Search

Abstract Germinal center (GC) formation, which is an integrant part of humoral immunity, involves energy-consuming metabolic reprogramming. Rag-GTPases are known to signal amino acid availability to cellular pathways that regulate nutrient distribution such as the mechanistic target of rapamycin complex 1 (mTORC1) pathway and the transcription factors TFEB and TFE3. However, the contribution of these factors to humoral immunity remains undefined. Here, we show that B cell-intrinsic Rag-GTPases are critical for the development and activation of B cells. RagA/RagB deficient B cells fail to form GCs, produce antibodies, and to generate plasmablasts during both T-dependent (TD) and T-independent (TI) humoral immune responses. Deletion of RagA/RagB in GC B cells leads to abnormal dark zone (DZ) to light zone (LZ) ratio and reduced affinity maturation. Mechanistically, the Rag-GTPase complex constrains TFEB/TFE3 activity to prevent mitophagy dysregulation and maintain mitochondrial fitness in B cells, which are independent of canonical mTORC1 activation. TFEB/TFE3 deletion restores B cell development, GC formation in Peyer’s patches and TI humoral immunity, but not TD humoral immunity in the absence of Rag-GTPases. Collectively, our data establish the Rag GTPase-TFEB/TFE3 pathway as a likely mTORC1 independent mechanism to coordinating nutrient sensing and mitochondrial metabolism in B cells.

Abstract Due to the powerful ability in capturing the global information, transformer has become an alternative architecture of CNNs for hyperspectral image classification. However, general transformer mainly considers the global spectral information while ignores the multiscale spatial information of the hyperspectral image. In this paper, we propose a multiscale spectral–spatial convolutional transformer (MultiFormer) for hyperspectral image classification. First, the developed method utilizes multiscale spatial patches as tokens to formulate the spatial transformer and generates multiscale spatial representation of each band in each pixel. Second, the spatial representation of all the bands in a given pixel are utilized as tokens to formulate the spectral transformer and generate the multiscale spectral–spatial representation of each pixel. Besides, a modified spectral–spatial CAF module is constructed in the MultiFormer to fuse cross‐layer spectral and spatial information. Therefore, the proposed MultiFormer can capture the multiscale spectral–spatial information and provide better performance than most of other architectures for hyperspectral image classification. Experiments are conducted over commonly used real‐world datasets and the comparison results show the superiority of the proposed method.

Abstract. Background:. China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019. Methods:. The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported. Results:. The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends. Conclusions:. The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

Despite extensive research, determining the optimal level of sunlight exposure for human health remains a challenge, emphasizing the need for ongoing scientific inquiry into this critical aspect of human well-being. This review aims to elucidate how different components of the solar spectrum, particularly near-infrared (NIR) radiation and ultraviolet radiation (UVR) affect human health in diverse ways depending on factors such as time of day and duration of exposure. Sunlight has beneficial effects from the production of melatonin by NIR and vitamin D by UVB. Sunlight also causes harmful effects as evidenced by oxidative stress and DNA damage. Exposure to morning and evening sunlight when the UV index is below 3 is suggested to be beneficial for harnessing its positive effects while avoiding the harmful effects of UVR when the UV index is 3 or higher. Understanding the optimal timing and duration of sunlight exposure is crucial for harnessing its beneficial effects while minimizing its harmful consequences by adopting appropriate sun protection measures. By adhering to sun protection guidelines when the UV index is 3 or more and incorporating strategic exposure to NIR rays when the UV index is less than 3, individuals can optimize their health outcomes while mitigating the risks associated with sun exposure. Given that the effects of sun exposure can be both harmful and beneficial, and Australia’s unique geographical position where it experiences the highest levels of exposure to sunlight, it is vital to understand the appropriate level and timing of sun exposure to live healthy under the Australian sun.

The functional endophytic bacterial community can effectively degrade polycyclic aromatic hydrocarbons (PAHs), thereby reducing their accumulation in vegetables grown on contaminated sites. However, the biological mechanisms underlying this reduction remain unclear. In this study, we analyzed the efficacy of different colonization methods of the functional endophytic bacterial community m5 in reducing PAHs in vegetables, with a particular focus on the leaf painting method. The results demonstrated that various colonization methods effectively reduced PAHs in vegetables, with leaf painting proving to be a cost-effective and efficient approach. Compared to the non-inoculated control, PAH content in the edible parts of amaranth was reduced by 40.63 % using the leaf painting method. High-throughput sequencing and quantitative PCR revealed that leaf painting altered the bacterial community structure and key components of the bacterial network, enhancing bacterial cooperation. After 20 days of colonization, the abundance of phe and nidA genes in vegetables increased significantly, by tens to hundreds of times, compared to uninoculated controls, thereby promoting the degradation of PAHs in vegetables. This study enhances our understanding of the biological mechanisms by which endophytic bacterial communities reduce PAHs in vegetables.

Abstract Background Recently, the application of deep learning (DL) has made great progress in various fields, especially in cancer research. However, to date, the bibliometric analysis of the application of DL in cancer is scarce. Therefore, this study aimed to explore the research status and hotspots of the application of DL in cancer. Methods We retrieved all articles on the application of DL in cancer from the Web of Science database Core Collection database. Biblioshiny, VOSviewer and CiteSpace were used to perform the bibliometric analysis through analyzing the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results We found 6,016 original articles on the application of DL in cancer. The number of annual publications and total citations were uptrend in general. China published the greatest number of articles, USA had the highest total citations, and Saudi Arabia had the highest centrality. Chinese Academy of Sciences was the most productive institution. Tian, Jie published the greatest number of articles, while He Kaiming was the most co-cited author. IEEE Access was the most popular journal. The analysis of references and keywords showed that DL was mainly used for the prediction, detection, classification and diagnosis of breast cancer, lung cancer, and skin cancer. Conclusions Overall, the number of articles on the application of DL in cancer is gradually increasing. In the future, further expanding and improving the application scope and accuracy of DL applications, and integrating DL with protein prediction, genomics and cancer research may be the research trends.

Abstract Background Bowel urgency is a highly burdensome symptom among patients with inflammatory bowel disease (IBD). Objectives To assess changes in severity of bowel urgency and identify predictors of worsening or improvement among patients with Crohn’s disease (CD) and ulcerative colitis (UC) at 6 months from their enrollment visit. Methods Data from patients in the Study of a Prospective Adult Research Cohort with IBD were analyzed. Enrolled patients with CD or UC with 6-month visits were included. Changes and predictors of bowel urgency severity over 6 months in patients with CD or UC were examined using two separate analyses: (a) “worsening” versus “no change” excluding those with moderate-to-severe bowel urgency at enrollment, and (b) “improvement” versus “no change” excluding those with no bowel urgency at enrollment. The enrollment characteristics were compared within these groups. Results At baseline, in both CD and UC, use of biologics and/or immunomodulators at enrollment was similar across cohorts. Among patients with CD, 206 of 582 (35.4%) reported worsening, and 195 of 457 (42.7%) reported improvement in bowel urgency. Younger age (P = 0.013) and moderate-to-severe bowel urgency (P < 0.001) were associated with improvement. Moderate bowel urgency (P = 0.026) and bowel incontinence while awake (P = 0.022) were associated with worsening. Among patients with UC, 84 of 294 (28.6%) reported worsening, and 111 of 219 (50.7%) reported improvement in bowel urgency. Higher symptomatic disease severity (P = 0.011) and more severe bowel urgency (P

Mitochondria and lysosomes play a very important role in maintaining cellular homeostasis, and the dysfunction of these organelles is closely related to many diseases. Recent studies have revealed direct interactions between mitochondria and lysosomes, forming mitochondria-lysosome contact sites that regulate organelle network dynamics and mediate the transport of metabolites between them. Impaired function of these contact sites is not only linked to physiological processes such as glucose and cholesterol transport but also closely related to the pathological processes of metabolic diseases. Here, we highlight the recent progress in understanding the mitochondria-lysosome contact sites, elucidate their role in regulating metabolic homeostasis, and explore the potential implications of this pathway in metabolic disorders.

Abstract Background Nymphaea (waterlily) is known for its rich colors and role as an important aquatic ornamental plant globally. Nymphaea atrans and some hybrids, including N. ‘Feitian 2,’ are more appealing due to the gradual color change of their petals at different flower developmental stages. The petals of N. ‘Feitian 2’ gradually change color from light blue-purple to deep rose-red throughout flowering. The mechanism of the phenomenon remains unclear. Results In this work, flavonoids in the petals of N. ‘Feitian 2’ at six flowering stages were examined to identify the influence of flavonoid components on flower color changes. Additionally, six cDNA libraries of N. ‘Feitian 2’ over two blooming stages were developed, and the transcriptome was sequenced to identify the molecular mechanism governing petal color changes. As a result, 18 flavonoid metabolites were identified, including five anthocyanins and 13 flavonols. Anthocyanin accumulation during flower development is the primary driver of petal color change. A total of 12 differentially expressed genes (DEGs) in the flavonoid biosynthesis pathway were uncovered, and these DEGs were significantly positively correlated with anthocyanin accumulation. Six structural genes were ultimately focused on, as their expression levels varied significantly across different flowering stages. Moreover, 104 differentially expressed transcription factors (TFs) were uncovered, and three MYBs associated with flavonoid biosynthesis were screened. The RT-qPCR results were generally aligned with high-throughput sequencing results. Conclusions This research offers a foundation to clarify the mechanisms underlying changes in the petal color of waterlilies.

A taxonomic revision and redescription of the genus Eurymesosa Breuning, 1938 are presented, including a key to species. Three of the five currently accepted species are considered valid: Eurymesosa ventralis (Pascoe, 1865), Eurymesosa allapsa (Pascoe, 1866) and Eurymesosa ziranzhiyi Yamasako & Lin, 2016. Three junior synonyms are proposed for E. ventralis: Eurymesosa albostictica Breuning, 1962, syn. nov., Eurymesosa affinis Breuning, 1970, syn. nov., and Eurymesosa multinigromaculata Breuning, 1974, syn. nov. Additionally, E. allapsa (Pascoe, 1866) is resurrected from synonyms of E. ventralis. Females of E. allapsa and E. ziranzhiyi Yamasako & Lin, 2016 are described for the first time.

In the field of engineering management, teaching emphasizes the cultivation of applied talents within the context of new engineering disciplines. Evaluating the effectiveness of this cultivation is particularly necessary. The evaluation system for teaching effectiveness plays a crucial role in enhancing teaching quality, promoting students’ comprehensive development, and driving educational reforms. In recent years, there have been numerous research achievements on the evaluation system for practice-oriented teaching quality. However, compared with other disciplines, the field of engineering management remains in its infancy. Therefore, this study clarified the ability goals that talents in this major should possess by studying the evaluation indicators of teaching effectiveness in the field. Based on an emphasis on cultivating different abilities, a practical teaching effectiveness evaluation system was constructed. This study used the Delphi method and the analytic hierarchy process (AHP) to construct a teaching evaluation indicator system for engineering management majors. The system assigns weights to each indicator based on the “Four Abilities”, including professional competence, practical skills, innovation abilities, and employability. This results in the establishment of a relatively scientific and reasonable teaching effectiveness evaluation system. Furthermore, based on the research results, teaching reform studies related to ability cultivation in the “Building Structures” course were carried out. The teaching effectiveness was verified through post-class student feedback, and a student assessment method was established. This study contributes to a better understanding of the path of practical teaching reform and provides a reference value for teaching practice research in related majors.

Summary: Mosaic analysis with double markers (MADM) mouse models closely mimic the clonal origin of human cancers by generating sporadic, GFP-labeled cancer-initiating cells. Traditional clonal analysis pipelines are labor intensive, hindering throughput and disrupting the 3D architecture. Here, we present a protocol that integrates tissue clearing and light-sheet imaging to analyze pre-malignant clones in whole-mount MADM-labeled tissues. We describe steps for generating mosaic-labeled cancer mouse models, tissue harvesting, fixation, and clearing. We then detail procedures for light-sheet imaging and clonal size analysis.For complete details on the use and execution of this protocol, please refer to Zeng et al.1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract 4‐Coumarate‐CoA ligase (4CL) gene plays vital roles in plant growth and development, especially the regulation of lignin metabolism and flavonoid synthesis. To investigate the potential function of 4CL in the lignin biosynthesis of Ginkgo biloba, this study identified two 4CL genes, Gb4CL1 and Gb4CL2, from G. biloba genome. Based on the phylogenetic tree analysis, Gb4CL1 and Gb4CL2 protein were classified into Class I, which has been confirmed to be involved in lignin biosynthesis. Therefore, it can be inferred that these two genes may also participate in lignin metabolism. The tissue‐specific expression patterns of these two genes revealed that Gb4CL1 was highly expressed in microstrobilus, whereas Gb4CL2 was abundant in immature leaves. The onion transient expression assay indicated that Gb4CL1 was predominantly localized in the nucleus, indicating its potential involvement in nuclear functions, while Gb4CL2 was observed in the cell wall, suggesting its role in cell wall‐related processes. Phytohormone response analysis revealed that the expression of both genes was upregulated in response to indole acetic acid, while methyl jasmonate suppressed it, gibberellin exhibited opposite effects on these genes. Furthermore, Gb4CL1 and Gb4CL2 expressed in all tissues containing lignin that showed a positive correlation with lignin content. Thus, these findings suggest that Gb4CL1 and Gb4CL2 are likely involved in lignin biosynthesis. Gb4CL1 and Gb4CL2 target proteins were successfully induced in Escherichia coli BL21 with molecular weights of 85.5 and 89.2 kDa, proving the integrity of target proteins. Our findings provided a basis for revealing that Gb4CL participated in lignin synthesis in G. biloba.

Recent advances in the microbial degradation of persistent organic pollutants have the potential to mitigate the damage caused by anthropogenic activities that are harmfully impacting agriculture soil ecosystems and human health. In this paper, we summarize the pollution characteristics of neonicotinoid insecticides (NNIs) in agricultural fields in China and other countries and then discuss the existing research on screening for NNI-degrading functional bacterial strains, their degradation processes, the construction of microbial consortia, and strategies for their application. We explore the current needs and solutions for improving the microbial remediation rate of NNI-contaminated soil and how these solutions are being developed and applied. We highlight several scientific and technological advances in soil microbiome engineering, including the construction of microbial consortia with a broad spectrum of NNI degradation and microbial immobilization to improve competition with indigenous microorganisms through the provision of a microenvironment and niche suitable for NNI-degrading bacteria. This paper highlights the need for an interdisciplinary approach to improving the degradation capacity and in situ survival of NNI-degrading strains/microbial consortia to facilitate the remediation of NNI-contaminated soil using strains with a broad spectrum and high efficiency in NNI degradation.

Prescription data is an important focus and breakthrough in the study of clinical treatment rules, and the complex multidimensional relationships between Traditional Chinese medicine (TCM) prescription data increase the difficulty of extracting knowledge from clinical data. This paper proposes a complex prescription recognition algorithm (MTCMC) based on the classification and matching of TCM prescriptions with classical prescriptions to identify the classical prescriptions contained in the prescriptions and provide a reference for mining TCM knowledge. The MTCMC algorithm first calculates the importance level of each drug in the complex prescriptions and determines the core prescription combinations of patients through the Analytic Hierarchy Process (AHP) combined with drug dosage. Secondly, a drug attribute tagging strategy was used to quantify the functional features of each drug in the core prescriptions; finally, a Bidirectional Long Short-Term Memory Network (BiLSTM) was used to extract the relational features of the core prescriptions, and a vector representation similarity matrix was constructed in combination with the Siamese network framework to calculate the similarity between the core prescriptions and the classical prescriptions. The experimental results show that the accuracy and F1 score of the prescription matching dataset constructed based on this paper reach 94.45% and 94.34% respectively, which is a significant improvement compared with the models of existing methods.

Objective: This study aimed to conduct the first meta-analysis to comprehensively evaluate the clinical effectiveness and safety of Xiaochaihu Decoction in treating Cancer-related Fever (CRF).Methods: Eight databases were systematically searched in September 2023. The risk of bias (ROB) 2.0 tool recommended by Cochrane Handbook was applied to evaluate the ROB of the included randomized controlled trials (RCTs). Additionally, the quality of evidence was assessed using the Grading of recommendations assessment, development and evaluation (GRADE) tool.Results: We included 18 RCTs involving 1,424 patients. Compared to Western medicine or Xinhuang Tablets, Xiaochaihu Decoction significantly improved clinical effectiveness in CRF patients (risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.17, 1.32) and expedited the normalization of body temperature (mean difference [MD] = −5.29, 95%CI: −5.59, −4.99). It also demonstrated a reduction in tumor necrosis factor-α (TNF-α) levels (MD = −0.63, 95%CI: −0.84, −0.41) and an increase in IL-2 levels (MD = 1.42, 95%CI: −1.09, 1.74). Analysis of Karnofsky Performance Status (KPS) scores showed that the use of Xiaochaihu Decoction improved the quality of life in CRF patients (RR = 1.57, 95%CI: 1.11, 2.22) and reduced the incidence of adverse events. However, it is important to note that the majority of included studies showed “some concerns” in risk of bias based on ROB 2.0, and the evidence quality assessed by GRADE method was rated as “low”.Conclusion: While this study suggests the clinical effectiveness and safety of Xiaochaihu Decoction in treating patients with CRF, confirming these findings will necessitate additional high-quality, large-scale RCTs in future research.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023484068.

Abstract Background Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development. Methods Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH. Results Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice. Conclusions Augmented PLK1 is essential for the development of PH and is a druggable target for PH.

Intelligence data, as a high-value data asset, is stored on different platforms and held by different subjects, and has the characteristics of high dispersion and low availability.Due to the different structural forms and storage methods, it is non-trivial to achieve efficient aggregation and sharing of multi-source heterogeneous intelligence data, and there are great difficulties in the fusion and comprehensive analysis and utilization of intelligence information among multiple subjects.Therefore, there is an urgent need to establish a secure and trustworthy sharing and interoperability mechanism among cross-domain intelligence subjects to meet management requirements such as data validation and security auditing, while realizing correlation analysis and cross-validation of intelligence information and deeply mining the intelligence value therein.To address the needs and application characteristics of cross-domain intelligence data trustworthy sharing, this paper proposes a data object-based intelligence management method and adopts the digital object architecture and blockchain trusted access control technology to build a cross-domain intelligence data trustworthy sharing system, realizing the view unification and cross-domain trustworthy sharing of multisource heterogeneous intelligence data, providing technical support for intelligence data fusion and convergence and intelligence information intelligent analysis, and fully exploiting the huge potential of intelligence information.This will provide technical support for intelligence data convergence and intelligent analysis, and fully exploit the huge potential of intelligence information.

A dose-effect relationship analysis of traditional Chinese Medicine (TCM) is crucial to the modernization of TCM. However, due to the complex and nonlinear nature of TCM data, such as multicollinearity, it can be challenging to conduct a dose-effect relationship analysis. Partial least squares can be applied to multicollinearity data, but its internally extracted principal components cannot adequately express the nonlinear characteristics of TCM data. To address this issue, this paper proposes an analytical model based on a deep Boltzmann machine (DBM) and partial least squares. The model uses the DBM to extract nonlinear features from the feature space, replaces the components in partial least squares, and performs a multiple linear regression. Ultimately, this model is suitable for analyzing the dose-effect relationship of TCM. The model was evaluated using experimental data from Ma Xing Shi Gan Decoction and datasets from the UCI Machine Learning Repository. The experimental results demonstrate that the prediction accuracy of the model based on the DBM and partial least squares method is on average 10% higher than that of existing methods.

The utilization of dredged sediment (DS) as a transformative material in building applications presents an ideal consumption strategy. This study endeavors to create a novel ceramsite lightweight aggregate (LWA) through the co-sintering of DS and rice husks (RHs), further integrating this LWA into the construction of pervious concrete. Results revealed that the optimum production procedure for the DS-based LWA incorporated a 21% RH addition, a sintering temperature of 1100 °C, and a sintering duration of 21 min. Notably, the optimal ceramsite LWA, denoted as SDC-H, exhibited a cylinder compressive strength of 28.02 MPa and an adsorption efficiency for Pb2+ of 94.33%. Comprehensive analysis (encompassing bulk density, cylinder compressive strength, water absorption, and the leaching concentrations of heavy metals) confirmed that SDC-H impacted the specification threshold of high-strength light aggregate derived from solid waste (T/CSTM 00548-2022). Substituting 50% of SDC-H led to a diminution in the mechanical properties but an improvement in the dynamic adsorption capacity of the innovative pervious concrete, registering a mechanical strength of 26.25 MPa and a cumulative adsorption capacity for Pb2+ of 285 mg/g. These performances of pervious concrete containing 50% SDC-H might correlate with the evolution of an interconnected and open-pore structure.

Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS.

Long-chain polyunsaturated omega-3 fatty acids (n-3 PUFAs), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are recommended as beneficial dietary supplements for enhancing cognitive function. Although fish oil (FO) is renowned for its abundant n-3 PUFA content, combining FO with other natural products is considered as a viable option to support the sustainable development of FO products. This review aims to provide comprehensive insights into the advanced effects of combining FO or its components of DHA and EPA with natural products on protecting cognitive function. In two double-blind random control trials, no advanced effects were observed for adding curcumin to FO on cerebral function protection. However, 16 week’s treatment of FO combined with vitamin E did not yield any advanced effects in cognitive factor scores. Several preclinical studies have demonstrated that combinations of FO with natural products can exhibit advanced effects in addressing pathological components in cognitive impairment, including neuroinflammation, oxidative stress, and neuronal survival. In conclusion, evidence from clinical trials for beneficial use of FO and natural ingredients combination is lacking. Greater cohesion is needed between preclinical and clinical data to substantiate the efficacy of FO and natural product combinations in preventing or slowing the progression of cognitive decline.

Background: Mitochondria are dynamic organelles, and mitochondrial dynamics are important for the maintenance of mitochondrial inheritance and function. Recently, an increasing number of studies have shown that mitochondrial dynamics play an important role in the occurrence and development of hepatocellular carcinoma (HCC). However, bibliometric analyses of mitochondrial dynamics in HCC are scarce. Therefore, we conducted a bibliometric analysis to explore the current global research status and trends in mitochondrial dynamics and HCC. Methods: Global publications on mitochondrial dynamics and HCC published between 2007 and May 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using Bibliometrix, VOSviewer, and CiteSpace to analyze the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results: A total of 518 publications were retrieved fromthe WoSCC database. China and The Fourth Military Medical University were the most productive countries and institutions. Zorzano, A published the most literature whereas Chen, HC was the author with the highest number of co-citations. Plos One was the most popular journal, whereas the Journal of Biological Chemistry had the highest number of co-citations. The most frequently used keyword was “mitochondria”. Further analysis of the references and keywords showed that the molecular mechanisms linking them to drug therapy targets should be the focus of future studies. Conclusions: Research on mitochondrial dynamics in HCC has received much attention, and many studies have been published. However, research on mitochondrial dynamics and HCC has been limited by insufficient regional development imbalances and global cooperation. Nevertheless, future research on mitochondrial dynamics and HCC is promising, especially regarding the molecular mechanisms of mitochondrial fission and fusion and how to link the currently known molecular mechanisms with drug therapy targets for HCC.

Objective: The present study aimed to characterize the genotype distribution and clinical characteristics of HCV monoinfected and HCV/HIV coinfected patients in the Liangshan Prefecture, Sichuan Province, China. Methods: All the patients were divided into HCV monoinfection and HCV/HIV coinfection groups according to whether they were complicated with HIV infection. The data from the two groups were collected. Results: In this study, HCV genotype 3 was the most common genotype in both groups, while HCV genotype 6 was significantly higher in the coinfection group than in the monoinfection group ( p = 0.046). The white blood cell count, total bilirubin level, and HCV RNA were significantly higher in the HCV monoinfection group than that in the HCV/HIV coinfection group ( p = 0.031; p

Abstract Background PRPP synthase (PRPS) transfers the pyrophosphate groups from ATP to ribose-5-phosphate to produce 5-phosphate ribose-1-pyrophosphate (PRPP), a key intermediate in the biosynthesis of several metabolites including nucleotides, dinucleotides and some amino acids. There are three PRPS isoforms encoded in human genome. While human PRPS1 (hPRPS1) and human PRPS2 (hPRPS2) are expressed in most tissues, human PRPS3 (hPRPS3) is exclusively expressed in testis. Although hPRPS1 and hPRPS2 share 95% sequence identity, hPRPS2 has been shown to be less sensitive to allosteric inhibition and specifically upregulated in certain cancers in the translational level. Recent studies demonstrate that PRPS can form a subcellular compartment termed the cytoophidium in multiple organisms across prokaryotes and eukaryotes. Forming filaments and cytoophidia is considered as a distinctive mechanism involving the polymerization of the protein. Previously we solved the filament structures of Escherichia coli PRPS (ecPRPS) using cryo-electron microscopy (cryo-EM) 1. Results Order to investigate the function and molecular mechanism of hPRPS2 polymerization, here we solve the polymer structure of hPRPS2 at 3.08 Å resolution. hPRPS2 hexamers stack into polymers in the conditions with the allosteric/competitive inhibitor ADP. The binding modes of ADP at the canonical allosteric site and at the catalytic active site are clearly determined. A point mutation disrupting the inter-hexamer interaction prevents hPRPS2 polymerization and results in significantly reduced catalytic activity. Conclusion Findings suggest that the regulation of hPRPS2 polymer is distinct from ecPRPS polymer and provide new insights to the regulation of hPRPS2 with structural basis.

The working temperature of boron-based catalysts reduces their thermodynamic advantages in the oxidative dehydrogenation of propane (ODHP). Here the authors demonstrate encapsulated Ni nanoparticles as effective subsurface promoters to enhance the low temperature activity and selectivity of the boron oxide overlayer in ODHP.

Objective: The objective of this study was to investigate the mechanism by which total ginseng extract (TGE) inhibits the progression of lung cancer through network pharmacology and experimentation. Materials and Methods: A Lewis lung carcinomas (LLC) model was established by injecting cancer cells through the tail vein and through administering different doses of TGE. The infiltrated immune cells into the microenvironment of lung cancer metastasis through flow cytometry were evaluated, and the messenger RNA (mRNA) expression levels of various immune cell-related chemokines were determined using quantitative reverse transcription–polymerase chain reaction. Therapeutic targets and signaling pathways of TGE in nonsmall cell lung cancer were investigated using systematic pharmacology and virtual docking. Immunoblotting was performed to determine the impacts of TGE on migration-related proteins. Results: Flow cytometry showed that 1.82 g/kg TGE increased the infiltrated T cells and inhibited the recruitment of myeloid cells, which was caused by decreased mRNA expression of chemokines after TGE treatment. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the delayed progression of lung cancer by TGE might be related to the promotion of lung cancer cell apoptosis-associated signaling pathways. The virtual docking results indicated that the active components of ginseng are directly bound to apoptosis-related proteins. Immunoblotting showed that TGE inhibited tumor metastasis by regulating the expression of migration-related proteins. Conclusions: The study reveals the potential mechanism of ginseng extract in the treatment of lung cancer progression and provides a reliable basis for its clinical application.

Optical switch is one of the key components in the time-division multiplexing fiber-optic seismometer array and has significant influence on the crosstalk of the array.The source of crosstalk in the array was analyzed based on differential delay heterodyne demodulation scheme.The expression of crosstalk appearing in the seismometer’s output was deduced with the limited extinction ratio.Via simulation, the relationship between the extinction ratio of optical switch and the seismometer’s crosstalk was presented under different array scales, i.e.basically the crosstalk decreases linearly with the increase of optical switch’s extinction ratio, and increases linearly with the increase of the array scale.Finally, an 8-element fiber-optic seismometer array was set up in the experiment, on which different optical switches (acousto-optic modulator and electro-optic modulator) owning distinct extinction ratios could be applied to generate pulse light.Experimental results verified the theoretical analysis as well as the simulation results.

Dendrobium mixture (DM) is a patented Chinese herbal medicine which has been shown to ameliorate type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. We aimed to investigate the underlying mechanism of DM as a therapeutic agent in attenuating liver steatosis in relation to type 2 diabetes mellitus (T2DM).DM (16.2 g/kg/d) was administered to db/db mice for 4 weeks. The db/m mice and db/db mice in the control and model groups were given normal saline. Additionally, DM (11.25 g/kg/d) was administered to Sprague-Dawley (SD) rats, and the serum was collected and used in an experiment involving palmitic acid (PA)-induced human liver HepG2 cells with abnormal lipid and glucose metabolism.In db/db mice, the administration of DM significantly alleviated liver steatosis, including histological damage and cell apoptosis. DM was found to prevent the upregulation of the RAGE and AKT1 proteins in liver tissues. The underlying mechanism of DM was further studied in PA-induced HepG2 cells. Post-DM administration serum from SD rats reduced lipid accumulation and regulated glucose metabolism in HepG2 cells. Consequently, it inhibited RAGE/AKT signaling and restored autophagy activity. The upregulated autophagy was associated with the mTOR-AMPK signaling pathway. Furthermore, post-DM administration serum reduced apoptosis of hepatocytes in PA-induced HepG2 cells. Our study supports the potential use of DM as a therapeutic agent for the treatment of NAFLD in T2DM. The mechanism underlying this therapeutic potential is associated with the downregulation of the AGE/RAGE/Akt signaling pathway.

As single-mode-fiber transmission systems are reaching their capacity limits, spatial-division multiplexing (SDM) techniques have been investigated to increase the per-fiber capacity. However, the compatibility with current single-mode transponders severely hinders the near-term deployment of SDM systems. In this paper, we experimentally propose two real-time SDM transmission schemes using commercial single-mode 400 G dual-polarized 16 quadrature amplitude modulation equipment. In the first experiment, 60 km weakly coupled single-mode 7-core fiber with a pair of fan-in and fan-out devices are adopted. In the second experiment, the fiber link consists of 60 km/150 km weakly coupled few-mode fiber (FMF) and low-modal-crosstalk mode multiplexers, in which only non-degenerate LP01 and LP02 modes are utilized. In order to investigate the effect of splice on SDM fiber links, 20-roll, 3 km multicore fibers (MCFs) and FMFs are spliced and tested in the experiments. The bit error rates of all SDM experiments are all below 4.75 × 10−2 forward-error-correction threshold of the 400 G transponders. The experimental results prove that the near-term deployment of SDM systems could be accelerated by utilizing weakly coupled MCFs or non-degenerate modes of weakly coupled FMFs which are compatible with commercial single-mode transponders without any software or hardware modifications.

Weakly coupled mode-division multiplexing (MDM) techniques supporting intensity modulation and direct detection (IM/DD) transmission are promising methods of enhancing the capacity of short-reach scenarios in which low-modal-crosstalk-mode demultiplexers for degenerate linear polarized (LP) modes are highly desired. In this paper, we review two degenerate-mode reception schemes. Firstly, a low-modal-crosstalk orthogonal combined reception method for degenerate modes is proposed based on all-fiber mode-selective couplers, in which signals in both degenerate modes are demultiplexed into the LP01 mode of single-mode fibers and then are multiplexed into the mutually orthogonal LP01 and LP11 modes of a two-mode fiber (TMF) for simultaneous detection. Secondly, a novel degenerate-mode-selective coupler consisting of an input few-mode fiber and an output TMF is proposed, which could demultiplex degenerate LP modes without any digital signal processing (DSP). Both demultiplexers are achieved based on the taper and polish process. The fabricated devices are characterized and compared. The results show that the proposed schemes can pave the way to the practical implementation of DSP-free IM/DD LP-mode MDM transmission systems.

Abstract With the advent of the 5G era, people's demand for information and bandwidth is increasing. The signal source will mainly be high‐frequency radio waves with high bandwidth. However, the coverage of high‐frequency radio waves is very limited, which leads to the emergence of micro base stations. Opportunistic social networks are just suitable for this new transmission method, it is easy for users to simultaneously request content with high popularity in a short time, which will cause a heavy load on the micro base station and a high transmission delay. This paper establishes the community mechanism and proposes a user cache management and cooperative transmission mechanism (CMCT) based on edge community computing by using the predictability of users' requests for popular content. The free user equipment space is used to manage cache distribution through the edge community computing to perform cooperative transmission, thereby reducing the content delivery delay and the load of the micro base station. Simulation experiments show that the CMCT algorithm can reduce end‐to‐end delay and overhead, and improve data transmission efficiency.

IntroductionThe longitudinal responses towards multiple doses of COVID-19 mRNA vaccines in patients with systemic autoimmune diseases remain incompletely understood. While observational studies suggested the safety of COVID-19 mRNA vaccines in rheumatic disease patients, laboratory evidence is lacking.MethodsHere we evaluated seroreactivity, clinical manifestions, and multiple disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases.ResultsMost patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Patients with systemic lupus erythematosus (SLE) or psoriatic arthritis (PsA) remained without significant flares post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I interferon (IFN) signature genes were highly variable but did not show consistent or significant increases. Frequency of double negative 2 (DN2) B cells remained largely stable.DiscussionOur data provide experimental evidences indicating the efficacy and safety of repeated COVID-19 mRNA vaccination in rheumatic disease patients.

The coupling of acetonitrile into succinonitrile via a dehydrogenative route is highly attractive in terms of valuable chemical synthesis and green hydrogen energy production. Here, the authors report succinonitrile synthesis with high selectivity and rate via a light driven dehydrogenative coupling reaction of CH3CN over the anatase TiO2 supported Pt catalyst.

Objective: Granules of herbal extracts are a popular medicinal preparation consumed in traditional Chinese medicine clinical practice. However, their quality and efficacy evaluation are lacking. This study aimed to compare the quality and anti-oxidant activity of Dan Shen (Salvia miltiorrhiza Radix & Rhizoma) granule extracts with their herbal extracts. Methods: Chromatographic method was used to determine the content of 7 marker compounds in the water extracts of the herb compared to that of 12 granule extracts. Agglomerative hierarchical clustering (AHC) and principal component analysis (PCA) distinguished the herbal and granule extracts based on the content of the marker compounds. The antioxidant activities of herbal and granule extracts were evaluated by 2, 2′-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS), organic chemical compound 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. Results: The herbal extracts group showed significantly higher contents of salvianolic acid B, sodium danshensu and cryptotanshinone compared with that of the granule group. This corresponded to significantly higher ABTS, DPPH and FRAP (P

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds—cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis’s bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis’s sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis’s complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis’s full therapeutic potential within the realm of natural plant-based medicine.

For low-cost and high chromatic dispersion (CD) robustness single sideband (SSB) with direct detection (DD), three schemes of SSB with pulse amplitude modulation (PAM) were investigated.Among that, the highest spectral efficiency was achieved by the scheme of adding the frequency down-conversion at the transmitter.However, that scheme reduces the tolerance for laser linewidth.Hence, based on the character of the SSB-PAM signal, a DSP scheme was proposed, including a modified equalization algorithm with phase distortion immunity and blind phase search algorithm.The simulation results show that the modified scheme can tolerate 1 MHz linewidth for 112 Gbit/s SSB-PAM-DD, while the original scheme for SSB-PAM was only 100 kHz at the same bit error rate (BER) threshold.Therefore, the proposed scheme can achieve a high frequency efficiency, high linewidth tolerance, and low-cost SSB-PAM signaling transmission.

Introduction: Puerarin (PUE) is a natural compound isolated from Puerariae Lobatae Radix, which has a neuroprotective effect on IS. We explored the therapeutic effect and underlying mechanism of PUE on cerebral I/R injury by inhibiting oxidative stress related to the PI3K/Akt/Nrf2 pathway in vitro and in vivo.Methods: The middle cerebral artery occlusion and reperfusion (MCAO/R) rats and oxygen-glucose deprivation and reperfusion (OGD/R) were selected as the models, respectively. The therapeutic effect of PUE was observed using triphenyl tetrazolium and hematoxylin-eosin staining. Tunel-NeuN staining and Nissl staining to quantify hippocampal apoptosis. The reactive oxygen species (ROS) level was detected by flow cytometry and immunofluorescence. Biochemical method to detect oxidative stress levels. The protein expression related to PI3K/Akt/Nrf2 pathway was detected by using Western blotting. Finally, co-immunoprecipitation was used to study the molecular interaction between Keap1 and Nrf2.Results:In vivo and vitro studies showed that PUE improved neurological deficits in rats, as well as decreased oxidative stress. Immunofluorescence and flow cytometry indicated that the release of ROS can be inhibited by PUE. In addition, the Western blotting results showed that PUE promoted the phosphorylation of PI3K and Akt, and enabled Nrf2 to enter the nucleus, which further activated the expression of downstream antioxidant enzymes such as HO-1. The combination of PUE with PI3K inhibitor LY294002 reversed these results. Finally, co-immunoprecipitation results showed that PUE promoted Nrf2-Keap1 complex dissociation.Discussion: Taken together, PUE can activate Nrf2 via PI3K/Akt and promote downstream antioxidant enzyme expression, which could further ameliorate oxidative stress, against I/R-induced Neuron injury.

Abstract Zanthoxylum armatum is an important cash crop for medicinal and food purposes in Asia. However, its stems and leaves are covered with a large number of prickles, which cause many problems in the production process. The homeodomain leucine zipper (HD‐ZIP) gene family is a class of transcription factors unique to plants that play an important role in biological processes such as morphogenesis, signal transduction, and secondary metabolite synthesis. However, little is known about HD‐ZIP gene information that may be involved in prickle development of Z. armatum. Here, we identified 76 ZaHDZ genes from the Z. armatum genome and classified them into four subfamilies (I–IV) based on phylogenetic analysis, a classification further supported by gene structure and conserved motif analysis. Seventy‐six ZaHDZ genes were unevenly distributed on chromosomes. Evolutionary analysis revealed that the expansion of ZaHDZ genes mainly were due to whole‐genome duplication (WGD) or segmental duplication, and they experienced strong purifying selection pressure in the process of evolution. A total of 47 cis‐elements were identified in the promoter region of ZaHDZ genes. Quantitative real‐time polymerase chain reaction analysis was performed on subfamily IV ZaHDZ gene expression levels in five tissues and under four hormone treatments. Finally, ZaHDZ16 was predicted to be the candidate gene most likely to be involved in prickle development of Z. armatum. These results contribute to a better understanding of the characteristics of HD‐ZIP gene family and lay a foundation for further study on the function of genes related to prickle development of Z. armatum.

Abstract Background Largely due to incidental detection, asymptomatic pancreatic cystic lesions (PCLs) have become prevalent in recent years. Among them, intraductal papillary mucinous neoplasm (IPMN) infrequently advances to pancreatic ductal adenocarcinoma (PDAC). Conservative surveillance versus surgical intervention is a difficult clinical decision for both caregivers and PCL patients. Because RNF43 loss‐of‐function mutations and KRAS gain‐of‐function mutations concur in a subset of IPMN and PDAC, their biological significance and therapeutic potential should be elucidated. Methods Pancreatic Rnf43 knockout and Kras activated mice (Rnf43−/−; KrasG12D) were generated to evaluate their clinical significance in pancreatic pre‐neoplastic initiation and malignant transformation. Results Loss of Rnf43 potentiated the occurrence and severity of IPMN and PDAC in oncogenic Kras mice. The Wnt/β‐catenin signaling pathway was activated in pancreatic KrasG12D and Rnf43 knockout mice and the PORCN inhibitor LGK974 blocked pancreatic IPMN initiation and progression to PDAC accordingly. Conclusions Rnf43 is a tumor suppressor in the prevention of pancreatic malignant transformation. This genetically reconstituted autochthonous pancreatic Rnf43−/−; KrasG12D preclinical cancer model recapitulates the pathological process from pancreatic cyst to cancer in humans and can be treated with inhibitors of Wnt/β‐catenin signaling. Since the presence of RNF43 and KRAS mutations in IPMNs predicts future development of advanced neoplasia from PCLs, patients with these genetic anomalies warrant surveillance, surgery, and/or targeted therapeutics such as Wnt/β‐catenin inhibitors.

Five genera from China of the leafhopper tribe Typhlocybini are treated. Linnavuoriana Dlabola, 1958 and Shamala Dworakowska, 1980 and seven known species, Edwardsiana corylicola Vilbaste, 1968, E. praedestina Dlabola, 1967, E. singularis Anufriev, 1975, Hiratettix distanti Dworakowska, 1982, H. malaisei Dworakowska, 1982, L. antiqua Dworakowska, 1982, and L. malicola Zachvatkin, 1949 are newly recorded from China. Two new species, Shamala annulata and Paracyba biprocessa spp. nov., are described and illustrated. Keys to Chinese species of each genus are also provided.

The inter-data center links are meeting the challenge of increasing transmission capacity continuously. Here, the tradeoff between transmission capacity and cost and power consumption especially needs to be considered. The field modulation polarization-division-multiplexed (PDM) four-level pulse amplitude modulation (PAM4) with coherent detection is a potential candidate for 400 Gb/s and beyond inter-data center transmissions, which has several advantages including low-cost, low optical signal to noise ratio (OSNR) requirement and high receiver sensitivity. In this paper, the feasibility and effectiveness of the field PDM-PAM4 coherent system are investigated over multi core fiber (MCF). In order to adapt to the field PAM signals, the signal-phase aid least-mean square (SP-LMS) and training multi-modulus algorithm (TMMA) are modified and analyzed for equalization and polarization demultiplexing. Finally, it is demonstrated that 4×112 Gb/s field PDM-PAM4 is successful transmitted over 16 km MCF and 384 km SSMF in C-band with a BER below 3.8e-3.

Fiber-optic seismic sensor has become an emerging effective tool for microseismic monitoring, which is of importance for oil and gas production improvement. When processing the fiber-optic data, the recognition of microseismic events is the first crucial step, which is rarely reported due to the lack of such data. In this paper, based on the features of central data distribution, skewness, kurtosis, energy entropy, etc., the classification accuracy of microseismic (MS) events obtained by fiber-optic MS monitoring system and electronic one is compared using machine learning algorithm (e. g. SVM and KNN) for the first time. The results show that fiber-optic data has higher classification accuracy than electronic data when using the feature of central data distribution owing to the high signal-to-noise ratio of fiber-optic data. However, when choosing the features of energy entropy, zero-crossing rate and the energy proportion of specific frequency band, electronic data has higher classification accuracy than fiber-optic data benefiting from the longer events duration and the lower frequency components of electronic data. When using skewness and kurtosis, the classification performance in fiber-optic data is almost consistent with the electronic one. Moreover, the results indicate that the characteristics of MS signal itself have a greater impact on the discrimination ability of MS events than the applied machine learning classification algorithm.

Introduction: Neuroinflammation is an important pathological event contributing to the onset and progression of neurodegenerative diseases. The hyperactivation of microglia triggers the release of excessive proinflammatory mediators that lead to the leaky blood-brain barrier and impaired neuronal survival. Andrographolide (AN), baicalein (BA) and 6-shogaol (6-SG) possess anti-neuroinflammatory properties through diverse mechanisms of action. The present study aims to investigate the effects of the pair-combinations of these bioactive compounds in attenuating neuroinflammation.Methods: A tri-culture model with microglial N11 cells, microvascular endothelial MVEC(B3) cells, and neuroblastoma N2A cells was established in a transwell system. AN, BA and 6-SG used alone (25 µM) or in pair-wised combinations (12.5 + 12.5 µM) were subjected to the tri-culture system. Upon the stimulation of lipopolysaccharides (LPS) at 1 μg/mL, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) levels were determined by ELISA assays. Immunofluorescence staining was applied to investigate the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) on N11 cells, expressions of protein zonula occludens-1 (ZO-1) on MVEC cells and phosphorylated tau (p-tau) on N2A cells, respectively. The endothelial barrier permeability of MVEC cells was assessed by the Evans blue dye, and the resistance from the endothelial barrier was measured by transepithelial/endothelial electrical resistance (TEER) value. Neuronal survival of N2A cells was determined by Alamar blue and MTT assays.Results: Combinations of AN-SG and BA-SG synergistically lowered the TNF and IL-6 levels in LPS-induced N11 cells. Remarkably, the combined anti-neuroinflammatory effects of AN-SG and BA-SG remained significantly greater compared to their individual components at the same concentration level. The molecular mechanism of the attenuated neuroinflammation was likely to be mediated by downregulation of NF-κB p65 translocation (p < 0.0001 vs. LPS stimulation) in N11 cells. In the MVEC cells, both AN-SG and BA-SG restored TEER values, ZO-1 expression and reduced permeability. Furthermore, AN-SG and BA-SG significantly improved neuronal survival and reduced expressions of p-tau on N2A cells.Discussion: The AN-SG and BA-SG combinations showed greater anti-neuroinflammatory potential than those used alone in mono- and tri-cultured N11 cells, thereby further protecting endothelial tight junction and neuronal survival. Taken together, AN-SG and BA-SG may provide improved anti-neuroinflammatory and neuroprotective activities.

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might contribute to the development of AD, including amyloid peptide and tau deposition, but more recent evidence suggests that neuroinflammation may also play an—at least partial—role in its pathogenesis. In recent years, emerging research has explored the possible involvement of external, invading pathogens in starting or accelerating the neuroinflammatory processes in AD. In this narrative review, we advance the hypothesis that neuroinflammation in AD might be partially caused by viral, bacterial, and fungal pathogens entering the brain through the nose and the olfactory system. The olfactory system represents a plausible route for pathogen entry, given its direct anatomical connection to the brain and its involvement in the early stages of AD. We discuss the potential mechanisms through which pathogens may exploit the olfactory pathway to initiate neuroinflammation, one of them being accidental exposure of the olfactory mucosa to hands contaminated with soil and feces when picking one’s nose.

Tribes of the leafhopper subfamily Typhlocybinae have traditionally been defined based on differences in forewing and hindwing venation. Except for Typhlocybini (sensu lato), the classification of tribes is relatively stable. The monophyly of Typhlocybini needs to be examined, and the relationships among genera within Typhlocybini have not been resolved. Few mitogenome sequences representative of major lineages of Typhlocybini have been available to facilitate a comprehensive phylogenetic analysis of the tribe. In this study, the complete mitogenomes of 19 species of Typhlocybini were sequenced. The gene arrangements of the 19 new mitogenomes are consistent with ancestral insect mitogenomes. Phylogenetic analyses by both maximum-likelihood and Bayesian methods of 67 species of Typhlocybinae suggest that Zyginellini is paraphyletic with respect to Typhlocybini. The phylogenetic relationships within Typhlocybini are discussed, and the major results show that the Farynala and Linnavuoriana complexes previously recognized based on morphological characters correspond to monophyletic lineages.

Fusarium wilt, mainly caused by Fusarium oxysporum, affects ginger yield and quality worldwide. To explore a safe and sustainable method of preventing and controlling Fusarium wilt, the inhibitory effects of eugenol on F. oxysporum FOX-1 were analysed in this study. The results showed that eugenol inhibited the reproductive and vegetative growth of F. oxysporum FOX-1 in vitro. Microscopic observations revealed that eugenol disrupted the hyphal morphology of F. oxysporum. In addition, eugenol destroyed the cell membrane integrity of the pathogenic fungi, resulting in the leakage of F. oxysporum FOX-1 intercellular contents, including electrolytes, soluble proteins, nucleic acids, and malonydialdehyde. Results of an in vivo inoculation test showed that eugenol exerted a strong inhibitory effect on Fusarium wilt in ginger seedlings. In summary, eugenol had an inhibitory effect on the growth of F. oxysporum FOX-1 and controlled Fusarium wilt in ginger seedlings. These findings provide a foundation for future development of botanical antifungal agents to manage Fusarium wilt.

Vaccination is considered the most effective way to reduce the impact of coronavirus disease 2019 (COVID-19). Several new vaccines have been manufactured. This study aimed to assess the current status and prospects of COVID-19 vaccine research using a bibliometric analysis. We analyzed 3,954 scientific articles on COVID-19 vaccines in the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer were used for bibliometric visualization. Original articles and reviews were used for the analysis. A total of 2,783 (70.38%) studies were published in 2021. The USA contributed the highest, publishing 1,390 articles with 41,788 citations, followed by China and the UK. The USA’s primary collaborators were the UK (n = 133), China (n = 87), and Canada (n = 65). The most active institutions were the University of Oxford and Harvard Medical School, while Emory University was the most influential. The Vaccines journal had the most number of publications (402). The most cited journal was the New England Journal of Medicine. In 2021, the focus was on RNA vaccines, attitudes toward vaccination, and hesitancy. In contrast, studies in 2022 focused on vaccine double-blind trials, viral mutations, and antibodies. In the context of rapid virus transmission, vaccine studies on immunogenicity, spike proteins, efficacy, safety, and antibody response have been prioritized. Additional phased clinical trials are needed to determine the effectiveness, acceptance, and side effects of vaccines against mutated strains of the virus.