bluuebunny/crossref_metadata_2025 huggingface dataset:
Agricultural machinery service adoption and farmland transfer-in decision: evidence from rural China
Authors: Zhang Yujiao , Zhang Jian , Liu Yang , Zhu Peixin
Published: August 2023

With the deepening of China’s agricultural labor division, the rapid development of agricultural machinery service has had a profound impact on farmland scale management. Based on the new classical economic and transaction cost theories, this paper investigates the impact mechanism of agricultural machinery service on farmers’ farmland transfer-in decision from the dual perspectives of transaction cost and benefit of labor division, and uses the national rural survey data on the Chinese Family Database to conduct empirical research by using the ordinary least square (OLS) model and limited information maximum likelihood (LIML) method. The study finds that, first, agricultural machinery service expands farmers’ farmland transfer-in decision by encouraging them to obtain the economic efficiency of labor division. Not only agricultural machinery service can alleviate the constraint of farmers’ farmland transfer in labor and capital but also reduce the service transaction cost and increase farmers’ share of the division of labor economy, which further stimulates farmers to expand the scale of management. Second, with the deepening of labor division of agricultural machinery services, the higher transaction efficiency of agricultural machinery service promotes farmers’ farmland transfer-in participation. As long as the marginal net benefit obtained is greater than zero, farmers have incentives to expand the scale of farmland. Therefore, in order to promote China’s farmland scale management, the professional, whole-process, and large-scale development of agricultural machinery services should be further promoted, and the service capacity and fields should be expanded so that outsourcing services can be better provided to agricultural production demanders. At the same time, the technical standards, supervision system, and service platform of agricultural machinery should be established and improved so as to enhance the bargaining position of farmers in service outsourcing transactions, thus promoting the development of agricultural division of labor to a higher level and realizing the mutual promotion and mutual benefit of agricultural machinery service subjects and agricultural land scale management subjects.
Community conservation and remote sensing of the desert-adapted lions in northwest Namibia
Authors: Heydinger John
Published: August 2023

Community-based conservation of the desert-adapted lions takes place within the semi-arid and arid environments of northwest Namibia. This area is primarily designated as communal conservancies, a form of community-based natural resource management (CBNRM). The article describes the activities of the Lion Rangers program, a CBNRM organization, emphasizing how the use of remote sensing techniques, including the Spatial Analysis and Report Tools (SMART) software and mobile-app, GPS/satellite collars, and trail cameras, contribute to lion monitoring and limiting human–lion conflict (HLC). Remote sensing data are being integrated with historical and sociological research, with applicable lessons for lion conservation and conservation of other problem-causing species.
The complex HLA-E-nonapeptide in Behçet disease
Authors: Castaño-Núñez Ángel Luís , Montes-Cano Marco-Antonio , García-Lozano José-Raúl , Ortego-Centeno Norberto , García-Hernández Francisco José , Espinosa Gerard , Graña-Gil Genaro , Sánchez-Bursón Juan , Juliá María Rosa , Solans Roser , Blanco Ricardo , Barnosi-Marín Ana-Celia , Gómez de la Torre Ricardo , Fanlo Patricia , Rodríguez-Carballeira Mónica , Rodríguez-Rodríguez Luis , Camps Teresa , Castañeda Santos , Alegre-Sancho Juan-Jose , Martín Javier , González-Escribano María Francisca
Published: August 2023

Introduction

The knowledge of the aetiology of Behçet disease (BD), an immune-mediated vasculitis, is limited. HLA-B, mainly HLA-B51, and HLA-A molecules are associated with disease, but the ultimate cause of this association remains obscure. There is evidence that NK cells participate in the etiopathology of BD. NK cells have activator and inhibitor surface receptors, like the KIR and the NKG2 families. Classical HLA-class I molecules (A, B and C) are keys in the activity control of the NK because they are KIR ligands. Most NKG2 receptors bind HLA-E, which presents only nonapeptides derived from the signal peptide of other class-I molecules.

Objective

This study investigates the contribution of the pair HLA-E and ligand, nonapeptide derived from the 3-11 sequence of the signal peptides of class I classical molecules, to the susceptibility to BD.

Methods

We analyzed the frequency of the HLA-derivated nonapeptide forms in 466 BD patients and 444 controls and an HLA-E functional dimorphism in a subgroup of patients and controls. Results: In B51 negative patients, the frequency of VMAPRTLLL was lower (70.4% versus 80.0% in controls; P=0.006, Pc=0.04, OR=0.60, 95%CI 0.41-0.86), and the frequency of VMAPRTLVL was higher (81.6% versus 71.4% in controls; P=0.004, Pc=0.03, OR=1.78, 95%CI 1.20-2.63). In homozygosity, VMAPRTLLL is protective, and VMAPRTLVL confers risk. The heterozygous condition is neutral. There were no significant differences in the distribution of the HLA-E dimorphism.

Discussion

Our results explain the association of BD with diverse HLA-A molecules, reinforce the hypothesis of the involvement of the NK cells in the disease and do not suggest a significant contribution of the HLA-E polymorphism to disease susceptibility.
Characterization of papillary and clear cell renal cell carcinoma through imaging mass cytometry reveals distinct immunologic profiles
Authors: Govindarajan Ameish , Salgia Nicholas J. , Li Haiqing , Castro Daniela V. , Mirzapoiazova Tamara , Armstrong Brian , Zhao Dan , Mercier Benjamin D. , Dizman Nazli , Chawla Neal , Zengin Zeynep , Meza Luis , Tripathi Nishita , Sayegh Nicolas , Chehrazi-Raffle Alex , Tripathi Abhishek , Pal Sumanta K.
Published: August 2023

Objective

To characterize and further compare the immune cell populations of the tumor microenvironment (TME) in both clear cell and papillary renal cell carcinoma (RCC) using heavy metal-labeled antibodies in a multiplexed imaging approach (imaging mass cytometry).

Materials and methods

Formalin-fixed paraffin-embedded (FFPE) baseline tumor tissues from metastatic patients with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were retrospectively requisitioned from an institutional biorepository. Pretreated FFPE samples from 33 RCC patients (10 ccRCC, 23 pRCC) were accessioned and stained for imaging mass cytometry (IMC) analysis. Clinical characteristics were curated from an institutional RCC database. FFPE samples were prepared and stained with heavy metal-conjugated antibodies for IMC. An 11-marker panel of tumor stromal and immune markers was used to assess and quantify cellular relationships in TME compartments. To validate our time-of-flight (CyTOF) analysis, we cross-validated findings with The Cancer Genome Atlas Program (TCGA) analysis and utilized the CIBERSORTx tool to examine the abundance of main immune cell types in pRCC and ccRCC patients.

Results

Patients with ccRCC had a longer median overall survival than did those with pRCC (67.7 vs 26.8 mo, respectively). Significant differences were identified in the proportion of CD4+ T cells between disease subtypes (ccRCC 14.1%, pRCC 7.0%, p<0.01). Further, the pRCC cohort had significantly more PanCK+ tumor cells than did the ccRCC cohort (24.3% vs 9.5%, respectively, p<0.01). There were no significant differences in macrophage composition (CD68+) between cohorts. Our results demonstrated a significant correlation between the CyTOF and TCGA analyses, specifically validating that ccRCC patients exhibit higher levels of CD4+ T cells (ccRCC 17.60%, pRCC 15.7%, p<0.01) and CD8+ T cells (ccRCC 17.83%, pRCC 11.15%, p<0.01). The limitation of our CyTOF analysis was the large proportion of cells that were deemed non-characterizable.

Conclusions

Our findings emphasize the need to investigate the TME in distinct RCC histological subtypes. We observed a more immune infiltrative phenotype in the TME of the ccRCC cohort than in the pRCC cohort, where a tumor-rich phenotype was noted. As practical predictive biomarkers remain elusive across all subtypes of RCC, further studies are warranted to analyze the biomarker potential of such TME classifications.
Histone deacetylase 6’s function in viral infection, innate immunity, and disease: latest advances
Authors: Qu Min , Zhang Huijun , Cheng Pengyuan , Wubshet Ashenafi Kiros , Yin Xiangping , Wang Xiangwei , Sun Yuefeng
Published: August 2023

In the family of histone-deacetylases, histone deacetylase 6 (HDAC6) stands out. The cytoplasmic class IIb histone deacetylase (HDAC) family is essential for many cellular functions. It plays a crucial and debatable regulatory role in innate antiviral immunity. This review summarises the current state of our understanding of HDAC6’s structure and function in light of the three mechanisms by which it controls DNA and RNA virus infection: cytoskeleton regulation, host innate immune response, and autophagy degradation of host or viral proteins. In addition, we summed up how HDAC6 inhibitors are used to treat a wide range of diseases, and how its upstream signaling plays a role in the antiviral mechanism. Together, the findings of this review highlight HDAC6’s importance as a new therapeutic target in antiviral immunity, innate immune response, and some diseases, all of which offer promising new avenues for the development of drugs targeting the immune response.
Uncovering the shared molecule and mechanism between ulcerative colitis and atherosclerosis: an integrative genomic analysis
Authors: Huang Jinke , Wang Fengyun , Tang Xudong
Published: August 2023

Background

Ulcerative colitis (UC) and atherosclerosis (AS) are closely related. However, the pathologic mechanisms underlying the co-occurrence of UC and AS are not well understood.

Objects

To reveal the hub molecule and mechanism involved in the co-occurrence of UC and AS.

Methods

Differentially expressed genes (DEGs) of UC and AS were obtained, and the shared DEGs of UC and AS were explored for biological function. Next, the hub genes were explored using the cytoHubba plugin. The predictive ability of the hub genes was measured by constructing the receiver operating characteristic curve. Analyses of immune infiltration and the single-gene gene set enrichment analysis (GSEA) for the hub genes were further carried out.

Results

Identification of 59 DEGs (55 were upregulated and four were downregulated) shared by both UC and AS was performed. Enriched pathways of the shared DEGs were mainly related to immunity and inflammation. Protein tyrosine phosphatase, receptor type, C (PTPRC) was identified as the hub crosstalk gene for the comorbidity of UC and AS. The upregulation of PTPRC was correlated with mast cells resting, T cells CD4 memory resting, macrophages M0, and macrophages M1. Pathways of immune and inflammatory processes, including NF-kappa B, viral protein interaction with cytokine and cytokine receptor, and cytokine–cytokine receptor interaction, were significantly correlated with high expression of PTPRC in UC and AS.

Conclusion

At the transcriptional level, our study reveals that imbalanced inflammatory and immune responses are the key pathological mechanisms underlying the comorbidity of UC and AS and that PTPRC is a key biomarker for the comorbidity of UC and AS.
Animal models for COVID-19 and tuberculosis
Authors: Corleis Björn , Bastian Max , Hoffmann Donata , Beer Martin , Dorhoi Anca
Published: August 2023

Respiratory infections cause tremendous morbidity and mortality worldwide. Amongst these diseases, tuberculosis (TB), a bacterial illness caused by Mycobacterium tuberculosis which often affects the lung, and coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), stand out as major drivers of epidemics of global concern. Despite their unrelated etiology and distinct pathology, these infections affect the same vital organ and share immunopathogenesis traits and an imperative demand to model the diseases at their various progression stages and localizations. Due to the clinical spectrum and heterogeneity of both diseases experimental infections were pursued in a variety of animal models. We summarize mammalian models employed in TB and COVID-19 experimental investigations, highlighting the diversity of rodent models and species peculiarities for each infection. We discuss the utility of non-human primates for translational research and emphasize on the benefits of non-conventional experimental models such as livestock. We epitomize advances facilitated by animal models with regard to understanding disease pathophysiology and immune responses. Finally, we highlight research areas necessitating optimized models and advocate that research of pulmonary infectious diseases could benefit from cross-fertilization between studies of apparently unrelated diseases, such as TB and COVID-19.
Analysis of the impact of handling and culture on the expansion and functionality of NK cells
Authors: Martin-Iglesias Sara , Herrera Lara , Santos Silvia , Vesga Miguel Ángel , Eguizabal Cristina , Lanceros-Mendez Senentxu , Silvan Unai
Published: August 2023

Natural killer (NK) cells are lymphocytes of the innate immune system that play a key role in the elimination of tumor and virus-infected cells. Unlike T cells, NK cell activation is governed by their direct interaction with target cells via the inhibitory and activating receptors present on their cytoplasmic membrane. The simplicity of this activation mechanism has allowed the development of immunotherapies based on the transduction of NK cells with CAR (chimeric antigen receptor) constructs for the treatment of cancer. Despite the advantages of CAR-NK therapy over CAR-T, including their inability to cause graft-versus-host disease in allogenic therapies, a deeper understanding of the impact of their handling is needed in order to increase their functionality and applicability. With that in mind, the present work critically examines the steps required for NK cell isolation, expansion and storage, and analyze the response of the NK cells to these manipulations. The results show that magnetic-assisted cell sorting, traditionally used for NK isolation, increases the CD16+ population of NK cultures only if the protocol includes both, antibody incubation and passage through the isolation column. Furthermore, based on the importance of surface potential on cellular responses, the influence of surfaces with different net surface charge on NK cells has been evaluated, showing that NK cells displayed higher proliferation rates on charged surfaces than on non-charged ones. The present work highlights the relevance of NK cells manipulation for improving the applicability and effectiveness of NK cell-based therapies.
IRF7: role and regulation in immunity and autoimmunity
Authors: Ma Wei , Huang Gang , Wang Zhi , Wang Li , Gao Qiangguo
Published: August 2023

Interferon regulatory factor (IRF) 7 was originally identified as master transcriptional factor that produced IFN-I and regulated innate immune response, subsequent studies have revealed that IRF7 performs a multifaceted and versatile functions in multiple biological processes. In this review, we provide a comprehensive overview on the current knowledge of the role of IRF7 in immunity and autoimmunity. We focus on the latest regulatory mechanisms of IRF7 in IFN-I, including signaling pathways, transcription, translation, and post-translational levels, the dimerization and nuclear translocation, and the role of IRF7 in IFN-III and COVID-19. In addition to antiviral immunity, we also discuss the role and mechanism of IRF7 in autoimmunity, and the further research will expand our understanding of IRF7.
“Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations
Authors: Hatano Yutaka , Elias Peter M.
Published: August 2023

Permeability barrier disruption has been shown to induce immunological alterations (i.e., an “outside-to-inside” pathogenic mechanism). Conversely, several inflammatory and immunological mechanisms reportedly interrupt permeability barrier homeostasis (i.e., an “inside-to-outside” pathogenic mechanism). It is now widely recognized that alterations of even a single molecule in keratinocytes can lead to not only permeability barrier dysfunction but also to immunological alterations. Such a simultaneous, bidirectional functional change by keratinocytes is herein named an “intrinsic” pathogenic mechanism. Molecules and/or pathways involved in this mechanism could be important not only as factors in disease pathogenesis but also as potential therapeutic targets for inflammatory cutaneous diseases, such as atopic dermatitis, psoriasis, and prurigo nodularis. Elevation of skin surface pH following permeability barrier abrogation comprises one of the key pathogenic phenomena of the “outside-to-inside” mechanism. Not only type 2 cytokines (e.g., IL-4, IL-13, IL-31) but also type 1 (e.g. IFN-γ), and type 3 (e.g., IL-17, IL-22) as well as several other inflammatory factors (e.g. histamine) can disrupt permeability barrier homeostasis and are all considered part of the “inside-to-outside” mechanism. Finally, examples of molecules relevant to the “intrinsic” pathogenic mechanism include keratin 1, filaggrin, and peroxisome proliferator-activated receptor-α (PPARα).
Microstructure quality control of steels using deep learning
Authors: Durmaz Ali Riza , Potu Sai Teja , Romich Daniel , Möller Johannes J. , Nützel Ralf
Published: August 2023

In quality control, microstructures are investigated rigorously to ensure structural integrity, exclude the presence of critical volume defects, and validate the formation of the target microstructure. For quenched, hierarchically-structured steels, the morphology of the bainitic and martensitic microstructures are of major concern to guarantee the reliability of the material under service conditions. Therefore, industries conduct small sample-size inspections of materials cross-sections through metallographers to validate the needle morphology of such microstructures. We demonstrate round-robin test results revealing that this visual grading is afflicted by pronounced subjectivity despite the thorough training of personnel. Instead, we propose a deep learning image classification approach that distinguishes steels based on their microstructure type and classifies their needle length alluding to the ISO 643 grain size assessment standard. This classification approach facilitates the reliable, objective, and automated classification of hierarchically structured steels. Specifically, an accuracy of 96% and roughly 91% is attained for the distinction of martensite/bainite subtypes and needle length, respectively. This is achieved on an image dataset that contains significant variance and labeling noise as it is acquired over more than 10 years from multiple plants, alloys, etchant applications, and light optical microscopes by many metallographers (raters). Interpretability analysis gives insights into the decision-making of these models and allows for estimating their generalization capability.
Role of probiotics in preventing Clostridioides difficile infection in older adults: an integrative review
Authors: Barbosa Maria Lucianny Lima , Albano Mariana Oliveira , Martins Conceição da Silva , Warren Cirle Alcantara , Brito Gerly Anne de Castro
Published: August 2023

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. This infection can particularly affect older adults, the most susceptible to CDI. Currently, the standard therapeutic measure is antibiotic therapy, which in turn increases the risk of recurrence of the infection by its collateral damage to the patient’s microbiota. Probiotics are live microorganisms capable of maintaining balance in the intestinal microbiota. This study aims to perform an integrative review of the protective benefit of probiotics in CDI and diarrhea associated with C. difficile. The PubMed, Scopus, and Web of Science databases, the 10-year time cutoff, and the Prism Flow diagram were used for data collection. We observed no consensus among the studies; however, three of the seven evaluated studies demonstrated that the use of probiotics in older adults could contribute to reducing the incidence of hospital-onset CDI. We also found that the studies evaluated a wide variety of microorganisms, particularly Saccharomyces boulardii, associated with beneficial effects. More research is needed to understand the successful use of probiotics in the prevention of CDI in hospitalized older adults receiving antibiotics.
Screening and genome-wide analysis of lignocellulose-degrading bacteria from humic soil
Authors: Zhang Tianjiao , Wei Shuli , Liu Yajie , Cheng Chao , Ma Jie , Yue Linfang , Gao Yanrong , Cheng Yuchen , Ren Yongfeng , Su Shaofeng , Zhao Xiaoqing , Lu Zhanyuan
Published: August 2023

Crop straw contains huge amounts of exploitable energy, and efficient biomass degradation measures have attracted worldwide attention. Mining strains with high yields of cellulose-degrading enzymes is of great significance for developing clean energy and industrial production of related enzymes. In this study, we reported a high-quality genome sequence of Bacillus velezensis SSF6 strain using high-throughput sequencing technology (Illumina PE150 and PacBio) and assessed its lignocellulose degradation potential. The results demonstrated that the genome of B. velezensis SSF6 was 3.89 Mb and contained 4,015 genes, of which 2,972, 3,831 and 158 genes were annotated in the COGs (Clusters of Orthologous Groups), KEGG (Kyoto Encyclopedia of Genes and Genomes) and CAZyme (Carbohydrate-Active enZymes) databases, respectively, and contained a large number of genes related to carbohydrate metabolism. Furthermore, B. velezensis SSF6 has a high cellulose degradation capacity, with a filter paper assay (FPA) and an exoglucanase activity of 64.48 ± 0.28 and 78.59 ± 0.42 U/mL, respectively. Comparative genomic analysis depicted that B. velezensis SSF6 was richer in carbohydrate hydrolase gene. In conclusion, the cellulose-degrading ability of B. velezensis SSF6 was revealed by genome sequencing and the determination of cellulase activity, which laid a foundation for further cellulose degradation and bioconversion.
Different responses of the rhizosphere microbiome to Verticillium dahliae infection in two cotton cultivars
Authors: Tie Zhanjiang , Wang Peng , Chen Weijian , Tang Binghui , Yu Yu , Liu Zheng , Zhao Sifeng , Khan Faisal Hayat , Zhang XueKun , Xi Hui
Published: August 2023

Verticillium wilt is a disastrous disease caused by Verticillium dahliae that severely damages the production of cotton in China. Even under homogeneous conditions, the same cotton cultivar facing V. dahliae tends to either stay healthy or become seriously ill and die. This binary outcome may be related to the interactions between microbiome assembly and plant health. Understanding how the rhizosphere microbiome responds to V. dahliae infection is vital to controlling Verticillium wilt through the manipulation of the microbiome. In this study, we evaluated the healthy and diseased rhizosphere microbiome of two upland cotton cultivars that are resistant to V. dahliae, Zhong 2 (resistant) and Xin 36 (susceptible), using 16S rRNA and ITS high-throughput sequencing. The results showed that the healthy rhizosphere of both resistant cultivar and susceptible cultivar had more unique bacterial ASVs than the diseased rhizosphere, whereas fewer unique fungal ASVs were found in the healthy rhizosphere of resistant cultivar. There were no significant differences in alpha diversity and beta diversity between the resistant cultivar and susceptible cultivar. In both resistant cultivar and susceptible cultivar, bacterial genera such as Pseudomonas and Acidobacteria bacterium LP6, and fungal genera such as Cephalotrichum and Mortierella were both highly enriched in the diseased rhizosphere, and Pseudomonas abundance in diseased rhizospheres was significantly higher than that in the healthy rhizosphere regardless of the cultivar type. However, cultivar and V. dahliae infection can cause composition changes in the rhizosphere bacterial and fungal communities, especially in the relative abundances of core microbiome members, which varied significantly, with different responses in the two cotton cultivars. Analysis of co-occurrence networks showed that resistant cultivar has a more complex network relationship than susceptible cultivar in the bacterial communities, and V. dahliae has a significant impact on the bacterial community structure. These findings will further broaden the understanding of plant-rhizosphere microbiome interactions and provide an integrative perspective on the cotton rhizosphere microbiome, which is beneficial to cotton health and production.
Exploring the efficacy of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a natural compound in strengthening maize resistance against biotic and abiotic stressors: an empirical computational study
Authors: Debnath Sandip , Elgorban Abdallah M. , Bahkali Ali H. , Eswaramoorthy Rajalakshmanan , Verma Meenakshi , Tiwari Pragya , Wang Shifa , Wong Ling Shing , Syed Asad
Published: August 2023

Objective

This study aims to understand plant-bacteria interactions that enhance plant resistance to environmental stressors, with a focus on maize (Zea mays L.) and its vulnerability to various pathogenic organisms. We examine the potential of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a compound to boost maize’s resilience against stressors and pathogens.

Background

With the growing global population and increased food demand, the study of endophytes, comprising bacteria and fungi, becomes crucial. They reside within plant tissues, affecting their hosts either beneficially or detrimentally. Agrobacteria are of specific interest due to their potential to contribute to developing strategies for plant resistance enhancement.

Methods

We conducted exhaustive research on the defense-related proteins and mechanisms involved in maize-pathogen interactions. The efficacy of ACCA as a natural-compound that could enhance maize’s resistance was examined.

Results

Our research indicates that ACCA, having a binding energy of −9.98 kcal/mol, successfully strengthens maize resistance against pathogenic assaults and drought stress. It plays a crucial protective role in maize plants as they mature, outperforming other ligands in its effectiveness to improve productivity and increase yield.

Conclusion

Applying ACCA to maize plants has considerable potential in enhancing their resilience and tolerance to stress, proving to be an effective strategy to boost crop yield and productivity. This could help address the increasing global food demand. However, more research is needed to optimize ACCA application methods and to gain a comprehensive understanding of its long-term effects on maize cultivations and the environment.
Anti-quorum sensing potential of selenium nanoparticles against LasI/R, RhlI/R, and PQS/MvfR in Pseudomonas aeruginosa: a molecular docking approach
Authors: Kanak Kanak Raj , Dass Regina Sharmila , Pan Archana
Published: August 2023

Pseudomonas aeruginosa is an infectious pathogen which has the ability to cause primary and secondary contagions in the blood, lungs, and other body parts of immunosuppressed individuals, as well as community-acquired diseases, such as folliculitis, osteomyelitis, pneumonia, and others. This opportunistic bacterium displays drug resistance and regulates its pathogenicity via the quorum sensing (QS) mechanism, which includes the LasI/R, RhlI/R, and PQS/MvfR systems. Targeting the QS systems might be an excellent way to treat P. aeruginosa infections. Although a wide array of antibiotics, namely, newer penicillins, cephalosporins, and combination drugs are being used, the use of selenium nanoparticles (SeNPs) to cure P. aeruginosa infections is extremely rare as their mechanistic interactions are weakly understood, which results in carrying out this study. The present study demonstrates a computational approach of binding the interaction pattern between SeNPs and the QS signaling proteins in P. aeruginosa, utilizing multiple bioinformatics approaches. The computational investigation revealed that SeNPs were acutely ‘locked’ into the active region of the relevant proteins by the abundant residues in their surroundings. The PatchDock-based molecular docking analysis evidently indicated the strong and significant interaction between SeNPs and the catalytic cleft of LasI synthase (Phe105-Se = 2.7 Å and Thr121-Se = 3.8 Å), RhlI synthase (Leu102-Se = 3.7 Å and Val138-Se = 3.2 Å), transcriptional receptor protein LasR (Lys42-Se = 3.9 Å, Arg122-Se = 3.2 Å, and Glu124-Se = 3.9 Å), RhlR (Tyr43-Se = 2.9 Å, Tyr45-Se = 3.4 Å, and His61-Se = 3.5 Å), and MvfR (Leu208-Se = 3.2 Å and Arg209-Se = 4.0 Å). The production of acyl homoserine lactones (AHLs) was inhibited by the use of SeNPs, thereby preventing QS as well. Obstructing the binding affinity of transcriptional regulatory proteins may cause the suppression of LasR, RhlR, and MvfR systems to become inactive, thereby blocking the activation of QS-regulated virulence factors along with their associated gene expression. Our findings clearly showed that SeNPs have anti-QS properties against the established QS systems of P. aeruginosa, which strongly advocated that SeNPs might be a potent solution to tackle drug resistance and a viable alternative to conventional antibiotics along with being helpful in therapeutic development to cure P. aeruginosa infections.
Regeneration of the cerebral cortex by direct chemical reprogramming of macrophages into neuronal cells in acute ischemic stroke
Authors: Ninomiya Itaru , Koyama Akihide , Otsu Yutaka , Onodera Osamu , Kanazawa Masato
Published: August 2023

Theoretically, direct chemical reprogramming of somatic cells into neurons in the infarct area represents a promising regenerative therapy for ischemic stroke. Previous studies have reported that human fibroblasts and astrocytes transdifferentiate into neuronal cells in the presence of small molecules without introducing ectopic transgenes. However, the optimal combination of small molecules for the transdifferentiation of macrophages into neurons has not yet been determined. The authors hypothesized that a combination of small molecules could induce the transdifferentiation of monocyte-derived macrophages into neurons and that the administration of this combination may be a regenerative therapy for ischemic stroke because monocytes and macrophages are directly involved in the ischemic area. Transcriptomes and morphologies of the cells were compared before and after stimulation using RNA sequencing and immunofluorescence staining. Microscopic analyses were also performed to identify cell markers and evaluate functional recovery by blinded examination following the administration of small molecules after ischemic stroke in CB-17 mice. In this study, an essential combination of six small molecules [CHIR99021, Dorsomorphin, Forskolin, isoxazole-9 (ISX-9), Y27632, and DB2313] that transdifferentiated monocyte-derived macrophages into neurons in vitro was identified. Moreover, administration of six small molecules after cerebral ischemia in model animals generated a new neuronal layer in the infarct cortex by converting macrophages into neuronal cells, ultimately improving neurological function. These results suggest that altering the transdifferentiation of monocyte-derived macrophages by the small molecules to adjust their adaptive response will facilitate the development of regenerative therapies for ischemic stroke.
Advances in understanding the pathogenesis of post-traumatic epilepsy: a literature review
Authors: Fang Mingzhu , Liu Wanyu , Tuo Jinmei , Liu Mei , Li Fangjing , Zhang Lijia , Yu Changyin , Xu Zucai
Published: August 2023

Severe head trauma can lead to seizures. Persistent epileptic seizures and their progression are associated with the severity of trauma. Although case reports have revealed that early use of anti-seizure drugs after trauma can prevent epilepsy, clinical case–control studies have failed to confirm this phenomenon. To date, many brain trauma models have been used to study the correlation between post-traumatic seizures and related changes in neural circuit function. According to these studies, neuronal and glial responses are activated immediately after brain trauma, usually leading to significant cell loss in injured brain regions. Over time, long-term changes in neural circuit tissues, especially in the neocortex and hippocampus, lead to an imbalance between excitatory and inhibitory neurotransmission and an increased risk of spontaneous seizures. These changes include alterations in inhibitory interneurons and the formation of new, over-recurrent excitatory synaptic connections. In this study, we review the progress of research related to post-traumatic epilepsy to better understand the mechanisms underlying the initiation and development of post-traumatic seizures and to provide theoretical references for the clinical treatment of post-traumatic seizures.
Pregnancy characteristics and adverse outcomes in offspring of women with epilepsy: a prospective registry study from Mainland China
Authors: Li Rui , Chen Qian , Cao Xing , Yan Hua , Wang Pei , Huang Qun , Li Xiaoyi , Chen Fang , Li Yangchao , Kong Qingxia , Guo Chonglun , Zhang Qi , Hong Qiulei , Liu Yong , Xiong Xiaoli , Han Yanbing , Xiao Xiaohua , Wang Kuiyun , Wu Xunyi , Zhu Xi , Zhang Qing , Chen Lei
Published: August 2023

Objective

This study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the epilepsy knowledge popularization campaign in China (EKPCIC).

Methods

This nested case-control study focused on WWE and their offspring from a female epilepsy cohort in mainland China. From January 2009 to August 2022, WWE was prospectively enrolled in 32 study centers. This study aimed to observe the health outcomes of their offspring within 1 year of age. The main outcome measure assessed the health status of the offspring within their first year of age. We aimed to analyze the effects of seizures, anti-seizure medicines (ASMs), and a lack of folic acid supplementation on adverse outcomes in the offspring of WWE and to explore the changes in perinatal management and adverse outcomes of the offspring after dissemination of the EKPCIC in 2015. Additionally, subgroup analyses were conducted to compare seizure control during pregnancy between the valproate and non-valproate groups.

Results

In total, 781 pregnancies in 695 WWE were included, of which 186 (23.69%) had adverse outcomes. The National Hospital Epilepsy Severity Scale score, number of seizures, status epilepticus, ASM type, and valproate and folic acid doses were associated with a high risk of adverse outcomes. After the EKPCIC, the use of ASMs (P = 0.013) and folic acid (P < 0.001), the seizure-free rate during pregnancy (P = 0.013), and the breastfeeding rate (P < 0.001) increased, whereas the incidence of complications during pregnancy decreased (P = 0.013). However, there was no significant difference in the incidence of adverse outcomes between the analyzed offspring pre-/post-EKPCIC. Additionally, there was no association between the frequency of seizures at different time points during pregnancy and the use of valproate (F = 1.514, P = 0.221).

Conclusion

Possible factors influencing adverse outcomes in the offspring of WWE include seizures, type and number of ASM usage, and a lack of folic acid supplementation. Although the management of WWE during pregnancy is now more standardized, further efforts are needed to reduce adverse outcomes in offspring.
Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative ‘window of discovery’
Authors: Di Stadio Arianna , De Luca Pietro , Koohi Nehzat , Kaski Diego , Ralli Massimo , Giesemann Anja , Hartung Hans-Peter , Altieri Marta , Messineo Daniela , Warnecke Athanasia , Frohman Teresa , Frohman Elliot M.
Published: August 2023

Background

Hearing can be impaired in many neurological conditions and can even represent a forme fruste of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear’s perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function.

Methods

A systematic review of the literature was performed, searching for papers with case–control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated.

Results

Patients with neurological disorders (headache, Parkinson’s disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals.

Conclusion

Existing data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.
What is the effect of benzodiazepines on deep brain activity? A study in pediatric patients with dystonia
Authors: Hernandez-Martin Estefania , Vidmark Jessica S. L. , MacLean Jennifer A. , Sanger Terence D.
Published: August 2023

Introduction

Benzodiazepines (BDZs) are commonly used to treat the symptoms of movement disorders; however, deep brain stimulation (DBS) has become a popular treatment for these disorders. Previous studies have investigated the effects of BDZ on cortical activity, no data are currently available on their effects on deep brain regions, nor on these regions’ responses to DBS. How the BDZ affects the thalamus and basal ganglia in dystonia patients remains unknown.

Methods

DBS recordings were performed in ventral oralis anterior/posterior (VoaVop), ventral intermediate (VIM) and ventral anterior (VA) thalamic subnuclei, as well as globus pallidus interna (GPi) and subthalamic nucleus (STN). Evoked potentials (EP) and frequency domain analysis were performed to determine the BDZ effect on neural activities compared to the control condition (off-BDZ). Three male pediatric patients with dystonia treated with BDZ and undergoing depth electrode evaluation for clinical targeting were recruited for the study. Stimulation was administered at 25 and 55 Hz frequencies and recordings were simultaneously gathered through pairs of externalized stereoelectroencephalography (sEEG) electrodes. EP amplitude and the effect of stimulation on the frequency spectrum of activity were compared at baseline and following clinical administration of BDZ.

Results

Frequency analysis showed consistent reductions in activity during BDZ treatment in all studied brain regions for all patients. Evoked potential (EP) analysis showed increased subthalamic nucleus (STN) EP amplitude and decreased ventral intermediate (VIM) and STN EP amplitude during BDZ treatment.

Interpretation

BDZs reduce thalamic and basal ganglia activity in multiple regions and alter the efficacy of transmission between these regions. While the mechanism is unknown our results confirm the known widespread effects of this class of medications and identify specific areas within the motor system that are directly affected.
Ticagrelor versus clopidogrel after intracranial stent angioplasty: a real-world study
Authors: Sun Lili , Wang Shuzhen , Song Yun , Zhao Wei , Zheng Meimei , Yin Hao , Zhang Jun , Meng Yao , Wang Wei , Han Ju
Published: August 2023

Objective

It was unknown whether a regimen of aspirin plus ticagrelor (aspirin-ticagrelor) attenuates ischemic vascular events without increasing bleeding risk in patients who had undergone intracranial stenting compared with an aspirin plus clopidogrel (aspirin-clopidogrel) regimen. This article compares the efficacy and safety outcomes of the two double antibody regimens in patients undergoing intracranial stent and investigates whether aspirin-ticagrelor could be an alternative antiplatelet agent without increasing the risk of bleeding.

Methods

We conducted a retrospective analysis of our database for patients who had undergone intracranial stenting. From January 2017 to May 2021, consecutive patients treated with endovascular stenting were identified and dichotomized by whether aspirin-ticagrelor or aspirin-clopidogrel were used. The outcomes were compared by propensity score matching.

Results

A total of 340 patients treated with intracranial stent were included. Of all, 132 patients were matched. At 180 days, ischemic vascular events occurred in one patient (1.5%) in the aspirin-ticagrelor group and in six patients (9.1%) in the aspirin-clopidogrel group. Although the absolute incidence of ischemic vascular events [1.5% (1/66) vs. 9.1% (6/66), p = 0.125] was lower in the aspirin-ticagrelor group than in the aspirin-clopidogrel group, there were no statistical differences. There were no statistical differences in ischemic vascular events, ischemic stroke, or death up to 180 days between the two groups. In addition, the incidence of bleeding did not differ. No intracranial hemorrhage or mild bleeding occurred. No statistically significant difference was noted in restenosis and symptomatic restenosis at follow-up.

Conclusion

In our study involving patients with acute ischemic stroke who had undergone intracranial stenting, aspirin-ticagrelor was not found to be superior to aspirin-clopidogrel in reducing the rate of ischemic vascular events. The risk of bleeding did not differ between the two groups. Aspirin-ticagrelor does not lower total restenosis and symptomatic restenosis risk at follow-up.
LITE-1 mediates behavioral responses to X-rays in Caenorhabditis elegans
Authors: Cannon Kelli E. , Ranasinghe Meenakshi , Millhouse Paul W. , Roychowdhury Ayona , Dobrunz Lynn E. , Foulger Stephen H. , Gauntt David M. , Anker Jeffrey N. , Bolding Mark
Published: August 2023

Rapid sensory detection of X-ray stimulation has been documented across a wide variety of species, but few studies have explored the underlying molecular mechanisms. Here we report the discovery of an acute behavioral avoidance response in wild type Caenorhabditis elegans to X-ray stimulation. The endogenous C. elegans UV-photoreceptor protein LITE-1 was found to mediate the locomotory avoidance response. Transgenic expression of LITE-1 in C. elegans muscle cells resulted in paralysis and egg ejection responses to X-ray stimulation, demonstrating that ectopic expression of LITE-1 can confer X-ray sensitivity to otherwise X-ray insensitive cells. This work represents the first demonstration of rapid X-ray based genetically targeted (X-genetic) manipulation of cellular electrical activity in intact behaving animals. Our findings suggest that LITE-1 has strong potential for use in this minimally invasive form of neuromodulation to transduce transcranial X-ray signals for precise manipulation of neural activity in mammals, bypassing the need for invasive surgical implants to deliver stimulation.
Metabolic syndrome in relation to dietary acid load: a dose–response meta-analysis of observational studies
Authors: Al-Hawary Sulieman Ibraheem Shelash , Mushabab Faris , Abullais Shahabe Saquib , Althomali Raed H. , Saleh Ebraheem Abdu Musad , Alnajjar Serar Nassir , Oudaha Khulood H. , Romero-Parra Rosario Mireya , Hussien Beneen M. , Garousi Nazila
Published: August 2023

Background and aim

Several studies have identified that dietary acid load (DAL) may be associated with the odds of metabolic syndrome (MetS); however, the evidence is inconclusive. This dose–response meta-analysis aimed to examine the relation of DAL to MetS.

Methods

A systematic literature search was carried out in PubMed and Scopus up to April 2023 for pertinent studies evaluating the relation of DAL scores, including potential renal acid load (PRAL) and net endogenous acid production (NEAP), to the odds of MetS. The odds ratios (OR) with 95% confidence intervals (CI) were pooled using a random-effects meta-analysis to test the association.

Results

Eight studies, with an overall sample size of 31,351 participants, were included in this meta-analysis. Higher DAL scores were significantly related to the elevated odds of MetS (NEAP: OR = 1.42, 95%CI = 1.12–1.79; PRAL: OR = 1.76, 95%CI = 1.11–2.78), with significant evidence of heterogeneity across studies. The linear dose–response analysis proposed that a 10 mEq/day elevation in NEAP and PRAL was linked to a 2% (OR = 1.02, 95%CI = 1.001–1.05) and 28% (OR = 1.28, 95%CI = 1.11–1.47) increased odds of MetS, respectively. No non-linear association was observed between MetS and NEAP (P-non-linearity = 0.75) and PRAL (P-non-linearity = 0.92).

Conclusion

This study revealed a significant direct relationship between DAL and MetS. Therefore, lower acidogenic diets are suggested for the prevention of MetS.
Efficacy and safety of nintedanib in patients with non-small cell lung cancer, and novel insights in radiation-induced lung toxicity
Authors: Yan Shu , Xue Shuyu , Wang Tiantian , Gao Ruihang , Zeng Hanqiao , Wang Qianmeng , Jia Xiaojing
Published: August 2023

Nintedanib is a tyrosine kinase inhibitor of fibroblast growth factor-, vascular endothelial growth factor-, and platelet-derived growth factor receptors. These three receptors promote new blood vessel formation and maintenance, which is essential for tumor growth and spread. Several trials have shown that nintedanib plays a substantial role in treating patients with non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis. Recently, several clinical trials of nintedanib to treat NSCLC have been reported. In this review, we focus on our current understanding of nintedanib treatment for advanced NSCLC patients and summarize the literature on using nintedanib in radiation-induced lung toxicity and the efficacy and tolerability of nintedanib.