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1.
Intern Med J ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563467

RESUMO

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

2.
Molecules ; 29(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542839

RESUMO

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3-H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.

3.
Genes Genet Syst ; 992024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38417894

RESUMO

Homeostasis is essential for muscle repair and regeneration after skeletal muscle exercise. This study investigated the role of methyltransferase-like 21C (METTL21C) in skeletal muscle of mice after exercise and the potential mechanism. First, muscle samples were collected at 2, 4 and 6 weeks after exercise, and liver glycogen, muscle glycogen, blood lactic acid and triglyceride were assessed. Moreover, the expression levels of autophagy markers and METTL21C in skeletal muscle were analyzed. The results showed that the expression levels of METTL21C and MYH7 in the gastrocnemius muscle of mice in the exercise group were significantly higher after exercise than those in the control group, which suggested that long-term exercise promoted the formation of slow-twitch muscle fibers in mouse skeletal muscle. Likewise, the autophagy capacity was enhanced with the prolongation of exercise in muscles. The findings were confirmed in mouse C2C12 cells. We discovered that knockdown of Mettl21c reduced the expression of MYH7 and the autophagy level in mouse myoblasts. These findings indicate that METTL21C promotes skeletal muscle homeostasis after exercise by enhancing autophagy, and also contributes to myogenic differentiation and the formation of slow muscle fibers.


Assuntos
Autofagia , Metiltransferases , Fibras Musculares de Contração Lenta , Cadeias Pesadas de Miosina , Condicionamento Físico Animal , Animais , Camundongos , Metiltransferases/metabolismo , Metiltransferases/genética , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Fibras Musculares de Contração Lenta/metabolismo , Masculino , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Linhagem Celular , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular
4.
Front Microbiol ; 15: 1349151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333587

RESUMO

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A-H (1-8), and two new eudesmane-type sesquiterpenes, eutypellaolides I-J (9-10), along with four known 12,8-eudesmanolide compounds 11-14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 µg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 µM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 µM, respectively.

5.
Clin Exp Immunol ; 216(2): 132-145, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38386917

RESUMO

Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and activating receptor cluster of differentiation 226 (CD226) are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS. We comparatively assessed the changes of CD56brightNK, CD56dimNK, and NK-like cells in 70 pAPS patients compared with control groups, including systemic lupus erythematosus, asymptomatic antiphospholipid antibodies carriers (asymp-aPLs carriers), and healthy controls and their expression diversities of CD226/TIGIT by flow cytometry. CD25, CD69, CD107α expression, and interferon gamma (IFN-γ) secretion levels of NK subsets were detected to determine the potential association of CD226/TIGIT expression with NK subsets phenotypes. CD226/TIGIT expression levels were compared among different subgroups divided by aPLs status. Moreover, in vitro cultures were conducted to explore the potential mechanisms of CD226/TIGIT expression imbalance. CD56brightNK and CD3+CD56+NK-like cells were significantly increased while CD56dimNK cells were obviously decreased in pAPS, and CD56brightNK and NK-like cells exhibited significantly higher CD226 but lower TIGIT expressions. CD226+CD56brightNK and TIGIT-CD56brightNK cells show higher CD69 expression and IFN-γ secretion capacity, and CD226+NK-like and TIGIT-NK-like cells showed higher expressions of CD25 and CD69 but lower apoptosis rate than CD226- and TIGIT+CD56brightNK/NK-like cells, respectively. The imbalanced CD226/TIGIT expressions were most significant in aPLs triple-positive group. Imbalanced expressions of CD226/TIGIT on CD56brightNK and NK-like cells were aggravated after interleukin-4 (IL-4) stimulation and recovered after tofacitinib blocking. Our data revealed significant imbalanced CD226/TIGIT expressions on NK subsets in pAPS, which closely associated with NK subsets phenotypes and more complicated autoantibody status. CD226/TIGIT imbalanced may be affected by IL-4/Janus Kinase (JAK) pathway activation.

6.
Cell Mol Biol Lett ; 29(1): 5, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172714

RESUMO

BACKGROUND: The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. METHODS: R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. RESULTS: MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. CONCLUSION: This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Linfoma Difuso de Grandes Células B , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Regiões Promotoras Genéticas , Linfoma Difuso de Grandes Células B/genética , Hematopoese , Linhagem Celular Tumoral , Proteínas Nucleares/metabolismo
7.
Org Lett ; 26(2): 477-482, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38194611

RESUMO

A palladium/norbornene catalyzed two-component coupling process involving acylation/cyanation of aryl iodides is reported. In this work, aryl acyl nitrile compounds are cleverly selected to provide both nitrile and acyl sources by palladium-catalyzed cleavage of the C-CN bond as both an electrophilic reagent and a termination reagent. This is the first example of C-CN bond cleavage bifunctionalization of aryl iodides. After a series of important NBE derivatives are screened, the products resulting from the bifunctionalization of aryl iodides are smoothly obtained. This strategy has a wide range of substrates and good functional group compatibility. Moreover, this synthetic protocol demonstrated a good application for the synthesis of diverse O,N,C-substituted isoindolinones.

8.
iScience ; 26(9): 107609, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37664593

RESUMO

Tubulointerstitial abnormalities contribute to the progression of diabetic kidney disease (DKD). However, the underlying mechanism of the pathobiology of tubulointerstitial disease is largely unknown. Here, we showed that MYCT1 expression was downregulated in in vitro and in vivo DKD models. Adeno-associated virus (AAV)-Myct1 significantly attenuated renal dysfunction and tubulointerstitial fibrosis in diabetic db/db mice and downregulated Sp1 transcription and TGF-ß1/SMAD3 pathway activation. In human proximal tubular epithelial cells, high glucose-induced high expression of SP1 and TGF-ß1/SMAD3 pathway activation as well as overaccumulation of extracellular matrix (ECM) were abrogated by MYCT1 overexpression. Mechanistically, the binding of VDR to the MYCT1 promoter was predicted and confirmed using dual-luciferase reporter and ChIP analysis. VDR transcriptionally upregulates MYCT1. Our data reveal MYCT1 as a new and potential therapeutic target in treating DKD.

9.
Biomed Environ Sci ; 36(8): 715-724, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37711083

RESUMO

Objective: This study aimed to reveal the insomnia burden and relevant influencing factors among informal caregivers (ICs) of hospitalized patients with lung cancer. Methods: A cross-sectional study on ICs of hospitalized patients with lung cancer was conducted from December 31, 2020 to December 31, 2021. ICs' burden was assessed using the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Linear and logistic regression models were used to identify the influencing factors. Results: Among 289 ICs of hospitalized patients with lung cancer, 83 (28.72%), 53 (18.34%), and 14 (4.84%) ICs experienced mild, moderate, and severe insomnia, respectively. The scores concerning self-esteem, lack of family support, financial problems, disturbed schedule, and health problems were 4.32 ± 0.53, 2.24 ± 0.79, 2.84 ± 1.14, 3.63 ± 0.77, and 2.44 ± 0.95, respectively. ICs with higher Activities of Daily Living Scale (ADLS) scores were associated with a lower risk of insomnia, with an odd ratio ( OR) and 95% confidence interval ( CI) of 0.940 (0.898-0.983). Among the ICs, female gender ( OR = 2.597), alcohol consumption ( OR = 3.745), underlying medical conditions ( OR = 11.765), long-term caregiving experience ( OR = 37.037), and higher monthly expenses ( OR = 5.714) were associated with a high risk of insomnia. Conclusion: Of the hospitalized patients with lung cancer, 51.9% experienced insomnia. Patients' ADL, ICs gender, alcohol consumption, underlying medical conditions, caregiving duration, and monthly expenses were influencing factors. Therefore, prompt screening and early intervention for ICs of patients with lung cancer is necessary.


Assuntos
Neoplasias Pulmonares , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Cuidadores , Atividades Cotidianas , Estudos Transversais , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Neoplasias Pulmonares/epidemiologia
10.
Chem Commun (Camb) ; 59(72): 10781-10784, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37593789

RESUMO

Multinary intermetallic compounds with rich chemical compositions enable one to achieve a logical design for desired materials based on the required function. In this work, we have demonstrated a step-by-step strategy to design a quaternary intermetallic compound that exhibits highly active and stable performance for the hydrogen evolution reaction (HER). With binary intermetallic TaCo2 as the starting point, the minor inclusion of a ductile Cu element in TaCo2 to form ternary TaCu0.25Co1.75 can substantially lower the degradation rate from ca. 20% to 5% after sintering treatment (i.e., enhance connectivity between particles). However, the overpotential at a current density of 10 mA cm-2 (η10) increases by ca. 20 mV from TaCo2 to TaCu0.25Co1.75. Further incorporation of a HER active Ru element to cast quaternary TaCu0.125Ru0.125Co1.75 can decrease ca. 70 mV of η10 while maintaining long-term stability. This proves that one can design functional intermetallic compounds intentionally, which may be extended to different fields of application.

11.
Inorg Chem ; 62(31): 12175-12180, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37490593

RESUMO

The higher population of the antibonding state around the Fermi level will result in better activity yet lower stability of HER (Re vs Ru metal). There seems to be a limitation or balance for using a single metal since the bonding scheme of a single metal is relatively simple. Combining Re (strong bonding), Ru (HER active), and Zr metal (corrosion-resistant) grants ternary intermetallic compound ZrRe1.75Ru025, exhibiting excellent HER activity and stability in acidic and alkaline electrolytes. The overpotential at a current density of 10 mA/cm2 (η10) for ZrRe1.75Ru025 is much lower compared to that of ZrRe2. Although the HER activity of ZrRe1.75Ru025 is not comparable to that of ZrRu2, it demonstrates outstanding HER stability, while the current density of ZrRu2 is over ca. 16% after 6 h. This suggests that intermetallic compounds can break the constraint between activity and stability in a single metal for HER, which may be applied in other fields as well.

12.
Viruses ; 15(7)2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37515214

RESUMO

The large population movement during the Spring Festival travel in China can considerably accelerate the spread of epidemics, especially after the relaxation of strict control measures against COVID-19. This study aims to assess the impact of population migration in Spring Festival holiday on epidemic spread under different scenarios. Using inter-city population movement data, we construct the population flow network during the non-holiday time as well as the Spring Festival holiday. We build a large-scale metapopulation model to simulate the epidemic spread among 371 Chinese cities. We analyze the impact of Spring Festival travel on the peak timing and peak magnitude nationally and in each city. Assuming an R0 (basic reproduction number) of 15 and the initial conditions as the reported COVID-19 infections on 17 December 2022, model simulations indicate that the Spring Festival travel can substantially increase the national peak magnitude of infection. The infection peaks arrive at most cities 1-4 days earlier as compared to those of the non-holiday time. While peak infections in certain large cities, such as Beijing and Shanghai, are decreased due to the massive migration of people to smaller cities during the pre-Spring Festival period, peak infections increase significantly in small- or medium-sized cities. For a less transmissible disease (R0 = 5), infection peaks in large cities are delayed until after the Spring Festival. Small- or medium-sized cities may experience a larger infection due to the large-scale population migration from metropolitan areas. The increased disease burden may impose considerable strain on the healthcare systems in these resource-limited areas. For a less transmissible disease, particular attention needs to be paid to outbreaks in large cities when people resume work after holidays.


Assuntos
COVID-19 , Epidemias , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Férias e Feriados , China/epidemiologia , Epidemias/prevenção & controle , Viagem
13.
Sci Rep ; 13(1): 9256, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286786

RESUMO

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2- and triple-negative breast cancer (TNBC). Among HR+HER2- breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. HR+HER2- breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Linfócitos do Interstício Tumoral , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2
14.
PhytoKeys ; 221: 117-129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250354

RESUMO

Sedumjinglanii, a new species of Crassulaceae from Mount Danxia in Guangdong, China, is described and illustrated. Phylogenetic analysis based on the internal transcribed spacer (ITS) region of nrDNA suggests that the new species belongs to S.sect.Sedum sensu Fu and Ohba (2001) in the "Flora of China", and is sister to a clade comprising S.alfredi and S.emarginatum with high support values (SH-aLRT = 84, UFBS = 95) but is distantly related to S.baileyi. The new species is morphologically similar to S.alfredi but it can be distinguished from the latter in its opposite leaves (vs. alternate leaves), its usually wider leaves (0.4-1.2 cm vs. 0.2-0.6 cm), its usually shorter petals (3.4-4.5 mm vs. 4-6 mm), its shorter nectar scales (0.4-0.5 mm vs. 0.5-1 mm), its shorter carpels (1.5-2.6 mm vs. 4-5 mm), and its shorter styles (0.6-0.9 mm vs. 1-2 mm). The new species can be easily distinguished from S.emarginatum which both have opposite leaves by its short, erect or ascending rhizome (vs. long and prostrate rhizome in the latter), shorter petals (3.4-4.5 mm vs. 6-8 mm) and shorter carpels (1.5-2.6 mm vs. 4-5 mm). It can also be easily distinguished from S.baileyi by its short, erect or ascending rhizome (vs. long and prostrate rhizome) and its shorter style (0.6-0.9 mm vs. 1-1.5 mm).

15.
J Agric Food Chem ; 71(16): 6277-6287, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37068196

RESUMO

In moths, the interactions between chemosensory proteins (CSPs) and sex pheromones have yet to be comprehensively investigated. Here, we examined the function of AlepCSP2 in male Athetis lepigone based on protein expression, molecular docking, site-directed mutagenesis, fluorescence competitive binding analyses, and RNA interference (RNAi) experiments. We found that AlepCSP2 showed strong binding affinity for two sex pheromones and five maize volatiles and that binding was optimal under neutral conditions. Furthermore, we identified six amino acids as being key residues involved in the interaction between AlepCSP2 and multiple ligands. Further RNAi showed that siCSP2 males displayed consistently lower electroantennography responses to two sex pheromones and three maize volatiles at different dosages tested, and the mating rate also decreased significantly by 37.50%. These findings will contribute to characterizing the binding mechanisms of moth CSPs to sex pheromones and host volatiles and also identify unique targets for developing novel pest behavior disruptors.


Assuntos
Mariposas , Atrativos Sexuais , Masculino , Animais , Atrativos Sexuais/metabolismo , Zea mays/genética , Zea mays/metabolismo , Simulação de Acoplamento Molecular , Mariposas/metabolismo , Proteínas de Insetos/metabolismo , Percepção , Feromônios/metabolismo
16.
Heliyon ; 9(4): e15197, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37095921

RESUMO

Glycocalyx is located outside the vascular endothelial cells playing an important role in vascular homeostasis. However, lacking efficient detection methods is one of the biggest obstacles to study the glycocalyx. In this study, three dehydration methods were used to compare the preservation of HUVEC, aorta and kidney glycocalyx by transmission electron microscope. The chemical pre-fixation was performed by lanthanum nitrate staining, and the mice aorta and renal glycocalyx were prepared by different dehydration methods such as ethanol gradient, acetone gradient and low temperature dehydration. HUVEC glycocalyx was prepared by acetone gradient and low temperature dehydration. Low temperature dehydration method preserves HUVEC and mice aortic glycocalyx completely, which had a certain thickness and presented a needle-like structure. But for mice kidney, the acetone gradient dehydration preparation method could better preserve the glycocalyx integrity than other two methods. In conclusion, low temperature dehydration method is suitable for HUVEC and aortic glycocalyx preservation, acetone gradient dehydration method is more suitable for kidney glycocalyx preservation.

17.
Molecules ; 27(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36234926

RESUMO

A cascade 6-endo-dig cyclization reaction was developed for the switchable synthesis of halogen and non-halogen-functionalized pyrazolo[3,4-b]pyridines from 5-aminopyrazoles and alkynyl aldehydes via C≡C bond activation with silver, iodine, or NBS. In addition to its wide substrate scope, the reaction showed good functional group tolerance as well as excellent regional selectivity. This new protocol manipulated three natural products, and the arylation, alkynylation, alkenylation, and selenization of iodine-functionalized products. These reactions demonstrated the potential applications of this new method.


Assuntos
Produtos Biológicos , Iodo , Aldeídos/química , Iodo/química , Estrutura Molecular , Pirazóis , Piridinas/química , Prata
18.
Breast Cancer Res Treat ; 196(1): 45-56, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36056297

RESUMO

INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Inibidores de Checkpoint Imunológico , Ligantes , Linfócitos do Interstício Tumoral , Mutação , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/terapia , Tirosina/metabolismo
19.
J Org Chem ; 87(18): 12460-12469, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36067376

RESUMO

A high efficiency protocol was developed for the synthesis of 2,5-disubstituted oxazoles via iodine-promoted oxidative domino cyclization. These reactions were performed with readily available methyl azaarenes and α-amino ketones under metal-free conditions. This protocol is a simple method with high functional group compatibility, a wide range of substrates, and excellent yield, providing a new way to synthesize azaarene-attached oxazoles.


Assuntos
Iodo , Cetonas , Catálise , Iodetos , Estrutura Molecular , Oxazóis , Estresse Oxidativo
20.
Ying Yong Sheng Tai Xue Bao ; 33(9): 2431-2440, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36131659

RESUMO

To understand the development mechanism of the epiphyllous bud of waterlily, we examined the morphological anatomy of the leaf-navel epiphyllous bud by paraffin section technique at four stages, and compared the differences of carbohydrate metabolism between viviparous and non-viviparous waterlily leaves. Three tropical waterlily cultivars of Brachyceras were used, including two viviparous cultivars Nymphaea 'Margaret Mary', Nymphaea 'Ruby', and a non-viviparous cultivar Nymphaea 'Pink Star'. The results showed that parenchyma cells below the epidermis of leaf-navel divided and grew continuously after the leaf unfolded, forming a closely arranged cell cluster in viviparous waterlily and raised upward to a spherical shape. In contrast, no change was observed in leaf-navel of non-viviparous waterlily with the expansion of leaves. With the development of leaves, the contents of all physiological variables except sucrose and enzyme activities in the leaves of viviparous waterlily showed a first increase and then a decrease, which was significantly higher than those of non-viviparous waterlily. The carbohydrate contents in different parts showed the order of leaf > leaf-navel > petiole (except for starch content, which was highest in the leaf-navel). The activities of sucrose synthase (SS) and acid invertase (AI) were higher than those of sucrose phosphate synthase (SPS) and neutral invertase (NI). The activities of SPS and NI in different tissues of viviparous waterlily were significantly higher than those in non-viviparous one, but SS and AI did not show pronounced cultivar advantage in viviparous cultivars. AI activity varied greatly among cultivars, whereas NI activity varied less and was at a low level in different tissues. The sucrose of Nymphaea 'Ruby' leaves was positively correlated with the SPS and AI, and significantly associated with NI. The accumulation of sucrose content increased the activities of SS and NI of waterlily leaves, which was conducive to promoting the formation of epiphyllous buds.


Assuntos
Nymphaea , beta-Frutofuranosidase , Metabolismo dos Carboidratos , Nymphaea/metabolismo , Parafina/metabolismo , Folhas de Planta/metabolismo , Amido/metabolismo , Sacarose/metabolismo , beta-Frutofuranosidase/metabolismo
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