bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyzing Distance-Based Registration with Two Location Areas: A Semi-Markov Process Approach
Authors: Baek Jang-Hyun
Published: January 2024

In order to connect an incoming call to the user equipment (UE) in a mobile communication network, the location information of the UE must be always kept in the network database. Therefore, the efficiency of the location registration method of reporting new location information to a mobile communication network whenever the location information of the UE changes directly affects the performance of the radio channel, which is a limited resource in a mobile communication network. This study deals with distance-based registration (DBR). DBR does not cause the ping-pong phenomenon known to be a main problem in zone-based registration. It shows good performance when assuming a random walk mobility model. To improve the performance of the original DBR with one location area (1D), a DBR with two location areas (2D) was proposed. It is known that 2D is better than 1D in most cases. However, unlike 1D, an accurate mathematical model for 2D has not been presented in previous studies, raising questions about whether an accurate performance comparison has been performed. In this study, we present an accurate mathematical model based on the semi-Markov process for performance analysis of 2D. We compared performances of 1D and 2D using the proposed mathematical model. Various numerical results showed that 2D with two-step paging was superior to 1D in most cases. However, when simultaneous paging was applied to 2D, 1D was better than 2D in most cases. In real situations, optimal performance can be achieved by reflecting the network situation in real time and dynamically changing the operating method using a better-performing model among these two methods.
A Comprehensive Review on Matrix-Integrated Single-Stage Isolated MF/HF Converters
Authors: Mahmud Tahmin , Gao Hang
Published: January 2024

A matrix-integrated single-stage isolated MF/HF AC-AC/DC-AC/AC-DC converter topology stands out as an innovative concept, offering a multitude of advantages including minimal output current THDs, near UPF, 4Q operation, smooth BPF capability, and increased power density leading to the converter’s enhanced efficiency, cost-effectiveness, and reliability. These characteristics render it an exemplary choice for RE-based power conversion applications. In fact, the matrix-integrated single-stage isolated MF/HF converters have witnessed an increased adoption of RE-based grid interconnection in recent years, specifically within solar PV, WECS, grid-tied offshore WF, and FC-based applications. RE sources produce variable and intermittent AC power by nature, further necessitating conversion to a stable and grid-compatible AC voltage and frequency. This is where MCs offer distinct advantages when contrasted with the conventional indirect dual-stage VSC-based rectifier–inverter topology. In this paper, a total of 22 matrix-integrated HF isolated converter topologies are broadly explored. Our study provides a comprehensive analysis and classification of matrix-integrated isolated single-stage MF/HF AC-AC converters, DC-AC inverters, and AC-DC rectifier topologies including modified topology architectures, control method, modulation techniques along with significant applications. Within this scope, the matrix-integrated converter topologies are categorized based on their architectures and other relevant subvariants. Our primary objective of this study is to impart a clear understanding of the overarching framework and principles of the matrix-integrated single-stage isolated MF/HF converter topologies and stimulate the creation of new topologies that cater to specific requirements for grid-interconnected systems.
Using Carbon Sequestration as a Remote-Monitoring Approach for Reclamation’s Effectiveness in the Open Pit Coal Mine: A Case Study of Mae Moh, Thailand
Authors: Somprasong Komsoon , Hutayanon Thitinan , Jaroonpattanapong Pirat
Published: January 2024

Reclamation is regarded as one of the mining processes that can lessen the environmental impact of its production, particularly for large-scale coal mines that emit significant quantities of greenhouse gases. However, the assessment and evaluation of the reclamation process primarily rely on qualitative methods. Utilizing LANSAT8 Operational Land Imager (OLI) remote sensing in conjunction with GIS, this study aimed to develop a quantitative method for validating the efficacy of a reclamation procedure applicable to the emerging trend of carbon reduction. The empirical formula utilized to compute the annual carbon sequestrations of the reclamation area in the Mae Moh mine exhibited the appropriate spatial relative standard deviation (S-RSD) at 98.25%. The findings indicate that the reclamation area reached its highest level of carbon sequestration in 2022, at 331.28 ± 11.89 ktCO2e, surpassing the baseline of 126.53 ktCO2e. Furthermore, the approach demonstrates significant potential in improving the standard method for assessing reclamation through reforestation.
Electrochromic Polymers: From Electrodeposition to Hybrid Solid Devices
Authors: Sare Hadarou , Dong Dongmei
Published: January 2024

This paper reports on the linear colorimetric and electrochromic (EC) characteristics of electrodeposited polyaniline (PANI) films. This paper also investigates the infrared EC properties of acid-doped PANI films. The electrochemical polymerization method was employed to create a porous and thin PANI film layer onto PET-ITO substrates. This layer was capped with WO3 film to create a gel electrolyte sandwich structure that demonstrates the compatibility of PANI films with cathodic WO3 films in full devices. The electrodeposition of the film was fabricated by applying different voltages and time, with the optimal film quality achieved with the 1.7 V voltage and a 20 min deposition period. The surface morphology, optical performance, electrochemical behavior, and molecular structure evolution are comprehensively studied in this work. The linear colorimetric behaviors and the corresponding significant changes in the structure in Raman spectra build direct strong quantitative relations in EC polymers. The well-defined oxidation and reduction peaks observed in the cyclic voltammetry indicate the ion-diffusion dominant process in the electrochromism of PANI. Significant transitions between the benzene and quinone phases in the Raman spectra are found in the bleached and colored states of polymers. This study enhances the understanding of PANI film structure and electrochemical and associated optical properties, providing more insights into the dual-function EC charge storage polymers and other energy-related functional materials.
Influence of Wind-Turbine-Generator Power Control on the Performance of a Virtual Synchronous Machine
Authors: Orihara Dai , Taoka Hisao , Otani Kenji
Published: January 2024

Implementation of renewable energy sources (RESs) in power systems can reduce the dependence on fossil-fuel-based thermal power generation systems. At the same time, however, the system inertia decreases as synchronous generators decrease; this is crucial for maintaining the stability of the power system. Virtual inertia control (VIC) can regulate the output of an inverter-based resource (IBR) by increasing the inertia. For a wind turbine generator (WTG), output control factors such as pitch angle control and maximum power point tracking (MPPT) significantly affect the performance of the VIC. This paper theoretically clarifies that the pitch angle control contributes to improvements in the performance of the VIC and helps avoid a loss of operation of the WTG in frequency drop events by analyzing the movement of the operational point of the WTG based on the physical characteristic of the WTG and control characteristics of the pitch angle control and MPPT; an electromagnetic transient (EMT) simulation, performed to verify the analysis, is also presented.
Economic Feasibility Study of the Production of Biogas, Coke and Biofuels from the Organic Fraction of Municipal Waste Using Pyrolysis
Authors: Rodrigues Benedito Franciano Ferreira , Amaral Anderson Rocha , Assunção Fernanda Paula da Costa , Bernar Lucas Pinto , Santos Marcelo Costa , Mendonça Neyson Martins , Pereira José Almir Rodrigues , Castro Douglas Alberto Rocha de , Duvoisin Sergio , Oliveira Pablo Henrique Ataide , Borges Luiz Eduardo Pizarro , Machado Nélio Teixeira
Published: January 2024

The objective of this study is to analyze the economic viability of municipal household solid waste (organic matter + paper) for the production of gas, coke and biofuel through the pyrolysis and distillation process. The waste was collected in the city of Belém do Pará-Brazil and pretreated at the Federal University of Pará. The analyzed fraction (organic matter + paper) was subjected to the pretreatment of drying, crushing, and sieving and was subsequently subjected to proximate characterization and, finally, pyrolysis of the organic fraction (organic matter + paper) in a fixed bed reactor. Initially, it was necessary to review the literature, and with the yields obtained by pyrolysis of the fraction, economic feasibility analyses were carried out. The economic indicators for evaluating the most viable pyrolysis process were basic payback, discounted payback, net present value, internal rate of return, and profitability index, which are all financial metrics commonly used in investment analysis and decision making. These metrics provide valuable insights into the financial viability and attractiveness of investment projects. They are essential tools for assessing the feasibility and profitability of various ventures, helping decision-makers make informed choices in allocating resources. The analysis of the indicators showed the economic viability considering an analysis horizon of 10 years of materials based on organic material and paper. The breakeven point obtained was USD 0.96/dm3 and the minimum biofuel sales price found in this project was USD 1.30/dm3. The sensitivity research found that material costs (organic matter + paper), bio-oil yield, total project investment and electricity, respectively, are the variables that most affect the minimum biofuel sales price.
Screening and Expression Characteristics of Plant Type Regulatory Genes in Salix psammophila
Authors: Zhao Kai , He Rong , Zhang Guosheng , Qin Fucang , Yue Yongjie , Li Long , Dong Xiaoyu
Published: January 2024

Salix psammophila is an important tree species adapted to sand-fixing afforestation in arid areas, and its different plant type characteristics can have different ecological functions. To identify the genes affecting the plant type of S. psammophila, this study used RT-qPCR and RNA-seq technology to establish a method for screening the candidate genes of the S. psammophila plant type based on the correlation coefficient of the crown–height ratio. We then screened out the gene combination that can best control the expression of the S. psammophila plant type. The results show the following: (1) The expression levels of the FHY1 and TAC2 genes were positively correlated with the crown–height ratio, whereas those of the ATX1, RFK1, PYL1, ABF2, SPA2, TB1, ZFP4, and LAZY1b genes were negatively correlated with the crown–height ratio. (2) The ATX1 + FHY1 gene combination had the greatest influence on the plant type traits of S. psammophila, and the correlation between the gene combination and the crown–height ratio reached 0.74. (3) The double- gene combination screening method improved the screening efficiency and accuracy, as well as the sensitivity and specificity, indicating certain universality. This strategy can be used for the determination of other plants or other traits, providing a theoretical basis for the directional breeding of forest trees.
Control of Browning, Enzyme Activity, and Quality in Stored Fresh-cut Fruit Salads through Chitosan Coating Enriched with Bergamot Juice Powder
Authors: Demircan Bahar , Velioglu Yakup Sedat
Published: January 2024

In this study, fresh-cut fruit salads composed of apples, pears, kiwis, and pineapples were stored at +4 °C for 18 days under distinct conditions: non-coated (NC), chitosan-coated (CH), and bergamot juice powder extract-enriched chitosan-coated (CHBE). Storage endpoint decay percentages were as follows: NC group: 100%, CH group: 26.67–53.3%, CHBE group: 13.33–26.67%. CHBE had the highest moisture content (87.05–89.64%), soluble solids (12.40–13.26%), and chroma values (2.35–6.60). CHBE and NC groups had 2.10% and 6.61% weight loss, respectively. The NC group had the highest polyphenol oxidase activity (19.48 U mL−1) and browning index (0.70 A420/g); CH group: 0.85 U mL−1, 0.35 A420/g; CHBE group: 0.57 U mL−1, 0.27 A420/g. CHBE showed a titratable acidity of 1.33% and pH 3.73 post-storage, impeding microbial proliferation with the lowest counts (2.30–3.24 log CFU g−1). The microbial suitability of the NC group diminished after day 6, with an overall preference score of 1.00. Conversely, the CH and CHBE groups scored 3.15 and 4.56, highlighting the coatings’ effectiveness. Bergamot juice powder extract further enhanced this, mitigating browning and enhancing quality. Results reveal tailored coatings’ potential to extend shelf life, improve quality, and enhance fruit salads’ acceptability. This study underscores the importance of edible coatings in addressing preservation challenges, emphasizing their role in enhancing food quality and consumer acceptability. Incorporating edible coatings is pivotal in mitigating deterioration issues and ensuring the overall success of fresh-cut fruit products in the market.
Changes in Meat of Hu Sheep during Postmortem Aging Based on ACQUITY UPLC I-Class Plus/VION IMS QTof
Authors: Xu Jie , Wang Qiang , Wang Yimeng , Bao Menghuan , Sun Xiaomei , Li Yongjun
Published: January 2024

Meat and meat products have a critical role in the human diet as important high-nutrient foods that are widely consumed worldwide. This study evaluated the effects of postmortem aging on Hu sheep’s meat quality in the longissimus dorsi (LD) muscle during postmortem aging. The samples were stored at 4 ± 1 °C; the meat quality was measured at 6 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, and 168 h of postmortem aging. The results showed that, during the postmortem aging process, the pH of the muscles first decreased and then increased, and the shear force first increased and then decreased. The muscle fiber skeleton began to degrade, and the overall meat quality was improved to some extent. In addition, through ACQUITY UPLC I-Class Plus IMS Qtof identification of the muscle samples at different time points during the postmortem maturation process of the meat of Hu sheep, a total of 2168 metabolites were identified, and 470 metabolites were screened based on the VIP, P, and FC values, of which 79 were involved in KEGG pathways. In addition, pathways such as sphingolipid metabolism, glycerophospholipid metabolism, phenylalanine metabolism, and fatty acid elongation and degradation play an important role in the metabolic product changes in the meat of Hu sheep throughout the entire maturation process. These findings provide some insights into the changes in meat quality during the post-slaughter maturation process of lake lamb.
Editorial on Special Issue “Design and Optimization of Pharmaceutical Gels”
Authors: Zhang Xuejuan , Huang Ying , Huang Zhengwei
Published: January 2024

The efficacy of many bioactive agents, including drugs, food supplements, and vaccines, is limited because of their poor chemical stability, low water solubility, and low oral bioavailability [...]
Differential Gene Expression Patterns in Peach Roots under Non-Uniform Soil Conditions in Response to Organic Matter
Authors: Lawrence Brian T. , Calle Alejandro , Saski Christopher A. , Melgar Juan Carlos
Published: January 2024

Organic matter (OM) amendments are often encouraged in sustainable agriculture programs but can create heterogeneous soil environments when applied to perennial crops such as peaches (Prunus persica (L.) Batsch). To better understand the responses of peach roots to non-uniform soil conditions, transcriptomic analysis was performed in a split-root study using uniform soil (the same soil type for all roots) or non-uniform soil (different soil types for each half of the root system) from either (1) autoclaved sand (S), (2) autoclaved sand with autoclaved compost (A), or (3) autoclaved sand with compost which included inherent biological soil life (B). Each uniform soil type (S, A, and B) was grouped and compared by uniform and non-uniform soil comparisons for a total of nine treatments. Comparisons revealed peach roots had differentially expressed genes (DEGs) and gene ontology terms between soil groups, with the S and B groups having a range of 106–411 DEGs and the A group having a range of 19–94 DEGs. Additionally, six modules were identified and correlated (p > 0.69) for six of the nine treatment combinations. This study broadly highlights the complexity of how OM and biological life in the rhizosphere interact with immediate and distant roots and sheds light on how non-homogenous soil conditions can influence peach root gene expression.
The Influence of Socioeconomic and Educational Factors on the Level of Anxiety and Fear of COVID-19
Authors: Coronado-Vázquez Valle , Ramírez-Durán María del Valle , Barrio-Cortes Jaime , Benito-Alonso Elena , Holgado-Juan Marina , Dorado-Rabaneda María Silvia , Gómez-Salgado Juan
Published: January 2024

During the COVID-19 pandemic, there were reports of heightened levels of anxiety and fear of contagion in the general population. Such psychological responses may be influenced by the socio-environmental context in which individuals reside. This study aimed to examine the relationship between socioeconomic and educational factors and the level of anxiety and fear related to COVID-19. A multicenter, cross-sectional design was used, including patients aged 18 years or older who attended primary care physician consultations at various primary health centers in Toledo, Spain, between October 2020 and January 2021. By means of a non-probabilistic sampling, a total of 150 participants were selected for the study, with 146 of them providing responses to the AMICO questionnaire The level of fear and anxiety associated with COVID-19 was assessed using the validated Anxiety and Fear of COVID-19 Assessment Scale (AMICO). A significant linear relationship was revealed between social class, employment status, and anxiety levels. Specifically, as social class decreased (p = 0.001) and employment situation worsened (unemployment) (p = 0.037), the proportion of participants reporting a high level of anxiety increased. During the second phase of the pandemic, more than half of the patients attending family medicine consultations exhibited a high level of fear and anxiety towards COVID-19, which was significantly associated with lower social class and unemployment.
The Patterns and Mechanisms of Residential Mobility in Nanjing, China: Insights from the Mantel Test
Authors: Ye Ling , Song Weixuan , He Miao , Liu Chunhui
Published: January 2024

Residential mobility serves as a pivotal determinant in reshaping urban social spaces and driving spatial differentiation and segregation within cities. This study harnesses a rich dataset from surveys and the housing market in Nanjing, China to dissect the spatial distribution patterns of its mobile population. Employing the Mantel Test—a novel approach in this context—we assess the interplay between spatial shifts in residential locations and the socio-demographic attributes of individuals, thereby shedding light on the socio-spatial dynamics across various migration categories. Our findings underscore a pronounced trend in the post-2000 era of China’s housing marketization: residential migrations occur predominantly within a five-year cycle. The decay in migration distances aligns with the migration field formula, suggesting a systematic attenuation of mobility over spatial extents. The study identifies a strong congruence between the mobility rings—zones of frequent residential movement—and the micro-level characteristics of residents, reflecting the nuanced fabric of urban stratification. Furthermore, we unveil how macro-level institutional frameworks and the housing market milieu substantially shape and limit the migration frequency, hinting at the overarching impact of policy and economic landscapes on residential mobility patterns. The paper culminates by articulating the underlying dynamics of urban residential migration, providing a comprehensive account that contributes to the discourse on sustainable urban development and planning.
Transcription Factors and Their Regulatory Roles in the Male Gametophyte Development of Flowering Plants
Authors: Qian Zhihao , Shi Dexi , Zhang Hongxia , Li Zhenzhen , Huang Li , Yan Xiufeng , Lin Sue
Published: January 2024

Male gametophyte development in plants relies on the functions of numerous genes, whose expression is regulated by transcription factors (TFs), non-coding RNAs, hormones, and diverse environmental stresses. Several excellent reviews are available that address the genes and enzymes associated with male gametophyte development, especially pollen wall formation. Growing evidence from genetic studies, transcriptome analysis, and gene-by-gene studies suggests that TFs coordinate with epigenetic machinery to regulate the expression of these genes and enzymes for the sequential male gametophyte development. However, very little summarization has been performed to comprehensively review their intricate regulatory roles and discuss their downstream targets and upstream regulators in this unique process. In the present review, we highlight the research progress on the regulatory roles of TF families in the male gametophyte development of flowering plants. The transcriptional regulation, epigenetic control, and other regulators of TFs involved in male gametophyte development are also addressed.
Sulforaphane Is Protective against Warm Ischemia/Reperfusion Injury and Partial Hepatectomy in Rats
Authors: Nakatake Richi , Okuyama Tetsuya , Hashimoto Yuki , Ishizaki Morihiko , Yanagida Hidesuke , Kitade Hiroaki , Yoshizawa Katsuhiko , Nishizawa Mikio , Sekimoto Mitsugu
Published: January 2024

Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion injury (HIRI) is unclear. To investigate the hepatoprotective effects of SFN using an in vivo model of HIRI and partial hepatectomy (HIRI + PH), rats were subjected to 15 min of hepatic ischemia with blood inflow occlusion, followed by 70% hepatectomy and release of the inflow occlusion. SFN (5 mg/kg) or saline was randomly injected intraperitoneally 1 and 24 h before ischemia. Alternatively, ischemia was prolonged for 30 min to evaluate the effect on mortality. The influence of SFN on the associated signaling pathways was analyzed using the interleukin 1β (IL-1β)-treated primary cultured rat hepatocytes. In the HIRI + PH-treated rats, SFN reduced serum liver enzyme activities and the frequency of pathological liver injury, such as apoptosis and neutrophil infiltration. SFN suppressed tumor necrosis factor-alpha (TNF-α) mRNA expression and inhibited nuclear factor-kappa B (NF-κB) activation by HIRI + PH. Mortality was significantly reduced by SFN. In IL-1β-treated hepatocytes, SFN suppressed the expression of inflammatory cytokines and NF-κB activation. Taken together, SFN may have hepatoprotective effects in HIRI + PH in part by inhibiting the induction of inflammatory mediators, such as TNF-α, via the suppression of NF-κB in hepatocytes.
Urinary Angiotensinogen Displays Sexual Dimorphism in Non-Diabetic Humans and Mice with Overweight
Authors: Gonzalez Alexis A. , Visniauskas Bruna , Reverte Virginia , Sure Ventaka N. , Vallotton Zoe , Torres Bryan S. , Acosta Marco A. , Zemedkun Mahlet , Katakam Prasad V. , Prieto Minolfa C.
Published: January 2024

Increased body weight (BW) induces inappropriate renin–angiotensin system (RAS) activation. The activation of the intrarenal RAS is associated with increased urinary angiotensinogen (uAGT), blood pressure (BP), and kidney damage. Here, we examined uAGT excretion levels in young non-diabetic human subjects with overweight (OW) and non-diabetic mice with high-fat diet (HFD)-induced OW. Human subjects (women and men; 20–28 years old) included two groups: (a) overweight (OW, n = 17, BMI ≥ 25); and (b) controls (normal weight (NW; n = 26, BMI ≤ 25). In these subjects, we measured BP, albuminuria, and protein levels of uAGT by ELISA adjusted by urinary creatinine (expressed by uAGT/uCrea). Mice (female and male C57BL/6J mice, 8 ± 2 weeks of age) also included two groups: HFD or normal fat diet (NFD) fed for 8 weeks. We measured BW, fasting blood glucose (FBG), BP by telemetry, albuminuria, and uAGT by ELISA. In humans: (i) no significant changes were observed in BP, albuminuria, and FBG when comparing NW and OW subjects; (ii) multivariate logistic regression analysis of independent predictors related to uAGT/uCrea levels demonstrated a strong association between uAGT and overweight; (iii) urinary reactive oxygen species (ROS) were augmented in men and women with OW; (iv) the uAGT/uCrea ratio was higher in men with OW. However, the uAGT/uCrea values were lower in women even with OW. In mice: (i) males fed an HFD for 8 weeks became OW while females did not; (ii) no changes were observed either in FBG, BP, or albuminuria; (iii) kidney ROS were augmented in OW male mice after 28 weeks but not in females; (iv) OW male mice showed augmented excretion of uAGT but this was undetectable in females fed either NFD or HFD. In humans and mice who are OW, the urinary excretion of AGT differs between males and females and overcomes overt albuminuria.
Editorial for the Special Issue “Advances in the Development of Anticancer Drugs”
Authors: Fotie Jean
Published: January 2024

As mortality rates for other leading causes of death, such as stroke and coronary heart disease, decline in many parts of the world, cancer is becoming the leading cause of death worldwide, with the number of yearly new cases expected to rise to about 30 million by 2040 [...]
Cytoskeleton Rearrangement in Podocytopathies: An Update
Authors: Ma Sijia , Qiu Yang , Zhang Chun
Published: January 2024

Podocyte injury can disrupt the glomerular filtration barrier (GFB), leading to podocytopathies that emphasize podocytes as the glomerulus’s key organizer. The coordinated cytoskeleton is essential for supporting the elegant structure and complete functions of podocytes. Therefore, cytoskeleton rearrangement is closely related to the pathogenesis of podocytopathies. In podocytopathies, the rearrangement of the cytoskeleton refers to significant alterations in a string of slit diaphragm (SD) and focal adhesion proteins such as the signaling node nephrin, calcium influx via transient receptor potential channel 6 (TRPC6), and regulation of the Rho family, eventually leading to the disorganization of the original cytoskeletal architecture. Thus, it is imperative to focus on these proteins and signaling pathways to probe the cytoskeleton rearrangement in podocytopathies. In this review, we describe podocytopathies and the podocyte cytoskeleton, then discuss the molecular mechanisms involved in cytoskeleton rearrangement in podocytopathies and summarize the effects of currently existing drugs on regulating the podocyte cytoskeleton.
Descriptive and Functional Genomics in Neonatal Respiratory Distress Syndrome: From Lung Development to Targeted Therapies
Authors: Anciuc-Crauciuc Mădălina , Cucerea Manuela Camelia , Tripon Florin , Crauciuc George-Andrei , Bănescu Claudia Violeta
Published: January 2024

In this up-to-date study, we first aimed to highlight the genetic and non-genetic factors associated with respiratory distress syndrome (RDS) while also focusing on the genomic aspect of this condition. Secondly, we discuss the treatment options and the progressing therapies based on RNAs or gene therapy. To fulfill this, our study commences with lung organogenesis, a highly orchestrated procedure guided by an intricate network of conserved signaling pathways that ultimately oversee the processes of patterning, growth, and differentiation. Then, our review focuses on the molecular mechanisms contributing to both normal and abnormal lung growth and development and underscores the connections between genetic and non-genetic factors linked to neonatal RDS, with a particular emphasis on the genomic aspects of this condition and their implications for treatment choices and the advancing therapeutic approaches centered around RNAs or gene therapy.
Genome-Wide Identification and Characterization of Effector Candidates with Conserved Motif in Falciphora oryzae
Authors: Dai Mengdi , Su Zhenzhu , Zhu Xueming , Li Lin , Ye Ziran , Tan Xiangfeng , Kong Dedong , Liu Xiaohong , Lin Fucheng
Published: January 2024

Microbes employ effectors to disrupt immune responses and promote host colonization. Conserved motifs including RXLR, LFLAK-HVLVxxP (CRN), Y/F/WxC, CFEM, LysM, Chitin-bind, DPBB_1 (PNPi), and Cutinase have been discovered to play crucial roles in the functioning of effectors in filamentous fungi. Nevertheless, little is known about effectors with conserved motifs in endophytes. This research aims to discover the effector genes with conserved motifs in the genome of rice endophyte Falciphora oryzae. SignalP identified a total of 622 secreted proteins, out of which 227 were predicted as effector candidates by EffectorP. By utilizing HMM features, we discovered a total of 169 effector candidates with conserved motifs and three novel motifs. Effector candidates containing LysM, CFEM, DPBB_1, Cutinase, and Chitin_bind domains were conserved across species. In the transient expression assay, it was observed that one CFEM and one LysM activated cell death in tobacco leaves. Moreover, two CFEM and one Chitin_bind inhibited cell death induced by Bax protein. At various points during the infection, the genes’ expression levels were increased. These results will help to identify functional effector proteins involving omics methods using new bioinformatics tools, thus providing a basis for the study of symbiosis mechanisms.
Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome
Authors: Arai Hironori , Matsui Hirotaka , Chi SungGi , Utsu Yoshikazu , Masuda Shinichi , Aotsuka Nobuyuki , Minami Yosuke
Published: January 2024

Due to the proliferation of genetic testing, pathogenic germline variants predisposing to hereditary hematological malignancy syndrome (HHMS) have been identified in an increasing number of genes. Consequently, the field of HHMS is gaining recognition among clinicians and scientists worldwide. Patients with germline genetic abnormalities often have poor outcomes and are candidates for allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT using blood from a related donor should be carefully considered because of the risk that the patient may inherit a pathogenic variant. At present, we now face the challenge of incorporating these advances into clinical practice for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and optimizing the management and surveillance of patients and asymptomatic carriers, with the limitation that evidence-based guidelines are often inadequate. The 2016 revision of the WHO classification added a new section on myeloid malignant neoplasms, including MDS and AML with germline predisposition. The main syndromes can be classified into three groups. Those without pre-existing disease or organ dysfunction; DDX41, TP53, CEBPA, those with pre-existing platelet disorders; ANKRD26, ETV6, RUNX1, and those with other organ dysfunctions; SAMD9/SAMD9L, GATA2, and inherited bone marrow failure syndromes. In this review, we will outline the role of the genes involved in HHMS in order to clarify our understanding of HHMS.
Characterization of the Effect of N-(2-Methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, Compound 8, against Leishmania mexicana and Its In Vivo Leishmanicidal Activity
Authors: Nieto-Meneses Rocío , Castillo Rafael , Hernández-Campos Alicia , Nogueda-Torres Benjamín , López-Villegas Edgar Oliver , Moreno-Rodríguez Adriana , Matadamas-Martínez Félix , Yépez-Mulia Lilián
Published: January 2024

Chemotherapy currently available for leishmaniasis treatment has many adverse side effects and drug resistance. Therefore, the identification of new targets and the development of new drugs are urgently needed. Previously, we reported the synthesis of a N-(2-methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, named compound 8, with an IC50 value in the micromolar range against L. mexicana, it also inhibited 68.27% the activity of recombinant L. mexicana arginase. Herein, we report studies carried out to characterize the mechanism of action of compound 8, as well as its in vivo leishmanicidal activity. It was shown in our ultrastructural studies that compound 8 induces several changes, such as membrane blebbing, the presence of autophagosomes, membrane detachment and mitochondrial and kinetoplast disorganization, among others. Compound 8 triggers the production of ROS and parasite apoptosis. It reduced 71% of the parasite load of L. mexicana in an experimental model of cutaneous leishmaniasis in comparison with a control. Altogether, the data obtained suggest the potential use of compound 8 in the treatment of cutaneous leishmaniasis.
Identification of Muscle Strength-Related Gut Microbes through Human Fecal Microbiome Transplantation
Authors: Ahn Ji-Seon , Koo Bon-Chul , Choi Yu-Jin , Jung Woon-Won , Kim Hyun-Sook , Lee Suk-Jun , Hong Seong-Tshool , Chung Hea-Jong
Published: January 2024

The gut microbiome is well known for its influence on human physiology and aging. Therefore, we speculate that the gut microbiome may affect muscle strength in the same way as the host’s own genes. To demonstrate candidates for gut microbes affecting muscle strength, we remodeled the original gut microbiome of mice into human intestinal microbiome through fecal microbiome transplantation (FMT), using human feces and compared the changes in muscle strength in the same mice before and three months after FMT. After comparing before and after FMT, the mice were divided into three groups based on the observed changes in muscle strength: positive, none, and negative changes in muscle strength. As a result of analyzing the α-diversity, β-diversity, and co-occurrence network of the intestinal microbial community before and after FMT, it was observed that a more diverse intestinal microbial community was established after FMT in all groups. In particular, the group with increased muscle strength had more gut microbiome species and communities than the other groups. Fold-change comparison showed that Eisenbergiella massiliensis and Anaeroplasma abactoclasticum from the gut microbiome had positive contributions to muscle strength, while Ileibacterium valens and Ethanoligenens harbinense had negative effects. This study identifies candidates for the gut microbiome that contribute positively and those that contribute negatively to muscle strength.
Combination Therapy with a TLR7 Agonist and a BRD4 Inhibitor Suppresses Tumor Growth via Enhanced Immunomodulation
Authors: Liu Yong-Si , Wang Jia-Xin , Jin Guang-Yi , Hu Ming-Hao , Wang Xiao-Dong
Published: January 2024

JQ-1 is a typical BRD4 inhibitor with the ability to directly fight tumor cells and evoke antitumor immunity via reducing the expression of PD-L1. However, problems arise with the development of JQ-1 in clinical trials, such as marked lymphoid and hematopoietic toxicity, leading to the investigation of combination therapy. SZU-101 is a TLR7 agonist designed and synthesized by our group with potent immunostimulatory activity. Therefore, we hypothesized that combination therapy of SZU-101 and JQ-1 would target innate immunity and adaptive immunity simultaneously, to achieve a better antitumor efficacy than monotherapy. In this study, the repressive effects of the combination administration on tumor growth and metastasis were demonstrated in both murine breast cancer and melanoma models. In 4T1 tumor-bearing mice, i.t. treatment with SZU-101 in combination with i.p. treatment with JQ-1 suppressed the growth of tumors at both injected and uninjected sites. Combination therapy increased M1/M2 ratio in TAMs, decreased PD-L1 expression and promoted the recruitment of activated CD8+ T cells in the TME. In summary, the improved therapeutic efficacy of the novel combination therapy appears to be feasible for the treatment of a diversity of cancers.
Isorhamnetin Regulates Programmed Death Ligand-1 Expression by Suppressing the EGFR–STAT3 Signaling Pathway in Canine Mammary Tumors
Authors: Mei Chen , Zhang Xue , Zhi Yan , Liang Zhixuan , Xu Haojun , Liu Zhenyi , Liu Ying , Lyu Yanli , Wang Hongjun
Published: January 2024

Programmed death ligand-1 (PD-L1) is highly expressed in a variety of cancer cells and suggests a poorer prognosis for patients. The natural compound isorhamnetin (ISO) shows promise in treating cancers and causing damage to canine mammary tumor (CMT) cells. We investigated the mechanism of ISO in reducing PD-L1 expression in CMT cells. Clustered, regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) was used to mediate CD274 knockout in U27 cells. Then, monoclonal cells were screened and cultured. Nucleotide sequencing and expression of PD-L1 were detected. Additionally, we examined cell migration, invasion, and damage. Immunofluorescent staining of PD-L1 was examined in U27 cells. The signaling pathways were measured by Western blotting. Murine xenotransplantation models and murine immunocompetent allograft mammary tumor models were established to evaluate the effect of ISO therapy. Expression of Ki-67, caspase3, and PD-L1 were analyzed by immunohistochemistry. A pull-down assay was used to explore which proteins could bind to ISO. Canine EGFR protein was purified and used to detect whether it directly binds to ISO using a surface plasmon resonance assay. ISO inhibited the EGFR-STAT3-PD-L1 signaling pathway and blocked cancer growth, significantly increasing the survival rate of healthy cells. The cell membrane receptor EGFR was identified as a direct target of ISO. ISO could be exploited as an antineoplastic treatment of CMT by targeting EGFR to suppress PD-L1 expression.
Block Synthesis and Step-Growth Polymerization of C-6-Sulfonatomethyl-Containing Sulfated Malto-Oligosaccharides and Their Biological Profiling
Authors: Herczeg Mihály , Demeter Fruzsina , Nagy Tibor , Rusznyák Ágnes , Hodek Jan , Sipos Éva , Lekli István , Fenyvesi Ferenc , Weber Jan , Kéki Sándor , Borbás Anikó
Published: January 2024

Highly sulfated malto-oligomers, similar to heparin and heparan-sulfate, have good antiviral, antimetastatic, anti-inflammatory and cell growth inhibitory effects. Due to their broad biological activities and simple structure, sulfated malto-oligomer derivatives have a great therapeutic potential, therefore, the development of efficient synthesis methods for their production is of utmost importance. In this work, preparation of α-(1→4)-linked oligoglucosides containing a sulfonatomethyl moiety at position C-6 of each glucose unit was studied by different approaches. Malto-oligomeric sulfonic acid derivatives up to dodecasaccharides were prepared by polymerization using different protecting groups, and the composition of the product mixtures was analyzed by MALDI-MS methods and size-exclusion chromatography. Synthesis of lower oligomers was also accomplished by stepwise and block synthetic methods, and then the oligosaccharide products were persulfated. The antiviral, anti-inflammatory and cell growth inhibitory activity of the fully sulfated malto-oligosaccharide sulfonic acids were determined by in vitro tests. Four tested di- and trisaccharide sulfonic acids effectively inhibited the activation of the TNF-α-mediated inflammatory pathway without showing cytotoxicity.
Weight Loss Following Bariatric Surgery in People with or without Metabolic Syndrome: A 5-Year Observational Comparative Study
Authors: Ragavan Sharanniyan , Elhelw Omar , Majeed Waseem , Alkhaffaf Bilal , Senapati Siba , Ammori Basil J. , Mudaliar Rajshekhar N. , Syed Akheel A.
Published: January 2024

Aim: Whilst bariatric surgery is the most effective treatment for severe obesity, the aim of this study was to evaluate whether postoperative weight loss is similar in patients with or without metabolic syndrome. Methods: We performed a 5-year observational retrospective comparative cohort analysis of bariatric surgery in 333 patients (72% women) without (Group A, n = 133) or with (Group B, n = 200) metabolic syndrome at baseline. Results: Overall mean (SD) baseline body mass index was 51.7 (7.5) with no significant difference between groups. Overall mean percent total weight loss (%TWL) was 31.9% by 24 months after surgery. Although %TWL was greater in Group A (34.9%) than in Group B (30.2%, p = 0.006) at 24 months, there were no significant differences between groups subsequently up to 60 months of follow-up. Systolic and diastolic blood pressures and lipid profiles improved in both groups. In patients with metabolic syndrome at baseline, mean HbA1c reduced by 36.4% at 12 months and was sustained over the study period. Conclusions: We report that bariatric surgery results in comparable long-term weight loss in patients with or without metabolic syndrome alongside expected improvements in metabolic comorbidities.
Trends of Diagnosis, Disease Course, and Treatment of Atopic Dermatitis 2012–2021: Real-World Data from a Large Healthcare Provider
Authors: Weil Clara , Adiri Roni , Chodick Gabriel , Gersten Merril , Cohen Barak Eran
Published: January 2024

In the last decade, new treatments for atopic dermatitis (AD) have emerged. We aimed to describe trends of the diagnosis, disease course, and treatment of AD over a decade (2012–2021) using data from Maccabi Healthcare Services (a 2.7-million-member healthcare provider in Israel). The AD prevalence was stable (4.0% on 31 December 2021 vs. 4.3% on 31 December 2012). The annual AD incidence was also stable (5.8/1000 in 2012 and 5.7/1000 in 2021). AD-related treatment use was highest in the first year post-diagnosis, and it included, among children (n = 87,414) vs. adults (n = 36,865), low-potency topical corticosteroids (TCS) (41.8% vs. 27.1%), mid-potency TCS (30.1% vs. 28.1%), high-potency TCS (34.9% vs. 60.3%), topical calcineurin inhibitor (10.8% vs. 10.1%), phosphodiesterase-4-inhibitor (0.3% vs. 0.7% overall; approved in 2019), phototherapy (0.1% vs. 2.3%), and systemic/biologic treatments (13.0% vs. 13.3%). Among children diagnosed in 2012 and followed through to 2021 (n = 5248), 21.5% had ≥1 AD diagnosis/treatment 10 years later (among 3223 adults: 38.3%). We conclude that the incidence and prevalence rates of AD were comparable to those in similar database studies and remained relatively stable over the past decade. The results underscore the burden of medication use among children and adults, particularly in the first year after AD diagnosis, and the low rate of AD diagnosis among patients originally diagnosed as children 10 years earlier.
Ranibizumab Modifies the Expression of Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Mononuclear Cells in Patients with Exudative Age-Related Macular Degeneration
Authors: Strzalka-Mrozik Barbara , Paprzycka Olga , Gruszka Oliwia , Madej Marcel , Kruszniewska-Rajs Celina , Gola Joanna Magdalena , Turek Artur
Published: January 2024

Background: Age-related macular degeneration (AMD) is the leading cause of vision loss in people over 60 years of age. Despite research, the causes of AMD remain unclear. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are known to be involved in AMD development, and anti-vascular endothelial growth factor therapy has revolutionized its treatment. This study aims to analyze the changes in gene expression in MMPs and TIMPS in patients with neovascular AMD before and after three doses of ranibizumab. Methods: The study involved 29 patients with neovascular AMD treated with ranibizumab. Peripheral blood mononuclear cells were collected before treatment and 24 h after the third dose of ranibizumab. We assessed MMP and TIMP gene expression profiles through oligonucleotide microarrays and validated selected differential genes using RT-qPCR. Results: A statistically significant change in the expression of six MMP- and TIMP-related genes was observed using oligonucleotide microarray. The mRNA levels of the two genes with the most significant fold changes, MMP15 and TIMP2, were then quantified using RT-qPCR. The results confirmed a statistically significant increase in MMP15 expression and a decrease in TIMP2 levels, although this change was not statistically significant in the group before and after the third dose of ranibizumab. Conclusion: Ranibizumab affects the systemic expression of MMP and TIMP-related genes in patients with neovascular AMD. Results from our exploratory study suggest that MMP15, in particular, may play a role in the treatment response, but further research is necessary.
Anterior Column Reconstruction of Destructive Vertebral Osteomyelitis at the Thoracolumbar Spine with an Expandable Vertebral Body Replacement Implant: A Retrospective, Monocentric Radiological Cohort Analysis of 24 Cases
Authors: Klute Lisa , Esser Marie , Henssler Leopold , Riedl Moritz , Schindler Melanie , Rupp Markus , Alt Volker , Kerschbaum Maximilian , Lang Siegmund
Published: January 2024

Background: Vertebral osteomyelitis (VO) often necessitates surgical intervention due to bone loss-induced spinal instability. Anterior column reconstruction, utilizing expandable vertebral body replacement (VBR) implants, is a recognized approach to restore stability and prevent neurological compromise. Despite various techniques, clinical evidence regarding the safety and efficacy of these implants in VO remains limited. Methods: A retrospective cohort analysis, spanning 2000 to 2020, was conducted on 24 destructive VO cases at a Level 1 orthopedic trauma center. Diagnosis relied on clinical, radiological, and microbiological criteria. Patient demographics, clinical presentation, surgical interventions, and radiological outcomes were assessed. Results: The study included 24 patients (62.5% male; mean age 65.6 ± 35.0 years), with 58% having healthcare-associated infections (HAVO). The mean radiological follow-up was 137.2 ± 161.7 weeks. Surgical intervention significantly improved the bi-segmental kyphotic endplate angle (BKA) postoperatively (mean −1.4° ± 13.6°). However, a noticeable loss of correction was observed over time. The study reported a mortality rate of 1/24. Conclusions: Anterior column reconstruction using expandable VBR effectively improved local spinal alignment in destructive VO. However, the study underscores the necessity for prolonged follow-up and continuous research to refine surgical techniques and postoperative care. Addressing long-term complications and refining surgical approaches will be pivotal as the field progresses.