bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Analysis of the BrHAT Gene Family and Physiological Characteristics of Brassica rapa L. Treated with Histone Acetylase and Deacetylase Inhibitors under Low Temperature
Authors: Bian Liang , Fahim Abbas Muhammad , Wu Junyan , Liu Lijun , Pu Yuanyuan , Ma Li , Fang Yan , Zhang Dan , Yang Gang , Wang Wangtian , Fan Tingting , Yang Xiuguo , Wang Jingyu , Shi Yangyang , Sun Wancang
Published: August 2024

Brassica rapa L. is an important overwintering oilseed crop in Northwest China. Histone acetyltransferases (HATs) play an important role in epigenetic regulation, as well as the regulation of plant growth, development, and responses to abiotic stresses. To clarify the role of histone acetylation in the low-temperature response of B. rapa L., we identified 29 HAT genes in B. rapa L. using bioinformatics tools. We also conducted a comprehensive analysis of the physicochemical properties, gene structure, chromosomal localization, conserved structural domains and motifs, cis-acting regulatory elements, and evolutionary relationships of these genes. Using transcriptome data, we analyzed the expression patterns of BrHAT family members and predicted interactions between proteins; the results indicated that BrHATs play an important role in the low-temperature response of B. rapa L. HAT inhibitor (curcumin; CUR) and histone deacetylase inhibitor (Trichostatin A; TSA) were applied to four B. rapa L. varieties varying in cold resistance under the same low-temperature conditions, and changes in the physiological indexes of these four varieties were analyzed. The inhibitor treatment attenuated the effect of low temperature on seed germination, and curcumin treatment was most effective, indicating that the germination period was primarily regulated by histone acetylase. Both inhibitor treatments increased the activity of protective enzymes and the content of osmoregulatory substances in plants, suggesting that histone acetylation and deacetylation play a significant role in the response of B. rapa L. to low-temperature stress. The qRT-PCR analyses showed that the expression patterns of BrHATs were altered under different inhibitor treatments and low-temperature stress; meanwhile, we found three significantly differentially expressed genes. In sum, the process of histone acetylation is involved in the cold response and the BrHATs gene plays a role in the cold stress response.
Lipid Peroxidation Regulators GPX4 and FSP1 as Prognostic Markers and Therapeutic Targets in Advanced Gastric Cancer
Authors: Tamura Kazuhiro , Tomita Yoshinobu , Kanazawa Takumi , Shinohara Hajime , Sakano Masayoshi , Ishibashi Sachiko , Ikeda Masumi , Kinoshita Mayumi , Minami Junko , Yamamoto Kurara , Kato Yuki , Furukawa Asuka , Haruki Shigeo , Tokunaga Masanori , Kinugasa Yusuke , Kurata Morito , Kitagawa Masanobu , Ohashi Kenichi , Yamamoto Kouhei
Published: August 2024

Gastric cancer is one of the most common cancers worldwide, and new therapeutic strategies are urgently needed. Ferroptosis is an intracellular iron-dependent cell death induced by the accumulation of lipid peroxidation, a mechanism different from conventional apoptosis and necrosis. Therefore, induction of ferroptosis is expected to be a new therapeutic strategy. Glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) have been identified as the major inhibitors of ferroptosis. Herein, we performed immunohistochemistry for GPX4, FSP1, and 4-HNE using tissues from patients with gastric cancer and investigated the relationship between these factors and prognosis. Patients with high GPX4 expression or high GPX4 expression and low 4-HNE accumulation tended to have a poor prognosis (p = 0.036, 0.023), whereas those with low FSP1 expression and high 4-HNE accumulation had a good prognosis (p = 0.033). The synergistic induction of cell death by inhibiting GPX4 and FSP1 in vitro was also observed, indicating that the cell death was non-apoptotic. Our results indicate that the expression and accumulation of lipid peroxidation-related factors play an important role in the clinicopathological significance of gastric cancer and that novel therapeutic strategies targeting GPX4 and FSP1 may be effective in treating patients with gastric cancer who have poor prognosis.
Crosstalk between Dysfunctional Mitochondria and Proinflammatory Responses during Viral Infections
Authors: Sun Zitao , Wang Yanjin , Jin Xin , Li Su , Qiu Hua-Ji
Published: August 2024

Mitochondria play pivotal roles in sustaining various biological functions including energy metabolism, cellular signaling transduction, and innate immune responses. Viruses exploit cellular metabolic synthesis to facilitate viral replication, potentially disrupting mitochondrial functions and subsequently eliciting a cascade of proinflammatory responses in host cells. Additionally, the disruption of mitochondrial membranes is involved in immune regulation. During viral infections, mitochondria orchestrate innate immune responses through the generation of reactive oxygen species (ROS) and the release of mitochondrial DNA, which serves as an effective defense mechanism against virus invasion. The targeting of mitochondrial damage may represent a novel approach to antiviral intervention. This review summarizes the regulatory mechanism underlying proinflammatory response induced by mitochondrial damage during viral infections, providing new insights for antiviral strategies.
microRNAs as New Biomolecular Markers to Estimate Time since Death: A Systematic Review
Authors: Cianci Vincenzo , Mondello Cristina , Sapienza Daniela , Guerrera Maria Cristina , Cianci Alessio , Cracò Annalisa , Luppino Francesco , Gioffrè Vittorio , Gualniera Patrizia , Asmundo Alessio , Germanà Antonino
Published: August 2024

Estimating the post-mortem interval is still one of the most complex challenges in forensics. In fact, the main tools currently used are burdened by numerous limitations, which sometimes allow the time of death to be placed only within too large time intervals. In recent years, researchers have tried to identify new tools to try to narrow down the interval within which to place the time of death; among these, the analysis of microRNAs seems to be promising. An evidence-based systematic review of the literature has been conducted to evaluate the state of the art of knowledge, focusing on the potential correlation between miRNA degradation and PMI estimation. The research has been performed using the electronic databases PubMed, Scopus, and WOS. The results allowed us to highlight the usefulness of miRNAs both as markers for PMI estimation and for normalization, especially due to their stability. In fact, some miRNAs remain particularly stable for long periods and in different tissues, while others degrade faster. Furthermore, there are numerous factors capable of influencing the behavior of these molecules, among which the type of tissue, the cause of death, and the circadian rhythm appear to be the most relevant. Despite the promising results of the few articles present in the literature, because of the numerous limitations they are burdened by, further research is still necessary to achieve more solid and shareable results.
Design, Synthesis, and Nematocidal Evaluation of Waltherione A Derivatives: Leveraging a Structural Simplification Strategy
Authors: Hu Zhan , Yang Bin , Zheng Shuai , Zhao Ke , Wang Kaifeng , Sun Ranfeng
Published: August 2024

Southern root-knot nematodes are among the most pernicious phytoparasites; they are responsible for substantial yield losses in agricultural crops worldwide. The limited availability of nematicides for the prevention and control of plant-parasitic nematodes necessitates the urgent development of novel nematicides. Natural products have always been a key source for the discovery of pesticides. Waltherione A, an alkaloid, exhibits potent nematocidal activity. In this study, we designed and synthesized a series of quinoline and quinolone derivatives from Waltherione A, leveraging a strategy of structural simplification. Bioassays have revealed that the quinoline derivatives exhibit better activity than quinolone derivatives in terms of both nematocidal and fungicidal activities. Notably, compound D1 demonstrated strong nematocidal activity, with a 72 h LC50 of 23.06 μg/mL, and it effectively controlled the infection of root-knot nematodes on cucumbers. The structure–activity relationship suggests that the quinoline moiety is essential for the nematocidal efficacy of Waltherione A. Additionally, compound D1 exhibited broad-spectrum fungicidal activity, with an EC50 of 2.98 μg/mL against Botrytis cinerea. At a concentration of 200 μg/mL, it significantly inhibited the occurrence of B. cinerea on tomato fruits, with an inhibitory effect of 96.65%, which is slightly better than the positive control (90.30%).
Spectroscopic Studies of Lanthanide(III) Complexes with L-Malic Acid in Binary Systems
Authors: Zabiszak Michał , Frymark Justyna , Grajewski Jakub , Jastrzab Renata
Published: August 2024

Binary systems of lanthanide ions (La, Nd, Gd, Ho, Tb, and Lu) with L-malic acid in molar ratios of 1:1 and 1:2 were studied. This study was carried out in aqueous solutions, and the composition of the formed complexes was confirmed using computer data analysis. The overall stability constants of the complexes and the equilibrium constants of the reaction were determined. The effect of ligand concentration on the composition of the internal coordination sphere of the central atom was observed. Changes in the coordination sphere of lanthanide ions were confirmed by spectroscopic measurements.
In Silico Screening of Therapeutic Targets as a Tool to Optimize the Development of Drugs and Nutraceuticals in the Treatment of Diabetes mellitus: A Systematic Review
Authors: Gomes Ana Francisca T. , de Medeiros Wendjilla F. , Medeiros Isaiane , Piuvezam Grasiela , da Silva-Maia Juliana Kelly , Bezerra Ingrid Wilza L. , Morais Ana Heloneida de A.
Published: August 2024

The Target-Based Virtual Screening approach is widely employed in drug development, with docking or molecular dynamics techniques commonly utilized for this purpose. This systematic review (SR) aimed to identify in silico therapeutic targets for treating Diabetes mellitus (DM) and answer the question: What therapeutic targets have been used in in silico analyses for the treatment of DM? The SR was developed following the guidelines of the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis, in accordance with the protocol registered in PROSPERO (CRD42022353808). Studies that met the PECo strategy (Problem, Exposure, Context) were included using the following databases: Medline (PubMed), Web of Science, Scopus, Embase, ScienceDirect, and Virtual Health Library. A total of 20 articles were included, which not only identified therapeutic targets in silico but also conducted in vivo analyses to validate the obtained results. The therapeutic targets most frequently indicated in in silico studies were GLUT4, DPP-IV, and PPARγ. In conclusion, a diversity of targets for the treatment of DM was verified through both in silico and in vivo reassessment. This contributes to the discovery of potential new allies for the treatment of DM.
H3K9me3 Levels Affect the Proliferation of Bovine Spermatogonial Stem Cells
Authors: Yang Rui , Zhang Boyang , Wang Yueqi , Zhang Yan , Zhao Yansen , Jiang Daozhen , Chen Lanxin , Tang Bo , Zhang Xueming
Published: August 2024

Spermatogonial stem cells (SSCs) possess the characteristics of self-renewal and differentiation, as well as the ability to generate functional sperm. Their unique stemness has broad applications in male infertility treatment and species preservation. In rodents, research on SSCs has been widely reported, but progress is slow in large livestock such as cattle and pigs due to long growth cycles, difficult proliferation in vitro, and significant species differences. Previously, we showed that histone 3 (H3) lysine 9 (K9) trimethylation (H3K9me3) is associated with the proliferation of bovine SSCs. Here, we isolated and purified SSCs from calf testicular tissues and investigated the impact of different H3K9me3 levels on the in vitro proliferation of bovine SSCs. The enriched SSCs eventually formed classical stem cell clones in vitro in our feeder-free culture system. These clones expressed glial cell-derived neurotrophic factor family receptor alpha-1 (GFRα1, specific marker for SSCs), NANOG (pluripotency protein), C-KIT (germ cell marker), and strong alkaline phosphatase (AKP) positivity. qRT-PCR analysis further showed that these clones expressed the pluripotency genes NANOG and SOX2, and the SSC-specific marker gene GFRα1. To investigate the dynamic relationship between H3K9me3 levels and SSC proliferation, H3K9me3 levels in bovine SSCs were first downregulated using the methyltransferase inhibitor, chaetocin, or transfection with the siRNA of H3K9 methyltransferase suppressor of variegation 3-9 homologue 1 (SUV39H1). The EDU (5-Ethynyl-2′-deoxyuridine) assay revealed that SSC proliferation was inhibited. Conversely, when H3K9me3 levels in bovine SSCs were upregulated by transfecting lysine demethylase 4D (KDM4D) siRNA, the EDU assay showed a promotion of cell proliferation. In summary, this study established a feeder-free culture system to obtain bovine SSCs and explored its effects on the proliferation of bovine SSCs by regulating H3K9me3 levels, laying the foundation for elucidating the regulatory mechanism underlying histone methylation modification in the proliferation of bovine SSCs.
Identification of Drought Stress-Responsive Genes in Rice by Random Walk with Multi-Restart Probability on MultiPlex Biological Networks
Authors: Liu Jiacheng , Zhu Liu , Cao Dan , Zhu Xinghui , Zhang Hongyan , Zhang Yinqiong , Liu Jing
Published: August 2024

Exploring drought stress-responsive genes in rice is essential for breeding drought-resistant varieties. Rice drought resistance is controlled by multiple genes, and mining drought stress-responsive genes solely based on single omics data lacks stability and accuracy. Multi-omics correlation analysis and biological molecular network analysis provide robust solutions. This study proposed a random walk with a multi-restart probability (RWMRP) algorithm, based on the Restarted Random Walk (RWR) algorithm, to operate on rice MultiPlex biological networks. It explores the interactions between biological molecules across various levels and ranks potential genes. RWMRP uses eigenvector centrality to evaluate node importance in the network and adjusts the restart probabilities accordingly, diverging from the uniform restart probability employed in RWR. In the random walk process, it can be better to consider the global relationships in the network. Firstly, we constructed a MultiPlex biological network by integrating the rice protein–protein interaction, gene pathway, and gene co-expression network. Then, we employed RWMRP to predict the potential genes associated with rice tolerance to drought stress. Enrichment and correlation analyses resulted in the identification of 12 drought-related genes. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) analysis on these 12 genes, ultimately identifying 10 genes responsive to drought stress.
miR156-SPL and miR169-NF-YA Modules Regulate the Induction of Somatic Embryogenesis in Arabidopsis via LEC- and Auxin-Related Pathways
Authors: Nowak Katarzyna , Wójcik Anna M. , Konopka Katarzyna , Jarosz Alicja , Dombert Katarzyna , Gaj Małgorzata D.
Published: August 2024

The embryogenic transition of plant somatic cells to produce somatic embryos requires extensive reprogramming of the cell transcriptome. The prominent role of transcription factors (TFs) and miRNAs in controlling somatic embryogenesis (SE) induction in plants was documented. The profiling of MIRNA expression in the embryogenic culture of Arabidopsis implied the contribution of the miR156 and miR169 to the embryogenic induction. In the present study, the function of miR156 and miR169 and the candidate targets, SPL and NF-YA genes, were investigated in Arabidopsis SE. The results showed that misexpression of MIRNA156 and candidate SPL target genes (SPL2, 3, 4, 5, 9, 10, 11, 13, 15) negatively affected the embryogenic potential of transgenic explants, suggesting that specific fine-tuning of the miR156 and target genes expression levels seems essential for efficient SE induction. The results revealed that SPL11 under the control of miR156 might contribute to SE induction by regulating the master regulators of SE, the LEC (LEAFY COTYLEDON) genes (LEC1, LEC2, FUS3). Moreover, the role of miR169 and its candidate NF-YA targets in SE induction was demonstrated. The results showed that several miR169 targets, including NF-YA1, 3, 5, 8, and 10, positively regulated SE. We found, that miR169 via NF-YA5 seems to modulate the expression of a master SE regulator LEC1/NF-YA and other auxin-related genes: YUCCA (YUC4, 10) and PIN1 in SE induction. The study provided new insights into miR156-SPL and miR169-NF-YA functions in the auxin-related and LEC-controlled regulatory network of SE.
Effects of Dietary Bio-Fermented Selenium Supplementation on Growth, Immune Performance, and Intestinal Microflora of Chinese Mitten Crabs, Eriocheir sinensis
Authors: Yang Zhichao , Li Jialin , Ma Yuhan , Wu Zihao , Li Jiaming , Wang Fengchi , Xi Yuting , Jiang Yusheng , Huang Shu , Yi Qilin
Published: August 2024

Selenium is a vital trace mineral that is crucial for maintaining regular biological processes in aquatic animals. In this study, a four-week dietary trial was carried out to assess the impact of bio-fermented selenium (Bio−Se) on the growth and immune response of Chinese mitten crabs, Eriocheir sinensis. The crabs were randomly allocated to five dietary treatment groups, each receiving a different dose of Bio−Se. The doses included 0, 0.3, 0.6, 1.5, and 3.0 mg/kg and were accurately measured in basal diet formulations. The results showed the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) in the 1.5 mg/kg Bio−Se group were the highest, and 3.0 mg/kg of Bio−Se has an inhibitory effect on the WGR, SGR, and SR. The activities of the immune enzymes, including glutathione peroxidase (GPX), superoxide dismutase (SOD), and acid phosphatase (ACP), of the hepatopancreas were significantly (p < 0.05) increased in the 1.5 mg/kg Bio−Se group, while they decreased (p < 0.05) in the 3.0 mg/kg feeding group compared to the 0 mg/kg feeding group. The concentration of maleic dialdehyde (MDA) exhibited the opposite pattern. Similarly, the mRNA expression levels of antimicrobial peptides (ALF-1, Crus-1, and LYS), ERK, and Relish genes were also observed to be the highest in the 1.5 mg/kg Bio−Se group compared with the other groups. Furthermore, the administration of 1.5 mg/kg of Bio−Se resulted in an increase in the thickness of the intestinal plica and mucosal layer, as well as in alterations in the intestinal microbial profile and bacterial diversity compared to the dose of 0 mg/kg of Bio−Se. Notably, the population of the beneficial bacterial phylum Fusobacteria was increased after crabs were fed the 1.5 mg/kg Bio−Se diet. In conclusion, the oral administration of 1.5 mg/kg of Bio−Se improved the growth efficiency, antioxidant capabilities, immunity, and intestinal health of E. sinensis. Through a broken-line analysis of the WGR against dietary Bio−Se levels, optimal dietary Bio−Se levels were determined to be 1.1 mg/kg. These findings contribute valuable insights to the understanding of crab cultivation and nutrition.
Multi-Omics Integration Analysis Pinpoint Proteins Influencing Brain Structure and Function: Toward Drug Targets and Neuroimaging Biomarkers for Neuropsychiatric Disorders
Authors: Wang Yunzhuang , Zhang Sunjie , Gong Weiming , Liu Xinyu , Mo Qinyou , Shen Lujia , Zhao Yansong , Wang Shukang , Yuan Zhongshang
Published: August 2024

Integrating protein quantitative trait loci (pQTL) data and summary statistics from genome-wide association studies (GWAS) of brain image-derived phenotypes (IDPs) can benefit in identifying IDP-related proteins. Here, we developed a systematic omics-integration analytic framework by sequentially using proteome-wide association study (PWAS), Mendelian randomization (MR), and colocalization (COLOC) analyses to identify the potentially causal brain and plasma proteins for IDPs, followed by pleiotropy analysis, mediation analysis, and drug exploration analysis to investigate potential mediation pathways of pleiotropic proteins to neuropsychiatric disorders (NDs) as well as candidate drug targets. A total of 201 plasma proteins and 398 brain proteins were significantly associated with IDPs from PWAS analysis. Subsequent MR and COLOC analyses further identified 313 potentially causal IDP-related proteins, which were significantly enriched in neural-related phenotypes, among which 91 were further identified as pleiotropic proteins associated with both IDPs and NDs, including EGFR, TMEM106B, GPT, and HLA-B. Drug prioritization analysis showed that 6.33% of unique pleiotropic proteins had drug targets or interactions with medications for NDs. Nine potential mediation pathways were identified to illustrate the mediating roles of the IDPs in the causal effect of the pleiotropic proteins on NDs, including the indirect effect of TMEM106B on Alzheimer’s disease (AD) risk via radial diffusivity (RD) of the posterior limb of the internal capsule (PLIC), with the mediation proportion being 11.18%, and the indirect effect of EGFR on AD through RD of PLIC, RD of splenium of corpus callosum (SCC), and fractional anisotropy (FA) of SCC, with the mediation proportion being 18.99%, 22.79%, and 19.91%, respectively. These findings provide novel insights into pathogenesis, drug targets, and neuroimaging biomarkers of NDs.
Lipopolysaccharide Core Truncation in Invasive Escherichia coli O157:H7 ATCC 43895 Impairs Flagella and Curli Biosynthesis and Reduces Cell Invasion Ability
Authors: Sheng Haiqing , Ndeddy Aka Robinson J. , Wu Sarah
Published: August 2024

Escherichia coli O157:H7 (E. coli O157) is known for causing severe foodborne illnesses such as hemorrhagic colitis and hemolytic uremic syndrome. Although E. coli O157 is typically regarded as an extracellular pathogen and a weak biofilm producer, some E. coli O157 strains, including a clinical strain ATCC 43895, exhibit a notable ability to invade bovine crypt cells and other epithelial cells, as well as to form robust biofilm. This invasive strain persists in the bovine host significantly longer than non-invasive strains. Various surface-associated factors, including lipopolysaccharides (LPS), flagella, and other adhesins, likely contribute to this enhanced invasiveness and biofilm formation. In this study, we constructed a series of LPS-core deletion mutations (waaI, waaG, waaF, and waaC) in E. coli O157 ATCC 43895, resulting in stepwise truncations of the LPS. This approach enabled us to investigate the effects on the biosynthesis of key surface factors, such as flagella and curli, and the ability of this invasive strain to invade host cells. We confirmed the LPS structure and found that all LPS-core mutants failed to form biofilms, highlighting the crucial role of core oligosaccharides in biofilm formation. Additionally, the LPS inner-core mutants ΔwaaF and ΔwaaC lost the ability to produce flagella and curli. Furthermore, these inner-core mutants exhibited a dramatic reduction in adherence to and invasion of epithelial cells (MAC-T), showing an approximately 100-fold decrease in cell invasion compared with the outer-core mutants (waaI and waaG) and the wild type. These findings underscore the critical role of LPS-core truncation in impairing flagella and curli biosynthesis, thereby reducing the invasion capability of E. coli O157 ATCC 43895.
Navigating the Landscape of CMT1B: Understanding Genetic Pathways, Disease Models, and Potential Therapeutic Approaches
Authors: McCulloch Mary Kate , Mehryab Fatemeh , Rashnonejad Afrooz
Published: August 2024

Charcot–Marie–Tooth type 1B (CMT1B) is a peripheral neuropathy caused by mutations in the gene encoding myelin protein zero (MPZ), a key component of the myelin sheath in Schwann cells. Mutations in the MPZ gene can lead to protein misfolding, unfolded protein response (UPR), endoplasmic reticulum (ER) stress, or protein mistrafficking. Despite significant progress in understanding the disease mechanisms, there is currently no effective treatment for CMT1B, with therapeutic strategies primarily focused on supportive care. Gene therapy represents a promising therapeutic approach for treating CMT1B. To develop a treatment and better design preclinical studies, an in-depth understanding of the pathophysiological mechanisms and animal models is essential. In this review, we present a comprehensive overview of the disease mechanisms, preclinical models, and recent advancements in therapeutic research for CMT1B, while also addressing the existing challenges in the field. This review aims to deepen the understanding of CMT1B and to encourage further research towards the development of effective treatments for CMT1B patients.
Formulation and Development of Nanofiber-Based Ophthalmic Insert for the Treatment of Bacterial Conjunctivitis
Authors: Farkas Eszter , Abboud Houssam , Nagy Nándor , Hofmeister Bálint , Ostorházi Eszter , Tóth Bence , Pinke Balázs , Mészáros László , Zelkó Romána , Kazsoki Adrienn
Published: August 2024

A novel ophthalmic delivery system utilizing levofloxacin-loaded, preservative-free, nanofiber-based inserts was investigated. Polyvinyl alcohol (PVA) and Poloxamer 407 (Polox)were employed as matrix materials, while hydroxypropyl-beta-cyclodextrin (HP-β-CD) was a solubilizer. The formulations were prepared via electrospinning and characterized for fiber morphology, drug dissolution, cytotoxicity, and antimicrobial activity. Scanning electron microscopy confirmed uniform fibrous structures. Fourier Transform Infrared spectroscopy and X-ray diffraction analyses demonstrated the amorphous state of levofloxacin within the fibers. In vitro dissolution studies revealed a rapid (within 2 min) and complete drug release, with higher HP-β-CD levels slightly delaying the release. Cytotoxicity tests showed increased HP-β-CD concentrations induced irritation, that was mitigated by sodium hyaluronate. The antimicrobial efficacy of the nanofibers was comparable to conventional eye drops, with lower minimum inhibitory concentrations for most tested strains. The nanofibrous formulation prepared from a PVA–Polox-based viscous solution of the drug:CD 1:1 mol ratio, containing 0.4% (w/w) sodium hyaluronate) was identified as a particularly promising alternative formulation due to its rapid and complete dissolution, good biocompatibility, and effective antimicrobial properties. Its gelling properties indicate that the residence time on the eye surface can be increased, potentially reducing discomfort and enhancing therapeutic outcomes. The nanofibrous formulations enhanced antimicrobial efficacy, providing a preservative-free alternative that minimizes the potential eye irritation that might occur because of the preservative agent and reduces the administrated dose frequency by extending the drug’s retention time on the eye’s surface. Subsequently, it improves patients’ adherence, which would reflect positively on the bioavailability. The levofloxacin-HP-β-CD nanofibers demonstrate promise as an alternative to traditional eye drops, offering advantages in solubility, stability, and patient compliance for ocular infection treatment.
Genome-Wide Analysis and Expression Profiling of Soybean RbcS Family in Response to Plant Hormones and Functional Identification of GmRbcS8 in Soybean Mosaic Virus
Authors: Zhou Fangxue , Feng Wenmi , Mou Kexin , Yu Zhe , Zeng Yicheng , Zhang Wenping , Zhou Yonggang , Li Yaxin , Gao Hongtao , Xu Keheng , Feng Chen , Jing Yan , Li Haiyan
Published: August 2024

Rubisco small subunit (RbcS), a core component with crucial effects on the structure and kinetic properties of the Rubisco enzyme, plays an important role in response to plant growth, development, and various stresses. Although Rbcs genes have been characterized in many plants, their muti-functions in soybeans remain elusive. In this study, a total of 11 GmRbcS genes were identified and subsequently divided into three subgroups based on a phylogenetic relationship. The evolutionary analysis revealed that whole-genome duplication has a profound effect on GmRbcSs. The cis-acting elements responsive to plant hormones, development, and stress-related were widely found in the promoter region. Expression patterns based on the RT-qPCR assay exhibited that GmRbcS genes are expressed in multiple tissues, and notably Glyma.19G046600 (GmRbcS8) exhibited the highest expression level compared to other members, especially in leaves. Moreover, differential expressions of GmRbcS genes were found to be significantly regulated by exogenous plant hormones, demonstrating their potential functions in diverse biology processes. Finally, the function of GmRbcS8 in enhancing soybean resistance to soybean mosaic virus (SMV) was further determined through the virus-induced gene silencing (VIGS) assay. All these findings establish a strong basis for further elucidating the biological functions of RbcS genes in soybeans.
Plasmodium falciparum Mitochondrial Complex III, the Target of Atovaquone, Is Essential for Progression to the Transmissible Sexual Stages
Authors: Sheokand Pradeep Kumar , Pradhan Sabyasachi , Maclean Andrew E. , Mühleip Alexander , Sheiner Lilach
Published: August 2024

The Plasmodium falciparum mitochondrial electron transport chain (mETC) is responsible for essential metabolic pathways such as de novo pyrimidine synthesis and ATP synthesis. The mETC complex III (cytochrome bc1 complex) is responsible for transferring electrons from ubiquinol to cytochrome c and generating a proton gradient across the inner mitochondrial membrane, which is necessary for the function of ATP synthase. Recent studies have revealed that the composition of Plasmodium falciparum complex III (PfCIII) is divergent from humans, highlighting its suitability as a target for specific inhibition. Indeed, PfCIII is the target of the clinically used anti-malarial atovaquone and of several inhibitors undergoing pre-clinical trials, yet its role in parasite biology has not been thoroughly studied. We provide evidence that the universally conserved subunit, PfRieske, and the new parasite subunit, PfC3AP2, are part of PfCIII, with the latter providing support for the prediction of its divergent composition. Using inducible depletion, we show that PfRieske, and therefore, PfCIII as a whole, is essential for asexual blood stage parasite survival, in line with previous observations. We further found that depletion of PfRieske results in gametocyte maturation defects. These phenotypes are linked to defects in mitochondrial functions upon PfRieske depletion, including increased sensitivity to mETC inhibitors in asexual stages and decreased cristae abundance alongside abnormal mitochondrial morphology in gametocytes. This is the first study that explores the direct role of the PfCIII in gametogenesis via genetic disruption, paving the way for a better understanding of the role of mETC in the complex life cycle of these important parasites and providing further support for the focus of antimalarial drug development on this pathway.
Lectin-Based Fluorescent Comparison of Glycan Profile—FDA Validation to Expedite Approval of Biosimilars
Authors: Niazi Sarfaraz K. , Omarsdottir Sesselja
Published: August 2024

Glycan profile comparisons are one of the most tedious analytical exercises for establishing compliance with recombinant therapeutic protein batches. Based on its intensive research, the FDA has confirmed that lectin array binding with fluorescent monitoring is the fastest and most reliable method for profile comparisons. Using a database of over 150 biological products expressed in nine diverse mammalian cell systems, the FDA immobilized 74 lectins to study their binding using fluorescently labeled glycoproteins. The FDA identified nine distinct lectins from a custom-designed lectin microarray: rPhoSL, rOTH3, RCA120, rMan2, MAL_I, rPSL1a, PHAE, rMOA, and PHALs, which detect core fucose, terminal GlcNAc, terminal β-galactose, high mannose, α-2,3-linked sialic acids, α-2,6-linked sialic acids, bisecting GlcNAc, terminal α-galactose, and triantennary structures, respectively. This method can be used for screening and routine testing and to monitor batch-to-batch variability of therapeutic proteins, including establishing analytical similarity as a crucial part of biosimilar development.
Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations
Authors: Valdez Benigno C. , Tsimberidou Apostolia M. , Yuan Bin , Baysal Mehmet A. , Chakraborty Abhijit , Andersen Clark R. , Andersson Borje S.
Published: August 2024

Breast and ovarian cancers pose significant therapeutic challenges. We explored the synergistic cytotoxicity of histone deacetylase inhibitors (HDACis), poly(ADP-ribose) polymerase inhibitors (PARPis), and decitabine in breast (MDA-MB-231 and MCF-7) and ovarian (HEY-T30 and SKOV-3) cancer cell lines that were exposed to HDACi (panobinostat or vorinostat), PARPi (talazoparib or olaparib), decitabine, or their combinations. HDACi, PARPi, and decitabine combinations had synergistic cytotoxicity (assessed by MTT and clonogenic assays) in all cell lines (combination index < 1). Clonogenic assays confirmed the sensitivity of breast and ovarian cancer cell lines to the three-drug combinations (panobinostat, talazoparib, and decitabine; panobinostat, olaparib, and decitabine; vorinostat, talazoparib, and decitabine; vorinostat, olaparib, and decitabine). Cell proliferation was inhibited by 48–70%, and Annexin V positivity was 42–59% in all cell lines exposed to the three-drug combinations. Western blot analysis showed protein PARylation inhibition, caspase 3 and PARP1 cleavage, and c-MYC down-regulation. The three-drug combinations induced more DNA damage (increased phosphorylation of histone 2AX) than the individual drugs, impaired the DNA repair pathways, and altered the epigenetic regulation of gene expression. These results indicate that HDACi, PARPi, and decitabine combinations should be further explored in these tumor types. Further clinical validation is warranted to assess their safety and efficacy.
Metabolite and Transcriptome Profiling Analysis Provides New Insights into the Distinctive Effects of Exogenous Melatonin on Flavonoids Biosynthesis in Rosa rugosa
Authors: Xu Yong , Wang Ruotong , Ma Yuanxiao , Li Meng , Bai Mengjuan , Wei Guo , Wang Jianwen , Feng Liguo
Published: August 2024

Although the petals of Rosa rugosa are rich in flavonoids and their bioactivity has a significant impact on human health, the flavonoid content decreases during flower development. In this study, R. rugosa ‘Feng hua’ was used to investigate the effects of the melatonin foliar spray on enhancing the quality of rose by focusing on major flavonoids. The results showed that the contents of total flavonoids in rose petals at the full bloom stage induced by melatonin obeyed a bell-shaped curve, with a maximum at 0.3 mM, indicating the concentration-dependent up-regulation of flavonoid biosynthesis. In the treatment with 0.3 mM melatonin, metabolomic analyses showed that the concentrations of ten main flavonoids were identified to be increased by melatonin induction, with high levels and increases observed in three flavonols and two anthocyanins. KEGG enrichment of transcriptomic analysis revealed a remarkable enrichment of DEGs in flavonoid and flavonol biosynthesis, such as Rr4CL, RrF3H, and RrANS. Furthermore, functional validation using virus-induced gene silencing technology demonstrated that Rr4CL3 is the crucial gene regulating flavonoid biosynthesis in response to the stimulant of melatonin. This study provides insights into the exogenous melatonin regulation mechanism of biosynthesis of flavonoids, thereby offering potential industrial applications.
Exogenous Substances Used to Relieve Plants from Drought Stress and Their Associated Underlying Mechanisms
Authors: Feng Di , Liu Wenxin , Chen Ke , Ning Songrui , Gao Qian , Chen Jiao , Liu Jiao , Sun Xiaoan , Xu Wanli
Published: August 2024

Drought stress (DS) is one of the abiotic stresses that plants encounter commonly in nature, which affects their life, reduces agricultural output, and prevents crops from growing in certain areas. To enhance plant tolerance against DS, abundant exogenous substances (ESs) have been attempted and proven to be effective in helping plants relieve DS. Understanding the effect of each ES on alleviation of plant DS and mechanisms involved in the DS relieving process has become a research focus and hotspot that has drawn much attention in the field of botany, agronomy, and ecology. With an extensive and comprehensive review and summary of hundred publications, this paper groups various ESs based on their individual effects on alleviating plant/crop DS with details of the underlying mechanisms involved in the DS-relieving process of: (1) synthesizing more osmotic adjustment substances; (2) improving antioxidant pathways; (3) promoting photosynthesis; (4) improving plant nutritional status; and (5) regulating phytohormones. Moreover, a detailed discussion and perspective are given in terms of how to meet the challenges imposed by erratic and severe droughts in the agrosystem through using promising and effective ESs in the right way and at the right time.
Recurrent Neural Networks: A Comprehensive Review of Architectures, Variants, and Applications
Authors: Mienye Ibomoiye Domor , Swart Theo G. , Obaido George
Published: August 2024

Recurrent neural networks (RNNs) have significantly advanced the field of machine learning (ML) by enabling the effective processing of sequential data. This paper provides a comprehensive review of RNNs and their applications, highlighting advancements in architectures, such as long short-term memory (LSTM) networks, gated recurrent units (GRUs), bidirectional LSTM (BiLSTM), echo state networks (ESNs), peephole LSTM, and stacked LSTM. The study examines the application of RNNs to different domains, including natural language processing (NLP), speech recognition, time series forecasting, autonomous vehicles, and anomaly detection. Additionally, the study discusses recent innovations, such as the integration of attention mechanisms and the development of hybrid models that combine RNNs with convolutional neural networks (CNNs) and transformer architectures. This review aims to provide ML researchers and practitioners with a comprehensive overview of the current state and future directions of RNN research.
Multi-Robot Navigation System Design Based on Proximal Policy Optimization Algorithm
Authors: Wong Ching-Chang , Weng Kun-Duo , Yu Bo-Yun
Published: August 2024

The more path conflicts between multiple robots, the more time it takes to avoid each other, and the more navigation time it takes for the robots to complete all tasks. This study designs a multi-robot navigation system based on deep reinforcement learning to provide an innovative and effective method for global path planning of multi-robot navigation. It can plan paths with fewer path conflicts for all robots so that the overall navigation time for the robots to complete all tasks can be reduced. Compared with existing methods of global path planning for multi-robot navigation, this study proposes new perspectives and methods. It emphasizes reducing the number of path conflicts first to reduce the overall navigation time. The system consists of a localization unit, an environment map unit, a path planning unit, and an environment monitoring unit, which provides functions for calculating robot coordinates, generating preselected paths, selecting optimal path combinations, robot navigation, and environment monitoring. We use topological maps to simplify the map representation for multi-robot path planning so that the proposed method can perform path planning for more robots in more complex environments. The proximal policy optimization (PPO) is used as the algorithm for deep reinforcement learning. This study combines the path selection method of deep reinforcement learning with the A* algorithm, which effectively reduces the number of path conflicts in multi-robot path planning and improves the overall navigation time. In addition, we used the reciprocal velocity obstacles algorithm for local path planning in the robot, combined with the proposed global path planning method, to achieve complete and effective multi-robot navigation. Some simulation results in NVIDIA Isaac Sim show that for 1000 multi-robot navigation tasks, the maximum number of path conflicts that can be reduced is 60,375 under nine simulation conditions.
Deep Learning-Based Flood Detection for Bridge Monitoring Using Accelerometer Data
Authors: Deng Penghao , Yang Jidong J. , Yee Tien
Published: August 2024

Flooding and consequential scouring are the primary causes of bridge failures, making the detection of such events crucial for structural safety. This study investigates the characteristics of accelerometer data from bridge pier vibrations and proposes a flood detection method with deep learning-based models based on ResNet18 and 1D Convolution architectures. These models were comprehensively evaluated for (1) detecting vehicles passing on bridges and (2) detecting flood events based on axis-specific accelerometer data under various traffic conditions. Continuous Wavelet Transform (CWT) was employed to convert the accelerometer data into richer time-frequency representations, enhancing the detection of passing vehicles. Notably, when vehicles are passing over bridges, the vertical direction exhibits a magnified and more sustained energy distribution across a wider frequency range. Additionally, under flooding conditions, time-frequency representations from the bridge direction reveal a significant increase in energy intensity and continuity compared with non-flooding conditions. For detection of vehicles passing, ResNet18 outperformed the 1D Convolution model, achieving an accuracy of 97.2% compared with 91.4%. For flood detection without vehicles passing, the two models performed similarly well, with accuracies of 97.3% and 98.3%, respectively. However, in scenarios with vehicles passing, the 1D Convolution model excelled, achieving an accuracy of 98.6%, significantly higher than that of ResNet18 (81.6%). This suggests that high-frequency signals, such as vertical vibrations induced by passing vehicles, are better captured by more complex representations (CWT) and models (e.g., ResNet18), while relatively low-frequency signals, such as longitudinal vibrations caused by flooding, can be effectively captured by simpler 1D Convolution over the original signals. Consequentially, the two model types are deployed in a pipeline where the ResNet18 model is used for classifying whether vehicles are passing the bridge, followed by two 1D Convolution models: one trained for detecting flood events under vehicles-passing conditions and the other trained for detecting flood events under no-vehicles-passing conditions. This hierarchical approach provides a robust framework for real-time monitoring of bridge response to vehicle passing and timely warning of flood events, enhancing the potential to reduce bridge collapses and improve public safety.
Selective State DOT Lane Width Standards and Guidelines to Reduce Speeds and Improve Safety
Authors: Ewing Reid , Yang Wookjae , Promy Noshin Siara , Kaniewska Justyna , Tabassum Nawshin
Published: August 2024

This research investigates the lane width standards and guidelines implemented by various State Departments of Transportation (DOTs) to reduce vehicle speeds and enhance road safety. Lane width reduction is often perceived as a strategy to mitigate speed and improve safety. Still, its effectiveness and implications vary across different contexts, including regions, urban/rural settings, or other geometric design features. Drawing from interviews with five State DOTs and a review of their road design manuals, this study aims to identify suggested lane widths depending on the contexts, design exception process when narrowing or widening lane widths, and introduce representative before/after studies. The findings indicate that State DOTs tend to have lower recommended lane widths in urban areas than in rural areas. Moreover, lane width standards among these states vary due to several factors, including the geographical location of roadways (urban or rural areas), design or posted speeds, traffic volume, road classification, and geometric road design features. Design exceptions are required if the existing or proposed design element is incompatible with both AASHTO and department governing criteria. In conclusion, the findings will provide valuable insights and recommendations for policymakers, transportation planners, and road engineers to inform optimal lane width and decision-making processes.
A Checklist of the Olethreutini Obraztsov, 1946 (Lepidoptera: Tortricidae) of Taiwan, with the Distribution in Mainland China
Authors: Sun Yinghui , Li Houhun
Published: August 2024

Thirty-five genera and one hundred and two species of the tortricid tribe Olethreutini documented from Taiwan are listed, two genera and six species of which are newly recorded for China and two genera and eighteen species of which are newly recorded for Taiwan. Nine species are recorded in the mainland of China for the first time, which were endemic to Taiwan before this study. The local monographs of China and references are summarized with the examined specimens. The synonymies and geographic distribution in China are provided for each species, and a list of examined specimens is provided when applicable.
Use of Periplaneta americana as a Soybean Meal Substitute: A Step towards Sustainable Transformative Poultry Feeds
Authors: Mustafa Farwa , Sajjad Asif , Tahir Roughaina , Ali Mudssar , Sajjad Muhammad , Abbasi Asim , Khan Ehsaan Ullah , Zafar Saba , Hashem Abeer , Avila-Quezada Graciela Dolores , Abd_Allah Elsayed Fathi
Published: August 2024

Insects are becoming increasingly popular as a sustainable and nutritious alternative protein source in poultry feeds, due to their high protein content, low environmental impact, and efficient feed conversion rates. Using insect-based feeds can reduce the need for traditional protein sources like soybean meal (SBM), which often contribute to environmental issues such as deforestation and high water consumption. The current experiments were devised to assess the impacts of the partial replacement of SBM with the American cockroach Periplaneta americana and black soldier fly Hermetia illucens on the performances, hematology, gut morphometry, and meat quality of male broilers (Ross 308). A total of 350, 1-day-old chicks weighing 40.05 ± 0.27 g were divided into 7 dietary treatments (5 pens/treatment and 10 birds/pen) at random, i.e., a 4, 8, or 12% SMB replacement with P. americana and H. illucens. Soybean meal was used as a basal diet and taken as a control. The results indicated that broilers fed on 12% P. americana or H. illucens showed significant improvements (p < 0.05) in feed conversion ratio, live weight, and daily weight gain. Hematological traits significantly improved (p < 0.05). A gut histology showed increased villus height, villus width, crypt depth, and villus height/crypt depth ratios, indicating improved nutrient absorption. Broiler meat fed on 12% P. americana meal had significantly higher redness and yellowness (p < 0.05). Substituting soybean meal with up to 12% P. americana or H. illucens meal in poultry feed can enhance the broilers’ growth performance, hematology, gut morphometry, and meat quality. Hence, these findings imply that P. americana or H. illucens meal are viable and constructive alternative protein sources in poultry nutrition, offering a sustainable approach to meet the increasing demand for animal protein across the world.