bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring mental health in veterinary students: common stressors and effective coping strategies: a narrative review
Authors: Islam Rahib K. , Cobb Emily K. , McCowan Hannah K. , Watson Kylie , Bhattacharya Kaustuv , Chandra Anjali , Mohiuddin Warda , Gruszynski Karen , Wilkerson Amanda H. , Dascanio John J. , Davis Robert E. , Nahar Vinayak K.
Published: February 2025

Introduction

Veterinary students face significant challenges impacting their mental health and wellbeing. The rigorous academic curriculum, high expectations, and demanding clinical training create an environment of intense pressure and constant stress. This review explores the demographic and psychosocial variables influencing mental health outcomes, highlighting common stressors and coping strategies.

Methods

A systematic literature search was conducted using PubMed, CAB Abstracts, and Google Scholar. Studies published up to 2021 involving veterinary students were included. Twenty-one peer-reviewed studies met the inclusion criteria. Demographic data, stressors, mental health measures, and coping strategies were extracted and analyzed. Studies focused on various mental health aspects, including stress, anxiety, depression, and coping mechanisms. The final selection was based on relevance, quality, and comprehensiveness.

Results

The reviewed studies indicated that rigorous academic demands, high expectations, and clinical training contribute to elevated stress levels among veterinary students. Women reported higher levels of stress, anxiety, and depression compared to men, necessitating gender-specific interventions. Social support and relationship quality were crucial for mental wellbeing, with students in supportive environments experiencing lower stress. Effective coping strategies included exercise and social activities; whereas, harmful behaviors like substance misuse exacerbated mental health issues. Despite using mental health services, barriers such as stigma and lack of awareness hindered access for some students.

Conclusion

The findings underscore the need for targeted support systems to enhance the mental health and resilience of veterinary students. Interventions to promote healthy coping mechanisms, reduce stigma, and improve access to mental health resources are essential. Veterinary schools should prioritize creating a supportive environment to ensure students can manage the demands of their profession while maintaining their mental health and wellbeing.
Effects of Bacillus coagulans on Growth Performance, Digestive Enzyme Activity, and Intestinal Microbiota of the Juvenile Fourfinger Threadfin (Eleutheronema tetradactylum)
Authors: Zheng Anna , Hu Jiaqin , Moses Mkulo Evodia , Jin Minxuan , Wang Linjuan , Zhang Huijuan , Tang Baogui , Zhou Hui , Wang Bei , Huang Jiansheng , Wang Zhongliang
Published: February 2025

The effects of Bacillus coagulans (BC) T-21 on growth performance, intestinal digestive enzyme activity, intestinal morphology, and intestinal microbiota of juvenile fourfinger threadfin (Eleutheronema tetradactylum) were investigated in the present study. Healthy juvenile E. tetradactylum with an initial body weight of 4.2 ± 0.5 g were fed a basal diet sprayed with 1 × 108 cfu/g B. coagulans for eight weeks, and the growth parameters, intestinal digestive enzyme activities, HE-stained intestinal sections, and intestinal microbiota of the juvenile fish were measured. The differences in the feed conversion ratio between the experimental and control groups (fed the basal diet) were extremely significant (p < 0.01), whereas the differences in weight gain rate, specific growth rate, survival rate, and condition factor were significant (p < 0.05). In the experimental group, trypsin and amylase activities decreased significantly, whereas there were no significant differences in lipase activity between the two groups. Compared to the control group, the height of the intestinal villi was greater. No significant differences were observed in the diversity of intestinal microbiota and microbial species at the genus level (p > 0.05). Based on the function prediction analysis, the count values for the glycan biosynthesis, metabolism, and digestive system pathways were significantly increased in the experimental group (p < 0.05). However, there were no significant differences in the counts of other functional pathways (p > 0.05). These results indicate that dietary B. coagulans supplementation is effective in promoting the growth performance and intestinal health of juvenile E. tetradactylum.
Immune Cell Engagers: Advancing Precision Immunotherapy for Cancer Treatment
Authors: In Hyukmin , Park Minkyoung , Lee Hyeonsik , Han Kyung Ho
Published: February 2025

Immune cell engagers (ICEs) are an emerging class of immunotherapies designed to harness the immune system’s anti-tumor potential through precise targeting and activation of immune effector cells. By engaging T cells, natural killer (NK) cells, and phagocytes, ICEs overcome challenges such as immune evasion and MHC downregulation, addressing critical barriers in cancer treatment. T-cell engagers (TCEs), led by bispecific T-cell engagers (BiTEs), dominate the field, with innovations such as half-life-extended BiTEs, trispecific antibodies, and checkpoint inhibitory T-cell engagers driving their application in hematologic and solid malignancies. NK cell engagers (NKCEs) and phagocyte cell engagers (PCEs) are rapidly progressing, drawing on NK cells’ innate cytotoxicity and macrophages’ phagocytic abilities to target tumors, particularly in immunosuppressive microenvironments. Since the FDA approval of Blinatumomab in 2014, ICEs have transformed the oncology landscape, with nine FDA-approved products and numerous candidates in clinical trials. Despite challenges such as toxicity, resistance, and limited efficacy in solid tumors, ongoing research into advanced platforms and combination therapies highlights the growing potential of ICEs to provide personalized, scalable, and effective cancer treatments. This review investigates the mechanisms, platforms, research trends, and clinical progress of ICEs, emphasizing their pivotal role in advancing precision immunotherapy and their promise as a cornerstone of next-generation cancer therapies.
Exploring Antimycobacterial Potential: Safety Evaluation and Active Compound Isolation from Gymnopilus junonius
Authors: Didloff Jenske , Boukes Gerhardt J. , Nyambe Mutenta N. , Beukes Denzil R. , Lerata Mookho S. , Vilane Velile , Lee Michael , Govender Sharlene , van de Venter Maryna
Published: February 2025

Background/Objectives: Tuberculosis remains a major public health crisis, and it is imperative to search for new antimycobacterial drugs. Natural products, including medicinal macrofungi, have been used as sources for the discovery of pharmaceuticals; however, research on their antimycobacterial activity remains limited. This study aimed to isolate and identify the bioactive compound responsible for antimycobacterial activity, thereby expanding on the limited knowledge regarding the antimicrobial activity and bioactive compounds present in Gymnopilus junonius. Methods: Bioassay-guided fractionation using column chromatography and preparative thin-layer chromatography were employed to isolate the active compound. Antimycobacterial activity against Mycobacterium tuberculosis H37 was assessed using a resazurin microplate assay (REMA). The chemical structure was determined by 1H nuclear magnetic resonance (NMR) spectroscopy, heteronuclear single quantum coherence (HSQC) spectroscopy, heteronuclear multiple bond correlation (HMBC) spectroscopy, and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes in M. tuberculosis induced by the compound. Cytotoxicity was evaluated in African green monkey kidney cells (Vero), human liver cells (C3A), and zebrafish embryos/larvae. Results: Bioassay-guided fractionation led to the isolation of gymnopilene, which showed inhibitory activity against M. tuberculosis (MIC: 31.25 µg/mL). TEM analysis revealed that treatment with gymnopilene caused ultrastructural damage observed as the disruption and disintegration of the cell wall. While gymnopilene demonstrated cytotoxicity in Vero and C3A cells, no toxicity was observed in zebrafish embryos/larvae for the crude extract. Conclusions: This study highlights that macrofungi, such as G. junonius, could be a valuable resource of bioactive compounds.
The Smart Buildings Revolution: A Comprehensive Review of the Smart Readiness Indicator Literature
Authors: Delavar Taraneh , Borgentorp Eerika , Junnila Seppo
Published: February 2025

The construction industry is embracing advanced digital technologies, such as the Internet of Things and automation systems, to enhance energy management and occupant comfort in smart buildings. Recognizing the need to assess the readiness of buildings to support energy-efficient and adaptive functionalities, the European Commission introduced the smart readiness indicator (SRI) in 2018. While the SRI provides a standardized framework, its adoption, limitations, and potential to drive the evolution of smart buildings remain underexplored. This study addresses these gaps through a systematic literature review, incorporating bibliometric and qualitative analyses to evaluate the state of research on the SRI. The bibliometric analysis reveals that research on smart readiness is growing rapidly, with a strong focus on energy efficiency and smart buildings. This literature primarily evaluates and promotes the adoption of the SRI within buildings, aligning with the need to explore the paths for the evolution of smart buildings. The qualitative review summarizes six understudied research topic required to drive the evolution of smart buildings in the literature: The applicability of the SRI to different contexts, including various building types and climatic conditions; the subjectivity in the framework; the alignment with other certificates and standards; the SRI as a tool for smart retrofit; expansion to the neighborhood and district levels; and the score correlation with energy performance. The findings show that, although the SRI was originally introduced for buildings, it has much wider applicability, at the more detailed building component level as well as at the broader neighborhood and district levels. Future research could focus on the role of the SRI in evaluating smart readiness at the neighborhood scale and determining the minimum acceptable SRI score.
Single-Glazed Vacuum Tube Collector with SnAl2O3 Selective Flat Absorber Plate and Gravity Single-Stage Direct Water Flow: A Comprehensive Geometric Optimization
Authors: Nešović Aleksandar , Kowalik Robert
Published: February 2025

This paper continues the mathematical research of the novel glass tube collectors for water heating. The subject of this research is a vacuum solar collector composed of a glass tube and a selective (using the SnAl2O3 coating) flat absorber plate. Water heating is performed using gravitational driving force and single-stage direct flow. The thermal performance with the geometric optimization (absorber width and glass tube thickness) of the presented solar collector type was determined using the specially designed iterative calculation algorithm (phase 1) and the double multi-criteria analysis (phase 2). Different operational (absorber temperature, ambient temperature and wind speed), geometric (mass, surface occupation, total surface occupation and volume occupation), economic (manufacturing costs and exploitation costs) and ecological (embodied energy and greenhouse gas emission) indicators were taken into account. The results showed that the useful heat power has an increasing trend if the flat absorber plate width increases, while the thermal efficiency has a decreasing trend. It was also determined that the glass tube thickness and the thermal performance of the solar collector are oppositely dependent. The main conclusion of this paper is that the optimal performance of such non-conventional solar systems is achieved when the absorber plate width is between 85 and 90 mm.
A Comparative Study on Room Impulse Response Reconstruction Using Pattern-Coupled Sparse Bayesian Learning with Different Coupling Structures
Authors: Chen Simiao , Gu Shenyuan , Zhao Yilin , Feng Xuelei , Shen Yong
Published: February 2025

Sparse Bayesian learning (SBL) is widely used for sound field reconstruction (SFR). Among various SBL approaches, pattern-coupled SBL has been demonstrated to achieve superior performance. Building on the pattern-coupled SBL framework, this study replaces matrix multiplication with tensor and matrix cross-correlation operations, significantly reducing the algorithm’s spatial and temporal complexity. Furthermore, we compare the performance of different coupling structures within the pattern-coupled SBL method for reconstructing room impulse responses (RIRs) in the time domain. Specifically, we analyze nine coupling structures that incorporate both temporal and spatial coupling terms and validate their performance via experiments using two datasets. The results indicate that the coupling structure known as CPC-ST (Centered Pattern-Coupled with Spatio-Temporal Coupling) achieves the best performance, especially in the extrapolation of the sound field. For lightweight systems, where a slight performance trade-off is acceptable, the coupling structure known as CPC-S (Centered Pattern-Coupled with Spatial Coupling) is also recommended due to its balance between effectiveness and simplicity.
Research on the Reciprocating Friction and Installation Force of Seals in Deep-Sea Samplers
Authors: Zhang Hao , Wang Yongjun , Chen Jiawang , Sun Yanjie , Shen Yongchun , Wang Hao
Published: February 2025

It is crucial to accurately characterize the static and dynamic properties of seals for the design of deep-sea equipment. This study investigated the movement resistance of O-rings under high pressure (up to 30 MPa) and low temperature (2 °C). Numerical simulation models were set up to investigate the effects of material properties and seal structure dimensions on the reciprocating friction and installation force of O-rings. Furthermore, a novel resistance testing rig was developed to facilitate the measurement of reciprocating friction and installation force of O-rings under high pressure and low temperature. The results of this study indicate that nitrile rubber (NBR) has a reduced sensitivity to temperature variations, and the hardening of the material due to the low temperatures encountered in deep-sea environments does not substantially increase its movement resistance. Conversely, fluororubber (FKM) exhibits superior static sealing reliability. We optimized the sealing structure of the pressure-maintaining trapping instrument (PMTI) and successfully conducted field tests at the South China Sea. The results of this study may serve as a valuable reference for the sealing design of deep-sea equipment.
Characterizing Metabolic Shifts in Septic Murine Kidney Tissue Using 2P-FLIM for Early Sepsis Detection
Authors: Greiner Stella , Ebrahimi Mahyasadat , Rodewald Marko , Urbanek Annett , Meyer-Zedler Tobias , Schmitt Michael , Neugebauer Ute , Popp Jürgen
Published: February 2025

In this study, thin mouse kidney sections from healthy mice and those infected leading to acute and chronic sepsis were examined with two-photon excited fluorescence lifetime imaging (2P-FLIM) using the endogenous fluorescent coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD). The results presented show that this approach is a powerful tool for investigating cell metabolism in thin tissue sections. An adapted measurement routine was established for these samples by performing a spectral scan, identifying a combination of two excitation wavelengths and two detection ranges suitable for detailed scan images of NADH and FAD. Selected positions in thin slices of the renal cortex of nine mice (three healthy, three with chronic sepsis, and three with acute sepsis) were studied using 2P-FLIM. In addition, overview images were obtained using two-photon excited fluorescence (2PEF) intensity. This study shows that healthy kidney slices differ considerably from those with acute sepsis with regard to their fluorescence lifetime signatures. The latter shows a difference in metabolism between the inner and outer cortex, indicating that outer cortical tubular cells switch their metabolism from oxidative phosphorylation to glycolysis in kidneys from mice with acute sepsis and back in later stages, as seen for mice with chronic infections. These findings suggest that 2P-FLIM could serve as a powerful tool for early-stage sepsis diagnosis and monitoring metabolic recovery during treatment.
Phi-Value and NMR Structural Analysis of a Coupled Native-State Prolyl Isomerization and Conformational Protein Folding Process
Authors: Weininger Ulrich , von Delbrück Maximilian , Schmid Franz X. , Jakob Roman P.
Published: February 2025

Prolyl cis/trans isomerization is a rate-limiting step in protein folding, often coupling directly to the acquisition of native structure. Here, we investigated the interplay between folding and prolyl isomerization in the N2 domain of the gene-3-protein from filamentous phage fd, which adopts a native-state cis/trans equilibrium at Pro161. Using mutational and Φ-value analysis, we identified a discrete folding nucleus encompassing the β-strands surrounding Pro161. These native-like interactions form early in the folding pathway and provide the energy to shift the cis/trans equilibrium toward the cis form. Variations distant from the Pro161-loop have minimal impact on the cis/trans ratio, underscoring the spatial specificity and localized control of the isomerization process. Using NMR spectroscopy, we determined the structures for both native N2 forms. The cis- and trans-Pro161 conformations are overall identical and exhibit only slight differences around the Pro161-loop. The cis-conformation adopts a more compact structure with improved backbone hydrogen bonding, explaining the approximately 10 kJ·mol−1 stability increase of the cis state. Our findings highlight that prolyl isomerization in the N2 domain is governed by a localized folding nucleus rather than global stability changes. This localized energetic coupling ensures that proline isomerization is not simply a passive, slow step but an integral component of the folding landscape, optimizing both the formation of native structure and the establishment of the cis-conformation.
Organocyclophosphazenes and Materials Based on Them for Pharmaceuticals and Biomedicine
Authors: Yudaev Pavel , Tupikov Anton , Chistyakov Evgeniy
Published: February 2025

This review examines representatives of organocyclophosphazenes that can act against tumor cells of the ovaries, prostate gland, mammary gland, and colon, etc., and have antimicrobial action against mycobacteria M. tuberculosis, Gram-positive bacteria B. cereus, Gram-negative bacteria K. pneumaniae, fungi of the genus Candida, and other microorganisms. Cyclomatric phosphazenes can be used as carriers of physiologically active substances and in the field of detection, as well as gels for wound surgery and drug delivery platforms. In gels, cyclophosphazenes are used as cross-linking agents. Cyclophosphazenes containing multiple bonds in organic radicals are proposed to be used in dentistry as additives to basic dental compositions. Particular attention in the review is paid to the cytotoxic and antimicrobial action of materials containing cyclophosphazenes and their advantages over commercial physiologically active substances. The review presents the prospects for the practical application of cyclophosphazenes containing various functional groups (chalcone, anthraquinone, pyrrolidine, morpholine, and ferrocene, etc.) in pharmaceuticals. The review may be of interest to researchers working in the field of organoelement chemistry, medicine, and pharmacy.
Alpha-Lipoic Acid Treatment Reduces the Levels of Advanced End Glycation Products in Type 2 Diabetes Patients with Neuropathy
Authors: Csiha Sára , Hernyák Marcell , Molnár Ágnes , Lőrincz Hajnalka , Katkó Mónika , Paragh György , Bodor Miklós , Harangi Mariann , Sztanek Ferenc , Berta Eszter
Published: February 2025

Background/Objectives: Type 2 diabetes mellitus (T2DM) and its macro- and microvascular complications are major health concerns with multiple factors, like advanced end glycation products (AGEs), in the background. AGEs induce long-lasting functional modification of the proteins and collagen in the vascular wall and nerve tissue. We investigated the effect of alpha-lipoic acid (ALA) treatment on AGEs, soluble AGE receptor (sRAGE), the AGE/sRAGE ratio, and the parameters of endothelial dysfunction and their correlations. Methods: In our 6-month intervention study, 54 T2DM patients with neuropathy treated according to the actual therapeutic guidelines with unchanged oral antidiabetic drugs were included and treated by daily oral administration of 600 mg ALA. A total of 24 gender and age-matched T2DM patients without neuropathy served as controls. Results: In our work, we first demonstrated the attenuating effect of alpha lipoic acid therapy on AGEs in humans (11.89 (9.44–12.88) to 10.95 (9.81–12.82) AU/μg (p = 0.017)). sRAGE levels or the AGEs/sRAGE ratio were not affected by ALA treatment or by the presence of neuropathy. We found a correlation between the changes of AGEs and the improvement of current perception threshold and progranulin levels, and an inverse correlation with the change of asymmetric dimethylarginine. Conclusions: According to our results, ALA decreases AGEs, which may contribute to the clinically well-known beneficial effect in diabetic neuropathy and improvement of endothelial function.
Antitumor Potential of Different Treatment Approaches Using Cold Atmospheric Pressure Plasma on Oral Squamous Cell Carcinoma Models: In Vitro Study
Authors: Pavlović Ognjan , Lazarević Miloš , Jakovljević Aleksandar , Škoro Nikola , Puač Nevena , Mojsilović Slavko , Miletić Maja
Published: February 2025

Background/Objectives: Cold atmospheric plasma (CAP) has shown a strong anticancer effect on a variety of tumors, presenting a new approach for the effective treatment of oral squamous cell carcinoma (OSCC), one of the most prevalent malignant neoplasms with a high mortality rate. Here, we aimed to comprehensively investigate the antitumor potential of two approaches of CAP treatment on both two-dimensional and three-dimensional OSCC cell line models, as well as to analyze whether plasma treatment enhances the sensitivity of OSCC to chemotherapy. Methods: An in-house designed plasma needle, with helium as a working gas, was used to treat the SCC-25 cell line directly or indirectly via plasma-treated medium (PTM). The antitumor effect of CAP was assessed by measuring cell viability, apoptosis, adhesion, and migration. In addition, the combined effect of PTM and cisplatin was analyzed in SCC-25 tumor spheroids, as a more complex and reliable in vitro model. Results: Both plasma treatments showed time-dependent antitumor effects affecting their viability, adhesion, and migration. The rate of apoptosis was higher after incubation with PTM and is mediated by the intrinsic pathway. By utilizing the 3D spheroid carcinoma model, we confirmed the antitumor potential of CAP and additionally demonstrated an increased chemosensitivity of PTM-treated carcinoma cells. Conclusions: The results of our study illustrate a promising avenue for the application of CAP as a therapeutic option for OSCC, either as a standalone treatment or in combination with cisplatin.
(Bio)Electroanalysis of Tetracyclines: Recent Developments
Authors: Madej Maria , Knihnicki Paweł , Porada Radosław , Kochana Jolanta
Published: February 2025

Tetracyclines (TCs) are antibiotics used extensively in medicine, veterinary science, and animal husbandry. Their overuse and the widespread presence of their residues in the environment contribute to intensifying the phenomenon of antibiotic resistance (ABR). The efforts are being made to reduce the spread of antibiotics and control the phenomenon of ABR, and one of the key methods is monitoring the presence of antibiotic residues in the environment and food of animal origin. Herein, we provide the overview of the recent developments in electrochemical (bio)sensing of tetracyclines in different types of samples. The review presents a comprehensive view of such aspects of the practical (bio)sensor application as sample preparation, the reusability of (bio)sensors, and the possibility of determining antibiotics at levels required by regulations. Advances, existing challenges, and future trends in the development of novel (bio)electrochemical methods of tetracycline quantification were discussed.
The Incidence and Variants of the Reno-Hemiazygos Connection
Authors: Damen Nawwaf Sebastian , Jianu Adelina Maria , Lazăr Mihai , Rusu Mugurel Constantin , Piţigoi Gabriel , Petrescu Silviu
Published: February 2025

Background/Objectives: Although common anomalies of the left renal vein (LRV) are pretty well documented in the literature, the drainage of the left renal blood via the hemiazygos vein lacks comprehensive support. We, therefore, aimed to study the incidence of the reno-hemiazygos connection (RHC). Methods: A total of 150 computed tomography scans (85 men and 65 women) were documented for the origin of an RHC from the LRV. Results: RHCs were found in 14/150 cases (9.34%). They were more prevalent in women (71.43%). In 11/14 cases, type 1 RHCs ascended directly along the postero-lateral left side of the aorta (direct hemiazygos flow). In 3/14 cases, type 2 RHCs (indirect hemiazygos flow) had a lumbar segment corresponding to the second lumbar vein and a pretransversary segment corresponding to an ascending lumbar vein. In 9/14 cases (64.29%), the RHC was connected to a typical LRV. In 1/14 cases (7.14%), the RHC was connected to the junction between the LRV and a left retropelvic tributary. In another case (7.14%), the RHC was connected to a retroaortic LRV and, in three cases (21.43%), to a circumaortic LRV. Triple left renal arteries were found in type 1 and, respectively, type 2 cases. The vertebral level of the inferior end of the RHC was variable, from the L1/L2 disc level to the L3 level. Conclusions: When present, the RHC serves to connect the superior and inferior caval systems. This may be physiologically of use or not, but surgically, it is a major anatomical risk factor for bleeding if its presence is not checked preoperatively.
The Roles of Anxiety and Depressive Symptoms in the Relationship Between School Bullying Victimization and Suicidal Ideation Among South Korean College Students: A Serial Multiple Mediation Model
Authors: Park Aely
Published: February 2025

This study examined the sequential mediating roles of anxiety and depressive symptoms in the effect of school bullying victimization on suicidal ideation. This study utilized a convenience sample of college students across South Korea, and an online survey was conducted. This quantitative research analyzed data collected from 1037 participants. The sample consisted of an equal gender distribution, with a mean age of 23.65 years (range: 18–30). Additionally, 30% of participants reported a household income of four million won or less (approximately USD $3076). More than half of the participants’ parents had attained a college education or higher. Also, multiple mediation analyses were conducted to examine whether anxiety and depressive symptoms mediated the relationship between school bullying victimization and suicidal ideation. In the results, multiple mediation analyses showed that school bullying victimization does not have a direct effect on suicidal ideation. On the other hand, school bullying victimization has an indirect effect on suicidal ideation through anxiety and depressive symptoms, controlling for covariates. Based on these research results, implications for school bullying prevention and intervention were discussed.
Astragalus Mongholicus Polysaccharides Alleviate Kidney Injury in Rats with Type 2 Diabetes Through Modulation of Oxidation, Inflammation, and Gut Microbiota
Authors: Xu Guoquan , Yuan Haisheng , Liu Jingran , Wang Xianjue , Ma Li , Wang Yuzhen , Dong Guicheng
Published: February 2025

We aimed to uncover the underlying mechanisms contributing to the therapeutic efficacy of Astragalus mongholicus Polysaccharides (mAPS) in alleviating diabetic nephropathy (DN). The rat model of DN was subjected to a high-sugar and high-fat diet (HSHFD) coupled with streptozotocin (STZ) injection. Our findings revealed that mAPS administration decreased fasting blood glucose (FBG), BUN, SCR, UA, and MDA levels, while elevating serum GSH, GSH-PX, and SOD activities in DN rats (p < 0.05). Furthermore, there was a notable rise in the mRNA and protein expression of renal Nrf-2, GCLC, NQO1, and HO-1 post mAPS treatment (p < 0.05). Additionally, mAPS supplementation led to reduced protein expression of TLR4, NLRP3, p-NF-κB, TGF-β, and Smad4. Concurrently, mAPS exerted a modulatory effect on gut microbiota, as evidenced by the increased abundance of Muribaculaceae, Ruminococcus_1, Phascolarctobacterium, and Lachnoclostridium-related genera. Spearman correlation analysis illustrated a negative association between the abundance of microbiota (Muribaculaceae, Lachnospiraceae_NK4A136, Ruminococcus_1, Clostridiales) and the levels of serum parameters (BUN, CR, UA, TC, TG). In summary, our data robustly attests to the potential of mAPS in modulating oxidative stress, inflammation, and gut microbiota, ultimately resulting in improved renal function in DN rats.
Arthrocolin B Impairs Adipogenesis via Delaying Cell Cycle Progression During the Mitotic Clonal Expansion Period
Authors: Cao Guang , Liao Xuemei , Zhao Shuang , Li Mengwen , Xie Zhengyuan , Yang Jinglan , Li Yanze , Zhu Zihao , Jin Xiaoru , Huang Rui , Guo Ziyin , Niu Xuemei , Ji Xu
Published: February 2025

Obesity and its related diseases severely threaten people’s health, causing persistently high morbidity and mortality worldwide. The abnormal proliferation and hypertrophy of adipocytes mediate the expansion of adipose tissue, which is the main cause of obesity-related diseases. Inhibition of cell proliferation during the mitotic clonal expansion (MCE) period of adipogenesis may be a promising strategy for preventing and treating obesity. Arthrocolins are a series of fluorescent dye-like complex xanthenes from engineered Escherichia coli, with potential anti-tumor and antifungal activities. However, the role and underlying mechanisms of these compounds in adipocyte differentiation remain unclear. In this study, we discovered that arthrocolin B, a member of the arthrocolin family, significantly impeded adipogenesis by preventing the accumulation of lipid droplets and triglycerides, as well as by downregulating the expression of key factors involved in adipogenesis, such as SREBP1, C/EBPβ, C/EBPδ, C/EBPα, PPARγ, and FABP4. Moreover, we revealed that this inhibition might be a consequence of cell cycle arrest during the MCE of adipocyte differentiation, most likely by modulating the p53, AKT, and ERK pathways, upregulating the expression of p21 and p27, and repressing the expression of CDK1, CDK4, Cyclin A2, Cyclin D1, and p-Rb. Additionally, arthrocolin B could promote the expression of CPT1A during adipocyte differentiation, implying its potential role in fatty acid oxidation. Overall, our research concludes that arthrocolin B has the ability to suppress the early stages of adipocyte differentiation mainly by modulating the signaling proteins involved in cell cycle progression. This work broadens our understanding of the function and mechanisms of arthrocolins in regulation of adipogenesis and might provide a potential lead compound for treating the obesity.
Low-Dose Docetaxel Is Effective in Reducing Atherogenic Lipids and Atherosclerosis
Authors: Choi Hong Y. , Ruel Isabelle , Choi Shiwon , Iatan Iulia , Choi Senna , Lee Jyh-Yeuan , Genest Jacques
Published: February 2025

High-density lipoprotein (HDL) particles form during cellular cholesterol removal, positioning HDL biogenesis as a potential strategy to combat atherosclerosis. We identified desmocollin 1 (DSC1) as a negative regulator of HDL biogenesis and discovered that docetaxel (DTX) effectively inhibits DSC1 activity. This study assessed the efficacy of DTX in reducing atherosclerosis in ApoE−/− mice. After two weeks on a high-fat diet, mice were divided into baseline, vehicle-treated, and DTX-treated groups. Baseline mice were sacrificed at the end of the two weeks, while the other groups received a vehicle or DTX (1 μg/μL) via subcutaneously implanted osmotic pumps delivering 0.15 μL/h for six weeks, with the high-fat diet continued. The controlled drug delivery system maintained stable DTX blood concentrations (2.7–4.3 nM) over six weeks without hematologic toxicity. DTX treatment significantly reduced circulating atherogenic lipids, including triglycerides, non-esterified fatty acids, low-density lipoprotein cholesterol, and total cholesterol, while increasing the HDL cholesterol/total cholesterol ratio. These improvements were associated with significant reductions in atherosclerotic lesions in the aortic sinus and arch. Notably, these effects occurred without altering circulating inflammatory cytokine levels. These results demonstrate that DTX effectively reduces dyslipidemia-induced atherosclerosis. Its HDL-biogenic and anti-atherosclerotic effects establish DTX as a promising candidate for developing HDL-directed therapies for atherosclerosis.
Combination of Saffron (Crocus sativus), Elderberry (Sambucus nigra L.) and Melilotus officinalis Protects ARPE-19 Cells from Oxidative Stress
Authors: Puddu Alessandra , Nicolò Massimo , Maggi Davide C.
Published: February 2025

Oxidative stress is considered a common underlying mechanism in many retinal degenerative diseases and is often associated with inflammation. The use of dietary supplements containing Saffron has beneficial effects in ocular diseases, though the molecular mechanisms are still unclear. In this study, we investigated how Saffron can exert protective effects against oxidative damage in retinal pigment epithelial cells (ARPE-19) and whether its combination with Elderberry and Melilotus may have additive beneficial effects. ARPE-19 cells were pretreated with Saffron alone or in a mix containing Saffron, Elderberry and Melilotus, then exposed to hydrogen peroxide (H2O2) for 3 h. Afterwards, we evaluated cell viability, oxidative stress and inflammatory status. Our results showed that H2O2 reduced cell viability and total glutathione levels, while increasing caspase-3, caspase-1 and LDH activity. Moreover, H2O2 triggered ROS production, glutathione oxidation and IL-1β secretion. Pretreatments with Saffron alone or with the mix counteract these damaging effects by improving cell viability, reducing oxidative stress and enhancing SOD2 expression. Pretreatment with the mix activated the NRF2 pathway and was more effective than Saffron alone in preventing caspase-1 activation. These findings suggest that the combination of Saffron, Elderberry and Melilotus could have therapeutic potential in the prevention and treatment of retinal degenerative diseases.
Ultrastructure and Transcriptome Analysis of the Larval Integument in Solitary and Gregarious Phases of Mythimna separata
Authors: Li Lingling , Li Wenmeng , Liao Jing , Fu Junhong , Dai Changgeng , Hu Yang , Li Hongbo
Published: February 2025

Mythimna separata larvae exhibit both solitary and gregarious phases under low and high population density, respectively; furthermore, differences in morphology, behavior and physiology have been observed in the two phases. The integument plays an essential role in the fitness, general metabolism, communication, and survival of insects; however, differences in the integument ultrastructure and gene expression in the solitary and gregarious phases are largely unknown. In this study, the integument ultrastructure of larvae in the solitary and gregarious phases was compared, and transcriptome analysis was conducted to identify which genes were differentially expressed in the two phases. The results showed that the gregarious larvae had thicker integuments and more polygonal particles on the cuticle surface than solitary larvae. Using the Illumina HiSeq™ sequencing platform, 2774 differentially expressed genes (DEGs) were generated. Among these, many transcripts were identified with roles in the synthesis of fatty acids; structural components of the integument and the insecticide detoxification were differentially expressed in the integument of the two larval phases. qRT-PCR was used to validate expression patterns of the selected transcripts. This study provides a valuable resource for understanding the molecular basis of behavioral and physiological differences in the two phases of M. separata.
Clinical Outcomes of Machine Perfusion and Temperature Control Systems in Heart Transplantation: Where We Stand
Authors: Nasim Umar , Dorken-Gallastegi Ander , Dadson Peter , Hong Yeahwa
Published: February 2025

Heart transplantation remains the preferred treatment for carefully selected patients with end-stage heart failure refractory to medical therapy. Advances in donor management, organ preservation, donor and recipient selection, immunosuppressive strategies, and mechanical circulatory support have significantly improved the safety and efficacy of heart transplantation. However, the persistent shortage of donor hearts and their limited preservation period continues to restrict access to this lifesaving procedure. The advent of innovative machine perfusion and temperature control systems for heart allograft preservation offers a promising avenue to address these challenges. These technologies aim to extend preservation times and enable the use of extended-criteria donors, thereby expanding the donor pool. In this review, we examine the outcomes from clinical trials, registry data, and single-center studies, utilizing the TransMedics Organ Care System Heart, Paragonix SherpaPak Cardiac Transport System, and XVIVO Heart Preservation System. As the field of heart transplantation evolves to accommodate longer ischemia times, expand organ sharing, and utilize donors previously considered marginal, the integration of these advanced technologies will be essential for optimizing post-transplant outcomes.
Geriatric Approaches to Rectal Cancer: Moving Towards a Patient-Tailored Treatment Era
Authors: Vallicelli Carlo , Barbara Silvia Jasmine , Fabbri Elisa , Perrina Daniele , Griggio Giulia , Agnoletti Vanni , Catena Fausto
Published: February 2025

Rectal cancer is a significant global health concern, particularly amongst the elderly population, with rectal cancer accounting for approximately one-third of cancer cases in this population. Older adults often present with advanced disease stages and unique clinical manifestations, such as tumors closer to the anal verge and with greater size. Diagnosis typically involves a series of screening and imaging strategies, culminating in accurate staging through pelvic MRI, endoscopic ultrasound, and CT scan. Management of rectal cancer in older adults emphasizes individualized treatment plans that consider both the cancer stage and the patient’s overall health status, including frailty and comorbidities. A multidisciplinary approach, including a mandatory geriatric assessment, is essential for optimizing outcomes, in order to improve survival and quality of life for elderly patients with rectal cancer.
Essential Tremor and Mortality in Older Adults: The Role of Word Recall, a Measure of Episodic Memory, in a 23-Year Follow-Up Study
Authors: Benito-León Julián , Lapeña-Motilva José , Ghosh Ritwik , Giménez de Béjar Verónica , Benito-Rodríguez Carla Mª , Bermejo-Pareja Félix
Published: February 2025

Background: The association between essential tremor (ET) and mortality risk remains uncertain. This study investigated the impact of episodic memory performance, measured through a word recall task, on mortality risk in ET within the Neurological Disorders in Central Spain (NEDICES) cohort, a population-based study of older adults. Methods: Participants were followed until death or 31 December 2017, and divided into four groups based on ET status and memory performance (errors in the 37-Minimental Examination’s three-word recall task). Cox proportional hazards models estimated mortality hazard ratios (HRs), and the Relative Excess Risk due to Interaction (RERI) assessed additive interactions. Results: Among 3998 participants, 3432 (85.8%) died over a median follow-up of 11.2 years. ET patients with episodic memory impairments had a higher mortality risk (HR = 1.25, 95% CI: 1.06–1.46) compared with controls with similar deficits (HR = 1.19, 95% CI: 1.09–1.28), whereas no significant increase was observed for ET patients without memory impairments (HR = 0.95, 95% CI: 0.74–1.21). RERI analysis revealed no significant additive interaction between ET and memory impairment (fully adjusted RERI: 0.11 [95% CI: −0.19–0.41]). Episodic memory impairments, regardless of ET status, were strongly associated with Alzheimer’s disease as a primary cause of death. Conclusions: These findings highlight the independent contribution of episodic memory impairment to increased mortality risk, with ET modestly amplifying this effect without significant interaction. Further research is needed to explore shared pathophysiological mechanisms between ET and neurodegenerative conditions.
Contrast-Induced Nephropathy in Endovascular Patients: A Retrospective Cohort Study from a Vascular Surgery Clinic in Eastern Europe
Authors: Olariu Nicu , Maralescu Felix-Mihai , Bob Flaviu , Grosu Iulia Dana , Dragota-Pascota Razvan , Marc Luciana , Chisavu Lazar , Albai Oana , Ratiu Ioana Adela , Barac Sorin , Rață Andreea Luciana , Mzi Adelina , Mihaescu Adelina
Published: February 2025

Introduction: Contrast-induced nephropathy (CIN) has emerged as a prevalent and serious complication associated with the administration of iodinated contrast media during diagnostic and therapeutic procedures. Given the rising global prevalence of chronic kidney disease(CKD,) it is crucial to gain a deeper understanding of the risks linked to contrast media exposure. Therefore, the aim of this study, conducted at the Vascular Surgery Clinic in a tertiary hospital in Eastern Europe (Timisoara, Romania), is to assess the incidence of CIN and identify its associated risk factors among patients undergoing endovascular interventions. Methods: This retrospective cohort study was conducted using data from patients treated at a vascular surgery clinic in Timisoara, Romania, between 1 January 2018 and 31 December 2023. The study population included adult patients who underwent scheduled endovascular procedures and had serum creatinine measurements both before and after the procedure. Results: A total of 331 patients were included in the analysis (71.42% males with a mean age of 66.79 ± 9.86 years). In total, 9.22% of the patients had CKD, while 23.8% developed CIN. The mean age was significantly higher in the CIN group (68.4 years) compared to the non-CIN group (66.32 years) with a p-value of 0.093, indicating that older age is associated with a higher risk of CIN. A multivariate logistic regression analysis was performed to assess the association between various factors and the development of CIN. Higher hemoglobin levels were associated with reduced odds of CIN (OR = 0.792, 95% CI: 0.659–0.952, p = 0.0148), indicating that anemia is a significant risk factor for CIN, while CKD significantly increased the odds of CIN by 85.8% (OR = 1.858, 95% CI: 1.105–3.125, p = 0.0023), establishing CKD as a critical risk factor for CIN. Conclusions: While anemia and CKD were found to be significant predictors of CIN, further research on a wider population is required to validate these findings and explore additional risk factors. Our study shows that, in the context of elective endovascular procedures, addressing anemia correction and stabilizing creatinine levels to baseline represents a crucial strategy for reducing the risk of CIN.
Applying Nociplastic Pain Criteria in Chronic Musculoskeletal Conditions: A Vignette Study
Authors: Bilika Paraskevi , Nijs Jo , Billis Evdokia , Dimitriadis Zacharias , Paliouras Achilleas , Savvoulidou Konstantina , Strimpakos Nikolaos , Kapreli Eleni
Published: February 2025

Background/Objectives: The International Association for the Study of Pain (IASP) recently introduced clinical criteria and a grading system to identify nociplastic pain, marking a pivotal step toward improving diagnostic accuracy. This study aimed to evaluate the reliability and validity of the IASP criteria using clinical vignettes, assessing their effectiveness in identifying nociplastic pain in clinical settings. Methods: A reliability and diagnostic accuracy study was conducted using 32 clinical vignettes based on the literature and pre-existing clinical data. The vignettes represented patients with and without the characteristics of nociplastic pain and were reviewed independently by two expert physiotherapists. Inter-rater and intra-rater reliability were evaluated with a 1-month interval between assessments. Criterion validity was analyzed by comparing the IASP criteria against the standardized vignettes as the reference standard. Sensitivity, specificity, and predictive values were calculated to assess diagnostic accuracy. Results: The IASP criteria demonstrated moderate-to-perfect intra-rater agreement (κ = 0.71–1.00, p < 0.05) and weak-to-perfect inter-rater agreement (κ = 0.52–1.00, p < 0.05). Criterion validity was moderate (κ = 0.68), with strong specificity (89.0%) and moderate sensitivity (69.0%). Positive and negative predictive values were high at 81.8% and 81.0%, respectively, supporting the criteria’s accuracy in identifying and excluding nociplastic pain. Conclusions: The IASP criteria for nociplastic pain exhibited satisfactory reliability and criterion validity in this preliminary study, particularly after initial rater familiarization. Future research should evaluate their application in real-world clinical settings, explore concurrent and prognostic validity, and involve a broader range of raters to enhance generalizability.
Current Issues and Future Perspectives of Targeted Therapies in Primary Mediastinal Large B-Cell Lymphoma
Authors: Liaskas Athanasios , Dimopoulou Maria N. , Piperidou Alexia , Angelopoulou Maria K. , Vassilakopoulos Theodoros P.
Published: February 2025

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare, aggressive B-cell lymphoma, sharing common features with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). PMLBCL is usually cured with single-hit immunochemotherapy in the first-line setting. Relapses tend to be aggressive and may be unresponsive to conventional chemotherapy. Autologous stem cell transplant (ASCT) remains a viable option for chemosensitive patients; nevertheless, targeted therapies appear to be highly promising. Checkpoint inhibitors (CPIs) have already transformed the course of relapse/refractory disease, while CD-19-directed Chimeric Antigen Receptor (CAR) T-cell therapy may produce remarkably favorable outcomes. The exact position of CAR T-cells and CPIs in the treatment algorithm, along with the role of radiotherapy and ASCT, remains to be precisely determined. In the current review, we aim to present the recent research on targeted agents in PMLBCL and define their sequencing within the treatment algorithm, mainly in the relapse/refractory setting.