bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3): Role in Retinal Development and Disease
Authors: Toms Maria , Ward Natasha , Moosajee Mariya
Published: June 2023

NR2E3 is a nuclear hormone receptor gene required for the correct development of the retinal rod photoreceptors. Expression of NR2E3 protein in rod cell precursors suppresses cone-specific gene expression and, in concert with other transcription factors including NRL, activates the expression of rod-specific genes. Pathogenic variants involving NR2E3 cause a spectrum of retinopathies, including enhanced S-cone syndrome, Goldmann–Favre syndrome, retinitis pigmentosa, and clumped pigmentary retinal degeneration, with limited evidence of genotype–phenotype correlations. A common feature of NR2E3-related disease is an abnormally high number of cone photoreceptors that are sensitive to short wavelength light, the S-cones. This characteristic has been supported by mouse studies, which have also revealed that loss of Nr2e3 function causes photoreceptors to develop as cells that are intermediate between rods and cones. While there is currently no available cure for NR2E3-related retinopathies, there are a number of emerging therapeutic strategies under investigation, including the use of viral gene therapy and gene editing, that have shown promise for the future treatment of patients with NR2E3 variants and other inherited retinal diseases. This review provides a detailed overview of the current understanding of the role of NR2E3 in normal development and disease, and the associated clinical phenotypes, animal models, and therapeutic studies.
Comparative Analysis of CRISPR-Cas Systems in Pseudomonas Genomes
Authors: Parra-Sánchez Ángel , Antequera-Zambrano Laura , Martínez-Navarrete Gema , Zorrilla-Muñoz Vanessa , Paz José Luis , Alvarado Ysaias J. , González-Paz Lenin , Fernández Eduardo
Published: June 2023

Pseudomonas is a bacterial genus with some saprophytic species from land and others associated with opportunistic infections in humans and animals. Factors such as pathogenicity or metabolic aspects have been related to CRISPR-Cas, and in silico studies into it have focused more on the clinical and non-environmental setting. This work aimed to perform an in silico analysis of the CRISPR-Cas systems present in Pseudomonas genomes. It analyzed 275 complete genomic sequences of Pseudomonas taken from the NCBI database. CRISPR loci were obtained from CRISPRdb. The genes associated with CRISPR (cas) and CAS proteins, and the origin and diversity of spacer sequences, were identified and compared by BLAST. The presence of self-targeting sequences, PAMs, and the conservation of DRs were visualized using WebLogo 3.6. The CRISPR-like RNA secondary structure prediction was analyzed using RNAFold and MFold. CRISPR structures were identified in 19.6% of Pseudomonas species. In all, 113 typical CRISPR arrays with 18 putative cas were found, as were 2050 spacers, of which 52% showed homology to bacteriophages, 26% to chromosomes, and 22% to plasmids. No potential self-targeting was detected within the CRISPR array. All the found DRs can form thermodynamically stable secondary RNA structures. The comparison of the CRISPR/Cas system can help understand the environmental adaptability of each evolutionary lineage of clinically and environmentally relevant species, providing data support for bacterial typing, traceability, analysis, and exploration of unconventional CRISPR.
Integrative Genetic Approach Facilitates Precision Strategies for Acute Myocardial Infarction
Authors: Khawaja Muzamil , Siddiqui Rehma , Virani Salim S. , Amos Christopher I. , Bandyopadhyay Dhrubajyoti , Virk Hafeez Ul Hassan , Alam Mahboob , Jneid Hani , Krittanawong Chayakrit
Published: June 2023

Acute myocardial infarction remains a significant cause of mortality worldwide and its burden continues to grow. Its pathophysiology is known to be complex and multifactorial, with several acquired and inherited risk factors. As advances in technology and medical therapy continue, there is now increasing recognition of the role that genetics play in the development and management of myocardial infarction. The genetic determinants of acute coronary syndrome are still vastly understudied, but the advent of whole-genome scanning and genome-wide association studies has significantly expanded the current understanding of genetics and simultaneously fostered hope that genetic profiling and gene-guided treatments could substantially impact clinical outcomes. The identification of genes associated with acute myocardial infarction can help in the development of personalized medicine, risk stratification, and improved therapeutic strategies. In this context, several genes have been studied, and their potential involvement in increasing the risk for acute myocardial infarction is being investigated. As such, this article provides a review of some of the genes potentially related to an increased risk for acute myocardial infarction as well as the latest updates in gene-guided risk stratification and treatment strategies.
Interpretation of Hyperspectral Shortwave Infrared Core Scanning Data Using SEM-Based Automated Mineralogy: A Machine Learning Approach
Authors: Rotem Amit , Vidal Alexander , Pfaff Katharina , Tenorio Luis , Chung Matthias , Tharalson Erik , Monecke Thomas
Published: June 2023

Understanding the mineralogy and geochemistry of the subsurface is key when assessing and exploring for mineral deposits. To achieve this goal, rapid acquisition and accurate interpretation of drill core data are essential. Hyperspectral shortwave infrared imaging is a rapid and non-destructive analytical method widely used in the minerals industry to map minerals with diagnostic features in core samples. In this paper, we present an automated method to interpret hyperspectral shortwave infrared data on drill core to decipher major felsic rock-forming minerals using supervised machine learning techniques for processing, masking, and extracting mineralogical and textural information. This study utilizes a co-registered training dataset that integrates hyperspectral data with quantitative scanning electron microscopy data instead of spectrum matching using a spectral library. Our methodology overcomes previous limitations in hyperspectral data interpretation for the full mineralogy (i.e., quartz and feldspar) caused by the need to identify spectral features of minerals; in particular, it detects the presence of minerals that are considered invisible in traditional shortwave infrared hyperspectral analysis.
Management and Prevention of Pre-Eclampsia in Nigeria
Authors: Adeyeye Oluwabunmi Victoria , Ebubechukwu Nwikwu Vivian , Olanrewaju Omotayo Faith , Eniayewun Aderayo Grace , Nwuta Chidinma , Effiong Fortune Benjamin , Unim Brigid
Published: June 2023

This research paper analyses the management and prevention of pre-eclampsia in Nigeria. Although efforts have been made to reduce outcomes due to pre-eclampsia, it still rears its head in the form of high maternal and perinatal morbidity and mortality. The aim of this review was to identify the main obstacles, gaps, and interventions related to the prevention and management of pre-eclampsia in order to be fully knowledgeable of the magnitude of the issue at the national level, to assess if current government policies are adequate and to recommend solutions. A search was performed on online databases and it was completed with hand searches related to the subject matter. Screening tests for early detection of pre-eclampsia are hardly available in Nigeria as many hospitals rely on the history of previous and current pregnancies, blood pressure monitoring and urinalysis–proteinuria. The administration of low-dose aspirin, antihypertensive drugs and magnesium sulphate, coupled with calcium in calcium deficit regions, was recommended. The main barriers to the wider implementation of these strategies are inadequacy of the antenatal care services in providing appropriate care, lack of resources and trained personnel, high healthcare costs, and low antennal care attendance. Improving education and awareness, use of low-cost screening modalities and low-dose aspirin can be deployed in developing countries to curb pre-eclampsia.
The Effect of Cardiorespiratory Exercise in the Prevention and Treatment of Hypertension among HIV-Infected Individuals on Antiretroviral Therapy in Mthatha, South Africa
Authors: Tsuro Urgent , Oladimeji Kelechi Elizabeth , Pulido-Estrada Guillermo-Alfredo , Apalata Teke Ruffin
Published: June 2023

The prevalence of hypertension among people living with HIV (PLHIV) on antiretroviral therapy (ART) is concerning. Physical activity is a proposed approach for managing and avoiding hypertension in this population. While cardiorespiratory exercises (CET) have been efficacious in the general population, its effectiveness in PLHIV on ART, especially in the study setting, in Mthatha is unknown. Consequently, the purpose of this study was to see if CET improves cardiorespiratory fitness in HAART-treated PLHIV with blood flow restriction (BFR) in Mthatha, South Africa. A quasi-experimental study with 98 participants (49 of whom were cases) was carried out. Cases were participants assigned to the CET intervention group that comprised of concurrent training as it included both aerobic and resistance exercise, matched on age and gender. The relationship between CET and hypertension was assessed using logistic regression after adjusting for possible confounding variables. At baseline, there was no significant difference between the physical characteristics of the two groups, and after the intervention, there was a significant difference. Obesity and central adiposity were identified as strong risk factors for hypertension. The findings also indicated that a reduction in waist circumference and body mass index had a significant positive association with hypertension treatment amongst the intervention group (p < 0.05). According to the results of the study, CET has the potential to be an efficient and economical non-pharmacological intervention for the management and control of hypertension in PLHIV. However, further study is required to establish how long, how intense, and what kind of exercise is best for this population.
Empirical Analysis of Preferences of Older Adults for Care Facilities in Japan: Focusing on Household Structure and Economic Status
Authors: Wang Jinhan , Wang Ziyan , Niu Bing
Published: June 2023

Japan is advancing into a super-aged society at an unprecedented speed, and the proportion of the elderly population will continue to rise. The number of older adults needing nursing care will also increase with the aging population. We used a cross-sectional dataset of older Japanese adults to examine their future preferences for care facilities and their relationship with individual characteristics, household structure, and economic status. We further focused on a subgroup of those who lived alone and were experiencing poverty and examined their care needs through their choice of care facilities. We found the following results from multinomial logit and probit regressions. First, compared with living alone, older adults who live with their spouses or other members prefer to live in their own houses. Second, older adults experiencing poverty preferred to choose facilities geared towards low-income groups, while wealthy older adults preferred to choose fee-based nursing homes/nursing homes with diverse services and high costs. Third, single older adults in poverty were less likely to choose to live in facilities. Covariates such as sex, age, and health status also mattered in their choices. Therefore, tailoring the formal care services to the preferences and actual needs of older adults is imperative.
The Impact on Urology Residents’ Learning of Social Media and Web Technologies after the Pandemic: A Step Forward through the Sharing of Knowledge
Authors: Rodler Severin , Bujoreanu Cristina Eliza , Baekelandt Loic , Volpi Gabriele , Puliatti Stefano , Kowalewski Karl-Friedrich , Belenchon Ines Rivero , Taratkin Mark , Rivas Juan Gomez , Veccia Alessandro , Piazza Pietro , Carrion Diego M. , Cacciamani Giovanni Enrico , Esperto Francesco , Checcucci Enrico
Published: June 2023

The COVID-19 pandemic has impacted urology residents and their training. However, several new technologies or knowledge platforms as social media (SoMe) and web-based learning solutions have filled this gap. Therefore, we aimed to analyze resident’s learning curves of new learning modalities, identify the evidence that is provided in the literature, and evaluate the possible impact of such solutions in the future. We conducted a non-systematic literature search using Medline, PubMed, and Embase. In addition, online resources of national and international urology resident societies were queried. The identified paper described SoMe, webinars, podcasts, pre-recorded surgical videos, educational platforms, and mobile apps in the field of urology that are used to gain access to information, teach and provide feedback to residents, and were used under the conditions of the pandemic. The application of those technologies harbors the risk of mis- and disinformation, but have the potential to provide access to education and validated knowledge, training, and feedback and thereby might democratize training of residents in urology globally.
e-Health Interventions Targeting Pain-Related Psychological Variables in Fibromyalgia: A Systematic Review
Authors: Donisi Valeria , De Lucia Annalisa , Pasini Ilenia , Gandolfi Marialuisa , Schweiger Vittorio , Del Piccolo Lidia , Perlini Cinzia
Published: June 2023

There is growing evidence to support the potential benefit of e-Health interventions targeting psychosocial outcomes and/or pain-related psychological variables for chronic pain conditions, including fibromyalgia syndrome (FMS). This systematic review aims at providing an in-depth description of the available e-Health psychological and/or multicomponent interventions for patients with FMS. Searches were made in PubMed, Cochrane, Web of Science, and PsycINFO up to 15 May 2023, finally including twenty-six articles. The quality of the included articles was medium–high (average quality assessment score of 77.1%). 50% of studies were randomized controlled trials (RCTs) (n = 13), and the majority of them focused exclusively on adult patients with FMS (n = 23) who were predominantly female. Four categories of e-Health modalities were identified: web-based (n = 19), mobile application (m-Health) (n = 3), virtual reality (VR) (n = 2), and video consulting (n = 2). Interventions were mainly based on the cognitive behavioral therapy (CBT) approach (n = 14) and mostly involved contact with a healthcare professional through different digital tools. Overall, a growing number of psychological and multicomponent interventions have been created and delivered using digital tools in the context of FMS, showing their potentiality for improving psychosocial outcomes and pain-related psychological variables. However, some digital tools resulted as underrepresented, and the literature on this topic appears highly heterogeneous precluding robust conclusions.
Osteonecrosis Related to Steroid and Alcohol Use—An Update on Pathogenesis
Authors: Konarski Wojciech , Poboży Tomasz , Konarska Klaudia , Śliwczyński Andrzej , Kotela Ireneusz , Hordowicz Martyna , Krakowiak Jan
Published: June 2023

Osteonecrosis (ON) is usually a progressive disease that negatively affects the quality of life and leads to significant disability. Most patients are aged 30–50 years and require multiple surgical interventions throughout their lifetime. In non-traumatic ON, alcohol abuse and corticosteroids are involved in up to 80% of cases. This narrative review aims to summarize data on their impact on healthy bone and the development of pathophysiological processes leading to ON development. We conducted EMBASE and MEDLINE database reviews to identify relevant research. We found that for both agents, the risk was time and dose-dependent. ON in alcohol and steroid use shared many pathogenetic mechanisms leading to the development of necrosis, including increased adipogenesis, the induction of chronic inflammation, vascular alterations, and impaired bone-cell differentiation. Because both alcohol and steroid use are modifiable factors, both general physicians and orthopedic surgeons should encourage patients to limit ethanol intake and avoid corticosteroid overuse. In the presence of ON, because both alcohol- and steroid-induced disease tend to be multifocal, addiction treatment and limiting steroid use are justified.
The Communication Challenge in Archaeological Museums in Puglia: Insights into the Contribution of Social Media and ICTs to Small-Scale Institutions
Authors: Lerario Antonella
Published: June 2023

Archaeological museums play a vital role in regions with ancient roots, holding a millennial image as the cradle of civilization. In the South of Italy (former “Magna Graecia”) and particularly in Puglia—a melting pot of cultures where ancient Messapian, Byzantine, Roman, and Greek civilizations followed one another in ages, bequeathing a wealth of testimonies—institutions are disseminated across the region, and almost every small municipality has its own archaeological museum hosting a wealth of valuable objects and remains. The gradual structural changes in the role of museums over the last decades and the recent COVID-19 pandemic outbreak, with the sudden closing and subsequent re-opening of facilities, forced institutions to re-think and re-develop their communication practices everywhere. Museums across the world have since been conceiving original and effective strategies based on social media and ICTs. After framing the problem background, the article introduces an overview of good practice and virtuous examples in the museum field and a questionnaire-based focus survey on a sample of archaeological museums in Puglia in order to assess the status of local communication strategies’ implementation against the potential of modern technologies. The survey results allowed identifying a peculiar mix of “emergency” and evolutional approaches in the sample analyzed, main concerns and barriers to the adoption of digital strategies, but also specific strategic drivers for innovation in the very nature of local small institutions. The study’s outcomes offer a potential contribution to the alignment of institutions to current standards through informed policies that can be usefully shared in other similar contexts across Europe.
Egyptian Opuntia ficus-indica (OFI) Residues: Recovery and Characterization of Fresh Mucilage from Cladodes
Authors: Elshewy Ahmed , Blando Federica , Bahlol Hammam , El-Desouky Ahmed , De Bellis Palmira , Khalifa Ibrahim
Published: June 2023

The utilization of biopolymers gained recent attention worldwide due to their effective role in producing eco-friendly and economical products. Mucilage from Opuntia ficus-indica (OFI, and other succulent plants) has the capacity to absorb huge amounts of water, forming a viscous colloid with interesting rheological properties. It also had the potential ability for use as food additives or food technological products. We, therefore, aimed at extracting and characterizing pure liquid mucilage from the cladodes of OFI (Egyptian variety) using multidimensional approaches including HPLC-RID, FTIR, XRD, NMR, DSC, and TGA assays. The chemical composition, total polyphenols, total flavonoids, total flavonols, and antioxidant capacity by DPPH and ABTS assays were also measured. HPLC-RID analysis showed that the mucilage’s sugars are composed of glucose, xylose, rhamnose, galacturonic acid, arabinose, galactose, and fucose with total sugars of 0.375 mg/mL, which were subsequently confirmed by FTIR and NMR results. The specific signals of these sugars were also observed in 13C and 1H NMR spectra and their chemical fingerprint was obtained by FTIR. XRD patterns showed that mucilage has high calcium content, and the glass transition temperature was observed at 85.9 °C. Meanwhile, total phenolic content, flavonoids, and flavonols were about 7.96 mg GAE/g FW, 3.61 mg QE/g FW, and 1.47 mg QE/g FW, respectively. The antioxidant capacity of mucilage was around 26.15 and 22.5 µmol TE/g FW for DPPH and ABTS methods, respectively. It can be concluded that OFI cladode mucilage showed promising properties that would improve and open new opportunities and trends in the food, pharmaceutical, cosmetic, and other industries. The use of pure liquid mucilage could also be economically profitable due to its low cost, availability, and effectiveness for many edible applications.
Evaluation of Genetic Variability within a Collection of Cumin Genotypes Using RAPD, ISSR, SRAP and SCoT Markers and Variability of In Vitro Callus Induced Therefrom
Authors: Mousa Magdi A. A. , Abo-Elyousr Kamal A. M. , Ibrahim Omer H. M.
Published: June 2023

The availability of adequate information about the documentation and characterization of germplasm is fundamental for any crop improvement program. The importance of cumin as a medicinal plant yet the lack of information about its genetic variability encouraged us to initiate the current study aiming at assessing the genetic variability among 17 cumin genotypes from different geographical regions using four molecular markers (RAPD, ISSR, SRAP and SCoT). Further, the potential of six accessions to induce callus was studied under in vitro conditions on MS and B5 basal media supplemented with various combinations between 2,4-D and kinetin. Our findings showed that combining 87 primers, including 42, 15, 7 and 23 primers of RAPD, ISSR, SCoT and SRAP, respectively, facilitated detecting the relationship among the assessed cumin accessions. A total number of 765 bands were analyzed, among which only 74 bands were polymorphic. The polymorphism was low (9.67%) and varied among and within markers. The SCoT markers exposed the highest average values of polymorphism information content (0.06), resolving power (0.91) and diversity index (0.08), while ISSR induced the highest expected heterozygosity (0.06) and marker index (0.08). The UPGMA dendrogram based on data from all the molecular markers separated the genotypes into three main clusters, with a partial geographic-based relationship among the genotypes. Out of the six accessions evaluated for callus induction in vitro, five were potent to induce callus, with a frequency ranging from 90.4 to 97.5% and no significant differences among the five accessions tested using ANOVA. Two medium combinations showed superior results: MS amended with 2,4-D (4.44 mg/L) + Kin (0.22 mg/L) and B5 with 2,4-D (8.88 mg/L) + Kin (0.22 mg/L). Statistically significant variations in the relative growth rate of the produced callus were detected among accessions, where EG-4 accessions induced the highest values, followed by EG-5. All medium combinations, including 2,4-D alone, exhibited significant superiority compared with those including both 2,4-D and Kin. Our findings exposed low variability among the studied cumin accessions, implying the real need for more effort to assess wider populations from different geographic regions together with the need for reliable diversification programs.
Combined Analysis of Volatile Compounds and Extraction of Floral Fragrance Genes in Two Dendrobium Species
Authors: Yang Yanni , Xia Ke , Wu Qiaofen , Lu Xi , Lu Shunjiao , Zhao Zhiguo , Qiu Shuo
Published: June 2023

Many species of the Dendrobium genus are traditional Chinese herbal medicine and ornamental plants. Flower fragrance is one of the most important horticultural ornamental characters and plays a crucial role in the ecology, economy, and aesthetics of plants. However, the volatile constituents and key regulatory genes related to floral biosynthesis are poorly understood. In this experiment, the flowers from two species of Dendrobium with high-scent smells, Dendrobium moniliforme (L.) Sw. (D. moniliforme), and light-scent smells, Dendrobium nobile “H1” (D. “H1”), were selected. The aim of this study was to explore the key gene expression profiles of floral biosynthesis by combining volatile constituent determination and transcriptome analysis in two different Dendrobium species. Physiological determination results showed that 60 volatile compounds were identified in D. moniliforme and 52 volatile compounds were identified in D. ‘H1’ flowers in four flowering stages, and the full bloom stage was the most complicated stage because there were 41 and 33 volatile compounds, respectively. These compounds belong to terpenes, aromatics, fatty acids, nitrogenous compounds, ketones, alcohols, and alkanes, respectively. The components identified in the gynandrium and petals revealed that the petals were probably the most important sites affecting the release of volatiles. The relative content of terpene compounds was the highest, with 77.25% (D. moniliforme) and 50.38% (D. “H1”), respectively. Transcriptome analysis showed that differentially expressed genes (DEGs) were highly enriched in terpenoid backbone biosynthesis and that four linalool synthetase (LIS) genes were up-regulated in high-scent smell species. This study is helpful to explore the key genes of flower fragrance and provides a theoretical basis for further understanding of the regulatory molecular functions of floral synthesis and release, as well as for the cultivation of new aromatic species.
Maternal Exposure to Potentially Toxic Metals and Birth Weight: Preliminary Results from the DSAN-12M Birth Cohort in the Recôncavo Baiano, Brazil
Authors: Bah Homègnon A. Ferréol , dos Santos Nathália R. , Gomes Junior Erival A. , Costa Daisy O. , Martinez Victor O. , Pires Elis Macêdo , Santana João V. Araújo , Cerqueira Filipe da Silva , Menezes-Filho José A.
Published: June 2023

Prenatal exposure to potentially toxic metals (PTM) may impair fetal growth (FG). We investigated the relationship between maternal exposure to lead (Pb), cadmium (Cd) and manganese (Mn) and birth weight (BW) of 74 newborns. Blood was collected during the second trimester of pregnancy to determine Pb (PbB) and Cd (CdB), while hair (MnH) and toenails (MnTn) were used for Mn. Samples were analyzed by graphite furnace atomic absorption spectrophotometry (GFAAS). Sociodemographic and BW data were collected from questionnaires and maternity records, respectively. The medians (P25th–P75th) of PbB, CdB, MnH, and MnTn were, respectively, 0.9 (0.5–1.8) µg/dL; 0.54 (0.1–0.8) µg/L; 0.18 (0.1–0.4) µg/g; and 0.65 (0.37–1.22) µg/g. The means (standard deviation) of birth weight according to sex were 3067 (426.3) and 3442 (431) grams, respectively, for girls and boys. MnTn presented an inverse correlation with the BW/gestational age ratio for girls (rho = −0.478; p = 0.018), suggesting the effect of sex modification. Although BW correlation with CdB was not statistically significant, hierarchical linear regression (beta = −2.08; 95% CI–4.58 to 0.41) suggested a fetotoxic effect. These results confirmed the threat PTMs may represent and the need for more extensive research to elucidate their role in inadequate FG in developing countries.
Phosphoryl Trichloride–Method of Determination in Workplace Air
Authors: Kowalska Joanna , Wasilewski Paweł
Published: June 2023

The aim of this study was to develop and validate a method for determining phosphoryl trichloride in workplace air. The method is based on passing the tested air through a sodium carbonate-impregnated quartz fiber sampling filter. The substance collected on the sampling filter is extracted with ultrapure water. Phosphoryl trichloride is determined as chloride ions (the product of the hydrolysis of phosphoryl trichloride) in the obtained aqueous solutions by ion chromatography with conductometric detection. The developed method enables the determination of phosphoryl trichloride in the air in the concentration range from 0.004 to 0.160 mg/m3. The method is not applicable in the presence of phosphorus trichloride, hydrochloric acid, and its salts in the air. Good validation results were obtained. All requirements of the norm PN-EN 482 were met while developing and validating the method. This method can be used to measure workplace air in order to assess workers’ occupational exposure.
Investigation of Potential Drug Targets for Cholesterol Regulation to Treat Alzheimer’s Disease
Authors: Passero Marina , Zhai Tianhua , Huang Zuyi
Published: June 2023

Despite extensive research and seven approved drugs, the complex interplay of genes, proteins, and pathways in Alzheimer’s disease remains a challenge. This implies the intricacies of the mechanism for Alzheimer’s disease, which involves the interaction of hundreds of genes, proteins, and pathways. While the major hallmarks of Alzheimer’s disease are the accumulation of amyloid plaques and tau protein tangles, excessive accumulation of cholesterol is reportedly correlated with Alzheimer’s disease patients. In this work, protein-protein interaction analysis was conducted based upon the genes from a clinical database to identify the top protein targets with most data-indicated involvement in Alzheimer’s disease, which include ABCA1, CYP46A1, BACE1, TREM2, GSK3B, and SREBP2. The reactions and pathways associated with these genes were thoroughly studied for their roles in regulating brain cholesterol biosynthesis, amyloid beta accumulation, and tau protein tangle formation. Existing clinical trials for each protein target were also investigated. The research indicated that the inhibition of SREBP2, BACE1, or GSK3B is beneficial to reduce cholesterol and amyloid beta accumulation, while the activation of ABCA1, CYP46A1, or TREM2 has similar effects. In this study, Sterol Regulatory Element-Binding Protein 2 (SREBP2) emerged as the primary protein target. SREBP2 serves a pivotal role in maintaining cholesterol balance, acting as a transcription factor that controls the expression of several enzymes pivotal for cholesterol biosynthesis. Novel studies suggest that SREBP2 performs a multifaceted role in Alzheimer’s disease. The hyperactivity of SREBP2 may lead to heightened cholesterol biosynthesis, which suggested association with the pathogenesis of Alzheimer’s disease. Lowering SREBP2 levels in an Alzheimer’s disease mouse model results in reduced production of amyloid-beta, a major contributor to Alzheimer’s disease progression. Moreover, its thoroughly analyzed crystal structure allows for computer-aided screening of potential inhibitors; SREBP2 is thus selected as a prospective drug target. While more protein targets can be added onto the list in the future, this work provides an overview of key proteins involved in the regulation of brain cholesterol biosynthesis that may be further investigated for Alzheimer’s disease intervention.
Microfinance, an Alternative for Financing Entrepreneurship: Implications and Trends-Bibliometric Analysis
Authors: Coronel-Pangol Katherine , Heras-Tigre Doménica , Jiménez Yumbla Jonnathan , Aguirre Quezada Juan , Mora Pedro
Published: June 2023

Microfinance has become one of the most important financing alternatives for business start-ups, especially for vulnerable groups in poor regions. Microfinance provides access to financial products, especially to people who have been excluded from the traditional financial system. However, the mainstream literature on microfinance shows its impact on poverty alleviation, but it is not yet well developed to understand its dynamizing role in the entrepreneurial sector. There is still a large gap in the literature on analyzing microfinance as a financing alternative, so this paper seeks to find this relationship in the literature. A bibliometric analysis is applied, both of the performance of the publications and a word co-occurrence analysis during the period 2017–2022. The articles indexed in the Web of Science have been considered and systematized through the SCIMAT software v1.1.04, developed by the Soft Computing and Intelligent Information Systems Research Group, University of Granada, Granada, Spain. Microfinance institutions, education, entrepreneurship, organizational performance, business microcredits, and women microentrepreneurs have been identified as driving themes to be considered in future analyses. At the end of the document, the proposed future lines of research are presented. In addition, the results show the growing interest of the academic community in the topic, with 2022 being the year with the highest number of articles published on the topic.
Macrophages and Urokinase Plasminogen Activator Receptor System in Multiple Myeloma: Case Series and Literature Review
Authors: Manzo Paola , Giudice Valentina , Napolitano Filomena , De Novellis Danilo , Serio Bianca , Moscato Paolo , Montuori Nunzia , Selleri Carmine
Published: June 2023

The microenvironment plays an essential role in multiple myeloma (MM) development, progression, cell proliferation, survival, immunological escape, and drug resistance. Mesenchymal stromal cells and macrophages release tolerogenic cytokines and favor anti-apoptotic signaling pathway activation, while the urokinase plasminogen activator receptor (uPAR) system contributes to migration through an extracellular matrix. Here, we first summarized the role of macrophages and the uPAR system in MM pathogenesis, and then we reported the potential therapeutic effects of uPAR inhibitors in a case series of primary MM-derived adherent cells. Our preliminary results showed that after uPAR inhibitor treatments, interleukein-6 (mean ± SD, 8734.95 ± 4169.2 pg/mL vs. 359.26 ± 393.8 pg/mL, pre- vs. post-treatment; p = 0.0012) and DKK-1 levels (mean ± SD, 7005.41 ± 6393.4 pg/mL vs. 61.74 ± 55.2 pg/mL, pre- vs. post-treatment; p = 0.0043) in culture medium were almost completely abolished, supporting further investigation of uPAR blockade as a therapeutic strategy for MM treatment. Therefore, uPAR inhibitors could exert both anti-inflammatory and pro-immunosurveillance activity. However, our preliminary results need further validation in additional in vitro and in vivo studies.
Central and Peripheral Inflammation in Mild Cognitive Impairment in the Context of Alzheimer’s Disease
Authors: Schmidt-Morgenroth Inès , Michaud Philippe , Gasparini Fabrizio , Avrameas Alexandre
Published: June 2023

Mild cognitive impairment (MCI) is characterized by an abnormal decline in mental and cognitive function compared with normal cognitive aging. It is an underlying condition of Alzheimer’s disease (AD), an irreversible neurodegenerative disease. In recent years, neuroinflammation has been investigated as a new leading target that contributes to MCI progression into AD. Understanding the mechanism underlying inflammatory processes involved in the early onset of the disease could help find a safe and effective way to diagnose and treat patients. In this article, we assessed over twenty different blood and cerebrospinal fluid (CSF) inflammatory biomarker concentrations with immunoassay methods in patients with MCI (mild cognitive impairment), non-impaired control (NIC), and serum healthy control (HC). We performed group comparisons and analyzed in-group correlations between the biomarkers. We included 107 participants (mean age: 64.7 ± 7.8, women: 58.9%). CSF osteopontin and YKL-40 were significantly increased in the MCI group, whereas serum C-reactive protein and interleukin-6 were significantly higher (p < 0.001) in the NIC group compared with the MCI and HC groups. Stronger correlations between interleukin-1β and inflammasome markers were observed in the serum of the MCI group. We confirmed specific inflammatory activation in the central nervous system and interleukin-1β pathway upregulation in the serum of the MCI cohort.
A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation
Authors: Zhang Li , Zou Jiyuan , Wang Zhihao , Li Lin
Published: June 2023

Long non-coding RNAs (lncRNAs) are emerging as a critical regulator in controlling the expression level of genes involved in cell differentiation and development. Primordial follicle activation (PFA) is the first step for follicle maturation, and excessive PFA results in premature ovarian insufficiency (POI). However, the correlation between lncRNA and cell differentiation was largely unknown, especially during PFA. In this study, we observed the expression level of lncRNA was more specific than protein-coding genes in both follicles and granulosa cells, suggesting lncRNA might play a crucial role in follicle development. Hence, a systematical framework was needed to infer the functions of lncRNAs during PFA. Additionally, an increasing number of studies indicate that the subpathway is more precise in reflecting biological processes than the entire pathway. Given the complex expression patterns of lncRNA target genes, target genes were further clustered based on their expression similarity and classification performance to reveal the activated/inhibited gene modules, which intuitively illustrated the diversity of lncRNA regulation. Moreover, the knockdown of SBF2-AS1 in the A549 cell line and ZFAS1 in the SK-Hep1 cell line further validated the function of SBF2-AS1 in regulating the Hippo signaling subpathway and ZFAS1 in the cell cycle subpathway. Overall, our findings demonstrated the importance of subpathway analysis in uncovering the functions of lncRNAs during PFA, and paved new avenues for future lncRNA-associated research.
Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments
Authors: Ostrówka Michał , Duda-Madej Anna , Pietluch Filip , Mackiewicz Paweł , Gagat Przemysław
Published: June 2023

Lactoferrin, an iron-binding glycoprotein, plays a significant role in the innate immune system, with antibacterial, antivirial, antifungal, anticancer, antioxidant and immunomodulatory functions reported. It is worth emphasizing that not only the whole protein but also its derived fragments possess antimicrobial peptide (AMP) activity. Using AmpGram, a top-performing AMP classifier, we generated three novel human lactoferrin (hLF) fragments: hLF 397-412, hLF 448-464 and hLF 668-683, predicted with high probability as AMPs. For comparative studies, we included hLF 1-11, previously confirmed to kill some bacteria. With the four peptides, we treated three Gram-negative and three Gram-positive bacterial strains. Our results indicate that none of the three new lactoferrin fragments have antimicrobial properties for the bacteria tested, but hLF 1-11 was lethal against Pseudomonas aeruginosa. The addition of serine protease inhibitors with the hLF fragments did not enhance their activity, except for hLF 1-11 against P. aeruginosa, which MIC dropped from 128 to 64 µg/mL. Furthermore, we investigated the impact of EDTA with/without serine protease inhibitors and the hLF peptides on selected bacteria. We stress the importance of reporting non-AMP sequences for the development of next-generation AMP prediction models, which suffer from the lack of experimentally validated negative dataset for training and benchmarking.
Genome-Wide Identification and Expression Analysis of AS2 Genes in Brassica rapa Reveal Their Potential Roles in Abiotic Stress
Authors: Jiang Qiwei , Wu Xiaoyu , Zhang Xiaoyu , Ji Zhaojing , Cao Yunyun , Duan Qiaohong , Huang Jiabao
Published: June 2023

The ASYMMETRIC LEAVES2/LATERAL ORGAN BOUNDARIES (AS2/LOB) gene family plays a pivotal role in plant growth, induction of phytohormones, and the abiotic stress response. However, the AS2 gene family in Brassica rapa has yet to be investigated. In this study, we identified 62 AS2 genes in the B. rapa genome, which were classified into six subfamilies and distributed across 10 chromosomes. Sequence analysis of BrAS2 promotors showed that there are several typical cis-elements involved in abiotic stress tolerance and stress-related hormone response. Tissue-specific expression analysis showed that BrAS2-47 exhibited ubiquitous expression in all tissues, indicating it may be involved in many biological processes. Gene expression analysis showed that the expressions of BrAS2-47 and BrAS2-10 were significantly downregulated under cold stress, heat stress, drought stress, and salt stress, while BrAS2-58 expression was significantly upregulated under heat stress. RT-qPCR also confirmed that the expression of BrAS2-47 and BrAS2-10 was significantly downregulated under cold stress, drought stress, and salt stress, and in addition BrAS2-56 and BrAS2-4 also changed significantly under the three stresses. In addition, protein–protein interaction (PPI) network analysis revealed that the Arabidopsis thaliana genes AT5G67420 (homologous gene of BrAS2-47 and BrAS2-10) and AT3G49940 (homologous gene of BrAS2-58) can interact with NIN-like protein 7 (NLP7), which has been previously reported to play a role in resistance to adverse environments. In summary, our findings suggest that among the BrAS2 gene family, BrAS2-47 and BrAS2-10 have the most potential for the regulation of abiotic stress tolerance. These results will facilitate future functional investigations of BrAS2 genes in B. rapa.
Positive Chemotaxis of the Entomopathogenic Nematode Steinernema australe (Panagrolaimorpha: Steinenematidae) towards High-Bush Blueberry (Vaccinium corymbosum) Root Volatiles
Authors: Ceballos Ricardo , Palma-Millanao Rubén , Navarro Patricia D. , Urzúa Julio , Alveal Juan
Published: June 2023

The foraging behavior of the infective juveniles (IJs) of entomopathogenic nematodes (EPNs) relies on host-derived compounds, but in a tri-trophic context, herbivore-induced root volatiles act as signals enhancing the biological control of insect pests by recruiting EPNs. In southern Chile, the EPN Steinernema australe exhibits the potential to control the raspberry weevil, Aegorhinus superciliosus, a key pest of blueberry Vaccinium corymbosum. However, there is no information on the quality of the blueberry root volatile plume or the S. australe response to these chemicals as putative attractants. Here, we describe the root volatile profile of blueberries and the chemotaxis behavior of S. australe towards the volatiles identified from Vaccinium corymbosum roots, infested or uninfested with A. superciliosus larvae. Among others, we found linalool, α-terpineol, limonene, eucalyptol, 2-carene, 1-nonine, 10-undecyn-1-ol, and methyl salicylate in root volatiles and, depending on the level of the emissions, they were selected for bioassays. In the dose–response tests, S. australe was attracted to all five tested concentrations of methyl salicylate, 1-nonine, α-terpineol, and 2-carene, as well as to 100 µg mL−1 of 10-undecyn-1-ol, 0.1 and 100 µg mL−1 of linalool, and 100 µg mL−1 of limonene, whereas eucalyptol elicited no attraction or repellency. These results suggest that some volatiles released from damaged roots attract S. australe and may have implications for the biocontrol of subterranean pests.
Effects of L-Cysteine and γ-Aminobutyric Acid Treatment on Postharvest Quality and Antioxidant Activity of Loquat Fruit during Storage
Authors: Zhang Huifen , Pu Jing , Liu Han , Wang Miao , Du Ying , Tang Xiaofu , Luo Xian , Wang Yongqing , Deng Qunxian
Published: June 2023

Sichuan is the China’s leading producer of loquat, with the largest cultivation area and yield ranked first in China. Loquat is a seasonal fruit highly appreciated by consumers; however, the fruit is prone to browning and lignification after harvest, affecting its storage quality. The effects of L-Cysteine (L-Cys, 0.01, 0.05, 0.1, 0.2%) and γ-aminobutyric acid (GABA, 0.025, 0.05, 0.075, 0.1%) on the sensory quality and antioxidant activity of loquat fruit during cold storage at 4 °C for 35 days and simulated shelf life for 5 days were investigated. The results showed that after 40 days of storage, compared with the control, 0.05% L-Cys and 0.05% GABA treatment of ‘Zaozhong No. 6’ loquat fruit effectively reduced the weight loss rate, browning index, decay index, respiratory rate, firmness, and lignin content and slowed the decreases in total soluble solids, soluble sugar, titratable acidityand vitamin C contents. The application of 0.05% L-Cys and 0.05% GABA significantly increased the contents of total phenols, total flavonoids, flavanols, and carotenoids; delayed the increase of relative electric conductivity, MDA, POD, and PPO activities; and significantly enhanced the activities of SOD and CAT, DPPH free radical scavenging ability, and FRAP, thereby improving antioxidant capacity. In summary, 0.05% L-Cys and 0.05% GABA treatment promotes the quality of loquat fruit after 40 days of storage, and significantly enhances antioxidant capacity, thus delaying senescence after harvest.
Differential Pattern of Cell Death and ROS Production in Human Airway Epithelial Cells Exposed to Quinones Combined with Heated-PM2.5 and/or Asian Sand Dust
Authors: Honda Akiko , Inoue Ken-ichiro , Higashihara Makoto , Ichinose Takamichi , Ueda Kayo , Takano Hirohisa
Published: June 2023

The combined toxicological effects of airborne particulate matter (PM), such as PM2.5, and Asian sand dust (ASD), with surrounding chemicals, particularly quinones, on human airway epithelial cells remain underexplored. In this study, we established an in vitro combination exposure model using 1,2-naphthoquinones (NQ) and 9,10-phenanthroquinones (PQ) along with heated PM (h-PM2.5 and h-ASD) to investigate their potential synergistic effects. The impacts of quinones and heated PM on tetrazolium dye (WST-1) reduction, cell death, and cytokine and reactive oxygen species (ROS) production were examined. Results revealed that exposure to 9,10-PQ with h-PM2.5 and/or h-ASD dose-dependently increased WST-1 reduction at 1 μM compared to the corresponding control while markedly decreasing it at 10 μM. Higher early apoptotic, late apoptotic, or necrotic cell numbers were detected in 9,10-PQ + h-PM2.5 exposure than in 9,10-PQ + h-ASD or 9,10-PQ + h-PM2.5 + h-ASD. Additionally, 1,2-NQ + h-PM2.5 exposure also resulted in an increase in cell death compared to 1,2-NQ + h-ASD and 1,2-NQ + h-PM2.5 + h-ASD. Quinones with or without h-PM2.5, h-ASD, or h-PM2.5 + h-ASD significantly increased ROS production, especially with h-PM2.5. Our findings suggest that quinones, at relatively low concentrations, induce cell death synergistically in the presence of h-PM2.5 rather than h-ASD and h-PM2.5 + h-ASD, partially through the induction of apoptosis with increased ROS generation.
Influence of the Type of Nanofillers on the Properties of Composites Used in Dentistry and 3D Printing
Authors: Noworyta Małgorzata , Topa-Skwarczyńska Monika , Jamróz Paweł , Oksiuta Dawid , Tyszka-Czochara Małgorzata , Trembecka-Wójciga Klaudia , Ortyl Joanna
Published: June 2023

Photopolymerization is a growing field with an extensive range of applications and is environmentally friendly owing to its energy-efficient nature. Such light-assisted curing methods were initially used to cure the coatings. However, it has become common to use photopolymerization to produce 3D objects, such as bridges or dental crowns, as well as to cure dental fillings. In this study, polymer nanocomposites containing inorganic nanofillers (such as zinc nano-oxide and zinc nano-oxide doped with two wt.% aluminum, titanium nano-oxide, kaolin nanoclay, zirconium nano-oxide, aluminum nano-oxide, and silicon nano-oxide) were fabricated and studied using Real Time FT-IR to investigate the effects of these nanoadditives on the final conversion rates of the obtained nanocomposites. The effects of the fillers on the viscosity of the produced nanocomposites were also investigated, and 3D prints of the selected nanocomposites were presented.