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1.
Nanotechnology ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569481

RESUMO

Conductive Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has been extensively used as non-metallic electrodes. However, the relatively low electrical conductivity of pristine PEDOT:PSS film restricts its further application. Although doping high content conductive filler or increasing the film thickness are effective for enhancing the electrical property, the transparency is sacrificed, which limits the application of PEDOT:PSS films. In this study, preparing PEDOT:PSS composite film with highly conductive and transparent property was the primary purpose. To achieve this goal, single-walled carbon nanotubes (SWCNTs) and dimethyl sulfoxide (DMSO) was chosen to composite with PEDOT:PSS. The spin-coated SWCNT/PEDOT:PSS composite film exhibited excellent electrical conductivity and transparency. The electrical conductivity of composite film with desired transmittance property (78%) reached the highest value (1060.96 S cm-1) at the SWCNTs content was 6 wt%. Under the modification process applied in this work, the non-conductive PSS was partially removed by incorporated DMSO and SWCNTs. Then, the molecular chains of PEDOT stretched and adsorbed onto the surface of SWCNTs, forming a highly efficient three-dimensional conductive structure, which contributed to the enhancement of electrical conductivity and transparency. Additionally, the spin-coating process allowed for the reduction of film thickness, ensuring better transparency. This research contributed to expanding the further applications of PEDOT:PSS films in high-performance transparent film electrodes. .

2.
Heliyon ; 10(7): e28570, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560186

RESUMO

Numerous social media platforms have evolved into fertile grounds for the proliferation of irrational information, expanding the avenues of information dissemination. This paper initially utilized the Weibo and Bilibili social platforms as exemplars and devised a cross-platform two-layer network SEIaIbR-FXYaYbZ dissemination model grounded in classical infectious disease models. Subsequently, this research computed the model equilibrium point, basic reproduction number, and information entropy through dynamic equations. Finally, the model equations were fitted to real cases to determine optimal parameter solutions and conduct simulation analysis. The simulation results reveal that: (i) information entropy values on both platforms are low, with irrational information predominantly influencing public opinion; (ii) concerning various types of information, the augmentation of rational information results in a reduction of irrational information, while the quantity of rational information remains largely unaffected by changes in the quantity of irrational information; (iii) examining different platforms for information dissemination, alterations in the circulation rate and quantity of rational information on the Weibo platform impact the quantity of rational and irrational information on the Bilibili platform, while those changes on the Bilibili platform exert minimal influence on public opinion information on the Weibo platform. The results and corresponding strategies obtained from this study on the cross-platform dissemination of rational and irrational information on Weibo and Bilibili can provide a reference for relevant departments to guide the rational development of online information and enhance the effective management of public opinion in social media platforms.

3.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38539042

RESUMO

OBJECTIVES: It has been demonstrated that neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy was safe and feasible referred to neoadjuvant chemotherapy for patients with non-small cell lung cancer undergoing sleeve lobectomy. Nevertheless, no survival data were reported in the previous researches. Therefore, we conducted this study to compare neoadjuvant ICI plus chemotherapy versus neoadjuvant chemotherapy followed by sleeve lobectomy for long-term survival outcomes. METHODS: Patients who underwent bronchial sleeve lobectomy following neoadjuvant ICI plus chemotherapy or neoadjuvant chemotherapy were retrospectively identified. Treatment response, perioperative outcomes, event-free survival and overall survival were compared between groups in the overall and the inverse probability of treatment weighting-adjusted cohort. RESULTS: A total of 139 patients with 39 lung cancer recurrence and 21 death were included. Among them, 83 (59.7%) and 56 (40.3%) patients received neoadjuvant chemotherapy and neoadjuvant ICI plus chemotherapy, respectively. After inverse probability of treatment weighting, more patients achieved complete pathological response in the neoadjuvant ICI plus chemotherapy group (6.0% vs 26.3%, P < 0.001). There was no significant difference regarding overall postoperative complication (23.8% vs 20.2%, P = 0.624) and specific complications (all P > 0.05). Patients receiving neoadjuvant ICI plus chemotherapy had favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.16-0.85, P = 0.020) and overall survival (hazard ratio 0.23, 95% confidence interval 0.06-0.80, P = 0.021). Multivariable analysis revealed that neoadjuvant ICI plus chemotherapy was an independent predictor for favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.15-0.86, P = 0.020, adjusted for clinical TNM stage). CONCLUSIONS: Neoadjuvant ICI plus chemotherapy was correlated with favourable long-term survival in patients with non-small cell lung cancer undergoing sleeve lobectomy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Terapia Neoadjuvante/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia/etiologia
4.
Lung Cancer ; 189: 107472, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38320371

RESUMO

OBJECTIVES: The Lepidic Component (LP) identifies a subgroup with an excellent prognosis for lung adenocarcinoma (LUAD). Our research aimed to propose an improved pathological T (pT) stage for LUAD based on LP. MATERIALS AND METHODS: Totally, 3335 surgical patients with pathological stage I LUAD were incorporated. Factors affecting survival were investigated by analyzing recurrence-free survival (RFS) and overall survival (OS) using the Kaplan-Meier method and Cox regression analyses. Subgroup analysis based on Lepidic Ratio (LR) was further evaluated. The net benefit from the modified pT category (pTm) was assessed using the Area Under the time-dependent Receiver Operating Curve (AUC), Harrell's Concordance Index (C-index), Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). RESULTS: The presence of LP (LP+) was identified in 1425 (42.7 %) patients, indicating a significantly better RFS (P < 0.001) and OS (P < 0.001) than those without LP, and similar results were reproduced in pT1a-pT2a subcategory (P < 0.050 for all). Multivariable Cox analysis revealed LP+ as an independent prognostic factor for both RFS (HR, 0.622; P < 0.001) and OS (HR, 0.710; P = 0.019). However, lepidic ratio (LR) was not independently associated with both RFS and OS for LP+ patients. The 5-year RFS and OS rates between T1a (LP-) and T1b (LP+), T1b (LP-) and T1c (LP+), and T1b (LP-) and T2a (LP+) were comparable (P > 0.050 for all). After modification, compared with current 8th edition pT stage system (pT8), pTm independently predicted RFS and OS, and AUCs, c-index, NRI, and IDI analysis all demonstrated pTm holds better discrimination performances than pT8 for LUAD prognosis. CONCLUSION: LP can be an additional down-staged T descriptor for pathological stage I LUAD and improve the survival predictive performance of reclassification.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Área Sob a Curva
5.
Eur J Cardiothorac Surg ; 65(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38001033

RESUMO

OBJECTIVES: Limited data exist on the characteristics of atypical epidermal growth factor receptor (EGFR) mutations in early-stage lung cancer. Our goal was to elucidate the associations with outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical EGFR mutations. METHODS: Eligible patients between 2014 and 2019 were retrospectively identified and grouped into exon20 insertion mutations and major atypical mutations, which included G719X, L861Q and S768I. Disease-free survival (DFS) was evaluated in the entire cohort and stratified by radiologic characteristics. Recurrence patterns were investigated and compared between groups. A competing risk model was used to estimate the cumulative incidence of recurrence. RESULTS: A total of 710 patients were finally included. Among them, 289 (40.7%) patients had exon 20 insertion mutations and 421 (59.3%) patients had major atypical mutations. There was no significant difference regarding DFS (P = 0.142) between groups in the entire cohort. The interaction between mutation subtype and the presence of ground-glass opacities was significant (hazard ratio 2.00, 95% confidence interval 1.59-2.51, P < 0.001), indicating DFS between exon 20 insertion mutations and major atypical mutations may be different among subsolid and solid tumours. Survival analysis consistently revealed no significant difference in subsolid tumours (P = 0.680), but favourable DFS of exon 20 insertion mutations in solid tumours (P = 0.037). Furthermore, patients with exon 20 insertion mutations had a lower risk of developing bone metastases did those with radiologic solid tumours (Gray's test, P = 0.012). CONCLUSIONS: Exon 20 insertion mutations were correlated with favourable DFS and lower incidence of bone metastases in radiologic solid lung adenocarcinomas harbouring atypical EGFR mutations.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Prognóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Receptores ErbB/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Mutação
6.
Immunol Rev ; 321(1): 169-180, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37950410

RESUMO

Cancer arises from the growth and division of uncontrolled erroneous cells. Programmed cell death (PCD), or regulated cell death (RCD), includes natural processes that eliminate damaged or abnormal cells. Dysregulation of PCD is a hallmark of cancer, as cancer cells often evade cell death and continue to proliferate. Exosomes nanoscale extracellular vesicles secreted by different types of cells carrying a variety of molecules, including nucleic acids, proteins, and lipids, to have indispensable role in the communication between cells, and can influence various cellular processes, including PCD. Exosomes have been shown to modulate PCD in cancer cells by transferring pro- or antideath molecules to neighboring cells. Additionally, exosomes can facilitate the spread of PCD to surrounding cancer cells, making them promising in the treatment of various cancers. The exosomes' diagnostic potential in cancer is also an active area of research. Exosomes can be isolated from a wide range of bodily fluids and tissues, such as blood and urine, and can provide a noninvasive way to monitor cancer progression and treatment response. Furthermore, exosomes have also been employed as a delivery system for therapeutic agents. By engineering exosomes to carry drugs or other therapeutic molecules, they can be targeted specifically to cancer cells, reducing toxicity to healthy tissues. Here, we discussed exosomes in the diagnosis and prevention of cancers, tumor immunotherapy, and drug delivery, as well as in different types of PCD.


Assuntos
Exossomos , Vesículas Extracelulares , Neoplasias , Humanos , Exossomos/metabolismo , Exossomos/patologia , Neoplasias/tratamento farmacológico , Vesículas Extracelulares/patologia , Apoptose
7.
Eur J Nucl Med Mol Imaging ; 51(2): 521-534, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37725128

RESUMO

PURPOSE: No consensus on a grading system for invasive lung adenocarcinoma had been built over a long period of time. Until October 2020, a novel grading system was proposed to quantify the whole landscape of histologic subtypes and proportions of pulmonary adenocarcinomas. This study aims to develop a deep learning grading signature (DLGS) based on positron emission tomography/computed tomography (PET/CT) to personalize surgical treatments for clinical stage I invasive lung adenocarcinoma and explore the biologic basis under its prediction. METHODS: A total of 2638 patients with clinical stage I invasive lung adenocarcinoma from 4 medical centers were retrospectively included to construct and validate the DLGS. The predictive performance of the DLGS was evaluated by the area under the receiver operating characteristic curve (AUC), its potential to optimize surgical treatments was investigated via survival analyses in risk groups defined by the DLGS, and its biological basis was explored by comparing histologic patterns, genotypic alternations, genetic pathways, and infiltration of immune cells in microenvironments between risk groups. RESULTS: The DLGS to predict grade 3 achieved AUCs of 0.862, 0.844, and 0.851 in the validation set (n = 497), external cohort (n = 382), and prospective cohort (n = 600), respectively, which were significantly better than 0.814, 0.810, and 0.806 of the PET model, 0.813, 0.795, and 0.824 of the CT model, and 0.762, 0.734, and 0.751 of the clinical model. Additionally, for DLGS-defined high-risk population, lobectomy yielded an improved prognosis compared to sublobectomy p = 0.085 for overall survival [OS] and p = 0.038 for recurrence-free survival [RFS]) and systematic nodal dissection conferred a superior prognosis to limited nodal dissection (p = 0.001 for OS and p = 0.041 for RFS). CONCLUSION: The DLGS harbors the potential to predict the histologic grade and personalize the surgical treatments for clinical stage I invasive lung adenocarcinoma. Its applicability to other territories should be further validated by a larger international study.


Assuntos
Adenocarcinoma de Pulmão , Produtos Biológicos , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Microambiente Tumoral
8.
Patient Educ Couns ; 119: 108089, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38008646

RESUMO

OBJECTIVE: This study aimed to describe the association between empathy and residents' clinical performance and investigate whether work-related perception mediates this relationship. METHODS: A multi-center cross-sectional study was conducted, including 1160 residents from 10 cities in Liaoning Province between March and October 2020. The participants completed various self-reported questionnaires regarding demographic characteristics, work-related perceptions, self-perceived clinical performance, and empathy. The relationships among empathy, work-related perception, and self-perceived clinical performance were examined using a structural equation model (SEM). RESULTS: Of the 1160 residents, 961 (82.8 %) completed the questionnaires. The SEM path analysis showed that the direct effect of empathy on self-perceived clinical performance was significant and positive (ß = 0.34, P < 0.001). There existed significant effects of empathy on work-related perception (ß = 0.26, P < 0.001) and work-related perception on performance (ß = 0.31, P < 0.001). The path coefficients of empathy concerning self-perceived clinical performance decreased significantly (ß = 0.26, P < 0.001) when work-related perception was modeled as a mediator. The bias-corrected and accelerated bootstrap test revealed that work-related perception significantly mediated the relationship between empathy and self-perceived clinical performance (a*b = 0.08, BCa 95 % CI: 0.05-0.13). However, the correlation between the sub-scales of empathy and the items of self-perceived clinical performance was not substantial, even if most of them were statistically significant. The final SEM produced a good fit to the sample data, with CMIN/DF = 2.07 (P < 0.001), CFI = 0.99, GFI = 0.99, AGFI = 0.98, TLI = 0.98, NFI = 0.97, RMSEA (90 % CI) = 0.033 (0.017, 0.049), and SRMR = 0.024. CONCLUSION: Empathy might significantly affect self-perceived clinical performance both directly and indirectly through the mediating role of work-related perception. PRACTICE IMPLICATIONS: Efforts to improve clinical performance among residents might benefit from interventions for cultivating empathy and practices for improving work-related perceptions of residents.


Assuntos
Competência Clínica , Empatia , Internato e Residência , Humanos , China , Estudos Transversais , Autorrelato , Inquéritos e Questionários
9.
Animals (Basel) ; 13(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38066949

RESUMO

The beneficial effects of butyric acid in poultry production are well documented, while the relationship between sodium butyrate (SB) and microcapsule sustained-release sodium butyrate (MSSB), especially in yellow broilers, remains poorly investigated. This study was designed to elucidate the function as well as the potential mechanisms of SB and MSSB in enhancing health in yellow broilers. In total, 360 one-day-old yellow broilers were allocated to three treatment groups. The control group (CON) received a basic diet, while the SB group was provided with 1000 mg/kg of sodium butyrate (SB), and the MSSB received microcapsule sustained-release sodium butyrate (MSSB), all over a period of 56 days. Compared to the CON group, the dietary supplementation of both SB and MSSB showed a lower feed:gain ratio (p < 0.01). No significant (p > 0.05) difference in antioxidant capacity was observed between the three groups. We observed significantly higher levels (p < 0.05) of immunoglobulins and a reduction in concentrations in both the SB and MSSB groups compared to the CON group. Furthermore, both SB and MSSB induced alterations in the diversity, structure, and function of gut microbiota. MSSB demonstrated even more pronounced beneficial effects than SB, particularly in regard to the serum IgA level (p = 0.05), cecal isovalerate concentration (p < 0.05), and villus height (p < 0.01). The sequencing of the gut microbiota revealed that MSSB led to a significant increase in the relative abundance of Clostridia UCG-014, Bacilli RF39, and Oscillospiraceae UCG-005. Predictions of bacterial function indicated changes in KEGG pathways, including an enrichment of tryptophan metabolism (ko00380), and a reduction in fructose and mannose metabolism (ko00051), chloroalkane and chloroalkene degradation (ko00625), and naphthalene degradation (ko00626) in yellow broilers fed with MSSB. Among these, the mediation analysis revealed a causal effect between the Clostridia UCG-014 in the gut and serum IgA, with tryptophan metabolism being a key mediator in this relationship. Our results suggest that dietary MSSB can improve the growth performance, immunity, and gut microbiota of yellow broilers. MSSB increased the abundance of Clostridia UCG-014 and activated the tryptophan metabolism pathway (ko00380), contributing to IgA levels in yellow broilers through this mechanism.

10.
Nat Commun ; 14(1): 7513, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980411

RESUMO

Occult nodal metastasis (ONM) plays a significant role in comprehensive treatments of non-small cell lung cancer (NSCLC). This study aims to develop a deep learning signature based on positron emission tomography/computed tomography to predict ONM of clinical stage N0 NSCLC. An internal cohort (n = 1911) is included to construct the deep learning nodal metastasis signature (DLNMS). Subsequently, an external cohort (n = 355) and a prospective cohort (n = 999) are utilized to fully validate the predictive performances of the DLNMS. Here, we show areas under the receiver operating characteristic curve of the DLNMS for occult N1 prediction are 0.958, 0.879 and 0.914 in the validation set, external cohort and prospective cohort, respectively, and for occult N2 prediction are 0.942, 0.875 and 0.919, respectively, which are significantly better than the single-modal deep learning models, clinical model and physicians. This study demonstrates that the DLNMS harbors the potential to predict ONM of clinical stage N0 NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Estudos Retrospectivos , Metástase Linfática/patologia , Estadiamento de Neoplasias , Linfonodos/diagnóstico por imagem , Linfonodos/patologia
11.
JTO Clin Res Rep ; 4(10): 100574, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37822700

RESUMO

Introduction: To validate the residual tumor (R) classification proposed by the International Association for the Study of Lung Cancer (IASLC) in NSCLC after sleeve lobectomy. Methods: A total of 682 patients were analyzed. The R status, on the basis of the Union for International Cancer Control (UICC) criteria, was recategorized according to the IASLC descriptors. Recurrence-free survival (RFS) and overall survival (OS) among different R classifications were assessed for the entire cohort and pathologic node (pN) subgroups. Results: All in all, 631 (92.5%), 48 (7.1%), and three patients (0.4%) were classified as R0, R1, and R2, respectively, by the UICC criteria, whereas 489 (71.7%), 110 (16.1%), and 83 patients (12.2%), received R0, uncertain resection (R[un]), and R1/2 resection, respectively, according to the IASLC criteria. There were 96 patients (15.2%) with UICC R0 who were reclassified as R(un), mainly because of the positive highest mediastinal node station (82 of 96, 85.4%). A total of 46 patients (7.3%) were reassigned from UICC R0 to IASLC R1/2 owing to extracapsular extension. For the entire cohort, patients with R(un) and R1/2 exhibited worse RFS (R[un], adjusted p = 0.023; R1/2, adjusted p = 0.001) and OS (R[un], adjusted p = 0.040; R1/2, adjusted p = 0.051) compared with R0. No significant differences were observed between R(un) and R1/2 (RFS, adjusted p = 0.586; OS, adjusted p = 0.781). Furthermore, subgroup analysis revealed a distinct prognostic impact of the IASLC R status-with prognostic significances in the pN1 and pN2 subgroups, but not in the pN0 subgroup. Conclusions: The IASLC R descriptors helped to stratify the prognosis of NSCLC after sleeve lobectomy, with its prognostic impact varied among pN stages.

12.
Eur J Med Chem ; 261: 115823, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37839345

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) causes severe public health challenges throughout the world, and the multi-drug resistance (MDR) of MRSA to antibiotics necessitates the development of more effective antibiotics. Natural 2,4-diacetylphloroglucinol (DAPG), produced by Pseudomonas, displays moderate inhibitory activity against MRSA. A series of DAPG derivatives was synthesized and evaluated for their antibacterial activities, and some showed excellent activities (MRSA MIC = 0.5-2 µg/mL). Among these derivatives, 7g demonstrated strong antibacterial activity without resistance development over two months. Mechanistic studies suggest that 7g asserted its activity by targeting bacterial cell membranes. In addition, 7g exhibited significant synergistic antibacterial effects with oxacillin both in vitro and in vivo, with a tendency to eradicate MRSA biofilms. 7g is a promising lead for the treatment of MRSA.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Sinergismo Farmacológico , Antibacterianos/farmacologia , Oxacilina/farmacologia , Testes de Sensibilidade Microbiana
14.
Int J Mol Sci ; 24(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37445924

RESUMO

Grain size is one of the most frequently selected traits during domestication and modern breeding. The continued discovery and characterization of new genes and alleles in controlling grain size are important in safeguarding the food supply for the world's growing population. Previously, a small grain size was observed in a rice restorer line 'Fuhui212', while the underlying genetic factors controlling this trait were unknown. In this study, by combining QTL mapping, variant effect prediction, and complementation experiments, we recovered a novel allele RGA1-FH that explains most of the phenotypic changes. The RGA1-FH allele contains an A-to-T splicing site variant that disrupts the normal function of RGA1. While population analysis suggests extremely strong artificial selection in maintaining a functional allele of RGA1, our study is the first, to the best of our knowledge, to prove that a dysfunctional RGA1 allele can also be beneficial in real agricultural production. Future breeding programs would benefit from paying more attention to the rational utilization of those overlooked 'unfavored' alleles.


Assuntos
Oryza , Alelos , Oryza/genética , Locos de Características Quantitativas , Cromossomos de Plantas/genética , Melhoramento Vegetal , Grão Comestível/genética
15.
Angew Chem Int Ed Engl ; 62(35): e202308041, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37428115

RESUMO

While chain-walking stimulates wide interest in both polymerization and organic synthesis, site- and stereoselective control of chain-walking on rings is still a challenging task in the realm of organometallic catalysis. Inspired by a controllable chain-walking on cyclohexane rings in olefin polymerization, we have developed a set of chain-walking carboborations of cyclohexenes based on nickel catalysis. Different from the 1,4-trans-selectivity disclosed in polymer science, a high level of 1,3-regio- and cis-stereoselectivity is obtained in our reactions. Mechanistically, we discovery that the base affects the reduction ability of B2 pin2 and different bases lead to different catalytic cycles and different regioselective products (1,2- Vs 1,3-addition). This study provides a concise and modular method for the synthesis of 1,3-disubstituted cyclohexylboron compounds. The incorporation of a readily modifiable boronate group greatly enhances the value of this method, the synthetic potential of which was highlighted by the synthesis of a series of high-valued commercial chemicals and pharmaceutically interesting molecules.

16.
J Antimicrob Chemother ; 78(7): 1795-1799, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37279764

RESUMO

OBJECTIVES: The 'treat-all' strategy was implemented in Shenzhen, China in 2016. The effect of this extensive treatment on transmitted drug resistance (TDR) of HIV is unclear. METHODS: TDR analysis was performed, based on the partial HIV-1 pol gene obtained from the newly reported HIV-1 positive cases from 2011 to 2019 in Shenzhen, China. The HIV-1 molecular transmission networks were inferred to analyse the spread of TDR. Logistic regression was used to identify the potential risk factors with TDR mutations (TDRMs) to cluster. RESULTS: A total of 12 320 partial pol sequences were included in this study. The prevalence of TDR was 2.95% (363/12 320), which increased from 2.57% to 3.52% after 'treat-all'. The TDR prevalence was increased in populations with the characteristics of CRF07_BC, being single, educated to junior college level and above, MSM and male. The sensitivities of viruses to six antiretroviral drugs were decreased. The clustering rate of TDRMs remained stable, and the sequences in the three drug resistance transmission clusters (DRTCs) were mainly found during 2011-16. CRF07_BC and CRF55_01B were the factors associated with TDRMs clustering in the networks. CONCLUSIONS: The 'treat-all' strategy might have contributed to a small increase in TDR, while most of the TDRMs were distributed sporadically, which implies that the 'treat-all' strategy is helpful for the control of TDR in high-risk populations.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Minorias Sexuais e de Gênero , Humanos , Masculino , Homossexualidade Masculina , HIV-1/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Prevalência , Farmacorresistência Viral/genética , China/epidemiologia , Filogenia , Genótipo
17.
Pharmacol Res ; 193: 106812, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37271425

RESUMO

Polyphenols, also known as phenolic compounds, are chemical substances containing aromatic rings as well as at least two hydroxyl groups. Natural phenolic compounds exist widely in plants, which protect plants from ultraviolet radiation and other insults. Phenolic compounds have superior pharmacological and nutritional properties (antimicrobial, antibacterial, antiviral, anti-sclerosis, antioxidant, and anti-inflammatory activities), which have been paid more and more attention by the scientific community. Phenols can protect key cellular components from reactive free radical damage, which is mainly due to their property to activate antioxidant enzymes and alleviate oxidative stress and inflammation. It can also inhibit or isolate reactive oxygen species and transfer electrons to free radicals, thereby avoiding cell damage. It has a regulatory role in glucose metabolism, which has a promising prospect in the prevention and intervention of diabetes. It also prevents cardiovascular disease by regulating blood pressure and blood lipids. Polyphenols can inhibit cell proliferation by affecting Erk1/2, CDK, and PI3K/Akt signaling pathways. Polyphenols can function as enhancers of intrinsic defense systems, including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Simultaneously, they can modulate multiple proteins and transcription factors, making them promising candidates in the investigation of anti-cancer medications. This review focuses on multiple aspects of phenolic substances, including their natural origins, production process, disinfection activity, oxidative and anti-inflammatory functions, and the effects of different phenolic substances on tumors.


Assuntos
Antioxidantes , Neoplasias , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Raios Ultravioleta , Estresse Oxidativo , Fenóis/farmacologia , Fenóis/uso terapêutico , Neoplasias/tratamento farmacológico , Polifenóis/farmacologia , Radicais Livres/metabolismo , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química
18.
ACS Cent Sci ; 9(4): 756-762, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37122460

RESUMO

Direct functionalization of inert C-H bonds is one of the most attractive yet challenging strategies for constructing molecules in organic chemistry. Herein, we disclose an unprecedented and Earth abundant Cu/Cr catalytic system in which unreactive alkyl C-H bonds are transformed into nucleophilic alkyl-Cr(III) species at room temperature, enabling carbonyl addition reactions with strong alkyl C-H bonds. Various aryl alkyl alcohols are furnished under mild reaction conditions even on a gram scale. Moreover, this new radical-to-polar crossover approach is further applied to the 1,1-difunctionalization of aldehydes with alkanes and different nucleophiles. Mechanistic investigations reveal that the aldehyde not only acts as a reactant but also serves as a photosensitizer to recycle the Cu and Cr catalysts.

19.
Transl Lung Cancer Res ; 12(3): 566-579, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37057115

RESUMO

Background: There is a risk of over investigation and delayed treatment in the work up of solid nodules. Thus, the aim of our study was to develop and validate an integrated model that estimates the malignant risk for indeterminate pulmonary solid nodules (IPSNs). Methods: Patients included in this study with IPSNs who was diagnosed malignant or benign by histopathology. Univariate and multivariate logistic regression were used to build integrated model based on clinical, circulating tumor cells (CTCs) and radiomics features. The performance of the integrated model was estimated by applying receiver operating characteristic (ROC) analysis, and tested in different nodules size and intermediate risk IPSNs. Net reclassification index (NRI) was applied to quantify the additional benefit derived from the integrated model. Results: The integrated model yielded areas under the ROC curves (AUCs) of 0.83 and 0.76 in internal and external set, respectively, outperforming CTCs (0.70, P=0.001; 0.68, P=0.128), the Mayo clinical model (0.68, P<0.001; 0.55, P=0.007), the and radiomics model (0.72, P=0.002; 0.67, P=0.050) in both validation sets. Robust performance with high sensitivity up to 98% was also maintained in IPSNs with different solid size and intermediate risk probability. The performance of the integrated model was comparable with positron emission tomography/computed tomography (PET-CT) examination (P=0.308) among the participants with established PET-CT records. NRI demonstrated that the integrated model provided net reclassification of at least 10% on the external validation set compared with single CTCs test. Conclusions: The integrated model could complement conventional risk models to improve the diagnosis of IPSNs, which is not inferior to PET-CT and could help to guide clinician's decision-making on clinically specific population.

20.
Pharmacol Res ; 191: 106766, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37061144

RESUMO

Digestive tract diseases are presently the hotspot of clinical diagnosis and treatment, and the incidence of digestive tract tumor is increasing annually. Surgery remains the main therapeutic schedule for digestive tract tumor. Though benefits were brought by neoadjuvant chemotherapy, a part of patients lose the chance of surgery because of late detection or inappropriate intervention. Therefore, the treatment of inoperable patients has become an urgent need. At the same time, tumor metabolism is an extremely complex and diverse process. Natural products are confirmed effective to inhibit the development of tumors in vitro and in vitro. There are many kinds of natural products and their functions remain not clear. However, some natural products such as polyphenols have been proven to have definite anti-cancer effects, and some terpenoids have definite anti-inflammatory, anti-ulcer, anti-tumor, and other effects. Therefore, the anti-tumor characteristics of natural products should arouse our high attention. Although there are many obstacles to study the activities of natural products in tumor, including the difficulty in detection or distinguishing each component due to their low levels in tumor tissue, etc., the emergence of highly sensitive and locatable spatial metabolomics make the research and application of natural products a big step forward. In this review, natural products such as phenols, terpenoids and biotinoids were summarized to further discuss the development and therapeutic properties of natural metabolites on digestive tract tumors.


Assuntos
Produtos Biológicos , Gastroenteropatias , Neoplasias Gastrointestinais , Humanos , Produtos Biológicos/uso terapêutico , Produtos Biológicos/farmacologia , Neoplasias Gastrointestinais/tratamento farmacológico , Terpenos
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