bluuebunny/crossref_metadata_2025 huggingface dataset:
Historical and Future Changes in Meteorological–Hydrological Compound Drought in China
Authors: Li Zhuoyuan , Lu Er , Tu Juqing , Yuan Dian
Published: December 2024

Drought is typically divided into meteorological, agricultural, hydrological, and socioeconomic categories. Generally, the transition from meteorological drought to other types of droughts is known as drought propagation. When drought propagation occurs, different types of droughts may still exist simultaneously or successively. In this study, compound droughts are divided into three categories: hydrological meteorological compound drought (HMD), meteorological hydrological compound drought (MHD), and simultaneous compound drought (SD). ERA5 and CMIP6 data are used for analysis under historical and future scenarios. Different types of compound droughts have emerged in extreme centers in different basins. Our analysis indicates a significant upward trend in the duration of these three compound droughts from 1979 to 2022. Additionally, our projections under SSP5-8.5 and SSP2-4.5 suggest a substantial increase in the occurrence of various compound droughts. HMD, MHD and SD all show a consistent upward trend under the future scenario above the moderate-drought level. MHDs are projected to experience the most significant increase compared to the historical period in the far-future period (2066–2099) under SSP5-8.5.
Antibiotic Resistance as a Functional Characteristic of Urban Dust Particles’ Microbial Communities
Authors: Vetrova Anna A. , Ivanova Anastasia A. , Petrikov Kirill V. , Gavrichkova Olga , Korneykova Maria V. , Sazonova Olesya I.
Published: December 2024

Urban dust samples were collected in Moscow (Russia) in June 2021. The samples were collected in three functional zones of Moscow (traffic, residential, and recreational) and included air microparticles, leaf dust, and paved dust. Data on the taxonomic composition of bacterial communities were obtained for dust samples, and their functional characteristics were predicted using PICRUSt2 2.5.0 and FAPROTAX 1.8.0 software. The culturable part of the bacterial community was examined for the presence of antibiotic-resistant strains with respect to β-lactams, tetracyclines, amphenicols, and aminoglycosides. The presence of bacteria resistant to ceftazidime, cefepime, and tetracycline was detected in all dust samples. The presence of bacteria resistant to meropenem and amikacin was only observed in the dust collected from leaves in the residential and traffic zones. The overall abundance of cultured antibiotic-resistant bacteria from the total heterotrophs ranged from 0.03% to 1.88%, with the highest percentage observed in dust from the residential zone. Notably, strains resistant to all antibiotics tested were observed in the leaf dust bacterial community.
Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells
Authors: Kolotyeva Nataliya A. , Groshkov Alexander A. , Rozanova Nataliya A. , Berdnikov Arseniy K. , Novikova Svetlana V. , Komleva Yulia K. , Salmina Alla B. , Illarioshkin Sergey N. , Piradov Mikhail A.
Published: December 2024

NAD+ plays a pivotal role in energy metabolism and adaptation to external stimuli and stressful conditions. A significant reduction in intracellular NAD+ levels is associated with aging and contributes to the development of chronic cardiovascular, neurodegenerative, and metabolic diseases. It is of particular importance to maintain optimal levels of NAD+ in cells with high energy consumption, particularly in the brain. Maintaining the tissue level of NAD+ with pharmacological tools has the potential to slow down the aging process, to prevent the development of age-related diseases. This review covers key aspects of NAD+ metabolism in terms of brain metabolic plasticity, including NAD+ biosynthesis and degradation in different types of brain cells, as well as its contribution to the development of neurodegeneration and aging, and highlights up-to-date approaches to modulate NAD+ levels in brain cells.
Lipid Nanoparticles Enable Efficient In Vivo DNA Knock-In via HITI-Mediated Genome Editing
Authors: Hirose Jun , Aizawa Emi , Yamamoto Shogo , Xu Mingyao , Iwai Shigenori , Suzuki Keiichiro
Published: December 2024

In vivo genome editing holds great therapeutic potential for treating monogenic diseases by enabling precise gene correction or addition. However, improving the efficiency of delivery systems remains a key challenge. In this study, we investigated the use of lipid nanoparticles (LNPs) for in vivo knock-in of ectopic DNA. Our in vitro experiments demonstrated that the homology-independent targeted integration (HITI)-mediated genome-editing method achieved significantly higher knock-in efficiency at the Alb locus in hepatic cells compared to the traditional homology-directed repair (HDR)-mediated approach. By optimizing LNP composition and administration routes, we successfully achieved HITI-mediated GFP knock-in (2.1–2.7%) in the livers of mice through intravenous delivery of LNP-loaded genome editing components. Notably, repeated intravenous dosing led to a twofold increase in liver GFP knock-in efficiency (4.3–7.0%) compared to a single dose, highlighting the potential for cumulative genome editing effects. These findings provide a solid foundation for the use of LNPs in in vivo knock-in strategies, paving the way for future genome-editing therapies.
Mutations in the PIK3C2B, ERBB3, KIT, and MLH1 Genes and Their Relationship with Resistance to Temozolomide in Patients with High-Grade Gliomas
Authors: Ortiz Gómez León Darío , Contreras Martínez Heidy Johanna , Galvis Pareja David Andrés , Vélez Gómez Sara , Salazar Flórez Jorge Emilio , Monroy Fernando P. , Peláez Sánchez Ronald Guillermo
Published: December 2024

Introduction. The treatment for patients with high-grade gliomas includes surgical resection of tumor, radiotherapy, and temozolomide chemotherapy. However, some patients do not respond to temozolomide due to a methylation reversal mechanism by the enzyme O6-methylguanine-DNA-methyltransferase (MGMT). In patients receiving treatment with temozolomide, this biomarker has been used as a prognostic factor. However, not all patients respond in the same way, which suggests the existence of other proteins involved in resistance to temozolomide chemotherapy. Methods. A group of thirty-one patients was recruited who were clinically and pathologically diagnosed with high-grade gliomas. The sequencing of 324 genes related to different types of cancer was performed to detect mutations. Subsequently, a statistical analysis was conducted to determine the mutated genes that were most related to resistance to treatment. Results. According to the Stupp protocol and metronomic dose of the temozolomide treatment, the mutated genes related to the second relapse of patients with high-grade glioma were PIK3C2B, KIT, ERBB3, and MLH1. Conclusions. Considering the results obtained, we suggest that mutations in the four genes and methylation of the gene promoter that codes for the MGMT protein could be related to response to treatment with temozolomide.
Adalimumab Autoantibodies in Uveitis Patients: Do We Need Routine Drug Monitoring?
Authors: zur Bonsen Lynn S. , Knecht Vitus A. , Rübsam Anne , Pohlmann Dominika , Pleyer Uwe
Published: December 2024

Background: Adalimumab, an anti-TNF-α biologic agent, has emerged as a principal treatment option for patients with non-infectious uveitis. The influence of adalimumab anti-drug antibodies (AAA) on the efficacy of adalimumab therapy is not yet fully understood. We aim to understand their clinical implications in the context of therapeutic drug monitoring and the factors contributing to the formation of these antibodies. Methods: We conducted a retrospective analysis of 114 patients with non-infectious uveitis who developed AAA while undergoing adalimumab therapy. Results: Among the 114 AAA-positive uveitis patients, a significant correlation was observed between AAA levels and reduced adalimumab serum levels (r = −0.58, p < 0.001). The mean time to AAA detection was 2.1 years (range 0.1–11.9 years), with 45.6% of cases identified through routine testing. If AAA levels were initially low, subsequent measurements for AAA were more likely to become negative during treatment (r = 0.63, p < 0.001). Higher AAA concentrations were associated with a shorter time to detection (r = −0.27, p = 0.01) and younger age (r = −0.21, p = 0.03). There was a trend, though no significant influence, of concomitant immunosuppression with prednisolone ≤ 7.5 mg or methotrexate on antibody formation (p = 0.18). No significant difference was observed in AAA levels between uveitis subtypes. Conclusions: Higher AAA concentrations are associated with lower adalimumab serum levels in uveitis patients. Routine clinical testing is essential for optimal therapeutic drug monitoring to prevent early loss of effectiveness.
A Biomimetic Pose Estimation and Target Perception Strategy for Transmission Line Maintenance UAVs
Authors: Zhuo Haoze , Yang Zhong , Zhang Chi , Xu Nuo , Xue Bayang , Zhu Zekun , Xie Yucheng
Published: December 2024

High-voltage overhead power lines serve as the carrier of power transmission and are crucial to the stable operation of the power system. Therefore, it is particularly important to detect and remove foreign objects attached to transmission lines, as soon as possible. In this context, the widespread promotion and application of smart robots in the power industry can help address the increasingly complex challenges faced by the industry and ensure the efficient, economical, and safe operation of the power grid system. This article proposes a bionic-based UAV pose estimation and target perception strategy, which aims to address the lack of pattern recognition and automatic tracking capabilities of traditional power line inspection UAVs, as well as the poor robustness of visual odometry. Compared with the existing UAV environmental perception solutions, the bionic target perception algorithm proposed in this article can efficiently extract point and line features from infrared images and realize the target detection and automatic tracking function of small multi-rotor drones in the power line scenario, with low power consumption.
Protected Areas Do Not Outweigh the Species Richness or Functional Diversity and Traits of Birds in Brazil
Authors: Cavarzere Vagner
Published: December 2024

Protected areas (PAs) are widely recognized as being essential for maintaining global biodiversity. In this study, I aimed to determine whether PAs support a greater richness of forest bird species than unprotected habitats and whether they exhibit functional diversity indices and traits comparable to those found in protected forests in the eastern Brazilian Semideciduous Atlantic Forest. I conducted bird surveys across 20 forest fragments of varying sizes (43 to 37,000 ha), 12 of which were legally designated as PAs. The results indicated that species richness was not significantly higher in PAs and that there were no significant differences in functional diversity indices and traits between unprotected and protected forests. In eastern Brazil, some forest remnants were designated as PAs merely because they were among the last remaining patches within a heavily fragmented landscape. Therefore, protected areas do not necessarily serve as accurate proxies for well-preserved habitats.
The Influence of Episodic Future Thinking on Prospective Memory in Older Adults
Authors: Ma Zhanyu , Zhang Xinyuan
Published: December 2024

Previous research has demonstrated that episodic future thinking (EFT) can enhance prospective memory (PM); however, its effects on older adults have been less explored. This study examines the impact of EFT training on PM in both older and younger adults under varying delay intervals. Experiment 1 employed a 2 (EFT training: present vs. absent) × 2 (age: younger adults vs. older adults) × 2 (delay interval: 5 min vs. 20 min) between-subjects design. The results revealed a significant main effect of EFT training (p < 0.001), indicating that such training improves PM performance. Among younger adults, a significant difference in PM performance was found between the trained and untrained groups (p = 0.03), while among older adults, this difference was only marginally significant. This suggests that the facilitative effect of EFT training is more pronounced in younger adults. Additionally, there was a significant main effect of delay interval (p = 0.01), with shorter intervals yielding better PM performance than longer intervals. Experiment 2 focused on the impact of specificity in EFT training on PM in both age groups. A 2 (training: specific vs. non-specific) × 2 (age: younger vs. older adults) × 2 (delay interval: 5 min vs. 20 min) between-subjects design was used. Results indicated that older adults in the specific training group outperformed those in the non-specific training group (p = 0.03), whereas no difference was observed among younger adults. This finding suggests that specific training is more effective for enhancing prospective memory in older adults. Moreover, older adults exhibited differences based on the delay interval, with a 20 min interval impairing performance (p = 0.04), while younger adults showed no difference between the two intervals. These findings will be discussed in relation to the Multiprocess Model and the Preparatory Attention and Memory Processes Theory.
Disparities Between Older Adults’ Potential and Realized Access to Community-Based Care: A Multilevel Analysis of Geo-Referenced Check-In Data from Senior Centers in Nanjing, China
Authors: Li Xiaoming , Xu Zhixin
Published: December 2024

Community-based care services offered by senior centers are vital for supporting older adults’ independent living. The number of senior centers has escalated in China in recent years. Despite scholarly interest in the potential accessibility of senior centers, research on older adults’ realized access remains scarce. Using the geo-referenced check-in data of 2382 users of senior centers in Nanjing, China, this study aims to fill this gap by examining the disparities between older adults’ potential and realized access to senior centers and the influence of multilevel spatial and non-spatial factors. This study indicates that potential access is often significantly overestimated compared with the actual accessibility of senior centers, with older adults’ distances of realized access (mean = 1319 m) being considerably greater than potential access (mean = 325 m). Spatial and regression analyses confirm that older adults living in newly built, lower-priced houses in the inner city are more likely to travel longer distances to reach senior centers. Spatial proximity is less effective in predicting realized access for those living further from senior centers. Instead, the location and service quality of senior centers play a more prominent role. These findings enrich our understanding of older adults’ access to community-based care, informing planning and policy interventions for the development of age-friendly communities.
Digital Rehabilitation Program for Breast Cancer Survivors on Adjuvant Hormonal Therapy: A Feasibility Study
Authors: Chan Wing-Lok , Wong Yat-Lam , Tai Yin-Ling , Liu Michelle , Yun Bryan , Zhang Yuning , Hou Holly Li-Yu , Kwong Dora , Lee Victor Ho-Fun , Lam Wendy Wing-Tak
Published: December 2024

Background: Breast cancer survivors often face physical and psychological challenges, including weight gain, metabolic syndrome, and reduced quality of life. To address these concerns, a mobile app-based rehabilitation program called “THRIVE” was developed to improve physical activity, medication adherence, and health-related quality of life (HRQoL) in this population. Methods: This prospective, single-arm study assessed the feasibility and effectiveness of the “THRIVE” app among breast cancer survivors undergoing hormonal therapy. Participants were recruited from Queen Mary Hospital in Hong Kong between December 2022 and June 2023. Eligible survivors had completed treatment within the last five years or had stable advanced disease on hormonal therapy. Participants monitored their exercise, medication adherence, and self-care via the app and a Fitbit activity tracker for 16 weeks. Primary outcomes included recruitment, dropout, adherence rates, and safety. Secondary outcomes, measured at baseline and week 16, included physical activity intensity, HRQoL, psychological stress, body composition, and app satisfaction. Results: A total of 50 participants, with a median age of 53 years, completed the study. The recruitment rate was 70.4% with no dropouts. The adherence rate, measured by completing exercises recommended in the mobile app at least three times per week, was 74%. No severe adverse events were reported. While physical activity intensity showed no significant changes from baseline to week 16 (p = 0.24), cognitive function (p = 0.021), future perspective (p = 0.044), arm symptoms (p = 0.042), depression (p = 0.01), and anxiety (p = 0.004) improved. All participants reported perfect medication compliance (100%). Satisfaction with the app was high. Conclusions: This mobile app-based rehabilitation program demonstrated good feasibility, with satisfactory recruitment, adherence, and safety, providing valuable insights into future definitive studies.
Plakin Expression in Serous Epithelial Ovarian Cancer Has the Potential to Impede Metastatic Spread and Epithelial–Mesenchymal Transition: A Comparative Expression Analysis of Immunohistochemical and In Silico Datasets
Authors: Wesley Tamsin , Escalona Ruth M. , Kannourakis George , Ahmed Nuzhat
Published: December 2024

Epithelial ovarian cancer is aggressive and causes high mortality among women worldwide. Members of the plakin family are essential to maintain cytoskeletal integrity and key cellular processes. In this study we characterised the expression of plakins, particularly plectin (PLEC), periplakin (PPL), envoplakin (EVPL), and EMT-related proteins by immunohistochemistry in n = 48 patients’ samples to evaluate a potential correlation of plakin expression with EMT as EOC progresses. These tissue plakin and EMT expression analyses were further evaluated by in vitro cell line expression and correlated with the expression of these molecules using publicly available datasets such as Cancer Genome Atlas (TCGA) and Clinical Proteome Tumour Analysis Consortium (CPTAC) datasets. We demonstrate that the expression of PPL and PLEC plakins is decreased in high-grade compared to low-grade EOCs with mixed EMT marker protein expression. This is supported by the correlation of high PPL and PLEC expression with an epithelial rather than mesenchymal phenotype. Our data suggest a partial loss of plakin expression as EOC tumours progress. This may impact the connections of plakins with membrane-bound receptors, which impede the downstream signalling required for the initiation of EMT as the tumours progress.
Frequency and Significance of Body Weight Loss During Immunochemotherapy in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Taoka Masataka , Ichihara Eiki , Yokoyama Toshihide , Inoue Koji , Tamura Tomoki , Sato Akiko , Oda Naohiro , Kano Hirohisa , Nakamura Kayo , Kawai Haruyuki , Inoue Masaaki , Ochi Nobuaki , Fujimoto Nobukazu , Ichikawa Hirohisa , Ando Chihiro , Oze Isao , Kiura Katsuyuki , Maeda Yoshinobu , Hotta Katsuyuki
Published: December 2024

Background: Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes. Methods: Using the clinical data of 370 patients with NSCLC who received a combination of ICI and chemotherapy at 13 institutions, this study investigated the frequency of body weight loss > 5% during treatment and determined the impact of body weight loss on patient outcomes. Results: Of the 370 included patients, 141 (38.1%) lost more than 5% of their body weight during ICI plus chemotherapy (WL group). The 2-month landmark analysis showed that patients who experienced body weight loss of >5% during treatment had worse overall survival (OS) and progression-free survival (PFS) than those who did not (OS 14.0 and 31.1 months in the WL non-WL groups, respectively, p < 0.001; PFS 6.8 and 10.9 months in the WL non-WL groups, respectively, p = 0.002). Furthermore, a negative impact of body weight loss on survival was observed even in those who had obesity (body mass index [BMI] ≥ 25.0) at the start of therapy (OS 12.8 and 25.4 months in the WL non-WL groups, respectively, p < 0.001; PFS 5.7 and 10.7 months in the WL non-WL groups, respectively, p = 0.038). Conclusions: In conclusion, weight loss of >5% during ICI plus chemotherapy negatively influenced patient outcomes. Further and broader studies should investigate the role of nutritional status, specifically weight change and nutritional support, in responsiveness to ICI plus chemotherapy.
Clinical Characteristics, Cytogenetic Risks, and Prognoses of Young Multiple Myeloma Patients in the Era of Novel Therapies
Authors: Borst Nathalie , Ihorst Gabriele , Wenger Sina , Räder Jan , Wäsch Ralph , Engelhardt Monika , Rassner Michael
Published: December 2024

Background/Objectives: In recent years, there have been significant advances in the understanding and treatment of multiple myeloma (MM). Despite this progress, there is still limited information on the disease in patients aged 50 or younger, including the impact of young age on disease characteristics, treatment, and outcome. Methods: In this retrospective study, we analyzed 68 newly diagnosed MM patients aged ≤ 50 years (y) who had undergone at least one peripheral blood stem cell transplantation (PBSCT). Additionally, we reviewed data published during 2008–2022 and compared these to our cohort. Results: Of note, the disease characteristics in our cohort were similar to those in older patients. However, the incidence of bone lesions was higher in younger patients (84%). Moreover, 33% had LC-only MM and 7% had high-risk (del17p, t(14;16), t(4;14)) cytogenetics. Advanced ISS and R-ISS II/III were observed in 57% and 78%, respectively. Therapy was intense, with 53% of patients undergoing ≥2 SCTs. Median follow-up was 75 months, median progression-free survival was 57 months, and median overall survival (OS) was not reached. The 10-year OS rate was 72%, with only 19% succumbing to the disease. Notably, no specific therapeutic regimen or risk factors for worse outcomes were identified through uni- or bivariate analyses, even in subgroup analyses of younger patients aged ≤ 40 y. Conclusions: Our, and prior, results of young (<50 y) and very young (<40 y) MM patients underscore the need for further comprehensive studies focused on this significantly affected cohort.
Long-Term Breast Cancer Risk in Hodgkin Lymphoma Survivors: Evaluating Background Parenchymal Enhancement and Radiotherapy-Induced Toxicity
Authors: Laddaga Filomena Emanuela , Telegrafo Michele , Garzillo Carmela , Fiorentino Alba , Sardaro Angela , Martinotti Stefano , Moschetta Marco , Gaudio Francesco
Published: December 2024

Hodgkin lymphoma (HL) treatment has dramatically improved, with high survival rates in early stages. However, long-term survivors face an increased risk of secondary cancers, particularly breast cancer (BC), which emerge as a leading cause of mortality decades after therapy. Background/Objectives: This study explores the risk of BC and the toxic effects of radiation therapy (RT) in long-term HL survivors compared to age-matched high-risk women, including BRCA1 and BRCA2 mutation carriers. A prospective study was conducted on 62 women who had undergone chemotherapy and involved-field RT for HL, with MRI used to assess breast tissue changes. This study’s primary endpoint was to analyze BC incidence in HL survivors, while secondary objectives focused on the analysis of background parenchymal enhancement (BPE) in irradiated areas. Results: The findings revealed a 5% incidence of BC in HL survivors, with 50% showing moderate or marked BPE, similar to that observed in high-risk BC controls. No significant differences in BPE distribution were found between the two groups. Conclusions: The study highlights the long-term risk of BC in HL survivors and suggests that advanced RT techniques and targeted therapies may help reduce the incidence of secondary tumors. Future research should focus on understanding the genetic and biological mechanisms behind treatment-induced cancers
Plasticity and Tumor Microenvironment in Pancreatic Cancer: Genetic, Metabolic, and Immune Perspectives
Authors: Hashimoto Ari , Hashimoto Shigeru
Published: December 2024

Cancer has long been believed to be a genetic disease caused by the accumulation of mutations in key genes involved in cellular processes. However, recent advances in sequencing technology have demonstrated that cells with cancer driver mutations are also present in normal tissues in response to aging, environmental damage, and chronic inflammation, suggesting that not only intrinsic factors within cancer cells, but also environmental alterations are important key factors in cancer development and progression. Pancreatic cancer tissue is mostly comprised of stromal cells and immune cells. The desmoplasmic microenvironment characteristic of pancreatic cancer is hypoxic and hypotrophic. Pancreatic cancer cells may adapt to this environment by rewiring their metabolism through epigenomic changes, enhancing intrinsic plasticity, creating an acidic and immunosuppressive tumor microenvironment, and inducing noncancerous cells to become tumor-promoting. In addition, pancreatic cancer has often metastasized to local and distant sites by the time of diagnosis, suggesting that a similar mechanism is operating from the precancerous stage. Here, we review key recent findings on how pancreatic cancers acquire plasticity, undergo metabolic reprogramming, and promote immunosuppressive microenvironment formation during their evolution. Furthermore, we present the following two signaling pathways that we have identified: one based on the small G-protein ARF6 driven by KRAS/TP53 mutations, and the other based on the RNA-binding protein Arid5a mediated by inflammatory cytokines, which promote both metabolic reprogramming and immune evasion in pancreatic cancer. Finally, the striking diversity among pancreatic cancers in the relative importance of mutational burden and the tumor microenvironment, their clinical relevance, and the potential for novel therapeutic strategies will be discussed.
Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications
Authors: Chouhan Surbhi , Kumar Anil , Muhammad Naoshad , Usmani Darksha , Khan Tabish H.
Published: December 2024

Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal cancers, marked by rapid progression, pronounced chemoresistance, and a complex network of genetic and epigenetic dysregulation. Within this challenging context, sirtuins, NAD+-dependent deacetylases, have emerged as pivotal modulators of key cellular processes that drive pancreatic cancer progression. Each sirtuin contributes uniquely to PDAC pathogenesis. SIRT1 influences apoptosis and chemoresistance through hypoxia, enhancing glycolytic metabolism and HIF-1α signaling, which sustain tumor survival against drugs like gemcitabine. SIRT2, conversely, disrupts cancer cell proliferation by inhibiting eIF5A, while SIRT3 exerts tumor-suppressive effects by regulating mitochondrial ROS and glycolysis. SIRT4 inhibits aerobic glycolysis, and its therapeutic upregulation has shown promise in curbing PDAC progression. Furthermore, SIRT5 modulates glutamine and glutathione metabolism, offering an avenue to disrupt PDAC’s metabolic dependencies. SIRT6 and SIRT7, through their roles in angiogenesis, EMT, and metastasis, represent additional targets, with modulators of SIRT6, such as JYQ-42, showing potential to reduce tumor invasiveness. This review aims to provide a comprehensive exploration of the emerging roles of sirtuins, a family of NAD+-dependent enzymes, as critical regulators within the oncogenic landscape of pancreatic cancer. This review meticulously explores the nuanced involvement of sirtuins in pancreatic cancer, elucidating their contributions to tumorigenesis and suppression through mechanisms such as metabolic reprogramming, the maintenance of genomic integrity and epigenetic modulation. Furthermore, it emphasizes the urgent need for the development of targeted therapeutic interventions aimed at precisely modulating sirtuin activity, thereby enhancing therapeutic efficacy and optimizing patient outcomes in the context of pancreatic malignancies.
Enhancing of Luminol-H2O2 Chemiluminescence System by Bimetallic Metal–Organic Frameworks with Mixed Ligands
Authors: Li Kuangjun , Li Yuting , Feng Rong , Wu Jing
Published: December 2024

Chemiluminescence (CL) is regarded as a better method for the detection of reactive oxygen species (ROS). However, the weak CL intensity prevents its further application. Many nanomaterials have been developed to enhance CL intensity, and mixed-ligand MOFs incorporating additional metals or organic ligands exhibit high efficiency in catalyzing. In this work, one kind of bimetallic mixed-ligand metal–organic framework (Ni-Co m-MOF) was synthesized using solvothermal methods. The material was morphologically characterized and demonstrated to be a dense and spherical flower-like structure. The addition of Ni-Co m-MOFs significantly enhanced the CL intensity of the luminol-H2O2 system by nearly 2,000-fold. The enhancement was found through further research as hydrogen peroxide was catalyzed to create hydroxyl radicals, etc., which reacted more easily with luminol. Herein, significant enhancement of the CL system by Ni-Co m-MOFs was identified, which provides ideas for improving the sensitivity and signal-to-noise ratio development of CL detectors.
Zn-Layered Double Hydroxide Intercalated with Graphene Oxide for Methylene Blue Photodegradation and Acid Red Adsorption Studies
Authors: Al-Ammari Rahmah H. , Al-Malwi Salwa D. , Abdel-Fadeel Mohamed A. , Bawaked Salem M. , Mostafa Mohamed Mokhtar M.
Published: December 2024

This study focuses on the synthesis of a novel layered double hydroxide and its application in two environmental remediation processes. Graphene oxide, a two-dimensional material, has potential applications in this field. However, its tendency to agglomerate restricts its usability. Our objective was to increase the morphology and performance of layered double hydroxide (LDH) by combining GO with hydrotalcite. The LDH/GO nanohybrids were utilized as photocatalysts for the degradation of methylene blue (MB) dye and were investigated as sorbents for acid red (A.R) dye in water. In order to achieve this objective, ZnAl-NO3 LDH was synthesized using the co-precipitation method, with a Zn:Al ratio of ~3. Subsequently, the LDH was intercalated with varying ratios of as-received graphene oxide. An array of analytical techniques, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) measurements, N2 physisorption, scanning electron microscopy–energy-dispersive X-ray analysis (SEM-EDX), and diffuse reflectance UV–vis spectra (DR UV-vis), were employed to examine the physicochemical properties of the synthesized LDH. These techniques confirmed that the obtained material is zinc-aluminum hydrotalcite intercalated with GO. The addition of graphene oxide (GO) to the layered double hydroxide (LDH) structure improved the performance of the hydrotalcite. As a result, the composite ZnAl-LDH-10 shows significant potential in the field of photocatalytic degradation of MB. Additionally, the incorporation of GO enhanced the absorption of light in the visible region of the spectra, leading to improved elimination of A.R compared to LDH without GO or other ratios of GO.
Identification of Novel Nexilin Splice Variants in Mouse and Human Tissues
Authors: Jung Paul , Fiedelak André , Dreeßen Celina , Huber Otmar , Reiche Juliane
Published: December 2024

There is no doubt that the proper development of the heart is important for its correct function, in addition, maturation processes of the heart are crucial as well. The actin-binding protein nexilin seems to take over central roles in the latter processes, as nexilin-deficient mice are phenotypically inconspicuous at birth but die within short time thereafter. Recently, it has been proposed that nexilin plays a role in the formation and function of transverse tubules (T-tubules), which are essential for excitation-contraction coupling in the hearts of mature animals. Although it has long been known that nexilin is subjected to alternative splicing, a molecular characterization of the respective isoforms is not yet available. Here, we describe novel nexilin splice variants and analyze their expression in tissues of mice and humans. Interestingly, nexilin isoforms segregate to myocyte- and epithelial-specific isoforms. Moreover, heart-specific isoforms of nexilin localize differently between atria and ventricles and are also expressed in the endothelial cells of blood vessels. Further, we narrowed down the critical exons in the actin-binding domains 1 and 2 (ABD1/2), and observed different self-interaction properties by recombinant protein interaction studies. Our results emphasize the diverse tissue and subcellular distribution of the individual nexilin isoforms and point to the importance of taking a closer look at the particular nexilin isoforms investigated.
Effects of TRPC1’s Lysines on Heteromeric TRPC5-TRPC1 Channel Function
Authors: Demaree Isaac S. , Kumar Sanjay , Tennessen Kayla , Hoang Quyen Q. , White Fletcher A. , Obukhov Alexander G.
Published: December 2024

Background: TRPC5 proteins form plasma membrane cation channels and are expressed in the nervous and cardiovascular systems. TRPC5 activation leads to cell depolarization and increases neuronal excitability, whereas a homologous TRPC1 inhibits TRPC5 function via heteromerization. The mechanism underlying the inhibitory effect of TRPC1 in TRPC5/TRPC1 heteromers remains unknown. Methods: We used electrophysiological techniques to examine the roles of subunit stoichiometry and positively charged luminal residues of TRPC1 on TRPC5/TRPC1 function. We also performed molecular dynamics simulations. Results: We found that increasing the relative amount of TRPC1 in TRPC5/TRPC1 heteromers reduced histamine-induced cation influx through the heteromeric channels. Consistently, histamine-induced cation influx was small in cells co-expressing TRPC5-TRPC1 concatemers and TRPC1, and large in cells co-expressing TRPC5-TRPC1 concatemers and TRPC5. Molecular dynamics simulations revealed that the TRPC1 protein has two positively charged lysine residues that are facing the heteromeric channel pore lumen. Substitution of these lysines with asparagines decreased TRPC1’s inhibitory effect on TRPC5/TRPC1 function, indicating that these lysines may regulate cation influx through TRPC5/TRPC1 heteromers. Additionally, we established that extracellular Mg2+ inhibits cation influx through TRPC5/TRPC1, contributing to channel regulation. Conclusions: We revealed that the inhibitory effect of TRPC1 on heteromeric TRPC5/TRPC1 function likely involves luminal lysines of TRPC1.
Cancer Cells in Sleep Mode: Wake Them to Eliminate or Keep Them Asleep Forever?
Authors: Liu Wenjie , Kovacs Antal H. , Hou Jinqiang
Published: December 2024

Cancer cell dormancy is a critical phase in cancer development, wherein cancer cells exist in a latent state marked by temporary but reversible growth arrest. This dormancy phase contributes to anticancer drug resistance, cancer recurrence, and metastasis. Treatment strategies aimed at cancer dormancy can be categorized into two contradictory approaches: inducing cancer cells into a dormant state or eliminating dormant cells. While the former seeks to establish permanent dormancy, the latter aims at eradicating this small population of dormant cells. In this review, we explore the current advancements in therapeutic methods targeting cancer cell dormancy and discuss future strategies. The concept of cancer cell dormancy has emerged as a promising avenue for novel cancer treatments, holding the potential for breakthroughs in the future.
Effect of Different Surface Treatments on the Performance of Earth Plasters
Authors: Santos Tânia , Faria Paulina , Sotomayor João , Silvestre José Dinis , Santos Silva António
Published: December 2024

Earth plasters have several advantages. Nevertheless, they are vulnerable when in contact with liquid water. For that reason, they have low durability when applied as an outdoor coating or in indoor areas with potential contact with water. In this study, the influence of six different surface treatments (traditional and innovative, based on raw materials and on waste) applied on a pre-mixed earth plaster, applied by a roller (r) or as a spray (s), was assessed. The treatments were: limewash (L), beeswax (BW), linseed oil (LO), graphene oxide dispersion (GO), water from paper immersion (WP) and water from gypsum plasterboard paper immersion (WPG). The application of L, BW and LO, despite the color change, improved the water resistance and the surface performance of the earth plaster (less than 80%–86%, 93%–98% and 97%–99% of mass loss from surface cohesion, from water erosion by dripping action and from dry abrasion, respectively, compared to the reference untreated plaster). However, the application of BW and LO had a negative effect on the hygroscopic capacity of the plaster (less than 28%–38% of water vapor adsorbed after 24 h and the MBV decreased 29%–50% compared to the reference plaster). Finally, the application of the remaining surface treatments did not significantly improve the characteristics of the plaster, having even worsened it in certain cases (more than 42%–149% of mass loss from water erosion, compared to the reference plaster). These results demonstrated that, among the treatments analyzed, the L, BW and LO treatments are the best options to apply on an earth plaster. In particular, the application of BW and LO are recommended in situations where it is necessary to improve water resistance and surface performance, and the hygroscopic capacity is not a conditioning characteristic, such as outdoor applications.
Integrating Blockchains with the IoT: A Review of Architectures and Marine Use Cases
Authors: Delladetsimas Andreas Polyvios , Papangelou Stamatis , Iosif Elias , Giaglis George
Published: December 2024

This review examines the integration of blockchain technology with the IoT in the Marine Internet of Things (MIoT) and Internet of Underwater Things (IoUT), with applications in areas such as oceanographic monitoring and naval defense. These environments present distinct challenges, including a limited communication bandwidth, energy constraints, and secure data handling needs. Enhancing BIoT systems requires a strategic selection of computing paradigms, such as edge and fog computing, and lightweight nodes to reduce latency and improve data processing in resource-limited settings. While a blockchain can improve data integrity and security, it can also introduce complexities, including interoperability issues, high energy consumption, standardization challenges, and costly transitions from legacy systems. The solutions reviewed here include lightweight consensus mechanisms to reduce computational demands. They also utilize established platforms, such as Ethereum and Hyperledger, or custom blockchains designed to meet marine-specific requirements. Additional approaches incorporate technologies such as fog and edge layers, software-defined networking (SDN), the InterPlanetary File System (IPFS) for decentralized storage, and AI-enhanced security measures, all adapted to each application’s needs. Future research will need to prioritize scalability, energy efficiency, and interoperability for effective BIoT deployment.
Impacts of Microplastics, Cadmium, and Their Mixtures on Biochemical Biomarkers in the Freshwater Bivalve Corbicula fluminea (Bivalvia, Corbiculidea)
Authors: Parra Susana , Santos Dércia , Luzio Ana , Cabecinha Edna , Saavedra Maria José , Gago Jesús , Varandas Simone , Monteiro Sandra Mariza
Published: December 2024

Microplastics (MPs) are a worldwide contaminant of significant environmental concern due to their persistence, widespread distribution, and toxic potential. These plastic particles are taken up by invertebrates such as bivalves. Previous studies have indicated that MPs can serve as carriers for other contaminants, such as heavy metals, thereby increasing their bioavailability to organisms, with unpredictable ecological consequences. Therefore, the main aim of this study was to evaluate the effects of exposure to MPs, cadmium (Cd), and their mixtures (Mix) in the gills, digestive gland, and gonad of the Asian clam, Corbicula fluminea, assessing the oxidative stress responses, LDH activity, and neurotoxicity over 7, 14, 21, and 30 days. The results show that exposure to MPs and their mixtures with the lowest Cd concentration led to the activation of the first line of antioxidant defenses, especially SOD and CAT, in the gills, digestive gland, and gonads. An increase in GST activity was also observed in the gonads. However, the response of GST activity in the gills and digestive gland was opposite that observed in the gonads. Furthermore, LDH activity exhibited contrasting responses, increasing in the digestive gland and decreasing in the gills and gonads. Exposure to MPs induced AChE activity, which contradicts previous findings. The results provide novel insights into the biological responses occurring in different target organs and shed light on the effects of MPs and their mixtures on C. fluminea.
Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis
Authors: González-García Karina , Santos-Álvarez Jovito Cesar , Velázquez-Enríquez Juan Manuel , Zertuche-Martínez Cecilia , Reyes-Jiménez Edilburga , Baltiérrez-Hoyos Rafael , Vásquez-Garzón Verónica Rocío
Published: December 2024

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, disabling disorder of unknown etiology, poor prognosis, and limited therapeutic options. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA) was shown to exert resolving effects in IPF, offering a promising alternative for treating this disease; however, the molecular mechanisms associated with this effect have not been explored. Objetive: We evaluated the potential antifibrotic mechanisms of 3′5-DMBA by network pharmacology (NP) and molecular docking (MD). Methods: 3′5-DMBA-associated targets were identified by screening in SwissTargetPrediction. IPF-associated targets were identified using lung tissue meta-analysis and public databases. Common targets were identified, and a protein–protein interaction (PPI) network was constructed; we ranked the proteins in the PPI network by topological analysis. MD validated the binding of 3′5-DMBA to the main therapeutic targets. Results: A total of 57 common targets were identified between 3′5-DMBA and IPF; caspase 8, 9, 3, and 7; myeloid leukemia-induced cell differentiation protein Mcl-1; and poly [ADP-ribose] polymerase 1 are primary targets regulating PPI networks. Functional analysis revealed that the common targets are involved in the pathological features of tissue fibrosis and primarily in the apoptotic process. MD revealed favorable interaction energies among the three main targets regulating PPI networks. Conclusions: NP results suggest that the antifibrotic effect of 3′5-DMBA is due to its regulation of the pathological features of IPF, mainly by modulating signaling pathways leading to apoptosis, suggesting its therapeutic potential to treat this disease.
Validity and Reliability of Wind Speed Calculated by Notio in Comparison with a Hot-Wire Anemometer
Authors: Ordiñana-Pérez Manuel , Mateo-March Manuel , Roldan Ainoa , Barranco-Gil David , Zabala Mikel , Blasco-Lafarga Cristina
Published: December 2024

Optimizing aerodynamic efficiency is crucial in competitive cycling, where aerodynamic resistance significantly limits performance. Devices like Notio have emerged to calculate the coefficient of drag area (CDA) considering dynamic pressure data calculated by an integrated Pitot-static tube. This study aimed to evaluate the validity and reliability of Pitot-static tube calculations through wind speed (WS) data against a hot-wire anemometer (HWA). Sixty recordings were made, lasting 30 s each, in a closed-circuit wind tunnel at four different WS (≈30 to ≈60 km/h), and at five different yaw angles (0° to 20°). Initially, Notio showed WS 6.44% higher than HWA. The calibration process recommended by the Notio manufacturer reduced the differences to a non-significant 0.76%. Comparison of the WS of Notio calibrated and HWA only showed significant differences in the WS group of ≈60 km/h. There were no significant differences in the comparison of yaw angles groups. The reliability of Notio was worse than that of the HWA. In conclusion, Notio calibrated at a speed close to its use allows for reliable and accurate calculation of WS over a wide range of yaw angles under controlled wind tunnel conditions without the presence of a cyclist and bicycle. However, due to the influence of WS on aerodynamic drag, small errors in WS could translate into considerable values of CDA for cycling performance.
Serum Tau Species in Progressive Supranuclear Palsy: A Pilot Study
Authors: Cristiani Costanza Maria , Scaramuzzino Luana , Parrotta Elvira Immacolata , Cuda Giovanni , Quattrone Aldo , Quattrone Andrea
Published: December 2024

Background/Objectives: Progressive Supranuclear Palsy (PSP) is a tauopathy showing a marked symptoms overlap with Parkinson’s Disease (PD). PSP pathology suggests that tau protein might represent a valuable biomarker to distinguish between the two diseases. Here, we investigated the presence and diagnostic value of six different tau species (total tau, 4R-tau isoform, tau aggregates, p-tau202, p-tau231 and p-tau396) in serum from 13 PSP and 13 PD patients and 12 healthy controls (HCs). Methods: ELISA commercial kits were employed to assess all the tau species except for t-tau, which was assessed by a single molecule array (SIMOA)-based commercial kit. Possible correlations between tau species and biological and clinical features of our cohorts were also evaluated. Results: Among the six tau species tested, only p-tau396 was detectable in serum. Concentration of p-tau396 was significantly higher in both PSP and PD groups compared to HC, but PSP and PD patients showed largely overlapping values. Moreover, serum concentration of p-tau396 strongly correlated with disease severity in PSP and not in PD. Conclusions: Overall, we identified serum p-tau396 as the most expressed phosphorylated tau species in serum and as a potential tool for assessing PSP clinical staging. Moreover, we demonstrated that other p-tau species may be present at too low concentrations in serum to be detected by ELISA, suggesting that future work should focus on other biological matrices.