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1.
Heliyon ; 10(9): e29928, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38698976

RESUMEN

Patients with non-small cell lung cancer (NSCLC) and anaplastic lymphoma kinase (ALK) mutations have previously derived substantial benefits from ALK tyrosine kinase inhibitors (ALK-TKIs). However, resistance may develop in some patients. We present a case of co-mutation with anaplastic lymphoma kinase (ALK) and rearranged during transfection (RET)-rearranged NSCLC, representing a novel resistance mechanism to ALK-TKIs, in which the patient exhibited a favorable response to combination therapy with ensartinib and pralsetinib. Notably, the patient survived 12 months without experiencing adverse events, a rare occurrence in ALK-rearranged lung adenocarcinoma cases. This case provides further evidence for the existence of RET rearrangements in ALK-positive lung cancer and their potential treatment response to a combination of ALK inhibitors and pralsetinib. This case underscores that a dual-target therapy involving ALK inhibitors, specifically ensartinib and pralsetinib, could be a viable approach in cases of RET-rearranged lung cancer with concurrent targetable ALK mutations. We propose the consideration of this dual-target approach, specifically employing ensartinib and pralsetinib, in managing RET-rearranged lung cancer coexisting with targetable ALK mutations. Given the potential efficacy of these treatments, it is imperative to proactively conduct molecular profiling tests in NSCLC patients upon the emergence of resistance.

2.
Chem Sci ; 15(17): 6522-6529, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38699280

RESUMEN

Site selective functionalization of inert remote C(sp3)-H bonds to increase molecular complexity offers vital potential for chemical synthesis and new drug development, thus it has been attracting ongoing research interest. In particular, typical ß-C(sp3)-H arylation methods using chelation-assisted metal catalysis or metal-catalyzed oxidative/photochemical in situ generated allyl C(sp3)-H bond processes have been well developed. However, radical-mediated direct ß-C(sp3)-H arylation of carbonyls remains elusive. Herein, we describe an iodoarene-directed photoredox ß-C(sp3)-H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). The method involves diethylaminoethyl radical-mediated generation of an aryl radical intermediate via XAT, then directed 1,5-HAT to form the remote alkyl radical intermediate and radical-radical coupling with cyanoarenes, and is applicable to a broad scope of unactivated remote C(sp3)-H bonds like ß-C(sp3)-H bonds of o-iodoaryl-substituted alkanones and α-C(sp3)-H bonds of o-iodoarylamides. Experimental findings are supported by computational studies (DFT calculations), revealing that this method operates via a radical-relay stepwise mechanism involving multiple SET, XAT, 1,5-HAT and radical-radical coupling processes.

3.
Heliyon ; 10(9): e30901, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38774103

RESUMEN

Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P < 0.001; EFS: P < 0.001) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P < 0.001; EFS: P < 0.001) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20highCD138low expression had a consistently favorable OS and EFS compared with those with CD20lowCD138high expression in both the training and validation cohorts (P < 0.0001 and P < 0.01, respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokine‒cytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma.

4.
Talanta ; 276: 126239, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38781912

RESUMEN

In this work, the oxidation of theaflavin-3-gallate (TF-3-G) was investigated using (-)-epicatechin (EC) and (-)-epigallocatechin gallate (EGCG) as substrates in a one-pot reaction. The resulting TF-3-G oxidation product was acquired by employing acetonitrile/water and ethanol/water as eluents, respectively, which was identified as theanaphthoquinone-3'-gallate (TNQ-3'-G). Surprisingly, we discovered that TNQ-3'-G could react with certain protic solvents to form new and unstable complexes through intermolecular hydrogen bond. This reactivity was also confirmed by the presence of irregular peaks in reverse-phase high-performance liquid chromatography (RP-HPLC) besides spectroscopic data. Therefore, we inferred that the number of carboxyl groups may increase through the successive oxidative polymerization of the TFs oxidation products. The high-molecular polymer could also interact with biomacromolecules in a similar manner to their interaction with protic solvents. This interaction might be one of the main factors contributing to the broad hump of thearubigins (TRs) on the RP-HPLC baseline. Additionally, these findings lay a solid foundation for interpreting the structures of TRs and understanding their generation mechanism.

5.
Adv Mater ; : e2403202, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38751336

RESUMEN

Conductive metal-organic frameworks (c-MOFs) and ionic liquids (ILs) have emerged as auspicious combinations for high-performance supercapacitors. However, the nanoconfinement from c-MOFs and high viscosity of ILs slow down the charging process. This hindrance can, however, be resolved by adding solvent. Here, constant-potential molecular simulations are performed to scrutinize the solvent impact on charge storage and charging dynamics of MOF-IL-based supercapacitors. Conditions for >100% enhancement in capacity and ≈6 times increase in charging speed are found. These improvements are confirmed by synthesizing near-ideal c-MOFs and developing multiscale models linking molecular simulations to electrochemical measurements. Fundamentally, the findings elucidate that the solvent acts as an "ionophobic agent" to induce a substantial enhancement in charge storage, and as an "ion traffic police" to eliminate convoluted counterion and co-ion motion paths and create two distinct ion transport highways to accelerate charging dynamics. This work paves the way for the optimal design of MOF supercapacitors.

6.
Front Sports Act Living ; 6: 1393988, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756186

RESUMEN

Background: Long-term skill learning can lead to structure and function changes in the brain. Different sports can trigger neuroplasticity in distinct brain regions. Volleyball, as one of the most popular team sports, heavily relies on individual abilities such as perception and prediction for high-level athletes to excel. However, the specific brain mechanisms that contribute to the superior performance of volleyball athletes compared to non-athletes remain unclear. Method: We conducted a study involving the recruitment of ten female volleyball athletes and ten regular female college students, forming the athlete and novice groups, respectively. Comprehensive behavioral assessments, including Functional Movement Screen and audio-visual reaction time tests, were administered to both groups. Additionally, resting-state magnetic resonance imaging (MRI) data were acquired for both groups. Subsequently, we conducted in-depth analyses, focusing on the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the brain for both the athlete and novice groups. Results: No significant differences were observed in the behavioral data between the two groups. However, the athlete group exhibited noteworthy enhancements in both the ALFF and ReHo within the visual cortex compared to the novice group. Moreover, the functional connectivity between the visual cortex and key brain regions, including the left primary sensory cortex, left supplementary motor cortex, right insula, left superior temporal gyrus, and left inferior parietal lobule, was notably stronger in the athlete group than in the novice group. Conclusion: This study has unveiled the remarkable impact of volleyball athletes on various brain functions related to vision, movement, and cognition. It indicates that volleyball, as a team-based competitive activity, fosters the advancement of visual, cognitive, and motor skills. These findings lend additional support to the early cultivation of sports talents and the comprehensive development of adolescents. Furthermore, they offer fresh perspectives on preventing and treating movement-related disorders. Trial registration: Registration number: ChiCTR2400079602. Date of Registration: January 8, 2024.

7.
Tissue Cell ; 88: 102383, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38613933

RESUMEN

BACKGROUND: Stem cell differentiation has opened up new avenues for disease treatment, tissue repair, and drug development in the study of regenerative medicine, and has huge application prospects. This study aimed to explore the mechanism of quercetin on the differentiation of mesenchymal stem cells (MSCs) into fibroblasts. METHODS: In this study, cell differentiation experiments and flow cytometry were used to detect the successful isolation of bone marrow MSCs from SD rats. Quercetin at 5, 10, and 20 µM was used as low, medium, and high doses to intervene in MSCs. The cell viability changes of ligament fibroblasts at 24, 48, and 72 hours after quercetin treatment were detected using a CCK-8 cell counting kit. Cell proliferative capacity was determined by flow cytometry. RT-qPCR measured the relative expression levels of TGF-ß1, IGF-1, COL-Ⅰ, COL-Ⅲ, FN (fibronectin), and TNMD (Tenomodulin) in different experimental groups. Molecular docking experiments were conducted to explore the binding effect of quercetin on TGF-ß1 and IGF-1 proteins. RESULTS: Flow cytometry verified the successful isolation of MSCs, which had high expression of CD29 and CD73, while lower expression of CD90 and CD45. Experimental results show that low and medium doses of quercetin can enhance cell proliferation, while high doses have no significant effect on cells. Detection of cell proliferation through flow cytometry yielded similar results to CCK-8. Transwell experiments have shown that low and medium doses of quercetin can increase cell migration ability. In addition, RT-qPCR detection showed that quercetin can increase the mRNA expression of TGF-ß1 and IGF-1, and promote the expression of COL-Ⅰ, COL-Ⅲ, FN, and TNMD genes in ligament fibroblasts. Molecular docking results showed that quercetin can bind firmly to TGF-ß1 and IGF-1. CONCLUSION: Overall, this study revealed the morphological characteristics and identification of MSCs, as well as the regulatory mechanism of quercetin on the behavior of ligament fibroblasts. Quercetin affects the proliferation and gene expression of ligament fibroblasts by regulating the expression of TGF-ß1 and IGF-1, which may provide a new perspective for biomedical research on the skeletal system.

8.
Acad Radiol ; 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38644089

RESUMEN

RATIONALE AND OBJECTIVES: Pulmonary nodules or masses are highly prevalent worldwide, and differential diagnosis of benign and malignant lesions remains difficult. Magnetic resonance imaging (MRI) can provide functional and metabolic information of pulmonary lesions. This study aimed to establish a nomogram model based on clinical features, imaging features, and multi-sequence MRI radiomics to identify benign and malignant solid pulmonary nodules or masses. MATERIALS AND METHODS: A total of 145 eligible patients (76 male; mean age, 58.4 years ± 13.7 [SD]) with solid pulmonary nodules or masses were retrospectively analyzed. The patients were randomized into two groups (training cohort, n = 102; validation cohort, n = 43). The nomogram was used for predicting malignant pulmonary lesions. The diagnostic performance of different models was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Of these patients, 95 patients were diagnosed with benign lesions and 50 with malignant lesions. Multivariate analysis showed that age, DWI value, LSR value, and ADC value were independent predictors of malignant lesions. Among the radiomics models, the multi-sequence MRI-based model (T1WI+T2WI+ADC) achieved the best diagnosis performance with AUCs of 0.858 (95%CI: 0.775, 0.919) and 0.774 (95%CI: 0.621, 0.887) for the training and validation cohorts, respectively. Combining multi-sequence radiomics, clinical and imaging features, the predictive efficacy of the clinical-imaging-radiomics model was significantly better than the clinical model, imaging model and radiomics model (all P < 0.05). CONCLUSION: The MRI-based clinical-imaging-radiomics model is helpful to differentiate benign and malignant solid pulmonary nodules or masses, and may be useful for precision medicine of pulmonary diseases.

9.
Huan Jing Ke Xue ; 45(5): 2507-2515, 2024 May 08.
Artículo en Chino | MEDLINE | ID: mdl-38629516

RESUMEN

To study the long-term variation in ozone (O3) pollution in Sichuan Basin,the spatiaotemporal distribution of O3 concentrations during 2017 to 2020 was analyzed using ground-level O3 concentration data and meteorological observation data from 18 cities in the basin. The dominant meteorological factors affecting the variation in O3 concentration were screened out,and a prediction model between meteorological factors and O3 concentration was constructed based on a random forest model. Finally,a prediction analysis of O3 pollution in the Sichuan Basin urban agglomeration during 2020 was carried out. The results showed that:① O3 concentrations displayed a fluctuating trend during the period from 2017 to 2020,with a downward trend in 2019 and a rebound in 2020. ② The fluctuating trend of O3 concentration was significantly influenced by relative humidity,daily maximum temperature,and sunshine hours,whereas wind speed,air pressure,and precipitation had less impact. The linear relationships between meteorological factors were different. Air pressure was negatively correlated with other meteorological factors,whereas the remaining meteorological factors had a positive correlation. ③ The goodness of fit statistics (R2) between the predicted and actual values of the O3 prediction model constructed based on random forest demonstrated a strong predictive performance and ability to accurately forecast the long-term daily variations in O3 concentration. The random forest O3 prediction model exhibited excellent stability and generalization capability. ④ The prediction analysis of O3 concentrations in 18 cities in the basin showed that the explanation rate of variables in the prediction model reached over 80% in all cities (except Ya'an),indicating that the random forest model predicted the trend of O3 concentration accurately.

10.
Mol Microbiol ; 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38629786

RESUMEN

Minute virus of canines (MVC) belongs to the genus Bocaparvovirus (formerly Bocavirus) within the Parvoviridae family and causes serious respiratory and gastrointestinal symptoms in neonatal canines worldwide. A productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. However, little is known about the MVC-host cell interactions. In this study, we identified that two cellular proteins (Hsc70 and Hsp70) interacted with NS1 and VP2 proteins of MVC, and both two domains of Hsc70/Hsp70 were mediated for their interactions. Functional studies revealed that Hsp70 was induced by MVC infection, knockdown of Hsc70 considerably suppressed MVC replication, whereas the replication was dramatically promoted by Hsp70 knockdown. It is interesting that low amounts of overexpressed Hsp70 enhanced viral protein expression and virus production, but high amounts of Hsp70 overexpression weakened them. Upon Hsp70 overexpressing, we observed that the ubiquitination of viral proteins changed with Hsp70 overexpression, and proteasome inhibitor (MG132) restored an accumulation of viral proteins. In addition, we verified that Hsp70 family inhibitors remarkably decreased MVC replication. Overall, we identified Hsc70 and Hsp70 as interactors of MVC NS1 and VP2 proteins and were involved in MVC replication, which may provide novel targets for anti-MVC approach.

11.
Curr Mol Pharmacol ; 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38676510

RESUMEN

BACKGROUND: Amplification of inosine monophosphate dehydrogenase II, EC 1,1,1,205 (IMPDH2) has been reported in various cancers, which results in transformation and tumorigenicity. In our current work, we have explored the oncogenic properties and the underlying pathophysiology of IMPDH2 in hepatoblastoma (HB). METHODS: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB. RESULTS: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB. CONCLUSION: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.

12.
Med ; 5(5): 445-458.e3, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38521070

RESUMEN

BACKGROUND: BEBT-109 is an oral pan-mutant-selective inhibitor of epidermal growth factor receptor (EGFR) that demonstrated promising antitumor potency in preclinical models. METHODS: This first-in-human study was a single-arm, open-label, two-stage study. Phase Ia dose-escalation study evaluated the safety and pharmacokinetics of BEBT-109 in 11 patients with EGFR T790M-mutated advanced non-small cell lung cancer (aNSCLC). Phase Ib dose-expansion study evaluated the safety and efficacy of BEBT-109 in 18 patients with EGFR exon 20 insertion (ex20ins)-mutated treatment-refractory aNSCLC. The primary outcomes were adverse events and antitumor activity. Clinical trial registration number CTR20192575. FINDINGS: The phase Ia study demonstrated no dose-limiting toxicity, no observation of the maximum tolerated dose, and no new safety signals with BEBT-109 in the dose range of 20-180 mg/d, suggesting that BEBT-109 had an acceptable safety profile among patients with EGFR T790M-mutated aNSCLC. Plasma pharmacokinetics of BEBT-109 showed a dose-proportional increase in the area under the curve and maximal concentration, with no significant drug accumulation. The dose-expansion study demonstrated that BEBT-109 treatment was tolerable across the three dose levels. The three most common treatment-related adverse events were diarrhea (100%; 22.2% ≥Grade 3), rash (66.7%; 5.6% ≥Grade 3), and anemia (61.1%; 0% ≥Grade 3). The objective response rate was 44.4% (8 of 18). Median progression-free survival was 8.0 months (95% confidence intervals, 1.33-14.67). CONCLUSION: Preliminary findings showed that BEBT-109 had an acceptable safety profile and favorable antitumor activity in patients with refractory EGFR ex20ins-mutated aNSCLC. FUNDING: National Natural Science Foundation of China.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Exones , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Femenino , Anciano , Exones/genética , Mutación , Dosis Máxima Tolerada , Adulto , Relación Dosis-Respuesta a Droga , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos
13.
Int J Surg ; 110(5): 2679-2691, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38489548

RESUMEN

AIMS: Chemotherapy resistance is an important cause of neoadjuvant therapy failure in pancreatic ductal adenocarcinoma (PDAC). BiTP (anti-PD-L1/TGF-ß bispecific antibody) is a single antibody that can simultaneously and dually target transforming growth factor-beta (TGF-ß) and programmed cell death ligand 1 (PD-L1). We attempted in this study to investigate the efficacy of BiTP in combination with first-line chemotherapy in PDAC. METHODS: Preclinical assessments of BiTP plus gemcitabine and nab-paclitaxel were completed through a resectable KPC mouse model (C57BL/6J). Spectral flow cytometry, tissue section staining, enzyme-linked immunosorbent assays, Counting Kit-8, transwell, and Western blot assays were used to investigate the synergistic effects. RESULTS: BiTP combinatorial chemotherapy in neoadjuvant settings significantly downstaged PDAC tumors, enhanced survival, and had a higher resectability for mice with PDAC. BiTP was high affinity binding to targets and reverse chemotherapy resistance of PDAC cells. The combination overcame immune evasion through reprogramming tumor microenvironment via increasing penetration and function of T cells, natural killer cells, and dendritic cells and decreasing the function of immunosuppression-related cells as regulatory T cells, M2 macrophages, myeloid-derived suppressor cells, and cancer-associated fibroblasts. CONCLUSION: Our results suggest that the BiTP combinatorial chemotherapy is a promising neoadjuvant therapy for PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Desoxicitidina , Gemcitabina , Ratones Endogámicos C57BL , Terapia Neoadyuvante , Paclitaxel , Neoplasias Pancreáticas , Factor de Crecimiento Transformador beta , Animales , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/terapia , Terapia Neoadyuvante/métodos , Ratones , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/terapia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/administración & dosificación , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Anticuerpos Biespecíficos/farmacología , Anticuerpos Biespecíficos/administración & dosificación , Modelos Animales de Enfermedad , Albúminas/farmacología , Albúminas/administración & dosificación , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Sinergismo Farmacológico , Línea Celular Tumoral
14.
Biomedicines ; 12(3)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38540186

RESUMEN

Microbial dysbiosis has an increasingly appreciated impact on carcinogenesis, and the cervicovaginal microbiome plays a critical role in microenvironmental inflammation. Here, we investigated the involvement of the female genital tract Peptostreptococcus species in gynecological cancer via indoleacrylic acid (IAA). IAA production from Peptostreptococcus species and the effect of bacterial culture on tumor growth in vivo were examined. The impact of IAA on cytokine production and indoleamine-2,3-dioxygenase 1 (IDO1) expression in an endometrial cancer (EC) cell line, as well as their effect on Treg and Teff cells, and M1 and M2 macrophage populations were examined in EC patients and tumor-grafted mice. Clinically, Peptostreptococcus species abundance, IAA, and IDO1 expression were verified in EC patients. The results showed that IAA production was induced in the uteri of BALB/c nude mice by Peptostreptococcus species transplantation, and the intratumoral injection of a conditioned medium from Peptostreptococcus cultures into tumor-grafted mice promoted tumor growth. IL-10 expression was upregulated by IAA; IFN-γ expression was increased by IL-10. IFN-γ induced IDO1 expression in the EC cell line. The co-culture of IDO1-expressing EC cells with peripheral blood mononuclear cells upregulated the Treg proportion and decreased the M1/M2 ratio. Clinically, P. anaerobius was more abundant amongst the uterine microbiota of EC patients than the control. The IAA, IDO1, and kynurenine/tryptophan ratios were all higher in EC tissue, and the M1/M2 ratio was lower. Our study sheds light on the link between IDO1 induction and uterine Peptostreptococcus dysbiosis and provides a potential rationale for the role of Peptostreptococcus species in immune tolerance induction in type I endometrial cancer.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38470598

RESUMEN

Cervical abnormal cell detection plays a crucial role in the early screening of cervical cancer. In recent years, some deep learning-based methods have been proposed. However, these methods rely heavily on large amounts of annotated images, which are time-consuming and laborintensive to acquire, thus limiting the detection performance. In this paper, we present a novel Semi-supervised Cervical Abnormal Cell detector (SCAC), which effectively utilizes the abundant unlabeled data. We utilize Transformer as the backbone of SCAC to capture long-range dependencies to mimic the diagnostic process of pathologists. In addition, in SCAC, we design a Unified Strong and Weak Augment strategy (USWA) that unifies two data augmentation pipelines, implementing consistent regularization in semisupervised learning and enhancing the diversity of the training data. We also develop a Global Attention Feature Pyramid Network (GAFPN), which utilizes the attention mechanism to better extract multi-scale features from cervical cytology images. Notably, we have created an unlabeled cervical cytology image dataset, which can be leveraged by semi-supervised learning to enhance detection accuracy. To the best of our knowledge, this is the first publicly available large unlabeled cervical cytology image dataset. By combining this dataset with two publicly available annotated datasets, we demonstrate that SCAC outperforms other existing methods, achieving state-of-theart performance. Additionally, comprehensive ablation studies are conducted to validate the effectiveness of USWA and GAFPN. These promising results highlight the capability of SCAC to achieve high diagnostic accuracy and extensive clinical applications. The code and dataset are publicly available at https://github.com/Lewisonez/cc_detection.

16.
Food Funct ; 15(8): 4262-4275, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38526548

RESUMEN

Changes in the chemical composition of white tea during storage have been studied extensively; however, whether such chemical changes impact the efficacy of white tea in ameliorating colitis remains unclear. In this study, we compared the effects of new (2021 WP) and 10-year-old (2011 WP) white tea on 3% dextrose sodium sulfate (DSS)-induced ulcerative colitis in mice by gavaging mice with the extracts at 200 mg kg-1 day-1. Chemical composition analysis showed that the levels of 50 compounds, such as flavanols, dimeric catechins, and amino acids, were significantly lower in the 2011 WP extract than in the 2021 WP extract, whereas the contents of 21 compounds, such as N-ethyl-2-pyrrolidinone-substituted flavan-3-ols, theobromine, and (-)-epigallocatechin-3-(3''-O-methyl) gallate, were significantly higher. Results of the animal experiments showed that 2011 WP ameliorated the pathological symptoms of colitis, which was superior to the activity of 2021 WP, and this effect was likely enhanced based on the decreasing of the relative abundance of the g_bacteroides and g_Escherichia-Shigella flora in mice with colitis and promoting the conversion of primary bile acids to secondary bile acids in the colon. These results will facilitate the development of novel functional products from white tea.


Asunto(s)
Colitis Ulcerosa , Sulfato de Dextran , Microbioma Gastrointestinal , , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Té/química , Sulfato de Dextran/efectos adversos , Masculino , Extractos Vegetales/farmacología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Camellia sinensis/química , Catequina/farmacología , Catequina/análogos & derivados , Colon/metabolismo , Colon/efectos de los fármacos , Colon/microbiología
17.
Org Lett ; 26(12): 2440-2444, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38502576

RESUMEN

An iodoarene-driven electroreductive remote C(sp3)-H arylation of unsymmetrical 1-(o-iodoaryl)alkyl ethers with cyanoarenes for the site selective synthesis of α-(hetero)aryl ethers is developed. With the introduction of cyanoarenes as both aryl sources and electron transfer mediators, this method includes an iodoarene-driven strategy to enable the regiocontrollable formation of two new bonds, one C(sp2)-H bond, and one C(sp2)-C(sp3) bond, in a single reaction step through the sequence of halogen atom transfer (XAT), hydrogen atom transfer (HAT), radical-radical coupling, and decyanation.

18.
J Hazard Mater ; 469: 133805, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38428293

RESUMEN

It has been reported that Cr(VI) can be reduced by biochar because of its redox activity. Considering the anionic form of Cr(VI), we hypothesize that the reduction in aqueous phase is significant. However, the contribution of different reactive oxygen species in the biochar-Cr(VI) reaction system has not been distinguished. Herein, we quantitatively identified Cr(VI) adsorption and reduction in biochar systems. The reduction content of Cr(VI) was 1.5 times higher in untreated conditions than in anaerobic conditions. The disappearance of·O2- under anaerobic conditions illustrated that·O2- may be involved in the reduction of Cr(VI). Quenching of·O2- resulted in a decrease of Cr(VI) reduction by 34%, while 1O2 was negligible, probably due to the stronger electron-donating capacity of·O2-. The degradation of nitrotetrazolium blue chloride (quenching agent of·O2-) confirmed that the reduction process of·O2- mainly occurred in the liquid-phase. Boehm titration and quantification of·O2- further elucidated the significant correlation (P < 0.05) between phenolic groups and the formation of·O2-, which implied that phenolic groups acted as the primary electron donors in generating·O2-. This study highlights the importance of the liquid-phase reduction process in removing Cr(VI), which provides theoretical support for biochar conversion of Cr(VI).


Asunto(s)
Superóxidos , Contaminantes Químicos del Agua , Carbón Orgánico , Cromo/análisis , Adsorción , Contaminantes Químicos del Agua/análisis
19.
Cancer Immunol Immunother ; 73(4): 74, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38451314

RESUMEN

BACKGROUND: Pembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H. METHODS: This retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting. We analyzed objective response rate (ORR) and progression-free survival (PFS). RESULTS: The top three cancer types were colorectal (48.6% MSI-H, 6.5% TMB-H), lung (15.4% MSI-H, 84.4% TMB-H), and gastric (15.4% MSI-H, 5.1% TMB-H). The ORR with pembrolizumab was 52.6%, including complete response (CR) observed in 8.6% (n = 10) of cases and partial responses (PR) in 43.9% (n = 51). Of the 93 patients who received first-line pembrolizumab, 52 patients achieved objective response (10 CR, 42 PR), with a median PFS of 14.0 months (95% confidence intervals [CI] 6.6-21.4). Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI 3.9-7.5). Treatment-related adverse events were observed in 32 patients (27.6%), with no reported treatment-related fatal adverse events. CONCLUSION: Our study provides real-world evidence on the clinical effectiveness of pembrolizumab with or without chemotherapy in the treatment of patients with MSI-H and TMB-H advanced solid cancers.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Inestabilidad de Microsatélites , Neoplasias , Humanos , Estudios Retrospectivos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , China , Respuesta Patológica Completa
20.
Ultrasonics ; 138: 107246, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38309037

RESUMEN

Themulti-modeanddispersionnature of Lamb waves means that a variety of modes with individual mode structures and distinct dispersion behaviors would propagate in the structures simultaneously. The existence of a corrosion would result in thickness reduction, which means the frequency-thickness product under a specific excitation would also decrease. Due to dispersion diversity, the interaction of each individual Lamb mode at the corrosion may be distinct, i.e., the velocity varies in different extent and even in opposite trends. In this paper, the combination of multiple modes, rather than a single sensitive mode, is used for structure diagnosis. Specifically, two Lamb modes both sensitive to corrosion but with opposite variation trends are taken and the corrosion index is defined on the ratio of their time-of-flight, so as to enhance the sensitivity to corrosion and eliminate the influence of difference path lengths in the sensor network. On this basis, a probabilistic reconstruction algorithm is introduced for corrosion detection and localization. Since the two modes are extracted from the same wideband Lamb wave response, the proposed method is baseline-free. The influence of mode conversion on the effectiveness of the proposed method is discussed. Ultimately, the performance of the proposed method is demonstrated by an experimental example. The results show that the defect could be correctly identified and accurately localized.

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