bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomass Energy for Environmental Sustainability
Authors: Ong Hwai Chyuan , Kusmayadi Adi , Amin Nor Aishah Saidina
Published: March 2023

Global population growth and rising living standards have significantly impacted global energy consumption [...]
Preliminary Study on Early Diagnosis and Rehabilitation Treatment of Pine Wood Nematode Disease Based on Partial Symptoms
Authors: Ni Anshun , Yang Dan , Cheng Hao , Ye Jianren
Published: March 2023

Pine wilt disease (PWD) is greatly serious to Pinus, and there are still no effective therapeutic measures at present. It is necessary to explore a method of early diagnosis of PWD and to study rehabilitation treatment technology for diseased plants diagnosed early. This paper searched for infected pine trees in natural pine forests according to various subtle symptoms and divided the disease development stages. Different doses of 20% emamectin benzoate were injected at different stages, and the symptom development of pine trees was observed after injection. According to different external symptoms, the stage after being infected by PWD was divided into early stage I and II, middle stage I and II, late stage. It was shown by the results that the diagnostic rate of initial diagnosis based on the symptoms of early stage II was as high as 80%. Additionally, for early stage infected pine trees, an injection of 5–10 mL of 20% emamectin benzoate can inhibit the expansion of symptoms of PWD. One year after injection of 20 mL and 10 mL of 20% emamectin benzoate, the residues measured in the lateral branches 4 m above the injection point were 0.18 mg kg−1 and 0.06 mg kg−1, respectively. In summary, the characteristics of early stage II are ideal for identifying early infection, it has a certain therapeutic effect on early infected pine trees by injection of emamectin benzoate.
Hydrochar Application Improves Growth and Intrinsic Water Use Efficiency of Populus alba, Especially during Hot Season
Authors: Battipaglia Giovanna , Niccoli Francesco , Kabala Jerzy Piotr , Marzaioli Rossana , Di Santo Teresa , Strumia Sandro , Castaldi Simona , Petriccione Milena , Zaccariello Lucio , Battaglia Daniele , Mastellone Maria Laura , Coppola Elio , Rutigliano Flora Angela
Published: March 2023

Hydrochar, carbon-rich material produced during the thermochemical processing of biomass, is receiving increased attention due to its potential value as soil amendment. It can increase agroforestry systems’ productivity through direct and indirect effects on growth and soil quality. Hydrochar may also directly help mitigate climate change by sequestering stable carbon compounds in the soil and perhaps indirectly through increased C uptake by trees. In this research, we aim to evaluate how the application of hydrochar produced by two feedstock types, Cynara cardunculus L. (Hc) residuals and sewage sludge (Hs), and in two different doses (3 and 6 kg m−2) could improve the growth and water use efficiency of Populus alba L., a fast-growing tree species largely used in agroforestry as bioenergy crops and in C sequestration. We considered five plants per treatment, and we measured apical growth, secondary growth, leaf area and intrinsic water use efficiency in each plant for the whole growing season from February to October 2022. Our results highlighted that hydrochar applications stimulate the growth and water use efficiency of plants and that the double dose (6 kg m−2) of both hydrochars, and particularly Hc, had positive effects on plant performance, especially during extremely hot periods. Indeed, the year 2022 was characterized by a heat wave during the summer period, and this condition allowed us to evaluate how plants, growing in soils amended with hydrochar, could perform under climate extremes. Our findings showed that the control plants experienced severe damage in terms of dried stems and dried leaves during summer 2022, while hydrochar applications reduced these effects.
Damage Investigation on the Carbon Tows during Rewinding and Braiding Processes
Authors: Calba Justine , Soulat Damien , Legrand Xavier , Renauld Sébastien
Published: March 2023

During the manufacturing process, the fibrous materials used in composite reinforcements are subjected to many sources of damage that must be managed if the best possible quality is to be reached for the final product. More specifically, carbon fibers are subjected, during reinforcement manufacturing, to friction with mechanical components and with other tows and to excessive tensile loads due to specific configurations required by textile devices, which results in degradation that affects their mechanical properties and those of final products. While many studies have focused on carbon tow damage during the weaving process, roving quality control during the post-braiding steps, such as the rewinding or braiding processes, is less studied in the literature. In this study, an experimental approach was developed to quantify the damage inflicted on 12 K carbon tows during the rewinding and braiding processes using image analysis software. Based on these images, a damage criterion is defined to quantify the influence of the parameters associated with rewinding and braiding processes on degradation of carbon tows. During the rewinding stage, the influence of the process parameters on the degradation by friction of the tows was significant, but the properties (linear density and tenacity) of these carbon tows were little-modified. On the other hand, the great influence of the tension applied on tows on the inflicted damage was experimentally demonstrated, during both the rewinding and braiding steps, which may have resulted in a loss of tenacity of up to 27%.
New Approaches for Improving the Quality of Processed Fruits and Vegetables and Their By-Products
Authors: Miller Fátima A. , Brandão Teresa R. S. , Silva Cristina L. M.
Published: March 2023

The 2030 Sustainable Development Agenda calls for all social actors to contribute to significant societal and environmental issues [...]
Can Citrus Fiber Improve the Quality of Gluten-Free Breads?
Authors: Bugarín Raquel , Gómez Manuel
Published: March 2023

Citrus fiber has a high water absorption capacity, and its properties can be modified by shearing. In this study, the influence of the addition of normal or shear-activated citrus fiber was analyzed in two gluten-free bread formulations. Citrus fiber increases bread optimal hydration and breadcrumb alveolus size due to this high water retention capacity. However, results are negative in the formula based on starches and rice flour because specific volume is significantly reduced, while bread quality improves in the formula based on starches (corn and tapioca). In this case, the breads become less hard and more cohesive, elastic, and resilient, reducing staling. Baking yield also increased due to a greater hydration and a reduced weight loss during baking, without losing acceptability. The mechanical pre-activation of the fiber further increases optimal hydration, without major changes in the quality of the final bread. These effects are associated with cell rupture, and thus the formation of a three-dimensional network, including the increase of surface area and its interaction with water. Citrus fiber increases the hydration of the dough, as well as the cohesiveness, resilience, and elasticity of the crumb, reducing the increase in hardness during storage without affecting acceptability or increasing it.
An Assessment of MT1A (rs11076161), MT2A (rs28366003) and MT1L (rs10636) Gene Polymorphisms and MT2 Concentration in Women with Endometrial Pathologies
Authors: Michalczyk Kaja , Kapczuk Patrycja , Witczak Grzegorz , Tousty Piotr , Bosiacki Mateusz , Kurzawski Mateusz , Chlubek Dariusz , Cymbaluk-Płoska Aneta
Published: March 2023

Several studies have indicated a relationship between metallothionein (MT) polymorphisms and the development of different pathologies, including neoplastic diseases. However, no studies thus far have been conducted on the influence of MT polymorphisms and the development of endometrial lesions, including endometrial cancer. This study included 140 patients with normal endometrial tissue, endometrial polyps, uterine myomas and endometrial cancer. The tissue MT2 concentration was determined using the ELISA method. MT1A, MT2A and MT1L polymorphisms were analyzed using TaqMan real-time PCR genotyping assays. We found no statistical difference between the tissue MT2 concentration in patients with EC vs. benign endometrium (p = 0.579). However, tissue MT2 concentration was significantly different between uterine fibromas and normal endometrial tissue samples (p = 0.019). Menopause status did not influence the tissue MT2 concentration (p = 0.282). There were no significant associations between the prevalence of MT1A, MT2A and MT1L polymorphisms and MT2 concentration. The age, menopausal status, and diabetes status of patients were identified as EC risk factors.
Professionals’ and Patients’ Perspectives on Criteria for Referring Hypertensive Patients to Comprehensive Medication Management Services in Public Primary Health Care
Authors: Sousa Maria do Carmo Vilas Boas , Nascimento Elizabeth do , Mendonça Simone de Araújo Medina , Chemello Clarice
Published: March 2023

Patient prioritization in comprehensive medication management services allows coordinating care and guiding patients according to their clinical profile and their medication use. The aim of the study is to identify and describe factors that indicate the need for comprehensive medication management services among primary care hypertension patients within a public health system from the perspective of patients, pharmacists, nurses and physicians. A qualitative study was carried out with interviews with nurses, pharmacists and physicians (n = 20), and two focus groups with hypertensive patients (n = 12) at primary health care facilities and a public outdoor fitness area between January and February 2019 in Brazil. All interviews were transcribed and analyzed using the Atlas.ti® software. The data analysis revealed the following factors indicative of the need to refer hypertension patients to a pharmacist: lifestyle habits, comorbidities, health care utilization and medication use. The issues identified and the information obtained from the qualitative research and compared with literature studies reviewed allowed defining dimensions that should be considered as an aid in the selection of uncontrolled hypertensive patients for comprehensive medication management services.
Objectively-Assessed Ultraviolet Radiation Exposure and Sunburn Occurrence
Authors: Stump Tammy K. , Fastner Suzanne , Jo Yeonjung , Chipman Jonathan , Haaland Benjamin , Nagelhout Elizabeth S. , Wankier Ali P. , Lensink Riley , Zhu Angela , Parsons Bridget , Grossman Douglas , Wu Yelena P.
Published: March 2023

Ultraviolet radiation (UVR) exposure is the primary modifiable risk factor for melanoma. Wearable UVR sensors provide a means of quantifying UVR exposure objectively and with a lower burden than self-report measures used in most research. The purpose of this study was to evaluate the relationship between detected UVR exposure and reported sunburn occurrence. In this study, a UVR monitoring device was worn by 97 parent–child dyads during waking hours for 14 days to measure instantaneous and accumulated UVR exposure. The results showed that the participants’ total UVR exposure was associated with reported sunburn after adjusting for Fitzpatrick skin type and geographic location. It was observed that one standard erythemal dose (SED) increase in the participants’ daily total UVR exposure was associated with reported sunburn (an odds ratio (OR) of 1.26 with a 95% CI of 1.13 and 1.41, and p < 0.001 for parents and an OR of 1.28 with a 95% CI of 1.12 and 1.47, and p < 0.001 for children). A one-SED increase in the participants’ UVR exposure from 10 am to 4 pm was also associated with reported sunburn (an OR of 1.31 with a 95% CI of 1.15 and 1.49, and p < 0.001 for parents and an OR of 1.33 with a 95% CI of 1.12 and 1.59, and p = 0.001 for children). We found that elevated UVR exposure recordings measured by the UVR sensor were associated with reported sunburn occurrence. Future directions for wearable UVR sensors may include their use as an intervention tool to support in-the-moment sunburn prevention.
Health-Promoting and Sustainable Behavior in University Students in Germany: A Cross-Sectional Study
Authors: Weber Andrea , Kroiss Katharina , Reismann Lydia , Jansen Petra , Hirschfelder Gunther , Sedlmeier Anja M. , Stein Michael J. , Bohmann Patricia , Leitzmann Michael F. , Jochem Carmen
Published: March 2023

Health-promoting and sustainable behaviors, such as active transportation and sustainable diets, are associated with positive effects on human health and the environment. In order to unlock the potential of university students as key actors and multipliers, it is of interest to investigate their level of knowledge about the health effects of climate change and their willingness toward and implementation of health-promoting and sustainable behaviors. In November 2021, an online survey was conducted among students at the University of Regensburg, Germany. A total of 3756 participants (response rate 18%; mean age 23 years; 69% women) provided valid data. A large proportion of medical students (48%) considered themselves well-informed about the health-related effects of climate change, while only a small proportion (22%) of students within economic/computer/data sciences and law felt informed. Most participants knew about the impact of climate change on malnutrition (78%), but considerably fewer were aware of its impact on cardiovascular diseases (52%). Participants who considered themselves informed were consistently more willing to engage in climate-friendly behavior, and this willingness was also reflected in their actions, as they simultaneously promoted a healthy lifestyle. Across all academic disciplines, there is a strong need for knowledge transfer regarding topics that combine health and sustainable development.
Using a Flexible Model to Compare the Efficacy of Geographical and Temporal Contextual Information of Location-Based Social Network Data for Location Prediction
Authors: Ghanaati Fatemeh , Ekbatanifard Gholamhossein , Khoshhal Roudposhti Kamrad
Published: March 2023

In recent years, next location prediction has been of paramount importance for a wide range of location-based social network (LBSN) services. The influence of geographical and temporal contextual information (GTCI) is crucial for analyzing individual behaviors for personalized point-of-interest (POI) recommendations. A number of studies have considered GTCI to improve the performance of POI prediction algorithms, but they have limitations. Moreover, reviewing the related literature revealed that no research has investigated and evaluated the GTCI of LBSN data for location prediction in the form presented in this study. Here, we extended the gated recurrent unit (GRU) model by adding additional attention gates to separately consider GTCI for location prediction based on LBSN data and introduced the extended attention GRU (EAGRU) model. Furthermore, we used the flexibility of the EAGRU architecture and developed it in four states to compare the efficacy of GTCI for location prediction for LBSN users. Real-world, large-scale datasets based on two LBSNs (Gowalla and Foursquare) were used for a complete review. The results revealed that the performance of the EAGRU model was higher than that of competitive baseline methods. In addition, the efficacy of the geographical CI was significantly higher than the temporal CI.
Efficient Knocking Out of the Organophosphorus Insecticides Degradation Gene opdB in Cupriavidus nantongensis X1T via CRISPR/Cas9 with Red System
Authors: Zhang Yufei , Geng Yuehan , Li Shengyang , Shi Taozhong , Ma Xin , Hua Rimao , Fang Liancheng
Published: March 2023

Cupriavidus nantongensis X1T is a type strain of the genus Cupriavidus, that can degrade eight kinds of organophosphorus insecticides (OPs). Conventional genetic manipulations in Cupriavidus species are time-consuming, difficult, and hard to control. The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) system has emerged as a powerful tool for genome editing applied in prokaryotes and eukaryotes due to its simplicity, efficiency, and accuracy. Here, we combined CRISPR/Cas9 with the Red system to perform seamless genetic manipulation in the X1T strain. Two plasmids, pACasN and pDCRH were constructed. The pACasN plasmid contained Cas9 nuclease and Red recombinase, and the pDCRH plasmid contained the dual single-guide RNA (sgRNA) of organophosphorus hydrolase (OpdB) in the X1T strain. For gene editing, two plasmids were transferred to the X1T strain and a mutant strain in which genetic recombination had taken place, resulting in the targeted deletion of opdB. The incidence of homologous recombination was over 30%. Biodegradation experiments suggested that the opdB gene was responsible for the catabolism of organophosphorus insecticides. This study was the first to use the CRISPR/Cas9 system for gene targeting in the genus Cupriavidus, and it furthered our understanding of the process of degradation of organophosphorus insecticides in the X1T strain.
Studying the Geroprotective Properties of YAP/TAZ Signaling Inhibitors on Drosophila melanogaster Model
Authors: Golubev Denis A. , Zemskaya Nadezhda V. , Gorbunova Anastasia A. , Kukuman Daria V. , Moskalev Alexey , Shaposhnikov Mikhail V.
Published: March 2023

The transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the main downstream effectors of the evolutionarily conserved Hippo signaling pathway. YAP/TAZ are implicated in the transcriptional regulation of target genes that are involved in a wide range of key biological processes affecting tissue homeostasis and play dual roles in the aging process, depending on the cellular and tissue context. The aim of the present study was to investigate whether pharmacological inhibitors of Yap/Taz increase the lifespan of Drosophila melanogaster. Real-time qRT-PCR was performed to measure the changes in the expression of Yki (Yorkie, the Drosophila homolog of YAP/TAZ) target genes. We have revealed a lifespan-increasing effect of YAP/TAZ inhibitors that was mostly associated with decreased expression levels of the wg and E2f1 genes. However, further analysis is required to understand the link between the YAP/TAZ pathway and aging.
Small Interfering Ribonucleic Acid as Lipid-Lowering Therapy: Inclisiran in Focus
Authors: Rakocevic Jelena , Dobric Milan , Vucic Rada , Furtula Matija , Zaletel Ivan , Milutinovic Katarina , Ilijevski Ana , Borovic Milica Labudovic , Tomasevic Miloje , Bajcetic Milos
Published: March 2023

The PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) enzyme interferes with the metabolism of low-density lipoprotein (LDL) cholesterol. Inhibition of PCSK9 results in lower LDL cholesterol levels, which can be achieved by different molecular pathways. Monoclonal antibodies targeting circulating PCSK9 have shown strong and persistent effects on lowering the LDL cholesterol level, while reducing the risk of future cardiovascular events. However, this therapy requires once- or twice-monthly administration in the form of subcutaneous injection. This dosing regimen might impact the therapy adherence in cardiovascular patients who often require multiple drugs with different dosing intervals. Small interfering ribonucleic acid (siRNA) represents a promising therapy approach for patients with elevated LDL cholesterol level despite optimized background statin therapy. Inclisiran is a synthesized siRNA which inhibits PCSK9 synthesis in the liver and provides sustained and durable lowering of LDL cholesterol with twice-yearly application and a good tolerability profile. Herein, we present an overview of the current available data and critical review of the major clinical trials which assessed safety and efficacy of inclisiran in different groups of patients with elevated LDL cholesterol level.
Inhibitory Activities of Samples on Tyrosinases Were Affected by Enzyme Species and Sample Addition Methods
Authors: Wang Wei , Yang Lijuan , Wang Weiwei , Zhang Jianyong , Engelhardt Ulrich H. , Jiang Heyuan
Published: March 2023

The inhibition of tyrosinase (TYR) activity is an effective measure to inhibit melanin synthesis. At present, there are many methods with discrepant details that study the TYR inhibitory activity of samples. Under the same experimental conditions, this paper systematically studies whether enzyme species and sample addition methods are the key factors that determine the TYR inhibitory activity of samples. TYRs extracted from B16F10 cells, apple and mushroom, called BTYR, ATYR and MTYR, respectively, were selected to implement this study. Results showed that TYR inhibitory activities of samples were obviously affected by the above two factors. It was necessary to select the appropriate enzyme according to the problems to be explained. It was speculated that indirectly inhibitory activity reflected the comprehensive effects of samples on TYR catalytic activity and intracellular TYR synthesis pathway, while directly inhibitory activity reflected the effects of samples on TYR catalytic activity. Additionally, kojic acid could be used as a positive control for both B16F10 cells and MTYR models. The TYR inhibitory activity of β-arbutin was complicated and fickle, while that of epigallocatechin gallate (EGCG) was universal and stable, which is to say, EGCG always inhibited TYR activity in a dose-dependent manner. In conclusion, the TYR inhibitory activities of samples were affected by enzyme species and sample addition methods. Compared with the unstable β-arbutin, EGCG was more valuable for clinical research.
The Potential Modulatory Effects of Exercise on Skeletal Muscle Redox Status in Chronic Kidney Disease
Authors: Mendes Sara , Leal Diogo V. , Baker Luke A. , Ferreira Aníbal , Smith Alice C. , Viana João L.
Published: March 2023

Chronic Kidney Disease (CKD) is a global health burden with high mortality and health costs. CKD patients exhibit lower cardiorespiratory and muscular fitness, strongly associated with morbidity/mortality, which is exacerbated when they reach the need for renal replacement therapies (RRT). Muscle wasting in CKD has been associated with an inflammatory/oxidative status affecting the resident cells’ microenvironment, decreasing repair capacity and leading to atrophy. Exercise may help counteracting such effects; however, the molecular mechanisms remain uncertain. Thus, trying to pinpoint and understand these mechanisms is of particular interest. This review will start with a general background about myogenesis, followed by an overview of the impact of redox imbalance as a mechanism of muscle wasting in CKD, with focus on the modulatory effect of exercise on the skeletal muscle microenvironment.
Silicon-Induced Morphological, Biochemical and Molecular Regulation in Phoenix dactylifera L. under Low-Temperature Stress
Authors: Bilal Saqib , Khan Taimoor , Asaf Sajjad , Khan Nasir Ali , Saad Jan Syed , Imran Muhammad , Al-Rawahi Ahmed , Khan Abdul Latif , Lee In-Jung , Al-Harrasi Ahmed
Published: March 2023

Climate changes abruptly affect optimum growth temperatures, leading to a negative influence on plant physiology and productivity. The present study aimed to investigate the extent of low-temperature stress effects on date palm growth and physiological indicators under the exogenous application of silicon (Si). Date palm seedlings were treated with Si (1.0 mM) and exposed to different temperature regimes (5, 15, and 30 °C). It was observed that the application of Si markedly improved fresh and dry biomass, photosynthetic pigments (chlorophyll and carotenoids), plant morphology, and relative water content by ameliorating low-temperature-induced oxidative stress. Low-temperature stress (5 and 15 °C), led to a substantial upregulation of ABA-signaling-related genes (NCED-1 and PyL-4) in non Si treated plants, while Si treated plants revealed an antagonistic trend. However, jasmonic acid and salicylic acid accumulation were markedly elevated in Si treated plants under stress conditions (5 and 15 °C) in comparison with non Si treated plants. Interestingly, the upregulation of low temperature stress related plant plasma membrane ATPase (PPMA3 and PPMA4) and short-chain dehydrogenases/reductases (SDR), responsible for cellular physiology, stomatal conductance and nutrient translocation under silicon applications, was observed in Si plants under stress conditions in comparison with non Si treated plants. Furthermore, a significant expression of LSi-2 was detected in Si plants under stress, leading to the significant accumulation of Si in roots and shoots. In contrast, non Si plants demonstrated a low expression of LSi-2 under stress conditions, and thereby, reduced level of Si accumulation were observed. Less accumulation of oxidative stress was evident from the expression of superoxide dismutase (SOD) and catalase (CAT). Additionally, Si plants revealed a significant exudation of organic acids (succinic acid and citric acid) and nutrient accumulation (K and Mg) in roots and shoots. Furthermore, the application of Si led to substantial upregulation of the low temperature stress related soybean cold regulated gene (SRC-2) and ICE-1 (inducer of CBF expression 1), involved in the expression of CBF/DREB (C-repeat binding factor/dehydration responsive element binding factor) gene family under stress conditions in comparison with non Si plants. The current research findings are crucial for exploring the impact on morpho-physio-biochemical attributes of date palms under low temperature and Si supplementation, which may provide an efficient strategy for growing plants in low-temperature fields.
Butein Inhibits Cell Growth by Blocking the IL-6/IL-6Rα Interaction in Human Ovarian Cancer and by Regulation of the IL-6/STAT3/FoxO3a Pathway
Authors: Park Sun-Ae , Seo Young Ju , Kim Lee Kyung , Kim Hee Jung , Yoon Kee Dong , Heo Tae-Hwe
Published: March 2023

Butea monosperma (Fabaceae) has been used in traditional Indian medicine to treat a variety of ailments, including abdominal tumors. We aimed to investigate the anti-IL-6 activity of butein in ovarian cancer and elucidate the underlying molecular mechanisms. Butein was isolated and identified from B. monosperma flowers, and the inhibition of IL-6 signaling was investigated using the HEK-Blue™ IL-6 cell line. The surface plasmon resonance assay was used to estimate the binding of butein to IL-6, IL-6Rα, and gp130. After treatment with butein, ovarian cancer cell migration, apoptosis, and tumor growth inhibition were evaluated in vitro and in vivo. Furthermore, we used STAT3 siRNA to identify the mechanistic effects of butein on the IL-6/STAT3/FoxO3a pathway. Butein suppressed downstream signal transduction through higher binding affinity to IL-6. In ovarian cancer, butein inhibited cell proliferation, migration, and invasion, and induced cell cycle arrest and apoptosis. In addition, it decreased the growth of ovarian cancer cells in xenograft tumor models. Butein inhibited STAT3 phosphorylation and induced FoxO3a accumulation in the nucleus by inhibiting IL-6 signaling. The anticancer activity of butein was mediated by blocking the IL-6/IL-6Rα interaction and suppressing IL-6 bioactivity via interfering with the IL-6/STAT3/FoxO3a pathway.
Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control
Authors: Youssef Mahmoud E. , Yahya Galal , Popoviciu Mihaela Simona , Cavalu Simona , Abd-Eldayem Marwa A. , Saber Sameh
Published: March 2023

The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.
Protein Arginine Methyltransferase 5 (PRMT5) Mutations in Cancer Cells
Authors: Rasheed Shayaan , Bouley Renee A. , Yoder Ryan J. , Petreaca Ruben C.
Published: March 2023

Arginine methylation is a form of posttranslational modification that regulates many cellular functions such as development, DNA damage repair, inflammatory response, splicing, and signal transduction, among others. Protein arginine methyltransferase 5 (PRMT5) is one of nine identified methyltransferases, and it can methylate both histone and non-histone targets. It has pleiotropic functions, including recruitment of repair machinery to a chromosomal DNA double strand break (DSB) and coordinating the interplay between repair and checkpoint activation. Thus, PRMT5 has been actively studied as a cancer treatment target, and small molecule inhibitors of its enzymatic activity have already been developed. In this report, we analyzed all reported PRMT5 mutations appearing in cancer cells using data from the Catalogue of Somatic Mutations in Cancers (COSMIC). Our goal is to classify mutations as either drivers or passengers to understand which ones are likely to promote cellular transformation. Using gold standard artificial intelligence algorithms, we uncovered several key driver mutations in the active site of the enzyme (D306H, L315P, and N318K). In silico protein modeling shows that these mutations may affect the affinity of PRMT5 for S-adenosylmethionine (SAM), which is required as a methyl donor. Electrostatic analysis of the enzyme active site shows that one of these mutations creates a tunnel in the vicinity of the SAM binding site, which may allow interfering molecules to enter the enzyme active site and decrease its activity. We also identified several non-coding mutations that appear to affect PRMT5 splicing. Our analyses provide insights into the role of PRMT5 mutations in cancer cells. Additionally, since PRMT5 single molecule inhibitors have already been developed, this work may uncover future directions in how mutations can affect targeted inhibition.
Genetics and Epigenetics: Implications for the Life Course of Gestational Diabetes
Authors: Lowe William L.
Published: March 2023

Gestational diabetes (GDM) is one of the most common complications of pregnancy, affecting as many as one in six pregnancies. It is associated with both short- and long-term adverse outcomes for the mother and fetus and has important implications for the life course of affected women. Advances in genetics and epigenetics have not only provided new insight into the pathophysiology of GDM but have also provided new approaches to identify women at high risk for progression to postpartum cardiometabolic disease. GDM and type 2 diabetes share similarities in their pathophysiology, suggesting that they also share similarities in their genetic architecture. Candidate gene and genome-wide association studies have identified susceptibility genes that are shared between GDM and type 2 diabetes. Despite these similarities, a much greater effect size for MTNR1B in GDM compared to type 2 diabetes and association of HKDC1, which encodes a hexokinase, with GDM but not type 2 diabetes suggest some differences in the genetic architecture of GDM. Genetic risk scores have shown some efficacy in identifying women with a history of GDM who will progress to type 2 diabetes. The association of epigenetic changes, including DNA methylation and circulating microRNAs, with GDM has also been examined. Targeted and epigenome-wide approaches have been used to identify DNA methylation in circulating blood cells collected during early, mid-, and late pregnancy that is associated with GDM. DNA methylation in early pregnancy had some ability to identify women who progressed to GDM, while DNA methylation in blood collected at 26–30 weeks gestation improved upon the ability of clinical factors alone to identify women at risk for progression to abnormal glucose tolerance post-partum. Finally, circulating microRNAs and long non-coding RNAs that are present in early or mid-pregnancy and associated with GDM have been identified. MicroRNAs have also proven efficacious in predicting both the development of GDM as well as its long-term cardiometabolic complications. Studies performed to date have demonstrated the potential for genetic and epigenetic technologies to impact clinical care, although much remains to be done.
Insecticide Resistance and Its Management in Two Invasive Cryptic Species of Bemisia tabaci in China
Authors: Wang Qian , Luo Chen , Wang Ran
Published: March 2023

The sweet potato whitefly Bemisia tabaci is a major agricultural pest with a wide host range throughout the world. The species designation for B. tabaci includes numerous distinct cryptic species or biotypes. Two invasive B. tabaci biotypes, MEAM1 (B) and MED (Q), were found in China at the end of the 20th century and at the beginning of the 21st century. MEAM1 (B) and MED (Q) show higher pesticide resistance levels than native strains, and the levels of resistance vary with changes in insecticide selection pressure. Recent studies have revealed metabolic resistance mechanisms and target site mutations in invasive B. tabaci strains that render them resistant to a range of insecticides and have uncovered the frequency of these resistance-related mutations in B. tabaci populations in China. Novel pest control agents, such as RNA-based pesticides and nano-pesticides, have achieved effective control effects in the laboratory and are expected to be applied for field control of B. tabaci in the future. In this review, we discuss the mechanisms of resistance developed by these invasive B. tabaci populations since their invasion into China. We also provide suggestions for ecologically sound and efficient B. tabaci control.
Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases
Authors: Lin Da-Wei , Hsu Yung-Chien , Chang Cheng-Chih , Hsieh Ching-Chuan , Lin Chun-Liang
Published: March 2023

Redox is a constant phenomenon in organisms. From the signaling pathway transduction to the oxidative stress during the inflammation and disease process, all are related to reduction-oxidation (redox). Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor targeting many antioxidant genes. In non-stressed conditions, NRF2 maintains the hemostasis of redox with housekeeping work. It expresses constitutively with basal activity, maintained by Kelch-like-ECH-associated protein 1 (KEAP1)-associated ubiquitination and degradation. When encountering stress, it can be up-regulated by several mechanisms to exert its anti-oxidative ability in diseases or inflammatory processes to protect tissues and organs from further damage. From acute kidney injury to chronic kidney diseases, such as diabetic nephropathy or glomerular disease, many results of studies have suggested that, as a master of regulating redox, NRF2 is a therapeutic option. It was not until the early termination of the clinical phase 3 trial of diabetic nephropathy due to heart failure as an unexpected side effect that we renewed our understanding of NRF2. NRF2 is not just a simple antioxidant capacity but has pleiotropic activities, harmful or helpful, depending on the conditions and backgrounds.
Kisspeptin-10 Mitigates α-Synuclein-Mediated Mitochondrial Apoptosis in SH-SY5Y-Derived Neurons via a Kisspeptin Receptor-Independent Manner
Authors: Simon Christopher , Soga Tomoko , Parhar Ishwar
Published: March 2023

The hypothalamic neurohormone kisspeptin-10 (KP-10) was inherently implicated in cholinergic pathologies when aberrant fluctuations of expression patterns and receptor densities were discerned in neurodegenerative micromilieus. That said, despite variable degrees of functional redundancy, KP-10, which is biologically governed by its cognate G-protein-coupled receptor, GPR54, attenuated the progressive demise of α-synuclein (α-syn)-rich cholinergic-like neurons. Under explicitly modeled environments, in silico algorithms further rationalized the surface complementarities between KP-10 and α-syn when KP-10 was unambiguously accommodated in the C-terminal binding pockets of α-syn. Indeed, the neuroprotective relevance of KP-10’s binding mechanisms can be insinuated in the amelioration of α-syn-mediated neurotoxicity; yet it is obscure whether these extenuative circumstances are contingent upon prior GPR54 activation. Herein, choline acetyltransferase (ChAT)-positive SH-SY5Y neurons were engineered ad hoc to transiently overexpress human wild-type or E46K mutant α-syn while the mitigation of α-syn-induced neuronal death was ascertained via flow cytometric and immunocytochemical quantification. Recapitulating the specificity observed on cell viability, exogenously administered KP-10 (0.1 µM) substantially suppressed wild-type and E46K mutant α-syn-mediated apoptosis and mitochondrial depolarization in cholinergic differentiated neurons. In particular, co-administrations with a GPR54 antagonist, kisspeptin-234 (KP-234), failed to abrogate the robust neuroprotection elicited by KP-10, thereby signifying a GPR54 dispensable mechanism of action. Consistent with these observations, KP-10 treatment further diminished α-syn and ChAT immunoreactivity in neurons overexpressing wild-type and E46K mutant α-syn. Overall, these findings lend additional credence to the previous notion that KP-10’s binding zone may harness efficacious moieties of neuroprotective intent.
Unraveling the Underlying Molecular Mechanism of ‘Silent Hypoxia’ in COVID-19 Patients Suggests a Central Role for Angiotensin II Modulation of the AT1R-Hypoxia-Inducible Factor Signaling Pathway
Authors: Devaux Christian Albert , Lagier Jean-Christophe
Published: March 2023

A few days after being infected with SARS-CoV-2, a fraction of people remain asymptomatic but suffer from a decrease in arterial oxygen saturation in the absence of apparent dyspnea. In light of our clinical investigation on the modulation of molecules belonging to the renin angiotensin system (RAS) in COVID-19 patients, we propose a model that explains ‘silent hypoxia’. The RAS imbalance caused by SARS-CoV-2 results in an accumulation of angiotensin 2 (Ang II), which activates the angiotensin 2 type 1 receptor (AT1R) and triggers a harmful cascade of intracellular signals leading to the nuclear translocation of the hypoxia-inducible factor (HIF)-1α. HIF-1α transactivates many genes including the angiotensin-converting enzyme 1 (ACE1), while at the same time, ACE2 is downregulated. A growing number of cells is maintained in a hypoxic condition that is self-sustained by the presence of the virus and the ACE1/ACE2 ratio imbalance. This is associated with a progressive worsening of the patient’s biological parameters including decreased oxygen saturation, without further clinical manifestations. When too many cells activate the Ang II-AT1R-HIF-1α axis, there is a ‘hypoxic spillover’, which marks the tipping point between ‘silent’ and symptomatic hypoxia in the patient. Immediate ventilation is required to prevent the ‘hypoxic spillover’.
Association between Previous CPAP and Comorbidities at Diagnosis of Obesity-Hypoventilation Syndrome Associated with Obstructive Sleep Apnea: A Comparative Retrospective Observational Study
Authors: Agossou Moustapha , Awanou Berenice , Inamo Jocelyn , Dufeal Marion , Arnal Jean-Michel , Dramé Moustapha
Published: March 2023

Obesity-hypoventilation syndrome (OHS) is associated with many comorbidities. The aim of this study was to evaluate the association between previous continuous positive airway pressure (CPAP) and the prevalence of comorbidities in OHS associated with obstructive sleep apnea (OSA). We performed a retrospective, single-center study at the University Hospital of Martinique, the referral hospital for the island of Martinique. A total of 97 patients with OHS associated with severe OSA on non-invasive ventilation (NIV) were included; 54 patients (56%) had previous treatment of OSA with a positive airway pressure (PAP) device before shifting to NIV (PAP group) and 43 (44%) had no previous treatment of OSA with a PAP device before initiating NIV PAP (no PAP group). Sociodemographic characteristics were similar between groups; there were 40 women (74%) in the PAP group versus 34 (79%) in the no PAP group, mean age at OHS diagnosis was 66 ± 15 versus 67 ± 16 years, respectively, and the mean age at inclusion 72 ± 14 versus 71 ± 15 years, respectively. The average number of comorbidities was 4 ± 1 in the PAP group versus 4 ± 2 in the no PAP group; the mean Charlson index was 5 ± 2 in both groups. The mean BMI was 42 ± 8 kg/m2 in both groups. The mean follow-up duration was 5.8 ± 4.4 years in the PAP group versus 4.7 ± 3.5 years in the no PAP group. Chronic heart failure was less common in patients who had a previous PAP 30% versus 53% (p = 0.02). It is also noted that these patients were diagnosed less often in the context of acute respiratory failure in patients with previous PAP: 56% versus 93% (p < 0.0001). In contrast, asthma patients were more frequent in patients with previous treatment of OSA with a PAP device at the time of OHS diagnosis but not significantly: 37% versus 19% (p = 0.07). Early treatment of severe OSA with a PAP device prior to diagnosis of OHS seems to be associated with a reduced prevalence of cardiac diseases, notably chronic heart failure, in patients diagnosed with OHS associated with severe OSA.
Predicting the Absolute Risk of Ischemic Stroke in Asian Patients with Atrial Fibrillation: Comparing the COOL-AF Risk Score with CARS/mCARS Models for Absolute Risk and the CHA2DS2-VASc Score
Authors: Krittayaphong Rungroj , Winijkul Arjbordin , Sairat Poom , Lip Gregory Y. H.
Published: March 2023

Background: The aims of this study were (1) to validate the CARS and mCARS methods in an Asian population with atrial fibrillation (AF) and (2) to compare the CARS and mCARS models for absolute risk using the COOL-AF method and CHA2DS2VASc scores for the prediction of ischemic stroke or systemic embolism (SSE). Methods: We analyzed the results from a prospective nationwide multicenter AF registry. Follow-up data were collected for 3 years. The main outcomes were SSE. Predictive models of the 3-year SSE of the COOL-AF model, the CHA2DS2VASc score, the CARS for the no-OAC group, and the mCARS for the OAC group were developed and evaluated by C-statistics, and calibration plots were created for the whole group, as well as for oral anticoagulant (OAC) users and no-OAC patients. Results: We studied 3405 patients (mean age: 67.8 years; 58.2% male, 75.4% OAC). The incidence rates of SSE were 1.51 (1.26–1.78), 1.93 (1.39–2.60), and 1.37 (1.10–1.68) for all patients, no-OAC patients, and OAC patients, respectively. For the whole population, the COOL-AF score had a C-statistic of 0.697 (0.682–0.713), which was superior to the CHA2DS2-VASc [0.655 (0.639–0.671)]. For the no-OAC group, the CARS predicted SSE with a C-statistic of 0.685 (0.652–0.716), which was similar to the CHA2DS2-VASc [0.684 (0.651–0.7150] and COOL-AF models [0.692 (0.659–0.723)]. For the OAC group, the mCARS had a C-statistic of 0.687 (0.669–0.705) that was similar to the COOL-AF [0.704 (0.686–0.721)] and better than the CHA2DS2-VASc score [0.655 (0.637–0.674)]. Conclusions: The calculation of the individual absolute risks using the CARS and mCARS models can predict SSE in an Asian population. Small differences were evident between the COOL-AF and CHA2DS2-VASc scores.
Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease
Authors: Orfanoudaki Eleni , Foteinogiannopoulou Kalliopi , Theodoraki Eirini , Koutroubakis Ioannis E.
Published: March 2023

Despite the evolution in inflammatory bowel disease (IBD) management during the last 20 years owing to the advent of new advanced therapies, anti-TNF agents still remain the cornerstone of therapy for both Crohn’s disease and ulcerative colitis. However, this does not only secure favorable outcomes for patients considering the progressive disease character and the high likelihood of primary or secondary loss of response. Therefore, trying to reach a better treatment approach and maximize the benefits anti-TNF agents offer, optimization strategies should be examined. It has been indicated that optimizing treatment with anti-TNF enhances drug efficacy and has been associated with improved disease outcomes and a complication-free disease course. From this perspective, we aim to provide an overview of currently available data and recent advances in the practices of anti-TNF treatment optimization. Special focus has been given to the role of therapeutic drug monitoring (TDM), as well as the utility of combining anti-TNF with an immunomodulator and the treat-to-target approach.
Can Zeolite-Supporting Acridines Boost Their Anticancer Performance?
Authors: Ranković Maja , Jevremović Anka , Janošević Ležaić Aleksandra , Arsenijević Aleksandar , Rupar Jelena , Dobričić Vladimir , Nedić Vasiljević Bojana , Gavrilov Nemanja , Bajuk-Bogdanović Danica , Milojević-Rakić Maja
Published: March 2023

Acridine and its derivatives (9-chloroacridine and 9-aminoacridine) are investigated here, supported on FAU type zeolite Y, as a delivery system of anticancer agents. FTIR/Raman spectroscopy and electron microscopy revealed successful drug loading on the zeolite surface, while spectrofluorimetry was employed for drug quantification. The effects of the tested compounds on cell viability were evaluated using in vitro methylthiazol-tetrazolium (MTT) colorimetric technique against human colorectal carcinoma (cell line HCT-116) and MRC-5 fibroblasts. Zeolite structure remained unchanged during homogeneous drug impregnation with achieved drug loadings in the 18–21 mg/g range. The highest drug release, in the µM concentration range, with favourable kinetics was established for zeolite-supported 9-aminoacridine. The acridine delivery via zeolite carrier is viewed in terms of solvation energy and zeolite adsorption sites. The cytotoxic effect of supported acridines on HCT-116 cells reveals that the zeolite carrier improves toxicity, while the highest efficiency is displayed by zeolite-impregnated 9-aminoacridine. The 9-aminoacridine delivery via zeolite carrier favours healthy tissue preservation while accompanying increased toxicity toward cancer cells. Cytotoxicity results are well correlated with theoretical modelling and release study, providing promising results for applicative purposes.