Functional Mechanisms Research Articles

Effects of inactivated Streptococcus iniae, Edwardsiella tarda, and Poly I:C on mRNA Expression Levels of CXCL-10 and CXCL-9 Genes in Japanese Flounder

The present study accomplished the successful cloning and sequencing of the JfCXCL9_L and JfCXCL10_L genes found in the spleen cDNA of the Japanese flounder (Paralichthys olivaceus). The tissue distribution of these two genes was determined before any stimuli administration at the zero-hour mark. The qRT-PCR analysis demonstrated that the expression of JfCXCL10_L closely mirrored that of IL1-β, displaying an upregulation following the application of Poly I:C (Viral mimic) and formalin-killed Edwardsiella tarda (Gram-Negative mimic), while showing a downregulation after the application of formalin-killed Streptococcus iniae (Gram-Positive mimic) treatment. These findings strongly suggest a role for JfCXCL10_L in the immune response to viral and gram-negative bacterial stimuli. Regarding JfCXCL9_L, mRNA levels were found to be significantly downregulated after FKCET and FKCSI treatments, though to varying extents. Interestingly, at specific time points, JfCXCL9_L levels were even lower compared to Poly I:C treatment. These intriguing findings shed valuable light on the roles of both JfCXCL9_L and JfCXCL10_L in potential functions of immune response mechanisms of the Japanese flounder'.

Comprehensive molecular analyses and experimental validation of CDCAs with potential implications in kidney renal papillary cell carcinoma prognosis

Previous reports have revealed that the abnormal expression of the cell division cycle-associated gene family (CDCAs) is closely associated with some human cancers. However, the precise functional roles and mechanisms of CDCAs in kidney renal papillary cell carcinoma (KIRP) remain unclear. In this study, RNA sequencing data from the Cancer Genome Atlas database and Genotype-Tissue Expression databases were utilized to perform the expression, correlation, survival, mutation, functional enrichment analysis, and immunoinfiltration analyses of CDCAs in KIRP. We found that the expression levels of CDCA genes were significantly increased in KIRP across multiple databases, as confirmed by immunohistochemistry and quantitative reverse transcription PCR (RT-qPCR). Moreover, increased expression of CDCA genes is significantly associated with poor prognosis. Univariate and multivariate Cox regression analyses demonstrated that pathologic T and N staging, NUF2, CDCA2, CDCA3, CDCA5, CBX2, CDCA7, and CDCA8 were independent prognostic factors for patients with KIRP. Utilizing these nine variables, we developed a nomogram prognostic model. Furthermore, the results of GO and KEGG functional enrichment analyses suggested that CDCA genes were associated with nuclear division, mitotic nuclear division, and chromosome segregation and were involved in the cell cycle, p53 signaling pathway, and cellular senescence. We found that the expression of NUF2, CDCA2, CDCA5, and CBX2 was closely associated with the expression of lymphocytes, immunostimulatory molecules, immunoinhibitory molecules, and chemokines. In summary, NUF2, CDCA2, CDCA3, CDCA5, CBX2, CDCA7, and CDCA8 are potential biomarkers for KIRP diagnosis and prognosis.

Acclimation mechanism of microalgal photosynthetic apparatus under low atmospheric pressures - new astrobiological perspectives in a Mars-like atmosphere.

This study reveals a new acclimation mechanism of the eukaryotic unicellular green alga Chlorella vulgaris in terms of the effect of varying atmospheric pressures on the structure and function of its photosynthetic apparatus using fluorescence induction measurements (JIP-test). The results indicate that low (400mbar) and extreme low (2 atmosphere (simulating the Mars atmosphere), reveals that the impact of extremely low atmospheric pressure on PQ mobility within the photosynthetic membrane, coupled with the low density of an almost 100% CO2 Mars-like atmosphere, results to a similar photosynthetic efficiency to that on Earth. These findings pave the way for the identification of novel functional acclimation mechanisms of microalgae to extreme environments that are vastly distinct from those found on Earth.

Structure, Function, and Physicochemical Properties of Pore-forming Antimicrobial Peptides.

Antimicrobial peptides (AMPs), a class of antimicrobial agents, possess considerable potential to treat various microbial ailments. The broad range of activity and rare complete bacterial resistance to AMPs make them ideal candidates for commercial development. These peptides with widely varying compositions and sources share recurrent structural and functional features in mechanisms of action. Studying the mechanisms of AMP activity against bacteria may lead to the development of new antimicrobial agents that are more potent. Generally, AMPs are effective against bacteria by forming pores or disrupting membrane barriers. The important structural aspects of cytoplasmic membranes of pathogens and host cells will also be outlined to understand the selective antimicrobial actions. The antimicrobial activities of AMPs are related to multiple physicochemical properties, such as length, sequence, helicity, charge, hydrophobicity, amphipathicity, polar angle, and also self-association. These parameters are interrelated and need to be considered in combination. So, gathering the most relevant available information will help to design and choose the most effective AMPs.

Understanding the dynamics of TKI-induced changes in the tumor immune microenvironment for improved therapeutic effect

BackgroundThe dynamic interplay between tyrosine kinase inhibitors (TKIs) and the tumor immune microenvironment (TME) plays a crucial role in the therapeutic trajectory of non-small cell lung cancer (NSCLC). Understanding the...

Trefoil factor 1 suppresses stemness and enhances chemosensitivity of pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial-mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor-suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer. To investigate the role of endogenous TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1-Cre/LSL-KRASG12D/LSL-p53R172H/TFF1-/-) were analyzed by immunohistochemistry (IHC). To explore the efficacy of extracellular administration of TFF1, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines, a xenograft mouse model and a transgenic mouse model. The deficiency of TFF1 was associated with increased EMT of cancer cells in mouse models of pancreatic cancer, KPC. The expression of TFF1 in cancer cells was associated with better survival rate of the patients who underwent chemotherapy, and loss of TFF1 deteriorated the benefit of gemcitabine in KPC mice. Extracellular administration of TFF1 inhibited gemcitabine-induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells invitro. Invivo, combined treatment of gemcitabine and subcutaneous administration of TFF1 arrested tumor growth in xenograft mouse model and resulted in the better survival of KPC mice by inhibiting EMT and cancer stemness. These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.

Factors affecting the effectiveness of law-enforcement acts

The paper is devoted to the study of factors affecting the effectiveness of law-enforcement acts. The paper analyzes the existing approaches to understanding the factors affecting the effectiveness of law-enforcement acts; the peculiarities of legal and non-legal factors of increasing the effectiveness of law-enforcement acts were investigated; the author's vision of the classification of factors affecting the effectiveness of law-enforcement acts is proposed. To achieve the purpose of the paper, a set of philosophical and worldview, general scientific, special scientific methods and principles of scientific knowledge were used, which provided an objective analysis of factors affecting the effectiveness of law-enforcement acts. It was established that the effectiveness of law-enforcement acts is the result of the general influence of both objective and specifically reproduced factors in their unity, and objective factors can both increase and decrease the effectiveness of purposefully used means. It was concluded that a positive impact on the effectiveness of law-enforcement acts can occur only if both legal and non-legal means are used in their unity and interrelationship. Legal means of ensuring the effectiveness of law-enforcement acts represent a three-unit system, which consists of means of standardizing, guaranteeing and ensuring the legal and technical perfection of law-enforcement acts. Standardization reflects the practice of creating special institutions, mechanisms and procedures that contribute to increasing the effectiveness of law-enforcement acts. Guaranteeing reflects the creation and implementation of means that ensure the practical operation (functionality) of such institutions, mechanisms and procedures. Implementation of techniques, rules, methods and means of legal technique reflects the most justified from the point of view of practical expediency method and technology of law enforcement. Among the non-legal factors affecting the effectiveness of law enforcement acts, spiritual and organizational factors are of particular importance. Along with this, it is also possible to single out social, economic, political and other factors that can positively affect the effectiveness of law-enforcement acts.

Clinical characteristics of post-stroke basal ganglia aphasia and the study of language-related white matter tracts based on diffusion spectrum imaging

BackgroundStroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. MethodsWe first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. ResultsCompared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). ConclusionPSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.

Sex-dependent intra-islet structural rearrangements affecting alpha-to-beta cell interactions lead to adaptive enhancements of Ca2+ dynamics in prediabetic beta cells

Aims/hypothesisPrediabetic pancreatic beta cells can adapt their function to maintain normoglycaemia for a limited period of time, after which diabetes mellitus will manifest upon beta cell exhaustion. Understanding sex-specific beta cell compensatory mechanisms and their failure in prediabetes (impaired glucose tolerance) is crucial for early disease diagnosis and individualised treatment. Our aims were as follows: (1) to determine the key time points of the progression from beta cells’ functional adaptations to their failure in vivo; and (2) to mechanistically explain in vivo sex-specific beta cell compensatory mechanisms and their failure in prediabetes.MethodsIslets from male and female transgenic Ins1CreERT2-GCaMP3 mice were transplanted into the anterior chamber of the eye of 10- to 12-week-old sex-matched C57BL/6J mice. Recipient mice were fed either a control diet (CD) or western diet (WD) for a maximum of 4 months. Metabolic variables were evaluated monthly. Beta cell cytoplasmic free calcium concentration ([Ca2+]i) dynamics were monitored in vivo longitudinally by image fluorescence of the GCaMP3 reporter islets. Global islet beta cell [Ca2+]i dynamics in line with single beta cell [Ca2+]i analysis were used for beta cell coordination studies. The glucagon receptor antagonist L-168,049 (4 mmol/l) was applied topically to the transplanted eyes to evaluate in vivo the effect of glucagon on beta cell [Ca2+]idynamics. Human islets from non-diabetic women and men were cultured for 24 h in either a control medium or high-fat/high-glucose medium in the presence or absence of the glucagon receptor antagonist L-168,049. [Ca2+]i dynamics of human islets were evaluated in vitro after 1 h exposure to Fura-10.ResultsMice fed a WD for 1 month displayed increased beta cell [Ca2+]i dynamics linked to enhanced insulin secretion as a functional compensatory mechanism in prediabetes. Recruitment of inactive beta cells in WD-fed mice explained the improved beta cell function adaptation observed in vivo; this occurred in a sex-specific manner. Mechanistically, this was attributable to an intra-islet structural rearrangement involving alpha cells. These sex-dependent cytoarchitecture reorganisations, observed in both mice and humans, induced enhanced paracrine input from adjacent alpha cells, adjusting the glucose setpoint and amplifying the insulin secretion pathway. When WD feeding was prolonged, female mice maintained the adaptive mechanism due to their intrinsically high proportion of alpha cells. In males, [Ca2+]i dynamics progressively declined subsequent to glucose stimulation while insulin secretion continue to increase, suggesting uncoordinated beta cell function as an early sign of diabetes.Conclusions/interpretationWe identified increased coordination of [Ca2+]i dynamics as a beta cell functional adaptation mechanisms in prediabetes. Importantly, we uncovered the mechanisms by which sex-dependent beta cell [Ca2+]i dynamics coordination is orchestrated by an intra-islet structure reorganisation increasing the paracrine input from alpha cells on beta cell function. Moreover, we identified reduced [Ca2+]i dynamics coordination in response to glucose as an early sign of diabetes preceding beta cell secretory dysfunction, with males being more vulnerable. Alterations in coordination capacity of [Ca2+]i dynamics may thus serve as an early marker for beta cell failure in prediabetes.Graphical

Whole transcriptome analysis revealed the regulatory network and related pathways of non-coding RNA regulating ovarian atrophy in broody hens.

Poultry broodiness can cause ovarian atresia, which has a detrimental impact on egg production. Non-coding RNAs (ncRNAs) have become one of the most talked-about topics in life sciences because of the increasing evidence of their novel biological roles in regulatory systems. However, the molecular mechanisms of ncRNAs functions and processes in chicken ovarian development remain largely unknown. Whole-transcriptome RNA sequencing of the ovaries of broodiness and laying chickens was thus performed to identify the ncRNA regulatory mechanisms associated with ovarian atresia in chickens. Subsequent analysis revealed that the ovaries of laying chickens and those with broodiness had 40 differentially expressed MicroRNA (miRNAs) (15 up-regulated and 25 down-regulated), 379 differentially expressed Long Noncoding RNA (lncRNAs) (213 up-regulated and 166 down-regulated), and 129 differentially expressed circular RNA (circRNAs) (63 up-regulated and 66 down-regulated). The competing endogenous RNAs (ceRNA) network analysis further revealed the involvement of ECM-receptor interaction, AGE-RAGE signaling pathway, focal adhesion, cytokine-cytokine receptor interaction, inflammatory mediator regulation of TRP channels, renin secretion, gap junction, insulin secretion, serotonergic synapse, and IL-17 signaling pathways in broodiness. Upon further analysis, it became evident that THBS1 and MYLK are significant candidate genes implicated in the regulation of broodiness. The expression of these genes is linked to miR-155-x, miR-211-z, miR-1682-z, gga-miR-155, and gga-miR-1682, as well as to the competitive binding of novel_circ_014674 and MSTRG.3306.4. The findings of this study reveal the existence of a regulatory link between non-coding RNAs and their competing mRNAs, which provide a better comprehension of the ncRNA function and processes in chicken ovarian development.

A genealogy of politics: Vindicatory, pragmatic, and realist

AbstractIn Western democracies, people harbor feelings of disgust or hatred for politics. Populists and technocrats even seemingly question the value of politics. Populists cry that they are not politicians and that politics is necessarily corrupt. From the opposite side, technocrats view politics as a pointless constraint on enacting the obviously right policies. Are Western democracies facing a rejection of politics? And is politics worth defending? This paper offers a vindicatory genealogy of politics, vindicating the need human beings have for this practice and clarifying the extent of its contemporary rejections. To achieve these contributions, the paper connects the literatures on pragmatic genealogy and on political realism, revealing how they can complement each other. Following pragmatic genealogy, the practice of politics is vindicated, because it meets an inevitable functional need for collectively binding decision‐making. However, and importantly, political realism allows us to see that the functional mechanisms through which politics fulfills this need vary contextually and thus require careful empirical scrutiny. The paper thus dispels confusion about seeming rejections of politics by clarifying what is unavoidable, and what is revisable about politics.

Recent advances in surface coating and atomic doping strategies for lithium-ion battery cathodes: implementation approaches and functional mechanisms

Recent advances in surface coating and atomic doping strategies for lithium-ion battery cathodes: implementation approaches and functional mechanisms

Knockdown of miR-361-5p promotes the induced activation of SHF-stem cells through FOXM1 mediated Wnt/β-catenin pathway in cashmere goats

The inducing activation event of secondary hair follicle (SHF)-stem cells is considered a key biological process in the SHF regeneration, and the morphogenesis of cashmere fiber in cashmere goats. The miR-361-5p was essentially implicated in the induced activation of SHF-stem cells of cashmere goats, but its functional mechanisms are unclear. Here, we confirmed miR-361-5p was significantly downregulated in anagen SHF bugle of cashmere goats compared with that at telogen, and miR-361-5p expression was significantly lower in SHF-stem cells after activation than its counterpart before activation. Further, we found that miR-361-5p could negatively regulate the induced activation event of SHF-stem cells in cashmere goats. Mechanistically, through dual-luciferase reporter assays, miR-361-5p specifically bound with FOXM1 mRNA in SHF-stem cells of cashmere goats and negatively regulated the expression of FOXM1 gene. Also, through overexpression/knockdown analysis of FOXM1 gene, our results indicated that FOXM1 upregulated the expression of Wnt/β-catenin pathway related genes in SHF-stem cells. Moreover, based on TOP/FOP-flash Wnt report assays, the knockdown of miR-361-5p promotes the Wnt/β-catenin pathway activation through upregulating the FOXM1 expression in SHF-stem cells. Finally, we demonstrated that miR-361-5p negatively regulated the induced activation of SHF-stem cells through FOXM1 mediated Wnt/β-catenin pathway in cashmere goats.

An isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn’s disease with defective antimicrobial activity

Despite major advances in linking single genetic variants to single causal genes, the significance of genetic variation on transcript-level regulation of expression, transcript-specific functions, and relevance to human disease has been poorly investigated. Strawberry notch homolog 2 (SBNO2) is a candidate gene in a susceptibility locus with different variants associated with Crohn’s disease and bone mineral density. The SBNO2 locus is also differentially methylated in Crohn’s disease but the functional mechanisms are unknown. Here we show that the isoforms of SBNO2 are differentially regulated by lipopolysaccharide and IL-10. We identify Crohn’s disease associated isoform quantitative trait loci that negatively regulate the expression of the noncanonical isoform 2 corresponding with the methylation signals at the isoform 2 promoter in IBD and CD. The two isoforms of SBNO2 drive differential gene networks with isoform 2 dominantly impacting antimicrobial activity in macrophages. Our data highlight the role of isoform quantitative trait loci to understand disease susceptibility and resolve underlying mechanisms of disease.

Prognostic significance of EGFR, AREG and EREG amplification and gene expression in muscle invasive bladder cancer.

Muscle invasive bladder cancer (MIBC) remains a prevalent cancer with limited therapeutic options, obviating the need for innovative therapies. The epidermal growth factor receptor (EGFR) is a linchpin in tumor progression and presents a potential therapeutic target in MIBC. Additionally, the EGFR ligands AREG and EREG have shown associations with response to anti-EGFR therapy and improved progression-free survival in colorectal carcinoma. We investigated the prognostic significance of EGFR, AREG, and EREG in MIBC. Gene expression and copy number analyses were performed via qRT-PCR on tissue samples from 100 patients with MIBC who underwent radical cystectomy at the University Hospital Mannheim (MA; median age 72, interquartile range [IQR] 64-78 years, 25% female). Results were validated in 361 patients from the 2017 TCGA MIBC cohort (median age 69, IQR 60-77 years, 27% female), in the Chungbuk and MDACC cohort. Gene expressions were correlated with clinicopathologic parameters using the Mann-Whitney test, Kruskal-Wallis- test and Spearman correlation. For overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) gene expression was analyzed with Kaplan-Meier and Cox-proportional hazard models. Significant gene expression differences in EGFR, AREG, and EREG could be detected in all cohorts. In the TCGA cohort, EGFR expression was significantly elevated in patients with EGFR amplification and KRAS wildtype. High AREG expression independently predicted longer OS (HR = 0.35, CI 0.19 - 0.63, p = 0.0004) and CSS (HR = 0.42, CI 0.18 - 0.95, p = 0.0378) in the MA cohort. In the TCGA cohort, high EGFR, AREG, and EREG expression correlated with shorter OS (AREG: HR = 1.57, CI 1.12 - 2.20, p = 0.0090) and DFS (EGFR: HR = 1.91, CI 1.31 - 2.8, p = 0.0008). EGFR amplification was also associated with reduced DFS. High EGFR and EREG indicate worse survival in patients with MIBC. The prognostic role of AREG should further be investigated in large, prospective series. Divergent survival outcomes between the four cohorts should be interpreted cautiously, considering differences in analysis methods and demographics. Further in vitro investigations are necessary to elucidate the functional mechanisms underlying the associations observed in this study.

Kaempferol alleviates neurodegenerative disorders induced by Naja nigricollis venom via mechanisms of antioxidants, anti-inflammatory, dopaminergic and neuronal functions

Naja nigricollis venom (NnV) contains neurotoxins that influence neurological functions. Kaempferol is a bioactive compound present in edible plants with numerous pharmacological activities. This study investigated the ameliorative potential of kaempferol against NnV-induced neurotoxicity in rats. Fifty male Wistar rats were randomized into five groups (n = 10). Group 1 rats were the control while 1.0 mg/kg−1 (LD50) of NnV was injected intraperitoneally into rats in groups 2–5 to observed neurotoxicity. Group 2 was untreated post envenomation, while groups 3–5 were treated with polyvalent antivenom, 4 and 8 mg/kg of kaempferol, respectively. The biochemical analysis, neurotoxicity, and pathomorphological defects were assessed in the brain of the envenomed treated rats. Envenomation with NnV elevated oxidative and inflammatory biomarkers, and induced neurotoxicity accompanied with neurobehavioral deficits, and severe pathohistological defects were seen in the brain of untreated envenomed rats. However, treatment with kaempferol significantly (p < 0.05) decreased malondialdehyde (MDA) levels and upregulated levels of reduce glutathione (GSH) antioxidant including superoxide dismutase (SOD) and glutathione peroxidase (GPX) antioxidant enzymes, while inflammatory biomarkers; nitric oxide (NO) levels and myeloperoxidase (MPO) activity significantly decreased in envenomed treated groups. Kaempferol upregulated dopamine concentration with significant suppression of acetylcholinesterase (AchE) activity, and restored neurobehavioral and locomotor activities in envenomed treated rats. Also, severe pathomorphological alterations observed in the cortex of the brain were attenuated after kaempferol treatment. The underlaying ameliorative mechanisms of kaempferol are linked to its antioxidant activity, lipid peroxidation inhibition, anti-inflammatory activity, acetylcholinesterase suppression, and alleviation of dopamine system and neurobehavioral abilities.

Effects of inter-stimulus and inter-trial intervals on somatosensory gating

Aim of the study Sensory gating is a human higher cognitive function that serves to suppress excessive sensory information and prevent brain overactivity. To elucidate this function, a paired-pulse stimulation paradigm has been used while recording electroencephalography (EEG), and evaluated as an amplitude ratio of responses to a second stimulus (S2) over responses to the first stimulus (S1). The present study investigated the effects of the inter-stimulus interval (ISI) and inter-trial interval (ITI) on somatosensory gating using somatosensory-evoked potentials (SEPs). Methods In Experiment 1, ISI was set at five conditions: 200, 400, 600, 800, and 1000 ms. In Experiment 2, ITI was set at four conditions: 1, 2, 4, and 8 s. Results ISI affected the S2/S1 amplitude ratios of P22 and N27 at C3’ and N30 at Fz, and these S2/S1 amplitude ratios decreased the most under the 200 and 400-ms conditions. ITI affected the S2/S1 amplitude ratios of P22, N27, and N60 at C3', and especially, the somatosensory gating did not work under the 1-s condition. These results suggest that not all SEP components are modulated in the same manner with changing ISI and ITI. The effects of ISI and ITI independently affected the somatosensory gating. Conclusions Based on our findings, preferable parameters are 200-400 ms for ISI and 4 s or longer for ITI to evaluate the functional mechanisms on somatosensory gating in SEPs.

Cytochalasin B‐Induced Membrane Vesicles of NK Cells for Efficient Tumor Immunotherapy

AbstractExtracellular vesicles (EVs) are crucial mediators of cell‐to‐cell communication and contain biological components such as lipids, proteins, and nucleic acids. EVs are studied for their crucial immunomodulatory roles, particularly in natural killer (NK) cells. NK vesicles, which share surface markers and biological components with the parental NK cells, are developed as anti‐cancer agents. However, their clinical application is hindered by their low productivity and an incomplete understanding of their functional mechanisms. In this study, EV‐mimicking vesicles are artificially induced from NK cells by cytochalasin B treatment. These cytochalasin B‐induced membrane vesicles (CIMVs) are 1.21‐fold more concentrated than isolated natural EVs from NK cells (NK‐EVs) and contain 1.66‐fold more proteins, including those with immunological activity against tumors. The induced ARF6‐positive microvesicles possess an immunological phenotype similar to that of the parental cells, while perforin, granzyme, and FasL proteins are more abundant compared to NK‐EVs. Administrating NK‐EVs and CIMVs to K562 and MCF‐7 tumor cells induces caspase‐dependent apoptosis, which leads to tumor cell cytotoxicity. These results significantly contribute to the understanding of the role of NK vesicles in cellular communication and immunity, and highlight the therapeutic potential of engineered NK‐EVs via their specific action on tumor cells.

Forms and Functions of Conversational Repair in Mandarin Corpus from the Perspective of Interactional Linguistics

Repair frequently appears in our daily conversations as a vital mechanism sustaining effective communication. The purpose of this study is twofold: one is to investigate the specific forms and functions of self-initiated repair and other-initiated repair in Mandarin corpus; the other is to examine, from the perspective of interactional linguistics, how various forms of repair can affect the ongoing dialogue between the speaker and the recipient in Mandarin conversation. Through a thorough examination of repair instances extracted from the speech corpora of naturally occurring, face-to-face Mandarin interaction, findings suggest that self-initiated repair takes the form of word searches and complement, cut-off and correction, as well as recycling and replacement, while other-initiated repair takes the form of interjection, yes-no question, and specific interrogation. Moreover, repair in Mandarin dialogue has the functions of turn maintenance, ambiguity elimination, speculation verification, information confirmation, problem location, and inquiry implementation. This study can not only help readers better understand the forms and functions of repair mechanisms in Mandarin corpus but also contribute to contemporary academic research, offering valuable insights into the dynamics of linguistic interaction.

Current research hotspots and frontier trends on carbon budget of coastal wetlands: A bibliometric analysis.

Coastal wetlands are the main distribution of blue carbon in coastal zones and well known for their high carbon sequestration capacity. Investigating the variation of carbon budget is crucial for understanding the functionality of coastal wetlands and effectively addressing climate change. In this study, a bibliometric analysis of 4,509 articles was conducted to reveal research progress, hot issues, and emerging trends in the coastal wetland carbon budget field. The number of publications and citations in this field increased exponentially from 1991 to 2022. The leading subject category was Environmental Sciences with 1,844 articles (40.9%). At present, studies have been focused on blue carbon, the effects of climate change and man-made disturbances on carbon cycle, and the restoration of coastal wetlands. Based on the hotspots and trends in this field, the future researches should include (1) exploring the functional mechanisms of various factors affecting carbon cycle and establishing a methodological system for the estimation of blue carbon in coastal wetlands; (2) researching restoration techniques of coastal wetland and constructing wetland restoration evaluation index system; and (3) formulating enforceable carbon trading policy and strengthening international cooperation.