from state F to C, amplitude of MMN, time coverage of state F, TP from state C to D, and mean duration of state E. Predictive models constructed for each component using support vector machine revealed that microstates had the highest AUC (0.95), followed by MMN and P3a (0.65), and finally spectral power (0.05).

Discussion

This study provides preliminary evidence for the application of microstate-based multiple EEG features for prognosis prediction in pDoC.

Clinical trial registration

chictr.org.cn, identifier ChiCTR2200064099.
The effect of AKT inhibition in α-synuclein-dependent neurodegeneration
Authors: Ranxhi Bedri , Bangash Zoya R. , Chbihi Zachary M. , Todi Sokol V. , LeWitt Peter A. , Tsou Wei-Ling
Published: February 2025

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions of individuals worldwide. A hallmark of PD pathology is the accumulation of α-synuclein (α-Syn), a small protein known to support neuronal development and function. However, in PD, α-Syn cumulatively misfolds into toxic aggregates that disrupt cellular processes and contribute to neuronal damage and neurodegeneration. Previous studies implicated the AKT signaling pathway in α-Syn toxicity in cellular models of PD, suggesting AKT as a potential therapeutic target. Here, we investigated the effect of AKT inhibition in a Drosophila model of synucleinopathy. We observed that administration of the AKT inhibitor, A-443654 led to mild improvements in both survival and motor function in flies expressing human α-Syn. Genetic studies revealed that reduction of AKT levels decreased α-Syn protein levels, concomitant with improved physiological outcomes. The protective effects of AKT reduction appear to operate through the fly ortholog of NF-κB, Relish, suggesting a link between AKT and NF-κB in regulating α-Syn levels. These findings highlight the AKT cascade as a potential therapeutic target for synucleinopathies and provide insights into mechanisms that could be utilized to reduce α-Syn toxicity in PD and related disorders, such as multiple system atrophy.
Uncovering proteome variations and concomitant quality changes of different drying methods Cordyceps sinensis by 4D-DIA structural proteomics
Authors: Xiao Mengjun , Tang Chuyu , Wang Tao , He Min , Li Yuling , Li Xiuzhang
Published: February 2025

Introduction

Cordyceps sinensis is a fungus, serves dual purposes as both a medicinal herb and a food source. Due to its high water content, fresh Cordyceps sinensis is difficult to preserve, necessitating the drying necessary to process Cordyceps sinensis.

Methods

Using 4D-DIA proteomics, researchers analyzed the proteome profiles of fresh Cordyceps sinensis (CK) under three different drying conditions: vacuum freeze-drying (FD), oven-drying (OD), and air-drying (AD). In addition, it was found that the protein and free sulfhydryl content of Cordyceps sinensis decreased significantly and the disulfide bond content increased after different drying methods.

Results and discussion

A total of 3762 proteins were identified, showing variations between groups and high protein content. In the control groups consisting of fresh Cordyceps sinensis samples and the three drying methods, FD. vs CK exhibited the fewest differentially abundant proteins, with the majority being upregulated. On the other hand, CK vs OD displayed the greatest amount of distinct proteins, with a significant rise in both up-regulated and down-regulated proteins. Analysis of KEGG indicated that the distinct proteins were predominantly concentrated in pathways like the ribosome, synthesis of coenzymes, and metabolism of amino sugar and nucleotide sugar. Notably, there was a significant overlap between ribosome and ribosome biogenesis in eukaryotes pathways. The process of drying Cordyceps sinensis resulted in a significant upregulation of the expression of proteins linked to various metabolic pathways. This observation suggests that the drying treatment might activate or enhance certain biochemical processes within the organism, potentially influencing its overall metabolic activity. This finding highlights the importance of post-harvest dry methods on the biochemical properties of Cordyceps sinensis, which could have implications for its nutritional and medicinal value.This study provides a theoretical basis for the realization of Cordyceps sinensis resource utilization and storage methods, and provides theoretical support for guaranteeing the sustainable development of Cordyceps sinensis resources.
Application of the Healthy Eating Index in a multicultural population: introduction of Adaptive Component Scoring
Authors: Katz David L. , Rhee Lauren Q. , Aronson Dina L.
Published: February 2025

The United States, and many modern nations, represent assemblies of many cultural groups. Such groups are often influenced, sometimes profoundly, by the culinary traditions of their countries of origin, resulting in a diversity of cultural dietary patterns. Such patterns all derive key elements of nutritional quality from essential food groups—such as vegetables and fruits—but vary in their inclusion of “discretionary” food groups, such as dairy. The application of robust, validated, and standardized diet quality scoring is important in nutrition research, and in the food-as-medicine movement at large if what is being “managed” is to be measured. While robustly validated, the Healthy Eating Index is closely aligned with the Dietary Guidelines for Americans, and thus may not readily account for all multicultural dietary variations. Other diet quality metrics account for deviation from the prevailing American dietary pattern, but none does so in a way that expressly adapts to food components included or excluded so that “credit” for nutritional quality is appropriately assigned in all cases using a standard metric. In this context, we introduce and explain Adaptive Component Scoring as applied to the Healthy Eating Index in the service of advancing fair and universal diet quality scoring. Implications for nutrition research and food-as-medicine initiatives are briefly enumerated.
Clinical calculator based on clinicopathological characteristics predicts local recurrence and overall survival following radical resection of stage II-III colorectal cancer
Authors: Huang Fei , Wei Ran , Mei Shiwen , Xiao Tixian , Zhao Wei , Zheng Zhaoxu , Liu Qian
Published: February 2025

Purpose

This study aimed to analyze the risk factors and survival prognosis of local recurrence in stage II-III colorectal cancer (CRC) and develop a clinical risk calculator and nomograms to predict local recurrence and survival in treated patients.

Methods

Patients who underwent radical surgery between January 2009 and December 2019 at the China National Cancer Center were included. Multivariate nomograms and a clinical risk calculator based on Cox regression were developed. Discrimination was measured with an area under curve (AUC) and variability in individual predictions was assessed with calibration curves. We stratified patients into different risk groups according to the established model to predict their prognosis and guide clinical practice.

Results

The clinical risk calculator incorporated six variables: tumor thrombus, perineural invasion, tumor grade, pathology T-stage, pathology N-stage, and whether more than 12 lymph nodes were harvested. Our clinical risk calculator provided good discrimination, with AUC values of local recurrence-free survival (LRFS) (0.764) and overall survival (OS) (0.815) in the training cohort and LRFS (0.740) and OS (0.730) in the test cohort. Calibration plots illustrated excellent agreement between the clinical risk calculator predictions and actual observations for 3- and 5-year LRFS and OS. Recurrence risk-stratified analysis showed that low-risk patients were more likely to undergo salvage radical surgery when recurrent disease existed.

Conclusion

The clinical calculator can better account for tumor and patient heterogeneity, providing a more individualized outcome prognostication. The model is expected to aid in treatment planning, such as resectability evaluation, and it can be used in postoperative surveillance (https://oldcoloncancer.shinyapps.io/dynnomapp/).
Efficacy and safety of immune checkpoint inhibitors in patients with advanced intrahepatic cholangiocarcinoma
Authors: Peng Ziting , Dong Jianhui , Tang Shuyao , Shi Jiaxu , Shi Tongdong
Published: February 2025

Background

To assess the efficacy and safety of PD-1 and PD-L1 immune checkpoint inhibitors (ICIs) in managing advanced intrahepatic cholangiocarcinoma (ICC).

Methods

A retrospective analysis of treatment data for patients with advanced ICC who received ICIs at the Second Affiliated Hospital of Chongqing Medical University from the inception of the inpatient medical record database until 30 April 2024. The analysis concentrated on the safety and efficacy of the treatment. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS) and safety. The Kaplan-Meier method was employed to plot survival curves, and differences between groups were assessed using log-rank tests.

Results

96 patients diagnosed with ICC were included, comprising 60 males (62.50%) and 36 females (37.50%). 85 patients exhibited disease progression, 22 patients succumbed, and 38 patients were lost to follow-up finally. Those who initiated immunotherapy promptly following first-line antitumor treatment exhibited a notably prolonged PFS compared to those experiencing tumor progression (5.63 months (95%CI: 3.12~8.14) vs 2.50 months (95%CI: 1.83~3.17), P=0.002). However, no significant disparity in the PFS with immunotherapy in different lines therapy(P=0.406) and the OS was observed between the two groups(P=0.360). 18 patients (18.75%) experienced treatment-emergent adverse events (AEs), with 3 patients encountering AEs of grade ≥3. All patients returned to normal after symptomatic treatment.

Conclusions

In patients with advanced ICC, the timely initiation of ICIs as adjuvant therapy following first-line antitumor treatment can result in favorable efficacy and a good safety profile.
Towards painless and productive research relationships: reflections on study design by a researcher with chronic pain for participants with chronic pain
Authors: Wilkinson Catherine
Published: February 2025

Building flexibility into the research design of a study allows for responsiveness to the embodied and fluctuating nature of participants’ chronic illnesses, which may be shaped, for instance, by flare-ups and periods of remission of acute pain. Whilst the methodology literature has, to some extent, considered how to accommodate the pain of research participants when designing a study, consideration of how methodological choices are responsive to the researcher's pain needs has not to date been foregrounded. From the perspective of a researcher with Ankylosing Spondylitis (AS), a form of inflammatory arthritis characterized by chronic pain, and Crohn's disease, a type of inflammatory bowel disease, characterized by stomach and joint pain, this paper provides insight into pain and researcher-participant relationships, from the perspective of a researcher in pain, designing a study to accommodate her own pain needs, as well as anticipating the needs of prospective participants in pain. This paper proposes the use of flexible, remote, and asynchronous research methods as ways to make studies inclusive for researchers living with pain, whilst fostering the most fruitful research relationships with participants who also live with pain, thereby moving towards a position of shared vulnerability. It also highlights the relative absence of the researcher's needs and possible vulnerability in ethics forms and considered by research ethics committees, in comparison to the needs and vulnerability of participants.
Exploration of the anti-inflammatory potential of Polygonum bistorta L.: protection against LPS-induced acute lung injury in rats via NF-ĸβ pathway inhibition
Authors: Parveen Sajida , Khan Kashif ur Rehman , Iqbal Shahid Muhammad , Aati Hanan Y. , Al-taweel Areej M. , Hussain Liaqat , Hussain Musaddique
Published: February 2025

Traditional medicine uses the roots and rhizomes of Polygonum bistorta L. (Polygonaceae) to treat cough, bronchitis, and other respiratory infections. Our goal was to gain insights into the lung protective effects of the roots of P. bistorta L. against lipopolysaccharide-induced acute lung injury in rats, along with the possible mechanism(s). The outcomes revealed deliberate quantities of the total phenolic and flavonoid contents of 156.2 ± 5.13 GAE/g and 179.45 ± 2.08 mg QE/g, respectively. Crude extract possesses a maximum inhibitory potential of 81.77% ± 0.62% for acetylcholinesterase against eserine. Acute oral toxicity study revealed LD50 beyond 7 g/kg. Plant extract markedly restored LPS-induced hypoxemia, pulmonary edema, histopathological alterations, and leukocyte infiltration in the lung. ELISA testing on BALF found that the plant extract efficiently reinstated superoxide dismutase, total anti-oxidant capacity, malondialdehyde, and total oxidative stress. qRT-PCR indicated a decline in the endotoxin-induced overproduction of pro-inflammatory markers, oxidative stress, transcription factor, and downregulated antioxidant potential in extract-treated groups. Furthermore, 24 metabolites were identified and quantified via GC-MS. A molecular docking procedure was implemented on the bioactive metabolites that were identified to evaluate their potential for inhibiting AChE. In conclusion, P. bistorta roots mitigate inflammation and oxidative stress by improving redox signaling and NF-ĸβ (p65) pathways and can thus play a role in strategies for overcoming therapeutic challenges.
A Chinese drug-compatibility-based approach to purslane hydrogels for acute eczema therapy
Authors: Wang Ling , Zhang Yuzhong , Geng Shenglin , Ma Lan , Wang Yiran , Han Dongxu , Fan Guojuan , Zhang Weifen , Lv Yanna , Ma Jinlong
Published: February 2025

Purslane (Portulaca oleracea L.) with heat-clearing and detoxicating, anti-inflammatory and resolving swelling, relieving itching and astringing function, has remarkable efficacy for acute eczema. However, most of the clinical applications of purslane are freshly prepared decoction, not as easy to apply as cream, because the decoction is easy to breed bacteria and easy to oxidize. Here, based on the theory of Chinese medicines compatibility, we made a purslane-tannic acid hydrogel (PL-HATA) by simple methods under mild conditions to solve the drawbacks of easy oxidation and inconvenience of use of Purslane. The antimicrobial activity of PL-HATA hydrogel can exert an excellent antimicrobial effect, reducing the flora on the skin of acute eczema and further relieving the symptoms of acute eczema. At the same time, it creates a normal reactive oxygen species (ROS) microenvironment for acute eczema and promotes recovery from acute eczema. It also improves the symptoms of acute eczema by promoting cell proliferation and migration. Importantly, it resulted in improved skin lesion scores, scratching behavior, eosinophil infiltration, swelling and inflammation levels, immune homeostasis, and histopathological changes in rats with acute eczema. Besides, HATA hydrogel is not only suitable for Purslane’s decocted metabolites but also for Purslane’s freshly squeezed metabolites. This purslane application protocol solved the drawbacks of Purslane’s decoction, improved its storage stability and convenience of use, which is the key issue to further promote its clinical application.
SOX9: a key transcriptional regulator in organ fibrosis
Authors: Li Yishuo , Xing Yue , Liu Ning , Liu Bin , Wang Zhihui
Published: February 2025

The SOX9 gene locus is not only extensive but also intricate, and it could promote fibrosis in different organs or tissues, including cardiac fibrosis, liver fibrosis, kidney fibrosis, pulmonary fibrosis, as well as other organ fibrosis. Many disorders are associated with the process of fibrosis; moreover, fibrosis is a common symptom of chronic inflammatory diseases, characterized by the accumulation of excessive components in the extracellular matrix through different signaling pathways. The advanced stage of the fibrotic process leads to organ dysfunction and, ultimately, death. In this review, we first give an overview of the original structure and functions of SOX9. Second, we will discuss the role of SOX9 in fibrosis in various organs or tissues. Third, we describe and reveal the possibility of SOX9 as an antifibrotic treatment target. Finally, we will focus on the application of novel technologies for SOX9 and the subsequent investigation of fibrosis.
Stachydrine targeting tumor-associated macrophages inhibit colorectal cancer liver metastasis by regulating the JAK2/STAT3 pathway
Authors: Gui Yang , Xue Gengchen , Yuan Yuyi , Wang Jingbo , Deng Shuangjiao , Gao Fei , Tian Yushi , Zhao Zhiqiang , Fan Heng
Published: February 2025

Introduction

Colorectal cancer (CRC) represents the third most prevalent form of cancer worldwide, with liver metastasis representing a significant contributor to mortality. The interaction between tumor-associated macrophages (TAMs) and tumor cells plays a pivotal role in the development of colorectal cancer liver metastases (CRLM) and represents a promising avenue for therapeutic intervention. Stachydrine (STA), a compound derived from the Leonurus heterophyllus plant, has been shown to effectively inhibit tumor growth through a range of mechanisms.

Methods

The study employed imaging and histopathology to evaluate the efficacy of STA monotherapy in preventing CRLM. The inhibition of M2 macrophage polarization by STA was confirmed through the use of flow cytometry and immunofluorescence. Subsequently, a series of assays, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, scratch, invasion, and tube formation assays, were conducted to confirm STA’s capacity to impede tumor cell migration, invasion, and angiogenesis in vitro. Western blotting and flow cytometry were employed to elucidate the mechanisms through which STA exerts its effects on tumor metastasis.

Results

In our research, STA has been shown to attenuate liver metastasis in CRC mouse models by inhibiting the polarization of macrophages to the M2 phenotype. This anti-metastatic effect is dependent on the presence of macrophages. In vitro, STA has been found to impede tumor cell migration, invasion, and angiogenesis by preventing TAMs from polarizing to the M2 phenotype via the JAK2/STAT3 signaling pathway. Moreover, the combination of STA with anti-PD-1 therapy has been observed to restore immune infiltration within the tumor microenvironment and inhibit tumor progression.

Conclusion

The findings of this study demonstrate that STA exerts an inhibitory effect on colorectal cancer liver metastasis by targeting macrophages and impeding their M2 polarization via the JAK2/STAT3 pathway. Furthermore, the combination of STA with anti-PD-1 therapy has been observed to enhance the effectiveness of immune checkpoint blockade and reduce tumor spread, indicating the potential of STA to improve the efficacy of immunotherapy for liver metastases.
The interplay of ferroptosis and oxidative stress in the pathogenesis of aortic dissection
Authors: Zhang Zhaoshan , Wang Haichao , Kan Xi , Zhang Xiaozhao , Xu Senping , Cai Jie , Guo Jiawei
Published: February 2025

Aortic dissection (AD) is a life-threatening vascular condition marked by the separation or tearing of the aortic media. Ferroptosis, a form of iron-dependent programmed cell death, occurs alongside lipid peroxidation and the accumulation of reactive oxygen species (ROS). The relationship between ferroptosis and AD lies in its damaging effect on vascular cells. In AD, ferroptosis worsens the damage to vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), thereby weakening the vascular wall’s structural integrity and accelerating the onset and progression of the condition. However, the molecular mechanisms through which ferroptosis regulates the onset and progression of AD remain poorly understood. This article explores the relationship between ferroptosis and AD.
Drug utilization study of antiparkinsonian medication in Romania during 25 years
Authors: Bucsa Camelia , Bruhs Denisa , Apan Anamaria , Francu Elena , Mogosan Cristina , Iaru Irina
Published: February 2025

Background

Antiparkinsonian medication has significantly evolved over the last 2 decades, offering various pharmacologic approaches. The aim of this study was to explore the trends and to determine the statistical significance of the observed changes in the antiparkinsonian medication utilization in Romania during 1998–2022.

Methods

This antiparkinsonian drug utilization study used data provided by CEGEDIM Romania, originating from the Pharma and Hospital Report. Quantitative data for each ATC N04 antiparkinsonian medication were converted to total defined daily doses (DDDs) and to DDD/1000inhabitants/day (DDD/TID). The autoregressive integrated moving average (ARIMA) model was employed to determine the statistical significance of the observed changes in the trends of antiparkinsonian drug use.

Results

The utilization of antiparkinsonian medication increased considerably (6-folds) in Romania during the 25 years, from 1.03 DDD/TID in 1998 to 6.22 DDD/TID in 2022. Starting 2005, dopamine precursor (levodopa) became the most used antiparkinsonian drug and remained on this position until the end of the study (13-fold increase from 0.17 in 1998 to 2.30 DDD/TID in 2022). MAO-B inhibitors represented the second most used antiparkinsonian drug class for the majority of the years. Selegiline was the most used until 2017 (0.82 DDD/TID), when a decrease in use was observed and continued until 2022 (0.49 DDD/TID). Utilization of dopamine agonists started in 1999, with less than 0.01 DDD/TID, and increased to 1.47 DDD/TID in 2022. Ropinirole was the most used dopamine agonist (0.56 DDD/TID in 2022). Anticholinergic agents represented the most used antiparkinsonian drugs until 2005. Trihexyphenidyl was the main anticholinergic prescribed with a maximum utilization of 0.82 DDD/TID in 2000 followed by a slight decrease until 2022 (0.56 DDD/TID). Amantadine utilization was mainly constant throughout the 25 years, with 0.32 DDD/TID prescribed in 2022. ARIMA analysis showed that the changes in antiparkinsonian drugs consumption were not statistically significant and overall, the trend for antiparkinsonian drug use demonstrates an upward trajectory.

Conclusion

Antiparkinsonian medication showed an increasing utilization trend in Romania during 1998–2022. Levodopa was the most used antiparkinsonian medicine after 2005, replacing anticholinergic agents. MAO-inhibitors utilization came in second and was followed by dopamine agonists. Observing the trend in antiparkinsonian medication utilization over time is essential for providing insights into their real-world use and uptake in a large population.
Multiscale Granger dependencies in the precipitation network of the island of Sicily
Authors: Pecorino Vera , Pluchino Alessandro , Rapisarda Andrea , Hlaváčková-Schindler Kateřina
Published: February 2025

The island of Sicily has been displaying unusual rainfall behavior and unexpected extreme precipitation events in recent decades. In this study, we investigate the Granger causal (GC) dependencies in the network of precipitation measurement sites of Sicily at different timescales (every 10 min, 1 h, 6 h, 12 h, and 24 h). We study, across seasons and years, different parameters that characterize the GC dependencies: the total in/out-degree of nodes, the total in/out strength of nodes, the total number of links in the network, the number of eastward/westward links, the strength of eastward/westward links, and the maximum strength of links. We then investigate GC statistic intensities, focusing on the temporal evolution of maximum values over multiple timescales. Our study of precipitation patterns in Sicily indicates that, since 2013, the southern regions near Mount Etna (Catania, Siracusa, and Ragusa) have been increasingly affected, while the western areas (Trapani, Palermo, and Agrigento) have been the most affected. Granger causality networks reveal scale-invariant dependencies, with stronger and sparser connections at timescales that extend beyond 6 h, with a notable westward flow of predictive information. These patterns, which are consistent across seasons, suggest localized perturbation fronts, with stronger links indicating a more significant influence on westward predictions. This study highlights shifts in Sicily’s water cycle that call for adaptive management strategies in the face of the increasing frequency of extreme events.
Effect of Cd–Zn compound contamination on the physiological response of broad bean and aphids
Authors: Chen Liya , Wan Sijing , Shen Qintian , Zhao Keting , He Yanlan , Xie Yexin , Tao Shiyu , Zheng Shuchang , Zhang Yi , Wang Shigui , Tang Bin , Li Yan
Published: February 2025

Introduction

The heavy metal elements cadmium (Cd) and zinc (Zn) often coexist in nature, making the environmental media more prone to compound pollution. However, research on the toxic effect of the Cd–Zn combination is still lacking, and the underlying toxic mechanisms remain unclear.

Methods

Therefore, in this experiment, we established four treatment groups with different ratios of Cd–Zn compound stress for the broad bean, Vicia faba L., and aphids, Megoura crassicauda, to explore the growth and physiological adaptation mechanisms under different levels of mixed heavy metal stress.

Results

By measuring the germination rate, seedling height, and chlorophyll content of broad beans, we found that Cd–Zn-mixed stress has a synergistic inhibitory effect on the growth and development of broad beans. Cd and Zn can be transferred through the food chain, while broad beans can resist complex stress by regulating the content of total soluble sugars and photosynthetic pigments in the body, as well as accumulating proline. In addition, in the first generation of adult aphids, treatment with Cd (12.5 mg/kg) + Zn (100 mg/kg) significantly affected the expression of trehalase (TRE) and trehalose-6-phosphate synthase (TPS) genes and influenced the carbohydrate content and trehalase activity in the aphids.

Discussion

The number of offspring produced by the second-generation aphids was significantly reduced under mixed heavy metal treatment, but it was not caused by changes in the vitellogenin (Vg) content. These related results provide new avenues for further exploration of plant responses to mixed heavy metal stress, pest control, and management of heavy metal pollution.
Phenotypic plasticity vs. local genetic adaptation: essential oil diversity of natural immortelle (Helichrysum italicum (Roth.) G.Don) populations along eastern Adriatic coast
Authors: Ninčević Runjić Tonka , Pljevljakušić Dejan , Runjić Marko , Grdiša Martina , Šatović Zlatko
Published: February 2025

The essential oil of Helichrysum italicum (Roth) G.Don, commonly known as immortelle, is produced in Mediterranean countries to meet the increasing demand of the cosmetic and pharmaceutical industries. This study focused on the analysis of secondary metabolites, specifically essential oils, extracted from plants grown from the seeds of natural immortelle populations collected along the eastern Adriatic coast and cultivated ex situ under uniform conditions. Field trials were conducted to determine whether the observed variability was due to phenotypic plasticity or local genetic adaptation. Eighteen natural immortelle populations were sampled, hydrodistilled and their essential oil composition determined by gas chromatography-mass spectrometry. A total of 84 compounds were identified. Eighteen essential oil compounds were present in concentrations greater than 5% in at least one sample of 18 populations. The populations differed significantly in nine essential oil compounds: Limonene, linalool, nerol, neryl acetate, trans-caryophyllene, neryl propionate, ar-curcumene, β-selinene and δ-selinene and the differences were attributed to genetic adaptation to the native environment. Three chemotypes were identified within which the populations were grouped. Results showed a significant and strong correlation between biochemical and bioclimatic distance, with 22.4% of biochemical differentiation between populations explained by bioclimatic distance. Correlations between the 18 main compounds and the bioclimatic variables of the populations’ native environment revealed that BIO14 Precipitation of driest month and BIO15 Precipitation seasonality, were the most informative. These results can serve as a first step for future selection of immortelle populations with desirable adaptations to obtain commercial cultivars that ensure high quality immortelle essential oil.
The politics of digital sovereignty and the European Union’s legislation: navigating crises
Authors: Hulkó Gábor , Kálmán János , Lapsánszky András
Published: February 2025

In recent years, the resistance of member states to the strengthening of the European Union and its ambition to extend the powers of nation states has become a dominant political element, especially in the countries of the Central and Eastern European region. At the same time, both nation states and the EU are facing a number of global challenges, one of the most significant of which, alongside climate change, is digitalization. At the dawn of the digital age, technological innovation and the free flow of information promised unprecedented opportunities. However, as digital technologies have increasingly permeated all aspects of economic, social and political life, they have created new crises and challenges, particularly with regard to digital sovereignty. This research explores the complex and interdisciplinary nature of digital sovereignty, with a particular focus on the crises that digitalization has triggered and caused. These crises manifest themselves in various forms, including cybersecurity threats, privacy issues and the economic dominance of global technology companies. The European Union’s legislative initiatives, including the Digital Services (DSA), Digital Markets (DMA) and European Media Freedom (EMFA) regulations, as well as the efforts to regulate artificial intelligence, are designed to address the crises inherent in the digital age, while at the same time posing new challenges to the sovereignty and perception of sovereignty of individual states. The research examines the EU’s legislative efforts in navigating the politics of digital crises. It sheds light on the interplay between national self-determination and the EU’s overall regulatory framework, highlighting the ongoing struggle to balance control and cooperation in a rapidly changing digital environment. The analysis will provide a deeper understanding of how digital sovereignty is shaped by and responds to crisis policy, and insights into the future of digital governance in an increasingly interconnected world. It also seeks to assess the extent to which recently introduced EU legislation can be harmonized with the policy objective of strengthening the autonomy of nation states. This is particularly important in the context of the legislation and practices observed in countries with relatively small populations, such as Hungary, Slovakia and the Czech Republic.
The mediating effects of self-concept on the relationship between parenting styles and young children’s social problem-solving in Türkiye
Authors: Ayık Ahmet , Sezer Türker , Koçyiğit Sinan
Published: February 2025

The aim of this study was to investigate the associations between parenting styles, young children’s social problem-solving skills, and the mediating role of self-concept in a sample of 200 Turkish preschoolers aged 48–72 months, with an equal distribution of male and female participants. The present study was designed using a cross-sectional survey model in order to achieve the descriptive and predictive aims of the research. Data were collected through individual sessions with the children. During these sessions, the children were administered the Wally Social Problems Test and the DeMoulin Self-Concept Development Scale, while the mothers completed the Parenting Attitudes Scale and the Demographic Information Form. The mediating role of self-esteem and self-efficacy in the relationship between parenting styles and children’s social problem-solving skills was examined using PROCESS MACRO. The results supported the proposed model, demonstrating that the impact of democratic parenting style on social problem-solving skills was partially mediated by self-concept, specifically self-esteem, as a parenting measure. These findings suggest that self-esteem is an essential individual characteristic to consider in relation to preschoolers’ social relationships, in addition to the influence of democratic parenting style behaviors.
The Chinese version of Selection, Optimization, and Compensation Questionnaire: psychometric properties among adolescent students
Authors: Zhu Mengjun , Yao Xing’an , Mansor Abu Talib
Published: February 2025

Objective

This study established the reliability and validity of the Selection, Optimization, and Compensation Questionnaire in a sample of senior secondary school students in China.

Methods

The data for this study were sourced from 1,080 students from multiple senior secondary schools using the SOC Questionnaire and the Learning Engagement Scale. This study conducted Exploratory Factor Analysis and Confirmatory Factor Analysis. The factor structure analysis of the psychometric properties of SOC Questionnaire were examined on reliability, convergent validity, concurrent criterion validity, and incremental validity.

Results

The EFA results suggested that a three-factor solution was most appropriate for the SOC Questionnaire. The three-factor CFA model of this study calculated correlations different from what was published with an American sample of adolescents by the questionnaire developers. The reliability coefficients (Cronbach’s α, McDonald’s ω), composite reliability (rho_c), and reliability coefficient (rho_a), convergent and discriminant validity were good. Concurrent criterion validity, and incremental validity were demonstrated by the SOC Questionnaire and the LES.

Conclusion

The 17-item, 3-factor SOC Questionnaire demonstrated strong reliability and validity, thus offering a new multidimensional of the SOC Questionnaire to evaluate intentional self-regulation among adolescents in schools.
Study and personal resources of university students’ academic resilience and the relationship with positive psychological outcomes
Authors: Bagdžiūnienė Dalia , Žukauskaitė Irena , Bulotaitė Laima , Sargautytė Rūta
Published: February 2025

Introduction

Embarking on university-level studies is a period of new challenges for young people as they meet new academic demands, environments, and teaching systems. Academic resilience, defined as students’ capacity to endure challenges while sustaining optimism, positive thinking, and emotional stability, is crucial in enabling individuals to navigate academic difficulties and foster future success. In this context, developing the role of contextual and personal factors in university students’ academic resilience and its role in predicting positive psychological outcomes is crucial. This study, grounded in the Study Demands–Resources framework, sought to examine study-related characteristics and self-efficacy as resources that support students’ academic resilience. Additionally, it aimed to explore the connections between academic resilience and positive psychological outcomes, such as student engagement and well-being.

Method

The convenience study sample included 350 students from Lithuanian universities: 79.14% were female, the mean age was 23.8 years (SD = 5.7). Students were in varying bachelor’s and master’s study programs. Data were collected using a self-administered online survey. Descriptive statistics, correlation, regression analyses, and structural equation modelling were applied for data analysis.

Results and conclusion

The study found that students’ academic resilience was positively influenced by the characteristics of their study environment and self-efficacy. Furthermore, academic resilience was positively associated with student engagement and well-being. Our findings highlight the role of academic resilience in mediating the interplay between study-related resources, student engagement, and well-being. This research study features practical implications for enhancing university students’ academic resilience, engagement, and well-being by strengthening both study-related and personal resources.