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1.
N Engl J Med ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38828946

RESUMO

BACKGROUND: Osimertinib is a recommended treatment for advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation and as adjuvant treatment for resected EGFR-mutated NSCLC. EGFR-tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with unresectable EGFR-mutated stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurred (as assessed by blinded independent central review) or the regimen was discontinued. The primary end point was progression-free survival as assessed by blinded independent central review. RESULTS: A total of 216 patients who had undergone chemoradiotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24; P<0.001). The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53). The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported in 48% and 38%, respectively. No new safety concerns emerged. CONCLUSIONS: Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC. (Funded by AstraZeneca; LAURA ClinicalTrials.gov number, NCT03521154.).

2.
Ther Adv Med Oncol ; 16: 17588359241242972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736554

RESUMO

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X-S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X-S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

3.
Nat Commun ; 15(1): 4182, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38755157

RESUMO

Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect different activation environments or maturation of their precursors. Here we define human BMPC heterogeneity and track the recruitment of antibody-secreting cells (ASC) from SARS-CoV-2 vaccine immune reactions to the bone marrow (BM). Trajectories based on single-cell transcriptomes and repertoires of peripheral and BM ASC reveal sequential colonisation of BMPC compartments. In activated B cells, IL-21 suppresses CD19 expression, indicating that CD19low-BMPC are derived from follicular, while CD19high-BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19low- and CD19high-BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19high-BMPC compartments, reflecting their origin from extrafollicular reactivations of memory B cells. A pattern also observable in vaccinated-convalescent individuals and upon diphtheria/tetanus/pertussis recall-vaccination. Thus, BMPC diversity reflects the evolution of a given humoral immune response.


Assuntos
Antígenos CD19 , Medula Óssea , Interleucinas , Plasmócitos , Humanos , Plasmócitos/imunologia , Interleucinas/imunologia , Interleucinas/metabolismo , Medula Óssea/imunologia , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Imunidade Humoral/imunologia , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/citologia , Análise de Célula Única , Adulto , Linfócitos B/imunologia , Células Produtoras de Anticorpos/imunologia , Feminino , Masculino , Vacinação , Pessoa de Meia-Idade , Vacina contra Difteria, Tétano e Coqueluche/imunologia
4.
J Autoimmun ; 147: 103243, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38788537

RESUMO

OBJECTIVES: Autoreactive B cells and interferon (IFN) signature are hallmarks of primary sjögren's syndrome (pSS), but how IFN signaling pathways influence autoantibody production and clinical manifestations remain unclear. More detailed studies hold promise for improved diagnostic methodologies and personalized treatment. METHODS: We analyzed peripheral blood T and B cell subsets from 34 pSS patients and 38 healthy donors (HDs) at baseline and upon stimulation regarding their expression levels of type I and II IFN signaling molecules (STAT1/2, IRF1, IRF9). Additionally, we investigated how the levels of these molecules correlated with serological and clinical characteristics and performed ROC analysis. RESULTS: Patients showed elevated IFN pathway molecules, including STAT1, STAT2 and IRF9 among most T and B cell subsets. We found a reduced ratio of phosphorylated STAT1 and STAT2 in patients in comparison to HDs, although B cells from patients were highly responsive by increased phosphorylation upon IFN stimulation. Correlation matrices showed further interrelations between STAT1, IRF1 and IRF9 in pSS. Levels of STAT1 and IRF9 in T and B cells correlated with the IFN type I marker Siglec-1 (CD169) on monocytes. High levels of STAT1 and IRF9 within pSS B cells were significantly associated with hypergammaglobulinemia as well as anti-SSA/anti-SSB autoantibodies. Elevated STAT1 levels were found in patients with extraglandular disease and could serve as a biomarker for this subgroup (p < 0.01). Notably, IRF9 levels in T and B cells correlated with EULAR Sjögren's syndrome disease activity index (ESSDAI). CONCLUSION: Here, we provide evidence that in active pSS patients, enhanced IFN signaling incl. unphosphorylated STAT1 and STAT2 with IRFs entertain chronic T and B cell activation. Furthermore, increased STAT1 levels candidate as biomarker of extraglandular disease, while IRF9 levels can serve as biomarker for disease activity.

5.
Heliyon ; 10(10): e31084, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803945

RESUMO

The study investigated the effectiveness of Mg/Al LDH-zeolite (MALZ) in immobilizing exchangeable Cr (e-Cr) within the soil. The research systematically evaluated various variables affecting the immobilization of e-Cr in contaminated soil (CS), including soil pH levels (ranging from 5.0 to 9.0), different weight ratios of MALZ (1 %, 3 %, and 5 %), durations of differing incubation periods (15, 30 and 45 days), and different SM content levels (30 %, 50 %, and 70 %). The initial concentration of Cr in the CS was maintained at 50 mg/kg. The investigation findings revealed that the optimal conditions for immobilizing the e-Cr were a soil pH of 5.0, an MALZ weight ratio of 3 %, an incubation period of 30 days, and an SM level of 70 %. Under these ideal conditions, the percentage of e-Cr within the CS decreased significantly, from 87.49 % (45.64 mg/kg) in the control treatment (CT) to just 19.82 % (10.08 mg/kg) when incubated with MALZ. The primary mechanisms responsible for immobilizing the e-Cr onto MALZ included pore filling, reduction processes, co-precipitation, organic interactions and electrostatic attractions leading to the formation of carbonate-bound complexes such as Cr(VI)-carbonate, Cr(III)-carbonate, and organic complexes. Surface functional groups on MALZ, housing iron and aluminium oxyhydroxides and silicon and oxygen elements, expedited these procedures. This study provided a valuable understanding of the mitigation of soils contaminated with chromium and contributed to understanding the relations between MALZ and the e-Cr in the soil. The discoveries carry substantial consequences for the advancement of efficient remediation technologies.

7.
A A Pract ; 18(4): e01767, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578015

RESUMO

Pulmonary embolism is a common complication after intracranial hemorrhage. As thrombolysis is contraindicated in this situation, surgical pulmonary embolectomy may be indicated in case of high-risk pulmonary embolism but requires transient anticoagulation with heparin during cardiopulmonary bypass. We report the case of a patient with a history of heparin-induced thrombocytopenia who presented with a high-risk pulmonary embolism 10 days after the spontaneous onset of a voluminous intracerebral hematoma. Despite high doses of heparin required to run the cardiopulmonary bypass and subsequent anticoagulation by danaparoid sodium, the brain hematoma remained stable and the patient was discharged without complications 30 days after surgery.


Assuntos
Embolia Pulmonar , Trombocitopenia , Humanos , Anticoagulantes/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Heparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/cirurgia , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/cirurgia , Embolia Pulmonar/complicações , Hemorragias Intracranianas/cirurgia , Hemorragias Intracranianas/complicações , Hemorragia Cerebral , Embolectomia/efeitos adversos , Hematoma/cirurgia
8.
Clin Case Rep ; 12(4): e8743, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38590331

RESUMO

Gallbladder volvulus (GV) is a medical emergency and a rare cause of acute abdominal pain among the pediatric population. GV is more prominent usually in boys in pediatric patients. If it is not diagnosed and surgically intervened promptly, GV will become a life-threating condition. Fortunately, a safe and effective laparoscopic cholecystectomy is now widely indicated. A 5 years old female patient with abdominal pain and heavy much vomiting was referred to the emergency room in our hospital. She was suspiciously diagnosed with acute inflammation of the gallbladder according to the results of abdominal ultrasound and computerized tomography (CT) scan already performed on admission. One day after the hospitalization, abdominal ultrasound, and CT scan were performed again because of intensification of her abdominal pain and revealed the clinical portrait of GV such as a "floating gallbladder" sign, an echogenic cone structure, an elongated axis displaced horizontally instead of vertically and a lack of intramural blood flow. The acute GV diagnosis was made and the patient was operated, using the laparoscopic cholecystectomy on time, the gallbladder was tightly twisted clockwise at approximately 720°. The operation and postoperative treatment went quite well and the patient was discharged from the hospital on postoperative Day 7. GV is very rare in children, easily omitted or misdiagnosed with cholecystitis. Imaging diagnosis such as ultrasound, CT with contrast helps make diagnosis promptly that avoids severe complications such as gallbladder perforation, necrosis, and biliary peritonitis.

9.
RSC Adv ; 14(17): 12081-12095, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38628478

RESUMO

Twelve compounds were isolated from Mussaenda saigonensis aerial parts through phytochemical analysis and the genus Mussaenda is the first place where the compounds 4-6 and 11-12 have been found. Based on the ability to inhibit NO production in RAW264.7 cells, compound 2 has demonstrated the strongest anti-inflammatory activity in vitro with an IC50 of 7.6 µM, as opposed to L-NMMA's IC50 of 41.3 µM. Compound 12 was found to be the most effective inhibitor of alpha-glucosidase enzyme in vitro, with an IC50 value of 42.4 µM (compared to 168 µM for acarbose). Compounds 1-12 were evaluated in vitro for antimicrobial activity using the paper dish method. Compound 11 demonstrated strong antifungal activity against M. gypseum with a MIC value of 50 µM. In silico docking for antimicrobial activity, pose 90 or compound 11 docked well to the 2VF5 enzyme, PDB, which explains why compound 11 had the highest activity in vitro. Entry 2/pose 280 demonstrated excellent anti-inflammatory activity in silico. The stability of the complex between pose 280 and the 4WCU enzyme for anti-inflammatory activity has been assessed using molecular dynamics over a simulation course ranging from 0 to 100 ns. It has been found to be stable from 60 and 100 ns. The Tyr 159 (95%, H-bond via water bridge), Asp 318 (200%, multiple contacts), Met 273 (75%, hydrophobic interaction via water bridge), and Gln 369 (75%, H-bond via water bridge) interacted well within the time range of 0 to 100 ns. It has more hydrophilic or polar pharmacokinetics.

10.
RSC Adv ; 14(13): 9326-9338, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38505391

RESUMO

Seven flavonoid glycosides were isolated from the aerial portions of Mussaenda recurvata during a phytochemical analysis. This comprised one novel component, ecurvoside, and six well-studied compounds, namely astragalin, isoquercitrin, nicotiflorin, rutin, hesperidin, and neohesperidin. The chemical structures of compounds were identified using spectroscopic techniques and a comparison with previously published studies. Alpha-glucosidase inhibition testing was carried out on all isolated compounds. The compounds evaluated have IC50 values between 35.6 and 239.1 g mL-1, indicating a moderate degree of inhibition. In vitro antimicrobial activities of compounds 1-7 have screened against the bacteria Pseudomonas aeruginosa (P. aeruginosa), methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus faecalis (Strep. faecalis), and fungi: Candida albicans (C. albicans), Trichophyton mentagrophytes (T. mentagrophytes), and Microsporum gypseum (M. gypseum), where compound 6 showed excellent activity against fungi T. mentagrophytes with an MIC value of 12.5 µM. In accordance with the molecular docking study, ecurvoside (1) or pose 472 interacted well with the 3TOP enzyme: PDB and the molecular dynamic simulations proved that the complex of ecurvoside and 3TOP has a stable simulation time of 50-100 ns and the significant residual amino acids in 3TOP are relative to interactions more than one time such as Asp 960, Glu 961, Lys 1088, Glu 1095, Arg 1097, Gly 1102, Thr 1103, Gln 1109, Glu 1178: A chain and Glu 1095, Thr 1101, and Asp 1107: B chain. The docking studies of compounds 1-7 to the enzyme 2VF5 explain the general mechanism to inhibit bacteria and proved that compound 6 (pose 370) inhibited stronger than compound 7 (pose 362) and compound 5 (pose 280), and compounds 1 to 4 do not interact well with 2VF5.

11.
Analyst ; 149(8): 2252-2271, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38470814

RESUMO

A convergent sector in microfluidic devices utilizing ion concentration polarization (ICP) can help increase the preconcentration rate and the concentration enhancement factor (CEF) of biomolecules. In this work, we present a detailed study of the nozzle-like-squeeze effect of a convergent channel on the preconcentration of biomolecules. By numerically solving coupled Nernst-Planck-Poisson-Navier-Stokes governing equations for the 2D channel model, we report the first study on the critical width of a convergent region in the channel to retain the advantage of the nozzle-like-squeeze effect in speeding up preconcentration and augmenting CEF. In addition, we investigated the impact of the location and the dimensions of a convergent sector on the mechanism of biomolecule preconcentration. The location of an ion-selective membrane was also determined to ensure that biomolecules are focused on the convergent region of the channel. Moreover, we introduce analytical studies to compare and verify simulation findings. Specifically, the formulas for the critical dimensions of a convergent channel, location of a preconcentrated biomolecule plug, and position of an ion-selective membrane are presented. Furthermore, important working parameters, including electric potentials and hydrostatic pressures, were examined to scrutinize their effect on convergent concentrators. These detailed analytical solutions and numerical simulation results are consistent with experimental observations, providing deep insights into the ICP phenomenon and the preconcentration mechanism of biomolecules in convergent microfluidic concentration devices.


Assuntos
Técnicas Analíticas Microfluídicas , Técnicas Analíticas Microfluídicas/métodos , Dispositivos Lab-On-A-Chip
12.
Nat Prod Res ; : 1-8, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38516731

RESUMO

The phytochemical composition of the Combretum trifoliatum leaves was studied for the first time. Two new triterpenoid saponins, named comtrifoside A (1) and comtrifoside B (2), together with two other saponins (3-4) were purified by variously chromatographic techniques. For the first time, compound 3 was informed from the Combretum genus, as well as all of the isolated compounds (1-4) were reported from C. trifoliatum. The chemical structures of them were clearly characterised using extensive UV-VIS, IR, HRMS-ESI, and NMR experimental data. The in vitro anti-inflammatory activities of 1 & 2 were examined against NO overproduction in LPS activation of RAW264.7.

13.
Orthop Rev (Pavia) ; 16: 94242, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469578

RESUMO

Background: The anatomical parameters of the acetabulum vary among races and geographical regions. Multislice Computed Tomography (CT) has proven to be a practical approach to assess morphological parameters of the acetabulum. The purpose of this study was to explore morphological characteristics of the acetabulum measured by CT scans in Vietnamese adults. Methods: Thirty-five consecutive patients aged 18 years and older received indications and eligibility for total hip replacement surgery. Sixty-three acetabulum were examined with multislice computed tomographic system (CT) with multiplanar reconstruction (MPR). Measured morphometric parameters of acetabulum included acetabular inclination angle (AIA), acetabular anteversion angle (AAA), acetabular angle of sharp (AAS), sagittal acetabular angle (SAA), acetabular horizontal offset (AHO), transverse acetabular ligament anteversion (TALA), transverse acetabular ligament inclination (TALI), acetabular depth (ADe), acetabular depth ratio (ADr) and acetabular diameter (ADi). Results: The mean values of acetabular diameter, femoral head diameter, AIA, AAA, AAS, SAA, TALA, TALI, AHO, ADe, ADr were 50.22±3.56 mm, 43.54±3.68 mm, 40.27±5.09 mm, 13.30±5.54 mm, 39.46±5.41 mm, 26.38±9.01 mm, 9.49±3.92 mm, 47.70±6.73 mm, 3.06±0.37 mm, 18.62±2.95 mm and 309.60±41.87 mm. Conclusion: Our initial data has showed morphological characteristics of the acetabulum in Vietnamese adults, different from the populations from other parts of world. Also, significant correlation between the orientation of the acetabulum and the transverse acetabular ligament was documented.

14.
Chem Biodivers ; 21(5): e202400380, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38498616

RESUMO

The chemical investigation of the stems of Knema globularia led to the isolation of two new benzoquinones derivatives, embenones A and B (1 and 2), along with three known compounds (3-5). The structures of the isolated compounds were determined using spectroscopic techniques, including HRESIMS, 1D and 2D NMR, in conjunction with comparison to existing literature data. Compounds 1 and 2 represent new carbon skeletons in nature. Furthermore, all isolated compounds were evaluated for their α-glucosidase inhibitory activity, with compounds 1-3 exhibiting superior potency relative to the positive control (acarbose, IC50 331 µM). Their IC50 values ranged from 1.40 to 96.1 µM.


Assuntos
Benzoquinonas , Inibidores de Glicosídeo Hidrolases , Caules de Planta , alfa-Glucosidases , Benzoquinonas/química , Benzoquinonas/isolamento & purificação , Benzoquinonas/farmacologia , Caules de Planta/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , alfa-Glucosidases/metabolismo , Vietnã , Relação Estrutura-Atividade , Estrutura Molecular , Conformação Molecular , População do Sudeste Asiático
15.
Langmuir ; 40(11): 6051-6064, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38437236

RESUMO

Preconcentration of biomolecules based on ion concentration polarization (ICP) has been splendidly applied to various biomedical and chemical processes. However, in many circumstances, biomolecule preconcentration could not occur due to the lack of full studies on the preconcentration mechanism, especially on the effect of microchannel dimensions. In this work, we provide analytical studies on the critical dimensions (minimum and maximum) of microchannels for the preconcentration of biomolecules. These formulas are verified with the numerical results by fully solving the coupled governing equations: Poisson-Nernst-Planck and Navier-Stokes experiments with appropriate boundary conditions and assumptions. In addition, we examine the impact of operational parameters, such as electric potentials and critical external pressures, on the formation of the preconcentration. Moreover, two important results are provided for the first time, including the position of the preconcentrated biomolecule region and the concentration enhancement factor of the biomolecules. These analytical and numerical results are consistent with experimental observations and, therefore, could provide sharp insight into the mechanism of biomolecule preconcentration and give useful guidelines to better design and optimize ICP-based microfluidic preconcentration devices.


Assuntos
Dispositivos Lab-On-A-Chip
16.
Heliyon ; 10(3): e25195, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38352799

RESUMO

Cuprous oxide/copper/cupric oxide nanoparticles were synthesized through a hybrid process involving anodic dissolution and a controlled redox reaction between NaOH and glucose in the solution. The study demonstrates the structural manipulation of the material by varying the reaction components within the solution. Morphology, structural analyses using SEM (Scanning Electron Microscope), EDX (Energy-dispersive X-ray spectroscopy), TEM (Transmission Electron Microscope), FTIR (Fourier Transform Infrared Spectroscopy), XRD (X-ray diffraction), and XPS (X-ray photoelectron spectroscopy) unveiled the tunability of the material's structure based on the reaction components. Nitrogen adsorption analysis employing the Brunauer-Emmett-Teller (BET) equation confirmed the material's porosity, while Dynamic Light Scattering (DLS) measurements provided insights into the materials' hydrodynamic size and zeta potential. The results demonstrated that by increasing the glucose/NaOH ratio during the reaction, the different structures and morphologies of the distinct products were obtained from the clustering of small nanoparticles to cubic shape and flower-like structure. Antibacterial activity tests conducted on various bacterial strains showed a correlation between the morphology and structure of the material and its antibacterial properties. The highest substantial antibacterial efficacy against all tested bacterial strains at a dosage of 100 µg/L was obtained for the samples with clustering morphology, whereas the remaining materials showed no discernible antibacterial effect against one of the studied bacteria. The results also demonstrated that the sample with a clustering structure exhibited superior antibacterial properties when dispersed in water containing dimethylsulfoxide.

17.
Microbiol Resour Announc ; 13(3): e0122623, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38358276

RESUMO

Extended-spectrum ß-lactamase-producing non-O1 Vibrio cholerae was isolated from edible Mastacembelus sp. in Vietnam. The genome sequence was sequenced using DNBSEQ-G400 and MinION Mk1b. A plasmid of approximately 183-kb encoding blaCTX-M-55 and blaTEM-1 was detected.

18.
ACS Appl Mater Interfaces ; 16(8): 9989-9998, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38358461

RESUMO

Oxygen evolution reaction (OER) plays a crucial role as a counter half-reaction for both electrochemical hydrogen production through water splitting and the generation of valuable carbon compounds via CO2 reduction. To overcome the sluggish kinetics of the OER, significant efforts have been devoted to developing cost-effective, sustainable, and efficient electrocatalysts, with transition-metal-based catalysts emerging as promising candidates. Herein, we successfully synthesized a core-shell type nanostructure of Fe-doped CoMoOx/CoMoOx (CMFO), which exhibits excellent electrocatalytic properties for OER. The presence of an amorphous layer of Fe-doped CoMoOx with abundant oxygen vacancies, along with the stability of a key OER intermediate, *O, contributes to the enhanced activity of CMFO catalyst compared to pristine CoMoOx (CMO). The optimized catalyst of CMFO-550 achieved much lower overpotential and Tafel slope and also exhibited better remarkable long-term stability for over 90 h compared to CMO-550. These findings highlight the potential of CMFO-550 as a cost-effective and highly efficient electrocatalyst for the OER. The successful development of this core-shell nanostructure opens up a new opportunity for the design and synthesis of advanced electrocatalysts for the OER, with implications for various applications in energy conversion and storage.

19.
BMC Cancer ; 24(1): 176, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317094

RESUMO

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.


Assuntos
Afatinib , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Afatinib/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Vietnã/epidemiologia
20.
J Fluoresc ; 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280054

RESUMO

SiO2@Ag nanocomposite (NC) has been synthesized by the chemical reduction and StÓ§ber method for Metal-enhanced fluorescence (MEF) of Rhodmine 6G (R6G) and Surface-enhanced Raman spectroscopy (SERS) of Malachite green (MG). As-synthesized SiO2@Ag NC indicated SiO2 nanosphere (NS) and Ag nanoparticle (NP) morphologies. The SiO2@Ag NC was high quality with a well-defined crystallite phase with average sizes of 24 nm and 132 nm for Ag NP and SiO2 NC, respectively. By using SiO2@Ag NC, the photoluminescence (PL) intensity of the R6G (at 59.17 ppm) was increased approximately 133 times. The SERS of the MG (at 1.0 ppm) with SiO2@Ag NC as substrate clearly observed vibrational modes in MG dye at 798, 916, 1172, 1394, and 1616 cm-1. As a result, the SERS enhancement factor (EFSERS) at 1172 cm-1 obtained 6.3 × 106. This initial study points to the potential of SiO2@Ag NC as a promising material for MEF and SERS substrates to detect dyes at low concentrations.

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