RESUMEN

Skin cutaneous melanoma (SKCM) is a highly fatal form of skin cancer that develops from the malignant transformation of epidermal melanocytes. There is substantial evidence linking autophagy to cancer etiology and immunotherapy efficacy. This study aimed to conduct a comprehensive analysis of autophagy-related genes (ARGs) using TCGA datasets and further explore the potential function of critical ARGs in SKCM progression. We performed comprehensive bioinformatics analysis uses the TCGA dataset. RT-PCR was applied to examine the expression of CAPNS1 in SKCM cells. Lost-of-function experiments were performed to detect the expression of the related proteins. In this search, we screed 70 differentially expressed autophagy-related genes (DE-ARGs), including 33 up-DE-ARGs and 37 down-DE-ARGs. Enrichment assays revealed that these 70 DE-ARGs may exert influence on critical cellular processes such as autophagy, protein kinase activity, and signaling pathways, impacting cell growth, differentiation, survival, and tumor development. Then, we further explore the prognostic value of 70 DE-ARGs and confirmed 18 survival-related DE-ARGs in SKCM patients. Nearly all the 18 DE-ARGs' methylation was negatively correlated with their corresponding expression in SKCM. The 12 survival-related DE-ARGs were used to develop a unique predictive model that effectively classified SKCM patients into high- and low-risk groups with regard to overall survival. Furthermore, tumor environment analysis indicated that the risk score was associated with several immune cells. Among the 12 survival-related DE-ARGs, our attention focused on CAPNS1 which was highly expressed in SKCM patients and predicted a poor prognosis. In addition, we confirmed that knockdown of CAPNS1 distinctly suppressed the proliferation, metastasis and EMT of SKCM cells, and promoted autophagy via regulating Notch signaling pathway. Overall, this study enhances our understanding of the intricate molecular landscape of SKCM progression and presents promising avenues for future research and clinical applications.

RESUMEN

Background: Aging is the primary risk factor for the onset of Alzheimer's disease (AD). Inflamma-aging is a major feature in the process of aging, and the chronic neuroinflammation caused by inflamma-aging is closely related to AD. As the main participant of neuroinflammation, the polarization of microglia (MG) could influence the development of neuroinflammation. Objective: This study aims to observe the impact of YHD on microglia (MG) polarization and neuroinflammation to delay the onset and progression of AD. Methods: In vivo experiment, four-month senescence accelerated mouse prone 8 (SAMP8) were used as the model group, the SAMR1 mice of the same age were used as the control group. In YHD group, 6.24 g/kg YHD was intragastrically administrated continuously for 12 weeks, and Ibuprofen 0.026 g/kg in positive control group. Morris Water Maze test was used to evaluate the learning and memory ability, Nissl's staining and immunofluorescence double staining for neuron damage and MG M1/M2 polarization, Enzyme-Linked Immunosorbent Assay (ELISA) for neuroinflammation biomarkers in hippocampus, Western blot for key protein expression of TREM2/NF-κB signaling pathway. In vitro experiments, 10 µM/l Aß1-42 induced BV-2 cell model was used to re-verify the effect of YHD regulating MG polarization to reduce neuroinflammation. Also, TREM2 small interfering RNA (siRNA) was used to clarify the key target of YHD. Results: YHD could improve the learning and memory ability of SAMP8 mice evaluated by the Morris Water Maze test. Like Ibuprofen, YHD could regulate the M1/M2 polarization of MG and the levels of neuroinflammatory markers TNF-α and IL-10 in hippocampus, and relieve neuroinflammation and neuron loss. In addition, YHD could also regulate the expression of PU.1, TREM2, p-NF-κB P65 in the TREM2/NF-κB signaling pathway. Further in vitro experiments, we found that YHD had a significant regulatory effect on Aß1-42-induced BV-2 cell polarization, and it could significantly increase PU.1, TREM2, decrease p-NF-κB P65, p-IKKß, TNF-α, IL-6, IL-1ß. At the same time, using siRNA to inhibit TREM2, it proved that TREM2 was a key target for YHD to promote Aß1-42-induced BV-2 cell M2 polarization to reduce neuroinflammation. Conclusions: YHD could regulate the TREM2/NF-κB signaling pathway through TREM2, thereby to adjust MG polarization and reduce AD-related neuroinflammation.

RESUMEN

This study investigated the role of O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2-3 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2-3 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR ≥100%), subtotal resection (STR >90%), and partial resection (PR ≤90%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1/2-mutant and 1p/19q non-codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1/2 mutation and 1p/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels >20%). Astrocytomas were more common in the low-methylated group (10%-20%), while IDH wild-type gliomas were mostly unmethylated (<10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low-methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low-methylated and unmethylated cases were more likely to invade the temporal-insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal-insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2-3 gliomas, providing insights into why astrocytomas and IDH wild-type lower-grade glioma might derive less benefit from chemotherapy.

RESUMEN

The catalytic asymmetric propargylation of enol(ate) intermediates is a well-established method for the synthesis of α-propargyl-substituted carbonyl compounds. However, the propargylation of homo-enol(ate) or its equivalents for the synthesis of ß-propargyl-substituted carbonyl compounds remains underdeveloped. A catalytic enantioselective decarboxylative intramolecular propargylation of cyclopropanols has been developed using a PyBox-complexed copper catalyst. This reaction offers an effective approach to assemble a cyclopentanone skeleton bearing an all-carbon quaternary stereogenic center and an adjacent quaternary gem-dimethyl carbon center, which is the core scaffold of the naturally occurring cuparenoids. Key to the success of this protocol is the use of a new structurally optimized PyBox ligand. This study represents the first example of catalytic asymmetric intramolecular propargylation of cyclopropanols.

RESUMEN

BACKGROUND: Recent human and animal studies have demonstrated that Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is closely involved in the development of allergic diseases. OBJECTIVE: To identify the mechanism underlying the activation of NLRP3 inflammasome signaling pathway in an ovalbumin (OVA)-induced allergic rhinitis (AR) mice model and to validate the effect of a specific inhibitor of the NLRP3, MCC950. METHODS: Mice were divided into three groups and each group consisted of ten mice (saline group, the negative control group; OVA group, the OVA-induced AR model group; and OVA+MCC group, treated with 10 mg/kg MCC950). MCC950 was administered intraperitoneally every second day. Multiple parameters of AR, including NLRP3, caspase-1, interleukin (IL)-1ß, and IL-18 were evaluated by using ELISA, RT-qPCR, histopathology, and immunohistochemistry. RESULTS: The mRNA and protein levels of NLRP3, caspase-1, IL-1ß and IL-18 were upregulated in the OVA group compared with those of the saline group. MCC950 significantly inhibited the mRNA and protein levels of NLRP3, caspase-1, IL-1ß and IL-18 in nasal tissue. Further, AR symptoms and eosinophil count were normalized after MCC950 treatment. However, OVA-specific IgE was not restored in the OVA+MCC group. CONCLUSION: NLRP3 inflammasome signaling pathway may be an alternative pathway to induce AR symptoms in OVA-induced AR model. MCC950 is a specific inhibitor of NLRP3 cascade, which attenuates AR symptoms regardless of IgE.

RESUMEN

A novel Gram-stain-negative strain, designated JM10B15T, was isolated from pond water for Litopenaeus vannamei collected from Jiangmen City, Guangdong province, south PR China. Cells of the strain were aerobic, rod-shaped, and motile by lateral flagella. JM10B15T could grow at 15-40 °C, pH 6.0-9.5, and in 0-3.0 % NaCl, with optimal growth at 25-35 °C, pH 7.5-8.5, and in 0 % NaCl, respectively. Furthermore, this strain grew well on Reasoner's 2A agar but not on nutrient broth agar or Luria-Bertani agar. JM10B15T was a denitrifying bacterium capable of removing nitrites and nitrates, and three key functional genes, nasA, nirS, and nosZ, were identified in its genome. The results of phylogenetic analyses based on the 16S rRNA gene and genome sequences indicated that JM10B15T belonged to the genus Gemmobacter. JM10B15T showed the highest 16S rRNA sequence similarity to Gemmobacter lutimaris YJ-T1-11T (98.8 %), followed by Gemmobacter aquatilis IFAM 1031T (98.6 %) and Gemmobacter serpentinus HB-1T (98.1 %). The average nucleotide identity and digital DNA-DNA hybridization values between JM10B15T and the other type strains of genus Gemmobacter were 78.1-82.1 % and 18.4-22.1 %, respectively. The major fatty acids of strain JM10B15T were summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c) and C18 : 1 ω7c 11-methyl. In addition, the major respiratory quinone of this novel strain was Q-10, and the predominant polar lipids were phosphatidylglycerol, phosphatidylethanolamine, four unidentified phospholipids, three unidentified lipids, and an unidentified aminophospholipid. Results of analyses of the phylogenetic, genomic, physiological, and biochemical characteristics indicated that JM10B15T represents a novel species of the genus Gemmobacter, for which the name Gemmobacter denitrificans sp. nov. is proposed. The type strain is JM10B15T (=GDMCC 1.4148T=KCTC 8140T).

Asunto(s)

RESUMEN

Clostridioides difficile infection (CDI) caused by toxigenic C. difficile is the leading cause of antimicrobial and healthcare-associated diarrhea. The pathogenicity of C. difficile relies on the synergistic effect of multiple virulence factors, including spores, flagella, type IV pili (T4P), toxins, and biofilm. Spores enable survival and transmission of C. difficile, while adhesion factors such as flagella and T4P allow C. difficile to colonize and persist in the host intestine. Subsequently, C. difficile produces the toxins TcdA and TcdB, causing pseudomembranous colitis and other C. difficile-associated diseases; adhesion factors bind to the extracellular matrix to form biofilm, allowing C. difficile to evade drug and immune system attack and cause recurrent infection. Cyclic diguanylate (c-di-GMP) is a near-ubiquitous second messenger that extensively regulates morphology, the expression of virulence factors, and multiple physiological processes in C. difficile. In this review, we summarize current knowledge of how c-di-GMP differentially regulates the expression of virulence factors and pathogenesis-related phenotypes in C. difficile. We highlight that C. difficile spore formation and expression of toxin and flagella genes are inhibited at high intracellular levels of c-di-GMP, while T4P biosynthesis, cell aggregation, and biofilm formation are induced. Recent studies have enhanced our understanding of the c-di-GMP signaling networks in C. difficile and provided insights for the development of c-di-GMP-dependent strategies against CDI.

Asunto(s)

RESUMEN

One of the ways in which macrophages support tumorigenic growth is by producing adenosine, which acts to dampen antitumor immune responses and is generated by both tumor and immune cells in the tumor microenvironment (TME). Two cell surface expressed molecules, CD73 and CD39, boost catalytic adenosine triphosphate, leading to further increased adenosine synthesis, under hypoxic circumstances in the TME. There are four receptors (A1, A2A, A2B, and A3) expressed on macrophages that allow adenosine to perform its immunomodulatory effect. Researchers have shown that adenosine signaling is a key factor in tumor progression and an attractive therapeutic target for treating cancer. Several antagonistic adenosine-targeting biological therapies that decrease the suppressive action of tumor-associated macrophages have been produced and explored to transform this result from basic research into a therapeutic advantage. Here, we'll review the newest findings from studies of pharmacological compounds that target adenosine receptors, and their potential therapeutic value based on blocking the suppressive action of macrophages in tumors.

Asunto(s)

RESUMEN

AIMS: This study was designed to develop a biosafety incident response competence scale and evaluate its validity and reliability among clinical nurses. DESIGN: This study employed a sequential approach, comprising four phases: (1) the establishment of a multidimensional conceptual model, (2) the preliminary selection of the items, (3) further exploration and psychometric testing of the items, (4) the application of the scale among clinical nurses. METHODS: The biosafety incident response competence conceptual model was developed through literature review and the Delphi method. A total of 1,712 clinical nurses participated in the preliminary items selection, while 1,027 clinical nurses were involved in the further psychometric testing from July 2023 to August 2023. The item analysis, exploratory factor analysis and confirmatory factor analysis were conducted to evaluate the construct validity. Reliability was measured using Cronbach's alpha, split-half reliability, and test-retest reliability, while validity analysis included content validity, structural validity, convergent validity, and discriminant validity. From September to November 2023, we conducted a survey using the established scale with a total of 4338 valid questionnaires collected. T-test and variance analysis was employed to determine potential variations in biosafety incident response competence based on participants characteristics. RESULTS: The final scale is composed of 4 factors and 29 items, including monitoring and warning abilities, nursing disposal abilities, biosafety knowledge preparedness, and infection protection abilities. The explanatory variance of the 4 factors was 75.100%. The Cronbach's alpha, split-half reliability and test-retest reliability were 0.974, 0.945 and 0.840 respectively. The Scale-level content validity index was 0.866. The Average Variance Extracted of the 4 factors was larger than 0.5, the Construct Reliability was larger than 0.7, and the Heterotrait-Monotrait ratio were less than 0.9. There were significant differences in the scores of response competence among nurses of different ages, working years, titles, positions, departments, marital status and participation in biosafety training (all P < 0.05). CONCLUSIONS: The biosafety incident response competence scale for nurses exhibits satisfactory reliability and validity, making it a valuable tool for assessing clinical nurses' abilities in responding to biosafety incidents.

RESUMEN

INTRODUCTION: The "obesity paradox" in elderly patients suffering from percutaneous coronary intervention (PCI) remains a source of controversy. The present meta-analysis focused on exploring the real existence of "obesity paradox" in these patients. METHODS: As of November 2022, PubMed, Cochrane, and Embase databases were comprehensively searched to identify articles reporting all-cause mortality according to diverse body mass index (BMI) categories after PCI among the old cases developing coronary artery disease (CAD). Summary estimates of relative risks (RRs) were assigned to four BMI groups, including underweight, normal weight, overweight, and obesity groups. RESULTS: There were altogether nine articles involving 25,798 cases selected for further analysis. Relative to normal weight group, overweight and obesity groups had decreased all-cause mortality (RR: 0.86, 95% CI: 0.77-0.95 for overweight group; RR: 0.57, 95% CI: 0.40-0.80 for obesity group), while underweight group had elevated all-cause mortality (RR: 1.52, 95% CI: 1.01-2.29). CONCLUSION: Our study revealed an "obesity paradox" relation of BMI with all-cause mortality in elderly cases receiving PCI. In comparison with normal weight group, overweight and obesity groups had decreased all-cause mortality, while underweight group had increased all-cause mortality.

Asunto(s)

RESUMEN

Thyroid dysfunction is common in critical illness and may influence prognosis. However, the value of TSH in patients with severe diseases remains unclear. The aim of this study was to investigate the association between TSH and the clinical prognosis of critically ill patients. Methods: This retrospective study identified patients who were admitted to the ICU in the Medical Information Mart for Intensive Care (MIMIC-IV) database (version 2.2). A total of 6432 patients were divided into four groups based on TSH quartiles (Q1, <0.92 mIU/L; Q2, 0.92-1.07 mIU/L; Q3, 1.07-3.10 mIU/L; Q4, >3.10 mIU/L). The clinical outcomes were defined as all-cause 7-, 30-, and 90-year mortality after ICU admission. Restricted cubic splines (RCSs) for nonlinear associations were generated to visualize the relationship between TSH levels and clinical outcomes. The survival differences among the four groups were also analyzed using Kaplan‒Meier curves and log rank tests. Univariable and multivariable Cox proportional hazards regression were further used to assess the association between TSH levels and clinical outcomes. Results: After multivariate adjustment, a U-shaped relationship was observed between TSH levels and all-cause 7-, 30-, and 90- mortality among patients with severe disease (all P < 0.05 for nonlinearity). The plot showed a risk reduction in the low range of TSH, which reached the lowest risk at approximately 2.9 µIU/mL and then increased thereafter. Compared with patients with Q3 TSH levels, those with Q1, Q2, and Q4 TSH levels had a significantly higher risk of all-cause 30-day mortality (Q1: hazard ratio, 1.28; 95% CI, 1.06-1.54; Q2: hazard ratio, 1.22; 95% CI, 1.01-1.48; Q4: hazard ratio, 1.25; 95% CI, 1.04-1.50). For all-cause 90-day mortality, only the Q4 group had a significantly higher mortality risk than the Q3 group (hazard ratio, 1.24; 95% CI, 1.07-1.44). In subgroup analyses, we found that Q1 TSH levels were associated with higher mortality risk in men and older (≥65 years) patients, while Q4 TSH had a greater risk in men and younger (<65 years) patients. Conclusions: TSH was significantly associated with all-cause 7-, 30-, and 90-day mortality in critically ill patients after admission to the ICU. TSH may serve as a valuable biomarker for risk stratification in critically ill patients.

RESUMEN

Background: Oral health problems seriously affect the quality of life of older adults. It is of great significance to investigate the statuses of oral health in older adults. The study aimed to analyze the current status, hotspots and frontiers of global oral health research in older adults through bibliometrics to provide references and guidance for future research in this field. Methods: Literature on oral health in older adults from 2013 to 2023 was retrieved from the Web of Science Core Collection (WoSCC) database. CiteSpace 6.2.R4 was used for bibliometric and visual analysis, including journal and co-cited journal, country/region, institution, author, co-cited references, and keyword analysis. Results: A total of 1430 publications related to oral health in older adults were included. The number of publications has gradually increased over the past decade. The most widely published and cited journal was Gerodontology. The most prominent contribution came from the United States of America, and the University of London and Hirohiko Hirano were the most prolific institution and author, respectively. The current research hotspots were summarized as oral hygiene interventions, oral health-related quality of life and oral health issues in older adults. Cohort studies of oral health, the relationship between oral health and frailty, and the correlation between oral health and nutritional status may be emerging research trends. Conclusions: This study systematically analyzed the hotspots and frontiers of oral health in older adults and called for increased collaboration among countries, institutions, and authors. In addition, oral hygiene interventions for older adults, oral health-related quality of life, oral health issues, cohort studies of oral health, and the relationship between oral health and frailty or nutritional status may be the focus of future research.

RESUMEN

Herein, we disclosed a highly chemoselective synthesis of quinoline-2-one and quinoline-2-thione derivatives using EtOS2K as the C1 source. Quinoline-2-one derivatives were synthesized selectively with NaCl as a catalyst in the solvent DMSO/H2O, while quinoline-2-thione derivatives were produced without the need for any catalyst in an environmentally friendly solvent EtOH/H2O. The reaction conditions were mild and had good functional group tolerance.

RESUMEN

BACKGROUND: High technical thresholds, long operative times, and the need for expensive and specialized equipment impede the widespread adoption of endodontic microsurgery in many developing countries. This study aimed to compare the effects of a simplified, cost-effective, and time-efficient surgical approach involving orthograde obturation using biological ceramic material greater than 6 mm combined with apicoectomy for single-rooted teeth with short lengths with those of the conventional and current standard methods. MATERIALS AND METHODS: Forty-five premolars equally categorized into three groups: conventional surgery group, standard surgery group, and modified surgery group. A µCT scan was used to calculate the volume of voids. A micro-leakage test and scanning electron microscope (SEM) were performed to assess the sealing effect. Additionally, four cases of chronic periapical periodontitis in the anterior region were selected, and the patients received either the modified approach or the standard surgery for endodontic microsurgery. RESULTS: The volumes of voids in the apical 0-3 mm of the modified group and the standard group were comparable. The micro-leakage test and SEM examination demonstrated closely bonded fillings in the dentinal walls in both the modified surgery group and standard surgery group. The outcomes of the preliminary application of this modified procedure on patients were successful at the time of the follow-up cutoff. CONCLUSIONS: The modified surgery group exhibited similar root canal filling and apical sealing abilities with the standard procedure for single-rooted teeth with short lengths (< 20 mm). The preliminary application of this modified surgical procedure achieved favorable results.

Asunto(s)

RESUMEN

BACKGROUND: Frailty contributes to adverse outcomes in older adults and places a heavy burden on healthcare resources. Dysphagia is associated with frailty, but the mechanisms by which dysphagia affects frailty in older adults are unclear. This study aimed to investigate a serial mediating effect of self-perceived oral health and self-reported nutritional status in the relationship between dysphagia and frailty among hospitalized older patients in China. METHODS: This cross-sectional study included 1200 patients aged ≥ 65 years in the Department of Geriatrics, Shaanxi Provincial People's Hospital. A structured face-to-face interview was used to survey the following questionnaires: General Information Questionnaire, Tilburg Frailty Indicators (TFI), Eating Assessment Tool-10 (EAT-10), 30mL Water Swallow Test (WST), Geriatric Oral Health Assessment Index (GOHAI), and Short-Form Mini-Nutritional Assessment (MNA-SF). A total of 980 participants with complete data were included in the analysis. Statistical analysis was performed using SPSS 26.0 and Amos 28.0 software. Spearman's correlation analysis was used for correlation analysis of study variables. The results of the multivariate linear regression analysis for frailty were used as covariates in the mediation analysis, and the structural equation model (SEM) was used to analyze the mediating effects among the study variables. RESULTS: Dysphagia, self-perceived oral health, self-reported nutritional status, and frailty were significantly correlated (P<0.001). Dysphagia was found to directly affect frailty (ß = 0.161, 95%CI = 0.089 to 0.235) and through three significant mediation pathways: (1) the path through self-perceived oral health (ß = 0.169, 95%CI = 0.120 to 0.221), accounting for 36.98% of the total effect; (2) the path through self-reported nutritional status (ß = 0.050, 95%CI = 0.023 to 0.082), accounting for 10.94% of the total effect; (3) the path through self-perceived oral health and self-reported nutritional status (ß = 0.077, 95%CI = 0.058 to 0.102), accounting for 16.85% of the total effect. The total mediation effect was 64.77%. CONCLUSIONS: This study indicated that dysphagia was significantly associated with frailty. Self-perceived oral health and self-reported nutritional status were serial mediators of this relationship. Improving the oral health and nutritional status of hospitalized older patients may prevent or delay the frailty caused by dysphagia.

Asunto(s)

RESUMEN

A novel Gram-stain-negative strain, designated S37H4T, was isolated from an intertidal surface sediment sample collected from Zhanjiang City, Guangdong province, south PR China. Cells of the strain were aerobic, non-flagellated, long rod-shaped and motile by gliding. S37H4T could grow at 4-40 °C, pH 7.0-8.5 and in 2.0-15.0 % NaCl, with optimal growth at 25-30 °C, pH 7.5 and 9.0 % NaCl, respectively. S37H4T was capable of nitrite removal under high-salt conditions, and there were three denitrification genes, nirK, norB and nosZ, in its genome. The results of phylogenetic analyses based on the 16S rRNA gene and genome sequences indicated that S37H4T represented a member of the genus Marivirga and formed a subclade with Marivirga lumbricoides JLT2000T. S37H4T showed the highest 16S rRNA sequence similarity to M. lumbricoides JLT2000T (98.3 %) and less than 97.0 % similarity with other type strains of species of the genus Marivirga. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between S37H4T and the reference type strains of species of the genus Marivirga were 70.7-74.3 % and 18.2-19.2 %, respectively. The major fatty acids of S37H4T were iso-C15 : 0, iso-C15 : 1G, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The major respiratory quinone of this novel strain was MK-7, and the predominant polar lipids were identified as phosphatidylethanolamine, an unidentified aminolipid, an unidentified phospholipid and three unidentified lipids. The results of analyses of phylogenetic, genomic, physiological and biochemical characteristics indicated that S37H4T represented a novel species of the genus Marivirga, for which the name Marivirga aurantiaca sp. nov. is proposed. The type strain is S37H4T (= GDMCC 1.1866T = KACC 21922T).

Asunto(s)

RESUMEN

Background: Liver metastasis is one of the primary causes of death for the patients with pancreatic neuroendocrine tumors (PNETs). However, no curative therapy has been developed so far. Methods: The anti-tumor efficacy of a genetically engineered tumor-targeting Salmonella typhimurium YB1 was evaluated on a non-functional INR1G9 liver metastasis model. Differential inflammatory factors were screened by Cytometric Bead Array. Antibody depletion assay and liver-targeted AAV2/8 expression vector were used for functional evaluation of the differential inflammatory factors. Results: We demonstrated that YB1 showed significant anti-tumor efficacy as a monotherapy. Since YB1 cannot infect INR1G9 cells, its anti-tumor effect was possibly due to the modulation of the tumor immune microenvironment. Two inflammatory factors IFNγ and CCL2 were elevated in the liver after YB1 administration, but only IFNγ was found to be responsible for the anti-tumor effect. Liver-targeted expression of IFNγ caused the activation of macrophages and NK cells, and reproduced the therapeutic effect of YB1 on liver metastasis. Conclusion: We demonstrated that YB1 may exhibit anti-tumor effect mainly based on IFNγ induction. Targeted IFNγ therapy can replace YB1 for treating liver metastasis of PNETs.

RESUMEN

BACKGROUND: The incidence of type 2 diabetes is rapidly increasing worldwide. Studies have shown that it is also associated with cancer-related morbidities. Early detection of cancer in patients with type 2 diabetes is crucial. OBJECTIVE: This study aimed to construct a model to predict cancer risk in patients with type 2 diabetes. METHODS: This study collected clinical data from a total of 5198 patients. A cancer risk prediction model was established by analyzing 261 items from routine laboratory tests. We screened 107 risk factors from 261 clinical tests based on the importance of the characteristic variables, significance of differences between groups (P< 0.05), and minimum description length algorithm. RESULTS: Compared with 16 machine learning classifiers, five classifiers based on the decision tree algorithm (CatBoost, light gradient boosting, random forest, XGBoost, and gradient boosting) had an area under the receiver operating characteristic curve (AUC) of > 0.80. The AUC for CatBoost was 0.852 (sensitivity: 79.6%; specificity: 83.2%). CONCLUSION: The constructed model can predict the risk of cancer in patients with type 2 diabetes based on tumor biomarkers and routine tests using machine learning algorithms. This is helpful for early cancer risk screening and prevention to improve patient outcomes.

RESUMEN

BACKGROUND: Glioblastoma is the most common type of glioma with a high incidence and poor prognosis, and effective medical treatment remains challenging. Pseudouridine (Ψ) is the first post-transcriptional modification discovered and one of the most abundant modifications to RNA. However, the prognostic value of Ψ-related lncRNAs (ΨrLs) for glioma patients has never been systematically evaluated. This study aims to construct a risk model based on ΨrLs signature and to validate the predictive efficiency of the model. METHOD: Transcriptomic data, genomic data, and relevant clinical data of glioma patients were extracted from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). ΨrLs with significant correlation with Ψ-related genes were identified, and univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were used to further select biomarkers and construct a ΨrLs signature risk model. Then, the expression of lncRNAs of ΨrLs signature in multiple glioma cell lines was detected by qPCR. Further, ROC analysis, stratification analysis, correlation analysis, survival analysis, nomogram, enrichment analysis, immune infiltration analysis, chemoradiotherapy sensitivity analysis, somatic mutation, and recurrent copy number variation (CNV) analysis were used to validate the predictive efficiency of ΨrLs signature in TCGA and CGGA datasets. RESULTS: A four-lncRNA ΨrLs signature (DNAJC27-AS1, GDNF-AS1, ZBTB20-AS4, and DNMBP-AS1) risk model was constructed. By ROC analysis, stratified analysis, correlation analysis, survival analysis, and nomogram, the signature showed satisfactory predictive efficiency. Functional enrichment analysis revealed the differences in immune-related biological processes between high- and low-risk groups. Immune infiltration analysis showed that the high-risk group had lower tumor purity and higher stromal, immune and ESTIMATE scores. Mitoxantrone was identified as effective drug for low-risk group of glioma patients. Key genes in glioma development, including IDH1, EGFR, PTEN, etc., were differentially mutated between risk groups. The main recurrent CNVs in low-risk groups were 19q13.42 deletion and 7q34 amplification; 10q23.31 deletion and 12q14.1 in the high-risk group. CONCLUSIONS: Our study identified a four-lncRNA ΨrLs signature that effectively predicts the prognosis of glioma patients and may serve as a diagnostic tool. Risk scores of glioma patients generated by the signature is associated with immune-related biological processes and chemoradiotherapy sensitivity. These findings may inform the development of more targeted and effective therapies for glioma patients.

RESUMEN

We report here a homo-Mannich reaction of cyclopropanol with an iminium ion, generated by an asymmetric allylic dearomatization of indole, to construct a tricyclic hydrocarbazole core, which is shared by a variety of monoterpenoid indole alkaloids across families. Through this approach, an all-carbon quaternary stereogenic center as well as an allyl and a ketone group were installed. Using this functionalized hydrocarbazole as the structural platform, D ring and E rings of different sizes (i.e., five-, six-, and seven-membered) were successively or simultaneously assembled, leading to a collective asymmetric synthesis of seven alkaloids belonging to the ibophyllidine, Aspidosperma, Kopsia, and Melodinus alkaloid families.

Asunto(s)