RESUMEN
Osteoarthritis (OA), a joint disease associated with inflammatory processes, contributes to joint destruction. Esculin (ESC) extracted from the stem bark of Fraxinus rhynchophylla Hance has been shown to possess anti-inflammatory properties. In this study, we investigated the effect of ESC on chondrocytes treated with IL-1ß and its molecular mechanism. The importance and potential mechanism of ESC in the progression of OA were evaluated. The viability of chondrocytes after exposure to ESC was examined through the CCK-8 assays. The cells were then subjected to quantitative polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assay (ELISA) techniques to analyze the degradation of the extracellular matrix (ECM) and occurrence of inflammation. The NF-κB mechanism was evaluated by western blot analysis, immunofluorescence (IF), and luciferase reporter assay. Molecular docking was performed to allow for predictions on proteins that interact with ESC. Moreover, the significance of Sirt1 was explored through a knockdown experiment based on siRNA. Micro-computed tomography (CT), H&E, Safranin O-Fast Green (S-O), and immunohistochemical analyses were carried out to assess the treatment efficacy of ESC on OA in destabilization of medial meniscus (DMM) models. ESC treatment effectively inhibited ECM degradation, modulated the levels of pro-inflammatory factors, and regulated the NF-κB signaling in chondrocytes exposed to IL-1ß. Mechanistically, we found that ESCs bound to Sirt1 to inhibit the activity of the NF-κB mechanism. Furthermore, ESC treatment suppressed OA progression in the DMM models. Our findings reveal that ESC ameliorates OA progression via modulating the Sirt1/NF-κB axis. This demonstrates that ESC has the potential to be applied in the treatment of OA.
RESUMEN
Conventional welding methods encounter significant challenges, including poor weldability, low joint strength, and the formation of brittle intermetallic compounds, primarily due to the substantial disparities in the physical and chemical properties of aluminum and iron. To mitigate these issues, the vaporizing foil actuator welding (VFAW) process has emerged as a highly promising solid-phase welding technology, particularly suitable for joining dissimilar metals with pronounced differences in properties, such as aluminum alloys and stainless steels. The present study provides an innovative quantitative analysis of the interfacial impact energy conversion mechanisms within the VFAW process. The analysis reveals that the energy responsible for accelerating the flyer workpiece comprises burst vaporization energy ( E d ) and continuous vaporization energy ( E p ), with E d identified as the primary energy source, contributing approximately 65-80% of the total energy required for acceleration. Further examination elucidates the mechanisms underlying heat generation and transfer during the interface collision. The investigation identifies the formation of an overheating zone at the interface, attributed to the combined effects of plastic deformation energy and adiabatic shear energy within the flyer workpiece. Consequently, the interface temperature can rise significantly, reaching up to 1394 K, with impact velocities as high as 925 m/s. The analyses contribute to establishing a theoretical foundation for understanding the interface bonding mechanisms characteristic of the vaporizing foil actuator welding method.
RESUMEN
Background: The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up. Methods: Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m2 twice daily on days 1-14 of each 21-day cycle) until disease progression or unacceptable toxicity. Secondary endpoints progression-free survival (PFS) and overall survival (OS) were updated, and post-hoc central nervous system (CNS)-PFS was analyzed. This study is registered with ClinicalTrials.gov (NCT03691051). Findings: As of February 2, 2023, the median follow-up duration was 30.9 months (interquartile range, 16.1-39.8). Median PFS was 10.9 months (95% confidence interval [CI], 7.6-14.6) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 35.9 months (95% CI, 24.4-not reached) in cohort A and 30.6 months (95% CI, 12.6-33.3) in cohort B. Median CNS-PFS was 13.6 months (95% CI, 9.0-15.8) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 34.1 months (95% CI, 21.7-not reached) for 14 patients with intracranial progression only in cohort A who restarted pyrotinib plus capecitabine after local radiotherapy. Interpretation: These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases. Funding: National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.
RESUMEN
OBJECTIVE: We aimed to explore the role of connexin26 (Cx26) and connexin30 (Cx30) in the cochlea in noise-induced permanent threshold shifts (PTS) and temporary threshold shift (TTS). STUDY DESIGN: Prospective, controlled. SETTING: Laboratory. METHODS: A mouse model of noise-induced PTS and TTS was constructed. Western blots were used to detect the expression of Cx26 and Cx30 in the cochlea. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the potential biological pathways. RESULTS: Both the expression of Cx26 and Cx30 showed a trend of first rising and then falling in noise-induced PTS. The expression of Cx26 increased greatly in the 24 hours noise exposure (P < .05) and reached the highest level in the 4 hours after noise exposure (P < .05), then decreased gradually and returned to the control level on the seventh day after the noise exposure, when compared with the control group. The expression of Cx30 showed a similar trend in noise-induced PTS. However, both the expression of Cx26 and Cx30 showed a trend of first falling and then rising in noise induced TTS. The expression of Cx26/Cx30 reached its lowest level in the 4 hours after noise exposure (P < .05), and then increased to the control level on the second day after noise exposure (P > .05), compared with the control group. The first KEGG and GO pathway may be related with oxidative phosphorylation. CONCLUSION: Cx26 and Cx30 may have an effect in noise induced PTS and TTS. Future studies are needed to confirm the results.
RESUMEN
BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n = 207; placebo: n = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n = 104; placebo: n = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02763566).
RESUMEN
Rheumatoid arthritis (RA) is marked by joint damage and inflammation, with B cells playing a key role by generating autoantibodies. This study shows that G protein-coupled receptor 40 (GPR40) deficiency in B cells leads to increased activation, proliferation, antibody production, germinal center formation, and class switch recombination. GPR40 regulates Plcγ2 phosphorylation and intracellular calcium flux downstream of the B cell receptor by binding to the Gαq protein. In GPR40-deficient mice, susceptibility to collagen-induced arthritis was higher. GPR40 agonists showed potential as therapeutic agents, and their reduced expression in patients with RA correlated with disease onset, suggesting GPR40 as a potential therapeutic target and diagnostic marker.
Asunto(s)
Artritis Reumatoide , Linfocitos B , Receptores Acoplados a Proteínas G , Animales , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Artritis Reumatoide/inmunología , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Ratones , Linfocitos B/metabolismo , Linfocitos B/inmunología , Artritis Experimental/inmunología , Artritis Experimental/patología , Artritis Experimental/metabolismo , Ratones Endogámicos C57BL , Masculino , Femenino , Ratones NoqueadosRESUMEN
BACKGROUND: Screen exposure, particularly recreational screen exposure, is an integral part of children's lives. However, little is known about how family factors influence children's excessive screen exposure, especially in the context of 69 million left-behind children experiencing parent-child separation in China. This study mainly concentrates on the correlation between parental migration, type of caregiver, depression and disciplinary practices of the caregiver and children's screen exposure, including average daily screen time (on weekdays or weekends) and screen content (recreational activities or learning activities). METHODS: For a cross-sectional study, we collected data of family basic features, parental migration status and children's screen use in the past week from caregivers of 1,592 children aged 1-66 months in Anhui province. Children were classified into left-behind children (LBC), previously left-behind children (PLBC) and never left-behind children (NLBC) based on their parental migration. Multiple linear regression and binary logistic regression were used to identified the association between family factors and children's screen exposure. RESULTS: Overall, PLBC had higher rates of screen exposure, as well as higher average daily exposure times, than NLBC and LBC. The results of logistic regression showed that PLBC had a higher likelihood of excessive screen use compared to NLBC (60 min/day, OR = 1.40, p < 0.05; 120 min/day, OR = 1.76, p < 0.05). The higher the score of disciplinary practices, the less time children spent on screens for entertainment (B = -3.37, p < 0.01). CONCLUSIONS: Our findings provide insights into the risks of children's screen exposure in different contexts of parental migration. The study emphasizes the urgent need to pay attention to PLBC's screen use and to strengthen caregivers' discipline and supervision over children's screen exposure.
Asunto(s)
Población Rural , Tiempo de Pantalla , Humanos , China , Femenino , Masculino , Estudios Transversales , Preescolar , Lactante , Población Rural/estadística & datos numéricos , Padres/psicología , Separación FamiliarRESUMEN
This study compared the physical properties and mechanical strength development of PCBAs with water, sealed, standard, and open ambient air curing over 28 days to find a suitable curing method for the production of phosphogypsum-based cold-bonded aggregates. The types and relative amounts of hydration products, microstructural morphology and pore structure parameters were characterized utilizing XRD, TGA, FTIR, SEM and nitrogen adsorption methods. According to the results, water curing leads to rapid increases in single aggregate strength, reaching 5.26 MPa at 7 d. The standard curing condition improved the 28 d mechanical strength of the aggregates by 19.3% over others by promoting the generation of hydration products and the transformation of the C-S-H gel to a higher degree of polymerization and by optimizing the pore structure. Further, PCBAs achieved an excellent solidification of phosphorus impurities under all four curing conditions. This work provides significant guidance for selecting an optimized PCBA curing method for industrial production.
RESUMEN
Peptidyl arginine deiminase 4 (PAD4)-mediated neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of ulcerative colitis (UC). The cGAS-STING intracellular DNA-sensing pathway has been recognized as a pivotal mediator of inflammation. This study aimed to explore how NETs contribute to intestinal inflammation and barrier dysfunction in UC, focusing on the cGAS-STING pathway. We observed a significant increase of STING expression in UC mouse colons, which was mitigated by blocking NET formation through PAD4 genetic knockout. Moreover, NETs were discovered to activate the cGAS-STING pathway in MC38 cells in a dose and time-dependent manner, leading to the secretion of inflammatory cytokines and impaired barrier function. Additionally, STING deficiency ameliorated the clinical colitis index, intestinal inflammation, and barrier dysfunction. These findings underscore the involvement of cGAS-STING in regulating NET-mediated intestinal inflammation, suggesting its potential as a novel therapeutic target for UC.
RESUMEN
This research aimed to address the potential bacterial contamination risks in developmental engineering (DE) using bacteriophages. To compare and contrast the exemplar Escherichia coli T4 and M13 bacteriophages, human dermal fibroblasts cultivated on culture plates, natural cellulosic scaffolds, and poly(methyl methacrylate) (PMMA) particles were utilized as two-dimensional (2D) cell, three-dimensional (3D) tissue, and modular tissue culture models, respectively. When directly introduced into these distinct culture systems, both phages survived, exhibited no significant effects on the cultured cells or tissues, yet displayed their potentials to alleviate the infections caused by corresponding bacterial host cells. Apart from direct addition into the culture medium, both phages were also coated on PMMA, polystyrene, poly(lactic acid) particles with different diameters (5, 10, 30, and 100 µm) and cellulosic scaffolds. The coated phages endured the coating processes and demonstrated their viabilities in plaque assays. Further testing indicated that the phages coated on the PMMA particles tolerated multiple deliberate rinses and centrifugations, but not thermal treatment at 60-80°C. In summary, T4 and M13 bacteriophages not only manifested their antibacterial functions in diverse 2D cell, 3D tissue, and modular tissue culture systems, but also demonstrated their potentials of coating modular scaffolds to alleviate the bacterial contamination risks in DE.
Asunto(s)
Escherichia coli , Humanos , Escherichia coli/virología , Escherichia coli/crecimiento & desarrollo , Ingeniería de Tejidos/métodos , Fibroblastos/virología , Fibroblastos/microbiología , Bacteriófago M13 , Células CultivadasRESUMEN
Purpose: Transformational leadership among core hospital leaders boosts medical organizations' competitiveness, adaptability, and sustainability, which is jointly affected by individual, organizational and environmental factors. This study aims to unpack its configurational framework and propose strategies to strengthen core hospital leaders' transformational leadership. Patients and Methods: Data were collected from an online questionnaire among 31 core hospital leaders. The fuzzy-set qualitative comparative analysis (fsQCA) was used to explore the causal mechanism of high-level transformational leadership. We enrich this mechanism by professional background, critical thinking, initiative spirit, family-work conflict, job satisfaction, subordinates' followership, and work pressure. Results: Result shows initiative spirit is the only necessary condition (consistency=0.911) for the formation of high-level transformational leadership among core hospital leaders. Three configurations are the sufficient conditions that lead to high-level transformational leadership among core hospital leaders with two different professional backgrounds (overall solution consistency= 0.952). Conclusion: Core hospital leaders' initiative spirit is an indispensable condition for improving high-level transformational leadership, emphasizing the necessity for core leaders to be proactive in order to develop such leadership. Besides, the study also uncovered three configurations are the sufficient conditions for core hospital leaders with diverse professional backgrounds to achieve high-level transformational leadership. This finding offers significant insights into hospital management practices, suggesting that core hospital leaders' work should be managed in a personalized manner based on their professional backgrounds, thereby fostering favorable conditions conducive to the development of their high-level transformational leadership capabilities. Furthermore, the central insight of this study is that the formation of high-level transformational leadership contingent upon the collaboration of professional background, critical thinking, initiative spirit, family-work conflict, job satisfaction, subordinates' followership, and work pressure, contributing to a holistic and more rigorous view for the development of transformational leadership.
RESUMEN
The widespread utilization of fossil fuels has emitted large amounts of CO2 into the atmosphere since the Industrial Revolution, leading to climate warming and frequent occurrence of extreme climate events. To effectively alleviate climate change, the international community has made various efforts to reduce carbon emissions and eliminate CO2 from the atmosphere. In 2020, the Chinese government announced that carbon emission peaking and carbon neutrality will be achieved by 2030 and 2060, respectively. According to the current forecast, by the time carbon neutrality is achieved in 2060, even under the minimum conditions of fossil energy use, production, and living emissions, China will still have to emit about 1/4 of the current total emissions. These carbon must primarily be absorbed by ecosystems. Furthermore, approximately 140 ppm increase in CO2 in the atmosphere since the Industrial Revolution still needs to be removed by ecosystems. Forests are the main component of terrestrial ecosystems, contributing more than 80% of the carbon sequestration capacity of all terrestrial ecosystems. However, due to the long periodicity, complexity and dynamic variability of forests, the basic concepts of ecosystem carbon sink and its time effect are still unclear, leading to problems, such as lacking technologies for improving carbon sink capacity and disorganized rules in the carbon sink trading market. In this review, we introduced carbon sink concept according to the processes of absorbing and fixing CO2 by plant photosynthesis in forest ecosystems. Then, we analyzed the processes of time-scale-dependent carbon sinks of forest ecosystems, discussed the time effects of forest carbon sinks, and suggested using "t-year" as the unit of carbon sink (taking 3-6 months as the minimum measurement time, i.e., the beginning of carbon sequestration). Third, we proposed the approaches to improve the carbon sink capacity of forest ecosystems. One way is to improve the carbon sink capacity (expanding forest area, improving forest quality, and increasing forest soil carbon storage) of forest ecosystems. Another approach is to maintain the carbon sink of forest ecosystems as long as possible, i.e., to reduce temporary carbon sink (definition: carbon in the forest ecosystems emit into the atmosphere for a certain period) and to increase persistent carbon sink (definition: carbon in the forest ecosystems no longer emit into the atmosphere for a certain period; according to the relevant provisions of the Paris Agreement, the upper time limit for carbon sink measurement can be considered to be the year 2100. In order to maintain the persistent carbon sink, strateges such as efficient use of wood products (replace steel, cement, plastic with wood), control of forest fires or other disturbances-induced emissions, and turning forest biomass into biochar should be taken. Finally, we proposed to develop climate-smart forestry driven by artificial intelligence (AI), which would provide new theoretical and technical support for improving the carbon sink of forest ecosystems and facilitating sustainable forest management.
Asunto(s)
Dióxido de Carbono , Secuestro de Carbono , Cambio Climático , Ecosistema , Bosques , Árboles , China , Dióxido de Carbono/análisis , Dióxido de Carbono/metabolismo , Árboles/crecimiento & desarrollo , Árboles/metabolismo , Factores de Tiempo , Carbono/metabolismo , Carbono/análisis , Monitoreo del AmbienteRESUMEN
Increasing the carbon sink capacity of terrestrial ecosystems is a primary strategy to mitigate climate change and achieve the "carbon neutrality" goal. Clarifying the status and future dynamics of carbon sink of terrestrial ecosystems in Northeast China is crucial for achieving "carbon neutrality" as this region is a core contributor to carbon sink in China's terrestrial ecosystems. Here, we systematically summarized current research on carbon sink of terrestrial ecosystems across Northeast China, including the measurements and spatial-temporal patterns of carbon sinks, driving mechanisms of carbon sinks, the assessments of carbon sink potential, and technologies for increasing carbon sequestration. There are substantial uncertainties in quantifying terrestrial ecosystem carbon sink in Northeast China due to differences in data sources and methods, especially for forest carbon sink measurements, ranging from 0.020 to 0.157 Pg C·a-1. Carbon sink function depends on carbon exchange processes across plant-soil-atmosphere interfaces. The key pathways to enhance carbon sequestration in Northeast China under different temporal and spatial scales remains unclear. Improving terrestrial ecosystem quality is the key and core of carbon sequestration and sink enhancement. However, there is an urgent need to develop a multi-ecosystem collaborative carbon sequestration and sink enhancement technology system for the "dual carbon" goal. Future research needs to develop an accurate carbon sink measurement system that integrates multi-source data and multi-scale technologies to accurately assess the function and potential of carbon sink in Northeast China, focus on the multi-scale driving mechanism of carbon sink functions, develop new technical systems for coordinated enhancement of carbon sink for the Northeast terrestrial ecosystems, and carry out demonstrations of carbon sink enhancement technologies. These efforts will provide the scientific and technological supports for achieving the "carbon neutrality" goal.
Asunto(s)
Secuestro de Carbono , Cambio Climático , Ecosistema , China , Carbono/análisis , Carbono/metabolismo , Suelo/química , Bosques , Árboles/crecimiento & desarrollo , Árboles/metabolismoRESUMEN
OBJECTIVES: Retirement represents a significant life transition, with post-retirement status serving as a pivotal aspect of aging research. Despite its potential significance, little research has delved into the relationship between continuing work after retirement and the frailty. This study aims to investigate the association between continuing work after retirement and the incidence of frailty among older individuals. DESIGN: A nationally representative cohort study. SETTING AND PARTICIPANTS: We utilized data from 4 waves (2011, 2013, 2015 and 2018) of the China Health and Retirement Longitudinal Study and a total of 5,960 participants were included in the study after applying specific inclusion and exclusion criteria. METHODS: Frailty was assessed using a Frailty Index. To balance baseline covariates between workers (n = 3,170) and non-workers (n = 2,790), we employed inverse propensity of treatment weighting. The relationship between work status and the incidence of frailty was examined using Cox proportional hazards analysis, with results reported as hazard ratios and 95% confidence intervals. RESULTS: A total of 5,960 participants (mean age 64 years; 42.1% male) were included in the analysis. Over a mean follow-up of 6.9 years, 2,105 cases of frailty were identified. In the cohort analysis, following adjustment using the inverse propensity of treatment weighting (IPTW), continuing work after retirement showed a negative association with frailty incidence, with an HR of 0.72 (95% CI, 0.65-0.79). Subgroup analysis revealed a more significant protective effect of continuing work beyond retirement age among individuals aged 65 or older, males, smokers, and those with limited social activities. CONCLUSIONS: In summary, this study identified a significant association between continuing work after retirement and a decreased risk of frailty. The findings underscore the potential benefits of policies promoting social engagement and extending working life in enhancing the quality of life for the aging population.
RESUMEN
Background: The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and reproducible diagnostic biomarkers for early GC are still lacking in multiple populations. Thus, this study aimed to characterize the gastrointestinal microbial communities involved in gastric carcinogenesis through a meta-analysis of multiple published and open datasets. Methods: We analyzed 16S rRNA sequencing data from 1,642 gastric biopsy samples and 394 stool samples across 11 independent studies. VSEARCH, QIIME and R packages such as vegan, phyloseq, cooccur, and random forest were used for data processing and analysis. PICRUSt software was employed to predict functions. Results: The α-diversity results indicated significant differences in the intratumoral microbiota of cancer patients compared to non-cancer patients, while no significant differences were observed in the fecal microbiota. Network analysis showed that the positive correlation with GC-enriched bacteria increased, and the positive correlation with GC-depleted bacteria decreased compared to healthy individuals. Functional analyses indicated that pathways related to carbohydrate metabolism were significantly enriched in GC, while biosynthesis of unsaturated fatty acids was diminished. Additionally, we investigated non-Helicobacter pylori (HP) commensals, which are crucial in both HP-negative and HP-positive GC. Random forest models, constructed using specific taxa associated with GC identified from the LEfSe analysis, revealed that the combination of Lactobacillus and Streptococcus included alone could effectively discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). This finding was also validated in an independent cohort (AUC = 0.7712). Conclusions: This study examined the intratumoral and fecal microbiota of GC patients from a dual microecological perspective and identified Lactobacillus, Streptococcus, Roseburia, Faecalibacterium and Phascolarctobacterium as intratumoral and intestinal-specific co-differential bacteria. Furthermore, it confirmed the validity of the combination of Lactobacillus and Streptococcus as GC-specific microbial markers across multiple populations, which may aid in the early non-invasive diagnosis of GC.
Asunto(s)
Heces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiología , Heces/microbiología , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Disbiosis/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , CarcinogénesisRESUMEN
Among women, breast cancer is the most prevalent form of a malignant tumour. Among the subtypes of breast cancer, hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative kinds make up the biggest proportion. The advent of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, which are dependent on cell cycle proteins, has greatly enhanced the prognosis of patients with advanced HR+/HER2- breast cancer. This is a specific treatment that stops the growth of cancer cells by preventing them from dividing. Nevertheless, the drug resistance of the disease unavoidably impacts the effectiveness of treatment and the prognosis of patients. This report provides a thorough analysis of the current research advancements about the resistance mechanism of CDK4/6 inhibitors in HR+/HER2- breast cancer. It presents an in-depth discussion from numerous viewpoints, such as aberrant cell cycle regulation and changes in signalling pathways. In response to the drug resistance problem, subsequent treatment strategies are also being explored, including switching to other CDK4/6 inhibitor drugs, a combination of novel endocrine therapeutic agents, an optimal combination of targeted therapies and switching to chemotherapy. An in-depth study of the resistance mechanism can assist in identifying creative tactics that can overcome or postpone drug resistance, alleviate the problem of restricted treatment strategies following drug resistance and enhance the prognosis of patients.
RESUMEN
Ophiocordyceps encompasses over 300 species, demonstrating a wide range of morphological features, hosts and habitats within its species diversity. In this study, two novel species in Ophiocordyceps were revealed parasitising Hepialidae larva buried in soil. Ophiocordycepsalbastroma was morphologically characterised by white stromata, solitary and cylindrical conidiogenous cells and smooth ovoid or ellipsoidal conidia. Ophiocordycepsnigristroma was characterised by woody and dark brown stromata, monophialidic, swollen base and lageniform conidiogenous cells and smooth fusiform or oval conidia. The two new species formed a separate clade, respectively, based on the phylogenetic analyses of a combined dataset including nrSSU, nrLSU, rpb1, rpb2, and tef-1α, as well as a dataset of mitochondrial 14 protein coding genes (PCGs). They were all closely grouped with O.sinensis. The mitochondrial genomes of them were first reported. Their mitogenomes were all typical of circular molecules, with positive AT and GC skew, similar GC content, similar genetic composition, similar codon usage and conservative gene positions. However, the length of the mitogenomes varied. Changes in the length of the genes were the leading cause of changes in the length of mitochondrial genome of Ophiocordyceps. The discovery and identification of new Ophiocordyceps species and analysis their mitochondrial genomes may serve as foundations for phylogeny and diversity research within the genus Ophiocordyceps.
RESUMEN
BACKGROUND AND PURPOSE: The triglyceride-glucose (TyG) index, a novel reliable biomarker for IR that incorporates blood glucose and triglyceride, is linked to intracranial atherosclerotic stenosis (ICAS). In this study, we aimed to further investigate the association between the TyG index and the outcomes of ICAS patients following extracranial-to-intracranial (EC-IC) bypass grafting. METHODS: 489 ICAS patients who underwent EC-IC bypass between Jan 2009 and Jan 2022 at our hospital were retrospectively collected. The major adverse cardiac and cerebrovascular events (MACCEs), and anastomotic restenosis, both of which are critical factors leading to poor prognosis of ICAS patients after EC-IC bypass, were mainly recorded and analyzed. Kaplan-Meier survival curve and Log-rank tests were sequentially conducted. Cox regression model was used to investigate the association between the TyG index and MACCEs & anastomotic stenosis. C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated the incremental predictive value of the TyG index. RESULTS: A higher incidence of MACCEs and anastomotic stenosis was found in higher-tertile TyG index group. The TyG index was significantly associated with an increased risk of MACCEs and anastomotic stenosis, independent of confounding factors, with a value of HR (1.30, 95%CI 1.10-1.51, p < 0.001) and (1.27, 95%CI 1.16-1.40, p < 0.001) respectively. The area under the curve (AUC) in the model with the TyG index for predicting the occurrence of MACCEs and anastomotic stenosis were 0.708 (95%CI 0.665-0.748) and 0.731 (95%CI 0.689-0.770) respectively. The addition of the TyG index significantly improved the global performance of the baseline model according to the C-statistics, NRI, and IDI (All p < 0.05). CONCLUSIONS: Higher TyG levels were associated with poorer outcomes in ICAS patients after EC-IC bypass. TyG could be a key factor in managing ICAS risk and standardizing the indications for EC-IC bypass.
Asunto(s)
Glucemia , Arteriosclerosis Intracraneal , Triglicéridos , Humanos , Masculino , Femenino , Arteriosclerosis Intracraneal/sangre , Arteriosclerosis Intracraneal/cirugía , Triglicéridos/sangre , Glucemia/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Pronóstico , Biomarcadores/sangre , Revascularización Cerebral , Factores de Riesgo , Constricción Patológica/sangre , Estimación de Kaplan-Meier , Modelos de Riesgos ProporcionalesRESUMEN
Cold atmospheric plasma (CAP) has been extensively utilized in medical treatment, particularly in cancer therapy. However, the underlying mechanism of CAP in skin cancer treatment remains elusive. In this study, we established a skin cancer model using CAP treatmentin vitro. Also, we established the Xenograft experiment modelin vivo. The results demonstrated that treatment with CAP induced ferroptosis, resulting in a significant reduction in the viability, migration, and invasive capacities of A431 squamous cell carcinoma, a type of skin cancer. Mechanistically, the significant production of reactive oxygen species (ROS) by CAP induces DNA damage, which then activates Ataxia-telangiectasia mutated (ATM) and p53 through acetylation, while simultaneously suppressing the expression of Solute Carrier Family 7 Member 11 (SLC7A11). Consequently, this cascade led to the down-regulation of intracellular Glutathione peroxidase 4 (GPX4), ultimately resulting in ferroptosis. CAP exhibits a favorable impact on skin cancer treatment, suggesting its potential medical application in skin cancer therapy.
Asunto(s)
Daño del ADN , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Gases em Plasma , Especies Reactivas de Oxígeno , Neoplasias Cutáneas , Proteína p53 Supresora de Tumor , Humanos , Animales , Gases em Plasma/farmacología , Gases em Plasma/uso terapéutico , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Ratones , Proteína p53 Supresora de Tumor/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Supervivencia Celular/efectos de la radiación , Movimiento Celular/efectos de la radiación , Ratones DesnudosRESUMEN
Physical reservoir-based reservoir computing (RC) systems for intelligent perception have recently gained attention because they require fewer computing resources. However, the system remains limited in infrared (IR) machine vision, including materials and physical reservoir expression power. Inspired by biological visual perception systems, the study proposes a near-infrared (NIR) retinomorphic device that simultaneously perceives and encodes narrow IR spectral information (at ≈980 nm). The proposed device, featuring core-shell upconversion nanoparticle/poly (3-hexylthiophene) (P3HT) nanocomposite channels, enables the absorption and conversion of NIR into high-energy photons to excite more photo carriers in P3HT. The photon-electron-coupled dynamics under the synergy of photovoltaic and photogating effects influence the nonlinearity and high dimensionality of the RC system under narrow-band NIR irradiation. The device also exhibits multilevel data storage capability (≥8 levels), excellent stability (≥2000 s), and durability (≥100 cycles). The system accurately identifies NIR static and dynamic handwritten digit images, achieving recognition accuracies of 91.13% and 90.07%, respectively. Thus, the device tackles intricate computations like solving second-order nonlinear dynamic equations with minimal errors (normalized mean squared error of 1.06 × 10â»3 during prediction).