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PURPOSE: This study explored the association between self-reported diabetes mellitus, glycaemic control, measured by glycohaemoglobin (HbA1c) levels, and untreated root caries among U.S. adults, exploring the impact of diabetes status and glycaemic control levels on root caries risk. MATERIALS AND METHODS: Analysing data from the National Health and Nutrition Examination Survey (NHANES) 2015 to 2018, we included 7490 participants aged 30 and above. We investigated the association between self-reported diabetes, glycaemic control, and untreated root caries, adjusting for demographic and health-related variables. Weighted logistic regression models estimated untreated root caries odds by diabetes status and HbA1c cutoffs (6.5-9%), adjusting for demographics, health behaviours, BMI, diet, oral health factors. RESULTS: A significant association was found between higher HbA1c levels and an increased risk of untreated root caries (odds ratio [OR]: 1.11, 95% CI: 1.01-1.22, p < .05). Self-reported diabetes was not significantly linked to untreated root caries after adjusting for HbA1c and other factors. Glycaemic control thresholds (HbA1c ≥8%) among diabetic participants were associated with higher odds of untreated root caries. CONCLUSIONS: Poorly controlled diabetes appears to be associated with untreated root caries among U.S. adults. This highlights the greater impact of glycaemic control versus self-reported diabetes on dental health and the need for regular oral screenings for patients with poor glycaemic control.
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Pancreatic ductal adenocarcinoma (PDAC) features substantial matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, the complex interplay between these traits and their impact on tumor advancement remains inadequately explored. Here, we integrated clinical, cellular, and bioinformatics approaches to explore the connection between matrix stiffness and the Warburg effect in PDAC, identifying CLIC1 as a key mediator. Elevated CLIC1 expression, induced by matrix stiffness through Wnt/ß-catenin/TCF4 signaling, signifies poorer prognostic outcomes in PDAC. Functionally, CLIC1 serves as a catalyst for glycolytic metabolism, propelling tumor proliferation. Mechanistically, CLIC1 fortifies HIF1α stability by curbing hydroxylation via reactive oxygen species (ROS). Collectively, PDAC cells elevate CLIC1 levels in a matrix-stiffness-responsive manner, bolstering the Warburg effect to drive tumor growth via ROS/HIF1α signaling. Our insights highlight opportunities for targeted therapies that concurrently address matrix properties and metabolic rewiring, with CLIC1 emerging as a promising intervention point.
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Recent evidence suggests that necroptosis may contribute to the development of kidney injury. Renalase is a novel secretory protein that exerts potent prosurvival and anti-inflammatory effects. We hypothesized that renalase could protect the kidney from salt-induced injury by modulating necroptosis. High salt and renalase treatments were administered to Dahl salt-sensitive (SS) rats, renalase knockout (KO) mice, and HK-2 cells. Furthermore, a cohort of 514 eligible participants was utilized to investigate the association between single nucleotide polymorphisms (SNPs) in the genes RIPK1, RIPK3, and MLKL, and the risk of subclinical renal damage (SRD) over 14 years. A high-salt diet significantly increased the expression of key components of necroptosis, namely RIPK1, RIPK3, and MLKL, as well as the release of inflammatory factors in SS rats. Treatment with recombinant renalase reduced both necroptosis and inflammation. In renalase KO mice, salt-induced kidney injury was more severe than in wild-type mice, but supplementation with renalase attenuated the kidney injury. In vitro experiments with HK-2 cells revealed high salt increased necroptosis and inflammation. Renalase exhibited a dose-dependent decrease in salt-induced necroptosis, and this cytoprotective effect was negated by the knockdown of PMCA4b, which is the receptor of renalase. Furthermore, the cohort study showed that SNP rs3736724 in RIPK1 and rs11640974 in MLKL were significantly associated with the risk of SRD over 14 years. Our analysis shows that necroptosis plays a significant role in the development of salt-induced kidney injury and that renalase confers its cytoprotective effects by inhibiting necroptosis and inflammation.
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BACKGROUND: Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. METHODS: A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. RESULTS: Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. CONCLUSIONS: Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.
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Dieta , Fragilidad , Humanos , Anciano , Femenino , Masculino , Fragilidad/epidemiología , China/epidemiología , Dieta/estadística & datos numéricos , Dieta/métodos , Estudios de Cohortes , Anciano Frágil/estadística & datos numéricos , Estudios Longitudinales , Anciano de 80 o más Años , Pueblo Asiatico/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Pueblos del Este de AsiaRESUMEN
PM2.5 pollution remains prominent in autumn, whereas O3 pollution gradually manifests in summer. To understand the dual high characteristics and meteorological effects of PM2.5 and O3 in the summer and early autumn of 2021 in the Beijing-Tianjin-Hebei and surrounding areas, the spatiotemporal distribution characteristics of PM2.5 and O3 concentrations, as well as meteorological conditions, subtropical high index, and weather situation in the Beijing-Tianjin-Hebei and surrounding areas were analyzed. The results showed that PM2.5 concentration and DPO3 ï¼O3 daily maximum 8h mean minus O3 concentration at 06ï¼00ï¼ from June to September 2021 decreased compared with those in the same period in 2020 and 2022, and high concentrations were mainly occurring in June. The overall PM2.5 concentration and DPO3 showed a gradual decrease from the middle to the north and south, with synchronous spatiotemporal changes. The hourly value of PM2.5 concentration presented a multimodal distribution, reaching the peak at 07ï¼00-10ï¼00 and 22ï¼00-24ï¼00. O3 concentration showed an opposite trend of change with PM2.5 concentration, reaching their peak from 14ï¼00-16ï¼00. When DPO3 and the concentration of PM2.5 were high, the characteristics of near-surface meteorological elements were characterized by temperatures ranging from 24.0-28.0â, relative humidity concentrated at 58.4%-76.3%, and wind speeds ranging from 1.5-3 m·s-1. There was a high lag correlation between the subtropical high index and DPO3. When the subtropical high was farther and stronger from the Beijing-Tianjin-Hebei and surrounding areas, DPO3 was higher. The major weather patterns with both high PM2.5 and O3 concentrations in the study area were near surface low-pressure front, high-pressure type, and frontal type. The high altitude was controlled by high-pressure ridges, and the subtropical high ridge line was stable between 21°-28°N.
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The field of nickel catalysis has witnessed remarkable growth in recent years. However, the use of nickel catalysts in enantioselective C-H activation remains a daunting challenge because of their variable oxidation states, intricate coordination chemistry, and unpredictable reactivity patterns. Herein, we report an enantioselective C-H activation reaction catalyzed by commercially available and air-stable nickel(II) catalyst. Readily available and simple (S)-BINOL is used as a chiral ligand. This operationally simple protocol enables the synthesis of planar chiral metallocenes in high yields with excellent enantioselectivity through desymmetrization and kinetic resolution. Air-stable planar chiral nickelacycle intermediates are first synthesized via enantioselective C-H nickelation and shown to be possible intermediates of the reaction. Deuterium-labeling studies, alongside the characterization and transformation of chiral nickel(II) species, suggest that C-H cleavage is the enantio-determining step. Moreover, the large-scale synthesis and diverse synthetic transformations underscore the practicality of this protocol.
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OBJECTIVES: The polymer polyetheretherketone (PEEK) is gradually being used in dental restorations because of its excellent mechanical properties, chemical resistance, fatigue resistance, thermal stability, radiation translucency and good biocompatibility. To process PEEK dentures with lower surface roughness as quickly as possible, the non-dominated sorting genetic algorithm-II (NSGA-II) integrated genetic algorithm back propagation (GABP) neural network was proposed, which can adjust the combination of process parameters for milling PEEK dentures. METHODS: The PEEK machining was conducted using a four-axis dental milling machine at different process parameters. The surface roughness of PEEK dentures was characterized using surface roughness profiler and scanning electron microscopy (SEM). The optimum machining performance of milling PEEK dentures was investigated using a multi-objective optimization model named as NSGA-II integrated GABP neural network algorithm. The surface roughness (Ra) and material removal rate (MRR) were used as optimization objectives. RESULTS: The multi-objective optimization model effectively improved surface roughness and machining efficiency for milling PEEK dentures. The validation experiments showed that the surface roughness of all PEEK dentures was less than 0.2µm, which was within the range of surface roughness set in this paper. The GABP surface roughness prediction model had an average error of 6 %. For the same surface roughness value, the optimized milling parameters all had a greater material removal rate. SIGNIFICANCE: The research results can improve current PEEK denture CAD/CAM technology by providing appropriate milling parameters using NSGA-II integrated GABP algorithm.
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OBJECTIVE: To explore safety differences and perform a gender-based analysis of adverse events related to gemcitabine and Bacillus Calmette-Guérin (BCG) vaccine using the U.S. FDA Adverse Event Reporting System (FAERS) database. METHODS: Using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods, adverse events associated with gemcitabine and BCG were mined from FAERS database reports spanning from Q1 2004 to Q3 2023. RESULTS: The study extracted 37,855 reports with gemcitabine and 5,455 reports with BCG as the primary suspected drugs. Adverse events were more prevalent in males (male-to-female ratio: gemcitabine 1.10, BCG 4.25). Differences in high-frequency adverse events among the top 20 signals were detected for both drugs. Both drugs affected similar organ systems, including potential pulmonary, ocular, and renal toxicity, with gemcitabine showing a broader range of adverse events. Gender analysis revealed fewer adverse reactions to gemcitabine in females, while males had fewer adverse reactions to BCG. CONCLUSION: Differences in high-frequency adverse events between gemcitabine and BCG, including some not listed on drug labels, were observed. Both drugs affect similar organ systems, with gemcitabine showing a broader range of adverse events. Gender differences in adverse events were notable.
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Hepatocellular carcinoma (HCC) is the most common type of liver cancer, characterized by a high morbidity rate. Long non-coding RNAs (lncRNAs) play an important role in regulating various cellular processes and diseases, including cancer. However, their specific roles and mechanisms in HCC are not fully understood. This study used a multi-cohort design to investigate necroptosis-related lncRNAs (NRLs) in patients with HCC. We curated a list of 1095 NRLs and 838 genes showing differential expression between tumor and normal tissues. Among them, we found 105 NRLs closely associated with the prognosis of HCC patients. The 10 lncRNAs (AC100803.3, AC027237.2, AL158166.1, LINC02870, AC026412.3, LINC02159, AC027097.1, AC139887.4, AC007405.1, AL023583.1) generated by LASSO-Cox regression analysis were used to create a prognostic risk model for HCC and group patients into groups based on risk. The KEGG analysis revealed distinct pathway enrichments in high-risk (H-R) and low-risk (L-R) subgroups. According to GO analysis, this study identified 230 differentially expressed genes (DEGs) that were significantly enriched in specific biological processes. Comparison of immune checkpoint-related genes (MCPGs) between H-R and L-R patients revealed significant differences. Moreover, we established a correlation between the risk scores of patients with liver cancer and their sensitivity to 16 chemotherapeutic agents. Employing protein-protein interaction (PPI) analysis, we identified 10 hub genes that potentially regulate the molecular networks involved in HCC development. This study is a pioneering effort to investigate the roles of NRLs in HCC. It opens a new avenue for potential targeted therapies and provides insights into the molecular mechanisms of HCC.
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Background and objectives: Lactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease. Materials and methods: This study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane's Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods. Results: By employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study. Conclusion: This study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.
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OBJECTIVE: The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms. METHODS: Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors. RESULTS: A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important "root" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types. CONCLUSION: This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms.
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OBJECTIVE: Bibliometrics was employed in this study to determine the research trends in the worldwide application of 3D printing technology to treat bone tumors over the previous 10 years. METHODS: Published from 2013 to 2022, the papers related to bone tumors treated with 3D printing were located in Web of Science Core Collection (WoSCC), PubMed, and Scopus. The screened articles were included in this bibliometric study. From these papers in WoSCC, information on annual publications, journals, keywords, countries, authors, institutions, and cited references were extracted and visualized with CiteSpace (version 6.1.R6) software to investigate the state of bone tumor treatment using 3D printing as well as research hotspots. The Carrot2 online visualization tool and Vosviewer software (version 1.6.20) were employed to visualize the publications from PubMed and Scopus, respectively, in order to ascertain the most popular research topics from both databases. RESULTS: A total of 606, 233, and 364 publications were obtained from WoSCC, PubMed, and Scopus, respectively, between the years 2013 and 2022. In WoSCC, the peak number of publications was found in 2021, with 145 publications published. Acta Biomaterialia (11 publications) and World Neurosurgery (10 publications) were the most prolific journals, and Biomaterials was the journal cited the most (244 times). Yong Zhou was the most productive author with 14 publications, while Kwok-Chuen Wong (69 citations) and William F Enneking, (69 citations) possessed the most citations. The country with the largest quantity of publications was China (207). Among all institutions, Shanghai Jiao Tong University produced the most publications (29). Rapid prototyping was the keyword with the strongest citation burst (4.73). 'Reconstruction', 'surgery', 'resection', and 'design' caught the significant attention of researchers. 3D-printed materials, pelvic reconstruction, mandibular reconstruction, computer-assisted surgical techniques, photothermal therapy, and in vitro experiments were recognized as hot subjects and trends in current research. The most frequently occurring topics in Scopus are not significantly different from those found in WoSCC. The most prevalent research areas in PubMed encompass implant, patient-specific, bioceramic, models, and pelvic.
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BACKGROUND AND AIMS: Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC. METHODS: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues, peritoneal metastases, and adjacent-normal peritoneal tissues. We employed whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM. RESULTS: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared to liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis. CONCLUSION: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes.
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OBJECTIVE: Meniscus progenitor cells (MPCs) have been identified as promising candidates for meniscus regeneration, and it is crucial for us to understand meniscus injury repair mechanism at the cellular level. In this study, we investigate the biological properties of MPCs isolated from different species using the differential adhesion to fibronectin (DAF) technique. We aim to characterize MPCs in different species and evaluate the feasibility of these models for future meniscal investigation. DESIGN: MPCs were isolated from freshly digested meniscus from rat, rabbit, goat, and human cells using DAF. Biological properties, including proliferation, colony-forming, multilineage differentiation, and migration abilities, were compared in MPCs and their corresponding mixed meniscus cell (MCs) population in each species. RESULTS: MPCs were successfully isolated by the DAF technique in all species. Rat MPCs appeared cobblestone-like, rabbit MPCs were more polygonal, goat MPCs had a spindle-shaped morphology, human MPCs appear more fibroblast-like. Compared with MCs, isolated MPCs showed progenitor cell characteristics, including multilineage differentiation ability and MSC (mesenchymal stem cells) markers (CD166, CD90, CD44, Stro-1) expression. They also highly expressed fibronectin receptors CD49e and CD49c. MPCs also showed greater proliferation capacity and retained colony-forming ability. Except for goat MPCs showed greater migration abilities than MCs, no significant differences were found in the migration ability between MPCs and MCs in other species. CONCLUSION: Our study shows that DAF is an effective method for isolating MPCs from rat, rabbit, goat, and human. MPCs in these species demonstrated similar characteristics, including greater proliferation ability and better chondrogenic potential.
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PURPOSE: Shaping and assembling contemporary external fixators rapidly for the severe mandibular fractures remains a challenge, especially in emergency circumstance. We designed a novel external fixator that incorporates universal joints to provide the stabilization for mandibular comminuted fractures. This study aims to confirm the efficacy of this novel external fixator through biomechanical tests in vitro and animal experiments. METHODS: In vitro biomechanical tests were conducted using 6 fresh canine with mandibular defect to simulate critical comminuted fractures. Three mandibles were stabilized by the novel external fixator and other mandibles were fixed by 2.5 mm reconstruction plates. All fixed mandibles were subjected to loads of 350 N on the anterior regions of teeth and 550 N on the first molar of the unaffected side. The stability was evaluated based on the maximum displacement and the slope of the load-displacement curve. In animal experiments, 9 beagles with comminuted mandibular fractures were divided into 3 groups, which were treated with novel external fixation, reconstruction plate, and dental arch bar, respectively. The general observation, the changes in animals' weight, and the surgical duration were recorded and compared among 3 groups. The CT scans were performed at various intervals of 0 day (immediately after the surgery), 3 days, 7 days, 14 days, 21 days, and 28 days to analyze the displacement of feature points on the canine mandible and situation of fracture healing at 28 days. The statistical significance was assessed by the two-way analysis of variance test followed by the Bonferroni test, enabling multiple comparisons for all tests using GraphPad Prism10.1.0 (GraphPad Inc, USA). RESULTS: The outcomes of the biomechanical tests indicated that no statistically significant differences were found in terms of the maximum displacement (p = 0.496, 0.079) and the slope of load displacement curves (p = 0.374, 0.349) under 2 load modes between the external and internal fixation groups. The animal experiment data showed that there were minor displacements of feature points between the external and internal fixation groups without statistic difference, while the arch bar group demonstrated inferior stability. The CT analysis revealed that the best fracture healing happened in the internal fixation group, followed by the external fixation and arch baring at 28 days after fixation. The external fixation group had the shortest fixation duration (25.67 ± 3.79) min compared to internal fixation ((70.67 ± 4.51) min, p < 0.001) and arch baring ((42.00 ± 3.00) min, p = 0.046). CONCLUSION: The conclusion of this study highlighted the efficacy and reliability of this novel external fixator in managing mandibular fractures rapidly, offering a viable option for the initial stabilization of comminuted mandibular fractures in the setting of emergency rescue.
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BACKGROUND: Atherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD). However, few studies have investigated association between AIP and all-cause mortality and specific-mortality in the general population. METHODS: This study included data from 14,063 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included all-cause mortality and specific-mortality. Survey-weighted cox regressions were performed to evaluate the relation between AIP and all-cause mortality and specific-mortality. Weighted restricted cubic spline was conducted to examin the non-linear relationship. RESULTS: During 10 years of follow-up, we documented 2,077, 262, 854, and 476 cases of all-cause mortality, diabetes mortality, CVD mortality and cancer mortality, respectively. After adjustment for potential confounders, we found that atherogenic index of plasma (AIP) was significantly associated with an increased risk of diabetes mortality when comparing the highest to the lowest quantile of AIP in female (p for trend = 0.001) or participants older than 65 years (p for trend = 0.002). AIP was not significantly associated with all-cause mortality, CVD mortality and cancer mortality (p > 0.05). Moreover, a non-linear association was observed between AIP and all-cause mortality in a U-shape (p for non-linear = 0.0011), while a linear relationship was observed with diabetes mortality and non-diabetes mortality (p for linear < 0.0001). CONCLUSIONS: In this study, there is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. Besides, a higher AIP was significantly associated with an increased risk of diabetes mortality, which only found in women older than 65 years. AIP was associated with all-cause mortality in a U-shape. This association could be explained by the finding that higher AIP predicted a higher risk of death from diabetes, and that lower AIP predicted a higher risk of death from non-diabetes causes.
We used a large national database and a prospective cohort study with a long follow-up period. Higher AIP was significantly associated with an increased risk of diabetes mortality, only in women older than 65 years. There is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. AIP was associated with all-cause mortality in a U-shape. This finding suggest that controlling AIP levels may have a positive effect on reducing diabetes mortality.
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Aterosclerosis , Biomarcadores , Causas de Muerte , HDL-Colesterol , Diabetes Mellitus , Triglicéridos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Medición de Riesgo , Biomarcadores/sangre , Aterosclerosis/mortalidad , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Factores de Riesgo , Factores de Tiempo , Adulto , Diabetes Mellitus/mortalidad , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , HDL-Colesterol/sangre , Estados Unidos/epidemiología , Triglicéridos/sangre , Pronóstico , Neoplasias/mortalidad , Neoplasias/sangre , Neoplasias/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnósticoRESUMEN
Cyclin-dependent kinases (CDKs) are overexpressed in tumor cells, and their aberrant activation can promote the progression of non-small-cell lung cancer (NSCLC). We utilized structure-based virtual screening and experimental validation to screen for potential CDKs antagonists among TargetMol natural products. Molecular docking and molecular dynamics simulation results indicate that Dolastatin 10 exhibits strong interactions with multiple subtypes of CDKs (CDK1, CDK2, CDK3, CDK4, and CDK6), forming stable CDKs-Dolastatin 10 complex compounds. Furthermore, in vitro experiments demonstrate that Dolastatin 10 significantly inhibits the viability, migration, and invasion of H1299 cells in a concentration-dependent manner, arresting the cell cycle at the G2/M phase by inducing cell senescence. These findings suggest that Dolastatin 10 may serve as a potential CDKs antagonist deserving further investigation.
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The rupture of atherosclerotic plaques remains one of the leading causes of morbidity and mortality worldwide. The plaques have certain pathological characteristics including a fibrous cap, inflammation, and extensive lipid deposition in a lipid core. Various invasive and noninvasive imaging techniques can interrogate structural aspects of atheroma; however, the composition of the lipid core in coronary atherosclerosis and plaques cannot be accurately detected. Fiber-optic Raman spectroscopy has the capability of in vivo rapid and accurate biomarker detection as an emerging omics technology. Previous studies demonstrated that an intravascular Raman spectroscopic technique may assess and manage the therapeutic and medication strategies intraoperatively. The Raman spectral information identified plaque depositions consisting of lipids, triglycerides, and cholesterol esters as the major components by comparing normal region and early plaque formation region with histology. By focusing on the composition of plaques, we could identify the subgroups of plaques accurately and rapidly by Raman spectroscopy. Collectively, this fiber-optic Raman spectroscopy opens up new opportunities for coronary atherosclerosis and plaque detection, which would assist optimal surgical strategy and instant postoperative decision-making. In this paper, we will review the advancement of label-free fiber-optic Raman probe spectroscopy and its applications of coronary atherosclerosis and atherosclerotic plaque detection.
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We present a method for modification of silicon nitride (Si3N4) waveguide resonators using femtosecond laser annealing. The quality (Q) factor of the waveguide resonators can be improved by approximately 1.3 times after annealing. Notably, waveguides that originally had a high Q value maintained their quality after the annealing process. However, those with a lower initial Q value experienced a noticeable improvement post-annealing. To characterize the annealing effect, the surface morphologies of Si3N4 films, both pre- and post-annealing, were analyzed using atomic force microscopy. The findings suggest a potential enhancement in surface refinement. Furthermore, Raman spectroscopy confirmed that the Si3N4 film's composition remains largely consistent with its original state within the annealing power range of 0.6-1.6 W. This research underscores the potential of femtosecond laser annealing as an efficient, cost-effective, and localized technique for fabricating low-loss integrated photonics.