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1.
Ann Intern Med ; 177(6): 719-728, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38801778

RESUMEN

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.


Asunto(s)
Circuncisión Masculina , Infecciones por VIH , Homosexualidad Masculina , Humanos , Masculino , Adulto , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Adulto Joven , Adolescente , Persona de Mediana Edad , China/epidemiología , Incidencia , Conducta Sexual , Análisis de Intención de Tratar
2.
Small ; 20(43): e2403118, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38990881

RESUMEN

Two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDCs) are extensively employed as channel materials in advanced electronic devices. The electrical contacts between electrodes and 2D semiconductors play a crucial role in the development of high-performance transistors. While numerous strategies for electrode interface engineering have been proposed to enhance the performance of n-type 2D transistors, upgrading p-type ones in a similar manner remains a challenge. In this work, significant improvements in a p-type WSe2 transistor are demonstrated by utilizing metallic MoO2 nanosheets as the electrode contact, which are controllably fabricated through physical vapor deposition and subsequent annealing. The MoO2 nanosheets exhibit an exceptional electrical conductivity of 8.4 × 104 S m‒1 and a breakdown current density of 3.3 × 106 A cm‒2. The work function of MoO2 nanosheets is determined to be ≈5.1 eV, making them suitable for contacting p-type 2D semiconductors. Employing MoO2 nanosheets as the electrode contact in WSe2 transistors results in a notable increase in the field-effect mobility to 92.0 cm2 V‒1 s‒1, which is one order of magnitude higher than the counterpart devices with conventional electrodes. This study not only introduces an intriguing 2D metal oxide to improve the electrical contact in p-type 2D transistors, but also offers an effective approach to fabricating all-2D devices.

3.
Microb Pathog ; 196: 106997, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39369754

RESUMEN

Porcine circovirus (PCV) is a group of DNA viruses that cause diseases in pigs, with multiple genotypes ranging from PCV1 to PCV4. PCV1 is generally considered non-pathogenic, while PCV2 can cause severe immune system damage, especially associated with porcine multisystemic wasting syndrome (PMWS). PCV2 has a genetic homology of about 68 % but differs from PCV1 in antigenicity and phenotype. PCV3 and PCV4 have lower genetic homology with PCV1 and PCV2, with limited research available on their pathogenicity. During virus infection, the host's innate immune system detects PCVs through pattern recognition receptors (PRRs) like TLRs and NLRs. PCV disrupts immune pathways, including interferon and NF-κB pathways, aiding viral replication and causing immunosuppression. This review systematically compares the characteristics and pathogenicity of different genotypes of PCV and their interactions with the host's immune system, aiming to better understand the mechanisms of PCV infection and provide a theoretical basis for prevention and treatment.


Asunto(s)
Infecciones por Circoviridae , Circovirus , Variación Genética , Genotipo , Enfermedades de los Porcinos , Circovirus/genética , Circovirus/inmunología , Circovirus/patogenicidad , Circovirus/clasificación , Animales , Porcinos , Infecciones por Circoviridae/virología , Infecciones por Circoviridae/veterinaria , Infecciones por Circoviridae/inmunología , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/inmunología , Inmunidad Innata , Replicación Viral
4.
Public Health ; 236: 115-124, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39180937

RESUMEN

OBJECTIVES: Mpox continues to spread in China, and stakeholders' experiences may help inform prevention and control strategies. STUDY DESIGN: Qualitative study. METHODS: A qualitative study across 14 Chinese cities recruited stakeholders from Centers for Disease Control and Prevention (CDCs), community-based organizations (CBOs), and hospitals involved in curbing mpox. Semi-structured interviews were conducted by telephone and analyzed using Colaizzi's phenomenological method. RESULTS: 15 CBOs workers, 14 CDCs staff, and 13 healthcare workers were recruited. Three theme categories were identified: "Efforts to curb mpox epidemic", including CDCs' epidemic management and health education, hospitals' diagnosis, treatment, and care, CBOs' counseling, publicity, and referrals. "Challenges to curb mpox epidemic", including negative impacts of hospital-based quarantine, lack of specific antiviral drugs, gay identity disclosure concerns, psychological problems, contact tracing difficulties, and inadequate communication and collaboration. "Recommendations for curbing mpox epidemic", including prioritizing supervised home-based quarantine, incorporating HIV-related indicators into hospital quarantine criteria, reducing the cost of hospital quarantine, accelerating the development of vaccines and drugs, enhancing patient privacy protection, psychological training for stakeholders, establishing a task force that comprises personnel who are experienced in contact tracing and strengthening communication and collaboration. CONCLUSIONS: Effective control of mpox spread requires strengthening collaboration with CBOs and community healthcare centers (CHCs) and working out a flexible and contextualized mechanism. It also needs to reinforce patient privacy protection and integrate stigma reduction into strategies. Additionally, it is important to include HIV-related indicators in the quarantine evaluation and provide psychological training for stakeholders to help them manage their mental health and improve counseling skills.

5.
Nano Lett ; 23(4): 1211-1218, 2023 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-36748951

RESUMEN

Interfacial atomic configuration and its evolution play critical roles in the structural stability and functionality of mixed zero-dimensional (0D) metal nanoparticles (NPs) and two-dimensional (2D) semiconductors. In situ observation of the interface evolution at atomic resolution is a vital method. Herein, the directional migration and structural evolution of Au NPs on anisotropic ReS2 were investigated in situ by aberration-corrected transmission electron microscopy. Statistically, the migration of Au NPs with diameters below 3 nm on ReS2 takes priority with greater probability along the b-axis direction. Density functional theory calculations suggest that the lower diffusion energy barrier enables the directional migration. The coalescence kinetics of Au NPs is quantitatively described by the relation of neck radius (r) and time (t), expressed as r2=Kt. Our work provides an atomic-resolved dynamic analysis method to study the interfacial structural evolution of metal/2D materials, which is essential to the study of the stability of nanodevices based on mixed-dimensional nanomaterials.

6.
Nano Lett ; 23(23): 11360-11367, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38010863

RESUMEN

The crystal growth kinetics is crucial for the controllable preparation and performance modulation of metal nanocrystals (NCs). However, the study of growth mechanisms is significantly limited by characterization techniques, and it is still challenging to in situ capture the growth process. Real-time and real-space imaging techniques at the atomic scale can promote the understanding of microdynamics for NC growth. Herein, the growth of Pd NCs on monolayer MoS2 under different atmospheres was in situ studied by environmental transmission electron microscopy. Introducing carbon monoxide can modulate the diffusion of Pd monomers, resulting in the epitaxial growth of Pd NCs with a uniform orientation. The electron energy loss spectroscopy and theoretical calculations showed that the CO adsorption assured the specific exposed facets and good uniformity of Pd NCs. The insight into the gas-solid interface interaction and the microscopic growth mechanism of NCs may shed light on the precise synthesis of NCs on two-dimensional (2D) materials.

7.
Angew Chem Int Ed Engl ; : e202409484, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39218790

RESUMEN

Utilizing hot carriers for efficient plasmon-mediated chemical reactions (PMCRs) to convert solar energy into secondary energy is one of the most feasible solutions to the global environmental and energy crisis. Finding a plasmonic heterogeneous nanostructure with a more efficient and reasonable hot carrier transport path without affecting the intrinsic plasmonic properties is still a major challenge that urgently needs to be solved in this field. Herein, the mechanism by which plasmon-promoted interatomic hot electron redistribution on the surface of Au3Cu alloy nanoparticles promotes the electrocatalytic nitrogen reduction reaction (ENRR) is successfully clarified. The localized surface plasmon resonance (LSPR) effect can boost the transfer of plasmon hot electrons from Au atoms to Cu atoms, trigger the interatomic electron regulation of Au3Cu alloy nanoparticles, enhance the desorption of ammonia molecules, and increase the ammonia yield by approximately 93.9 %. This work provides an important reference for rationally designing and utilizing the LSPR effect to efficiently regulate the distribution and mechanism of plasmon hot carriers on the surface of heterogeneous alloy nanostructures.

8.
J Med Virol ; 95(2): e28567, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36786385

RESUMEN

Men who have sex with men (MSM) have been recommended for targeted monkeypox vaccination. We aimed to investigate monkeypox awareness and explore the correlates of monkeypox vaccination hesitancy among MSM in China. We conducted a cross-sectional survey from August 10 to September 9, 2022. Awareness related to monkeypox and attitude toward monkeypox vaccination among MSM aged ≥18 years were collected. Multivariable logistic regression was applied to evaluate correlates of vaccination hesitancy. The discrepancy in awareness between subgroups regarding HIV status was assessed. A total of 1090 MSM were included (age: median 30 years, interquartile range [IQR], 25-35; HIV-infected: 53.12%). Only 13.85% of respondents expressed high monkeypox vaccination hesitancy. Hesitancy was associated with no fixed income (adjuster odds ratio [aOR], 2.46, 95% confidence interval [CI], 1.48-4.11), infrequent information following (sometimes, 3.01, 1.55-5.83; seldom or never, 5.66, 2.58-12.45), and lack of worries about monkeypox endemic (1.78, 1.11-2.87). Participants who believed that HIV-infected cases accounted for a smaller proportion (1.62, 1.01-2.60), disagreed that monkeypox virus could be detected in semen (2.21, 1.26-3.88), and considered either replication-competent (1.84, 1.14-2.96) or replication-deficient (4.80, 2.26-10.21) monkeypox vaccine unsuitable for HIV-infected people were generally more hesitant. Compared with HIV-uninfected MSM, HIV-infected MSM supported more for vaccination promotion. MSM in China had low hesitancy toward monkeypox vaccination. Safety and affordability of vaccine and availability of information were essential aspects to reduce hesitancy. Education on vaccination benefits should be encouraged to promote future vaccination plans.


Asunto(s)
Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Vacuna contra Viruela , Masculino , Humanos , Adolescente , Adulto , Homosexualidad Masculina , Estudios Transversales , Vacilación a la Vacunación , Vacunación , China/epidemiología
9.
AIDS Care ; 35(5): 634-638, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36223531

RESUMEN

Obtaining antiretroviral therapy (ART) was a challenge for people living with HIV (PLHIV) in China during the COVID-19 outbreak. On 26 January 2020, the Chinese Center for AIDS/STD Control and Prevention issued a nationwide directive to relax restrictions on where and when PLHIV could refill ART. This qualitative study explored unexpected barriers under this directive and recommendations to improve future ART delivery. Between February 11 and February 15 2020, in-depth interviews of 4 groups of stake holders related to ART refilling (i.e., PLHIV, community-based organization employees, CDC staff, infectious disease physicians and nurses), were conducted via WeChat. Data were managed by NVivo 11.0 and transcripts were coded using thematic analysis. Sixty-two interviews were conducted. The main barriers to refilling ART included: (1) inconsistent documentation requirements to refill ART, (2) lack of specific protocols on ART refilling, (3) insufficient staffing, and (4) regimen verification and drug shortages. The most common recommendations to improve future ART delivery were: (1) to establish a nationwide system to distribute ART and (2) increase the number of pills delivered with each ART refill. Strengthening protocols and systems to refill ART and improving collaboration is key to preventing interruptions in ART among PLHIV during public health emergencies.


Asunto(s)
COVID-19 , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , COVID-19/epidemiología , Pandemias , Investigación Cualitativa , China/epidemiología , Antirretrovirales/uso terapéutico
10.
Nanotechnology ; 34(36)2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37295408

RESUMEN

Formamidinium lead triiodide (FAPbI3) is considered as the prospective light-absorbing layer on account of the close-to-ideal bandgap of theα-phase, wide optical absorption spectrum and good thermal stability. Therefore, how to realizeδtoα-phase transition to obtain phase-pureα-FAPbI3without additives is important for FAPbI3perovskite films. Herein, a homologous post-treatment strategy (HPTS) without additives is proposed to prepare FAPbI3films with pureα-phase. The strategy is processed along with dissolution and reconstruction process during the annealing. The FAPbI3film has tensile strain with the substrate, and the lattice keeps tensile, and the film maintains in anα/δhybrid phase. The HPTS process releases the tensile strain between the lattice and the substrate. The process of strain release realizes the phase transition fromδtoα-phase during this process. This strategy can accelerate the transformation from hexagonalδ-FAPbI3to cubicα-FAPbI3at 120 °C. As a result, the acquiredα-FAPbI3films exhibit better film quality in optical and electrical properties, accordingly achieving device efficiency of 19.34% and enhanced stability. This work explores an effective approach to obtain additive-free and phase-pureα-FAPbI3films through a HPTS to fabricate uniform high-performanceα-FAPbI3perovskite solar cells.


Asunto(s)
Óxidos , Estudios Prospectivos , Transición de Fase
11.
Arch Sex Behav ; 52(5): 2065-2081, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37296334

RESUMEN

Voluntary medical male circumcision (VMMC) may be incorporated into HIV prevention services for men who have sex with men (MSM). We conducted a mixed-methods study to elucidate barriers and facilitators to, and experience of, VMMC among MSM. Participants were MSM aged 18 years and older who were enrolled in an ongoing multicenter randomized controlled trial (RCT) to evaluate VMMC to prevent HIV among MSM in China. RCT participants completed a questionnaire before and after VMMC to assess perceptions of and complications after the procedure. A subset of RCT participants were selected for in-depth interviews. Interviewees answered open-ended questions about barriers and facilitators to and experience of undergoing VMMC. Six-step thematic analysis incorporating inductive and deductive approaches was used to interpret interview responses. A total of 457 MSM completed the pre-VMMC survey, 115 circumcised MSM completed post-VMMC surveys, and 30 MSM completed an interview. Main barriers to VMMC uptake were concerns about pain, length of wound healing, cost, lack of knowledge about or misconceptions of VMMC, and stigma related to surgery. Facilitators to VMMC could be categorized as internal factors (foreskin) and external factors (motivation and follow-up care). Interestingly, the VMMC experiences of others could be transformed from a barrier into a facilitator to VMMC in some circumstances. After VMMC participants transitioned from a negative state of pain, remorse, difficulty sleeping, and discomfort to a positive state of symptom alleviation and personal hygiene improvement. Optimizing facilitators and addressing barriers may encourage VMMC among MSM. Joint efforts should be made by relevant stakeholders to improve the awareness and uptake of VMMC among MSM.


Asunto(s)
Circuncisión Masculina , Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Humanos , Infecciones por VIH/prevención & control , China , Dolor
12.
BMC Med ; 20(1): 453, 2022 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-36424628

RESUMEN

BACKGROUND: Conteltinib (CT-707) is a potent second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) showing promising anti-tumor activities in preclinical studies. This study aimed to assess the safety, pharmacokinetic (PK), and efficacy of conteltinib in patients with ALK-positive non-small cell lung cancer (NSCLC). METHODS: In this multicenter, single-arm, open-label, first-in-human phase 1 study, conteltinib was taken orally at doses of 50 to 800 mg quaque die (QD) in a dose-escalation phase. If the response was observed in a dose cohort of the dose-escalation phase, dose expansion was started. The primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and adverse events assessed by investigators. RESULTS: Between April 13, 2016, and February 8, 2020, 64 ALK-positive NSCLC patients were enrolled, including 41 (64.1%) patients with ALK TKI-naïve and 23 (35.9%) patients who received crizotinib previously. In the dose-escalation phase, 26 patients were treated with conteltinib at doses of 50 mg, 100 mg, 200 mg, 300 mg, 450 mg, 600 mg, and 800 mg QD. One DLT event was reported at the dose of 600 mg. MTD was not reached. Overall, 58 (90.6%) patients experienced treatment-related adverse events (TRAEs) and 9 (14.1%) patients had grade ≥ 3 TRAEs. The most common TRAEs were diarrhea (46 [71.9%]), serum creatinine elevated (29 [45.3%]), aspartate aminotransferase elevated (25 [39.1%]), and nausea (24 [37.5%]). Among 39 ALK TKI-naïve patients, the overall response rate (ORR) was 64.1% (25 of 39; 95% confidence interval [CI], 47.2-78.8), median progression-free survival (PFS) was 15.9 months (95% CI, 9.26-23.3), and median duration of response (DoR) was 15.0 months (95% CI, 9.06-25.8). Among 21 patients who received crizotinib previously, the ORR was 33.3% (7 of 21; 95% CI, 14.6-57.0), median PFS was 6.73 months (95% CI, 4.73-8.54), and median DoR was 6.60 months (95% CI, 3.77-13.3). CONCLUSIONS: In this study, conteltinib showed manageable safety profile, favorable PK properties, and anti-tumor activity in advanced ALK-positive NSCLC patients. The recommended phase 2 dose was determined to be 600 mg QD for ALK TKI-naïve patients and 300 mg bis in die (BID) for patients who received crizotinib previously. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02695550.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Crizotinib/efectos adversos , Quinasa de Linfoma Anaplásico , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Tirosina Quinasas
13.
Langmuir ; 38(49): 15384-15393, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36448653

RESUMEN

Interactions of enzymes with supports significantly affect the activity and stability of immobilized enzymes. Herein, amino-functionalized ionic liquid (IL)-grafted magnetic zeolitic imidazolate framework-90 (MZIF-90) was prepared and used to immobilize porcine pancreatic lipase (PPL). The nanocomposites were fully characterized; meanwhile, the interactions between ILs and ZIF-90 were calculated based on density functional theory. The prepared biocatalyst (PPL-ILs/MZIF-90) had a lipase loading of 178.3 mg/g and hydrolysis activity up to 287.5 U/g. When the biocatalyst was used to synthesize isoamyl acetate, the reaction media, molar ratio of alcohol/acid, temperature, and reaction time were optimized. Under the optimized reaction conditions (in hexane, alcohol/acid = 3:1, under 45 °C, reacted for 9 h), the ester yield reached 85.5%. The results of the stability test showed that PPL-ILs/MZIF-90 retained 88.7% of the initial activity after storing for 35 days and 92.5% of the initial activity after reusing for seven cycles for synthesizing isoamyl acetate. Moreover, the secondary structure analysis showed that the synthesized supports protected the active conformation of immobilized lipase, which lead to the enhanced catalytic performance. Additionally, the biocatalyst can be easily separated with a magnet, which facilitated the reusability. This study provides insights regarding the application of metal organic framework composites in the field of enzyme catalysis.


Asunto(s)
Enzimas Inmovilizadas , Lipasa , Porcinos , Animales , Lipasa/química , Esterificación , Enzimas Inmovilizadas/química , Fenómenos Magnéticos , Estabilidad de Enzimas
14.
Curr HIV/AIDS Rep ; 19(6): 516-521, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36350470

RESUMEN

PURPOSE OF REVIEW: Evidence from clinical trials identified the effectiveness of voluntary medical male circumcision (VMMC) as an additional strategy to reduce the risk of HIV transmission from women to men. However, concerns about post-circumcision sexual risk compensation may hinder the scale-up of VMMC programs. We reviewed the evidence of changes in risky sexual behaviors after circumcision, including condomless sex, multiple sex partners, and early resumption of sex after surgery. RECENT FINDINGS: Most clinical trial data indicate that condomless sex and multiple partners did not increase for men after circumcision, and early resumption of sex is rare. Only one post-trial surveillance reports that some circumcised men had more sex partners after surgery, but this did not offset the effect of VMMC. Conversely, qualitative studies report that a small number of circumcised men had increased risky sexual behaviors, and community-based research reports that more men resumed sex early after surgery. With the large-scale promotion and expansion of VMMC services, it may be challenging to maintain effective sexual health educations due to various restrictions. Misunderstandings of the effect of VMMC in preventing HIV infection are the main reason for increasing risky sexual behaviors after surgery. Systematic and practical sexual health counseling services should be in place on an ongoing basis to maximize the effect of VMMC.


Asunto(s)
Circuncisión Masculina , Infecciones por VIH , Masculino , Femenino , Humanos , Circuncisión Masculina/psicología , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Parejas Sexuales , Conducta Sexual/psicología , Sexo Inseguro
15.
Bioorg Med Chem Lett ; 75: 128973, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36075370

RESUMEN

In the past decade, Wee1 inhibition has received widespread attention as a cancer therapy. Our research aims to discover effective, selective and drug-like Wee1 inhibitors. Herein, a series of compounds with pyrrolo[2,3-d]pyrimidine-based heterocycles were designed, synthesized and confirmed to inhibit Wee1 kinase. The inhibitors afforded good potency in Wee1 Kinase inhibitory activity in enzymatic assays. These compounds showed strong proliferation inhibition against NCI-1299 cell lines and had acceptable pharmacokinetic properties. These derivatives are promising inhibitors that warrant further evaluation, towards the development of potential anticancer drug.


Asunto(s)
Antineoplásicos , Pirimidinas , Antineoplásicos/farmacología , Proteínas de Ciclo Celular , Línea Celular Tumoral , Inhibidores Enzimáticos , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología
16.
Acta Biochim Biophys Sin (Shanghai) ; 54(2): 252-260, 2022 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-35538024

RESUMEN

Focal adhesion kinase (FAK), a multi-functional cytoplasmic tyrosine kinase, plays a critical role in cancer migration, proliferation and metastasis via regulating multiple signaling pathways. SY-707 is an anaplastic lymphoma kinase (ALK)/FAK/type 1 insulin-like growth factor receptor (IGF1R) multi-kinase inhibitor which is now being evaluated in phase II clinical trials for ALK positive non-small cell lung cancer (NSCLC). However, the effect of SY-707 on breast cancer is unknown. In this study, we assessed preclinical the anti-growth and anti-metastasis potency of SY-707 in breast cancer cells. ATP content, PE-Annexin V, and would healing assays were used to examine cell proliferation, cell cycle and migration. Then, SD rat and beagle dog models were used to evaluate the pharmacokinetics profile of SY-707, and mouse xenograft model was used to evaluate the anti-cancer activities of SY-707 . We found that breast cancer cells apoptosis were induced by SY-707. Moreover, SY-707 exerted inhibition on cell migration and adhesion in a dose-dependent manner. In T47D xenograft mice, SY-707 had significant anti-tumor activities alone or synergistically with Paclitaxel. Meanwhile, SY-707 also displayed significant suppression on spontaneous metastasis of tumor to the lung in 4T1 murine breast cancer xenograft model. In conclusion, SY-707 has potent anti-proliferation and anti-migration potential in breast cancer and , implying its therapeutic application for the treatment of breast cancer in future clinical trials.


Asunto(s)
Neoplasias de la Mama , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular , Perros , Femenino , Proteína-Tirosina Quinasas de Adhesión Focal , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Ratones , Metástasis de la Neoplasia , Inhibidores de Proteínas Quinasas/farmacología , Ratas , Ratas Sprague-Dawley , Receptor IGF Tipo 1 , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Pharm Biol ; 59(1): 200-208, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33595422

RESUMEN

CONTEXT: Rotundic acid (RA), a plant-derived pentacyclic triterpene acid, has been reported to possess extensive pharmacological activities. The poor bioavailability limits its further development and potential clinic application. OBJECTIVE: To clarify the potential mechanism for poor oral bioavailability. MATERIALS AND METHODS: The single-dose pharmacokinetics of orally administered RA (10 mg/kg) in Sprague-Dawley rats without or with verapamil (25 or 50 mg/kg) were investigated. Additionally, MDCKII-MDR1 and Caco-2 cell monolayers, five recombinant human cytochrome P450 (rhCYP) enzymes (1A2, 2C8, 2C9, 2D6 and 3A4), and rat liver microsomes were also conducted to investigate its potential mechanism. RESULTS: Verapamil could significantly affect the plasma concentration of RA. Co-administered verapamil at 25 and 50 mg/kg, the AUC0-∞ increased from 432 ± 64.2 to 539 ± 53.6 and 836 ± 116 ng × h/mL, respectively, and the oral clearance decreased from 23.6 ± 3.50 to 18.7 ± 1.85 and 12.2 ± 1.85 L/h/kg, respectively. The MDCKII-MDR1 cell assay showed that RA might be a P-gp substrate. The rhCYPs experiments indicated that RA was mainly metabolized by CYP3A4. Additionally, verapamil could increase the absorption of RA by inhibiting the activity of P-gp, and slow down the intrinsic clearance of RA from 48.5 ± 3.18 to 12.0 ± 1.06 µL/min/mg protein. DISCUSSION AND CONCLUSIONS: These findings indicated that verapamil could significantly affect the pharmacokinetic profiles of RA in rats. It was demonstrated that P-gp and CYP3A were involved in the transport and metabolism of RA, which might contribute to the low oral bioavailability of RA.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Citocromo P-450 CYP3A/metabolismo , Triterpenos/farmacocinética , Verapamilo/farmacología , Administración Oral , Animales , Área Bajo la Curva , Disponibilidad Biológica , Células CACO-2 , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Humanos , Masculino , Microsomas Hepáticos/metabolismo , Ratas , Ratas Sprague-Dawley , Triterpenos/administración & dosificación , Verapamilo/administración & dosificación
18.
Small ; 15(9): e1804688, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30677227

RESUMEN

Methanol is extremely harmful to human health, since it is oxidized slowly and can accumulate in the human body. Therefore, it is essential to develop a methanol gas sensing technology with high sensitivity and selectivity for use in environmental monitoring and healthcare. In this work, a simple and low-cost sensor based on a Y2 O3 multishelled hollow structure (YMSH) to selectively detect methanol with an ultrasensitive limit of detection (71 ppb) is developed. The unique multishelled hollow structure with a large surface area and exposed {222} facets makes an important contribution to the ultrasensitive detection of methanol, which is further confirmed by subsequent theoretical simulations. Moreover, in situ Fourier transform infrared spectra verify that CO2 is the final product, which indicates a high catalytic activity of the YMSHs toward methanol oxidation. Interestingly, the sensor can also be applied to liquor samples that are mixtures of ethanol, methanol, and water, which provides a facile way to detect methanol in wines. This sensor represents a unique and highly sensitive means to detect methanol, which has great promise for potential application in environmental monitoring and food safety inspection.

19.
Small ; 15(35): e1901980, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31267654

RESUMEN

As one important electrode reaction in electrocatalytic and photoelectrochemical cells for renewable energy circulation, oxygen catalysis has attracted considerable research in developing efficient and cost-effective catalysts. Due to the inevitable formation of oxygenic intermediates on surface sites during the complex reaction steps, the surface structure dynamically evolves toward reaction-preferred active species. To date, transition metal compounds, here defined as TM-Xides, where "X" refers to typical nonmetal elements from group IIIA to VIA, including hydroxide as well, are reported as high-performance oxygen evolution reaction (OER) electrocatalysts. However, more studies observe at least exterior oxidation or amorphization of materials. Thus, whether the TM-Xides can be defined as OER catalysts deserves further discussion. This Review pays attention to recent progress on the surface reconstruction of TM-Xide OER electrocatalysts with an emphasis on the identification of the true active species for OER, and aims at disseminating the real contributors of OER performance, especially under long-duration electrocatalysis.

20.
Nanotechnology ; 30(35): 355701, 2019 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-31082809

RESUMEN

We report oxygen vacancies (OVs) rich hexagonal ReO3 nanostructured electrocatalysts for efficient hydrogen generation. Through a simple argon plasma exposure, OVs are introduced into the ReO3 nanoparticles (NP) and nanosheets to enhance electrocatalytic activities with decreasing overpotentails from 157 mV and 178 mV to 138 mV and 145 mV at the current density of 10 mA cm-2, respectively. As-processed OVs rich ReO3 NP exhibit a good stability during electrochemical measurements for 20 h in acidic electrolyte. The huge active surface area, abundant OVs and excellent conductivity contribute to the performance according to the experimental data. Further theoretical calculations show that the abundant OVs adsorb H with lower Gibbs free energy facilitating hydrogen evolution.

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