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Atrial fibrillation (AF) is a significant precursor to cerebral embolism. Our study sought to unearth new diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE) by meticulously examining multiple GEO datasets and meta-analysis. The gene expression omnibus (GEO) database provided RNA sequencing data associated with AF and stroke. We began by pinpointing genes with varied expressions in AF-CE patient blood samples. A meta-analysis was subsequently undertaken using several RNA sequencing datasets to verify these genes. LASSO regression discerned key genes for AF-CE, with their diagnostic prowess verified through ROC curve examination. Active signaling pathways within stroke patients were discerned via GO and KEGG enrichment, with PPI interactions detailing gene interplay. Differential gene analysis revealed an upregulation of sixteen genes and a downregulation of four in stroke patient blood samples. Eight genes showcased varied expression in the meta-analysis. LASSO regression zeroed in on five of these, culminating in HIST1H2BH's identification as a characteristic gene. HIST1H2BH's prowess in predicting AF-CE was confirmed through ROC. Integrin signaling, platelet activation, ECM interactions, and the PI3K-Akt pathway were found active in stroke victims. HIST1H2BH's interaction with the notably upregulated ITGA2B was spotlighted by PPI. Additionally, HIST1H2BH exhibited links with NK cells and eosinophils. HIST1H2BH emerges as an insightful diagnostic beacon for AF-CE. Its presence, post AF, potentially modulates pathways, accentuating platelet activation and consequent thrombus generation, leading to cerebral embolism.
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The lincoamide antibiotic lincomycin, derived from Streptomyces lincolnensis, is widely used for the treatment of infections caused by gram-positive bacteria. As a common global regulatory factor of GntR family, DasR usually exists as a regulatory factor that negatively regulates antibiotic synthesis in Streptomyces. However, the regulatory effect of DasR on lincomycin biosynthesis in S. lincolnensis has not been thoroughly investigated. The present study demonstrates that DasR functions as a positive regulator of lincomycin biosynthesis in S. lincolnensis, and its overexpression strain OdasR exhibits a remarkable 7.97-fold increase in lincomycin production compared to the wild-type strain. The effects of DasR overexpression could be attenuated by the addition of GlcNAc in the medium in S. lincolnensis. Combined with transcriptome sequencing and RT-qPCR results, it was found that most structural genes in GlcNAc metabolism and central carbon metabolism were up-regulated, but the lincomycin biosynthetic gene cluster (lmb) were down-regulated after dasR knock-out. However, DasR binding were detected with the DasR responsive elements (dre) of genes involved in GlcNAc metabolism pathway through electrophoretic mobility shift assay, while they were not observed in the lmb. These findings will provide novel insights for the genetic manipulation of S. lincolnensis to enhance lincomycin production. KEY POINTS: ⢠DasR is a positive regulator that promotes lincomycin synthesis and does not affect spore production ⢠DasR promotes lincomycin production through indirect regulation ⢠DasR correlates with nutrient perception in S. lincolnensis.
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Antibacterianos , Regulación Bacteriana de la Expresión Génica , Lincomicina , Streptomyces , Lincomicina/farmacología , Lincomicina/biosíntesis , Streptomyces/genética , Streptomyces/metabolismo , Streptomyces/efectos de los fármacos , Antibacterianos/biosíntesis , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Familia de Multigenes , Acetilglucosamina/metabolismo , Vías Biosintéticas/genética , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/genética , Estudios Prospectivos , Inteligencia Artificial , Ultrasonografía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Estudios RetrospectivosRESUMEN
CONTEXT: Accurately distinguishing between benign thyroid nodules (BTNs) and papillary thyroid cancers (PTCs) with current conventional methods poses a significant challenge. OBJECTIVE: We identify DNA methylation markers of immune response-related genes for distinguishing BTNs and PTCs. METHODS: In this study, we analyzed a public reduced representative bisulfite sequencing dataset and revealed distinct methylation patterns associated with immune signals in PTCs and BTNs. Based on these findings, we developed a diagnostic classifier named the Methylation-based Immune Response Signature (MeIS), which was composed of 15 DNA methylation markers associated with immune response-related genes. We validated MeIS's performance in 2 independent cohorts: Z.S.'s retrospective cohort (50 PTC and 18 BTN surgery-leftover samples) and Z.S.'s preoperative cohort (31 PTC and 30 BTN fine-needle aspiration samples). RESULTS: The MeIS classifier demonstrated significant clinical promise, achieving areas under the curve of 0.96, 0.98, 0.89, and 0.90 in the training set, validation set, Z.S.'s retrospective cohort, and Z.S.'s preoperative cohort, respectively. For the cytologically indeterminate thyroid nodules, in Z.S.'s retrospective cohort, MeIS exhibited a sensitivity of 91% and a specificity of 82%; in Z.S.'s preoperative cohort, MeIS achieved a sensitivity of 84% and a specificity of 74%. Additionally, combining MeIS and BRAF V600E detection improved the detecting performance of cytologically indeterminate thyroid nodules, yielding sensitivities of 98% and 87%, and specificities of 82% and 74% in Z.S.'s retrospective cohort and Z.S.'s preoperative cohort, respectively. CONCLUSION: The 15 markers we identified can be employed to improve the diagnostic of cytologically indeterminate thyroid nodules.
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Metilación de ADN , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/genética , Nódulo Tiroideo/patología , Nódulo Tiroideo/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/inmunología , Diagnóstico Diferencial , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/inmunología , Biomarcadores de Tumor/genética , Biopsia con Aguja Fina , AncianoRESUMEN
STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: There is some controversy about the effects of calcitonin (CT) on lumbar spinal stenosis (LSS). This systematic review and meta-analysis is to assess the strength of the evidence supporting the use of CT in the treatment of patients with LSS. MATERIAL AND METHOD: We performed an electronic search depicting randomized controlled trials (RCTs) through 4 databases from the date of database creation to January 2023. 3 different researchers conducted independent literature screening, data extractions, and quality assessments. The outcome measures included visual analogue scale (VAS), walking distance, and oswestry disability index (ODI). Meta-analysis and trial sequence analysis (TSA) were carried out using RevMan 5.4, Stata 16.0, and TSA 0.9. GRADE 3.6 was used to evaluate the evidence quality. RESULTS: We accepted 9 studies with 496 participants. The meta-analysis revealed that CT offered no significant improvement in VAS, walking distance, or ODI in patients with LSS. CONCLUSION: There is no evidence that CT has a benefit in patients with LSS, either alone or in combination with other treatments, or depending on the route of administration, according to the systematic review and meta-analysis of relevant RCTs.
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Calcitonina , Vértebras Lumbares , Estenosis Espinal , Humanos , Conservadores de la Densidad Ósea/uso terapéutico , Calcitonina/uso terapéutico , Evaluación de la Discapacidad , Vértebras Lumbares/diagnóstico por imagen , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Estenosis Espinal/tratamiento farmacológicoRESUMEN
Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1ß, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood-brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.
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Depresión , Lipopolisacáridos , Humanos , Ratones , Animales , Lipopolisacáridos/farmacología , Depresión/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Citocinas/metabolismo , Mesencéfalo/metabolismo , FormaldehídoRESUMEN
BACKGROUND: Serving as a stop signal of inflammation, the role of lipoxin A4 (LXA4) in periodontitis remains to be clarified. This study is aimed to examine the changes in LXA4 levels in gingival crevicular fluid (GCF) after scaling and root planing (SRP) and to determine the relationship between LXA4 levels and treatment outcomes and periodontal pathogens in severe periodontitis. METHODS: A total of 74 GCF samples were collected from 21 severe periodontitis participants at the deepest affected sites. These sites were re-sampled at 1, 3, and 6 months after SRP. Besides, GCF samples were also collected from 25 periodontally healthy participants. Clinical parameters including probing depth (PD) and clinical attachment level (CAL) in periodontitis group were recorded. LXA4 levels and periodontal pathogens in the GCF were analyzed by ELISA and PCR, respectively. Correlations between GCF LXA4 levels and treatment effect and periodontal pathogens were assessed. RESULTS: LXA4 levels in GCF significantly increased after SRP (p < 0.05), but remained lower than those observed in healthy individuals (p < 0.05). Sites with lower baseline LXA4 concentrations were more likely to experience greater improvements in PD at 6 months post-SRP (area under the curve [AUC] = 0.792), and the improvements were positively correlated with the increase of LXA4 at these sites post-treatment (p < 0.05). Furthermore, more elevated LXA4 levels were observed in sites that became negative for Prevotella intermedia or Tannerella forsythia after SRP. CONCLUSION: Baseline LXA4 in GCF has the potential to predict the site-specific response of severe periodontal lesions to SRP. The increase of LXA4 levels after treatment was positively correlated with clinical improvements and negatively correlated with the presence of Prevotella intermedia or Tannerella forsythia.
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Lipoxinas , Periodontitis , Humanos , Aplanamiento de la Raíz , Periodontitis/tratamiento farmacológico , Lipoxinas/uso terapéutico , Raspado Dental , Líquido del Surco Gingival , Prevotella intermediaRESUMEN
Conductive hydrogels have emerged as ideal candidate materials for strain sensors due to their signal transduction capability and tissue-like flexibility, resembling human tissues. However, due to the presence of water molecules, hydrogels can experience dehydration and low-temperature freezing, which greatly limits the application scope as sensors. In this study, an ionic co-hybrid hydrogel called PBLL is proposed, which utilizes the amphoteric ion betaine hydrochloride (BH) in conjunction with hydrated lithium chloride (LiCl) thereby achieving the function of humidity adaptive. PBLL hydrogel retains water at low humidity (<50%) and absorbs water from air at high humidity (>50%) over the 17 days of testing. Remarkably, the PBLL hydrogel also exhibits strong anti-freezing properties (-80 °C), high conductivity (8.18 S m-1 at room temperature, 1.9 S m-1 at -80 °C), high gauge factor (GF approaching 5.1). Additionally, PBLL hydrogels exhibit strong inhibitory effects against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as well as biocompatibility. By synergistically integrating PBLL hydrogel with wireless transmission and Internet of Things (IoT) technologies, this study has accomplished real-time human-computer interaction systems for sports training and rehabilitation evaluation. PBLL hydrogel exhibits significant potential in the fields of medical rehabilitation, artificial intelligence (AI), and the Internet of Things (IoT).
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Escherichia coli , Humedad , Hidrogeles , Staphylococcus aureus , Hidrogeles/química , Humanos , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Congelación , Internet de las CosasRESUMEN
The development of bioinspired gradient hydrogels with self-sensing actuated capabilities for remote interaction with soft-hard robots remains a challenging endeavor. Here, we propose a novel multifunctional self-sensing actuated gradient hydrogel that combines ultrafast actuation and high sensitivity for remote interaction with robotic hand. The gradient network structure, achieved through a wettability difference method involving the rapid precipitation of MoO2 nanosheets, introduces hydrophilic disparities between two sides within hydrogel. This distinctive approach bestows the hydrogel with ultrafast thermo-responsive actuation (21° s-1) and enhanced photothermal efficiency (increase by 3.7 °C s-1 under 808 nm near-infrared). Moreover, the local cross-linking of sodium alginate with Ca2+ endows the hydrogel with programmable deformability and information display capabilities. Additionally, the hydrogel exhibits high sensitivity (gauge factor 3.94 within a wide strain range of 600%), fast response times (140 ms) and good cycling stability. Leveraging these exceptional properties, we incorporate the hydrogel into various soft actuators, including soft gripper, artificial iris, and bioinspired jellyfish, as well as wearable electronics capable of precise human motion and physiological signal detection. Furthermore, through the synergistic combination of remarkable actuation and sensitivity, we realize a self-sensing touch bioinspired tongue. Notably, by employing quantitative analysis of actuation-sensing, we realize remote interaction between soft-hard robot via the Internet of Things. The multifunctional self-sensing actuated gradient hydrogel presented in this study provides a new insight for advanced somatosensory materials, self-feedback intelligent soft robots and human-machine interactions.
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The theory of band topology has inspired the discovery of various topologically protected states in the regime of photonics. It has led to the development of topological photonic devices with robust property and versatile functionalities, like unidirectional waveguides, compact power splitters, high-Q resonators, and robust lasers. These devices mainly rely on the on-chip photonic crystal (PhC) in Si or III-V compound materials with a fairly large bandgap. However, the topological designs have rarely been applied to the ultra-low-loss silicon nitride (SiN) platform which is widely used in silicon photonics for important devices and integrated photonic circuits. It is mainly hindered by the relatively low refractive index. In this work, we revealed that a rhombic PhC can open a large bandgap in the SiN slab, and thus support robust topological corner states stemming from the quantization of the dipole moments. Meanwhile, we propose the inclination angle of rhombic lattice, as a new degree of freedom, to manipulate the characteristics of topological states. Our work shows a possibility to further expand the topological protection and design flexibility to SiN photonic devices.
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Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer. Methylation of some genes plays a crucial role in the tendency to malignancy as well as poor prognosis of thyroid cancer, suggesting that methylation features can serve as complementary markers for molecular diagnosis. In this study, we aimed to develop and validate a diagnostic model for PTC based on DNA methylation markers. A total of 142 thyroid nodule tissue samples containing 84 cases of PTC and 58 cases of thyroid adenoma (TA) were collected for reduced representation bisulfite sequencing (RRBS) and subsequent analysis. The diagnostic model was constructed by the logistic regression (LR) method followed by 5-cross validation and based on 94 tissue methylation haplotype block (MHB) markers. The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.974 (95% CI, 0.964-0.981) on 108 training samples and 0.917 (95% CI, 0.864-0.973) on 27 independent testing samples. The diagnostic model scores showed significantly high in males (P = 0.0016), age ≤ 45 years (P = 0.026), high body mass index (BMI) (P = 0.040), lymph node metastasis (P = 0.00052) and larger nodules (P = 0.0017) in the PTC group, and the risk score of this diagnostic model showed significantly high in recurrent PTC group (P = 0.0005). These results suggest that the diagnostic model can be expected to be a powerful tool for PTC diagnosis and there are more potential clinical applications of methylation markers to be excavated.
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Carcinoma Papilar , Neoplasias de la Tiroides , Masculino , Humanos , Persona de Mediana Edad , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/genética , Metilación de ADN/genética , Haplotipos , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Recurrencia Local de Neoplasia/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patologíaRESUMEN
Hydrogels from natural polymers are eco-friendly, biocompatible and adjustable for manufacturing wearable sensors. However, it is still challenging to prepare natural polymer hydrogel sensors with excellent properties (e.g., high conductivity). Here, we developed a physically cross-linked, highly conductive and multifunctional hydrogel (named PPTP) to address this challenge. The natural renewable pectin-based PPTP hydrogel is synthesized by introducing tannic acid (TA), calcium chloride (CaCl2), and sodium chloride (NaCl) into the pectin/polyvinyl alcohol (PVA) dual network structure. The hydrogel exhibits excellent characteristics, including unique tensile strength (2.6155 MPa), high electrical conductivity (7 S m-1), and high sensitivity (GF = 3.75). It is also recyclable, further enhancing its eco-friendly nature. The PPTP hydrogel can be used for monitoring human joint activities, as flexible electrodes for monitoring electrocardiogram (ECG) signals, and touchable screen pen for electronic skin. Moreover, when combined with Morse code and wireless Bluetooth technology, PPTP hydrogels can be used for underwater and land information encryption, and decryption. Our unique PPTP hydrogel offers promising opportunities for medical monitoring, information transfer, and human-computer interaction.
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Hidrogeles , Pectinas , Polifenoles , Humanos , Polisacáridos , Conductividad Eléctrica , Polímeros , Cloruro de SodioRESUMEN
With the development of microfluidic technology, tumor-on-chip models have gradually become a new tool for the study of breast cancer because they can simulate more key factors of the tumor microenvironment compared with traditional models in vitro. Here, we review up-to-date advancements in breast tumor-on-chip models. We summarize and analyze the breast tumor microenvironment (TME), preclinical breast cancer models for TME simulation, fabrication methods of tumor-on-chip models, tumor-on-chip models for TME reconstruction, and applications of breast tumor-on-chip models and provide a perspective on breast tumor-on-chip models. This review will contribute to the construction and design of microenvironments for breast tumor-on-chip models, even the development of the pharmaceutical field, personalized/precision therapy, and clinical medicine.
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Neoplasias de la Mama , Neoplasias Mamarias Animales , Animales , Humanos , Femenino , Microambiente Tumoral , Simulación por Computador , MicrofluídicaRESUMEN
BACKGROUND: To subgroup Chinese patients with newly diagnosed type 2 diabetes (T2D) by K-means cluster analysis on clinical indicators, and to explore whether these subgroups represent different genetic features and calculated cardiovascular risks. METHODS: The K-means clustering analysis was performed on two cohorts (n = 590 and 392), both consisting of Chinese participants with newly diagnosed T2D. To assess genetic risks, multiple polygenic risk scores (PRSs) and mitochondrial DNA copy numbers (mtDNA-CN) were calculated for all participants. Furthermore, Framingham risk scores (FRS) of cardiovascular diseases in two cohorts were also calculated to verify the genetic risks. RESULTS: Four clusters were identified including the mild age-related diabetes (MARD)(35.08%), mild obesity-related diabetes (MOD) (34.41%), severe autoimmune diabetes (SAID) 19.15%, and severe insulin-resistant diabetes (SIRD) 11.36% subgroups in the MARCH (metformin, and acarbose in Chinese patients as the initial hypoglycemic treatment) cohort. There was a significant difference in PRS for cardiovascular diseases (CVD) across four subgroups in the MARCH cohort (p < 0.05). Compared with the SIDD and SIRD subgroups, patients in the MOD subgroup had a relatively lower PRS for CVD (p < 0.05) in the MARCH cohort. Females had a higher PRS compared to males, with no significant difference in FRS across the four clusters. The MOD subgroup had a significantly lower FRS which was consistent with the results of PRS. Similar results of PRS and FRS were also replicated in the CONFIDENCE (comparison of glycemic control and b-cell function among newly diagnosed patients with type 2 diabetes treated with exenatide, insulin or pioglitazone) cohort. CONCLUSION: There are different CVD risks in diabetic subgroups based on clinical and genetic evidence which may promote precision medicine.
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Empiric probiotics are commonly consumed by healthy individuals as a means of disease prevention, pathogen control, etc. However, controversy has existed for a long time regarding the safety and benefits of probiotics. Here, two candidate probiotics, Lactiplantibacillus plantarum and Pediococcus acidilactici, which are antagonistic to Vibrio and Aeromonas species in vitro, were tested on Artemia under in vivo conditions. In the bacterial community of Artemia nauplii, L. plantarum reduced the abundance of the genera Vibrio and Aeromonas and P. acidilactici significantly increased the abundance of Vibrio species in a positive dosage-dependent manner, while higher and lower dosages of P. acidilactici increased and decreased the abundance of the genus Aeromonas, respectively. Based on the liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) analyses of the metabolite of L. plantarum and P. acidilactici, pyruvic acid was used in an in vitro test to explain such selective antagonism; the results showed that pyruvic acid was conducive or suppressive to V. parahaemolyticus and beneficial to A. hydrophila. Collectively, the results of this study demonstrate the selective antagonism of probiotics on the bacterial community composition of aquatic organisms and the associated pathogens. IMPORTANCE Over the last decade, the common preventive method for controlling potential pathogens in aquaculture has been the use of probiotics. However, the mechanisms of probiotics are complicated and mostly undefined. At present, less attention has been paid to the potential risks of probiotic use in aquaculture. Here, we investigated the effects of two candidate probiotics, L. plantarum and P. acidilactici, on the bacterial community of Artemia nauplii and the in vitro interactions between these two candidate probiotics and two pathogens, Vibrio and Aeromonas species. The results demonstrated the selective antagonism of probiotics on the bacterial community composition of an aquatic organism and its associated pathogens. This research contributes to providing a basis and reference for the long-term rational use of probiotics and to reducing the inappropriate use of probiotics in aquaculture.
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Aeromonas , Pediococcus acidilactici , Probióticos , Vibrio , Humanos , Animales , Pediococcus acidilactici/metabolismo , Artemia/microbiología , Ácido Pirúvico/metabolismo , Probióticos/farmacologíaRESUMEN
Pneumonia is an acute inflammation of the lungs induced by pathogenic microorganisms, immune damage, physical and chemical factors, and other factors, and the latest outbreak of novel coronavirus pneumonia is also an acute lung injury (ALI) induced by viral infection. However, there are currently no effective treatments for inflammatory cytokine storms in patients with ALI/acute respiratory distress syndrome (ARDS). Protein kinase D (PKD) is a highly active kinase that has been shown to be associated with the production of inflammatory cytokines. Therefore, small-molecule compounds that inhibit PKD may be potential drugs for the treatment of ALI/ARDS. In the present study, we evaluated the ability of the small-molecule inhibitor CRT0066101 to attenuate lipopolysaccharide (LPS)-induced inflammatory cytokine production through in vitro cell experiments and a mouse pneumonia model. We found that CRT0066101 significantly reduced the protein and mRNA levels of LPS-induced cytokines (e.g., IL-6, TNF-α, and IL-1ß). CRT0066101 inhibited MyD88 and TLR4 expression and reduced NF-κB, ERK, and JNK phosphorylation. CRT0066101 also reduced NLRP3 activation, inhibited the assembly of the inflammasome complex, and attenuated inflammatory cell infiltration and lung tissue damage. Taken together, our data indicate that CRT0066101 exerts anti-inflammatory effects on LPS-induced inflammation through the TLR4/MyD88 signaling pathway, suggesting that CRT0066101 may have therapeutic value in acute lung injury and other MyD88-dependent inflammatory diseases.
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Lesión Pulmonar Aguda , COVID-19 , Neumonía , Síndrome de Dificultad Respiratoria , Ratones , Animales , Síndrome de Liberación de Citoquinas/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Lipopolisacáridos/farmacología , Receptor Toll-Like 4/metabolismo , COVID-19/metabolismo , Pulmón/patología , Neumonía/patología , Lesión Pulmonar Aguda/inducido químicamente , FN-kappa B/metabolismo , Inflamación/metabolismo , Citocinas/metabolismo , Síndrome de Dificultad Respiratoria/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: Diabetes is an important risk factor for periodontitis, and circular RNA (circRNA) may play an important role in aggravating inflammation and accelerating disease progression by regulating miRNA/mRNA. This study aimed to investigate the role and mechanism of the hsa_circ_0084054/miR-508-3p/PTEN axis in the progression of periodontitis with diabetes. METHODS: First, circRNA sequencing was used to screen the differentially expressed circRNAs of periodontal ligament cells (PDLCs) treated with high glucose and/or Porphyromonas gingivalis lipopolysaccharide (LPS) in vitro, and the overtly differentially expressed hsa_circ_0084054 was selected and was also verified in periodontal ligament (PDL) tissue from periodontitis patients with diabetes. Then, its ring structure was tested by Sanger sequencing, RNase R, and actinomycin D assays. The bioinformatics analysis, dual luciferase reporter assay, and RIP assay were used to explore the interaction of hsa_circ_0084054/miR-508-3p/PTEN axis, whose effects on inflammation, oxidative stress, and apoptosis of PDLCs were evaluated through the measurement of inflammatory factors, reactive oxygen species (ROS), total superoxide dismutase (SOD), malondialdehyde (MDA), and Annexin V/PI assay. RESULTS: By high-throughput sequencing, it was found that hsa_circ_0084054 was significantly increased in HG + LPS group compared with control group and LPS group, which was also verified in periodontal ligament (PDL) tissue from periodontitis patients with diabetes. Silencing hsa_circ_0084054 in PDLCs decreased the expression of inflammatory factors (IL-1ß, IL-6, TNF-α), the levels of ROS and MDA, and the proportion of apoptotic cells; conversely, SOD activity was enhanced. In addition, we found that hsa_circ_0084054 could up-regulate the expression of PTEN through sponge miR-508-3p to inhibit AKT phosphorylation, finally trigger the aggravation of oxidative stress and inflammation in periodontitis patients with diabetes. CONCLUSION: hsa_circ_0084054 can aggravate inflammation and promote the progression of periodontitis with diabetes by regulating miR-508-3p/PTEN signaling axis, which may serve as a new target for the intervention of periodontitis with diabetes.
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Diabetes Mellitus , MicroARNs , Periodontitis , Humanos , ARN Circular/genética , Lipopolisacáridos/farmacología , Especies Reactivas de Oxígeno , Periodontitis/genética , MicroARNs/genética , Inflamación/genética , Proliferación Celular , Fosfohidrolasa PTEN/genéticaRESUMEN
Multifunctional supramolecular ultra-tough bionic e-skin with unique durability for human-machine interaction in complex scenarios still remains challenging. Herein, we develop a skin-inspired ultra-tough e-skin with tunable mechanical properties by a physical cross-linking salting-freezing-thawing method. The gelling agent (ß-Glycerophosphate sodium: Gp) induces the aggregation and binding of PVA molecular chains and thereby toughens them (stress up to 5.79 MPa, toughness up to 13.96 MJ m-3). Notably, due to molecular self-assembly, hydrogels can be fully recycled and reprocessed by direct heating (100 °C for a few seconds), and the tensile strength can still be maintained at about 100% after six recoveries. The hydrogel integrates transparency (> 60%), super toughness (up to 13.96 MJ m-3, bearing 1500 times of its own tensile weight), good antibacterial properties (E. coli and S. aureus), UV protection (Filtration: 80%-90%), high electrical conductivity (4.72 S m-1), anti-swelling and recyclability. The hydrogel can not only monitor daily physiological activities, but also be used for complex activities underwater and message encryption/decryption. We also used it to create a complete finger joint rehabilitation system with an interactive interface that dynamically presents the user's health status. Our multifunctional electronic skin will have a profound impact on the future of new rehabilitation medical, human-machine interaction, VR/AR and the metaverse fields.
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Background: Intracranial aneurysm (IA) is an uncommon but severe subtype of cerebrovascular disease, with high mortality after aneurysm rupture. Current risk assessments are mainly based on clinical and imaging data. This study aimed to develop a molecular assay tool for optimizing the IA risk monitoring system. Methods: Peripheral blood gene expression datasets obtained from the Gene Expression Omnibus were integrated into a discovery cohort. Weighted gene co-expression network analysis (WGCNA) and machine learning integrative approaches were utilized to construct a risk signature. QRT-PCR assay was performed to validate the model in an in-house cohort. Immunopathological features were estimated using bioinformatics methods. Results: A four-gene machine learning-derived gene signature (MLDGS) was constructed for identifying patients with IA rupture. The AUC of MLDGS was 1.00 and 0.88 in discovery and validation cohorts, respectively. Calibration curve and decision curve analysis also confirmed the good performance of the MLDGS model. MLDGS was remarkably correlated with the circulating immunopathologic landscape. Higher MLDGS scores may represent higher abundance of innate immune cells, lower abundance of adaptive immune cells, and worse vascular stability. Conclusions: The MLDGS provides a promising molecular assay panel for identifying patients with adverse immunopathological features and high risk of aneurysm rupture, contributing to advances in IA precision medicine.
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Rh(III)-catalyzed synthesis of benzoisothiazole spiropyrrolidinediones using sulfoximine as a directing group under a C-H activation and [4 + 1] annulation strategy with maleimides as a coupling partner is reported. The cyclization reaction was compatible with various substituted sulfoximine and maleimides. The deuterium-labeling studies were performed to investigate the mechanism of the reaction.