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1.
Food Chem ; 403: 134441, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36358077

RESUMO

Flaxseed is categorized as a functional food due to its abundance in oil, α-linolenic acid, dietary fibre, and lignan. However, flaxseed contains cyanogenic glycosides (CGs). Ingestion of CGs can influence nutrient absorption and induce adverse health effects. Due to the presence of CGs in flaxseed many countries prohibit the import and sale of flaxseed and flaxseed-based foods. In this study, whole flaxseed was fermented with a mixed culture of Lactobacillaceae (i.e., Lactobacillus sp., Limosilactobacillus sp., and Lactiplantibacillus sp.) and the concentration of CGs was determined. This process succeeded in completely removing CGs within 72 h in both bench-scale and scale-up studies. In addition, fatty acid composition in flaxseed remained unchanged and concentrations of flaxseed oil, and SDG in flaxseed were increased after fermentation. CG-free flaxseed products are beneficial, as they can be sold as health product ingredients, or as animal feed in markets that currently restrict the use of materials that contain CGs.


Assuntos
Linho , Animais , Fermentação , Lactobacillaceae , Glicosídeos
2.
Phytomedicine ; 108: 154529, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36343550

RESUMO

BACKGROUND: Previous studies have shown that the anti-cholestatic effect of oleanolic acid (OA) is associated with FXR and NRF2. However, how the two signaling pathways cooperate to regulate the anti-cholestatic effect of OA remains unclear. PURPOSE: This study aimed to further demonstrate the effect of OA on alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury and the interaction mechanism between NRF2 and FXR signaling pathways in maintaining bile acid homeostasis. METHODS: Gene knockout animals and cell models, metabolomics analysis, and co-immunoprecipitation were used to investigate the mechanism of OA against cholestatic liver injury. RESULTS: The effect of OA against ANIT-induced liver injury in rats was dramatically reduced after Nrf2 gene knockdown. With the silencing of Fxr, the hepatoprotective effect of OA was weakened, but it still effectively alleviated cholestatic liver injury in rats. In L02 cells, OA can up-regulate the levels of NRF2, FXR, BSEP and UGT1A1, and reduce the expression of CYP7A1. Silencing of NRF2 or FXR significantly attenuated the protective effect of OA on ANIT-induced L02 cell injury and its regulation on downstream target genes, and the influence of NRF2 gene silencing on OA appeared to be greater. The NRF2 activator sulforaphane, and the FXR activator GW4064 both remarkably promoted NRF2 binding to P300 and FXR to RXRα, but reduced ß-catenin binding to P300 and ß-catenin binding to FXR. CONCLUSION: The effect of OA on cholestatic liver injury is closely related to the simultaneous activation of NRF2 and FXR dual signaling pathways, in which NRF2 signaling pathway plays a more important role. The dual signaling pathways of NRF2 and FXR cooperatively regulate bile acid metabolic homeostasis through the interaction mechanism with ß-catenin/P300.


Assuntos
Colestase , Ácido Oleanólico , Ratos , Animais , Ácido Oleanólico/farmacologia , Ácido Oleanólico/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , beta Catenina/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Colestase/tratamento farmacológico , Colestase/induzido quimicamente , Fígado , Ácidos e Sais Biliares/metabolismo , Transdução de Sinais , Fator de Transcrição de Proteínas de Ligação GA/metabolismo
3.
J Anim Sci Biotechnol ; 13(1): 121, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36329544

RESUMO

BACKGROUND: Organic selenium supplementation during gestation improves the antioxidant status and reproductive performance of sows and increases the antioxidative capacity of the intestines of their offspring. This study was conducted to investigate the effect of maternal basel diet (control) supplemented with an organic Se, 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), or inorganic sodium selenite (Na2SeO3) during gestation on the antioxidant status and development of muscle in newborn and weaned piglets. Newborn piglets before colostrum intake and weaned piglets were selected for longissimus dorsi (LD) muscle collection and analysis. RESULTS: The results showed that maternal HMSeBA supplementation increased the muscle area and content of Se in the LD muscle of newborn piglets, improved gene expression of selenoproteins, and decreased oxidative status in the LD muscle of both newborn and weaned piglets compared with the control. The expression of muscle development-related genes of newborn piglets in the HMSeBA group was lower than in the control group, whereas the expression of MRF4 in weaned piglets was higher in the HMSeBA group than in the control and Na2SeO3 groups. In addition, HMSeBA supplementation decreased the mRNA expressions of myosin heavy chains (MyHC) IIx and MyHC IIb and the percentage of MyHC IIb; increased the expression of PGC-1α in the LD muscle of newborn piglets; increased the gene expression of MyHC IIa; and decreased the protein expression of slow MyHC and the activity of malate dehydrogenase in the LD muscle of weaned piglets compared with the control group. CONCLUSIONS: Maternal HMSeBA supplementation during gestation can improve the antioxidative capacity of the muscle of their offspring and promote the maturity of muscle fibres in weaned offspring.

4.
Am J Transl Res ; 14(10): 7128-7134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36398267

RESUMO

OBJECTIVE: This retrospective study aimed to investigate the clinical efficacy and safety of carotid artery stenting (CAS) in elderly patients with internal carotid artery stenosis (ICS). METHODS: Ninety elderly ICS patients admitted between January 2019 - July 2021 were selected and divided into a control group and a research group according to different treatment method. The 42 cases in the control group were received carotid endarterectomy and the 48 cases in the research group were treated with CAS. The effects of the two intervention methods on the National Institutes of Health Stroke Scale (NIHSS) score, complication rate, oxidative stress, inflammatory cytokines and cognitive function were observed and evaluated. RESULTS: Compared to baseline (before treatment), the research group showed significantly reduced scores of NIHSS and activities of daily living, appreciably decreased levels of malonaldehyde, interleukin-6 and high-sensitivity C-reactive-protein, but increased superoxide dismutase, Rapid Verbal Retrieve score and Digit Span Test score after treatment. Also, the same trends were found when comparing the above results with those of the control group after treatment. The two groups showed a comparable complication rate. CONCLUSIONS: The above data indicate a definite clinical efficacy and a favorable safety profile of CAS for ICS in the elderly. CAS can effectively reduce the oxidative stress and inflammatory cytokines of patients and enhance their cognitive function.

5.
Mol Plant ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36419357

RESUMO

Aluminum (Al) toxicity can seriously restrict crop production in acidic soils, which comprise 40% of the world's potentially arable land. The zinc finger transcription factor STOP1 has a conserved and essential function mediating plant Al resistance. Aluminum stress induces STOP1 accumulation via post-transcriptional regulatory mechanisms. However, the upstream signaling pathway involved in Al-triggered STOP1 accumulation remains unclear. We herein report that the MEKK1-MKK1/2-MPK4 cascade positively regulates STOP1 phosphorylation and stability. Mutations of MEKK1, MKK1/2 or MPK4 lead to decreased STOP1 stability and Al resistance. Additionally, Al stress induces the kinase activity of MPK4, which interacts with and phosphorylates STOP1. The phosphorylation of STOP1 reduces its interaction with the F-box protein RAE1 that mediates STOP1 degradation, thereby leading to enhanced STOP1 stability and Al resistance. Taken together, our results suggest that the MEKK1-MKK1/2-MPK4 cascade is important for Al signaling and conferring Al resistance by phosphorylation-mediated enhancement of STOP1 accumulation in Arabidopsis.

6.
Front Immunol ; 13: 1035151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405695

RESUMO

Background: Since the global epidemic of the coronavirus disease 2019 (COVID-19), a large number of immunological studies related to COVID-19 have been published in various immunology journals. However, the results from these studies were discrete, and no study summarized the important immunological information about COVID-19 released by these immunology journals. This study aimed to comprehensively summarize the knowledge structure and research hotspots of COVID-19 published in major immunology journals through bibliometrics. Methods: Publications on COVID-19 in major immunology journals were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, and R-bibliometrix were comprehensively used for bibliometric and visual analysis. Results: 1,331 and 5,000 publications of 10 journals with high impact factors and 10 journals with the most papers were included, respectively. The USA, China, England, and Italy made the most significant contributions to these papers. University College London, National Institute of Allergy and Infectious Diseases, Harvard Medical School, University California San Diego, and University of Pennsylvania played a central role in international cooperation in the immunology research field of COVID-19. Yuen Kwok Yung was the most important author in terms of the number of publications and citations, and the H-index. CLINICAL INFECTIOUS DISEASES and FRONTIERS IN IMMUNOLOGY were the most essential immunology journals. These immunology journals mostly focused on the following topics: "Delta/Omicron variants", "cytokine storm", "neutralization/neutralizing antibody", "T cell", "BNT162b2", "mRNA vaccine", "vaccine effectiveness/safety", and "long COVID". Conclusion: This study systematically uncovered a holistic picture of the current research on COVID-19 published in major immunology journals from the perspective of bibliometrics, which will provide a reference for future research in this field.


Assuntos
COVID-19 , Publicações Periódicas como Assunto , Humanos , SARS-CoV-2 , Bibliometria
8.
Med Eng Phys ; 109: 103906, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36371083

RESUMO

The present study aims to reveal the operational characteristics of the needle-free injector. Effects of operating parameters on the injection performance were experimentally investigated. A visualization experiment was performed to describe the dispersion pattern of water in gel. The results show that the peak stagnation pressure increases continuously with the driving pressure. The injection process comprises two distinct stages, which are characterized by the penetration and the dispersion of the drug, respectively. The nozzle diameter imposes a significant effect on the penetration ability of the needle-free injector. As the nozzle diameter increases, the stagnation pressure decreases nearly linearly and the injection duration is considerably shortened, but the jet power is increased. Among the three nozzle diameters investigated, the nozzle diameter of 0.25 mm satisfies the proposed criterion of the injection power. It is evidenced through the visualization experiment that the maximum penetration depth increases with the nozzle diameter. The width of the projection area of the water bulk is insensitive to the nozzle diameter. For a certain nozzle diameter, the projection area of the diffused water bulk increases linearly with increasing liquid volume.


Assuntos
Sistemas de Liberação de Medicamentos , Água , Injeções a Jato/métodos , Injeções , Sistemas de Liberação de Medicamentos/métodos
9.
Int J Mol Med ; 50(6)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36367168

RESUMO

The activation of mammalian ste20­like kinase1 (Mst1) is a crucial event in cardiac disease development. The inhibition of Mst1 has been recently suggested as a potential therapeutic strategy for the treatment of diabetic cardiomyopathy. However, whether silencing Mst1 also protects against hypertensive (HP) myocardial injury, or the mechanisms through which this protection is conferred are not yet fully understood. The present study aimed to explore the role of Mst1 in HP myocardial injury using in vivo and in vitro hypertension (HP) models. Angiotensin II (Ang II) was used to establish HP mouse and cardiac microvascular endothelial cell (CMEC) models. CRISPR/adenovirus vector transfection was used to silence Mst1 in these models. Using echocardiography, hematoxylin and eosin staining, Masson's trichrome staining, the enzyme­linked immunosorbent assay detection of inflammatory factors, the enzyme immunoassay detection of oxidative stress markers, terminal deoxynucleotidyl transferase dUTP nick­end labeling staining, scanning electron microscopy, transmission electron microscopy, as well as immunofluorescence and western blot analysis of the autophagy markers, p62, microtubule­associated proteins 1A/1B light chain 3B and Beclin­1, it was found that Ang II induced HP myocardial injury with impaired cardiac function, increased the expression of inflammatory factors, and elevated oxidative stress in mice. In addition, it was found that Ang II reduced autophagy, enhanced apoptosis, and disrupted endothelial integrity and mitochondrial membrane potential in cultured CMECs. The silencing of Mst1 in both in vivo and in vitro HP models attenuated the HP myocardial injury. On the whole, these findings suggest that Mst1 is a key contributor to HP myocardial injury through the regulation of cardiomyocyte autophagy.


Assuntos
Traumatismos Cardíacos , Hipertensão , Animais , Camundongos , Angiotensina II/metabolismo , Apoptose/genética , Autofagia/genética , Células Endoteliais , Traumatismos Cardíacos/metabolismo , Hipertensão/metabolismo , Camundongos Knockout , Miócitos Cardíacos/metabolismo
10.
Front Vet Sci ; 9: 975726, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387378

RESUMO

At present, there is no effective experimental method for detecting whether the suid herpesvirus 1 (SHV-1) detected in pigs is infectious. Although the technique of quantitative polymerase chain reaction (qPCR) has significantly improved the detection rate and accuracy of the disease, it does not differentiate between infective and non-infective status of the virus. Propidium monoazide (PMA) is a dye that can be combined with DNA molecules. The decomposition of PMA produces an azene compound covalently crosslinked with DNA molecules, thereby inhibiting PCR amplification of DNA. In this study, the combination of PMA and qPCR was used to determine the infectivity of SHV-1. We optimized the method from the selection of primers, the working concentration of PMA, and the method of inactivation using UV or heat inactivation. We found that when specific primer 1 was used and a PMA working concentration was 50-100 µM, heat inactivation was able to distinguish whether SHV-1 was infectious or not. We also showed that UV prevented the virus from replicating, it did not destroy the capsid of the virus, and therefore, PMA cannot enter the virus and bind to the nucleic acid of the virus. Consequently, there is no way to identify the infectivity of the virus using UV inactivation. The study showed that the method was stable and the detection rate reached 96%. In conclusion, this method exhibited strong specificity and high sensitivity and can identify the infectivity of SHV-1. This method has practical significance for clinical virus isolation and the effects of disinfection of farms.

11.
Early Hum Dev ; 175: 105693, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36436312

RESUMO

BACKGROUND: Studies showed preterm children born with very low birth weight (VLBW, <1500 g) are at risk for poorer executive functions (EFs). However, very little research has been reported longitudinally on the development of both cool and hot EFs deficits in preschool to school-age VLBW preterm children with normal early development. AIMS: Present study aimed to investigate the development of cool and hot EFs in VLWB preterm children longitudinally. METHODS: Forty preterm children born VLBW were followed up at ages 6, 8, and 10. Fifty term-born controls were recruited at each age stage. Cool EFs was assessed using backward digit span subtest of WISC-IV, Knox's Cube Test, Comprehensive Non-verbal Attention Test Battery (CNAT), Tower of London (ToL), Wisconsin Card Sorting Test (WCST), and hot EFs was assessed using Theory of Mind (ToM) and Delay of Gratification (GIFT) tasks. RESULTS: The six-year-old VLBW preterm group showed significantly lower scores of planning in ToL, inhibition control in CNAT, and in both ToM and GIFT tasks. There is no significant difference in average cool and hot EFs between the eight and ten-year-old preterm group and the control group. CONCLUSIONS: At six, VLBW preterm infants with normal early development have delayed cool and hot EFs development. Although the average performance of EFs can reach the level of the control group with age increasing to eight and ten years, there are still individual differences. It is recommended that more complete development indicators be established in the future, and early intervention should be made for VLBW premature children with delayed EFs.

12.
Inorg Chem ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36410943

RESUMO

Two helical ligands (L1 and L2) were designed and synthesized by a Schiff base condensation reaction. Eight complexes, {[Zn(L1)I2]·H2O}n (1), [Cd2(L1)2I4(CH3OH)2] (2), [Hg2(L1)2I4] (3), [Ag(L1)NO3]n (4), [Ag2(L1)2(NO3)2DMSO]·H2O (5), {[Zn2(L2)2Cl4]·2CHCl3}n (6), {[Ag(L2)]·NO3}n (7), and {[Ag(L2)NO3]·CH3OH}n (8), were synthesized and characterized based on these two ligands. The crystal structures show that both Schiff base compounds exist as racemic ligands with equal amounts of P- and M-helicity, and the assembly of these racemic ligands with metal ions can lead to homochiral or heterochiral complexes via a chiral self-recognition or self-discrimination process. Complexes 2, 3, and 5 exist as heterochiral metallomacrocycles with a figure-eight conformation. Complexes 1, 6, and 8 exist as one-dimensional (1D) homochiral helical chain coordination polymers, while complexes 4 and 7 exist as 1D heterochiral helical chain coordination polymers. Furthermore, gas and vapor adsorption measurements show that all of the synthesized complexes exhibit good selective adsorption capacities toward methanol and ethanol vapor over N2, H2, and O2.

13.
Front Pharmacol ; 13: 1025618, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330100

RESUMO

Background: Nano drug delivery system (NDDS) can significantly improve the delivery and efficacy of drugs against pancreatic cancer (PC) in many ways. The purpose of this study is to explore the related research fields of NDDS for PC from the perspective of bibliometrics. Methods: Articles and reviews on NDDS for PC published between 2003 and 2022 were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel were comprehensively used for bibliometric and visual analysis. Results: A total of 1329 papers on NDDS for PC were included. The number of papers showed an upward trend over the past 20 years. The United States contributed the most papers, followed by China, and India. Also, the United States had the highest number of total citations and H-index. The institution with the most papers was Chinese Acad Sci, which was also the most important in international institutional cooperation. Professors Couvreur P and Kazuoka K made great achievements in this field. JOURNAL OF CONTROLLED RELEASE published the most papers and was cited the most. The topics related to the tumor microenvironment such as "tumor microenvironment", "tumor penetration", "hypoxia", "exosome", and "autophagy", PC treatment-related topics such as "immunotherapy", "combination therapy", "alternating magnetic field/magnetic hyperthermia", and "ultrasound", and gene therapy dominated by "siRNA" and "miRNA" were the research hotspots in the field of NDDS for PC. Conclusion: This study systematically uncovered a holistic picture of the performance of NDDS for PC-related literature over the past 20 years. We provided scholars to understand key information in this field with the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.

14.
Exp Cell Res ; 422(1): 113414, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36368567

RESUMO

CD276 has been studied in a variety of cancers and diseases, but its regulatory mechanisms in gastric cancer is still unclear. Mesenchymal stem cells (MSCs), one of the important members of tumor microenvironment, play an important role in the occurrence, development and metastasis of tumor, but the relationship between gastric cancer mesenchymal stem cells (GCMSCs) and CD276 in gastric cancer needs to be further explored. The differential expression of CD276 was identified via UCLAN and GEPIA databases. Then, the impacts of CD276 were calculated on clinical prognosis using the Kaplan-Meier plotter and Cox analysis. GO, KEGG and GSEA analysis were used to explore potential mechanism under CD276. Next, the expression of CD276 in gastric cell lines were detected by Western blot. Immunocoprecipitation was used to explore the association between CD276 and COL1A1. And the effect of condition medium (CM) from GCMSCs on gastric cell lines migration analyzed. GC-MSCs activated the AKT/c-Myc/mTOR pathway of gastric cell lines and upregulated CD276 expression. Moreover, the upregulation of CD276 promoted the migration of gastric cancer cells. Taken together, this study shown that GCMSCs could up-regulate the expression of CD276 of gastric cell lines to promote tumor migration. Our results provide a new basis for the treatment of gastric cancer.

16.
Pharmacol Res ; 187: 106563, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36410674

RESUMO

Ferroptosis has been implicated in the pathophysiological progression of a variety of diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant response and can counteract ferroptosis by inducing autophagy and targeting genes involved in iron metabolism and glutathione (GSH) synthesis/metabolism. This study investigated how Nrf2 and autophagy interact to prevent ferroptosis in acute liver injury under sulforaphane (SFN) intervention. The results showed that SFN could activate Nrf2 signaling pathway and its downstream target genes, promote cell autophagy, and then combat ferroptosis to alleviate liver injury. After inhibiting Nrf2, the autophagy activated by SFN almost disappeared, and the anti-ferroptosis effect was greatly weakened. After inhibiting autophagy, SFN can still activate Nrf2 and its downstream target gene, but solute carrier family 7 member 11 (SLC7A11) membrane transfer and its cystine transport ability are significantly weakened, thus ultimately attenuating the anti-ferroptosis effect of SFN. Further studies showed that Nrf2-dependent autophagy activation disrupted SLC7A11 binding to S93-phosphorylated coiled-coil myosin-like BCL2-interacting protein (BECN1) and increased SLC7A11 membrane transfer to combat ferroptosis. In conclusion, Nrf2-dependent autophagy activation is essential for promoting SLC7A11 membrane localization to inhibit ferroptosis. Activation of Nrf2 not only upregulates the expression of SLC7A11, glutathione peroxidase 4 (GPX-4) and autophagy-related proteins, but also destroys the binding of SLC7A11 and BECN1 by inducing autophagy, thereby promoting SLC7A11 membrane transfer and GSH synthesis, and finally suppressing ferroptosis. However, inhibition of autophagy had no significant effect on the expression of Nrf2 and downstream genes during SFN anti-liver injury intervention.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36449579

RESUMO

The partial discharge (PD) detection is of critical importance in the stability and continuity of power distribution operations. Although several feature engineering methods have been developed to refine and improve PD detection accuracy, they can be suboptimal due to several major issues: 1) failure in identifying fault-related pulses; 2) the lack of inner-phase temporal representation; and 3) multiscale feature integration. The aim of this article is to develop a learning-based multiscale feature engineering (LMFE) framework for PD detection of each signal in a three-phase power system, while addressing the above issues. The three-phase measurements are first preprocessed to identify the pulses together with the surrounded waveforms. Next, our feature engineering is conducted to extract the global-scale features, i.e., phase-level and measurement-level aggregations of the pulse-level information, and the local-scale features focusing on waveforms and their inner-phase temporal information. A recurrent neural network (RNN) model is trained, and intermediate features are extracted from this trained RNN model. Furthermore, these multiscale features are merged and fed into a classifier to distinguish the different patterns between faulty and nonfaulty signals. Finally, our LMFE is evaluated by analyzing the VSB ENET dataset, which shows that LMFE outperforms existing approaches and provides the state-of-the-art solution in PD detection.

18.
ACS Nano ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36445326

RESUMO

Two-dimensional conductive metal-organic frameworks (2D conductive MOFs) with π-d conjugations exhibit high electrical conductivity and diverse coordination structures, making them constitute a desirable platform for new electronic devices. Defects are inevitable in the self-assembly process of 2D conductive MOFs. Arguably, defect engineering that deliberately manipulates defects demonstrates great potential to enhance the electrocatalytic activity of this family of novel materials. Herein, a facile and universal defect engineering strategy is proposed and demonstrated for metal vacancy regulation of metal benzenehexathiolato (BHT) coordination polymer films. Controllable metal vacancies can be produced by simply tuning the proton concentration during the confined self-assembly process at the liquid-liquid interface. This facile but universal defect design strategy has been proven to be effective in a class of materials including Cu-BHT, Ni-BHT, and Ag-BHT for physicochemical regulation. To further demonstrate the feasibility and practicality in electrochemical applications, the elaborately fabricated Cu-BHT films with abundant Cu vacancies deliver competitive performance in electrocatalytic sensing of H2O2. Mechanistic analysis revealed that the Cu vacancies act as effective active sites for adsorption and reduction of H2O2, and the tuned electronic structure boosts the electrocatalytic reaction. The developed advanced sensing platform confirms the excellent commercial potential of Cu-BHT sensors for H2O2. The findings provide insights into the molecular structure design of 2D conducting MOFs by defect engineering and demonstrate the commercial potential of Cu-BHT electrochemical sensors.

19.
Pathology ; 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319485

RESUMO

PD-L1 immunohistochemistry has been approved as a diagnostic assay for immunotherapy. However, an international comparison across multiple cancers is lacking. This study aimed to assess the performance of PD-L1 diagnostic assays in non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC) and urothelial cancer (UC). The excisional specimens of NSCLC, HNSCC and UC were assayed by Ventana SP263 and scored at three sites in each country, including Australia, Brazil, Korea, Mexico, Russia and Taiwan. All slides were rotated to two other sites for interobserver scoring. The same cohort of NSCLC was assessed with Dako 22C3 pharmDx PD-L1 for comparison. The PD-L1 immunopositivity was scored according to the approved PD-L1 scoring algorithms which were the percentage of PD-L1-expressing tumour cell (TC) and tumour proportion score (TPS) by Ventana SP263 and Dako 22C3 staining, respectively. In NSCLC, the comparison demonstrated the comparability of the SP263 and 22C3 assays (cut-off of 1%, κ=0.71; 25%, κ=0.75; 50%, κ=0.81). The interobserver comparisons showed moderate to almost perfect agreement for SP263 in TC staining at 25% cut-off (NSCLC, κ=0.72 to 0.86; HNSCC, κ=0.60 to 0.82; UC, κ=0.68 to 0.91) and at 50% cut-off for NSCLC (κ=0.64 to 0.90). Regarding the immune cell (IC) scoring in UC, there was a lower correlation (concordance correlation coefficient=0.10 to 0.68) and poor to substantial agreements at the 1%, 5%, 10% and 25% cut-offs (κ= -0.04 to 0.76). The interchangeability of SP263 and 22C3 in NSCLC might be acceptable, especially at the 50% cut-off. In HNSCC, the performance of SP263 is comparable across five countries. In UC, there was low concordance of IC staining, which may affect treatment decisions. Overall, the study showed the reliability and reproducibility of SP263 in NSCLC, HNSCC and UC.

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