RESUMEN

As one of the common malignancies that threaten human life, bladder cancer occurs frequently with a high mortality rate in the world, due to its invasion, recurrence and drug resistance. Natural products from marine microorganisms are becoming the hotspots in discovery of new candidate drug entities, especially in the area of cancer. Brefeldin A (BFA) is a natural Arf-GEFs inhibitor, but due to the low aqueous solubility, strong toxicity, and poor bioavailability, it is urgent to conduct structural optimization research. Herein, a new BFA pyridine acrylate derivative CHNQD-01281 with improved solubility was prepared and found to exert moderate to strong antiproliferative activity on a variety of human cancer cell lines. It was noteworthy that CHNQD-01281 was most sensitive to two bladder cancer cell lines T24 and J82 (IC50 = 0.079 and 0.081 µmol/L) with high selectivity index (SI = 14.68 and 14.32), suggesting a superior safety to BFA. In vivo studies revealed that CHNQD-01281 remarkably suppressed tumor growth in a T24 nude mice xenograft model (TGI = 52.63%) and prolonged the survival time (ILS = 68.16%) in an MB49 allogeneic mouse model via inducing infiltration of cytotoxic T cells. Further mechanism exploration indicated that CHNQD-01281 regulated both EGFR/PI3K/AKT and EGFR/ERK pathways and mediated the chemotactic effect of chemokines on immune effector cells. Overall, CHNQD-01281 may serve as a potential therapeutic agent for bladder cancer through multiple mechanisms. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00246-w.

RESUMEN

Ovarian aging results in reproductive disorders and infertility in mammals. Previous studies have reported that the ferroptosis and autophagy caused by oxidative stress may lead to ovarian aging, but the mechanisms remain unclear. In this study, we compared the morphological characteristics between the aged and young ovaries of pigs and found that the aged ovaries were larger in size and showed more corpora lutea. TUNEL assay further showed that the apoptosis level of granulosa cells (GCs) was relatively higher in the aged ovaries than those in young ovaries, as well as the expressions of autophagy-associated genes, e.g., p62, ATG7, ATG5, and BECN1, but that the expressions of oxidative stress and aging-associated genes, e.g., SOD1, SIRT1, and SIRT6, were significantly lower. Furthermore, the RNA-seq, Western blotting, and immunofluorescence suggested that phospholipid phosphatase 3 (PLPP3) protein was significantly upregulated in the aged ovaries. PLPP3 was likely to decrease the expressions of SIRT1 and SIRT6 to accelerate cellular senescence of porcine GCs, inhibit the expressions of SOD1, CAT, FSP1, FTH1, and SLC7A11 to exacerbate oxidative stress and ferroptosis, and arouse autophagy to retard the follicular development. In addition, two SNPs of PLPP3 promoter were significantly associated with the age at puberty. g.155798586 (T/T) and g.155798718 (C/C) notably facilitated the mRNA and protein level of PLPP3. In conclusion, PLPP3 might aggravate the oxidative stress of GCs to accelerate ovarian aging, and two molecular markers of PLPP3 were identified for ovarian aging in pigs. This work not only contributes to investigations on mechanisms for ovarian aging but also provides valuable molecular markers to postpone ovarian aging in populations.

Asunto(s)

Envejecimiento , Células de la Granulosa , Ovario , Estrés Oxidativo , Animales , Femenino , Ovario/metabolismo , Ovario/patología , Porcinos , Envejecimiento/genética , Envejecimiento/metabolismo , Células de la Granulosa/metabolismo , Autofagia/genética , Apoptosis/genética , Senescencia Celular/genética , Fosfatidato Fosfatasa/metabolismo , Fosfatidato Fosfatasa/genética

RESUMEN

Spontaneous cerebellar hemorrhage (SCH) patients have a low success rate in extubation, but there are currently no guidelines establishing specifically for SCH patients extubation. The study included 68 SCH patients who received mechanical ventilation for more than 24 h, with 39 cases (57.3%) resulting in successful extubation. The multivariate analysis identified four factors significantly associated with extubation success: patient age under 66 years, an Intracerebral Hemorrhage (ICH) score less than 4 points, the presence of tissue shift, and a Glasgow Coma Scale (GCS) score (excluding language) above 6 points at extubation. By simplifying the prediction model, we obtained the Spontaneous Cerebellar Hemorrhage Extubation Success scoring system (SCHES-SCORE). Within the scoring system, 2 points were allocated for a GCS score (excluding language) above 6 at extubation, 1 point each for age under 66 years and an ICH score below 4, while tissue shift was assigned a negative point. A score of Grade A (SCHES-SCORE = 3-4) was found to correlate with a 92.9% success rate for extubation. The area under the receiver operating characteristic curve was 0.923 (95% CI, 0.863 to 0.983). Notably, successful extubation was significantly linked to reduced durations of mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay. In conclusion, the scoring system developed for assessing extubation outcomes in SCH patients has the potential to enhance the rate of successful extubation and overall patient outcomes.

RESUMEN

Modulating the A-site deficiency is a useful method to achieve the exsolution of nanoparticles on the surface of perovskite, improving the catalytic activity. However, rules for designing the deficiency value and its roles on the structure and performance remain unclear. In this study, a wide range of A-site deficiencies of (La0.4Sr0.6)1-αTi0.95Ni0.05O3±Î´ (LSTN, α = 0.00, 0.13, 0.15, and 0.18) titanate perovskite materials was designed to systematically investigate their crystal structure, binding energy, oxygen vacancy concentration, exsolution process, and electrochemical performance. An extremely high conductivity (e.g., 331.75 S cm-1@800 °C, 5% H2/Ar) was obtained in parallel with enhanced catalytical activity in SOFC and SOEC modes. The A-site-deficient samples displayed a higher conductivity, oxygen vacancy concentration, and power output than the stoichiometric samples (α = 0.00). The best maximum power density of 78.74 mW cm-2 and the highest population density of 25 particles per µm2 were obtained on the deficient LSTN with α = 0.13. These findings suggest that LSTN is an exceptionally promising material for solid oxide cell (SOC) electrodes.

RESUMEN

Tree-ring widths contain valuable historical information related to both forest disturbances and climate variability and changes within forests. However, current methods are still unable to accurately distinguish between disturbances and climate signals in tree rings, especially in the case of climate anomalies. To address this issue, we developed a novel method, called Growth Trends Clustering (GTC) that uses the distribution characteristics of tree-ring widths within a stand to distinguish the effects of climate and other forest disturbances. GTC employed a Gaussian mixture model to fit the probability density distribution of annual ring-width index (RWI) in a stand. Discriminative criteria were established to cluster diverse sub-distributions from the Gaussian mixture model into categories of growth release, suppression, or normal trends. This approach allowed us to identify the occurrence, duration, and severity of forest disturbances based on percentage changes in the growth release or suppression categories of trees. And the effect of climate on tree growth was assessed according to the mean statistics of the growth normal categories. Using common forest disturbances such as defoliating insects and thinning as examples, we validated our method using tree-ring collections from six sites in British Columbia and Quebec, Canada. We found that the GTC method was superior to traditional time-series analysis methods (e.g., Radial Growth Averaging, Boundary Line, Absolute Increase, and Curve Intervention Detection) for detecting past forest disturbances and was able to significantly enhance climate signals. In summary, the GTC method presented in this study introduces a novel statistical approach for accurately distinguishing between forest disturbances and climate signals in tree rings. This is particularly important for understanding forest disturbance regimes under climate change and for developing future disturbance mitigation strategies.

Asunto(s)

Cambio Climático , Monitoreo del Ambiente , Bosques , Árboles , Árboles/crecimiento & desarrollo , Monitoreo del Ambiente/métodos , Colombia Británica , Quebec , Clima , Análisis por Conglomerados

RESUMEN

Cyclic methylsiloxanes (CMSs), widely found in wastewater treatment plants (WWTPs), are potentially hazardous to the environment and human health. In this study, the environmental behavior and human exposure risks of three CMSs (D4-D6) were evaluated in WWTPs located in Beijing and Kunming, Yunnan province. D5 had the highest concentrations in air, water, and sludge, with seasonal variation that consisted of a high concentration in summer and low concentration in winter. The CMS concentrations in air were 3-4-fold higher in the A2/O (Anaerobic-Anoxic-Oxic) treatment units than in the other units. CMS emissions to air, soil, and water from the Beijing WWTP were in the ranges of 3.4 × 104-5.0 × 104 kg·a-1, 4.5 × 102-7.5 × 102 kg·a-1, and 2.5 × 102-2.9 × 102 kg·a-1, constituting 98 %, 1.3 %, and 0.7 % of the total emissions, respectively. Total daily inhalation exposure doses of CMSs (ADDinh,CMSs) associated with four different jobs in WWTPs showed that wastewater treatment technicians had the highest ADDinh,CMSs (51 µg/kg/day), indicating that these people had the highest occupational exposure risk in WWTPs. Therefore, this study identified that atmospheric emission was the main environmental fate of CMSs in WWTPs, and provide a basis for the improvement of WWTP process and risk management decisions. ENVIRONMENTAL IMPLICATION: Assessing the environmental fate and occupational exposure risk of cyclic methylsiloxanes (CMSs) found in wastewater treatment plants (WWTPs) is crucial. This is the first study to identify that atmospheric emission was the main environmental fate of CMSs in WWTPs, especially D5; the inhalation exposure doses of CMSs were all significantly higher in the occupational population working in WWTPs. The results described in our study will help enhance the understanding of current knowledge base of environmental fate and exposure risk of CMSs in WWTPs, and provide a basis for the improvement of WWTP process and risk management decisions.

Asunto(s)

Monitoreo del Ambiente , Exposición Profesional , Eliminación de Residuos Líquidos , Aguas Residuales , Exposición Profesional/análisis , Exposición Profesional/estadística & datos numéricos , Aguas Residuales/química , Siloxanos/análisis , Humanos , China , Contaminantes Químicos del Agua/análisis , Beijing

RESUMEN

BACKGROUND: China was once called the world's factory. Chinese workers had long weekly working hours. However, the empirical results of the relationship between overtime work and workers' health are mixed and remain inconclusive. OBJECTIVE: This study aimed to investigate how overtime work influenced workers' physical and mental health and the role of lifestyles, social support, and work value awareness. METHODS: Data from the China Labor-force Dynamics Survey 2016 (N = 14,205) was used. The instrumental variable approach was employed to overcome the endogeneity problem between overtime work and workers' health. The bootstrapping method was conducted to elicit the role of lifestyles, social support, and work value awareness. RESULTS: The results indicated that overtime work significantly and negatively influenced Chinese workers' physical and mental health. The results of the bootstrapping suggested that workers' social support and work value awareness partially mediated the relationship between overtime work and their physical and mental health. However, the mediating role of lifestyles was insignificant. CONCLUSION: Through using big data with national representativeness, this study suggests that overtime work negatively influences Chinese workers' physical and mental health. Our findings provide policy implications for improving workers' health rights and well-being in emerging economies.

RESUMEN

Sodium-ion layered oxides are one of the most highly regarded sodium-ion cathode materials and are expected to be used in electric vehicles and large-scale grid-level energy storage systems. However, highly air-sensitive issues limit sodium-ion layered oxide cathode materials to maximize cost advantages. Industrial and scientific researchers have been developing cost-effective air sensitivity treatment strategies with little success because the impurity formation mechanism is still unclear. Using density functional theory calculations and ab initio molecular dynamics simulations, this work shows that the poor air stability of O3-type NaMn1/3Fe1/3Ni1/3O2 (NMFNO) may be as follows: (1) low percentage of nonreactive (003) surface; (2) strong surface adsorption capacity and high surface reactivity; and (3) instability of the surface sodium ions. Our physical images point out that the high reactivity of the NMFNO surface originates from the increase in electron loss and unpaired electrons (magnetic moments) of the surface oxygen active site as well as the enhanced metal coactivation effect due to the large radius of the sodium ion. We also found that the hydrolysis reaction requires a higher reactivity of the surface oxygen active site, while the carbon hybridization mode transformation in carbonate formation depends mainly on metal activation and does not even require the involvement of surface oxygen active sites. Based on the calculation results and our proposed physical images, we discuss the feasibility of these treatment strategies (including surface morphology modulation, cation/anion substitution, and surface configuration design) for air-sensitive issues.

RESUMEN

OBJECTIVE: To analyze the efficacy of levonorgestrelintrauterine system, Drospirenone & ethinylestradiol tablets (II), and dydrogesterone in preventing the recurrence of endometrial polyps after hysteroscopic endometrial polypectomy. METHODS: One hundred seventy patients who underwent hysteroscopic endometrial polypectomy in the Gynecology Department of Tianmen First People's Hospital in Hubei Province from January 2022 to June 2023 were randomly divided into the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, dydrogesterone group, and a control group. The recurrence rates, endometrial thickness, and menstrual volume changes at 6 and 12 months post-operation were compared among these four groups. RESULTS: The recurrence rates in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group were lower than the control group, with statistical significance (P < 0.01), with the levonorgestrelintrauterine system group having the lowest recurrence rate. The endometrial thickness at 6 and 12 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was thinner than that of the control group and thinner than pre-operation, with statistical significance (P < 0.01). The menstrual volume at 3 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was significantly less than the control group, and less than the pre-operation volume. CONCLUSION: Dydrogesterone, drospirenone & ethinylestradiol tablets (II), and levonorgestrelintrauterine system all play a role in preventing the recurrence of endometrial polyps, but levonorgestrelintrauterine system is significantly better than dydrogesterone and Drospirenone & ethinylestradiol tablets (II) in terms of postoperative recurrence rate, endometrial thickness, menstrual changes, and compliance, and is worth promoting in clinical application.

Asunto(s)

Androstenos , Didrogesterona , Etinilestradiol , Levonorgestrel , Pólipos , Humanos , Femenino , Didrogesterona/administración & dosificación , Didrogesterona/uso terapéutico , Etinilestradiol/administración & dosificación , Adulto , Levonorgestrel/administración & dosificación , Androstenos/administración & dosificación , Androstenos/uso terapéutico , Pólipos/prevención & control , Pólipos/cirugía , Enfermedades Uterinas/prevención & control , Enfermedades Uterinas/cirugía , Persona de Mediana Edad , Prevención Secundaria/métodos , Combinación de Medicamentos , Endometrio/efectos de los fármacos , Endometrio/patología , Recurrencia

RESUMEN

Escherichia coli (E. coli) is commonly utilized as a vehicle for anti-tumor therapy due to its unique tumor-targeting capabilities and ease of engineering modification. To further explore the role of E. coli in tumor treatment, we consider that E. coli outer membrane vesicles (E. coli-OMVs) play a crucial role in the therapeutic process. Firstly, E. coli-OMVs were isolated and partially purified by filtration and ultracentrifugation, and were characterized using techniques such as nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western Blot (WB). The obtained extracellular nanoparticles, containing OMVs, were found to inhibited the growth of CT26 tumor in mice, while the expression of Bax protein was increased and the expression of Bcl-2 protein decreased. In vitro experiments showed that E. coli-OMVs entered CT26 cells and inhibited cell proliferation, invasion and migration. In addition, in the presence of E. coli-OMVs, we observed an increase in apoptosis rate and a decrease in the ratio of Bcl-2/Bax. These data indicate that E. coli-OMVs inhibits the growth of CT26 colon cancer by inducing apoptosis of CT26 cells. These findings propose E. coli-OMVs as a promising therapeutic drug for colorectal cancer (CRC), providing robust support for further research in related fields.

RESUMEN

The development and exploration of uranium decorporation agents with straightforward synthesis, high removal ability, and low toxicity are crucial guarantees for the safety of workers in the nuclear industry and the public. Herein, we report the use of traditional Chinese medicine licorice for uranium decorporation. Licorice has good adsorption performance and excellent selectivity for uranium in the simulated human environment. Glycyrrhizic acid (GL) has a high affinity for uranium (p(UO2) = 13.67) and will complex with uranium at the carbonyl site. Both licorice and GL exhibit lower cytotoxicity compared to the commercial clinical decorporation agent diethylenetriamine pentaacetate sodium salts (CaNa3-DTPA). Notably, at the cellular level, the uranium removal efficiency of GL is eight times higher than that of CaNa3-DTPA. Administration of GL by prophylactic intraperitoneal injection demonstrates that its uranium removal efficiency from kidneys and bones is 55.2 and 23.9%, while CaNa3-DTPA shows an insignificant effect. The density functional theory calculation of the bonding energy between GL and uranium demonstrates that GL exhibits a higher binding affinity (-2.01 vs -1.15 eV) to uranium compared to DTPA. These findings support the potential of licorice and its active ingredient, GL, as promising candidates for uranium decorporation agents.

Asunto(s)

Productos Biológicos , Glycyrrhiza , Ácido Glicirrínico , Uranio , Glycyrrhiza/química , Uranio/química , Uranio/aislamiento & purificación , Humanos , Ácido Glicirrínico/química , Ácido Glicirrínico/farmacología , Ácido Glicirrínico/aislamiento & purificación , Productos Biológicos/química , Productos Biológicos/farmacología , Productos Biológicos/aislamiento & purificación , Productos Biológicos/síntesis química , Animales , Teoría Funcional de la Densidad , Ratones , Supervivencia Celular/efectos de los fármacos

RESUMEN

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.

Asunto(s)

Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gemcitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Adulto , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Anciano , Supervivencia sin Progresión , China , Metástasis de la Neoplasia

RESUMEN

To enhance the energy absorption properties of the energy-absorbing structure, carbon fiber-reinforced polymer (CFRPs) with higher specific energy absorption and porous material aluminum foam with better compressive characteristics were organically combined, and a lighter aluminum foam winding carbon fiber-reinforced polymer structure (CFRP-FA-FW) was designed. Through quasi-static compression testing, the deformation mode and energy absorption properties of CFRP-FA-FW under axial load were examined. The energy absorption and specific energy absorption of CFRP-FA-FW are both increased by 113.55 % and 60.73 %, respectively, compared to the simple composite structure CFRP-FA. Finite element simulation was used for the parametric analysis of the CFRP-FA-FW structure to assess the effects of the relative density of the aluminum foam, the fiber lay-up angle, and the thickness. The results reveal that the change in the relative density of aluminum foam has little impact on the failure deformation mode of CFRP-FA-FW under axial load; the structure has a higher energy absorption capacity and a smoother energy absorption process when the fiber lay-up angle is [0°/90°]ns and [45°]ns; the energy absorption capacity of CFRP-FA-FW is significantly improved by increasing the thickness of the carbon fiber lay-up, and the procedure is also more efficient.

RESUMEN

BACKGROUND: Zinc has been proven to be effective against periodontitis, and also reported to reduce the risk of cardiovascular diseases (CVD). This study aims to explore the regulatory effect of zinc intake on the association between periodontitis and atherosclerotic cardiovascular disease (ASCVD). METHODS: This was a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). Logistic regression model was used to explore the association between zinc-RDA or periodontitis and 10-year ASCVD risk ≥ 20%, and results were shown as odds ratio (OR) and 95% confidence interval (95% CI). The regulatory effect of zinc intake on the association between periodontitis and 10-year ASCVD risk ≥ 20% was also assessed using logistic regression model. Subgroup analysis was performed based on age, gender, obesity, education level, lipid-lowering therapy, and dental floss. RESULTS: 6,075 patients were finally included for analysis. Zinc intake reaching the recommended level (OR = 0.82, 95%CI: 0.69-0.98) and periodontitis (OR = 2.47, 95%CI: 2.04-3.00) were found to be associated with 0.82-fold and 2.47-fold odds of 10-year ASCVD risk ≥ 20%, respectively. In addition, we found that the odds of 10-year ASCVD risk ≥ 20% was lower in patients with zinc intake reaching the recommended level than those without [OR (95%CI): 2.25 (1.81-2.80) vs. 2.72 (2.05-3.62)]. The similar regulatory effect was found in patients with age ≥ 60 years and < 60 years, in male and female, with or without obesity, in different education levels, with or without lipid lowering therapy, and with or without use of dental floss (all P < 0.05). CONCLUSIONS: This study found the regulatory effect of adequate zinc intake on the association between periodontitis and ASCVD, providing guidance for periodontitis patients to decrease the risk of ASCVD.

Asunto(s)

Aterosclerosis , Encuestas Nutricionales , Periodontitis , Zinc , Humanos , Estudios Transversales , Masculino , Femenino , Zinc/uso terapéutico , Persona de Mediana Edad , Aterosclerosis/prevención & control , Adulto , Anciano , Factores de Riesgo , Estados Unidos/epidemiología

RESUMEN

Purpose To introduce the cranial-dorsal-hip angle (∠CDH) as a novel quantitative tool for assessing fetal position in the first trimester and to validate its feasibility for future AI applications. Materials and Methods 2520 first-trimester fetal NT exams with 2582 CRL images (January-August 2022) were analyzed at a tertiary hospital as the pilot group. Additionally, 1418 cases with 1450 fetal CRL images (September-December 2022) were examined for validation. Three expert sonographers defined a standard for fetal positions. ∠CDH measurements, conducted by two ultrasound technicians, were validated for consistency using Bland-Altman plots and the intra-class correlation coefficient (ICC). This method allowed for categorizing fetal positions as hyperflexion, neutral, and hyperextension based on ∠CDH. Comparative accuracy was assessed against Ioannou, Wanyonyi, and Roux methods using the weighted Kappa coefficient (k value). Results The pilot group comprised 2186 fetal CRL images, and the validation group included 1193 images. Measurement consistency was high (ICCs of 0.993; P<0.001). The established 95% reference range for ∠CDH in the neutral fetal position was 118.3° to 137.8°. The ∠CDH method demonstrated superior accuracy over the Ioannou, Wanyonyi, and Roux methods in both groups, with accuracy rates of 94.5% (k values: 0.874, 95%CI: 0.852-0.896) in the pilot group, and 92.6% (k values: 0.838, 95%CI: 0.806-0.871) in the validation group. Conclusion The ∠CDH method has been validated as a highly reproducible and accurate technique for first-trimester fetal position assessment. This sets the stage for its potential future integration into intelligent assessment models.

RESUMEN

The progression of colorectal cancer is closely associated with diet. Fasting-mimicking diet (FMD) is a promising type of dietary intervention that have beneficial effects in the prevention and treatment of various cancers. We investigated the therapeutic effect of 4-day FMD against colorectal cancer in mice through immune cell analysis, microbiota composition analysis and anti-PD-1 treatment. These FMD cycles effectively suppressed colorectal cancer growth, reduced cell proliferation and angiogenesis, increased tumor-infiltration lymphocytes especially CD8+T cells. FMD stimulated protective gut microbiota, especially Lactobacillus. Supplementation of Lactobacillus johnsonii induced similar results as FMD intervention, which also suppressed tumor growth and increased CD45+ and CD8+ T cells. Additionally, FMD synthesizing with anti-PD-1 therapy effectively inhibited CRC progression. These findings suggest that Lactobacillus. johnsonii is necessary for the anticancer process of FMD in CRC. FMD through its effects on both gut microbiota and immune system, effectively suppressed colorectal cancer progression in mouse model.

Asunto(s)

Neoplasias Colorrectales , Progresión de la Enfermedad , Ayuno , Microbioma Gastrointestinal , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/prevención & control , Ratones , Modelos Animales de Enfermedad , Proliferación Celular/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Dieta/métodos , Línea Celular Tumoral , Ratones Endogámicos C57BL , Lactobacillus , Humanos

RESUMEN

Eucalyptus roots form symbiotic relationships with arbuscular mycorrhizal (AM) fungi in soil to enhance adaptation in challenging environments. However, the evolution of the AM fungal community along a chronosequence of eucalypt plantations and its relationship with soil properties remain unclear. In this study, we evaluated the tree growth, soil properties, and root AM fungal colonization of Eucalyptus grandis W. Hill ex Maiden plantations at different ages, identified the AM fungal community composition by high-throughput sequencing, and developed a structural equation model among trees, soil, and AM fungi. Key findings include the following: (1) The total phosphorus (P) and total potassium (K) in the soil underwent an initial reduction followed by a rise with different stand ages. (2) The rate of AM colonization decreased first and then increased. (3) The composition of the AM fungal community changed significantly with different stand ages, but there was no significant change in diversity. (4) Paraglomus and Glomus were the dominant genera, accounting for 70.1% and 21.8% of the relative abundance, respectively. (5) The dominant genera were mainly influenced by soil P, the N content, and bulk density, but the main factors were different with stand ages. The results can provide a reference for fertilizer management and microbial formulation manufacture for eucalyptus plantations.

RESUMEN

Traditional cancer chemotherapy suffers from low efficacy and severe side effects, limiting its use as a first-line treatment. To address this issue, we investigated a novel way to induce lipid peroxidation (LPO), which plays an essential role in ferroptosis and may be useful against cancer cells and tumors. In this study, a pH-responsive synergistic cancer therapy nanoplatform was prepared using CaCO3 co-loaded with oleanolic acid (OA) and lipoxygenase (LOX), resulting in the formation OLCaP NP. This nanoplatform exhibited good drug release properties in an acidic tumor environment owing to the presence of CaCO3. As a result of acidic stimulation at tumor sites, the OLCaP NP released OA and LOX. OA, a chemotherapeutic drug with anticancer activity, is already known to promote the apoptosis of cancer cells, and LOX is a natural enzyme that catalyzes the oxidation of polyunsaturated fatty acids, leading to the accumulation of lipid peroxides and promoting the apoptosis of cancer cells. More importantly, OA upregulated the expression of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), which promoted enzyme-mediated LPO. Based on our combined chemotherapy and nanocatalytic therapy, the OLCaP NP not only had remarkable antitumor ability but also upregulated ACSL4 expression, allowing further amplification of LPO to inhibit tumor growth. These findings demonstrate the potential of this nanoplatform to enhance the therapeutic efficacy against tumors by inducing oxidative stress and disrupting lipid metabolism, highlighting its clinical potential for improved cancer treatment. STATEMENT OF SIGNIFICANCE: This study presents a novel nanoplatform that combines oleanolic acid (OA), a chemotherapeutic drug, and lipoxygenase (LOX), which oxidizes polyunsaturated fatty acids to trigger apoptosis, for targeted cancer therapy. Unlike traditional treatments, our nanoplatform exhibits pH-responsive drug release, specifically in acidic tumor environments. This innovation enhances the therapeutic effects of OA and LOX, upregulating acyl-CoA synthetase long-chain family member 4 expression and amplifying lipid peroxidation to promote tumor cell apoptosis. Our findings significantly advance the existing literature by demonstrating a synergistic approach that combines chemotherapy and nanocatalytic therapy. The scientific impact of this work lies in its potential to improve cancer treatment efficacy and specificity, offering a promising strategy for clinical applications and future research in cancer therapy.

Asunto(s)

Peroxidación de Lípido , Nanopartículas , Ácido Oleanólico , Peroxidación de Lípido/efectos de los fármacos , Humanos , Animales , Nanopartículas/química , Ácido Oleanólico/farmacología , Ácido Oleanólico/química , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Lipooxigenasa/metabolismo , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Ratones Desnudos , Ratones Endogámicos BALB C , Catálisis , Femenino

RESUMEN

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an "all-in-one" red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are "immolated" under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.