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1.
J Hazard Mater ; 472: 134524, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38714058

RESUMEN

Developing semiconductor substrates with superior stability and sensitivity is challenging in surface-enhanced Raman scattering (SERS) research. Here, a snowflake Cu2S@ZIF-67 heterostructure was fabricated using a straightforward method, exhibiting a notable enhancement factor of 9.0 × 109 and a limit of detection (LOD) of 10-14 M for methylene blue (MB). In addition, the Cu2S@ZIF-67 heterostructure substrate demonstrates outstanding homogeneity (relative standard deviation (RSD) = 9.2%) and stability (120 days). Employing Cu2S generates highly sensitive hotspots via an electromagnetic (EM) mechanism, and the growth of ZIF-67 on its surface augments the adsorption capacity and charge transfer capability (chemical mechanism, CM), thereby enhancing the SERS detection sensitivity. Furthermore, the Cu2S@ZIF-67 heterostructure, which was used as a SERS substrate, facilitated the detection of bisphenol A (BPA) with an LOD of 10-11 M. The Cu2S@ZIF-67 heterostructure substrate has excellent selectivity and anti-interference, which is very suitable for BPA detection in complex environment applications. The accuracy of the Cu2S@ZIF-67 heterostructure as a SERS substrate for detecting BPA in real water samples (water bottles, tap water, and pure milk) was confirmed by comparison with high-performance liquid chromatography (HPLC). These results demonstrate that through the rational design of heterostructures can achieve the quantitative and accurate detection of hazardous substances in food and the environment can be achieved.

2.
AJR Am J Roentgenol ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691415

RESUMEN

Background: CT is increasingly detecting thyroid nodules. Prior studies indicated a potential role of CT-based radiomics models in characterizing thyroid nodules, although lacked external validation. Objectives: To develop and validate a CT-based radiomics model for the differentiation of benign and malignant thyroid nodules. Methods: This retrospective study included 378 patients (mean age, 46.3±13.9 years; 86 men, 292 women) with 408 resected thyroid nodules (145 benign, 263 malignant) from two centers (center 1: 293 nodules, January 2018-December 2022; center 2: 115 nodules, January 2020-December 2022), who underwent preoperative multiphase neck CT (noncontrast, arterial, and venous phases). Nodules from center 1 were divided into training (n=206) and internal validation (n=87) sets; all nodules from center 2 formed an external validation set. Radiologists assessed nodules for morphologic CT features. Nodules were manually segmented on all phases, and radiomic features were extracted. Conventional (clinical and morphologic CT), noncontrast radiomics, arterial-phase radiomics, venous-phase radiomics, multiphase radiomics, and combined (clinical, morphologic, and multiphase radiomics) models were established using feature selection methods and evaluated by ROC curve analysis, calibration curves, and decision-curve analysis. Results: The combined model included patient age, three morphologic features (cystic change, edge interruption sign, abnormal cervical lymph nodes), and 28 radiomic features (from all three phases). In the external validation set, the combined model had AUC of 0.923 and, at an optimal threshold derived in the training set, sensitivity of 84.0%, specificity of 94.1%, and accuracy of 87.0%. In the external validation set, AUC was significantly higher for the combined model than for the conventional model (0.827), noncontrast radiomics model (0.847), arterial-phase radimoics model (0.826), venous-phase radiomics model (0.773), and multiphase radiomics model (0.824) (all p<.05). In the external validation set, the calibration curves indicated lowest (i.e., best) Brier score for the combined model; in decision-curve analysis, the combined model had the highest net benefit for most of the range of threshold probabilities. Conclusion: A combined model incorporating clinical, morphologic CT, and multiphasic radiomics CT features, exhibited robust performing in differentiating benign and malignant thyroid nodules. Clinical Impact: The combined radiomics model may help guide further management for thyroid nodules detected on CT.

3.
Plant Cell Environ ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695280

RESUMEN

There is often a trade-off effect between different agronomic traits due to gene pleiotropy, leading to a negative correlation between yield and resistance. Consequently, using gene-editing techniques to develop superior traits becomes challenging. Genetic resources that defy this constraint are scarce but hold great potential as targets for improvement through the utilisation of CRISPR. Transcription factors are critical in modulating numerous gene expressions across diverse biological processes. Here, we found that the trihelix transcription factor SlGT30 plays a role in drought resistance and tomato fruit development. We edited the SlGT30 gene with CRISPR/Cas9 technology and found that the knockout lines showed decreased stomata density in the leaves and large fruits. Subsequent examination revealed that cell ploidy was impacted in the leaves and fruits of SlGT30 knockout lines. SlGT30 knockout affected cell size through the endoreduplication pathway, manifested in decreased stomata density and reduced water loss. Consequently, this resulted in an enhancement of drought resistance. For the fruit, both cell size and cell number increased in the fruit pericarp of knockout lines, improving the fruit size and weight accordingly. Therefore, SlGT30 represents a promising candidate gene for gene editing in breeding practice.

4.
Acta Biochim Pol ; 71: 12377, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721303

RESUMEN

Background: Goal-directed fluid therapy, as a crucial component of accelerated rehabilitation after surgery, plays a significant role in expediting postoperative recovery and enhancing the prognosis of major surgical procedures. Methods: In line with this, the present study aimed to investigate the impact of target-oriented fluid therapy on volume management during ERAS protocols specifically for gastrointestinal surgery. Patients undergoing gastrointestinal surgery at our hospital between October 2019 and May 2021 were selected as the sample population for this research. Results: 41 cases of gastrointestinal surgery patients were collected from our hospital over 3 recent years. Compared with T1, MAP levels were significantly increased from T2 to T5; cardiac output (CO) was significantly decreased from T2 to T3, and significantly increased from T4 to T5; and SV level was significantly increased from T3 to T5. Compared with T2, HR and cardiac index (CI) were significantly elevated at T1 and at T3-T5. Compared with T3, SVV was significantly decreased at T1, T2, T4, and T5; CO and stroke volume (SV) levels were increased significantly at T4 and T5. In this study, pressor drugs were taken for 23 days, PACU residence time was 40.22 ± 12.79 min, time to get out of bed was 12.41 ± 3.97 h, exhaust and defecation time was 18.11 ± 7.52 h, and length of postoperative hospital stay was 4.47 ± 1.98 days. The average HAMA score was 9.11 ± 2.37, CRP levels were 10.54 ± 3.38 mg/L, adrenaline levels were 132.87 ± 8.97 ng/L, and cortisol levels were 119.72 ± 4.08 ng/L. Prealbumin levels were 141.98 ± 10.99 mg/L at 3 d after surgery, and 164.17 ± 15.84 mg/L on the day of discharge. Lymphocyte count was 1.22 ± 0.18 (109/L) at 3 d after surgery, and 1.47 ± 0.17 (109/L) on the day of discharge. Serum albumin levels were 30.51 ± 2.28 (g/L) at 3 d after surgery, and 33.52 ± 2.07 (g/L) on the day of discharge. Conclusion: Goal-directed fluid therapy (GDFT) under the concept of Enhanced Recovery After Surgery (ERAS) is helpful in volume management during radical resection of colorectal tumors, with good postoperative recovery. Attention should be paid to the influence of pneumoperitoneum and intraoperative posture on GDFT parameters.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Fluidoterapia , Humanos , Fluidoterapia/métodos , Masculino , Femenino , Persona de Mediana Edad , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/rehabilitación , Anciano , Recuperación Mejorada Después de la Cirugía , Volumen Sistólico , Tiempo de Internación/estadística & datos numéricos , Gasto Cardíaco , Adulto
5.
World J Surg Oncol ; 22(1): 121, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711029

RESUMEN

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated. METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated. RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS. CONCLUSION: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.


Asunto(s)
Calcitonina , Carcinoma Neuroendocrino , Recurrencia Local de Neoplasia , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Calcitonina/sangre , Persona de Mediana Edad , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/mortalidad , Pronóstico , Adulto , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Estudios de Seguimiento , Tiroidectomía/métodos , Anciano , Tasa de Supervivencia , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Adulto Joven , Adolescente , Factores de Riesgo , Factores de Tiempo
6.
Huan Jing Ke Xue ; 45(5): 3027-3036, 2024 May 08.
Artículo en Chino | MEDLINE | ID: mdl-38629563

RESUMEN

Biochar and modified biochar have been widely used as remediation materials in heavy metal-contaminated agricultural soils. In order to explore economical and effective materials for the remediation of cadmium (Cd)-contaminated acidic purple soil, distillers 'grains were converted into distillers' grains biochar (DGBC) and modified using nano-titanium dioxide (Nano-TiO2) to produce two types of modified DGBCs:TiO2/DGBC and Fe-TiO2/DGBC. A rice pot experiment was used to investigate the effects of different biochar types and application rates (1%, 3%, and 5%) on soil properties, nutrient content, Cd bioavailability, Cd forms, rice growth, and Cd accumulation. The results showed that:① DGBC application significantly increased soil pH, cation exchange capacity (CEC), and nutrient content, with TiO2/DGBC and Fe-TiO2/DGBC exhibiting better effects. ② DGBC and modified DGBCs transformed Cd from soluble to insoluble forms, increasing residual Cd by 1.22% to 18.46% compared to that in the control. Cd bioavailability in soil decreased significantly, with available cadmium being reduced by 11.81% to 23.67% for DGBC, 7.64% to 43.85% for TiO2/DGBC, and 19.75% to 55.82% for Fe-TiO2/DGBC. ③ DGBC and modified DGBCs increased rice grain yield, with the highest yields observed at a 3% application rate:30.60 g·pot-1 for DGBC, 37.85 g·pot-1 for TiO2/DGBC, and 39.10 g·pot-1 for Fe-TiO2/DGBC, representing 1.13, 1.40, and 1.44 times the control yield, respectively. Cd content in rice was significantly reduced, with grain Cd content ranging from 0.24 to 0.30 mg·kg-1 for DGBC, 0.16 to 0.26 mg·kg-1 for TiO2/DGBC, and 0.14 to 0.24 mg·kg-1 for Fe-TiO2/DGBC. Notably, Cd content in rice grains fell below the food safety limit of 0.2 mg·kg-1 (GB2762-2022) at 5% for TiO2/DGBC and 3% and 5% for Fe-TiO2/DGBC. In conclusion, Nano-TiO2 modified DGBC effectively reduced the bioavailability of soil Cd through its own adsorption and influence on soil Cd forms distribution, thus reducing the absorption of Cd by rice and simultaneously promoting rice growth and improving rice yield. It is a type of Cd-contaminated soil remediation material with a potential application prospect. The results can provide scientific basis for farmland restoration and agricultural safety production of Cd-contaminated acidic purple soil.


Asunto(s)
Oryza , Contaminantes del Suelo , Cadmio/análisis , Oryza/química , Suelo/química , Contaminantes del Suelo/análisis , Carbón Orgánico/química , Grano Comestible/química
7.
Int J Environ Health Res ; : 1-16, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563461

RESUMEN

Epidemiologic studies have suggested a possible association between air pollution and chronic obstructive pulmonary disease (COPD), but it is controversial and difficult to draw causal inferences. Five methods were adopted to evaluate the causal relationship between air pollution and COPD in European and East Asian populations by using MR Analysis. A statistically significant causal relationship between PM2.5 and COPD was observed in the European population (OR: 2.34; 95% CI: 1.06-5.05; p = 0.033). Statistical significance remained after adjustment for confounding factors (adjusted OR: 2.28; 95% CI: 1.01-5.20; p = 0.048). In East Asian populations, PM2.5 absorbance, a proxy for black carbon, was statistically associated with COPD (OR: 1.41; 95% CI: 1.09-1.81; p = 0.007). We did not adjust for confounders in East Asian populations, as the association was independent of known confounders (e.g. smoking, respiratory tract infections, etc.). In conclusion, increased concentrations of PM2.5 and PM2.5 absorbance were associated with an increased risk of COPD.

8.
Opt Express ; 32(7): 10899-10909, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38570952

RESUMEN

We demonstrate an efficient and widely tunable synchronously pumped optical parametric oscillator (OPO) exploiting four-wave mixing (FWM) in a silicon nitride (Si3N4) waveguide with inverted tapers. At a pump pulse duration of 2 ps, the waveguide-based OPO (WOPO) exhibited a high external pump-to-idler conversion efficiency of up to -7.64 dB at 74% pump depletion and a generation of up to 387 pJ output idler pulse energy around 1.13 µm wavelength. Additionally, the parametric oscillation resulted in a 64 dB amplification of idler power spectral density in comparison to spontaneous FWM, allowing for a wide idler wavelength tunability of 191 nm around 1.15 µm. Our WOPO represents a significant improvement of conversion efficiency as well as output energy among χ3 WOPOs, rendering an important step towards a highly efficient and widely tunable chip-based light source for, e.g., coherent anti-Stokes Raman scattering.

9.
Analyst ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38624147

RESUMEN

Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has the advantages of high throughput (simultaneous detection of multiple ions), high separation efficiency (higher than 105 theoretical plates) and rapid analysis capability (less than 5 min for common inorganic ions). A compact CE-C4D system is ideal for water quality control and on-site analysis. It is suitable not only for common cations (e.g. Na+, K+, Li+, NH4+, Ca2+, etc.) and anions (e.g. Cl-, SO42-, BrO3-, etc.) but also for some ions (e.g. lanthanide ions, Pb2+, Cd2+, etc.) that require complex derivatization procedures to be detected by ion chromatography (IC). However, an obvious limitation of the CE-C4D method is that its sensitivity (e.g. 0.3-1 µM for common inorganic ions) is often insufficient for trace analysis (e.g. 1 ppb or 20 nM level for common inorganic ions) without preconcentration. For this technology to become a powerful and routine analytical technique, the system should be made compact while maintaining trace analysis sensitivity. In this study, we developed an all-in-one version of the CE-C4D instrument with custom-made modular components to make it a convenient, compact and high-performance system. The system was designed using direct digital synthesis (DDS) technology to generate programmable sinusoidal waveforms with any frequency for excitation, a kilovolt high-voltage power supply for capillary electrophoresis separation, and an "effective" differential C4D cell with a low-noise circuitry for high-sensitivity detection. We characterized the system with different concentrations of Cs+, and even a low concentration of 20 nM was detectable without preconcentration. Moreover, the optimized CE-C4D setup was applied to analyse mixed ions at a trace concentration of 200 nM with excellent signal-to-noise ratios. In typical applications, the limits of detection based on the 3σ criterion (without baseline filtering) were 9, 10, 24, 5, and 12 nM for K+, Cs+, Li+, Ca2+, and Mg2+, respectively, and about 7, 6, 6 and 6 nM for Br-, ClO4-, BrO3- and SO42-, respectively. Finally, the setup was also applied for the analysis of all 14 lanthanide ions and rare-earth minerals, and it showed an improvement in sensitivity by more than 25 times.

10.
Environ Int ; 187: 108672, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38648691

RESUMEN

Manganese (Mn) is an essential micronutrient required for various biological processes but excess exposure to Mn can cause neurotoxicity. However, there are few reports regarding the toxicity effect of Mn on the kidney as well as the underlying molecule mechanism. Herein, in vivo experiments were adopted to assess the toxicity effects associated with Mn, and found that chronic Mn treatment induced the injury of glomerular podocytes but not renal tubule in rats. Genome-wide CRISPR/Cas9 knockout screen was then employed to explore the biotargets of the toxic effect of Mn on podocytes. Through functional analyses of the enriched candidate genes, NLRP10 was found to be significantly up-regulated and mediated Mn-induced podocyte apoptosis. Further mechanism investigation revealed that NLRP10 expression was regulated by demethylase AlkB homolog 5 (ALKBH5) in an m6A-dependent fashion upon Mn treatment. Moreover, Mn could directly bind to Metadherin (MTDH) and promoted its combination with ALKBH5 to promote NLRP10 expression and cell apoptosis. Finally, logistic regressions, restricted cubic spline regressions and uniform cubic B-spline were used to investigate the association between Mn exposure and the risk of chronic kidney disease (CKD). A U-shaped nonlinear relationship between CKD risk and plasma Mn level, and a positive linear relationship between CKD risk and urinary Mn levels was found in our case-control study. To sum up, our findings illustrated that m6A-dependent NLRP10 regulation is indispensable for podocyte apoptosis and nephrotoxicity induced by Mn, providing fresh insight into understanding the health risk of Mn and a novel target for preventing renal injury in Mn-intoxicated patients.

12.
World J Clin Oncol ; 15(3): 419-433, 2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38576593

RESUMEN

BACKGROUND: Accurate preoperative prediction of lymph node metastasis (LNM) in esophageal cancer (EC) patients is of crucial clinical significance for treatment planning and prognosis. AIM: To develop a clinical radiomics nomogram that can predict the preoperative lymph node (LN) status in EC patients. METHODS: A total of 32 EC patients confirmed by clinical pathology (who underwent surgical treatment) were included. Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy, and its correlation with LNM was analyzed. Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python. Feature extraction, data dimensionality reduction, and feature selection were performed using XGBoost model and leave-one-out cross-validation. Multivariable logistic regression analysis was used to establish the prediction model, which included radiomics features, LN status from computed tomography (CT) reports, and B7-H3 mRNA expression, represented by a radiomics nomogram. Receiver operating characteristic area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical application value of the model. RESULTS: The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis, and the difference was statistically significant (P < 0.05). The AUC value in the receiver operating characteristic (ROC) curve was 0.718 (95%CI: 0.528-0.907), with a sensitivity of 0.733 and specificity of 0.706, indicating good diagnostic performance. The individualized clinical prediction nomogram included radiomics features, LN status from CT reports, and B7-H3 mRNA expression. The ROC curve demonstrated good diagnostic value, with an AUC value of 0.765 (95%CI: 0.598-0.931), sensitivity of 0.800, and specificity of 0.706. DCA indicated the practical value of the radiomics nomogram in clinical practice. CONCLUSION: This study developed a radiomics nomogram that includes radiomics features, LN status from CT reports, and B7-H3 mRNA expression, enabling convenient preoperative individualized prediction of LNM in EC patients.

13.
Int Immunopharmacol ; 133: 112079, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38615376

RESUMEN

Porcine rotavirus (PoRV) poses a threat to the development of animal husbandry and human health, leading to substantial economic losses. VP6 protein is the most abundant component in virus particles and also the core structural protein of the virus. Firstly, this study developed an antibiotic-resistance-free, environmentally friendly expression vector, named asd-araC-PBAD-alr (AAPA). Then Recombinant Lactiplantibacillus plantarum (L. plantarum) strains induced by arabinose to express VP6 and VP6-pFc fusion proteins was constructed. Subsequently, This paper discovered that NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S could enhance host immunity and prevent rotavirus infection in neonatal mice and piglets. The novel recombinant L. plantarum strains constructed in this study can serve as oral vaccines to boost host immunity, offering a new strategy to prevent PoRV infection.

14.
Drug Resist Updat ; 74: 101085, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38636338

RESUMEN

Enhanced DNA repair is an important mechanism of inherent and acquired resistance to DNA targeted therapies, including poly ADP ribose polymerase (PARP) inhibition. Spleen associated tyrosine kinase (Syk) is a non-receptor tyrosine kinase acknowledged for its regulatory roles in immune cell function, cell adhesion, and vascular development. This study presents evidence indicating that Syk expression in high-grade serous ovarian cancer and triple-negative breast cancers promotes DNA double-strand break resection, homologous recombination (HR), and subsequent therapeutic resistance. Our investigations reveal that Syk is activated by ATM following DNA damage and is recruited to DNA double-strand breaks by NBS1. Once localized to the break site, Syk phosphorylates CtIP, a pivotal mediator of resection and HR, at Thr-847 to promote repair activity, particularly in Syk-expressing cancer cells. Inhibition of Syk or its genetic deletion impedes CtIP Thr-847 phosphorylation and overcomes the resistant phenotype. Collectively, our findings suggest a model wherein Syk fosters therapeutic resistance by promoting DNA resection and HR through a hitherto uncharacterized ATM-Syk-CtIP pathway. Moreover, Syk emerges as a promising tumor-specific target to sensitize Syk-expressing tumors to PARP inhibitors, radiation and other DNA-targeted therapies.


Asunto(s)
Roturas del ADN de Doble Cadena , Resistencia a Antineoplásicos , Recombinación Homóloga , Quinasa Syk , Quinasa Syk/metabolismo , Quinasa Syk/genética , Quinasa Syk/antagonistas & inhibidores , Humanos , Roturas del ADN de Doble Cadena/efectos de los fármacos , Femenino , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Fosforilación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Reparación del ADN/efectos de los fármacos , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/antagonistas & inhibidores , Proteínas de la Ataxia Telangiectasia Mutada/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Animales , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos
15.
Aging (Albany NY) ; 16(7): 6488-6509, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38579171

RESUMEN

BACKGROUND: Thyroid cancer represents the most prevalent malignant endocrine tumour, with rising incidence worldwide and high mortality rates among patients exhibiting dedifferentiation and metastasis. Effective biomarkers and therapeutic interventions are warranted in aggressive thyroid malignancies. The transcription factor 19 (TCF19) gene has been implicated in conferring a malignant phenotype in cancers. However, its contribution to thyroid neoplasms remains unclear. RESULTS: In this study, we performed genome-wide and phenome-wide association studies to identify a potential causal relationship between TCF19 and thyroid cancer. Our analyses revealed significant associations between TCF19 and various autoimmune diseases and human cancers, including cervical cancer and autoimmune thyroiditis, with a particularly robust signal for the deleterious missense variation rs2073724 that is associated with thyroid function, hypothyroidism, and autoimmunity. Furthermore, functional assays and transcriptional profiling in thyroid cancer cells demonstrated that TCF19 regulates important biological processes, especially inflammatory and immune responses. We demonstrated that TCF19 could promote the progression of thyroid cancer in vitro and in vivo and the C>T variant of rs2073724 disrupted TCF19 protein binding to target gene promoters and their expression, thus reversing the effect of TCF19 protein. CONCLUSIONS: Taken together, these findings implicate TCF19 as a promising therapeutic target in aggressive thyroid malignancies and designate rs2073724 as a causal biomarker warranting further investigation in thyroid cancer.


Asunto(s)
Polimorfismo de Nucleótido Simple , Neoplasias de la Tiroides , Animales , Humanos , Ratones , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Tiroiditis/genética
17.
Heliyon ; 10(8): e29857, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38681571

RESUMEN

Objective: Medullary thyroid carcinoma (MTC) is a rare malignancy secreting calcitonin (Ctn). We aimed to analyze the relationship between Ctn levels at different time points in patients with MTC, and evaluate its predictive effect on recurrence. Methods: A retrospective study of patients diagnosed with MTC in a large medical center were conducted in northern China. The interrelationships between preoperative Ctn, normalization of postoperative serum Ctn at the first month (NPS), and long-term biochemical cure as well as their predicting roles on structural recurrence were assessed. Results: A total of 212 patients were included in this study. The median follow-up time was 59.5 months. The 5- and 10-year cumulative disease-free survival rates were 81.5 % and 66.8 %, respectively. NPS (OR: 216.33, 95 % CI: 28.69-1631.09, P < 0.001) and absence of structural recurrence (OR: 61.71, 95 % CI: 3.90-975.31; P = 0.003) were associated with biochemical cure. Non-biochemical cure (OR: 28.76; 95 % CI: 2.84-290.86; P = 0.004, HR: 14.63, 95 % CI: 2.27-94.07, P = 0.005), larger tumor size (OR: 8.79, 95 % CI: 2.12-36.40, P = 0.003, HR: 5.41, 95 % CI: 2.04-14.37, P = 0.001), and multifocality (OR: 4.02, 95 % CI: 1.06-15.17, P = 0.040, HR: 3.00, 95 % CI: 1.18-7.60, P = 0.021) were unfavorable independent predictors of structural recurrence and disease-free survival. For sporadic MTC confined to the thyroid lobe, there was no difference in biochemical or structural prognosis between the different surgeries in the subgroup analysis. Conclusions: NPS, rather than preoperative Ctn, predicted long-term biochemical cure for MTC. Non-biochemical cure, larger tumor burden including larger tumor size and multifocality at initial surgery, served as worse prognostic predictors.

18.
PLoS Pathog ; 20(4): e1012141, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38626263

RESUMEN

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus etiologically associated with multiple malignancies. Both latency and sporadic lytic reactivation contribute to KSHV-associated malignancies, however, the specific roles of many KSHV lytic gene products in KSHV replication remain elusive. In this study, we report that ablation of ORF55, a late gene encoding a tegument protein, does not impact KSHV lytic reactivation but significantly reduces the production of progeny virions. We found that cysteine 10 and 11 (C10 and C11) of pORF55 are palmitoylated, and the palmytoilation is essential for its Golgi localization and secondary envelope formation. Palmitoylation-defective pORF55 mutants are unstable and undergo proteasomal degradation. Notably, introduction of a putative Golgi localization sequence to these palmitoylation-defective pORF55 mutants restores Golgi localization and fully reinstates KSHV progeny virion production. Together, our study provides new insight into the critical role of pORF55 palmitoylation in KSHV progeny virion production and offers potential therapeutic targets for the treatment of related malignancies.


Asunto(s)
Aparato de Golgi , Herpesvirus Humano 8 , Lipoilación , Proteínas Virales , Virión , Replicación Viral , Herpesvirus Humano 8/fisiología , Herpesvirus Humano 8/metabolismo , Aparato de Golgi/metabolismo , Aparato de Golgi/virología , Humanos , Virión/metabolismo , Proteínas Virales/metabolismo , Proteínas Virales/genética , Replicación Viral/fisiología , Células HEK293
19.
Plants (Basel) ; 13(8)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38674466

RESUMEN

This study aimed to explore the impact of L-arginine (Arg) on the development of resistance to Alternaria tenuissima (A. tenuissima) in blueberries. The metabolism of reactive oxygen species, pathogenesis-related proteins (PRs), and jasmonic acid (JA) biosynthesis pathways were analyzed, including changes in activity and gene expression of key enzymes. The results indicated that Arg treatment could prevent the development of Alternaria fruit rot in postharvest blueberries. In addition, it was also found to induce a burst of hydrogen peroxide in the blueberries early on during storage, thereby improving their resistance to A. tenuissima. Arg treatment was observed to increase the activity of antioxidant enzymes (peroxidase, catalase, superoxide dismutase, and ascorbate peroxidase) and related gene expression, as well as the total levels of phenolics, flavonoids, and anthocyanin in the blueberries. The activity and gene expression of the PRs (chitinase and ß-1,3-glucanase) were elevated in Arg-treated blueberries, boosting their resistance to pathogens. Additionally, a surge in endogenous JA content was detected in Arg-treated blueberries, along with upregulated expression of key genes related the JA biosynthesis pathway (VcLOX1, VcAOS1, VcAOC, VcAOC3, VcOPR1, VcOPR3, VcMYC2, and VcCOI1), thereby further bolstering disease resistance. In conclusion, Arg treatment was determined to be a promising prospective method for controlling Alternaria fruit rot in blueberries.

20.
ACS Chem Neurosci ; 15(9): 1893-1903, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38613492

RESUMEN

Depression is a common mental disorder. In recent years, more and more attention has been paid to depression and its etiology and pathogenesis. This review aims to explore the neuroprotective and antidepressant effects of hop components. By establishing an in vitro cell damage model using PC12 cells induced by corticosterone (CORT) and an in vivo depression model through the intracranial injection of lipopolysaccharide (LPS) in mice, hop ethyl acetate extract (HEA) was used to study the protective effect and mechanism of HEA on neuronal cells in vitro and the antidepression effect and mechanism in vivo. The results showed that HEA increased the survival and decreased the rate of lactate dehydrogenase (LDH) release, apoptosis, and the ROS and NO content of CORT-induced PC12 cells. HEA alleviated depressive-like behavior, neuroinflammation, reduction of norepinephrine, and dendritic spines induced by intracerebroventricular injection of LPS in mice and increases the expression levels of BDNF, SNAP 25, and TrkB proteins without any significant side effects or toxicity. Hops demonstrated significant comprehensive utilization value, and this work provided an experimental basis for the role of hops in the treatment of depression and provided a basis for the development of HEA for antidepressant drugs or dietary therapy products.


Asunto(s)
Acetatos , Antidepresivos , Corticosterona , Depresión , Humulus , Fármacos Neuroprotectores , Extractos Vegetales , Animales , Células PC12 , Ratones , Depresión/tratamiento farmacológico , Extractos Vegetales/farmacología , Acetatos/farmacología , Antidepresivos/farmacología , Ratas , Fármacos Neuroprotectores/farmacología , Masculino , Humulus/química , Lipopolisacáridos/farmacología , Modelos Animales de Enfermedad , Conducta Animal/efectos de los fármacos
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