bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Concentrated COVID-19 Outbreaks in Elderly Facilities in Suita City, Osaka Prefecture, Japan
Authors: Shibata Toshiyuki , Okano Sawa , Onozuka Daisuke , Ohta Etsuko , Kutsuna Satoshi
Published: October 2023

There are several types of facilities for elderly individuals in Japan. Infection control efforts, such as care provision and medical care access, differ according to the type of facility. Elderly individuals at these facilities who were infected with coronavirus disease 2019 (COVID-19) experienced severe illness and mortality. This study aimed to determine the characteristics of concentrated COVID-19 outbreaks that occurred in nursing homes and care facilities in Suita City. During this study, twenty-five elderly facilities in Suita City with a capacity of 40 or more individuals where an outbreak occurred during the sixth or seventh wave of infection were included. We investigated whether there was a difference in the COVID-19 incidence and the percentage of positive cases according to the type of facility. We also investigated the relationship between the facility capacity and positive case rate and that between the number of positive cases and outbreak duration. The incidence rate of COVID-19 was significantly different according to the facility type (p < 0.001). No association was found between the facility capacity and positive case rate. The outbreak duration increased as the number of positive cases increased (p = 0.004).
Potential Theranostic Roles of SLC4 Molecules in Human Diseases
Authors: Zhong Jingwen , Dong Jing , Ruan Wenyan , Duan Xiaohong
Published: October 2023

The solute carrier family 4 (SLC4) is an important protein responsible for the transport of various ions across the cell membrane and mediating diverse physiological functions, such as the ion transporting function, protein-to-protein interactions, and molecular transduction. The deficiencies in SLC4 molecules may cause multisystem disease involving, particularly, the respiratory system, digestive, urinary, endocrine, hematopoietic, and central nervous systems. Currently, there are no effective strategies to treat these diseases. SLC4 proteins are also found to contribute to tumorigenesis and development, and some of them are regarded as therapeutic targets in quite a few clinical trials. This indicates that SLC4 proteins have potential clinical prospects. In view of their functional characteristics, there is a critical need to review the specific functions of bicarbonate transporters, their related diseases, and the involved pathological mechanisms. We summarize the diseases caused by the mutations in SLC4 family genes and briefly introduce the clinical manifestations of these diseases as well as the current treatment strategies. Additionally, we illustrate their roles in terms of the physiology and pathogenesis that has been currently researched, which might be the future therapeutic and diagnostic targets of diseases and a new direction for drug research and development.
Luminescence of In(III)Cl-etioporphyrin-I
Authors: Koptyaev Andrey I. , Zhabanov Yuriy A. , Pakhomov Georgy L. , Pershukevich Piotr P. , Arabei Serguei M. , Stuzhin Pavel A.
Published: October 2023

The luminescent and photophysical properties of the etioporphyrin-I complex with indium(III) chloride, InCl-EtioP-I were experimentally studied at room and liquid nitrogen temperatures in pure and mixed toluene solutions. At 77 K, in a 1:2 mixture of toluene with diethyl ether, the quantum yield of phosphorescence reaches 10.2%, while the duration of phosphorescence is 17 ms. At these conditions, the ratio of phosphorescence-to-fluorescence integral intensities is equal to 26.1, which is the highest for complexes of this type. At 298 K, the quantum yield of the singlet oxygen generation is maximal in pure toluene (81%). Quantum-chemical calculations of absorption and fluorescence spectra at temperatures of 77 K and 298 K qualitatively coincide with the experimental data. The InCl-EtioP-I compound will further be used as a photoresponsive material in thin-film optoelectronic devices.
A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis
Authors: Brandenburg Klaus , Ferrer-Espada Raquel , Martinez-de-Tejada Guillermo , Nehls Christian , Fukuoka Satoshi , Mauss Karl , Weindl Günther , Garidel Patrick
Published: October 2023

Sepsis is a life-threatening condition caused by the body’s overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which rank among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection is frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. In the present review, we will analyze similarities and differences between COVID-19 and sepsis at the pathophysiological, epidemiological, and molecular levels.
Vascular Endothelial Growth Factor A (VEGFA) Regulates Hepatic Lipid and Glycogen Metabolism in Schizothorax prenanti
Authors: Wang Yan , Ni Jiahui , Wang Aiyu , Zhang Run , Wang Linjie
Published: October 2023

Vascular endothelial growth factor A (VEGFA) plays important roles in angiogenesis, inflammatory response as well as energy metabolism in mammals. However, its effect on glycolipid metabolism in fish has not been reported. In this study, we cloned and characterized the vegfa gene of Schizothorax prenanti (S. prenanti). vegfa expression was significantly higher in liver and muscle than that in other tissues. Then, the VEGFA recombinant protein was expressed in Escherichia coli and obtained after purification. VEGFA i.p. injection significantly increased the serum glucose and TG content compared with the control group. Moreover, VEGFA protein aggravated the glycogen and lipid deposition in the liver of S. prenanti. In addition, we found that VEGFA treatment increased hepatocyte glycogen and lipid droplet content and increased the levels of pAMPKα (T172). Furthermore, AMPKα inhibition attenuated the ability of VEGFA to induce TG and glycogen accumulation. These results demonstrate that VEGFA regulates hepatic lipid and glycogen metabolism through AMPKα in S. prenanti, which may contribute to a better understanding of VEGFA functions in the glycolipid metabolism of fish.
Quercetin Ameliorates Deoxynivalenol-Induced Intestinal Injury and Barrier Dysfunction Associated with Inhibiting Necroptosis Signaling Pathway in Weaned Pigs
Authors: Liu Jiahao , Zhou Mohan , Xu Qilong , Lv Qingqing , Guo Junjie , Qin Xu , Xu Xiaoye , Chen Shaokui , Zhao Jiangchao , Xiao Kan , Liu Yulan
Published: October 2023

Quercetin (Que) is a flavonol compound found in plants, which has a variety of biological activities. Necroptosis, a special form of programmed cell death, plays a vital role in the development of many gastrointestinal diseases. This study aimed to explore whether Que could attenuate the intestinal injury and barrier dysfunction of piglets after deoxynivalenol (DON) exposure through modulating the necroptosis signaling pathway. Firstly, twenty-four weaned piglets were used in a 2 × 2 factorial design and the main factors, including Que (basal diet or diet supplemented with 100 mg/kg Que) and DON exposure (control feed or feed contaminated with 4 mg/kg DON). After feeding for 21 d, piglets were killed for samples. Next, the intestinal porcine epithelial cell line (IPEC-1) was pretreated with or without Que (10 μmol/mL) in the presence or absence of a DON challenge (0.5 μg/mL). Dietary Que increased the body weight, average daily gain, and average daily feed intake (p < 0.05) through the trial. Que supplementation improved the villus height, and enhanced the intestinal barrier function (p < 0.05) indicated by the higher protein expression of occludin and claudin-1 (p < 0.05) in the jejunum of the weaned piglets after DON exposure. Dietary Que also down-regulated the protein abundance of total receptor interacting protein kinase 1 (t-RIP1), phosphorylated RIP1 (p-RIP1), p-RIP3, total mixed lineage kinase domain-like protein (t-MLKL), and p-MLKL (p < 0.05) in piglets after DON exposure. Moreover, Que pretreatment increased the cell viability and decreased the lactate dehydrogenase (LDH) activity (p < 0.05) in the supernatant of IPEC-1 cells after DON challenge. Que treatment also improved the epithelial barrier function indicated by a higher transepithelial electrical resistance (TEER) (p < 0.001), lower fluorescein isothiocyanate-labeled dextran (FD4) flux (p < 0.001), and better distribution of occludin and claudin-1 (p < 0.05) after DON challenge. Additionally, pretreatment with Que also inhibited the protein abundance of t-RIP1, p-RIP1, t-RIP3, p-RIP3, t-MLKL, and p-MLKL (p < 0.05) in IPEC-1 cells after DON challenge. In general, our data suggest that Que can ameliorate DON-induced intestinal injury and barrier dysfunction associated with suppressing the necroptosis signaling pathway.
Searching for Atherosclerosis Biomarkers by Proteomics: A Focus on Lesion Pathogenesis and Vulnerability
Authors: Nieddu Gabriele , Formato Marilena , Lepedda Antonio Junior
Published: October 2023

Plaque rupture and thrombosis are the most important clinical complications in the pathogenesis of stroke, coronary arteries, and peripheral vascular diseases. The identification of early biomarkers of plaque presence and susceptibility to ulceration could be of primary importance in preventing such life-threatening events. With the improvement of proteomic tools, large-scale technologies have been proven valuable in attempting to unravel pathways of atherosclerotic degeneration and identifying new circulating markers to be utilized either as early diagnostic traits or as targets for new drug therapies. To address these issues, different matrices of human origin, such as vascular cells, arterial tissues, plasma, and urine, have been investigated. Besides, proteomics was also applied to experimental atherosclerosis in order to unveil significant insights into the mechanisms influencing atherogenesis. This narrative review provides an overview of the last twenty years of omics applications to the study of atherogenesis and lesion vulnerability, with particular emphasis on lipoproteomics and vascular tissue proteomics. Major issues of tissue analyses, such as plaque complexity, sampling, availability, choice of proper controls, and lipoproteins purification, will be raised, and future directions will be addressed.
Spatiotemporal Patterns of Five Small Heat Shock Protein Genes in Hyphantria cunea in Response to Thermal Stress
Authors: Zhao Shiyue , Liu Yukun , Li Hui , Li Zichun , Hao Dejun
Published: October 2023

Hyphantria cunea (Drury), a destructive polyphagous pest, has been spreading southward after invading northern China, which indicates that this insect species is facing a huge thermal challenge. Small heat shock proteins (sHSPs) function as ATP-independent molecular chaperones that protect insects from heat stress damage. In order to explore the role of sHSPs in the thermotolerance of H. cunea, five novel sHSP genes of H. cunea were cloned, including an orthologous gene (HcHSP21.4) and four species-specific sHSP genes (HcHSP18.9, HcHSP20.1, HcHSP21.5, and HcHSP29.8). Bioinformatics analysis showed that the proteins encoded by these five HcHSPs contained typical α-crystallin domains. Quantitative real-time PCR analysis revealed the ubiquitous expression of all HcHSPs across all developmental stages of H. cunea, with the highest expression levels in pupae and adults. Four species-specific HcHSPs were sensitive to high temperatures. The expression levels of HcHSPs were significantly up-regulated under heat stress and increased with increasing temperature. The expression levels of HcHSPs in eggs exhibited an initial up-regulation in response to a temperature of 40 °C. In other developmental stages, the transcription of HcHSPs was immediately up-regulated at 30 °C or 35 °C. HcHSPs transcripts were abundant in the cuticle before and after heat shock. The expression of HcHSP21.4 showed weak responses to heat stress and constitutive expression in the tissues tested. These results suggest that most of the HcHSPs are involved in high-temperature response and may also have functions in the normal development and reproduction of H. cunea.
Epigenetic Activation of TUSC3 Sensitizes Glioblastoma to Temozolomide Independent of MGMT Promoter Methylation Status
Authors: Wu Qiong , Berglund Anders E. , Macaulay Robert J. , Etame Arnold B.
Published: October 2023

Temozolomide (TMZ) is an important first-line treatment for glioblastoma (GBM), but there are limitations to TMZ response in terms of durability and dependence on the promoter methylation status of the DNA repair gene O6-methylguanine DNA methyltransferase (MGMT). MGMT-promoter-hypermethylated (MGMT-M) GBMs are more sensitive to TMZ than MGMT-promoter-hypomethylated (MGMT-UM) GBMs. Moreover, TMZ resistance is inevitable even in TMZ-sensitive MGMT-M GBMs. Hence, epigenetic reprogramming strategies are desperately needed in order to enhance TMZ response in both MGMT-M and MGMT-UM GBMs. In this study, we present novel evidence that the epigenetic reactivation of Tumor Suppressor Candidate 3 (TUSC3) can reprogram sensitivity of GBM stem cells (GSCs) to TMZ irrespective of MGMT promoter methylation status. Interrogation of TCGA patient GBM datasets confirmed TUSC3 promoter regulation of TUSC3 expression and also revealed a strong positive correlation between TUSC3 expression and GBM patient survival. Using a combination of loss-of-function, gain-of-function and rescue studies, we demonstrate that TUSC3 reactivation is associated with enhanced TMZ response in both MGMT-M and MGMT-UM GSCs. Further, we provide novel evidence that the demethylating agent 5-Azacitidine (5-Aza) reactivates TUSC3 expression in MGMT-M GSCs, whereas the combination of 5-Aza and MGMT inhibitor Lomeguatrib is necessary for TUSC3 reactivation in MGMT-UM GSCs. Lastly, we propose a pharmacological epigenetic reactivation strategy involving TUSC3 that leads to significantly prolonged survival in MGMT-M and MGMT-UM orthotopic GSCs models. Collectively, our findings provide a framework and rationale to further explore TUSC3-mediated epigenetic reprogramming strategies that could enhance TMZ sensitivity and outcomes in GBM. Mechanistic and translational evidence gained from such studies could contribute towards optimal design of impactful trials for MGMT-UM GBMs that currently do not have good treatment options.
Biotechnological Plastic Degradation and Valorization Using Systems Metabolic Engineering
Authors: Lee Ga Hyun , Kim Do-Wook , Jin Yun Hui , Kim Sang Min , Lim Eui Seok , Cha Min Ji , Ko Ja Kyong , Gong Gyeongtaek , Lee Sun-Mi , Um Youngsoon , Han Sung Ok , Ahn Jung Ho
Published: October 2023

Various kinds of plastics have been developed over the past century, vastly improving the quality of life. However, the indiscriminate production and irresponsible management of plastics have led to the accumulation of plastic waste, emerging as a pressing environmental concern. To establish a clean and sustainable plastic economy, plastic recycling becomes imperative to mitigate resource depletion and replace non-eco-friendly processes, such as incineration. Although chemical and mechanical recycling technologies exist, the prevalence of composite plastics in product manufacturing complicates recycling efforts. In recent years, the biodegradation of plastics using enzymes and microorganisms has been reported, opening a new possibility for biotechnological plastic degradation and bio-upcycling. This review provides an overview of microbial strains capable of degrading various plastics, highlighting key enzymes and their role. In addition, recent advances in plastic waste valorization technology based on systems metabolic engineering are explored in detail. Finally, future perspectives on systems metabolic engineering strategies to develop a circular plastic bioeconomy are discussed.
Combination of On-Line and Off-Line Two-Dimensional Liquid Chromatography-Mass Spectrometry for Comprehensive Characterization of mAb Charge Variants and Precise Instructions for Rapid Process Development
Authors: Jin Xiaoqing , He Bingfang
Published: October 2023

Charge variants, as an important quality attribute of mAbs, must be comprehensively characterized and monitored during development. However, due to their complex structure, the characterization of charge variants is challenging, labor-intensive, and time-consuming when using traditional approaches. This work combines on-line and off-line 2D-LC-MS to comprehensively characterize mAb charge variants and quickly offer precise instructions for process development. Six charge variant peaks of mAb 1 were identified using the developed platform. Off-line 2D-LC-MS analysis at the peptide level showed that the acidic peak P1 and the basic peaks P4 and P5 were caused by the deamidation of asparagine, the oxidation of methionine, and incomplete C-terminal K loss, respectively. On-line 2D-LC-MS at the intact protein level was used to identify the root causes, and it was found that the acidic peak P2 and the basic peak P6 were due to the glutathionylation of cysteine and succinimidation of aspartic acid, respectively, which were not found in off-line 2D-LC-MS because of the loss occurring during pre-treatment. These results suggest that process development could focus on cell culture for adjustment of glutathionylation. In this paper, we propose the concept of precision process development based on on-line 2D-LC-MS, which could quickly offer useful data with only 0.6 mg mAb within 6 h for precise instructions for process development. Overall, the combination of on-line and off-line 2D-LC-MS can characterize mAb charge variants more comprehensively, precisely, and quickly than other approaches. This is a very effective platform with routine operations that provides precise instructions for process development within hours, and will help to accelerate the development of innovative therapeutics.
Genome-Wide Identification and Characterization of the YTH Domain-Containing RNA-Binding Protein Family in Liriodendron chinense
Authors: Yao Sheng , Zhang Jingjing , Cheng Xiang , Wang Dengbao , Yu Wenya , Ji Kongshu , Yu Qiong
Published: October 2023

N6-methyladenosine (m6A) is becoming one of the most important RNA modifications in plant growth and development, including defense, cell differentiation, and secondary metabolism. YT521-B homology (YTH) domain-containing RNA-binding proteins, identified as m6A readers in epitranscriptomics, could affect the fate of m6A-containing RNA by recognizing and binding the m6A site. Therefore, the identification and study of the YTH gene family in Liriodendron chinense (L. chinense) can provide a molecular basis for the study of the role of m6A in L. chinense, but studies on the YTH gene in L. chinense have not been reported. We identified nine putative YTH gene models in the L. chinense genome, which can be divided into DF subgroups and DC subgroups. Domain sequence analysis showed that the LcYTH protein had high sequence conservation. A LcYTH aromatic cage bag is composed of tryptophan and tryptophan (WWW). PrLDs were found in the protein results of YTH, suggesting that these genes may be involved in the process of liquid–liquid phase separation. LcYTH genes have different tissue expression patterns, but the expression of LcYTHDF2 is absolutely dominant in all tissues. In addition, the expression of the LcYTH genes is changed in response to ABA and MeJA. In this study, We identified and analyzed the expression pattern of LcYTH genes. Our results laid a foundation for further study of the function of the LcYTH gene and further genetic and functional analyses of m6A RNA modification in forest trees.
Neurolysin Knockout Mice in a Diet-Induced Obesity Model
Authors: Caprioli Bruna , Eichler Rosangela A. S. , Silva Renée N. O. , Martucci Luiz Felipe , Reckziegel Patricia , Ferro Emer S.
Published: October 2023

Neurolysin oligopeptidase (E.C.3.4.24.16; Nln), a member of the zinc metallopeptidase M3 family, was first identified in rat brain synaptic membranes hydrolyzing neurotensin at the Pro-Tyr peptide bond. The previous development of C57BL6/N mice with suppression of Nln gene expression (Nln-/-), demonstrated the biological relevance of this oligopeptidase for insulin signaling and glucose uptake. Here, several metabolic parameters were investigated in Nln-/- and wild-type C57BL6/N animals (WT; n = 5–8), male and female, fed either a standard (SD) or a hypercaloric diet (HD), for seven weeks. Higher food intake and body mass gain was observed for Nln-/- animals fed HD, compared to both male and female WT control animals fed HD. Leptin gene expression was higher in Nln-/- male and female animals fed HD, compared to WT controls. Both WT and Nln-/- females fed HD showed similar gene expression increase of dipeptidyl peptidase 4 (DPP4), a peptidase related to glucagon-like peptide-1 (GLP-1) metabolism. The present data suggest that Nln participates in the physiological mechanisms related to diet-induced obesity. Further studies will be necessary to better understand the molecular mechanism responsible for the higher body mass gain observed in Nln-/- animals fed HD.
Characterizing Early Cardiac Metabolic Programming via 30% Maternal Nutrient Reduction during Fetal Development in a Non-Human Primate Model
Authors: Pereira Susana P. , Diniz Mariana S. , Tavares Ludgero C. , Cunha-Oliveira Teresa , Li Cun , Cox Laura A. , Nijland Mark J. , Nathanielsz Peter W. , Oliveira Paulo J.
Published: October 2023

Intra-uterine growth restriction (IUGR) is a common cause of fetal/neonatal morbidity and mortality and is associated with increased offspring predisposition for cardiovascular disease (CVD) development. Mitochondria are essential organelles in maintaining cardiac function, and thus, fetal cardiac mitochondria could be responsive to the IUGR environment. In this study, we investigated whether in utero fetal cardiac mitochondrial programming can be detectable in an early stage of IUGR pregnancy. Using a well-established nonhuman IUGR primate model, we induced IUGR by reducing by 30% the maternal diet (MNR), both in males (MNR-M) and in female (MNR-F) fetuses. Fetal cardiac left ventricle (LV) tissue and blood were collected at 90 days of gestation (0.5 gestation, 0.5 G). Blood biochemical parameters were determined and heart LV mitochondrial biology assessed. MNR fetus biochemical blood parameters confirm an early fetal response to MNR. In addition, we show that in utero cardiac mitochondrial MNR adaptations are already detectable at this early stage, in a sex-divergent way. MNR induced alterations in the cardiac gene expression of oxidative phosphorylation (OXPHOS) subunits (mostly for complex-I, III, and ATP synthase), along with increased protein content for complex-I, -III, and -IV subunits only for MNR-M in comparison with male controls, highlight the fetal cardiac sex-divergent response to MNR. At this fetal stage, no major alterations were detected in mitochondrial DNA copy number nor markers for oxidative stress. This study shows that in 90-day nonhuman primate fetuses, a 30% decrease in maternal nutrition generated early in utero adaptations in fetal blood biochemical parameters and sex-specific alterations in cardiac left ventricle gene and protein expression profiles, affecting predominantly OXPHOS subunits. Since the OXPHOS system is determinant for energy production in mitochondria, our findings suggest that these early IUGR-induced mitochondrial adaptations play a role in offspring’s mitochondrial dysfunction and can increase predisposition to CVD in a sex-specific way.
Selection and Validation of Reference Genes for Reverse-Transcription Quantitative PCR Analysis in Sclerotium rolfsii
Authors: Jiang Chaofan , Zhou Lin , Zhao Qingchen , Wang Mengke , Shen Sirui , Zhao Te , Cui Kaidi , He Leiming
Published: October 2023

Reference genes are important for the accuracy of gene expression profiles using reverse-transcription quantitative PCR (RT-qPCR). However, there are no available reference genes reported for Sclerotium rolfsii; it actually has a pretty diverse and wide host range. In this study, seven candidate reference genes (UBC, β-TUB, 28S, 18S, PGK, EF1α and GAPDH) were validated for their expression stability in S. rolfsii under conditions of different developmental stages, populations, fungicide treatments, photoperiods and pHs. Four algorithm programs (geNorm, Normfinder, Bestkeeper and ΔCt) were used to evaluate the gene expression stability, and RefFinder was used to integrate the ranking results of four programs. Two reference genes were recommended by RefFinder for RT-qPCR normalization in S. rolfsii. The suitable reference genes were GAPDH and UBC across developmental stages, PGK and UBC across populations, GAPDH and PGK across fungicide treatments, EF1α and PGK across photoperiods, β-TUB and EF1α across pHs and PGK and GAPDH across all samples. Four target genes (atrB, PacC, WC1 and CAT) were selected for the validation of the suitability of selected reference genes. However, using one or two reference genes in combination to normalize the expression of target genes showed no significant difference in S. rolfsii. In short, this study provided reliable reference genes for studying the expression and function of genes in S. rolfsii.
A Narrative Review: The Effect and Importance of Carotenoids on Aging and Aging-Related Diseases
Authors: Bakac Elif Rabia , Percin Ece , Gunes-Bayir Ayse , Dadak Agnes
Published: October 2023

Aging is generally defined as a time-dependent functional decline that affects most living organisms. The positive increase in life expectancy has brought along aging-related diseases. Oxidative stress caused by the imbalance between pro-oxidants and antioxidants can be given as one of the causes of aging. At the same time, the increase in oxidative stress and reactive oxygen species (ROS) is main reason for the increase in aging-related diseases such as cardiovascular, neurodegenerative, liver, skin, and eye diseases and diabetes. Carotenoids, a natural compound, can be used to change the course of aging and aging-related diseases, thanks to their highly effective oxygen-quenching and ROS-scavenging properties. Therefore, in this narrative review, conducted using the PubMed, ScienceDirect, and Google Scholar databases and complying with the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines, the effects of carotenoids on aging and aging-related diseases were analyzed. Carotenoids are fat-soluble, highly unsaturated pigments that occur naturally in plants, fungi, algae, and photosynthetic bacteria. A large number of works have been conducted on carotenoids in relation to aging and aging-related diseases. Animal and human studies have found that carotenoids can significantly reduce obesity and fatty liver, lower blood sugar, and improve liver fibrosis in cirrhosis, as well as reduce the risk of cardiovascular disease and erythema formation, while also lowering glycated hemoglobin and fasting plasma glucose levels. Carotenoid supplementation may be effective in preventing and delaying aging and aging-related diseases, preventing and treating eye fatigue and dry eye disease, and improving macular function. These pigments can be used to stop, delay, or treat aging-related diseases due to their powerful antioxidant, restorative, anti-proliferative, anti-inflammatory, and anti-aging properties. As an increasingly aging population emerges globally, this review could provide an important prospective contribution to public health.
Modulation of Caecal Microbiota and Metabolome Profile in Salmonella-Infected Broilers by Phage Therapy
Authors: Lorenzo-Rebenaque Laura , Casto-Rebollo Cristina , Diretto Gianfranco , Frusciante Sarah , Rodríguez Juan Carlos , Ventero María-Paz , Molina-Pardines Carmen , Vega Santiago , Marin Clara , Marco-Jiménez Francisco
Published: October 2023

Bacteriophage therapy is considered one of the most promising tools to control zoonotic bacteria, such as Salmonella, in broiler production. Phages exhibit high specificity for their targeted bacterial hosts, causing minimal disruption to the niche microbiota. However, data on the gut environment’s response to phage therapy in poultry are limited. This study investigated the influence of Salmonella phage on host physiology through caecal microbiota and metabolome modulation using high-throughput 16S rRNA gene sequencing and an untargeted metabolomics approach. We employed 24 caecum content samples and 24 blood serum samples from 4-, 5- and 6-week-old broilers from a previous study where Salmonella phages were administered via feed in Salmonella-infected broilers, which were individually weighed weekly. Phage therapy did not affect the alpha or beta diversity of the microbiota. Specifically, we observed changes in the relative abundance of 14 out of the 110 genera using the PLS-DA and Bayes approaches. On the other hand, we noted changes in the caecal metabolites (63 up-accumulated and 37 down-accumulated out of the 1113 caecal metabolites). Nevertheless, the minimal changes in blood serum suggest a non-significant physiological response. The application of Salmonella phages under production conditions modulates the caecal microbiome and metabolome profiles in broilers without impacting the host physiology in terms of growth performance.
Alternative Splicing Variation: Accessing and Exploiting in Crop Improvement Programs
Authors: Dwivedi Sangam L. , Quiroz Luis Felipe , Reddy Anireddy S. N. , Spillane Charles , Ortiz Rodomiro
Published: October 2023

Alternative splicing (AS) is a gene regulatory mechanism modulating gene expression in multiple ways. AS is prevalent in all eukaryotes including plants. AS generates two or more mRNAs from the precursor mRNA (pre-mRNA) to regulate transcriptome complexity and proteome diversity. Advances in next-generation sequencing, omics technology, bioinformatics tools, and computational methods provide new opportunities to quantify and visualize AS-based quantitative trait variation associated with plant growth, development, reproduction, and stress tolerance. Domestication, polyploidization, and environmental perturbation may evolve novel splicing variants associated with agronomically beneficial traits. To date, pre-mRNAs from many genes are spliced into multiple transcripts that cause phenotypic variation for complex traits, both in model plant Arabidopsis and field crops. Cataloguing and exploiting such variation may provide new paths to enhance climate resilience, resource-use efficiency, productivity, and nutritional quality of staple food crops. This review provides insights into AS variation alongside a gene expression analysis to select for novel phenotypic diversity for use in breeding programs. AS contributes to heterosis, enhances plant symbiosis (mycorrhiza and rhizobium), and provides a mechanistic link between the core clock genes and diverse environmental clues.
The Evaluation and Obstacle Analysis of Urban Safety Resilience Based on Multi-Factor Perspective in Beijing
Authors: Liu Lu , Pei Jingjing , Wang Huiquan , Luo Yun
Published: October 2023

Urban resilience assessment is crucial to guarantee the safe and stable operation of our cities. Looking at the whole process of emergencies from the occurrence, development, causing disaster losses to taking emergency response measures, we combine the danger of urban accident and disaster, the capacity of disaster-bearing carriers, and the emergency management capacity as the influencing factors. Taking Beijing as an example, considering the completeness of the relevant indicators and the difficulty of obtaining data, TOPSIS is used to construct a multi-factor comprehensive assessment model of urban safety resilience; At the same time, the important factors constraining the improvement of safety resilience are further analyzed by using the obstacle degree model. The results show that: among the 16 districts in Beijing, Chaoyang and Haidian districts have the highest level of safety resilience; the level of the degree of disaster tolerance among the multi-factors has the greatest impact on the level of urban safety resilience in Beijing; and the multifactorial comprehensive assessment model of urban resilience is able to reflect the urban resilience distribution, discover the weaknesses that exist in the development of urban safety and provide decision-making aids for the relevant city managers to carry out urban resilience construction.
A Bibliometric Analysis of Child-Friendly Cities: A Cross-Database Analysis from 2000 to 2022
Authors: Liao Yuhui , Furuya Katsunori
Published: October 2023

This study performs a comprehensive bibliometric analysis of research on child-friendly cities (CFC) conducted from 2000 to 2022. It investigates the global and domestic research trends using two prominent databases, Web of Science (WOS) and China National Knowledge Infrastructure (CNKI). The study reveals increasing global and domestic research publications on CFC, demonstrating an expanding interest in the area. The contributions of this study are threefold. First, it describes the status of the CFC in two databases based on quantitative analysis and an intuitive visualization, identifying patterns, hotspots, trends, and gaps. Second, by comparing the two databases, we have the following four findings: (1) the advancement of CFC construction and research focus is linked to economic development; (2) collaborative efforts involving multiple parties are crucial for policy implementation and engaging children in decision making; (3) the two databases demonstrate differing research emphases on the environment; (4) it is essential to broaden the channels for child participation. Finally, we propose the PAF dynamic conceptual model call for the sustainable development of CFCs.
Stroke Recovery Is a Journey: Prediction and Potentials of Motor Recovery after a Stroke from a Practical Perspective
Authors: Li Sheng
Published: October 2023

Stroke recovery is a journey. Stroke survivors can face many consequences that may last the rest of their lives. Assessment of initial impairments allows reasonable prediction of biological spontaneous recovery at 3 to 6 months for a majority of survivors. In real-world clinical practice, stroke survivors continue to improve their motor function beyond the spontaneous recovery period, but management plans for maximal recovery are not well understood. A model within the international classification of functioning (ICF) theoretical framework is proposed to systematically identify opportunities and potential barriers to maximize and realize the potentials of functional recovery from the acute to chronic stages and to maintain their function in the chronic stages. Health conditions of individuals, medical and neurological complications can be optimized under the care of specialized physicians. This permits stroke survivors to participate in various therapeutic interventions. Sufficient doses of appropriate interventions at the right time is critical for stroke motor rehabilitation. It is important to highlight that combining interventions is likely to yield better clinical outcomes. Caregivers, including family members, can assist and facilitate targeted therapeutic exercises for these individuals and can help stroke survivors comply with medical plans (medications, visits), and provide emotional support. With health optimization, comprehensive rehabilitation, support from family and caregivers and a commitment to a healthy lifestyle, many stroke survivors can overcome barriers and achieve potentials of maximum recovery and maintain their motor function in chronic stages. This ICF recovery model is likely to provide a guidance through the journey to best achieve stroke recovery potentials.
Experimental Investigation of Tool Wear and Machining Quality of BTA Deep-Hole Drilling in Low-Carbon Alloy Steel SA-5083
Authors: Li Xubo , Zhai Chuanmiao , He Wenqi , Lu Ye , Zhang Bodong
Published: October 2023

Nuclear power tube plates are made from the high-strength, low-carbon alloy steel SA-5083, which has high values of toughness and plasticity, though it is forged with poor consistency and entails serious work hardening. It requires a large number of deep holes with a high machining accuracy and high surface quality to be processed. However, the quality of the processed holes is often not up to the standard of the Boring and Trepanning Association (BTA) for the deep-hole drilling of tube plates; this has led to deep-hole processing becoming a bottleneck in the manufacture of steam generators for the main equipment of nuclear power islands. The variation laws of the diameter, roundness, perpendicularity, roughness, microhardness, and residual stress in relation to the feed, speed, and drilling depth are explored in the macro- and micro-dimensions; also explored is the wear morphology of BTA drills. The internal influence mechanisms between them are revealed in order to provide a scientific basis for the control of surface quality and machining accuracy as well as the optimization of process parameters. Our research results indicate that the guide block wear is mainly concentrated at the top 1–2 mm and that the drilling depth and feed have a great influence on the machining diameter. The hole wall roughness is between 0.3 and 0.6 μm, the maximum microhardness is about 2.15 times the hardness of the matrix material, and the residual stress is compressive stress. With increases in the feed and drilling depth, the hole diameter and the roughness increase. With an increase in the speed, the roughness decreases and the compressive stress of the BTA deep-hole drilling wall increases.
Ulva rigida Valorization into Poly(3-hydroxybutyrate), Organic Acids and Functional Ingredients
Authors: Leandro Tânia , Teles Marco , Gomes-Dias Joana S. , Marques Mafalda , Rocha Cristina M. R. , da Fonseca M. Manuela R. , Cesário M. Teresa
Published: October 2023

Halomonas elongata 1H9T is a moderate halophilic strain able to produce poly(3-hydroxybutyrate) (P(3HB)), a biodegradable plastic, and gluconic acid, a valuable organic acid with wide industrial applications. In this work, the green alga Ulva rigida was used as platform to produce cultivation substrates for microbial conversion as well as functional ingredients, targeting its full valorization. The liquor obtained by autohydrolysis presented the highest concentration of oligosaccharides and protein, being an interesting feedstock to produce functional ingredients. The acid and/or enzymatic hydrolysis liquors are adequate as substrates for microbial processes. Shake flask assays with H. elongata revealed that the N-rich liquor produced after acidic treatment was the best suited for cell growth while the N-poor liquor produced by the enzymatic treatment of acid-pretreated algae residues produced the highest P(3HB) titers of 4.4 g/L. These hydrolysates were used in fed-batch cultivations as carbon and protein sources for the co-production of gluconic acid and polymer achieving titers of 123.2 g/L and 7.2 g/L, respectively. Besides gluconic acid, the Krebs cycle intermediate 2-oxoglutaric acid, also called alpha-ketoglutaric acid (KGA), was produced. Therefore, the co-production of P(3HB) and acids may be of considerable interest as an algal biorefinery valorization strategy.
Penidihydrocitrinins A–C: New Polyketides from the Deep-Sea-Derived Penicillium citrinum W17 and Their Anti-Inflammatory and Anti-Osteoporotic Bioactivities
Authors: Zhang Yong , Xie Chun-Lan , Wang Yuan , He Xi-Wen , Xie Ming-Min , Li You , Zhang Kai , Zou Zheng-Biao , Yang Long-He , Xu Ren , Yang Xian-Wen
Published: October 2023

Three new polyketides (penidihydrocitrinins A–C, 1–3) and fourteen known compounds (4–17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1–17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on LPS-stimulated nitric oxide production in murine brain microglial BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Additionally, compounds 6, 7, and 8 significantly enhanced osteoblast mineralization, which was comparable to that of the positive control, purmorphamine. Furthermore, these three compounds also suppressed osteoclastogenesis in a dose-dependent manner under the concentrations of 2.5 μM, 5.0 μM, and 10 μM.
Enhanced Sorption Performance of Natural Zeolites Modified with pH-Fractionated Humic Acids for the Removal of Methylene Blue from Water
Authors: Salvestrini Stefano , Debord Jean , Bollinger Jean-Claude
Published: October 2023

This work explores the effect of humic acids (HA) fractionation on the sorption ability of a natural zeolite (NYT)—HA adduct. HA were extracted from compost, fractionated via the pH fractionation method, and characterized via UV-Vis spectroscopy and gel permeation chromatography. The HA samples were immobilized onto NYT via thermal treatment. The resulting adducts (NYT-HA) were tested for their ability to remove methylene blue (MB) from an aqueous solution. It was found that the sorption performance of NYT-HA strongly depends on the chemical characteristics of humic acids. Sorption capacity increased with the molecular weight and hydrophobicity degree of the HA fractions. Hydrophobic and π–π interactions are likely the primary mechanisms by which MB interacts with HA. The sorption kinetic data conform to the pseudo-second-order model. The Freundlich isotherm model adequately described the sorption equilibrium and revealed that the uptake of MB onto NYT-HA is endothermic in nature.
In Vitro Permeability Study of Homotaurine Using a High-Performance Liquid Chromatography with Fluorescence Detection Pre-Column Derivatization Method
Authors: Ntorkou Marianna , Tsanaktsidou Eleni , Chachlioutaki Konstantina , Fatouros Dimitrios G. , Markopoulou Catherine K.
Published: October 2023

Homotaurine (HOM) is considered a promising drug for the treatment of Alzheimer’s and other neurodegenerative diseases. In the present work, a new high-performance liquid chromatography with fluorescence detection (HPLC–FLD) (λex. = 340 nm and λem. = 455 nm) method was developed and validated for the study of substance permeability in the central nervous system (CNS). Analysis was performed on a RP-C18 column with a binary gradient elution system consisting of methanol–potassium phosphate buffer solution (pH = 7.0, 0.02 M) as mobile phase. Samples of homotaurine and histidine (internal standard) were initially derivatized with ortho-phthalaldehyde (OPA) (0.01 M), N-acetylcysteine (0.01 M) and borate buffer (pH = 10.5; 0.05 M). To ensure the stability and efficiency of the reaction, the presence of different nucleophilic reagents, namely (a) 2-mercaptoethanol (2-ME), (b) N-acetylcysteine (NAC), (c) tiopronin (Thiola), (d) 3-mercaptopropionic acid (3-MPA) and (e) captopril, was investigated. The method was validated (R2 = 0.9999, intra-day repeatability %RSD < 3.22%, inter-day precision %RSD = 1.83%, limits of detection 5.75 ng/mL and limits of quantification 17.43 ng/mL, recovery of five different concentrations 99.75–101.58%) and successfully applied to investigate the in vitro permeability of homotaurine using Franz diffusion cells. The apparent permeability (Papp) of HOM was compared with that of memantine, which is considered a potential therapeutic drug for various CNSs. Our study demonstrates that homotaurine exhibits superior permeability through the simulated blood–brain barrier compared to memantine, offering promising insights for enhanced drug delivery strategies targeting neurological conditions.
From Plant to Chemistry: Sources of Active Opioid Antinociceptive Principles for Medicinal Chemistry and Drug Design
Authors: Turnaturi Rita , Piana Silvia , Spoto Salvatore , Costanzo Giuliana , Reina Lorena , Pasquinucci Lorella , Parenti Carmela
Published: October 2023

Pain continues to be an enormous global health challenge, with millions of new untreated or inadequately treated patients reported annually. With respect to current clinical applications, opioids remain the mainstay for the treatment of pain, although they are often associated with serious side effects. To optimize their tolerability profiles, medicinal chemistry continues to study novel ligands and innovative approaches. Among them, natural products are known to be a rich source of lead compounds for drug discovery, and they hold potential for pain management. Traditional medicine has had a long history in clinical practice due to the fact that nature provides a rich source of active principles. For instance, opium had been used for pain management until the 19th century when its individual components, such as morphine, were purified and identified. In this review article, we conducted a literature survey aimed at identifying natural products interacting either directly with opioid receptors or indirectly through other mechanisms controlling opioid receptor signaling, whose structures could be interesting from a drug design perspective.
Grignard Reagent-Catalyzed Hydroboration of Esters, Nitriles, and Imines
Authors: Han Hyun Ji , Park Suh Youn , Jeon So Eun , Kwak Jae Seok , Lee Ji Hye , Jaladi Ashok Kumar , Hwang Hyonseok , An Duk Keun
Published: October 2023

The reduction in esters, nitriles, and imines requires harsh conditions (highly reactive reagents, high temperatures, and pressures) or complex metal-ligand catalytic systems. Catalysts comprising earth-abundant and less toxic elements are desirable from the perspective of green chemistry. In this study, we developed a green hydroboration protocol for the reduction in esters, nitriles, and imines at room temperature (25 °C) using pinacolborane as the reducing agent and a commercially available Grignard reagent as the catalyst. Screening of various alkyl magnesium halides revealed MeMgCl as the optimal catalyst for the reduction. The hydroboration and subsequent hydrolysis of various esters yielded corresponding alcohols over a short reaction time (~0.5 h). The hydroboration of nitriles and imines produced various primary and secondary amines in excellent yields. Chemoselective reduction and density functional theory calculations are also performed. The proposed green hydroboration protocol eliminates the requirements for complex ligand systems and elevated temperatures, providing an effective method for the reduction in esters, nitriles, and imines at room temperature.