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1.
World J Clin Cases ; 12(14): 2308-2315, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38765748

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a leading risk factor for the development and progression of chronic kidney disease (CKD). However, an accurate and convenient marker for early detection and appropriate management of CKD in individuals with T2DM is limited. Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio (NLR) and CKD. Nonetheless, the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied. AIM: To investigate the relationship between NLR and renal function in T2DM patients. METHODS: This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center. The total number of neutrophils and lymphocytes was detected, and NLR levels were calculated. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m². Participants were divided into four groups based on NLR levels. The clinical data and biochemical characteristics were compared among groups. A multivariate logistic regression model was used to analyze the association between NLR levels and CKD. RESULTS: Significant differences were found in terms of sex, serum creatinine, blood urea nitrogen, total cholesterol, and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups (P < 0.0007). T2DM patients in the highest NLR quartile had a higher prevalence of CKD (P for trend = 0.0011). Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters (P = 0.0001, odds ratio = 1.41, 95% confidence intervals: 1.18-1.68). CONCLUSION: An elevated NLR in patients with T2DM is associated with higher prevalence of CKD, suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

2.
Front Psychol ; 15: 1340200, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721322

RESUMEN

Introduction: The study examines the interplay between gratitude and career success, with career resilience as the mediating mechanism and personality traits, i.e., conscientiousness and extraversion, as moderating factors. The overarching goal is to enhance our understanding of the complex dynamics that influence career outcomes of college students in China. Methods: Data are gathered through a survey-based technique, capturing responses from a diverse sample of participants. The analysis employs Structural Equation Modeling (SEM) to explore the relationships among gratitude, career resilience, personality traits, and career success. Results: The results reveal that gratitude impacts students' career success through the mediating mechanism of career resilience. In addition, conscientiousness and extraversion are found to positively intervene the direct effect between gratitude and career resilience and the indirect effect between gratitude and career success through career resilience. Discussion: The findings offer valuable insights for individuals, organizations, and career development practitioners, emphasizing the importance of cultivating gratitude and recognizing the differential impact of personality traits on this process. As organizations seek to foster resilient and successful career paths, acknowledging these nuanced dynamics can inform targeted interventions and strategies.

3.
BMC Cancer ; 24(1): 572, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720306

RESUMEN

BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.


Asunto(s)
Craneofaringioma , Diabetes Insípida Neurogénica , Neoplasias Hipofisarias , Complicaciones Posoperatorias , Humanos , Craneofaringioma/cirugía , Craneofaringioma/sangre , Craneofaringioma/complicaciones , Femenino , Masculino , Estudios Retrospectivos , Adulto , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/complicaciones , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Adolescente , Persona de Mediana Edad , Niño , Adulto Joven , Diabetes Insípida Neurogénica/sangre , Diabetes Insípida Neurogénica/etiología , Neutrófilos , Biomarcadores/sangre , Linfocitos , Inflamación/sangre , Recuento de Leucocitos , Periodo Preoperatorio , Preescolar , Pronóstico , Curva ROC
4.
Biol Res ; 57(1): 24, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711133

RESUMEN

Despite the record speed of developing vaccines and therapeutics against the SARS-CoV-2 virus, it is not a given that such success can be secured in future pandemics. In addition, COVID-19 vaccination and application of therapeutics remain low in developing countries. Rapid and low cost mass production of antiviral IgY antibodies could be an attractive alternative or complementary option for vaccine and therapeutic development. In this article, we rapidly produced SARS-CoV-2 antigens, immunized hens and purified IgY antibodies in 2 months after the SARS-CoV-2 gene sequence became public. We further demonstrated that the IgY antibodies competitively block RBD binding to ACE2, neutralize authentic SARS-CoV-2 virus and effectively protect hamsters from SARS-CoV-2 challenge by preventing weight loss and lung pathology, representing the first comprehensive study with IgY antibodies. The process of mass production can be easily implemented in most developing countries and hence could become a new vital option in our toolbox for combating viral pandemics. This study could stimulate further studies, optimization and potential applications of IgY antibodies as therapeutics and prophylactics for human and animals.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Pollos , Yema de Huevo , Inmunoglobulinas , SARS-CoV-2 , Animales , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Pollos/inmunología , Cricetinae , Inmunoglobulinas/inmunología , Yema de Huevo/inmunología , Anticuerpos Antivirales/inmunología , Femenino , Mesocricetus , Vacunas contra la COVID-19/inmunología
5.
Sensors (Basel) ; 24(9)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38733013

RESUMEN

During the operation of space gravitational wave detectors, the constellation configuration formed by three satellites gradually deviates from the ideal 60° angle due to the periodic variations in orbits. To ensure the stability of inter-satellite laser links, active compensation of the breathing angle variation within the constellation plane is achieved by rotating the optical subassembly through the telescope pointing mechanism. This paper proposes a high-performance robust composite control method designed to enhance the robust stability, disturbance rejection, and tracking performance of the telescope pointing system. Specifically, based on the dynamic model of the telescope pointing mechanism and the disturbance noise model, an H∞ controller has been designed to ensure system stability and disturbance rejection capabilities. Meanwhile, employing the method of an H∞ norm optimized disturbance observer (HODOB) enhances the nonlinear friction rejection ability of the telescope pointing system. The simulation results indicate that, compared to the traditional disturbance observer (DOB) design, utilizing the HODOB method can enhance the tracking accuracy and pointing stability of the telescope pointing system by an order of magnitude. Furthermore, the proposed composite control method improves the overall system performance, ensuring that the stability of the telescope pointing system meets the 10 nrad/Hz1/2 @0.1 mHz~1 Hz requirement specified for the TianQin mission.

6.
Front Plant Sci ; 15: 1336726, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38708388

RESUMEN

In the post-genomic era, virus-induced gene silencing (VIGS) has played an important role in research on reverse genetics in plants. Commonly used Agrobacterium-mediated VIGS inoculation methods include stem scratching, leaf infiltration, use of agrodrench, and air-brush spraying. In this study, we developed a root wounding-immersion method in which 1/3 of the plant root (length) was cut and immersed in a tobacco rattle virus (TRV)1:TRV2 mixed solution for 30 min. We optimized the procedure in Nicotiana benthamiana and successfully silenced N. benthamiana, tomato (Solanum lycopersicum), pepper (Capsicum annuum L.), eggplant (Solanum melongena), and Arabidopsis thaliana phytoene desaturase (PDS), and we observed the movement of green fluorescent protein (GFP) from the roots to the stem and leaves. The silencing rate of PDS in N. benthamiana and tomato was 95-100%. In addition, we successfully silenced two disease-resistance genes, SITL5 and SITL6, to decrease disease resistance in tomatoes (CLN2037E). The root wounding-immersion method can be used to inoculate large batches of plants in a short time and with high efficiency, and fresh bacterial infusions can be reused several times. The most important aspect of the root wounding-immersion method is its application to plant species susceptible to root inoculation, as well as its ability to inoculate seedlings from early growth stages. This method offers a means to conduct large-scale functional genome screening in plants.

7.
Neurol Sci ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714597

RESUMEN

BACKGROUND: Shunt obstruction is a type of ventriculoperitoneal shunt (VPS) failure. Whether changes in cerebrospinal fluid (CSF) parameters can influence shunt outcomes or not is debatable. METHODS: In this study, we retrospectively included adult hydrocephalus patients who received VPS from 6 general hospitals in different provinces of China from November 2013 to September 2021. The inclusion criteria: Patients with hydrocephalus of all etiologies underwent shunt surgery from 6 general hospitals in different provinces of China were included in the study. The exclusion criteria: 1.Patients under the age of 18; 2.Patients who had previous shunt surgery; 3. Shunt failure from other factors; 4.Patients died from other causes; 5. Patients with incomplete data. The CSF of shunt patients had been analyzed at the time of shunt insertion. The CSF samples were collected and analyzed when the shunt was implanted. The relationship between CSF parameters and the incidence rate of shunt obstruction in one year was analyzed. RESULTS: A total of 717 eligible patients from 6 hospitals were included, of whom 59(8.23%) experienced obstruction. Multivariate logistic regression analysis identified that protein level(odds ratio [OR] 1.161, 95% CI 1.005 ~ 1.341, p = 0.043), decreased glucose level(< 2.5 mmol/L)(odds ratio 3.784, 95% confidence interval 1.872 ~ 7.652, p = 0.001) and protein level increase(> 0.45 g/L) (odds ratio 3.653, 95% confidence interval 1.931 ~ 6.910, p = 0.001)were independent risk factors of shunt obstruction. CONCLUSION: This study suggested that increased protein level (> 0.45 g/L) and decreased glucose level (< 2.5 mmol/L) in CSF indicated an increased risk of shunt obstruction in a patient with hydrocephalus. Thus, shunt surgery should be more carefully considered when the CSF glucose and protein were abnormal.

8.
Heliyon ; 10(9): e30153, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38694064

RESUMEN

This paper provides a theoretical and empirical examination of the relationship between government subsidies, enterprise innovation, and Industry-University-Research (IUR) collaboration. The study begins with a theoretical analysis of the impact of government subsidies on IUR collaboration and enterprise innovation, employing a dynamic game model. Secondly, the research sample comprises A-share listed enterprises in China, and the theoretical findings are validated through empirical methods. Moreover, this study investigates the mediating influence of IUR collaboration and the heterogenous impacts of government subsidies. Research has shown that government subsidies can facilitate enterprises in establishing IUR collaboration, enhancing the extent of IUR collaboration, and effectively stimulating enterprises to participate in innovation. Government subsidies have a more pronounced impact on non-state-owned enterprises, high-tech enterprises, and enterprises in eastern regions in terms of incentivization. By enhancing IUR upgrade, government subsidies can offset the shortcomings in limited Research and Experimental Development (R&D) funding and inadequate technical reserves of non-high-technology enterprises. This could result in an improvement in the quality of innovation and the performance of the subsidized enterprises.

9.
Biomacromolecules ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700942

RESUMEN

The management of diabetic ulcers poses a significant challenge worldwide, and persistent hyperglycemia makes patients susceptible to bacterial infections. Unfortunately, the overuse of antibiotics may lead to drug resistance and prolonged infections, contributing to chronic inflammation and hindering the healing process. To address these issues, a photothermal therapy technique was incorporated in the preparation of wound dressings. This innovative solution involved the formulation of a self-healing and injectable hydrogel matrix based on the Schiff base structure formed between the oxidized Bletilla striata polysaccharide (BSP) and hydroxypropyltrimethylammonium chloride chitosan. Furthermore, the introduction of CuO nanoparticles encapsulated in polydopamine imparted excellent photothermal properties to the hydrogel, which promoted the release of berberine (BER) loaded on the nanoparticles and boosted the antibacterial performance. In addition to providing a reliable physical protection to the wound, the developed hydrogel, which integrated the herbal components of BSP and BER, effectively accelerated wound closure via microenvironment regulation, including alleviated inflammatory reaction, stimulated re-epithelialization, and reduced oxidative stress based on the promising results from cell and animal experiments. These impressive outcomes highlighted their clinical potential in safeguarding the wound against bacterial intrusion and managing diabetic ulcers.

10.
Biomed Pharmacother ; 175: 116689, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703508

RESUMEN

Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD+ synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD+ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.

11.
Neoplasia ; 53: 101004, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38733769

RESUMEN

Thioredoxin reductases are frequently overexpressed in various solid tumors as a protective mechanism against heightened oxidative stress. Inhibitors of this system, such as Auranofin, are effective in eradicating cancer cells. However, the clinical significance of thioredoxin reductase 1 (TrxR1) in lung cancer, as well as the potential for its antagonist as a treatment option, necessitated further experimental validation. In this study, we observed significant upregulation of TrxR1 specifically in non-small cell lung cancer (NSCLC), rather than small cell lung cancer. Moreover, TrxR1 expression exhibited associations with survival rate, tumor volume, and histological classification. We developed a novel TrxR1 inhibitor named LW-216 and assessed its antitumor efficacy in NSCLC. Our results revealed that LW-216 is effectively bound with intracellular TrxR1 at sites R371 and G442, facilitating TrxR1 ubiquitination and suppressing TrxR1 expression, while not affecting TrxR2 expression. Treatment of LW-216-induced DNA damage and cell apoptosis in NSCLC cells through the generation of reactive oxygen species (ROS). Importantly, supplementation with N-acetylcysteine (NAC) or ectopic TrxR1 expression reversed LW-216-induced apoptosis. Furthermore, LW-216 displayed potent tumor growth inhibition in NSCLC cell-implanted mice, reducing TrxR1 expression in xenografts. Remarkably, LW-216 exhibited superior antitumor activity compared to Auranofin in vivo. Collectively, our research provides compelling evidence supporting the potential of targeting TrxR1 by LW-216 as a promising therapeutic strategy for NSCLC.

12.
PLoS One ; 19(5): e0303830, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38758773

RESUMEN

In numerous developing nations, the pervasive practice of crop residue incineration is a principal contributor to atmospheric contamination in agricultural operations. This study examines the repercussions of such biomass combustion on air quality during the autumnal harvest season, utilizing data acquired from satellite-based remote sensing of fire events and air pollution measurements. Employing wind direction information alongside difference-in-difference and fixed-effects methodologies, this investigation rectifies estimation inaccuracies stemming from the non-random distribution of combustion occurrences. The empirical findings reveal that agricultural residue burning precipitates an elevation in average PM2.5 and PM10 concentrations by approximately 27 and 22 µg/m3 during the autumnal incineration period, respectively. Furthermore, air pollution attributed to residue burning in prominent grain-producing regions exceeds the national average by approximately 40%. By integrating economic paradigms into agri-environmental inquiries, this study offers novel insights and substantiation of the environmental expenditures engendered by crop residue burning, juxtaposed with extant meteorological and ecological research findings.


Asunto(s)
Agricultura , Contaminación del Aire , Productos Agrícolas , Incendios , Contaminación del Aire/análisis , Productos Agrícolas/crecimiento & desarrollo , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Incineración , Monitoreo del Ambiente/métodos , Estaciones del Año
13.
Adv Mater ; : e2403880, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38723049

RESUMEN

Classic approaches to integrate flexible capacitive sensor performance are to on-demand microstructuring dielectric layers and to adjust dielectric material compositions via the introduction of insoluble carbon additives (to increase sensitivity) or dynamic interactions (to achieve self-healing). However, the sensor's enhanced performances often come with increased material complexity, discouraging its circular economy. Herein, a new intrinsic self-healable, closed-loop recyclable dielectric layer material, a fully nature-derived dynamic covalent poly(disulfide) decorated with rich H bonding and metal-catechol complexations is introduced. The polymer network possesses a mechanically ductile character with an Arrhenius-type temperature-dependent viscoelasticity. The assembled capacitive pressure sensor is able to achieve a sensitivity of up to 9.26 kPa-1, fast response/recovery time of 32/24 ms, and can deliver consistent signals of continuous consecutive cycles even after being self-healed or closed-loop recycled for real-time detection of human motions. This is expected to be of high interest for current capacitive sensing research to move toward a life-like, high performance, and circular economy direction.

14.
Asian J Androl ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38727211

RESUMEN

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

15.
Chemosphere ; 355: 141860, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38565377

RESUMEN

Soil salinization is a major environmental hazard that limits land availability. Human-induced salt pollutants (HISPs) are regularly presented in large quantities on the contaminated site (such as brine leakages and salt-water spills), causing a devastating shock with high salt stress to the ecosystem. For instance, Saskatchewan resulted in a 48% drop in wheat production and a 0.3% decline in provincial GDP. As the calcium-modified biochar can potentially ameliorate the negative effects of HISPs on plants and improve the plant, phytoremediation with calcium-modified biochar can have increased detoxification of hazardous pollutants from sites. Therefore, the objective of our study was to develop a biochar-assisted phytoremediation employing diverse approaches to calcium modification for the sustainable removal of HISPs. The co-pyrolyzed calcium biochar achieved a remarkable removal rate of 18.06%, reducing salinity from 9.44 to 7.81 dS/m. During a 90-day long-term phytoremediation, the overall reduction rate of calcium-modified biochar stimulated the germination and growth of Thinopyrum ponticum. The result of post-treatment further indicated that co-pyrolyzed biochar with Ca transferred salt into the plant compared to Ca-coated biochar, which only immobilized HISPs on its surface. These results offer two different treatment approaches for diverse situations involving HISPs contamination, addressing current in-situ spills and providing a calcium-related biochar technology for further research in desalination.


Asunto(s)
Contaminantes Ambientales , Contaminantes del Suelo , Humanos , Biodegradación Ambiental , Calcio , Ecosistema , Carbón Orgánico , Calcio de la Dieta , Suelo , Plantas
16.
Cells ; 13(7)2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38607071

RESUMEN

Adjuvant treatment for Glioblastoma Grade 4 with Temozolomide (TMZ) inevitably fails due to therapeutic resistance, necessitating new approaches. Apoptosis induction in GB cells is inefficient, due to an excess of anti-apoptotic XPO1/Bcl-2-family proteins. We assessed TMZ, Methotrexate (MTX), and Cytarabine (Ara-C) (apoptosis inducers) combined with XPO1/Bcl-2/Mcl-1-inhibitors (apoptosis rescue) in GB cell lines and primary GB stem-like cells (GSCs). Using CellTiter-Glo® and Caspase-3 activity assays, we generated dose-response curves and analyzed the gene and protein regulation of anti-apoptotic proteins via PCR and Western blots. Optimal drug combinations were examined for their impact on the cell cycle and apoptosis induction via FACS analysis, paralleled by the assessment of potential toxicity in healthy mouse brain slices. Ara-C and MTX proved to be 150- to 10,000-fold more potent in inducing apoptosis than TMZ. In response to inhibitors Eltanexor (XPO1; E), Venetoclax (Bcl-2; V), and A1210477 (Mcl-1; A), genes encoding for the corresponding proteins were upregulated in a compensatory manner. TMZ, MTX, and Ara-C combined with E, V, and A evidenced highly lethal effects when combined. As no significant cell death induction in mouse brain slices was observed, we conclude that this drug combination is effective in vitro and expected to have low side effects in vivo.


Asunto(s)
Amidas , Antineoplásicos , Compuestos Bicíclicos Heterocíclicos con Puentes , Glioblastoma , Pirimidinas , Sulfonamidas , Animales , Ratones , Temozolomida/farmacología , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Metotrexato/farmacología , Metotrexato/uso terapéutico , Citarabina/farmacología , Citarabina/uso terapéutico , Antineoplásicos Alquilantes/farmacología , Línea Celular Tumoral , Antineoplásicos/farmacología , Apoptosis
17.
Sci Rep ; 14(1): 7733, 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565963

RESUMEN

B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Animales , Ratones , Bortezomib/farmacología , Bortezomib/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Muerte Celular Inmunogénica , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Apoptosis
18.
Opt Express ; 32(7): 12200-12212, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571050

RESUMEN

As an integral component of the laser interferometry measurement system, the tilt-to-length (TTL) coupling noise inside the telescope stands out as a critical noise factor that requires meticulous consideration. In the TianQin project, the non-geometric TTL-coupled noise inside the telescope should be less than 0.22 pm/Hz1/2. Additionally, the wavefront aberration RMS at the small pupil of the telescope needs to be better than 0.0065 λ. These requirements set for the telescope are exceptionally stringent. To address this challenge, this study aims to relax the wavefront aberration requirements by mitigating non-geometric TTL coupling noise, while ensuring the non-geometric TTL coupling noise remains below 0.22 pm/Hz1/2. By controlling the coupling aberration proportion, the wavefront aberration RMS at the small pupil of the telescope can be relaxed to 0.014 λ. Alternatively, optimizing the Gaussian beam waist radius can relax the wavefront aberration RMS to 0.016 λ. By simultaneously utilizing two optimization methods, the wavefront aberration at the small pupil of the telescope can be reduced to 0.033 λ, resulting in an impressive success rate of 91.15% in meeting the noise requirements.

19.
IEEE Trans Med Imaging ; PP2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557622

RESUMEN

Ophthalmic diseases such as central serous chorioretinopathy (CSC) significantly impair the vision of millions of people globally. Precise segmentation of choroid and macular edema is critical for diagnosing and treating these conditions. However, existing 3D medical image segmentation methods often fall short due to the heterogeneous nature and blurry features of these conditions, compounded by medical image clarity issues and noise interference arising from equipment and environmental limitations. To address these challenges, we propose the Spectrum Analysis Synergy Axial-Spatial Network (SASAN), an approach that innovatively integrates spectrum features using the Fast Fourier Transform (FFT). SASAN incorporates two key modules: the Frequency Integrated Neural Enhancer (FINE), which mitigates noise interference, and the Axial-Spatial Elementum Multiplier (ASEM), which enhances feature extraction. Additionally, we introduce the Self-Adaptive Multi-Aspect Loss (LSM), which balances image regions, distribution, and boundaries, adaptively updating weights during training. We compiled and meticulously annotated the Choroid and Macular Edema OCT Mega Dataset (CMED-18k), currently the world's largest dataset of its kind. Comparative analysis against 13 baselines shows our method surpasses these benchmarks, achieving the highest Dice scores and lowest HD95 in the CMED and OIMHS datasets. Our code is publicly available at https://github.com/IMOP-lab/SASAN-Pytorch.

20.
Talanta ; 275: 126109, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38648686

RESUMEN

To investigate the metabolic alterations in maternal individuals with fetal congenital heart disease (FCHD), establish the FCHD diagnostic models, and assess the performance of these models, we recruited two batches of pregnant women. By metabolomics analysis using Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS), a total of 36 significantly altered metabolites (VIP >1.0) were identified between FCHD and non-FCHD groups. Two logistic regression models and four support vector machine (SVM) models exhibited strong performance and clinical utility in the training set (area under the curve (AUC) = 1.00). The convolutional neural network (CNN) model also demonstrated commendable performance and clinical utility (AUC = 0.89 in the training set). Notably, in the validation set, the performance of the CNN model (AUC = 0.66, precision = 0.714) exhibited better robustness than the six models above (AUC≤0.50). In conclusion, the CNN model based on pseudo-MS images holds promise for real-world and clinical applications due to its better repeatability.

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