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1.
Nature ; 632(8024): 313-319, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38885695

RESUMO

Oligosaccharides have myriad functions throughout biological processes1,2. Chemical synthesis of these structurally complex molecules facilitates investigation of their functions. With a dense concentration of stereocentres and hydroxyl groups, oligosaccharide assembly through O-glycosylation requires simultaneous control of site, stereo- and chemoselectivities3,4. Chemists have traditionally relied on protecting group manipulations for this purpose5-8, adding considerable synthetic work. Here we report a glycosylation platform that enables selective coupling between unprotected or minimally protected donor and acceptor sugars, producing 1,2-cis-O-glycosides in a catalyst-controlled, site-selective manner. Radical-based activation9 of allyl glycosyl sulfones forms glycosyl bromides. A designed aminoboronic acid catalyst brings this reactive intermediate close to an acceptor through a network of non-covalent hydrogen bonding and reversible covalent B-O bonding interactions, allowing precise glycosyl transfer. The site of glycosylation can be switched with different aminoboronic acid catalysts by affecting their interaction modes with substrates. The method accommodates a wide range of sugar types, amenable to the preparation of naturally occurring sugar chains and pentasaccharides containing 11 free hydroxyls. Experimental and computational studies provide insights into the origin of selectivity outcomes.


Assuntos
Glicosídeos , Oligossacarídeos , Ácidos Borônicos/química , Brometos/química , Catálise , Glicosídeos/química , Glicosídeos/síntese química , Glicosilação , Ligação de Hidrogênio , Oligossacarídeos/química , Oligossacarídeos/síntese química , Sulfonas/química
2.
EMBO Rep ; 25(2): 646-671, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177922

RESUMO

The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization. Overexpression of zswim4 decreases, whereas knockdown of zswim4 increases the expression levels of ventrolateral mesoderm marker genes. Mechanistically, ZSWIM4 attenuates the BMP signal by reducing the protein stability of SMAD1 in the nucleus. Stable isotope labeling by amino acids in cell culture (SILAC) identifies Elongin B (ELOB) and Elongin C (ELOC) as the interaction partners of ZSWIM4. Accordingly, ZSWIM4 forms a complex with the Cul2-RING ubiquitin ligase and ELOB and ELOC, promoting the ubiquitination and degradation of SMAD1 in the nucleus. Our study identifies a novel mechanism that restricts BMP signaling in the nucleus.


Assuntos
Proteínas Morfogenéticas Ósseas , Proteínas de Transporte , Animais , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Organizadores Embrionários/metabolismo , Xenopus laevis/metabolismo , Padronização Corporal/fisiologia , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Regulação da Expressão Gênica no Desenvolvimento
3.
Proc Natl Acad Sci U S A ; 120(21): e2303698120, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37186864

RESUMO

Hybrid incompatibility as a kind of reproductive isolation contributes to speciation. The nucleocytoplasmic incompatibility between Xenopus tropicalis eggs and Xenopus laevis sperm (te×ls) leads to specific loss of paternal chromosomes 3L and 4L. The hybrids die before gastrulation, of which the lethal causes remain largely unclear. Here, we show that the activation of the tumor suppressor protein P53 at late blastula stage contributes to this early lethality. We find that in stage 9 embryos, P53-binding motif is the most enriched one in the up-regulated Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) peaks between te×ls and wild-type X. tropicalis controls, which correlates with an abrupt stabilization of P53 protein in te×ls hybrids at stage 9. Inhibition of P53 activity via either tp53 knockout or overexpression of a dominant-negative P53 mutant or Murine double minute 2 proto-oncogene (Mdm2), a negative regulator of P53, by mRNA injection can rescue the te×ls early lethality. Our results suggest a causal function of P53 on hybrid lethality prior to gastrulation.


Assuntos
Sêmen , Proteína Supressora de Tumor p53 , Animais , Masculino , Camundongos , Cromossomos/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Sêmen/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Xenopus/metabolismo , Xenopus laevis/genética , Xenopus laevis/metabolismo
4.
Cell Mol Life Sci ; 81(1): 385, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235496

RESUMO

Cisplatin-induced renal tubular injury largely restricts the wide-spread usage of cisplatin in the treatment of malignancies. Identifying the key signaling pathways that regulate cisplatin-induced renal tubular injury is thus clinically important. PARVB, a focal adhesion protein, plays a crucial role in tumorigenesis. However, the function of PARVB in kidney disease is largely unknown. To investigate whether and how PARVB contributes to cisplatin-induced renal tubular injury, a mouse model (PARVB cKO) was generated in which PARVB gene was specifically deleted from proximal tubular epithelial cells using the Cre-LoxP system. In this study, we found depletion of PARVB in proximal tubular epithelial cells significantly attenuates cisplatin-induced renal tubular injury, including tubular cell death and inflammation. Mechanistically, PARVB associates with transforming growth factor-ß-activated kinase 1 (TAK1), a central regulator of cell survival and inflammation that is critically involved in mediating cisplatin-induced renal tubular injury. Depletion of PARVB promotes cisplatin-induced TAK1 degradation, inhibits TAK1 downstream signaling, and ultimately alleviates cisplatin-induced tubular cell damage. Restoration of PARVB or TAK1 in PARVB-deficient cells aggravates cisplatin-induced tubular cell injury. Finally, we demonstrated that PARVB regulates TAK1 protein expression through an E3 ligase ITCH-dependent pathway. PARVB prevents ITCH association with TAK1 to block its ubiquitination. Our study reveals that PARVB deficiency protects against cisplatin-induced tubular injury through regulation of TAK1 signaling and indicates targeting this pathway may provide a novel therapeutic strategy to alleviate cisplatin-induced kidney damage.


Assuntos
Cisplatino , MAP Quinase Quinase Quinases , Camundongos Knockout , Transdução de Sinais , Cisplatino/efeitos adversos , Cisplatino/toxicidade , Animais , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , Transdução de Sinais/efeitos dos fármacos , Camundongos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Antineoplásicos/farmacologia , Antineoplásicos/efeitos adversos , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal
5.
Anal Chem ; 96(11): 4544-4552, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38362708

RESUMO

Emerging contaminants have recently evolved into a severe worldwide environmental issue. Organophosphate flame retardants (OPFRs) with neurotoxicity, genotoxicity, and reproductive and developmental toxicity are a class of notorious emerging contaminants that cause great concern. The development of high-efficiency and portable sensors for rapid online monitoring of OPFRs has become the primary demand for the exploration of the environmental migration and transformation of OPFRs. In this work, interestingly, the cataluminescence (CTL) phenomenon of OPFRs is first observed, and an ingenious multidimensional ratiometric CTL sensing strategy is developed for the recognition of multiple OPFRs. Three characteristic ratios are extracted from the multipeak CTL spectral curves based on energy transfer of single Tb/Eu-modified MgO sensing material, and thus a novel three-dimensional (3D) code recognition could be mapped out. This obtained 3D coordinate is found to be a unique characteristic for a given OPFR, just like an exclusive person's ID number, which can successfully discriminate and detect 10 kinds of OPFR vapors, including homologous series and isomers. More importantly, CTL mechanism investigations for OPFRs demonstrate that OPFRs undergo a series of chemical reaction processes, e.g., oxidative pyrolysis and hydroxylation, and different high-energy excited intermediates are generated, which trigger discrepant energy-transfer efficiency toward rare earth ions, leading to multipeak spectral profiles. Briefly, this proposed CTL analytical platform for OPFRs recognition initiates a new sensing principle for the efficient identification of emerging contaminants and shows significant prospects on rapid on-site detection.

6.
Development ; 148(10)2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33999995

RESUMO

The focal adhesion protein Kindlin2 is essential for integrin activation, a process that is fundamental to cell-extracellular matrix adhesion. Kindlin 2 (Fermt2) is widely expressed in mouse embryos, and its absence causes lethality at the peri-implantation stage due to the failure to trigger integrin activation. The function of kindlin2 during embryogenesis has not yet been fully elucidated as a result of this early embryonic lethality. Here, we showed that kindlin2 is essential for neural crest (NC) formation in Xenopus embryos. Loss-of-function assays performed with kindlin2-specific morpholino antisense oligos (MOs) or with CRISPR/Cas9 techniques in Xenopus embryos severely inhibit the specification of the NC. Moreover, integrin-binding-deficient mutants of Kindlin2 rescued the phenotype caused by loss of kindlin2, suggesting that the function of kindlin2 during NC specification is independent of integrins. Mechanistically, we found that Kindlin2 regulates the fibroblast growth factor (FGF) pathway, and promotes the stability of FGF receptor 1. Our study reveals a novel function of Kindlin2 in regulating the FGF signaling pathway and provides mechanistic insights into the function of Kindlin2 during NC specification.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Proteínas de Membrana/metabolismo , Crista Neural/embriologia , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Animais , Sistemas CRISPR-Cas/genética , Linhagem Celular , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/genética , Desenvolvimento Embrionário/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Técnicas de Inativação de Genes , Células HEK293 , Células HeLa , Humanos , Integrinas/metabolismo , Proteínas de Membrana/genética , Morfolinos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/genética , Proteínas de Xenopus/genética
7.
Small ; 20(4): e2304119, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37759420

RESUMO

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.


Assuntos
NF-kappa B , Nanofibras , Nitritos , Elementos de Transição , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Cicatrização , Anti-Inflamatórios/farmacologia , Antibacterianos/farmacologia
8.
J Transl Med ; 22(1): 571, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38879493

RESUMO

BACKGROUND: No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. METHODS: In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. RESULTS: The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P < 0.05). CONCLUSIONS: The AKI-Pro score is a new clinical tool that could assist clinicians to identify early AKI patients at high risk for AKI progression or death.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Progressão da Doença , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Feminino , Masculino , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Estudos de Coortes , Índice de Gravidade de Doença , Curva ROC , Medição de Risco , Prognóstico
9.
Annu Rev Microbiol ; 73: 601-619, 2019 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-31283431

RESUMO

The blast disease, caused by the ascomycete Magnaporthe oryzae, poses a great threat to rice production worldwide. Increasing use of fungicides and/or blast-resistant varieties of rice (Oryza sativa) has proved to be ineffective in long-term control of blast disease under field conditions. To develop effective and durable resistance to blast, it is important to understand the cellular mechanisms underlying pathogenic development in M. oryzae. In this review, we summarize the latest research in phototropism, autophagy, nutrient and redox signaling, and intrinsic phytohormone mimics in M. oryzae for cellular and metabolic adaptation(s) during its interactions with the host plants.


Assuntos
Interações Hospedeiro-Patógeno , Magnaporthe/patogenicidade , Oryza/microbiologia , Doenças das Plantas/microbiologia , Adaptação Fisiológica , Ascomicetos/patogenicidade , Autofagia , Coevolução Biológica , Carbono/metabolismo , Relógios Circadianos/genética , Resistência à Doença , Genes de Plantas , Glucosiltransferases/metabolismo , Glicogênio/metabolismo , Magnaporthe/metabolismo , Nitrogênio/metabolismo , Oxirredução , Fototropismo , Doenças das Plantas/imunologia , Reguladores de Crescimento de Plantas/metabolismo , Imunidade Vegetal , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
10.
J Org Chem ; 89(16): 11173-11182, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39072554

RESUMO

Although the concerted [3 + 2] mechanism of osmium-catalyzed asymmetric dihydroxylation has been generally accepted, the unusual nonlinear Hammett relationship induced by amine-type ligands remains unexplained. To understand this, we carried out a density functional theory (DFT) study for the osmylation of substituted styrenes by the following: OsO4, OsO4-pyridine, OsO4-4-cyanopyridine, OsO4-4-pyrrolidinopyridine, and OsO4-quinuclidine. Calculations using the M06 functional successfully reproduce the experimentally observed nonlinear relationships. The transition states exhibit considerable singlet-diradical character, which causes the nonlinear Hammett relationship. Regardless of the presence or absence of an amine-type ligand, an electron donation from styrene to OsO4 is observed, indicating no mechanistic change. Calculations indicate that the electronic interaction between the amine-type ligand and styrene also influences the reaction rate.

11.
Inorg Chem ; 63(9): 4063-4071, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38364201

RESUMO

Treatment of Co(OTf)2·6H2O, Li[(pzTp)FeIII(CN)3], and H3PMo12O40·nH2O in protic solvents afforded two structurally related Fe-Co cyanometallate complexes: [{(pzTp)Fe(CN)3}3Co3(MeOH)10][PMo12O40]·H2O·11MeOH (1, pzTp- = tetra(pyrazolyl)borate) and {[(pzTp)Fe(CN)3]4Co3(MeOH)5(H2O)3}n[HPMo12O40]n·3 nMeOH·6.5nH2O (2). Complex 1 consists of a cyanide-bridged hexanuclear [Fe3Co3] cage, characterized by the fused conjunction of two mutually perpendicular trigonal bipyramids (TBPs, [Fe2Co3] and [Co2Fe3]), while complex 2 showcases an intricate cyanide-bridged Fe-Co tape comprising a central chain backbone of vertex-sharing [Fe2Co3] TBPs alongside peripheral [Fe2Co2] squares. Complex 2 is among the widest one-dimensional coordination assemblies characterized by the single-crystal X-ray diffraction technique. Magnetic studies revealed that complex 2 behaved as a single chain magnet with an effective energy barrier (Ueff/kB) of 46.8 K. Our findings highlight the possibilities in the development of cyanometallate-POM hybrid materials with captivating magnetic properties.

12.
Fish Shellfish Immunol ; 150: 109648, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38777253

RESUMO

Laminin receptor (LR), which mediating cell adhesion to the extracellular matrix, plays a crucial role in cell signaling and regulatory functions. In the present study, a laminin receptor gene (SpLR) was cloned and characterized from the mud crab (Scylla paramamosain). The full length of SpLR contained an open reading frame (ORF) of 960 bp encoding 319 amino acids, a 5' untranslated region (UTR) of 66 bp and a 3' UTR of 49 bp. The predicted protein comprised two Ribosomal-S2 domains and a 40S-SA-C domain. The mRNA of SpLR was highly expressed in the gill, followed by the hepatopancreas. The expression of SpLR was up-regulated after mud crab dicistrovirus-1(MCDV-1) infection. Knocking down SpLR in vivo by RNA interference significantly down-regulated the expression of the immune genes SpJAK, SpSTAT, SpToll1, SpALF1 and SpALF5. This study shown that the expression level of SpToll1 and SpCAM in SpLR-interfered group significantly increased after MCDV-1 infection. Moreover, silencing of SpLR in vivo decreased the MCDV-1 replication and increased the survival rate of mud crabs after MCDV-1 infection. These findings collectively suggest a pivotal role for SpLR in the mud crab's response to MCDV-1 infection. By influencing the expression of critical innate immune factors and impacting viral replication dynamics, SpLR emerges as a key player in the intricate host-pathogen interaction, providing valuable insights into the molecular mechanisms underlying MCDV-1 pathogenesis in mud crabs.


Assuntos
Sequência de Aminoácidos , Proteínas de Artrópodes , Braquiúros , Regulação da Expressão Gênica , Imunidade Inata , Filogenia , Receptores de Laminina , Alinhamento de Sequência , Animais , Braquiúros/genética , Braquiúros/imunologia , Receptores de Laminina/genética , Receptores de Laminina/imunologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Alinhamento de Sequência/veterinária , Perfilação da Expressão Gênica/veterinária , Sequência de Bases
13.
Fish Shellfish Immunol ; 154: 109872, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39244075

RESUMO

Scylla paramamosain, an economically significant crab, is widely cultivated worldwide. In recent years, S. paramamosain has faced a serious threat from viral diseases due to the expansion of culture scale and increased culture density. Among these, mud crab dicistrovirus-1 (MCDV-1) stands out as highly pathogenic, presenting substantial challenges to the healthy development of mud crab aquaculture. Therefore, a comprehensive understanding of the mud crab immune response to MCDV-1 infection is imperative for devising effective disease prevention strategies. In this study, transcriptomic analyses were conducted on the hepatopancreas of mud crabs infected with MCDV-1. The findings revealed a total of 5139 differentially expressed genes (DEGs) between healthy and MCDV-1 infected mud crabs, including 3327 upregulated and 1812 downregulated DEGs. Further analysis showed that mud crabs resist MCDV-1 infection by activating humoral immune-related pathways, including the MAPK signaling pathway, MAPK signaling pathway-fly, and Toll and Imd signaling pathway. In contrast, MCDV-1 infection triggers host metabolic disorders. Several immune-related vitamin metabolism pathways (ascorbate and aldarate metabolism, retinol metabolism, and nicotinate and nicotinamide metabolism) were significantly inhibited, which may create favorable conditions for the virus's self-replication. Notably, endocytosis emerged as significantly upregulated both in GO terms and KEGG pathways, with several viral endocytosis-related pathways showing significant activation. PPI network analysis identified 9 hub genes associated with viral endocytosis within the endocytosis. Subsequent GeneMANIA analysis confirmed the association of these hub genes with viral endocytosis. Both transcriptome data and qPCR analysis revealed a significant upregulation of these hub genes post MCDV-1 infection, suggesting MCDV-1 may use viral endocytosis to enter cells and facilitate replication. This study represents the first comprehensive report on the transcriptomic profile of mud crab hepatopancreas response to MCDV-1 infection. Future investigations should focus on elucidating the mechanisms through which MCDV-1 enters cells via endocytosis, as this may holds critical implications for the development of vaccine targets.

14.
BMC Gastroenterol ; 24(1): 240, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075402

RESUMO

PURPOSE: This study aimed to investigate clinical diagnostic values of mSEPT9 combined with NLR, PLR and LMR in CRC. METHODS: 329 subjects composed of 120 CRC patients, 105 polyps patients and 104 healthy participants were prospectively recruited. Clinicopathologic features were collected and analyzed. Plasma samples were collected for mSEPT9, NLR, PLR and LMR test. The sensitivity, specificity and AUC of each biomarker separately or in combination were estimated by the ROC curve. RESULTS: The levels of NLR, PLR and the PDR of mSEPT9 in CRC patients were significantly higher than those in non-CRC subjects, while LMR was the opposite. The PDR of mSEPT9 in CRC patients was significantly correlated with age, tumor size, tumor stage and M stage. ROC curve analysis demonstrated moderate diagnostic values of mSEPT9, NLR, PLR and LMR in CRC patients with AUC of 0.78 (Se = 0.68, and Sp = 0.89), 0.78 (Se = 0.68, and Sp = 0.83), 0.80 (Se = 0.68, and Sp = 0.81), and 0.77 (Se = 0.72, and Sp = 0.73), respectively. Moreover, combination of these four biomarkers dramatically enhanced the diagnostic accuracy of CRC (AUC = 0.92, Se = 0.90, and Sp = 0.87), especially for CRC patients with large tumors (AUC = 0.95) or distal metastasis (AUC = 0.95). CONCLUSION: mSEPT9, NLR, PLR and LMR showed the potential to be reliable biomarkers for the diagnosis of CRC. And the combined application of these biomarkers further improved the diagnostic accuracy of CRC significantly.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Septinas , Humanos , Septinas/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Sensibilidade e Especificidade , Curva ROC , Idoso , Estudos Prospectivos , Contagem de Plaquetas , Metilação de DNA , Adulto , Estudos de Casos e Controles , Neutrófilos , Estadiamento de Neoplasias , Plaquetas
15.
Nanotechnology ; 35(23)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38417161

RESUMO

Nanoclusters for fluorescence detection are generally comprised of rare and expensive noble metals, and the nanoclusters based on more affordable transition metal have attracted increasing attention. This study designed a ratiometric fluorescent probe to detect dopamine (DA), an important neurotransmitter. With carbon dots encapsulated within silica (CDs@SiO2) as the reference, the emitted reference signal was almost unchanged due to the protection of inert silicon shell. Meanwhile, copper nanoclusters modified with 3-aminophenyl boronic acid (APBA-GSH-CuNCs) provided the sensing signal, in which the phenylboric acid could specifically recognize the cis-diol structure of DA, and caused the fluorescence quenching by photoinduced electron transfer. This dual emission ratiometric fluorescent probe exhibited high sensitivity and anti-interference, and was able to selectively responded to DA with a linear range of 0-1.4 mM, the detection limit of 5.6 nM, and the sensitivity of 815 mM-1. Furthermore, the probe successfully detected DA in human serum samples, yielding recoveries ranging from 92.5% to 102.7%. Overall, this study highlights the promising potential of this ratiometric probe for detecting DA.


Assuntos
Pontos Quânticos , Humanos , Pontos Quânticos/química , Cobre/química , Dopamina , Carbono/química , Dióxido de Silício/química , Corantes Fluorescentes/química
16.
Int J Equity Health ; 23(1): 64, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504266

RESUMO

BACKGROUND: China has implemented policies to make rare diseases more affordable. While previous studies evaluated overall affordability, few have examined affordability differences across regions and disease types. Given the vastness of China and varying medical policies across cities, this study assesses the affordability of rare diseases based on China's First List of Rare Diseases (CFLRD), National Reimbursement Drug List (NRDL), and outpatient chronic and special disease policies in each prefecture. METHOD: Six rare diseases were selected and the average annual treatment cost of all relevant drugs in NRDL was calculated for each disease. Based on the WHO/HAI standardized approach, the study analyzed 289 cities with outpatient chronic and special disease policies, measured the security levels by the actual reimbursement ratio of Basic Medical Insurance (BMI) and affordability by the ratio of individual expenses after reimbursement to the annual disposable income of urban residents in the province. The security levels and affordability differences across disease types and provinces were analyzed using the Mann-Whitney U test and the K-W test. RESULT: The affordability of rare diseases varied significantly on the disease types and annual treatment cost. Diseases with an annual treatment cost below 100 000 yuan are affordable to all prefectures even with low reimbursement rates, while those with a higher treatment cost were not affordable in at least 80% of prefectures even though the reimbursement ratio is high. The affordability of the same disease varies significantly across provinces and municipalities. Outpatient chronic and special diseases insurance and critical illness insurance, and the inconsistencies between them, result in regional differences. CONCLUSION: Although China has made progress in improving the affordability of rare diseases, significant differences persist between cities and diseases. The study suggests the optimization of the BMI system and explores independent funds and innovative insurance models to enhance the affordability of rare diseases, particularly those with extremely high treatment costs.


Assuntos
Custos de Cuidados de Saúde , Doenças Raras , Humanos , Pacientes Ambulatoriais , China
17.
Plant Dis ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831590

RESUMO

Pumpkin (Cucurbita moschata), which belongs to the gourd family (Cucurbitaceae), is widely planted throughout the world. In June 2023, many pumpkin plants (cv. Miben) displayed leaf blight and chlorosis in fields located in Suizhou (31.99°N, 113.02°E), Hubei Province, China. The disease incidence ranged from 30 to 40% in nine fields, 6.3 ha in total. The symptoms were irregularly shaped lesions that expanded along the mid-vein until the leaf turned brown and wilted. Fungal isolations were performed as described previously (Liu et al. 2023). Twenty pumpkin leaf samples with typical symptoms were collected and cut into 1 cm×1 cm pieces. The diseased tissue was surface-sterilized in 75% ethanol for 30 sec, plated on potato dextrose agar (PDA) medium and incubated at 25℃ for 3 days. Then, the emerging single fungal hyphal tip was transferred onto PDA plates to obtain purified isolates. A total of eighteen isolates on PDA plates were initially white and then developed to dark gray. The 5-day-old cultures growing on mung bean medium produced conidia that were black, single-celled, smooth, spherical or oblate, and ranged in size from 14.5 to 20.8 µm×13.3 to 20.5 µm (n=50). Therefore, the isolates were morphologically identified as Nigrospora sphaerica. Moreover, the genomic DNA of the isolates (HB-P1,HB-P2, and HB-P3) was extracted for amplification and sequencing of the regions of internal transcribed spacer (ITS) (White et al. 1990), nuclear large subunit rRNA (nLSU) (O'Donnell 1992; Rehner and Samuels 1994), and ß-tubulin (TUB2) (Glass and Donaldson 1995), with primers ITS1/ITS4, LROR/LR3, and Bt2a/Bt2b, respectively. Sequences were submitted to GenBank under accession numbers PP348112, PP348113, PP348114 (ITS), PP411414, PP411415, PP411416 (nLSU), and PP357438, PP357439, PP357440 (TUB2). BLASTn showed that the sequences ITS, nLSU, and TUB2 of HB-P1, HB-P2, and HB-P3 had >99% nucleotide identities ((ITS: 100%, 508/508 bp, MF996488.1; 99.8%, 506/507, ON326588.1; 100%, 500/500 ,MK748317.1), (nLSU: 99.83%, 573/574, KT462720.1; 99.83% , 574/575 bp, KT462720.1; 99.65%, 575/577, KT462720.1), and (TUB2: 100%, 388/388, MN719407.1; 99.74%, 387/388, MN719407.1; 100%, 387/387, MN719407.1)) with Nigrospora sphaerica, respectively. A multilocus (ITS, nLSU and TUB2) phylogenetic analysis indicated that the isolates were Nigrospora sphaerica. Pathogenicity of three isolates were tested on pumpkin plants (cv. Miben). Fifteen pumpkin plants were inoculated by spraying the leaves (1×106 spores/ml), respectively, and 10 pumpkin plants were treated with sterile water as a negative control. All plants were incubated in an artificial climate box (LongYue, ShangHai) at 25℃ for 12 days. The experiment was repeated three times. Twelve days later, the inoculated pumpkin plants developed symptoms of leaf blight, while the control plants remained healthy. Then, pathogens were re-isolated from the each leaf of inoculated pumpkin plants and not from the control plants. Nigrospora sphaerica has been previously reported to cause leaf spot on watermelon in Malaysia (Ismail and Abd Razak 2021). To our knowledge, this is the first report of N. sphaerica causing leaf blight on pumpkin in China. This new disease can cause leaf blight, which may affect pumpkin productivity.

18.
Sensors (Basel) ; 24(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38894132

RESUMO

Partial discharge (PD) is a localized discharge phenomenon in the insulator of electrical equipment resulting from the electric field strength exceeding the local dielectric breakdown electric field. Partial-discharge signal identification is an important means of assessing the insulation status of electrical equipment and critical to the safe operation of electrical equipment. The identification effect of traditional methods is not ideal because the PD signal collected is subject to strong noise interference. To overcome noise interference, quickly and accurately identify PD signals, and eliminate potential safety hazards, this study proposes a PD signal identification method based on multiscale feature fusion. The method improves identification efficiency through the multiscale feature fusion and feature aggregation of phase-resolved partial-discharge (PRPD) diagrams by using PMSNet. The whole network consists of three parts: a CNN backbone composed of a multiscale feature fusion pyramid, a down-sampling feature enhancement (DSFB) module for each layer of the pyramid to acquire features from different layers, a Transformer encoder module dominated by a spatial interaction-attention mechanism to enhance subspace feature interactions, a final categorized feature recognition method for the PRPD maps and a final classification feature generation module (F-Collect). PMSNet improves recognition accuracy by 10% compared with traditional high-frequency current detection methods and current pulse detection methods. On the PRPD dataset, the validation accuracy of PMSNet is above 80%, the validation loss is about 0.3%, and the training accuracy exceeds 85%. Experimental results show that the use of PMSNet can greatly improve the recognition accuracy and robustness of PD signals and has good practicality and application prospects.

19.
J Clin Nurs ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519848

RESUMO

AIMS: To identify the contaminated areas of the hand collection and analyse the distribution characteristics of bacteria in the hand after swab collection. DESIGN: This study used a cross-sectional design. METHODS: A cross-sectional study sampling 50 pairs of hands (sampling hand and auxiliary hand) of healthcare workers was performed. Ten samples were collected from each participant. The optimal hand hygiene rates and bacterial colony counts of the whole hand and different hand sections without hand hygiene were identified as the primary outcomes. RESULTS: The optimal hand hygiene rates of the sampling hand and auxiliary hand were 88.8% (222/250) and 91.6% (229/250), respectively. The lowest optimal hand hygiene rates for the sampling hand and the auxiliary hand were both on the dorsal side of the finger and the dorsum of the hand (86.0%, 86.0% vs. 90.0%, 86.0%); the optimal hand hygiene rates for both sites of the sampling hand were 86.0% (43/50), and the optimal hand hygiene rates for the auxiliary hand were 90.0% (45/50) and 86.0% (43/50). The bacteria colony counts did not differ between the sampling hands and auxiliary hand. CONCLUSIONS: The dorsal side of the finger and dorsum of the hand were the most likely to be contaminated during oropharyngeal swab collection. Therefore, it is essential to pay extra attention to hand hygiene care of these two sites during the collection process to minimize the risk of cross-contamination. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were adopted in this study.

20.
Molecules ; 29(8)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38675603

RESUMO

Due to boron's metalloid properties, aromatic boron reagents are prevalent synthetic intermediates. The direct borylation of aryl C-H bonds for producing aromatic boron compounds offers an appealing, one-step solution. Despite significant advances in this field, achieving regioselective aryl C-H bond borylation using simple and readily available starting materials still remains a challenge. In this work, we attempted to enhance the reactivity of the electron-donor-acceptor (EDA) complex by selecting different bases to replace the organic base (NEt3) used in our previous research. To our delight, when using NH4HCO3 as the base, we have achieved a mild visible-light-mediated aromatic C-H bond borylation reaction with exceptional regioselectivity (rr > 40:1 to single isomers). Compared with our previous borylation methodologies, this protocol provides a more efficient and broader scope for aryl C-H bond borylation through the use of N-Bromosuccinimide. The protocol's good functional-group tolerance and excellent regioselectivity enable the functionalization of a variety of biologically relevant compounds and novel cascade transformations. Mechanistic experiments and theoretical calculations conducted in this study have indicated that, for certain arenes, the aryl C-H bond borylation might proceed through a new reaction mechanism, which involves the formation of a novel transient EDA complex.

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