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1.
Anal Chim Acta ; 1244: 340848, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36737149

RESUMO

Nanobody, a single domain antibody, has been shown a great promise for immunoassay (IA) applications. To improve the panning efficiency so as to obtain a valuable nanobody, anti-carrier protein phages in a phage display library were depleted to enhance the selection of nanobodies against the herbicide atrazine by using immunomagnetic beads conjugated with bovine serum albumin (IMB-BSA). The depletion of anti-carrier protein phages from the atrazine phage display library tripled the number of atrazine positive phage clones after four rounds of panning. One of the most sensitive phage clones Nb3 selected from the IMB-BSA depleted library was used to compare the performance with the monoclonal antibody (mAb 5D9) developed from the same immunogen. The Nb3-based IA exhibited similar specificity with the mAb 5D9-based IA, but greater thermostability and organic solvent tolerance. The half-maximum inhibition concentration (IC50) of the former was 3.5-fold greater than that of the latter (36.7 ng/mL versus 10.2 ng/mL). Because the Nb3-based IA was more robust than the mAb 5D9-based IA, the method detection limit of the two assays was 7.8 ng/mL of atrazine in river samples. The depletion strategy can increase the chance to acquire high quality nanobody and can be applicable for effective development of nanobodies against other small molecules.

2.
Nanoscale ; 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36723123

RESUMO

Zinc molybdate (ZMO) is a safe and effective grafting material for anticorrosion. Herein, we reported the synthesis of ZMO/h-BN with the labyrinth of capillary pores owing to the in situ growth of ZMO on flake hexagonal boron nitride (h-BN) using the hydrothermal method. The special morphological structure provided a tortuous path for aggressive species to the steel substrate, which extended and blocked the transmission of aggressive species, enhancing the physical corrosion barrier performance. In addition, the capillary pores of ZMO contributed to the competitive adsorption of Cl- in an electrolyte and reduced the diffusion of aggressive species, thus further delaying the corrosion process. Moreover, the capture of oxygen by forming a B-O bond with h-BN and the formation of a molybdate passive film are beneficial for the inhibition of cathodic and anodic reactions. As verified by electrochemical impedance spectroscopy (EIS), the anticorrosion performance of ZMO/h-BN coating increased by 49.58% and 130.72% compared with ZMO and epoxy resin (EP) coatings after immersing in a NaCl aqueous solution (3.50 wt%) for 72 h. This coating matrix provides an avenue for molybdate-based corrosion remediation.

3.
Phytomedicine ; 109: 154585, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610117

RESUMO

BACKGROUND: Hastatoside is an iridoid glycoside extracted from the herb, Verbena officinalis, that exerts various pharmacological effects, including anti-inflammatory, sleep-promoting, and analgesic effects. However, only a few studies have reported the efficacy of hastatoside in liver fibrosis. Liver fibrosis is a pathophysiological process, and its persistence can seriously affect the quality of life and well-being of the patients. HYPOTHESIS/PURPOSE: This study aimed to investigate the role of hastatoside on liver fibrosis and its possible underlying mechanisms. METHODS: C57BL/6 J mice with carbon tetrachloride (CCl4)-induced hepatic fibrosis were used as the in vivo models. Histological features of the liver were observed using Masson's trichrome and hematoxylin-eosin staining. Alanine aminotransferase and aspartate aminotransferase levels and the hepatic fibrosis indices (type 3 procollagen, laminin, and hyaluronic acid) were measured using corresponding assay kits. LX-2 human hepatic stellate cells (HSCs) stimulated with the transforming growth factor ß1 were used as the vitro models. Transfection of the glycogen synthase kinase (GSK)-3ß small interfering RNA (siRNA) and ß-catenin plasmids was also performed in vitro. Protein levels of GSK-3ß, phospho-GSK-3ß (Ser 9), α-smooth muscle actin, collagen type I alpha 1, c-Myc, cyclin D1, and ß-catenin were determined via western blotting. Moreover, the p-GSK-3ß:GSK-3ß ratio was calculated to determine the GSK-3ß activity. RESULTS: Hastatoside prevented CCl4-induced liver injury and histological damage. It inhibited the upregulation of α-SMA and Col1α1 levels in a CCl4-induced mouse hepatic fibrosis model. In vitro, hastatoside inhibited the proliferation and activation of HSCs by decreasing the expression levels of cyclin D1 and c-Myc and the proportion of LX-2 cells activated in the G0/G1 phase. Molecular docking results showed that hastatoside bound to GSK-3ß. Hastatoside significantly increased the GSK-3ß activity and inhibited the downstream effector expression of ß-catenin. CONCLUSION: These findings suggest that hastatoside can bind to GSK-3ß and promote its activity, while inhibiting the GSK-3ß downstream effector expression of ß-catenin, thereby inhibiting the activation and proliferation of HSCs, which further prevents the development of liver fibrosis. These results provide innovative insights into the underlying liver fibrosis. Moreover, hastatoside is a potential anti-fibrosis monomer that can potentially be used for the treatment of liver fibrosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Glicogênio Sintase Quinase 3 beta , Glicosídeos Iridoides , Animais , Humanos , Camundongos , beta Catenina/metabolismo , Ciclina D1/metabolismo , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Estreladas do Fígado , Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Qualidade de Vida , Transdução de Sinais , Glicosídeos Iridoides/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico
4.
J Integr Plant Biol ; 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36680412

RESUMO

Common buckwheat (Fagopyrum esculentum) and Tartary buckwheat (Fagopyrum tataricum), the two most widely cultivated buckwheat species, differ greatly in flavonoid content and reproductive mode. Here, we report the first high-quality and chromosome-level genome assembly of common buckwheat with 1.2 Gb. Comparative genomic analysis revealed that common buckwheat underwent a burst of long terminal repeat retrotransposons insertion accompanied by numerous large chromosome rearrangements after divergence from Tartary buckwheat. Moreover, multiple gene families involved in stress tolerance and flavonoid biosynthesis such as MATE and CHS underwent significant expansion in buckwheat, especially in common buckwheat. Integrated multi-omics analysis identified high expression of catechin biosynthesis-related genes in flower and seed in common buckwheat and high expression of rutin biosynthesis-related genes in seed in Tartary buckwheat as being important for the differences in flavonoid type and content between these buckwheat species. We also identified a candidate key rutin-degrading enzyme gene (Ft8.2377) that was highly expressed in Tartary buckwheat seed. In addition, we identified a haplotype-resolved candidate locus containing many genes reportedly associated with the development of flower and pollen, which was potentially related to self-incompatibility in common buckwheat. Our study provides important resources facilitating future functional genomics-related research of flavonoid biosynthesis and self-incompatibility in buckwheat. This article is protected by copyright. All rights reserved.

5.
Nanotechnology ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36720154

RESUMO

A Z-scheme Cd0.85Zn0.15S/Co9S8 (CZS-CS) photocatalyst was reasonably fabricated by a simple solvothermal method for the effective visible-light-driven H2 evolution and organic pollutants degradation. The precise construction of the CZS-CS composites provided an efficient heterogeneous contact interface and abundant reaction sites for the proposed photocatalytic reaction. The homogeneous Co9S8 nanocrystals were uniformly wrapped on the surface of Cd0.85Zn0.15S nanorods, forming an intimate-contact interface, markedly contributed to the light collection and effectively inhibited the charge-carrier recombination. The optimized CZS-CS-15 composites exhibited a special H2 production rate reaching 19.15 mmol·h-1·g-1, roughly 1915 and 4.5 times of pure Co9S8 and Cd0.85Zn0.15S samples and 85% of tetracycline (TC) molecule within 15 min was degraded. Furthermore, trapping experiments confirmed that h+ was the main active species for TC photodegradation. Moreover, the obtained photocatalysts manifested stability without apparent activity declines during the proposed reactions. Finally, the Z-scheme photocatalytic mechanism was verified to illustrate the characteristics of efficient charge transfer and high redox ability. This study provided a rational and learnable strategy for designing dual-functional Z-scheme heterojunction photocatalysts.

6.
J Am Chem Soc ; 145(4): 2098-2103, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36656917

RESUMO

The first and asymmetric total synthesis of bufogargarizins A and B, two unusual and highly oxygenated twin steroids with rearranged A/B rings, was achieved. The synthetically challenging [7-5-6-5] tetracyclic ring system of bufogargarizin A was efficiently constructed by the first intramolecular Ru-catalyzed [5 + 2] cycloaddition reaction of a vinyl ether cyclopropane-yne. Notably, the interesting [5-7-6-5] tetracyclic skeleton of bufogargarizin B was diastereoselectively reassembled by unique retro-aldol/transannular aldol cascade reactions from the [7-5-6-5] tetracyclic framework.

7.
Sci Rep ; 13(1): 543, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631556

RESUMO

To analyze alterations of the liver appearance during the hepatobiliary phase of individuals with type 2 diabetes who are receiving gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI). Fifty-seven individuals who received Gd-EOB-DTPA-enhanced MRI and had normal liver and renal function but did not have (control group) or have type 2 diabetes (observation group) were retrospectively included in this study. The liver enhancement ratio (LER) and contrast between liver parenchyma and portal vein (LPC) were calculated from hepatobiliary phase images. Utilizing liver to kidney signal intensity, signs of the biliary system, and signs of the portal vein, a functional liver imaging score (FLIS) was calculated. Wilcoxon rank-sum test was used to assess the between-group differences in LER, LPC, and FLIS. FLIS constituent ratios between the two groups were tested using the χ2 test. The effectiveness of LER, LPC, and FLIS for identifying type 2 diabetes was assessed by receiver operating characteristic curves (ROCs). The interobserver consistency of FLIS was evaluated using the intraclass correlation coefficients. The observation group's LER and LPC were lower than the control group. The constituent ratio of the FLIS score (liver to kidney signal intensity, p = 0.011) showed a significant between-group difference. According to ROCs, LER and LPC were associated with the identification of type 2 diabetes. LER = 0.54 and LPC = 1.46 were the optimal cutoff for identifying type 2 diabetes, respectively. FLIS demonstrated excellent inter-reader agreement. The relative signal intensity of the liver during the hepatobiliary phase is decreased in patients with type 2 diabetes. This should be considered when individuals with type 2 diabetes undergo Gd-EOB-DTPA-enhanced MRI to avoid misdiagnoses, such as small hepatocellular carcinoma or abnormal liver function.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Humanos , Meios de Contraste , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Gadolínio DTPA , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Hepáticas/patologia
8.
Sci Total Environ ; 865: 160894, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36563752

RESUMO

In recent years, eastern China has been identified as an important contributor to national and global emissions of halocarbons, some of which are ozone depletion substances (ODSs) that delay the recovery of the stratospheric ozone layer. However, the most recent characteristics and sources of halocarbons in eastern China remain unclear. Thus, hourly atmospheric observations of halocarbons were conducted in Hangzhou throughout 2021. The results showed that methylene chloride (CH2Cl2) was the most abundant halocarbon (2207 (25 %-75 % quantile: 1116-2848) ppt; parts per trillion) followed by chloromethane (CH3Cl) (912 (683-1043) ppt), and 1,2-dichloroethane (CH2ClCH2Cl) (596 (292-763) ppt). Then, backward trajectory and potential source contribution function (PSCF) analysis show that the emission hot spots of halocarbons were concentrated in adjacent cities in Zhejiang and neighboring provinces in eastern China. Moreover, based on positive matrix factorization (PMF) analysis, industrial emission (38.7 %), solvent usage (32.6 %), and the refrigeration sector and biomass burning (23.7 %) were the main sources of halocarbons (observed in this study). This study reveals high concentrations and potential sources of halocarbons in eastern China, which are important for studying the recovery of the ozone layer.

9.
Anal Chem ; 95(2): 1461-1469, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36575586

RESUMO

Gold nanoclusters (AuNCs) are promising electrochemiluminescence (ECL) signal probes for their outstanding biocompatibility, unusual molecule-like structures, and versatile optical and electrochemical properties. Nevertheless, their relatively low ECL efficiency and poor stability in aqueous solutions hindered their application in the ECL sensing field. Herein, a facile host-guest recognition strategy was proposed to enhance the ECL efficiency and stability of Au NCs by rigidifying the surface of ligand-stabilized AuNCs via supramolecular self-assembly between cucurbiturils[7] (CB[7]) and l-phenylalanine (l-Phe). Meanwhile, mercaptopropionic acid (MPA) was introduced as a ligand in order to cooperatively enhance the performance of the AuNCs and facilitate the link between AuNCs and bioactive substances. The prepared CB[7]/l-Phe/MPA-AuNCs had a higher ECL emission efficiency, achieving about 2-fold stronger ECL intensity than that of l-Phe/MPA-AuNCs. In addition, after non-covalent modification with CB[7], the finite stability of the papered AuNCs was significantly improved. The prepared CB[7]/l-Phe/MPA-AuNCs showed excellent D-dimer sensing results, exhibiting a linear range from 50.00 fg/mL to 100.0 ng/mL and a detection limit of 29.20 fg/mL (S/N = 3). Our work demonstrated that the host-guest self-assembly strategy provided a universal approach for strengthening the ECL efficiency and stability of nanostructures on an ultra-small scale.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Medições Luminescentes/métodos , Ouro/química , Ligantes , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Polímeros , Nanopartículas Metálicas/química , Limite de Detecção
11.
J Transl Med ; 20(1): 615, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564797

RESUMO

BACKGROUND: Breast cancer is a complex disease with a highly immunosuppressive tumor microenvironment, and has limited clinical response to immune checkpoint blockade (ICB) therapy. T-helper 2 (Th2) cells, an important component of the tumor microenvironment (TME), play an essential role in regulation of tumor immunity. However, the deep relationship between Th2-mediated immunity and immune evasion in breast cancer remains enigmatic. METHODS: Here, we first used bioinformatics analysis to explore the correlation between Th2 infiltration and immune landscape in breast cancer. Suplatast tosilate (IPD-1151 T, IPD), an inhibitor of Th2 function, was then employed to investigate the biological effects of Th2 blockade on tumor growth and immune microenvironment in immunocompetent murine breast cancer models. The tumor microenvironment was analyzed by flow cytometry, mass cytometry, and immunofluorescence staining. Furthermore, we examined the efficacy of IPD combination with ICB treatment by evaluating TME, tumor growth and mice survival. RESULTS: Our bioinformatics analysis suggested that higher infiltration of Th2 cells indicates a tumor immunosuppressive microenvironment in breast cancer. In three murine breast cancer models (EO771, 4T1 and EMT6), IPD significantly inhibited the IL-4 secretion by Th2 cells, promoted Th2 to Th1 switching, remodeled the immune landscape and inhibited tumor growth. Remarkably, CD8+ T cell infiltration and the cytotoxic activity of cytotoxic T lymphocyte (CTL) in tumor tissues were evidently enhanced after IPD treatment. Furthermore, increased effector CD4+ T cells and decreased myeloid-derived suppressor cells and M2-like macrophages were also demonstrated in IPD-treated tumors. Importantly, we found IPD reinforced the therapeutic response of ICB without increasing potential adverse effects. CONCLUSIONS: Our findings demonstrate that pharmaceutical inhibition of Th2 cell function improves ICB response via remodeling immune landscape of TME, which illustrates a promising combinatorial immunotherapy.


Assuntos
Imunoterapia , Neoplasias , Animais , Camundongos , Linfócitos T Citotóxicos , Linfócitos T CD8-Positivos , Preparações Farmacêuticas , Microambiente Tumoral , Linhagem Celular Tumoral
12.
Biosensors (Basel) ; 12(12)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36551146

RESUMO

Multifunctional, integrated, and reusable operating platforms are highly sought after in biochemical analysis and detection systems. In this study, we demonstrated a novel detachable, reusable acoustic tweezer manipulation platform that is flexible and versatile. The free interchangeability of different detachable microchannel devices on the acoustic tweezer platform was achieved by adding a waveguide layer (glass) and a coupling layer (polydimethylsiloxane (PDMS) polymer film). We designed and demonstrated the detachable multifunctional acoustic tweezer platform with three cell manipulation capabilities. In Demo I, the detachable acoustic tweezer platform is demonstrated to have the capability for parallel processing and enrichment of the sample. In Demo II, the detachable acoustic tweezer platform with capability for precise cell alignment is demonstrated. In Demo III, it was demonstrated that the detachable acoustic tweezer platform has the capability for the separation and purification of cells. Through experiments, our acoustic tweezer platform has good acoustic retention ability, reusability, and stability. More capabilities can be expanded in the future. It provides a simple, economical, and multifunctional reusable operating platform solution for biochemical analysis and detection systems.


Assuntos
Acústica , Polímeros , Vidro
13.
Drug Resist Updat ; 65: 100887, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36370664

RESUMO

Infections caused by multidrug-resistant fungi pose a devastating threat to human health worldwide, making new antifungal strategies urgently desired. Antimicrobial photodynamic therapy (aPDT) has gained increasing attention due to its potential in fighting against fungal infection. However, the preparation of highly efficient and water-soluble photosensitizers (PSs) for this purpose remains a challenge. Herein, we present a new strategy to prepare powerful PSs for efficient aPDT by introducing a porous cage compound, which could facilitate the transportation of O2 and reactive oxygen species (ROS). Specifically, the natural PS hypocrellin A (HA) was attached to a novel organic cage compound (covalent organic polyhedra 1 tied, COP1T) with polyethylene glycol (PEG) chains to improve its water solubility. It was found that the resulting COP1T-HA exhibited in vitro antifungal efficiency several folds higher compared to the free HA in fighting against four types of multidrug-resistant fungal planktonic cells and biofilms, including the "super fungus" Candida auris. Interestingly, the red-shift of COP1T-HA adsorption led to the realization of phototheranostic aPDT for cage-modified HA or derivatives. Additionally, COP1T-HA exhibited good biocompatibility, excellent disinfection capacity and wound healing efficiency without obvious toxic effects in vivo of rat model. With further development and optimization, COP1T-HA has great potential to become a new class of antifungal agent to fight against drug-resistant pathogens.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Humanos , Ratos , Animais , Fotoquimioterapia/métodos , Candida , Antifúngicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Penicilinas/farmacologia , Água/farmacologia
14.
World J Pediatr ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357648

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in extremely preterm neonates. The outcome and clinical burden vary dramatically according to severity. Although some prediction tools for BPD exist, they seldom pay attention to disease severity and are based on populations in developed countries. This study aimed to develop machine learning prediction models for BPD severity based on selected clinical factors in a Chinese population. METHODS: In this retrospective, single-center study, we included patients with a gestational age < 32 weeks who were diagnosed with BPD in our neonatal intensive care unit from 2016 to 2020. We collected their clinical information during the maternal, birth and early postnatal periods. Risk factors were selected through univariable and ordinal logistic regression analyses. Prediction models based on logistic regression (LR), gradient boosting decision tree, XGBoost (XGB) and random forest (RF) models were implemented and assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: We ultimately included 471 patients (279 mild, 147 moderate, and 45 severe cases). On ordinal logistic regression, gestational diabetes mellitus, initial fraction of inspiration O2 value, invasive ventilation, acidosis, hypochloremia, C-reactive protein level, patent ductus arteriosus and Gram-negative respiratory culture were independent risk factors for BPD severity. All the XGB, LR and RF models (AUC = 0.85, 0.86 and 0.84, respectively) all had good performance. CONCLUSIONS: We found risk factors for BPD severity in our population and developed machine learning models based on them. The models have good performance and can be used to aid in predicting BPD severity in the Chinese population.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36343751

RESUMO

OBJECTIVE: To compare the early and mid-term outcomes of three different strategies for an isolated left vertebral artery on the arch (LVoA) revascularization during thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing. METHODS: Between January 2016 and December 2021, 67 patients with LVoA and aortic arch pathologies who underwent zone 2-landing TEVAR at four medical centres were enrolled. These patients were divided into three groups for comparison: the novel chimney (group A, n = 28) with the right brachial-left brachial through-and-through (RLT) procedure, in-vitro fenestration (group B, n = 24), and transposition (group C, n = 15). The flow direction and velocity of LVoA was examined by the Doppler ultrasound in the pre-, intra-, and post-operation period. Primary outcomes were all-cause mortality and neurologic new symptoms. RESULTS: No deaths or neurologic new symptoms occurred within 30 days. The early type Ia endoleak rates were 17.9% (5/28), 16.7% (4/24), and 0.0% (0/15) in groups A, B, and C, respectively (p = .22). All patients had anterograde flow of the LVoA. The mean follow-up time was 63.6 ± 4.0 months. No mortality was observed during follow up. The neurologic new symptoms rates were 0.0%, 8.3%, and 33.3%, respectively. The mid-term type Ia endoleak rates were 7.1%, 12.5%, and 0.0% (p = .35). The bidirectional flow rates in the LVoA were 0.0%, 20.8%, and 26.7% (p = .02). Two cases (8.3%) and three (20.0%) in groups B and C underwent a secondary procedure because of mild-dizziness, but this was not necessary in group A (p = .06). CONCLUSION: The novel chimney technique of the RLT procedure may be feasible for patients with an LVoA requiring zone 2 anchoring. Accurate determination of the safety and feasibility of this novel technique requires larger samples size and longer follow-up time.

16.
Nat Commun ; 13(1): 6651, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333312

RESUMO

The exceptional mechanical strength of medium/high-entropy alloys has been attributed to hardening in random solid solutions. Here, we evidence non-random chemical mixing in a CrCoNi alloy, resulting from short-range ordering. A data-mining approach of electron nanodiffraction enabled the study, which is assisted by neutron scattering, atom probe tomography, and diffraction simulation using first-principles theory models. Two samples, one homogenized and one heat-treated, are observed. In both samples, results reveal two types of short-range-order inside nanoclusters that minimize the Cr-Cr nearest neighbors (L12) or segregate Cr on alternating close-packed planes (L11). The L11 is predominant in the homogenized sample, while the L12 formation is promoted by heat-treatment, with the latter being accompanied by a dramatic change in dislocation-slip behavior. These findings uncover short-range order and the resulted chemical heterogeneities behind the mechanical strength in CrCoNi, providing general opportunities for atomistic-structure study in concentrated alloys for the design of strong and ductile materials.

17.
Crit Care ; 26(1): 341, 2022 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335405

RESUMO

BACKGROUND: Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. METHODS: This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10-8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants. FINDINGS: We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10-8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury. INTERPRETATION: We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.


Assuntos
Estudo de Associação Genômica Ampla , Sepse , Adulto , Humanos , Estudo de Associação Genômica Ampla/métodos , Sepse/genética , Polimorfismo de Nucleotídeo Único , Peptídeos e Proteínas de Sinalização Intracelular/genética
18.
Dalton Trans ; 51(44): 16811-16815, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36321736

RESUMO

By reacting the semi-rigid PNP ligand with CoBr2, the corresponding complex PNPCoBr (1) was obtained. The reduction of 1 with excess amounts of KC8 in THF under a N2 atmosphere yielded a binuclear cobalt dinitrogen anion complex [Co(µ-Cy2P)PCyN2]2K (2) via the C-P bond cleavage of the PNP ligand. By adding 2,2,2-cryptand into complex 2, an ion pair Co complex, [Co(µ-Cy2P)PCyN2]2K(crypt-222) (3), could be effectively prepared. The structures of 1, 2, and 3 have been determined by single-crystal X-ray diffraction analysis, and N2 is moderately activated in complexes 2 and 3. There is a Co-Co bond in 2 and 3 suggested by DFT calculations. Compounds 1 and 2 display catalytic activity for the transformation of N2 into N(SiMe3)3.

19.
J Pharm Biomed Anal ; 224: 115159, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36442459

RESUMO

Currently, the use of targeted drugs such as tyrosine kinase inhibitors (TKIs) plays an important role in clinical therapy. As the number of approved TKIs continues to increase, existing analysis methods will not be able to meet the growing needs, and will hamper the development of therapeutic drug monitoring (TDM) of TKIs. Based on LC-MS/MS technology, this study tends to develop and validate a multi-component analysis method for simultaneous determination of the concentrations of 39 TKIs in plasma. Spiked plasma was blended with isotope labelled internal standards, and injected into the LC-MS/MS system after protein precipitation by acetonitrile. Chromatographic separation was achieved using an ODS-4 column with gradient elution of formic acid/water (1:1000; v/v) and acetonitrile. Analytes detection was conducted in positive ionisation mode using MRM. The total run time was 8 min. The method validation was conducted by assessing the following parameters: selectivity, linearity and the lower limit of qualification, accuracy and precision, stability, matrix effect and recovery. The concentrations of 39 TKIs showed good linearity within the range of their respective standard curves in plasma, the accuracy of all quality control samples ranged from 85.9% to 114.1%, and the precision was lower than 13.3%. The extraction recovery ranged from 92.6% to 114.7%, and the matrix effect of plasma was lower than 11.3%. This new method was successfully developed, can be used for the determination of drug concentrations in multiple patients with different kinds of TKIs, and will therefore be suitable for TDM of 39 TKIs.

20.
Neurosurg Focus Video ; 6(1): V2, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36284591

RESUMO

In this video, the authors highlight the applications of virtual reality and heads-up display in skull base surgery by presenting the case of a 45-year-old woman with an incidental large clinoid meningioma extending into the posterior fossa. The patient underwent preoperative endovascular tumor embolization to facilitate tumor resection and reduce blood loss, followed by a right pterional craniotomy. The use of intraoperative Doppler, intraoperative neurophysiological monitoring, and endoscope-assisted microsurgery is also featured. A subtotal resection was planned given tumor encasement of the posterior communicating and anterior choroidal arteries. No new neurological deficits were noted after the surgical procedure. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21177.

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