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1.
Opt Express ; 32(12): 21358-21373, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859491

RESUMO

Amplitude-modulated single-pixel ptychography (SPP) enables non-interferometric complex-field imaging of objects. However, the conventional iterative and nondeterministic reconstruction methods, based on the ptychography algorithm, pose challenges in fully understanding the role of critical optical parameters. In response, this paper introduces an innovative analytical approach that establishes a theoretical foundation for the uniqueness of SPP reconstruction results. The proposed method conceptualizes SPP as a system of linear equations in the frequency domain, involving both object and modulated illumination. Solving this equation system reveals a determined solution for the complex object, providing an alternative to iterative and nondeterministic techniques. Through a series of simulations, this approach not only validates the uniqueness of SPP reconstruction, but also explores key properties influencing accuracy.

2.
Am J Hematol ; 99(4): 774-779, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38343062

RESUMO

Jaktinib, a novel JAK and ACVR1 inhibitor, has exhibited promising results in treating patients with myelofibrosis (MF). ZGJAK002 is a Phase 2 trial aimed to assess the efficacy and safety of jaktinib 100 mg BID (N = 66) and 200 mg QD (N = 52) in JAK inhibitor-naive patients with intermediate- or high-risk MF. We herein present the long-term data with a median follow-up of 30.7 months. At data cutoff, 30.3% of patients in 100 mg BID and 28.8% in 200 mg QD were still continuing their treatment. The 100 mg BID group displayed a numerically higher best spleen response compared with the 200 mg QD group (69.7% vs. 46.2%), with 50.4% from the BID and 51.2% from the QD group maintaining spleen responses over 120 weeks. The 36-month survival rates were 78.2% in BID and 73.6% in QD group. The tolerability of jaktinib remained well, and common grade ≥3 adverse drug reactions included anemia (15.2% vs. 21.2%), thrombocytopenia (15.2% vs. 11.5%), and infectious pneumonia (10.6% vs. 1.9%) in BID and QD groups, respectively. By comparing the two groups, the incidence of adverse events (AEs) were similar, except for drug-related serious AEs (24.2% vs. 9.6%) and AEs leading to treatment discontinuation (15.2% vs. 7.7%), which were higher in BID group. The percentages of AEs resulting in death were comparable, with 6.1% in BID and 5.8% in QD group. These analyses further support the long-term durable efficacy and acceptable safety of jaktinib at 100 mg BID and 200 mg QD doses for treating MF.


Assuntos
Mielofibrose Primária , Humanos , Seguimentos , Mielofibrose Primária/tratamento farmacológico , Resultado do Tratamento
3.
Anal Bioanal Chem ; 416(4): 913-923, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38117323

RESUMO

Heat shock protein 90α (HSP90α) has been regarded as an important indicator for judging tumor metastasis and prognosis due to its significant upregulation in various tumors. Therefore, the accurate quantification of HSP90α is of great significance for clinical diagnosis and therapy of cancers. However, the lack of HSP90α certified reference material (CRM) leads to the accuracy and consistency of quantification methods not being effectively evaluated. Besides, quantitative results without traceability make comparisons between different studies difficult. In this study, an HSP90α solution CRM was developed from the recombinant protein raw material. The recombinant protein is a dimer, and the purity of the CRM candidate reached 96.71%. Both amino acid analysis-isotope dilution mass spectrometry (AAA-IDMS) and unique peptide analysis-isotope dilution mass spectrometry (UPA-IDMS) were performed to measure the content of HSP90α in the solution CRM candidate, and the certified value was assessed to be 66.2 ± 8.8 µg/g. Good homogeneity of the CRM was identified, and the stability examination suggested that the CRM was stable for at least 4 months at - 80 °C and for 7 days at 4 °C. With traceability to SI unit (kg), this CRM has potential to help establish a metrological traceability chain for quantification of HSP90α, which will make the quantification results standardized and comparable regardless of the quantitative methods.


Assuntos
Isótopos , Neoplasias , Padrões de Referência , Espectrometria de Massas/métodos , Calibragem , Proteínas Recombinantes/análise , Neoplasias/diagnóstico
4.
J Environ Sci (China) ; 142: 215-225, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38527887

RESUMO

Low-cost sensors are widely used to collect high-spatial-resolution particulate matter data that traditional reference monitoring devices cannot. In addition to the mass concentration, the number concentration and size distribution are also fundamental in determining the origin and hazard level of particulate pollution. Therefore, low-cost optical sensors have been improved to establish optical particle sizers (OPSs). In this study, a low-cost OPS, the Nova SDS029, is introduced, and it is evaluated in comparison to two reference instruments-the GRIMM 11-D and the TSI 3330. We first tested the sizing accuracy using polystyrene latex spheres. Then, we assessed the mass and number size distribution accuracy in three application scenarios: indoor smoking, ambient air quality, and mobile monitoring. The evaluations suggest that the low-cost SDS029 rivals research-grade optical sizers in many aspects. For example, (1) the particle diameters obtained with the SDS029 are close to the reference instruments (usually < 10%) in the 0.3-5 µm range; (2) the number of particles and mass concentration are highly correlated (r ≥ 0.99) with the values obtained with the reference instruments; and (3) the SDS029 slightly underestimates the number concentration, but the derived PM2.5 values are closer to monitoring station than the reference instruments. The successful application of the SDS029 in multiple scenarios suggests that a plausible particle size distribution can be obtained in an easy and cost-efficient way. We believe that low-cost OPSs will increasingly be used to map the sources and risk levels of particles at the city scale.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Tamanho da Partícula , Poluição do Ar/análise , Material Particulado/análise , Poeira , Poluentes Atmosféricos/análise
5.
J Environ Sci (China) ; 139: 320-333, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105058

RESUMO

Black carbon (BC) is associated with adverse human health and climate change. Mapping BC spatial distribution imperatively requires low-cost and portable devices. Several portable BC monitors are commercially available, but their accuracy and reliability are not always satisfactory during continuous field observation. This study evaluated three models of portable black carbon monitors, C12, MA350 and DST, and investigates the factors that affect their performance. The monitors were tested in urban Beijing, where portable devices running for one month alongside a regular-size reference aethalometer AE33. The study considers several factors that could influence the monitors' performance, including ambient weather, aerosol composition, loading artifacts, and built-in algorithms. The results show that MA350 and DST present considerable discrepancies to the reference instrument, mainly occurring at lower concentrations (0-500 ng/m3) and higher concentrations (2500-8000 ng/m3), respectively. These discrepancies were likely caused by the anomalous noise of MA350 and the loading artifacts of DST. The study also suggests that the ambient environment has limited influence on the monitors' performance, but loading artifacts and accompanying compensation algorithms can result in unrealistic data. Based on the evaluation, the study suggests that C12 is the best choice for unsupervised field measurement, DST should be used in scenarios where frequent maintenance is available, and MA350 is suitable for research purposes with post-processing applicable. The study highlights the importance of assigning portable BC monitors to appropriate applications and the need for optimized real-time compensation algorithms.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Humanos , Monitoramento Ambiental/métodos , Reprodutibilidade dos Testes , Pequim , Fuligem/análise , Carbono , Poluentes Atmosféricos/análise
6.
Anal Chem ; 95(43): 15875-15883, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37851939

RESUMO

In proteomics research, with advantages including short digestion times and reusable applications, immobilized enzyme reactors (IMERs) have been paid increasing attention. However, traditional IMERs ignore the reasonable spatial arrangement of trypsin on the supporting matrixes, resulting in the partial overlapping of the active domain on trypsin and reducing digesting efficiency. In this work, a DNA tetrahedron (DNA TET)-based IMER Fe3O4-GO-AuNPs-DNA TET-Trypsin was designed and prepared. The distance between vertices of DNA TETs effectively controls the distribution of trypsin on the nanomaterials; thus, highly efficient protein digestion and accurate quantitative results can be achieved. Compared to the in-solution digestion (12-16 h), the sequence coverage of bovine serum albumin was up to 91% after a 2-min digestion by the new IMER. In addition, 3328 proteins and 18,488 peptides can be identified from HeLa cell protein extract after a 20-min digestion. For the first time, human growth hormone reference material was rapidly and accurately quantified after a 4-h digestion by IMER. Therefore, this new IMER has great application potential in proteomics research and SI traceable quantification.


Assuntos
Nanopartículas Metálicas , Proteoma , Humanos , Proteoma/química , Tripsina/química , Ouro , Células HeLa , Enzimas Imobilizadas/química , Digestão
7.
Cancer Immunol Immunother ; 72(10): 3293-3307, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37462763

RESUMO

BACKGROUND: While epidemiological studies have established a firm link between circadian disruption and tumorigenesis, the role and mechanism are not fully understood, complicating the design of therapeutic targets related to circadian rhythms (CR). Here, we aimed to explore the intertumoral heterogeneity of CR and elucidate its impact on the tumor microenvironment (TME), drug sensitivity, and immunotherapy. METHODS: Based on unsupervised clustering of 28 CR genes, two distinct CR subtypes (cluster-A and cluster-B) were identified in the TCGA cohort. We further constructed a circadian rhythm signature (CRS) based on the CR genes primarily responsible for clustering to quantify CR activity and to distinguish CR subtypes of individual patients from external datasets. CR subtypes were evaluated by TME characteristics, functional annotation, clinical features, and therapeutic response. RESULTS: The cluster-B (low-CRS) group was characterized by highly enriched immune-related pathways, high immune cell infiltration, and high anti-tumor immunity, while the cluster-A (high-CRS) group was associated with immunosuppression, synaptic transmission pathways, EMT activation, poor prognosis, and drug resistance. Immunohistochemistry (IHC) results demonstrated that high CD8+ T cell infiltration was associated with low-CR-protein expression. Importantly, patients with low CRS were more likely to benefit from immune checkpoint blockade (ICB) treatment, possibly due to their higher tumor mutation burden (TMB), increased immune checkpoint expression, and higher proportion of "hot" immunophenotype. CONCLUSION: In a nutshell, the cross talk in CR could reflect the TME immunoreactivity in breast cancer. Besides providing the first comprehensive pathway-level analysis of CR in breast cancer, this work highlights the potential clinical utility of CR for immunotherapy.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Imunoterapia , Terapia de Imunossupressão , Linfócitos T CD8-Positivos , Carcinogênese , Microambiente Tumoral , Prognóstico
8.
Opt Express ; 31(21): 35143-35155, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37859252

RESUMO

By writing diffracted intensities as a set of linear equations with the self-correlation of sample's Fourier components as unknown terms and the self-correlation of illumination's Fourier components as coefficients, it was found that the number of unknown terms to be determined is much larger in partially coherent PIE than that in purely coherent PIE. When a partially coherent illumination composed of N modes was applied a unique reconstruction can be determined by scanning the sample to at least 4N positions and recording 4N frames of diffraction patterns. While mathematically illustrating the physical mechanism of multimode ptychography and numerically demonstrating its capability in generating unique reconstruction under partially coherent illumination, this study showed for the first time that multimode ptychography could be an analytic imaging method.

9.
Am J Hematol ; 98(10): 1588-1597, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37470365

RESUMO

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.


Assuntos
Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Inibidores de Janus Quinases/efeitos adversos , Mielofibrose Primária/tratamento farmacológico , Nitrilas/uso terapêutico , Pirimidinas/uso terapêutico , Resultado do Tratamento
10.
Am J Hematol ; 98(10): 1579-1587, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37466271

RESUMO

Ruxolitinib has demonstrated efficacy in patients with myelofibrosis (MF). However, substantial number of patients may not respond after 3-6 months of treatment or develop resistance over time. In this phase 2 trial, patients with a current diagnosis of intermediate or high-risk MF who either had an inadequate splenic response or spleen regrowth after ruxolitinib treatment were enrolled. All patients received jaktinib 100 mg Bid. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR 35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profile. From July 6, 2021, to January 24, 2022, 34 ruxolitinib-refractory or relapsed patients were enrolled, 52.9% (18 of 34) were DIPSS intermediate 2 or high risk. SVR 35 at week 24 was 32.4% (11 of 34, 95% CI 19.1%-49.2%) in all patients and 33.3% (6 of 18, 95% CI 16.3%-56.3%) in the intermediate 2 or high-risk group. A total of 50% (8 of 16) transfusion-independent patients with hemoglobin (HGB) <100 g/L at baseline had HGB elevation ≥20 g/L within 24 weeks. Furthermore, 46.4% (13 of 28) of patients had a ≥ 50% decrease in the total symptom score (TSS 50) at week 24. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (32.4%), anemia (32.4%), and leukocytosis (20.6%). In total, 13 (38.2%) of 34 patients had serious adverse events (SAE), of which drug-related SAEs were found in 5 patients (14.7%). These results indicate that jaktinib can be a promising treatment option for patients with MF who have either become refractory to or relapsed after ruxolitinib treatment.


Assuntos
Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Inibidores de Janus Quinases/efeitos adversos , Mielofibrose Primária/diagnóstico , Pirimidinas/efeitos adversos , Nitrilas , Resultado do Tratamento
11.
Anal Bioanal Chem ; 415(19): 4795-4804, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37291250

RESUMO

Here we proposed a method for peptide purity analysis using gas chromatography-isotope dilution infrared spectroscopy. The principle and feasibility of the proposed measurement method were investigated. The derivatization, separation, and infrared detection conditions for amino acids were optimized, and the performance of the method was investigated. Then, the proposed method was used for assessment of [Glu1]-fibrinopeptide B purity, and the results were compared with those obtained by high performance liquid chromatography-isotope dilution mass spectrometry. The average purity of six sub-samples using the proposed method was (0.755 ± 0.017) g/g, which agreed well with that obtained by isotope dilution mass spectrometry (0.754 ± 0.012) g/g. The repeatability of the proposed method was 2.2%, which was similar to that of isotope dilution mass spectrometry (1.7%). The proposed method has a similar principle and had similar accuracy, precision, and linearity to isotope dilution mass spectrometry; however, the developed method had higher limit of detection (LOD) and limit of quantitation (LOQ) values because of the low sensitivity of infrared detection. The results were also Système International d'Unités (SI) traceable. The developed method has the advantage of lower cost compared with isotope dilution mass spectrometry because only one isotope-labeled atom in an analog is required, and several infrared spectra can be extracted, averaged, and used for an amino acid calculation during one run, potentially leading to higher accuracy. This method could be easily expanded to the accurate quantitation of other organic compounds, including proteins. It is expected that the proposed method will be widely used in chemical and biological measurements as a new primary method.


Assuntos
Isótopos , Peptídeos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas/métodos , Técnicas de Diluição do Indicador , Aminoácidos/análise , Análise Espectral
12.
J Basic Microbiol ; 63(12): 1348-1360, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37495561

RESUMO

Indole is traditionally known as a metabolite of l-tryptophan and now as an important signaling molecule in bacteria, however, the understanding of its upstream synthesis regulation is very limited. Pantoea ananatis YJ76, a predominant diazotrophic endophyte isolated from rice (Oryza sativa), can produce indole to regulate various physiological and biochemical behaviors. We constructed a mutant library of YJ76 using the mTn5 transposon insertion mutation method, from which an indole-deficient mutant was screened out. Via high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR), the transposon was determined to be inserted in a gene (RefSeq: WP014605468.1) of unknown function that is highly conserved at the intraspecific level. Bioinformatics analysis implied that the protein (Protein ID: WP089517194.1) encoded by the mutant gene is most likely to be a new orphan substrate-binding protein (SBP) for amino acid ABC transporters. Amino acid supplement cultivation experiments and surface plasmon resonance revealed that the protein could bind to l-serine (KD = 6.149 × 10-5 M). Therefore, the SBP was named as SerBP. This is the first case that a SBP responds to l-serine ABC transports. As a precursor of indole synthesis, the transmembrane transported l-serine was directly correlated with indole signal production and the mutation of serBP gene weakened the resistance of YJ76 to antibiotics, alkali, heavy metals, and starvation. This study provided a new paradigm for exploring the upstream regulatory pathway for indole synthesis of bacteria.


Assuntos
Pantoea , Mutação , Pantoea/genética , Aminoácidos/metabolismo , Indóis/metabolismo , Serina/genética , Serina/metabolismo
13.
Eur J Nucl Med Mol Imaging ; 49(12): 4171-4181, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35781600

RESUMO

PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and we aimed to evaluate the safety and efficacy of a novel recombinant human thyroid-stimulating hormone (rhTSH, ZGrhTSH) as an alternative of THW in China. METHODS: Totally, 64 DTC patients were enrolled with 24 in the dose-escalation cohort equally grouped into 0.9 mg × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day dose-expansion cohort. All patients underwent both ZGrhTSH phase and levothyroxine (L-T4) withdrawal phase for self-comparison in terms of TSH levels, the radioactive iodine (RAI) uptake, stimulated thyroglobulin level, and the quality of life (QoL). RESULTS: In ZGrhTSH phase, no major serious adverse events were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and asthenia in 3.1% of the patients, and mostly resolved spontaneously within 2 days. Concordant RAI uptake was noticed in 89.1% (57/64) of the patients between ZGrhTSH and L-T4 withdrawal phases. The concordant thyroglobulin level with a cut-off of 1 µg/L was noticed in 84.7% (50/59) of the patients without the interference of anti-thyroglobulin antibody. The QoL was far better during ZGrhTSH phase than L-T4 withdrawal phase, with lower Billewicz (- 51.30 ± 4.70 vs. - 39.10 ± 16.61, P < 0.001) and POMS (91.70 ± 16.70 vs. 100.40 ± 22.11, P = 0.011) scores which indicate the lower the better. Serum TSH level rose from basal 0.11 ± 0.12 mU/L to a peak of 122.11 ± 42.44 mU/L 24 h after the last dose of ZGrhTSH. In L-T4 withdrawal phase, a median of 23 days after L-T4 withdrawal was needed, with the mean TSH level of 82.20 ± 31.37 mU/L. The half-life for ZGrhTSH clearance was about 20 h. CONCLUSION: The ZGrhTSH held the promise to be a safe and effective modality in facilitating RAI uptake and serum thyroglobulin stimulation, with better QoL of patients with DTC compared with L-T4 withdrawal.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Tirotropina Alfa , Humanos , Radioisótopos do Iodo/efeitos adversos , Qualidade de Vida , Hormônios Tireóideos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireotropina/uso terapêutico , Tirotropina Alfa/efeitos adversos , Tiroxina , Tomografia Computadorizada por Raios X
14.
Am J Hematol ; 97(12): 1510-1519, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36054786

RESUMO

Myelofibrosis (MF) is associated with several constitutional symptoms. Currently, there are few therapeutic options for MF. Jaktinib, a novel, small-molecule inhibitor of JAK, is currently being studied for its potential to treat MF. This phase 2 trial investigated efficacy and safety of jaktinib in the treatment of MF patients. The primary end point was the proportion of patients with ≥35% reduction in spleen volume (SVR35, proportion of patients with ≥35% reduction in spleen volume) at week 24. The secondary end points included improvement of anemia, rates of symptom response, and safety profile. Between January 8, 2019 and August 29, 2020, 118 patients were recruited and treated with either jaktinib 100 mg BID or 200 mg QD. At week 24, 54.8% (34/62) of patients in the 100 mg BID group and 31.3% (15/48) in the 200 mg QD group achieved SVR35 (p = .0199). Jaktinib treatment increased hemoglobin level to ≥20 g/L in 35.6% (21/59) of patients with hemoglobin ≤100 g/L at baseline. The proportion of patients who achieved a ≥50% improvement in total symptom score at week 24 was 69.6% (39/56) in the BID group and 57.5% (23/40) in the QD group. The most common ≥ grade 3 hematological treatment-emergent adverse events (TEAEs; ≥ 10%) were anemia (100 mg BID: 24.2%, 200 mg QD: 28.8%), thrombocytopenia (16.7%, 11.5%), and neutropenia (3.0%, 11.5%). All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability.


Assuntos
Anemia , Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Mielofibrose Primária/diagnóstico , Inibidores de Janus Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Pirazóis/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Nitrilas/uso terapêutico , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Resultado do Tratamento , Janus Quinase 2
15.
Anal Bioanal Chem ; 414(11): 3443-3457, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35201368

RESUMO

A human insulin (hINS) certified reference material (CRM) was developed by the National Institute of Metrology (NIM). Three milligrams of purified solid hINS was packed into a brown sealed tube. The candidate material was identified by de novo sequence using mass spectrometry and Edman degradation methods. The content of insulin-related impurities, aggregation, moisture, volatile organic compounds (VOCs), anions, and ignition residues was also determined. Both mass balance (MB) and amino acid analysis-based isotope dilution mass spectrometry (AAA-IDMS) were used for the certified value assessment, which was determined to be (0.857 ± 0.024) g/g. The certified value was validated by liquid chromatography-circular dichroism spectroscopy (LC-CD) and quantitative nuclear magnetic resonance (qNMR) methods, which were in good agreement. No inhomogeneity was observed during a homogeneity examination. A stability examination showed that the CRM was stable for at least 12 months when stored at - 70 °C, and for 7 days when stored at 4, 25, or 40 °C. The CRM is expected to be used as a primary calibrator for matrix insulin CRM development and for quality control in biopharmaceutical production and clinical diagnostics.


Assuntos
Aminoácidos , Insulina , Aminoácidos/análise , Cromatografia Líquida/métodos , Humanos , Espectrometria de Massas/métodos , Padrões de Referência
16.
Cell Mol Biol (Noisy-le-grand) ; 68(6): 62-66, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-36227677

RESUMO

This study aimed to investigate the formation mechanism of  Pseudoangiosarcoma squamous cell carcinoma (PASCC). The researchers reviewed ten cases of PASCC and summarize their clinical outcomes, pathological morphological traits, immunophenotypes, treatment plans and the corresponding follow-up data. Results showed that the pathological morphology revealed complex reticular structures, where numerous tracts of anastomose, and lacunar structures lined with atypical neoplastic cells, which resembles the histopathological appearance of angiosarcoma. Particularly, we observed pathologic patterns that resemble Sclerosing Epithelioid Fibrosarcoma (or Myxoid Fibrosarcoma) in the patients who suffered a relapse. All cases present negative results for vascular markers (CD31, ERG) and positive results for epithelial markers (CK-pan, p40). The average age of the participants is 60 years old (range: 48-79), relative aged, and there is no significant difference between male and female participants (6 men and 4 women). The locations of neoplasms involve face (n=3), upper limbs (n=1), waist(n=1), cervix uteri (n=1), lungs (n=2), thyroid (n=1), and breasts (n=1). All participants had received clinical follow-ups that range from 4 to 47 months, during which the researchers observed Lymph Node Metastases developed in three participants (out of 10; 30%); Distant Metastases in five participants (out of 10; 50%); two local recurrences at the site of surgical resection; and four deaths due to disease (out of 10; 40%), with 9.5 months estimated median survival time and 9 months mean survival time. It was concluded that PASCC presents the tendency for recurrence and metastasis. Accurate pathological diagnosis and standardized medical procedures are crucial to the treatment of PASCC. Epithelial-Mesenchymal Transformation (EMT) and P53 gene mutation are involved in the formation of PASCC.


Assuntos
Carcinoma de Células Escamosas , Fibrossarcoma , Hemangiossarcoma , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Diferenciação Celular , Feminino , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/patologia , Hemangiossarcoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
17.
Ecotoxicol Environ Saf ; 231: 113175, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35007828

RESUMO

Paraben preservatives have been listed as emerging pollutants due to their ubiquity in various environmental matrices, especially the water bodies. How to efficiently and practically eliminate these paraben pollutants is therefore of great importance. Herein, a designed S-scheme heterojunction photocatalyst, consisting of graphitic carbon nitride (g-C3N4) and monoclinic bismuth vanadate (BiVO4), was fabricated by a facile hydrothermal synthesis and employed to treat benzyl-paraben (BzP). TEM and XPS analysis testified the intimate interaction between g-C3N4 and BiVO4, and the consequently smoothed interfacial charge transfer rendered the feasible recombination of the photoexcited electrons (from BiVO4) and holes (from g-C3N4). The as-established S-scheme system enabled the left g-C3N4 electrons and BiVO4 holes to maintain the high redox abilities and accelerated the charge separation concurrently. In particular, the g-C3N4/BiVO4 composite generated much higher photocurrent response as compared with pure g-C3N4 and BiVO4, highlighting the improved separation of photoinduced charges. Therefore, under visible light and natural solar light irradiation, the g-C3N4/BiVO4 composite showed the significantly enhanced photocatalytic degradation of BzP, which was further optimized with 5 wt% g-C3N4 in the composite. According to the Mott-Schottky plots and identified active species, the mechanism of the g-C3N4/BiVO4 S-scheme heterojunction system was illustrated. In addition, during the photocatalytic degradation process, the acute toxicity of the reaction solutions on zebrafish embryos was notably reduced. In conclusion, the demonstrated strategy to enhance the photocatalytic performance by designing S-scheme heterostructure may provide more insights into the development of high-efficiency photocatalyst towards the solar energy utilization and environmental treatment. Furthermore, photocatalytic degradation had been proved to be an efficient method for eliminating the ecological risk of paraben pollutants, warranting more attention in future work.


Assuntos
Parabenos , Peixe-Zebra , Animais , Catálise , Luz , Luz Solar
18.
J Environ Sci (China) ; 114: 259-285, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35459491

RESUMO

Secondary organic aerosol (SOA) is a very important component of fine particulate matter (PM2.5) in the atmosphere. However, the simulations of SOA, which could help to elucidate the detailed mechanism of SOA formation and quantify the roles of various precursors, remains unsatisfactory, as SOA levels are frequently underestimated. It has been found that the performance of SOA formation models can be significantly improved by incorporating the emission and evolution of semivolatile and intermediate-volatility organic compounds (S/IVOCs). In order to explore the roles of S/IVOCs in SOA formation, this study reviews some simulation models which could consider S/IVOCs for SOA formation as well as the development of emission inventories of S/IVOCs and S/IVOC modules for SOA formation. In addition, the future research directions for simulations of the effect of S/IVOCs on SOA formation are suggested.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Aerossóis/análise , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise , Volatilização
19.
J Neurochem ; 158(2): 444-454, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33694231

RESUMO

Extracellular plaque deposits of ß-amyloid peptide (Aß) are one of the main pathological features of Alzheimer's disease (AD). The aggregation of Aß42 species, especially Aß42 oligomers, is still an active research field in AD pathogenesis. Secretory clusterin protein (sCLU), an extracellular chaperone, plays an important role in AD pathogenesis. Although sCLU interacts directly with Aß42 in vitro and in vivo, the mechanism is not clear. In this paper, His-tagged sCLU (sCLU-His) was cloned, expressed and purified, and we applied florescence resonance energy transfer-fluorescence correlation spectroscopy (FRET-FCS) to investigate the direct interaction of sCLU-His and Aß42 at the single-molecule fluorescence level in vitro. Here, we chose four different fluorescently labeled Aß42 oligomers to form two different groups of aggregation models, easy or difficult to aggregate. The results showed that sCLU-His could form complexes with both aggregation models, and sCLU-His inhibited the aggregation of Aß42/RB  ~ Aß42/Atto647 (easy to aggregate model). The complexes were produced as the Aß42/Label adhered to the sCLU-His, which is similar to a "strawberry model," as strawberry seeds are dotted on the outer surface of strawberries. This work provided additional insight into the interaction mechanism of sCLU and Aß42 .


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Clusterina/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Algoritmos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Clonagem Molecular , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Humanos , Modelos Químicos , Fragmentos de Peptídeos/metabolismo , Espectrometria de Fluorescência
20.
Anal Bioanal Chem ; 412(12): 2777-2784, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32076791

RESUMO

The activity of proteins rather than the concentration of proteins in biopharmaceutical and in vitro diagnostics are often the primary focus. Nonetheless, development of a calibration-free concentration analysis (CFCA) approach that accurately quantifies the concentration of proteins based on molecular interactions with specific monoclonal antibodies and without the requirement of external calibrators would be beneficial to diagnostics. Generally, only analytes that interact with the antibody (Ab) are quantified by CFCA. Moreover, protein concentrations measured by CFCA usually vary when different Abs are used, and are lower than those obtained by amino acid analysis because any non-native state population of the target protein is not captured by the Ab. To achieve comparable results between CFCA and traditional amino acid analysis (AAA), an Ab that recognizes the target protein irrespective of its conformation should be used. In this report, three different monoclonal antibodies were used to quantify purified human myoglobin in solution by CFCA. The concentrations obtain by the Abs (i.e., 2.985, 2.912, 3.032 mg mL-1) were comparable with that obtained by AAA. Moreover, isotope dilution mass spectrometry (IDMS) gave a human myoglobin concentration of 2.851 mg mL-1, which is also in agreement with the results from CFCA. The performance of CFCA was evaluated by measuring various parameters, including within-day and between-day precision. The results demonstrated that the active concentration measured by CFCA is comparable with that of IDMS when the appropriate Ab is used. Recommended procedures for performing the new CFCA approach are provided. This study shows that CFCA represents a primary method for accurate protein concentration determination, which should aid the development of certified reference materials. Graphical abstract.


Assuntos
Espectrometria de Massas/métodos , Mioglobina/análise , Ressonância de Plasmônio de Superfície/métodos , Calibragem , Humanos , Técnicas de Diluição do Indicador
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