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1.
Nature ; 623(7987): 544-549, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37821703

RESUMO

High Mountain Asia (HMA) has experienced a spatial imbalance in water resources in recent decades, partly because of a dipolar pattern of precipitation changes known as South Drying-North Wetting1. These changes can be influenced by both human activities and internal climate variability2,3. Although climate projections indicate a future widespread wetting trend over HMA1,4, the timing and mechanism of the transition from a dipolar to a monopolar pattern remain unknown. Here we demonstrate that the observed dipolar precipitation change in HMA during summer is primarily driven by westerly- and monsoon-associated precipitation patterns. The weakening of the Asian westerly jet, caused by the uneven emission of anthropogenic aerosols, favoured a dipolar precipitation trend from 1951 to 2020. Moreover, the phase transition of the Interdecadal Pacific Oscillation induces an out-of-phase precipitation change between the core region of the South Asian monsoon and southeastern HMA. Under medium- or high-emission scenarios, corresponding to a global warming of 0.6-1.1 °C compared with the present, the dipolar pattern is projected to shift to a monopolar wetting trend in the 2040s. This shift in precipitation patterns is mainly attributed to the intensified jet stream resulting from reduced emissions of anthropogenic aerosols. These findings underscore the importance of considering the impact of aerosol emission reduction in future social planning by policymakers.


Assuntos
Ar , Altitude , Clima , Chuva , Aerossóis/análise , Ásia , Aquecimento Global , Estações do Ano , Ar/análise , Ar/normas , Atividades Humanas , Oceano Pacífico
2.
Proc Natl Acad Sci U S A ; 120(52): e2312480120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38134197

RESUMO

Tetrafluoromethane (CF4), the simplest perfluorocarbons, is a permanently potent greenhouse gas due to its powerful infrared radiation adsorption capacity. The highly symmetric and robust C-F bond structure makes its activation a great challenge. Herein, we presented an innovated approach that efficiently activates C-F bond utilizing protonated sulfate (-HSO4) modified Al2O3@ZrO2 (S-Al2O3@ZrO2) catalyst, resulting in highly efficient CF4 decomposition. By combining in situ infrared spectroscopy tests and density function theory simulations, we demonstrate that the introduced -HSO4 proton donor has a stronger interaction on the C-F bond than the hydroxyl (-OH) proton donor, which can effectively stretch the C-F bond for its activation. Consequently, the obtained S-Al2O3@ZrO2 catalyst achieved a stable 100% CF4 decomposition at a record low temperature of 580 °C with a turnover frequency value of ~8.3 times higher than the Al2O3@ZrO2 catalyst without -HSO4 modification, outperforming the previously reported results. This work paves a new way for achieving efficient C-F bond activation to decompose CF4 at a low temperature.

3.
Plant J ; 118(5): 1500-1515, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38516730

RESUMO

Meloidogyne incognita is one of the most widely distributed plant-parasitic nematodes and causes severe economic losses annually. The parasite produces effector proteins that play essential roles in successful parasitism. Here, we identified one such effector named MiCE108, which is exclusively expressed within the nematode subventral esophageal gland cells and is upregulated in the early parasitic stage of M. incognita. A yeast signal sequence trap assay showed that MiCE108 contains a functional signal peptide for secretion. Virus-induced gene silencing of MiCE108 impaired the parasitism of M. incognita in Nicotiana benthamiana. The ectopic expression of MiCE108 in Arabidopsis suppressed the deposition of callose, the generation of reactive oxygen species, and the expression of marker genes for bacterial flagellin epitope flg22-triggered immunity, resulting in increased susceptibility to M. incognita, Botrytis cinerea, and Pseudomonas syringae pv. tomato (Pst) DC3000. The MiCE108 protein physically associates with the plant defense protease RD21A and promotes its degradation via the endosomal-dependent pathway, or 26S proteasome. Consistent with this, knockout of RD21A compromises the innate immunity of Arabidopsis and increases its susceptibility to a broad range of pathogens, including M. incognita, strongly indicating a role in defense against this nematode. Together, our data suggest that M. incognita deploys the effector MiCE108 to target Arabidopsis cysteine protease RD21A and affect its stability, thereby suppressing plant innate immunity and facilitating parasitism.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Nicotiana , Doenças das Plantas , Tylenchoidea , Animais , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/parasitologia , Tylenchoidea/fisiologia , Tylenchoidea/patogenicidade , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Doenças das Plantas/parasitologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Nicotiana/genética , Nicotiana/parasitologia , Nicotiana/imunologia , Nicotiana/metabolismo , Pseudomonas syringae/fisiologia , Pseudomonas syringae/patogenicidade , Botrytis/fisiologia , Botrytis/patogenicidade , Cisteína Proteases/metabolismo , Cisteína Proteases/genética , Imunidade Vegetal , Interações Hospedeiro-Parasita , Raízes de Plantas/parasitologia , Raízes de Plantas/genética , Raízes de Plantas/imunologia , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genética
4.
J Cell Physiol ; 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38946060

RESUMO

Skeletal muscle is crucial for animal movement and posture maintenance, and it serves as a significant source of meat in the livestock and poultry industry. The number of muscle fibers differentiated from myoblast in the embryonic stage is one of the factors determining the content of skeletal muscle. Insulin-like growth factor 2 (IGF2), a well-known growth-promoting hormone, is crucial for embryonic and skeletal muscle growth and development. However, the specific molecular mechanism underlying its impact on chicken embryonic myoblast differentiation remains unclear. To elucidate the molecular mechanism by which IGF2 regulates chicken myoblast differentiation, we manipulated IGF2 expression in chicken embryonic myoblast. The results demonstrated that IGF2 was upregulated during chicken skeletal muscle development and myoblast differentiation. On the one hand, we found that IGF2 promotes mitochondrial biogenesis through the PGC1/NRF1/TFAM pathway, thereby enhancing mitochondrial membrane potential, oxidative phosphorylation, and ATP synthesis during myoblast differentiation. This process is mediated by the PI3K/AKT pathway. On the other hand, IGF2 regulates BNIP3-mediated mitophagy, clearing dysfunctional mitochondria. Collectively, our findings confirmed that IGF2 cooperatively regulates mitochondrial biogenesis and mitophagy to remodel the mitochondrial network and enhance mitochondrial function, ultimately promoting myoblast differentiation.

5.
BMC Genomics ; 25(1): 615, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890582

RESUMO

BACKGROUND: Nematodes are the most abundant and diverse metazoans on Earth, and are known to significantly affect ecosystem functioning. A better understanding of their biology and ecology, including potential adaptations to diverse habitats and lifestyles, is key to understanding their response to global change scenarios. Mitochondrial genomes offer high species level characterization, low cost of sequencing, and an ease of data handling that can provide insights into nematode evolutionary pressures. RESULTS: Generally, nematode mitochondrial genomes exhibited similar structural characteristics (e.g., gene size and GC content), but displayed remarkable variability around these general patterns. Compositional strand biases showed strong codon position specific G skews and relationships with nematode life traits (especially parasitic feeding habits) equal to or greater than with predicted phylogeny. On average, nematode mitochondrial genomes showed low non-synonymous substitution rates, but also high clade specific deviations from these means. Despite the presence of significant mutational saturation, non-synonymous (dN) and synonymous (dS) substitution rates could still be significantly explained by feeding habit and/or habitat. Low ratios of dN:dS rates, particularly associated with the parasitic lifestyles, suggested the presence of strong purifying selection. CONCLUSIONS: Nematode mitochondrial genomes demonstrated a capacity to accumulate diversity in composition, structure, and content while still maintaining functional genes. Moreover, they demonstrated a capacity for rapid evolutionary change pointing to a potential interaction between multi-level selection pressures and rapid evolution. In conclusion, this study helps establish a background for our understanding of the potential evolutionary pressures shaping nematode mitochondrial genomes, while outlining likely routes of future inquiry.


Assuntos
Genoma Mitocondrial , Genômica , Nematoides , Filogenia , Seleção Genética , Animais , Nematoides/genética , Genômica/métodos , Composição de Bases , Evolução Molecular , Códon/genética
6.
J Am Chem Soc ; 146(11): 7779-7790, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38466142

RESUMO

The electrochemical nitrate reduction reaction (NO3RR) holds promise for converting nitrogenous pollutants to valuable ammonia products. However, conventional electrocatalysis faces challenges in effectively driving the complex eight-electron and nine-proton transfer process of the NO3RR while also competing with the hydrogen evolution reaction. In this study, we present the thermally enhanced electrocatalysis of nitrate-to-ammonia conversion over nickel-modified copper oxide single-atom alloy oxide nanowires. The catalyst demonstrates improved ammonia production performance with a Faradaic efficiency of approximately 80% and a yield rate of 9.7 mg h-1 cm-2 at +0.1 V versus a reversible hydrogen electrode at elevated cell temperatures. In addition, this thermally enhanced electrocatalysis system displays impressive stability, interference resistance, and favorable energy consumption and greenhouse gas emissions for the simulated industrial wastewater treatment. Complementary in situ analyses confirm that the significantly superior relay of active hydrogen species formed at Ni sites facilitates the thermal-field-coupled electrocatalysis of Cu surface-adsorbed *NOx hydrogenation. Theoretical calculations further support the thermodynamic and kinetic feasibility of the relay catalysis mechanism for the NO3RR over the Ni1Cu model catalyst. This study introduces a conceptual thermal-electrochemistry approach for the synergistic regulation of complex catalytic processes, highlighting the potential of multifield-coupled catalysis to advance sustainable-energy-powered chemical synthesis technologies.

7.
J Am Chem Soc ; 146(1): 468-475, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38150583

RESUMO

The in-tandem catalyst holds great promise for addressing the limitation of low *CO coverage on Cu-based materials for selective C2H4 generation during CO2 electroreduction. However, the potential mismatch between the CO-formation catalyst and the favorable C-C coupling Cu catalyst represents a bottleneck in these types of electrocatalysts, resulting in low tandem efficiencies. In this study, we propose a robust solution to this problem by introducing a wide-CO generation-potential window nickel single atom catalyst (Ni SAC) supported on a Cu catalyst. The selection of Ni SAC was based on theoretical calculations, and its excellent performance was further confirmed by using in situ IR spectroscopy. The facilitated carbon dimerization in our tandem catalyst led to a ∼370 mA/cm2 partial current density of C2H4, corresponding to a faradic efficiency of ∼62%. This performance remained stable and consistent for at least ∼14 h at a high current density of 500 mA/cm2 in a flow-cell reactor, outperforming most tandem catalysts reported so far.

8.
Anal Chem ; 96(3): 997-1002, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38176015

RESUMO

Single-atom catalysts (SACs), specifically iron single atoms dispersed on nitrogen-doped carbon (Fe-NC), have shown promising potential in the electrocatalytic reduction of nitrate to ammonia (NitRR), but there is a lack of understanding of their intrinsic activity. The conventional measurements often overlook the intrinsic performance of SACs, leading to significant underestimation. This study presents an in situ electrochemical probing protocol, using two poisoning molecules (SCN- and NO2-), to characterize the reactivity of Fe sites in Fe-NC SACs for NitRR. The technique aids in quantifying the yield rate of ammonia on Fe sites and the active site number. The findings reveal the intrinsic turnover frequency (TOF) based on the number and ammonia yield rate of Fe sites, challenging the current understanding of SACs' inherent performances. This unique approach holds considerable potential for determining the intrinsic activity of other SACs in complex reactions, opening new avenues for the exploration of electrocatalytic processes.

9.
Anal Chem ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960896

RESUMO

Microalgae metabolite analysis is fundamental for the rational design of metabolic engineering strategies for the biosynthesis of high-value products. Mass spectrometry (MS) has been utilized for single-cell microalgae analysis. However, limitations in the detection throughput and polarities of detectable substances make it difficult to realize high-throughput screening of high-performance microalgae. Herein, a plasma-assisted label-free mass cytometry, named as PACyESI-MS, was proposed combining the advantages of orthogonal hybrid ionization and high-throughput MS analysis, which realized rapid metabolite detection of single microalgae. The cell detection throughput of PACyESI-MS was up to 52 cells/min. Dozens of the critical primary and secondary metabolites within single microalgae were detected simultaneously, including pigments, lipids, and energy metabolites. Furthermore, metabolite changes of Chlamydomonas reinhardtii and Haematococcus pluvialis under nitrogen deficiency stress were studied. Discrimination of Chlamydomonas under different nutrient conditions was realized using single-cell metabolite profiles obtained by PACyESI-MS. The relationships between the accumulation of bioactive astaxanthin and changes in functional primary metabolites of Haematococcus were investigated. It was demonstrated that PACyESI-MS can detect the flexible change of metabolites in single microalgae cells under different nutritional conditions and during the synthesis of high-value products, which is expected to become an important tool for the design of metabolic engineering-based high-performance microalgae factories.

10.
Anal Chem ; 96(10): 4275-4281, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38409670

RESUMO

Surface-enhanced Raman scattering (SERS) can overcome the existing technological limitations, such as complex processes and harsh conditions in gaseous small-molecule detection, and advance the development of real-time gas sensing at room temperature. In this study, a SERS-based hydrogen bonding induction strategy for capturing and sensing gaseous acetic acid is proposed for the detection demands of gaseous acetic acid. This addresses the challenges of low adsorption of gaseous small molecules on SERS substrates and small Raman scattering cross sections and enables the first SERS-based detection of gaseous acetic acid by a portable Raman spectrometer. To provide abundant hydrogen bond donors and acceptors, 4-mercaptobenzoic acid (4-MBA) was used as a ligand molecule modified on the SERS substrate. Furthermore, a sensing chip with a low relative standard deviation (RSD) of 4.15% was constructed, ensuring highly sensitive and reliable detection. The hydrogen bond-induced acetic acid trapping was confirmed by experimental spectroscopy and density functional theory (DFT). In addition, to achieve superior accuracy compared to conventional methods, an innovative analytical method based on direct response hydrogen bond formation (IO-H/Iref) was proposed, enabling the detection of gaseous acetic acid at concentrations as low as 60 ppb. The strategy demonstrated a superior anti-interference capability in simulated breath and wine detection systems. Moreover, the high reusability of the chip highlights the significant potential for real-time sensing of gaseous acetic acid.

11.
Opt Express ; 32(8): 14405-14419, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859386

RESUMO

In recent years, attention has been directed towards cost-effective and compact freeform Schwarzschild imaging spectrometers with plane gratings. The utilization of tolerance analysis serves as a potent approach to facilitate the development of prototypes. Conventional tolerance analysis methods often rely solely on the modulation transfer function (MTF) criterion. However, for a spectrometer system, factors such as the keystone/smile distortion and spectral resolution performance also require consideration. In this study, a tailored comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers was developed, considering vital aspects such as the MTF, keystone/smile distortion, and spectral resolution. Through this approach, meticulous tolerance analysis was conducted for a freeform Schwarzschild imaging spectrometer, providing valuable insights for the prototype machining and assembly processes. Emphasis was placed on the necessity of precise control over the tilt and decenter between the first and third mirrors, whereas the other fabrication and assembly tolerances adhered to the standard requirements. Finally, an alignment computer-generated hologram (CGH) was employed for the preassembly of the first and third mirrors, enabling successful prototype development. The congruence observed between the measured results and tolerance analysis outcomes demonstrates the effectiveness of the proposed method.

12.
Cytokine ; 173: 156419, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976700

RESUMO

Coal dust is the main occupational hazard factor during coal mining operations. This study aimed to investigate the role of macrophage polarization and its molecular regulatory network in lung inflammation and fibrosis in Sprague-Dawley rats caused by coal dust exposure. Based on the key exposure parameters (exposure route, dose and duration) of the real working environment of coal miners, the dynamic inhalation exposure method was employed, and a control group and three coal dust groups (4, 10 and 25 mg/m3) were set up. Lung function was measured after 30, 60 and 90 days of coal dust exposure. Meanwhile, the serum, lung tissue and bronchoalveolar lavage fluid were collected after anesthesia for downstream experiments (histopathological analysis, RT-qPCR, ELISA, etc.). The results showed that coal dust exposure caused stunted growth, increased lung organ coefficient and decreased lung function in rats. The expression level of the M1 macrophage marker iNOS was significantly upregulated in the early stage of exposure and was accompanied by higher expression of the inflammatory cytokines TNF-α, IL-1ß, IL-6 and the chemokines IL-8, CCL2 and CCL5, with the most significant trend of CCL5 mRNA in lung tissues. Expression of the M2 macrophage marker Arg1 was significantly upregulated in the mid to late stages of coal dust exposure and was accompanied by higher expression of the anti-inflammatory cytokines IL-10 and TGF-ß. In conclusion, macrophage polarization and its molecular regulatory network (especially CCL5) play an important role in lung inflammation and fibrosis in SD rats exposed to coal dust by dynamic inhalation.


Assuntos
Exposição por Inalação , Pneumonia , Ratos , Animais , Ratos Sprague-Dawley , Exposição por Inalação/efeitos adversos , Pneumonia/induzido quimicamente , Fibrose , Poeira , Citocinas/metabolismo , Macrófagos/metabolismo , Carvão Mineral
13.
Microb Pathog ; 188: 106549, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281605

RESUMO

The five epidermal growth factor-like domains (EGF) of Eimeria tenella microneme protein 8 (EtMIC8) (EtMIC8-EGF) plays a vital role in host cell attachment and invasion. These processes require interactions between parasite proteins and receptors on the surface of host cells. In this study, five chicken membrane proteins potentially interacting with EtMIC8-EGF were identified using the GST pull-down assay and mass spectrometry analysis, and only chicken (Gallus gallus) epithelial cell adhesion molecule (EPCAM) could bind to EtMIC8-EGF. EPCAM-specific antibody and recombinant EPCAM protein (rEPCAM) inhibited the EtMIC8-EGF binding to host cells in a concentration-dependent manner. Furthermore, the rEPCAM protein showed a binding activity to sporozoites in vitro, and a significant reduction of E. tenella invasion in DF-1 cells was further observed after pre-incubation of sporozoites with rEPCAM. The specific anti-EPCAM antibody further significantly decreased weight loss, lesion score and oocyst output during E. tenella infection, displaying partial inhibition of E. tenella infection. These results indicate that chicken EPCAM is an important EtMIC8-interacting host protein involved in E. tenella-host cell adhesion and invasion. The findings will contribute to a better understanding of the role of adhesion-associated microneme proteins in E. tenella.


Assuntos
Coccidiose , Eimeria tenella , Doenças das Aves Domésticas , Animais , Eimeria tenella/química , Eimeria tenella/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Galinhas , Proteínas de Protozoários , Fator de Crescimento Epidérmico/metabolismo , Proteínas Recombinantes , Esporozoítos/metabolismo , Coccidiose/veterinária , Coccidiose/parasitologia , Doenças das Aves Domésticas/parasitologia
14.
Microb Pathog ; 192: 106709, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810766

RESUMO

This study prepared a novel monoclonal antibody (MAb) against mink enteritis parvovirus (MEV) and identified its antigen epitope. The antibody subclass is identified as IgG1, the titers of the MAb is up to 1:1 × 106 and keeps stably after low-temperature storage for 9 months or 11 passages of the MAb cells. The MAb can specifically recognize MEV in the cells in IFA, but not Aleutian disease virus (ADV) or canine distemper virus (CDV). Its antigen epitope was identified as a polypeptide containing 5 key amino acids (378YAFGR382) and the homology in 20 MEV strains, 4 canine parvovirus strains, and 4 feline panleukopenia virus strains was 100%. This study supplies a biological material for developing new methods to detect MEV.


Assuntos
Anticorpos Monoclonais , Anticorpos Antivirais , Vírus da Cinomose Canina , Epitopos , Vírus da Enterite do Vison , Animais , Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Vírus da Enterite do Vison/imunologia , Vírus da Cinomose Canina/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Vison/imunologia , Imunoglobulina G/imunologia , Vírus da Doença Aleutiana do Vison/imunologia , Parvovirus Canino/imunologia , Vírus da Panleucopenia Felina/imunologia , Mapeamento de Epitopos , Camundongos , Camundongos Endogâmicos BALB C , Enterite Viral do Vison/imunologia
15.
Br J Nutr ; 131(6): 956-963, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-37905696

RESUMO

To explore the relationship between dietary antioxidant quality score (DAQS) and Cd exposure both alone and in combination with osteoporosis and bone mineral density (BMD) among postmenopausal women. In total, 4920 postmenopausal women from the National Health and Nutrition Examination Survey were included in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses to assess the association between DAQS and Cd exposure with femur neck BMD, total femur BMD, osteoporosis among postmenopausal women, respectively, and the coexistence effect of DAQS and Cd exposure. Four hundred and ninety-nine had osteoporosis. DAQS (OR = 0·86, 95 % CI 0·77, 0·97) and high DAQS (OR = 0·60, 95 % CI 0·36, 0·99) were found to be associated with decreased odds of osteoporosis, while Cd exposure (OR = 1·34, 95 % CI 1·04, 1·72) and high Cd exposure (OR = 1·45, 95 % CI 1·02, 2·06) were related to increased odds of osteoporosis. A positive correlation was observed between high DAQS and both total femur BMD and femur neck BMD. Conversely, Cd exposure was found to be negatively correlated with total femur BMD and femur neck BMD. Additionally, taking low-Cd and high-quality DAQS group as reference, the joint effect of Cd exposure and DAQS showed greater increased odds of osteoporosis and decreased total femur BMD and femur neck BMD as Cd level and DAQS combinations worsened. There may be an interaction between Cd exposure and DAQS for femur neck BMD, total femur BMD, and osteoporosis in postmenopausal women.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Densidade Óssea , Cádmio/farmacologia , Antioxidantes/farmacologia , Inquéritos Nutricionais , Estudos Transversais , Osteoporose/etiologia , Colo do Fêmur , Osteoporose Pós-Menopausa/etiologia , Vértebras Lombares , Absorciometria de Fóton
16.
Anal Bioanal Chem ; 416(16): 3737-3750, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38503987

RESUMO

The D-dimer is a sensitive indicator of coagulation and fibrinolysis activation, especially valuable as a biomarker of intravascular thrombosis. Measurement of plasma D-dimer levels plays a crucial role in the diagnosis and monitoring of conditions such as deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. A variety of immunoassays, including enzyme-linked immunosorbent assays, latex-enhanced immunoturbidimetric assays, whole-blood aggregation analysis, and immunochromatography assays, are widely used in clinical settings to determine D-dimer levels. However, the results obtained from different D-dimer assays vary significantly. These assays exhibit intra-method coefficients of variation ranging from 6.4% to 17.7%, and the measurement discrepancies among different assays can be as high as 20-fold. The accuracy and reliability of D-dimer testing cannot be guaranteed due to the lack of an internationally endorsed reference measurement system (including reference materials and reference measurement procedures), which may lead to misdiagnosis and underdiagnosis, limiting its full clinical application. In this review, we present an in-depth analysis of clinical D-dimer testing, summarizing the existing challenges, the current state of metrology, and progress towards harmonization. We also review the latest advancements in D-dimer detection techniques, which include mass spectrometry and electrochemical and optical immunoassays. By comparing the basic principles, the definition of the measurand, and analytical performance of these methods, we provide an outlook on the potential improvements in D-dimer clinical testing.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Imunoensaio/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Biomarcadores/sangue
17.
Anal Bioanal Chem ; 416(14): 3447-3458, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642097

RESUMO

N-Terminal pro-B-type natriuretic peptide (NT-proBNP) is a pivotal biomarker for the diagnosis and prognosis of heart failure (HF). However, no SI-traceable certified reference material (CRM) or reference measurement procedure (RMP) is available for this biomarker, and so clinical testing results obtained in different laboratories cannot be traced to a higher-order standard, leading to incomparable measurements. Protein hydrolysis and protein cleavage isotope dilution mass spectrometry (AAA-IDMS and PepA-IDMS) were used to develop a CRM. Structurally related impurities were identified by high-resolution mass spectrometry. The quantitative AAA-IDMS results were corrected according to the amino acid compositions of the impurities. Using PepA-IDMS, two peptides from the proteolyzed product were confirmed as signature peptides. To obtain traceable and accurate results, the signature peptides were quantified using impurity-corrected AAA-IDMS. The candidate NT-proBNP solution was denatured and enzymatically digested using the Glu-C endoproteinase. The released signature peptides were measured using an isotopic dilution approach. The homogeneity and stability of the candidate CRM were characterized, and their uncertainties were combined with the value assignment process. The developed CRM can be considered a unique SI-traceable NT-proBNP reference material and is expected to be used as a primary calibrator for matrix NT-proBNP CRM development.


Assuntos
Espectrometria de Massas , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Padrões de Referência , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/análise , Humanos , Espectrometria de Massas/métodos , Biomarcadores/sangue , Biomarcadores/análise , Técnicas de Diluição do Indicador
18.
Bioorg Chem ; 148: 107433, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754311

RESUMO

Second-generation AR antagonists, such as enzalutamide, are the primary therapeutic agents for advanced prostate cancer. However, the development of both primary and secondary drug resistance leads to treatment failures and patient mortality. Bifunctional agents that simultaneously antagonize and degrade AR block the AR signaling pathway more completely and exhibit excellent antiproliferative activity against wild-type and drug-resistant prostate cancer cells. Here, we reported the discovery and optimization of a series of biphenyl derivatives as androgen receptor antagonists and degraders. These biphenyl derivatives exhibited potent antiproliferative activity against LNCaP and 22Rv1 cells. Our discoveries enrich the diversity of small molecule AR degraders and offer insights for the development of novel AR degraders for the treatment of enzalutamide-resistant prostate cancer.


Assuntos
Antagonistas de Receptores de Andrógenos , Antineoplásicos , Benzamidas , Compostos de Bifenilo , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Nitrilas , Feniltioidantoína , Neoplasias da Próstata , Receptores Androgênicos , Humanos , Masculino , Benzamidas/farmacologia , Benzamidas/química , Benzamidas/síntese química , Nitrilas/química , Nitrilas/farmacologia , Feniltioidantoína/farmacologia , Feniltioidantoína/análogos & derivados , Feniltioidantoína/química , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Receptores Androgênicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estrutura Molecular , Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/química , Antagonistas de Receptores de Andrógenos/síntese química , Antagonistas de Receptores de Andrógenos/uso terapêutico , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral
19.
J Enzyme Inhib Med Chem ; 39(1): 2292006, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38086769

RESUMO

In this study, seventeen isobavachalcone (IBC) derivatives (1-17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50 values of 4.35 and 14.21 µM, respectively. Compared with IBC, compound 16 exhibited up to 4.11-fold enhancement of cytotoxic activity on human non-small cell lung cancer H1975 cells. In addition, we found that compound 16 suppressed H1975 cells via inducing apoptosis and necroptosis. The initial mechanism of compound 16 induced cell death in H1975 cells involves the increasing of Bax/Bcl-2 ratio and Cyt C protein level, down-regulating of Akt protein level, and cleaving caspase-9 and -3 induced apoptosis; the up-regulation of RIP3, p-RIP3, MLKL, and p-MLKL levels induced necroptosis. Moreover, compound 16 also caused mitochondrial dysfunction, thereby decreasing cellular ATP levels, and resulting in excessive reactive oxygen species (ROS) accumulation.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Necroptose , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-38870504

RESUMO

Background: Vaginal Intraepithelial Neoplasia (VaIN) is a prevalent condition that can progress to invasive carcinoma if left untreated. Despite its significance, effective treatments for VaIN remain limited. Objective: This study aimed to analyze the efficacy of Paiteling in treating VaIN among patients who have undergone total hysterectomy due to high cervical lesions or invasive cervical cancer. Design: This study employed a retrospective design. Settings: The study was conducted at Ningxia General Hospital of Medical University from January 2019 to January 2023. Participants: A total of 67 cases diagnosed with VaIN were included in the study. Inclusion criteria comprised patients who had undergone total hysterectomy for high cervical lesions or invasive cervical cancer and had confirmed VaIN diagnosis through abnormal ThinPrep Cytology Test (TCT) and/or High-risk Human Papillomavirus (HR-HPV) results with colposcopy biopsy. Intervention: Patients were treated with Chinese patent medicines Paiteling and patulin according to their specific VaIN classification: VaIN1, VaIN2, and VaIN3. Primary Outcome Measures: The primary outcome measures included complete negative conversion rates for VaIN1, VaIN2, and VaIN3, as well as overall effective rate and complete negative rate across all VaIN cases. Statistical analysis was performed using IBM SPSS 24.0, with significance set at P < .05. Results: Patients with VaIN1, VaIN2, and VaIN3 were treated with Chinese patent medicines Paiteling, and patulin, respectively. Complete negative conversion rates were 100% for VaIN1, 72.73% for VaIN2, and 75.67% for VaIN3, resulting in an overall effective rate of 88.89% and a complete negative rate of 72.22% across all VaIN cases. Conclusion: This study underscores the efficacy of Chinese patent medicine Paiteling in managing post-total hysterectomy VaIN. It presents a conservative treatment option for vaginal stump diseases, addressing a crucial gap in therapeutic strategies. The findings advocate for further exploration of Paiteling's potential in VaIN management.

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