bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-, Dual-, and Multi-Stimuli-Responsive Nanogels for Biomedical Applications
Authors: Kumar Naveen , Singh Sauraj , Sharma Piyush , Kumar Bijender , Kumar Anuj
Published: January 2024

In recent years, stimuli-responsive nanogels that can undergo suitable transitions under endogenous (e.g., pH, enzymes and reduction) or exogenous stimuli (e.g., temperature, light, and magnetic fields) for on-demand drug delivery, have received significant interest in biomedical fields, including drug delivery, tissue engineering, wound healing, and gene therapy due to their unique environment-sensitive properties. Furthermore, these nanogels have become very popular due to some of their special properties such as good hydrophilicity, high drug loading efficiency, flexibility, and excellent biocompatibility and biodegradability. In this article, the authors discuss current developments in the synthesis, properties, and biomedical applications of stimulus-responsive nanogels. In addition, the opportunities and challenges of nanogels for biomedical applications are also briefly predicted.
Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects
Authors: Desai Shivam U. , Srinivasan Sai Sadhananth , Kumbar Sangamesh Gurappa , Moss Isaac L.
Published: January 2024

Millions of people worldwide suffer from low back pain and disability associated with intervertebral disc (IVD) degeneration. IVD degeneration is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and the annulus fibrosus (AF) fissures form, which often results in intervertebral disc herniation or disc space collapse and related clinical symptoms. Currently available options for treating intervertebral disc degeneration are symptoms control with therapy modalities, and/or medication, and/or surgical resection of the IVD with or without spinal fusion. As such, there is an urgent clinical demand for more effective disease-modifying treatments for this ubiquitous disorder, rather than the current paradigms focused only on symptom control. Hydrogels are unique biomaterials that have a variety of distinctive qualities, including (but not limited to) biocompatibility, highly adjustable mechanical characteristics, and most importantly, the capacity to absorb and retain water in a manner like that of native human nucleus pulposus tissue. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. In this review, we summarize the latest findings and developments in the application of hydrogel technology for the repair and regeneration of intervertebral discs.
Comprehensive Insights and Advancements in Gel Catalysts for Electrochemical Energy Conversion
Authors: Bari Gazi A. K. M. Rafiqul , Jeong Jae-Ho
Published: January 2024

Continuous worldwide demands for more clean energy urge researchers and engineers to seek various energy applications, including electrocatalytic processes. Traditional energy-active materials, when combined with conducting materials and non-active polymeric materials, inadvertently leading to reduced interaction between their active and conducting components. This results in a drop in active catalytic sites, sluggish kinetics, and compromised mass and electronic transport properties. Furthermore, interaction between these materials could increase degradation products, impeding the efficiency of the catalytic process. Gels appears to be promising candidates to solve these challenges due to their larger specific surface area, three-dimensional hierarchical accommodative porous frameworks for active particles, self-catalytic properties, tunable electronic and electrochemical properties, as well as their inherent stability and cost-effectiveness. This review delves into the strategic design of catalytic gel materials, focusing on their potential in advanced energy conversion and storage technologies. Specific attention is given to catalytic gel material design strategies, exploring fundamental catalytic approaches for energy conversion processes such as the CO2 reduction reaction (CO2RR), oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and more. This comprehensive review not only addresses current developments but also outlines future research strategies and challenges in the field. Moreover, it provides guidance on overcoming these challenges, ensuring a holistic understanding of catalytic gel materials and their role in advancing energy conversion and storage technologies.
Spatiotemporal Expression Characterization of KRTAP6 Family Genes and Its Effect on Wool Traits
Authors: Sun Hongxian , He Zhaohua , Zhao Fangfang , Hu Jiang , Wang Jiqing , Liu Xiu , Zhao Zhidong , Li Mingna , Luo Yuzhu , Li Shaobin
Published: January 2024

Keratin-related proteins (KAPs) are structural components of wool fibers and are thought to play a key role in regulating the physical and mechanical properties of fibers. Among all KAP genes (KRTAPs), KRTAP6 gene family (KRTAP6-1, KRTAP6-2, KRTAP6-3, KRTAP6-4, and KRTAP6-5) is a very important member with high polymorphism and notable association with some wool traits. In this study, we used real-time fluorescence quantitative PCR (RT-qPCR) and in situ hybridization to investigate spatiotemporal expression of KRTAP6s. The results revealed that KRTAP6 family genes were significantly expressed during anagen compared to other stages (p < 0.05). And it was found the five genes were expressed predominantly in the dermal papillae, inner and outer root sheaths, and showed a distinct spatiotemporal expression pattern. Also, it was found that KRTAP6-1 and KRTAP6-5 mRNA expression was negatively correlated with wool mean fiber diameter (MFD) and mean staple strength (MSS) (p < 0.05). In summary, the KRTAP6 family genes share a similar spatiotemporal expression pattern. And KRTAP6-1 and KRTAP6-5 may regulate the MFD and MSS of Gansu Alpine fine-wool sheep wool by changing the expression.
Polyploid Cancer Cell Models in Drosophila
Authors: Wang Yuqing , Tamori Yoichiro
Published: January 2024

Cells with an abnormal number of chromosomes have been found in more than 90% of solid tumors, and among these, polyploidy accounts for about 40%. Polyploidized cells most often have duplicate centrosomes as well as genomes, and thus their mitosis tends to promote merotelic spindle attachments and chromosomal instability, which produces a variety of aneuploid daughter cells. Polyploid cells have been found highly resistant to various stress and anticancer therapies, such as radiation and mitogenic inhibitors. In other words, common cancer therapies kill proliferative diploid cells, which make up the majority of cancer tissues, while polyploid cells, which lurk in smaller numbers, may survive. The surviving polyploid cells, prompted by acute environmental changes, begin to mitose with chromosomal instability, leading to an explosion of genetic heterogeneity and a concomitant cell competition and adaptive evolution. The result is a recurrence of the cancer during which the tenacious cells that survived treatment express malignant traits. Although the presence of polyploid cells in cancer tissues has been observed for more than 150 years, the function and exact role of these cells in cancer progression has remained elusive. For this reason, there is currently no effective therapeutic treatment directed against polyploid cells. This is due in part to the lack of suitable experimental models, but recently several models have become available to study polyploid cells in vivo. We propose that the experimental models in Drosophila, for which genetic techniques are highly developed, could be very useful in deciphering mechanisms of polyploidy and its role in cancer progression.
Tooth Wear in Older Adults: A Review of Clinical Studies
Authors: Chan Alice Kit Ying , Tsang Yiu Cheung , Lai Eddie Hsiang-Hua , Chu Chun Hung
Published: January 2024

Introduction: Tooth wear is a prevalent dental condition among older adults, leading to pain and adversely affecting aesthetics, functionality, and their overall quality of life. This review aims to update the information on tooth wear in older adults from the past five years and to provide guidance on the clinical management of tooth wear in older adults. Methods: A literature search was conducted in three electronic databases, Scopus, Pubmed, and Embase, for English publications from January 2019 to December 2023 on clinical studies with participants aged 65 or above on tooth wear. A total of 307 articles were retrieved and 14 articles were finally included as references for this study. Results: This review highlights the common causes of tooth wear and various risk factors, such as medical conditions, hyposalivation, dietary habits, oral hygiene practices, parafunctional habits, and occlusal factors, associated with tooth wear. It is crucial for oral health care professionals to diagnose and manage tooth wear at an early stage through a risk assessment and a clinical examination to avoid complex restorative procedures. Tooth wear management should prioritize prevention, aiming to control etiological and risk factors while employing non-restorative treatments. Restorative intervention, if indicated, should be simple, minimally invasive, and cost-effective. Tooth wear progression should be monitored regularly to determine if a further intervention is needed. Conclusion: Since the clinical studies on tooth wear in older adults over the past five years are limited and mainly cross-sectional, more interventional clinical studies are warranted to provide more clinical guidance on tooth wear management in older adults.
Impact of Long-Term Care Service Quality on User Cooperation/Participation: Mediating Effect of Self-Determination
Authors: Cho Hanra , Kim Junsu
Published: January 2024

The purpose of this study is to determine whether home care service quality affects users’ voluntary cooperation/participation through self-determination. For this purpose, survey data from 358 long-term care service users in Korea were analyzed by applying a structural equation model. Data collection was conducted from February to March 2019. Data collection was conducted in February–March 2019. The results showed that home care quality did not directly affect users’ voluntary cooperation/participation in the service delivery process, and self-determination fully mediated the relationship between quality and cooperation/participation. Based on these results, the importance of providing appropriate information, reflecting users’ voices, and the attitude and role of experts was emphasized in order to promote user participation/cooperation through self-determination.
Advance Directives in Portugal: A Qualitative Survey
Authors: Macedo João Carlos , Macedo Ermelinda , Nunes Rui
Published: January 2024

(1) Background: Advance directives (ADs) in Portugal have been legalized since 2012. What has been observed over time, from the few studies carried out, is that despite the positive attitudes in the population, there is a low level of adherence to ADs. To try to understand the reasons for these data, the current study aimed to explore and describe the experiences of the Portuguese population regarding AD. (2) Methods: For this exploratory and descriptive qualitative study, the researchers conducted open (unstructured) interviews with a convenience sample aged over 18 years until data saturation was achieved. (3) Results: A total of fifteen interviews were conducted—eight with women and seven with men. The following four categories emerged from the content analysis of the interviews: (1) AD literacy, (2) AD relevance, (3) AD attitudes, and (4) conditionalities for compiling the ADs. (4) Conclusions: The study pointed out the good receptivity of the participants to the ADs; however, literacy on this subject was low, and identifying the conditionalities in the development of ADs could contribute to improvements in implementation in the population. The data from this study suggest the need to implement measures to increase the literacy of the Portuguese population on ADs and review the legal framework for improving the accessibility of the citizen population. There is also a need to continue researching and obtain more evidence about the ways in which the Portuguese population perceives ADs; thus, in this way, a society can better respond to its citizens’ right to freely exercise their prospective autonomy at the end of their lives.
Assessment of Preferences in Taking Painkillers among Students of Medicine, Dentistry, and Pharmacy: A Pilot Study
Authors: Samorek Wiktoria , Przylepa Joanna , Urbaniak Joanna , Rogala Aleksandra , Pilimon Anna , Błochowiak Krzysztof , Błochowiak Katarzyna
Published: January 2024

Students of pharmacy, medicine, and dentistry are important for shaping drug policy. The aim of this study is to assess and compare students preferences in taking painkillers. The study group consists of 382 students of pharmacy (28.8%), medicine (40.0%), and dentistry (30.1%). An anonymous questionnaire consisting of 17 questions was prepared using the Google Forms platform and distributed through social media. Ibuprofen was the most frequently preferred, regardless of the study major (57.8%). Pharmacy students expressed the least concern about the possible side effects of analgesics (17.5%). The fast onset of painkillers was more important for dental students (59.1%) and pharmacy students (44.7%), compared to medical students (39.22%). Medicine and pharmacy students indicated their studies to be their main source of information about painkillers compared to dentistry students (p = 0.001). There are no differences in pain severity regarding which analgesics are used among student groups (p = 0.547). Dental students experienced odontogenic pain less frequently (57.3%) than medical (79.7%) and pharmacy students (79.8%), (p = 0.000). Ketoprofen was the most frequently chosen prescription painkiller for odontogenic pain in all groups (49.4%). Gastrointestinal complaints were the most often reported side effects, regardless of the study major (87.1%). Choice of studies, gender, and year of study were the most important determinants of the choice of painkillers.
A STEPwise Approach for Oral Hygiene Behavior of Schoolchildren in Romania
Authors: Perpelea Anca-Cristina , Sfeatcu Ruxandra , Tănase Mihaela , Meleșcanu Imre Marina , Ripszky Totan Alexandra , Cernega Ana , Funieru Cristian , Pițuru Silviu-Mirel
Published: January 2024

This research analyzes the dental hygiene habits of schoolchildren from parents’ perspectives, using the STEPS approach recommended by the World Health Organization. The key points of oral health care in children include the role of the family in encouraging and maintaining proper oral hygiene practices. This study aimed to assess the oral hygiene practices of schoolchildren with on-site dentists in Romania. Additionally, it sought to establish correlations between these behaviors and the educational levels of the adults with whom they live with. The participants were selected from the zero grade to the eighth grade, totaling 3843students. Statistical analysis involved the application of Fisher’s Exact Test and Z-tests with Bonferroni correction. Multinominal and binominal logistic regression models were employed to predict the impact of parents’ education on children’s oral health status and behavior. The oral health status of children evaluated by parents as poor was more frequent in children whose parents had a primary or gymnasium education (p < 0.001). Female adults with a university education evaluated the gum health of their children as very good to a much greater extent (41.7%, p < 0.001). Regarding the use of auxiliary means, the majority of parents with a university education mentioned that their children use dental floss (26.4% females/27.4% males) (p < 0.001), compared to those with primary education, where the percentage was only (1.2% males/3.5% females) (p < 0.001). The results of this study highlight that the education level of the adults with whom the children live with influences the perception of the teeth and gums health status, the frequency of oral hygiene, the use of fluoride toothpaste, and auxiliary brushing aids.
Ligament Injuries in Professional Male Handball Players: A 6-Year Longitudinal Study
Authors: Martínez-Aranda Luis Manuel , García-Esteban Sergio , Sanz-Matesanz Manuel , Raya-González Javier
Published: January 2024

Handball is a sport that involves high-intensity actions throughout the game, such as sprints, jumps, landings, and high-speed, repeated throws. This, along with competitive and tactical factors, congested schedules, and the need to maintain a high level of performance throughout the season, contributes to a high injury rate. This study aimed to analyse ligament injuries in a professional handball team over six consecutive seasons. A total of 68 elite male Spanish handball players participated, with 54 time-loss injuries (i.e., injuries involving at least one day of absence) observed during this study period. Ligament injury information was recorded following the International Olympic Committee consensus statement. The overall incidence was 0.89 ligament injuries per 1000 h of exposure. Additionally, a higher incidence and burden of ligament injuries was observed during match-play compared to training. Most ligament injuries were classified as minor or moderate (i.e., 79.63% of the total), and 46.29% were reinjuries. A significantly higher incidence of ligament injuries was suffered in the lower limbs compared to the upper limbs (0.81 vs. 0.08 ligament injuries per 1000 h; p < 0.001). Specifically, the highest incidence was observed in the anterior talofibular ligament of the ankle (0.57 injuries per 1000 h of exposure), while the greatest burden was related to the anterior cruciate ligament (24.08 absence days per 1000 h of exposure). This study provides an overview of ligament injuries among professional handball players, highlighting the need to implement strategies with positive effects during competition (e.g., specific activation strategies or training programmes based on strength and balance) and to reduce injury recurrences.
How Does Trauma Make You Sick? The Role of Attachment in Explaining Somatic Symptoms of Survivors of Childhood Trauma
Authors: Greenman Paul Samuel , Renzi Alessia , Monaco Silvia , Luciani Francesca , Di Trani Michela
Published: January 2024

Exposure to traumatic events during childhood is common, and the consequences for physical and mental health can be severe. Adverse childhood experiences (ACEs) such as physical abuse, sexual abuse, emotional abuse, and neglect appear to contribute to the onset and severity of a variety of somatic inflictions, including obesity, diabetes, cancer, and heart disease. The aim of this scoping review was to try to gain insight into how this might occur. Given the evidence of indirect (i.e., through unhealthy behaviours such as excessive drinking or poor eating habits) and direct (i.e., through its impact on the endocrine, immune, and cardiovascular systems as well as on the brain) effects of attachment on health, we examined the possibility that insecure attachment might contribute to the development of somatic symptoms in adult survivors of childhood trauma. Eleven studies met our inclusion criteria. Findings from this review suggest that insecure and disorganized attachment orientations are related to DNA damage, metabolic syndrome and obesity, physical pain, functional neurological disorder, and somatization in adults exposed to childhood trauma. We discuss the implications of this for the conceptualization and treatment of trauma and stress disorders.
Daily Moderate-to-Vigorous Activity of Native Hawaiians and Pacific Islanders and Seven Asian Subgroups by Types of Activities, American Time Use Survey, 2010–2019
Authors: Davis James , Taira Deborah A. , Lim Eunjung , Chen John
Published: January 2024

The study used the American Time Use Survey data from 2010 to 2019 to compare the daily moderate-to-vigorous activity of Native Hawaiians and Pacific Islanders (NHPI) and seven Asian ethnic subgroups. Adults aged 24 years and older were included. The study analyzed activities from sports and recreation, household activities, and all activities carried out during the day. Outcomes were determined by the completion of 30 min or more of moderate-to-vigorous activity and the type of activity carried out in the day. Significant ethnic differences were observed for sports and recreation but not for household activities and not for all activities carried out during the day. Of the ethnic populations, NHPI were the least active, and Asian Indians and Chinese were the most active. A majority achieved 30 min or more of moderate-to-vigorous activity during the day from all their activities. Physical activity from household activities exceeded physical activity from sports and recreation. The most physically active group was adults over the age of 65 years, perhaps reflecting more time to exercise or greater concerns about their health. For sports and recreation, exercising with someone doubled the minutes of moderate-to-vigorous activity. The results emphasize the importance of activities performed around the household in addition to sports and recreation and the benefit of exercising with someone. Ethnic populations may be receptive to interventions that emphasize activities they are performing in their daily lives.
Development and Evaluation of Nursing Clinical Practice Education Using M-Learning
Authors: Kim Sungeun , Im Mihae
Published: January 2024

This study aims to develop and evaluate the effectiveness of nursing practice education using mobile learning or m-learning for nursing students. A nonequivalent control group post-test design was used. Overall, 42 nursing students participated in the study. A three-week nursing practice education program was developed using the Analysis, Design, Development, Implementation, and Evaluation (ADDIE) model. The course was implemented on the basis of Gagne’s nine instructional situations. The findings demonstrated improvements in clinical competency (t = 7.44, p < 0.001) and problem solving (t = 2.29, p = 0.028). Accordingly, the study recommends introducing m-learning in nursing practice education using tablet PCs, as part of a newer nursing practicum training strategy that takes into account the factors identified in this study. It is also suggested that a continuous m-learning approach and development plan for nursing students be prepared to achieve technically advanced nursing practice education.
The Impact of Social Determinants of Health on Australian Women’s Capacity to Access and Understand Health Information: A Secondary Analysis of the 2022 National Women’s Health Survey
Authors: Davison Neve , Stanzel Karin , Hammarberg Karin
Published: January 2024

The ability to access, understand, judge, and use health information is crucial for making informed decisions about health and optimal health outcomes. This secondary data analysis investigated associations between social determinants of health and Australian women’s ability to access and understand health information using data from 10,652 women who responded to the 2022 National Women’s Health Survey. A score (0–5) was created based on five questions assessing the participants’ ability to access and understand health information, which was dichotomised into low (≤3) and high (≥4) scores. The data were analyzed using descriptive statistics, univariate comparisons, and multivariable binary logistic regression. Almost a quarter of the women had a low score. Non-native English speakers were approximately four times more likely to have low health literacy than native English speakers. Additionally, women without tertiary education, financially disadvantaged women, and First Nations women were almost twice as likely to have lower health literacy than other women. These findings suggest that social determinants of health decrease the capacity to access and understand health information. To reduce health inequalities, healthcare systems and health professionals must consider the factors that reduce women’s capacity to access and understand health information and address the health information needs of socioeconomically disadvantaged women.
Comparative Analysis of TPR Gene Family in Cucurbitaceae and Expression Profiling under Abiotic Stress in Cucumis melo L.
Authors: Wang Shuoshuo , Meng Yuchen , Ding Fei , Yang Kuo , Wang Chuang , Zhang Hengjia , Jin Han
Published: January 2024

Tetratricopeptide repeat (TPR) proteins play numerous roles in plant growth and development by mediating protein–protein interactions in biological systems by binding to peptide ligands. Although genome-wide analyses of the TPR gene family in other species have been performed, its evolution and function in Cucurbitaceae remain unclear. In this study, 144 TPR genes from 11 genomes of eight Cucurbitaceae species with a heterogeneous distribution on the chromosomes were characterized. Based on the homology between Cucurbitaceae and Arabidopsis, the TPR genes were divided into four groups, and the evolutionary relationships of the Benincaceae and Cucurbitaceae tribes were also represented in a phylogenetic tree. Using the ‘DHL92′ genome as a reference, an integrated chromosome map was obtained containing 34 loci, 4 of which were common to the Cucurbitaceae. Cis-regulatory element analysis showed that these elements are essential for melon development and responses to light, phytohormones, and various stresses. CmTPR tissue- and development-specific expression analysis revealed differential expression patterns under normal growth conditions. Furthermore, the CmTPR genes responded to various abiotic stressors. Overall, this study offers insights into the evolutionary history of the TPR gene family in Cucurbitaceae and provides valuable information for elucidating the potential role of CmTPR genes during development and under different stresses in melon.
Mediator Subunit RhMED15a Regulates Drought Tolerance in Rose
Authors: Shang Xiaoman , Xie Nanxin , Li Yalin , Zhao Zixin , Luo Ping , Cui Yongyi , Rao Xianlong , Chen Wen
Published: January 2024

Mediator is a multiprotein complex integral to the transcription machinery, mediated by RNA polymerase II. Some Mediator subunits have been found to have critical functions in plants’ responses to abiotic stresses. However, the role of plant Mediator subunits in drought responses remains largely enigmatic. Here, we identified a Mediator subunit, RhMED15a, in roses (Rosa hybrida). Its expression was greatly and swiftly induced by dehydration treatment in the root. The promoter sequence of RhMED15a contains cis-acting elements that respond to abscisic acid (ABA) and methyl jasmonate (MeJA). In addition, the expression of RhMED15a was significantly up-regulated with ABA treatment and inversely down-regulated with MeJA treatment. Silencing RhMED15a using virus-induced gene silencing (VIGS) in roses significantly reduced drought tolerance in rose plants. This resulted in a significant increase in the malondialdehyde (MDA) level and a decreased survival rate in comparison to TRV controls. Moreover, we found that the expression of five drought-related genes, including dehydration responsive element binding factor 1B (DREB1B), responsive to desiccation stress 29A (RD29A), responsive to desiccation stress 29B (RD29B), early response to dehydration 14 (ERD14), and 9-cis-epoxycarotenoid dioxygenase 1 (NCED1), was considerably suppressed in RhMED15a-silenced plants during drought stress. Taken together, our results present that the Mediator tail module subunit RhMED15a serves as an enhancer of drought tolerance in rose, probably through the modulation of the expression of some drought-related genes.
Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran
Authors: Zhang Kui , Hu Xin , Su Jingjing , Li Dong , Thakur Abhimanyu , Gujar Vikramsingh , Cui Hongjuan
Published: January 2024

Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3′-Geranyl-3-prenyl-5,7,2′,4′-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate significant anti-cancer properties against various gastrointestinal cancers, including colon, pancreatic, and gastric cancers. The anti-cancer mechanism of these chemical components was explored in gastric cancer cells, revealing that they inhibit cell cycle and DNA replication-related gene expression, leading to the effective suppression of tumor cell growth. Additionally, they induced unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, potentially resulting in DNA damage, autophagy, and cell death. Moracin P, an active monomer characterized as a 2-arylbenzofuran, was found to induce ER stress and promote apoptosis in gastric cancer cells, confirming its potential to inhibit tumor cell growth in vitro and in vivo. These findings highlight the therapeutic potential of Morus alba L. monomers in gastrointestinal cancers, especially focusing on Moracin P as a potent inducer of ER stress and apoptosis.
Metal-Based Nanoparticles for Cardiovascular Diseases
Authors: Scafa Udriște Alexandru , Burdușel Alexandra , Niculescu Adelina-Gabriela , Rădulescu Marius , Grumezescu Alexandru
Published: January 2024

Globally, cardiovascular diseases (CVDs) are the leading cause of death and disability. While there are many therapeutic alternatives available for the management of CVDs, the majority of classic therapeutic strategies were found to be ineffective at stopping or significantly/additionally slowing the progression of these diseases, or they had unfavorable side effects. Numerous metal-based nanoparticles (NPs) have been created to overcome these limitations, demonstrating encouraging possibilities in the treatment of CVDs due to advancements in nanotechnology. Metallic nanomaterials, including gold, silver, and iron, come in various shapes, sizes, and geometries. Metallic NPs are generally smaller and have more specialized physical, chemical, and biological properties. Metal-based NPs may come in various forms, such as nanoshells, nanorods, and nanospheres, and they have been studied the most. Massive potential applications for these metal nanomaterial structures include supporting molecular imaging, serving as drug delivery systems, enhancing radiation-based anticancer therapy, supplying photothermal transforming effects for thermal therapy, and being compounds with bactericidal, fungicidal, and antiviral qualities that may be helpful for cardiovascular diseases. In this context, the present paper aims to review the applications of relevant metal and metal oxide nanoparticles in CVDs, creating an up-to-date framework that aids researchers in developing more efficient treatment strategies.
General Analysis of Heat Shock Factors in the Cymbidium ensifolium Genome Provided Insights into Their Evolution and Special Roles with Response to Temperature
Authors: Zheng Ruiyue , Chen Jiemin , Peng Yukun , Zhu Xuanyi , Niu Muqi , Chen Xiuming , Xie Kai , Huang Ruiliu , Zhan Suying , Su Qiuli , Shen Mingli , Peng Donghui , Ahmad Sagheer , Zhao Kai , Liu Zhong-Jian , Zhou Yuzhen
Published: January 2024

Heat shock factors (HSFs) are the key regulators of heat stress responses and play pivotal roles in tissue development and the temperature-induced regulation of secondary metabolites. In order to elucidate the roles of HSFs in Cymbidium ensifolium, we conducted a genome-wide identification of CeHSF genes and predicted their functions based on their structural features and splicing patterns. Our results revealed 22 HSF family members, with each gene containing more than one intron. According to phylogenetic analysis, 59.1% of HSFs were grouped into the A subfamily, while subfamily HSFC contained only two HSFs. And the HSF gene families were differentiated evolutionarily between plant species. Two tandem repeats were found on Chr02, and two segmental duplication pairs were observed on Chr12, Chr17, and Chr19; this provided evidence for whole-genome duplication (WGD) events in C. ensifolium. The core region of the promoter in most CeHSF genes contained cis-acting elements such as AP2/ERF and bHLH, which were associated with plant growth, development, and stress responses. Except for CeHSF11, 14, and 19, each of the remaining CeHSFs contained at least one miRNA binding site. This included binding sites for miR156, miR393, and miR319, which were responsive to temperature and other stresses. The HSF gene family exhibited significant tissue specificity in both vegetative and floral organs of C. ensifolium. CeHSF13 and CeHSF15 showed relatively significant expression in flowers compared to other genes. During flower development, CeHSF15 exhibited markedly elevated expression in the early stages of flower opening, implicating critical regulatory functions in organ development and floral scent-related regulations. During the poikilothermic treatment, CeHSF14 was upregulated over 200-fold after 6 h of heat treatment. CeHSF13 and CeHSF14 showed the highest expression at 6 h of low temperature, while the expression of CeHSF15 and CeHSF21 continuously decreased at a low temperature. The expression patterns of CeHSFs further confirmed their role in responding to temperature stress. Our study may help reveal the important roles of HSFs in plant development and metabolic regulation and show insight for the further molecular design breeding of C. ensifolium.
Inherited Retinal Degeneration Caused by Dehydrodolichyl Diphosphate Synthase Mutation–Effect of an ALG6 Modifier Variant
Authors: Monson Elisha , Cideciyan Artur V. , Roman Alejandro J. , Sumaroka Alexander , Swider Malgorzata , Wu Vivian , Viarbitskaya Iryna , Jacobson Samuel G. , Fliesler Steven J. , Pittler Steven J.
Published: January 2024

Modern advances in disease genetics have uncovered numerous modifier genes that play a role in the severity of disease expression. One such class of genetic conditions is known as inherited retinal degenerations (IRDs), a collection of retinal degenerative disorders caused by mutations in over 300 genes. A single missense mutation (K42E) in the gene encoding the enzyme dehydrodolichyl diphosphate synthase (DHDDS), which is required for protein N-glycosylation in all cells and tissues, causes DHDDS-IRD (retinitis pigmentosa type 59 (RP59; OMIM #613861)). Apart from a retinal phenotype, however, DHDDS-IRD is surprisingly non-syndromic (i.e., without any systemic manifestations). To explore disease pathology, we selected five glycosylation-related genes for analysis that are suggested to have disease modifier variants. These genes encode glycosyltransferases (ALG6, ALG8), an ER resident protein (DDOST), a high-mannose oligosaccharyl transferase (MPDU1), and a protein N-glycosylation regulatory protein (TNKS). DNA samples from 11 confirmed DHDDS (K42E)-IRD patients were sequenced at the site of each candidate genetic modifier. Quantitative measures of retinal structure and function were performed across five decades of life by evaluating foveal photoreceptor thickness, visual acuity, foveal sensitivity, macular and extramacular rod sensitivity, and kinetic visual field extent. The ALG6 variant, (F304S), was correlated with greater macular cone disease severity and less peripheral rod disease severity. Thus, modifier gene polymorphisms may account for a significant portion of phenotypic variation observed in human genetic disease. However, the consequences of the polymorphisms may be counterintuitively complex in terms of rod and cone populations affected in different regions of the retina.
Free Energy Barriers for Passive Drug Transport through the Mycobacterium tuberculosis Outer Membrane: A Molecular Dynamics Study
Authors: Steshin Ilya S. , Vasyankin Alexander V. , Shirokova Ekaterina A. , Rozhkov Alexey V. , Livshits Grigory D. , Panteleev Sergey V. , Radchenko Eugene V. , Ignatov Stanislav K. , Palyulin Vladimir A.
Published: January 2024

The emergence of multi-drug-resistant tuberculosis strains poses a significant challenge to modern medicine. The development of new antituberculosis drugs is hindered by the low permeability of many active compounds through the extremely strong bacterial cell wall of mycobacteria. In order to estimate the ability of potential antimycobacterial agents to diffuse through the outer mycolate membrane, the free energy profiles, the corresponding activation barriers, and possible permeability modes of passive transport for a series of known antibiotics, modern antituberculosis drugs, and prospective active drug-like molecules were determined using molecular dynamics simulations with the all-atom force field and potential of mean-force calculations. The membranes of different chemical and conformational compositions, density, thickness, and ionization states were examined. The typical activation barriers for the low-mass molecules penetrating through the most realistic membrane model were 6–13 kcal/mol for isoniazid, pyrazinamide, and etambutol, and 19 and 25 kcal/mol for bedaquilin and rifampicin. The barriers for the ionized molecules are usually in the range of 37–63 kcal/mol. The linear regression models were derived from the obtained data, allowing one to estimate the permeability barriers from simple physicochemical parameters of the diffusing molecules, notably lipophilicity and molecular polarizability.
Peak Scores Significantly Depend on the Relationships between Contextual Signals in ChIP-Seq Peaks
Authors: Vishnevsky Oleg V. , Bocharnikov Andrey V. , Ignatieva Elena V.
Published: January 2024

Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) is a central genome-wide method for in vivo analyses of DNA-protein interactions in various cellular conditions. Numerous studies have demonstrated the complex contextual organization of ChIP-seq peak sequences and the presence of binding sites for transcription factors in them. We assessed the dependence of the ChIP-seq peak score on the presence of different contextual signals in the peak sequences by analyzing these sequences from several ChIP-seq experiments using our fully enumerative GPU-based de novo motif discovery method, Argo_CUDA. Analysis revealed sets of significant IUPAC motifs corresponding to the binding sites of the target and partner transcription factors. For these ChIP-seq experiments, multiple regression models were constructed, demonstrating a significant dependence of the peak scores on the presence in the peak sequences of not only highly significant target motifs but also less significant motifs corresponding to the binding sites of the partner transcription factors. A significant correlation was shown between the presence of the target motifs FOXA2 and the partner motifs HNF4G, which found experimental confirmation in the scientific literature, demonstrating the important contribution of the partner transcription factors to the binding of the target transcription factor to DNA and, consequently, their important contribution to the peak score.
Epigenetic Dysregulation in the Pathogenesis of Systemic Lupus Erythematosus
Authors: Araki Yasuto , Mimura Toshihide
Published: January 2024

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which immune disorders lead to autoreactive immune responses and cause inflammation and tissue damage. Genetic and environmental factors have been shown to trigger SLE. Recent evidence has also demonstrated that epigenetic factors contribute to the pathogenesis of SLE. Epigenetic mechanisms play an important role in modulating the chromatin structure and regulating gene transcription. Dysregulated epigenetic changes can alter gene expression and impair cellular functions in immune cells, resulting in autoreactive immune responses. Therefore, elucidating the dysregulated epigenetic mechanisms in the immune system is crucial for understanding the pathogenesis of SLE. In this paper, we review the important roles of epigenetic disorders in the pathogenesis of SLE.
The Concept behind the Suitability of Menstrual Blood-Derived Stem Cells for the Management of Vaginal Atrophy among BRCA Mutation Carriers after RRSO
Authors: Cordeiro Mariana Robalo , Laranjeiro Bárbara , Figueiredo-Dias Margarida
Published: January 2024

Risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended for breast cancer gene 1 (BRCA1) and 2 (BRCA2) mutation carriers. A major consequence of RRSO is surgical menopause associated with severe menopausal symptoms, mostly genitourinary complaints. Due to the inherent breast cancer risk, estrogen-based therapies are generally avoided in these patients. So far, the non-hormonal approaches available are not efficient to successfully treat the disabling vaginal atrophy-related symptoms. In regenerative medicine, mesenchymal stem cells (MSC) are the most frequently used cell type due to their remarkable and regenerative characteristics. Therapies based on MSC have revealed positive outcomes regarding symptoms and signs associated with vaginal atrophy by promoting angiogenesis, vaginal restoration, and the proliferation of vaginal mucosa cells. Menstrual blood-derived stem cells (MenSC) are a novel source of MSC, with promising therapeutic potential directly linked to their high proliferative rates; low immunogenicity; non-invasive, easy, and periodic acquisition; and almost no associated ethical issues. In this review, we update the current knowledge and research regarding the potential value of previously preserved MenSC in the therapy of vaginal atrophy among BRCA mutation carriers subjected to RRSO.
Comprehensive Investigation of Cu2+ Adsorption from Wastewater Using Olive-Waste-Derived Adsorbents: Experimental and Molecular Insights
Authors: Elboughdiri Noureddine , Ferkous Hana , Rouibah Karima , Boublia Abir , Delimi Amel , Yadav Krishna Kumar , Erto Alessandro , Ghernaout Djamel , Salih Alsamani A. M. , Benaissa Mhamed , Benguerba Yacine
Published: January 2024

This study investigates the efficacy of adsorbents from locally sourced olive waste—encompassing olive skins, leaves, and pits, recovered from the initial centrifugation of olives (OWP)—and a composite with sodium alginate (OWPSA) for the removal of Cu2+ ions from synthetic wastewater. Experimental analyses conducted at room temperature, with an initial Cu2+ concentration of 50 mg/L and a solid/liquid ratio of 1 g/L, showed that the removal efficiencies were approximately 79.54% and 94.54% for OWP and OWPSA, respectively, highlighting the positive impact of alginate on adsorption capacity. Utilizing statistical physics isotherm models, particularly the single-layer model coupled to real gas (SLMRG), allowed us to robustly fit the experimental data, providing insights into the adsorption mechanisms. Thermodynamic parameters affirmed the spontaneity and endothermic nature of the processes. Adsorption kinetics were interpreted effectively using the pseudo-second-order (PSO) model. Molecular modeling investigations, including the conductor-like screening model for real solvents (COSMO-RS), density functional theory (DFT), and atom-in-molecule (AIM) analysis, unveiled intricate molecular interactions among the adsorbent components—cellulose, hemicellulose, lignin, and alginate—and the pollutant Cu2+, confirming their physically interactive nature. These findings emphasize the synergistic application of experimental and theoretical approaches, providing a comprehensive understanding of copper adsorption dynamics at the molecular level. This methodology holds promise for unraveling intricate processes across various adsorbent materials in wastewater treatment applications.
Exposure to Secondhand Smoke Extract Increases Cisplatin Resistance in Head and Neck Cancer Cells
Authors: Sadhasivam Balaji , Manyanga Jimmy , Ganapathy Vengatesh , Acharya Pawan , Bouharati Célia , Chinnaiyan Mayilvanan , Mehta Toral , Mathews Basil , Castles Samuel , Rubenstein David A. , Tackett Alayna P. , Zhao Yan D. , Ramachandran Ilangovan , Queimado Lurdes
Published: January 2024

Chemotherapy and radiotherapy resistance are major obstacles in the long-term efficacy of head and neck squamous cell carcinoma (HNSCC) treatment. Secondhand smoke (SHS) exposure is common and has been proposed as an independent predictor of HNSCC recurrence and disease-free survival. However, the underlying mechanisms responsible for these negative patient outcomes are unknown. To assess the effects of SHS exposure on cisplatin efficacy in cancer cells, three distinct HNSCC cell lines were exposed to sidestream (SS) smoke, the main component of SHS, at concentrations mimicking the nicotine level seen in passive smokers’ saliva and treated with cisplatin (0.01–100 µM) for 48 h. Compared to cisplatin treatment alone, cancer cells exposed to both cisplatin and SS smoke extract showed significantly lower cisplatin-induced cell death and higher cell viability, IC50, and indefinite survival capacity. However, SS smoke extract exposure alone did not change cancer cell viability, cell death, or cell proliferation compared to unexposed control cancer cells. Mechanistically, exposure to SS smoke extract significantly reduced the expression of cisplatin influx transporter CTR1, and increased the expression of multidrug-resistant proteins ABCG2 and ATP7A. Our study is the first to document that exposure to SHS can increase cisplatin resistance by altering the expression of several proteins involved in multidrug resistance, thus increasing the cells’ capability to evade cisplatin-induced cell death. These findings emphasize the urgent need for clinicians to consider the potential role of SHS on treatment outcomes and to advise cancer patients and caregivers on the potential benefits of avoiding SHS exposure.
Targeting Alzheimer’s Disease: Evaluating the Efficacy of C-1 Functionalized N-Aryl-Tetrahydroisoquinolines as Cholinergic Enzyme Inhibitors and Promising Therapeutic Candidates
Authors: Jovanović Dunja , Filipović Ana , Janjić Goran , Lazarević-Pašti Tamara , Džambaski Zdravko , Bondžić Bojan P. , Bondžić Aleksandra M.
Published: January 2024

We have synthesized 22 C-1 functionalized-N-aryl-1,2,3,4-tetrahydroisoquinoline derivatives showing biological activities towards cholinergic enzymes. Synthesis was performed using visible-light-promoted photo-redox chemistry, starting from a common intermediate, and the application of this synthetic methodology drastically simplified synthetic routes and purification of desired compounds. All synthesized derivates were divided into four groups based on the substituents in the C-1 position, and their inhibition potencies towards two cholinergic enzymes, acetyl- and butyrylcholinesterase were evaluated. Most potent derivatives were selected, and kinetic analysis was further carried out to obtain insights into the mechanisms of inhibition of these two enzymes. Further validation of the mode of inhibition of cholinergic enzymes by the two most potent THIQ compounds, 3c and 3i, was performed using fluorescence-quenching titration studies. Molecular docking studies further confirmed the proposed mechanism of enzymes’ inhibition. In silico predictions of physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of the selected most potent derivatives were performed using Swiss ADME tool. This was followed by UPLC-assisted log P determination and in vitro BBB permeability studies performed in order to assess the potential of the synthesized compounds to pass the BBB.