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1.
ACS Appl Mater Interfaces ; 13(41): 48500-48507, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34617724

RESUMO

Perfluorobutyric acid (PFBA) is one type of perfluoroalkyl and polyfluoroalkyl substances (PFASs) and is widely used as an industrial compound. The removal of PFBA has attracted considerable scientific interests in recent decades because it causes environmental pollution and human diseases. Currently, the adsorption method has been used commonly to remove PFASs from wastewater. However, it is usually limited by the inevitable "secondary waste" produced in this treatment process. In this work, PFBA can be effectively removed by synergistic electrical switching ion exchange (ESIX) and a new type of nanostructured ion exchanger. Herein, the nanostructured ion exchanger has been designed and synthesized by coating a polypyrrole (PPy)@Fe2O3 nanoneedle on carbon cloth (PPy@Fe2O3 NN-CC). Results show that the PPy@Fe2O3 NN-CC nanocomposite enhances ion exchange speed and efficiency, which ensures its high adsorption capacity and rapid regeneration property, thereby reducing secondary waste. Moreover, ESIX based on the PPy@Fe2O3 NN-CC nanocomposite has high selectivity for adsorption of PFBA over other common anions in water, such as Cl-, SO42-, and NO3-.

2.
Natl Sci Rev ; 8(7): nwab024, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34691693

RESUMO

Loss-of-function mutations in sorting nexin 14 (SNX14) cause autosomal recessive spinocerebellar ataxia 20, which is a form of early-onset cerebellar ataxia that lacks molecular mechanisms and mouse models. We generated Snx14-deficient mouse models and observed severe motor deficits and cell-autonomous Purkinje cell degeneration. SNX14 deficiency disrupted microtubule organization and mitochondrial transport in axons by destabilizing the microtubule-severing enzyme spastin, which is implicated in dominant hereditary spastic paraplegia with cerebellar ataxia, and compromised axonal integrity and mitochondrial function. Axonal transport disruption and mitochondrial dysfunction further led to degeneration of high-energy-demanding Purkinje cells, which resulted in the pathogenesis of cerebellar ataxia. The antiepileptic drug valproate ameliorated motor deficits and cerebellar degeneration in Snx14-deficient mice via the restoration of mitochondrial transport and function in Purkinje cells. Our study revealed an unprecedented role for SNX14-dependent axonal transport in cerebellar ataxia, demonstrated the convergence of SNX14 and spastin in mitochondrial dysfunction, and suggested valproate as a potential therapeutic agent.

3.
J Int Med Res ; 49(10): 3000605211050799, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34637357

RESUMO

Malakoplakia, a rare acquired granulomatous disease, affects many systems, including the urogenital tract. The literature describes malakoplakia of different viscera, and satisfactory results have been obtained after treatment. We reported a 48-year-old patient with diabetes who received multiple treatments in our hospital for bladder malakoplakia near the ureteral orifice. Despite aggressive treatment, the patient had recurrent bladder malakoplakia and even developed right ureteral orifice stenosis, which resulted in urinary obstruction and hydronephrosis. We believe that malakoplakia in the bladder near ureteral orifice should receive more attention. Satisfactory results may not be obtained through antibiotic treatment alone, and early antibiotic therapy combined with full surgical excision may be a better choice.


Assuntos
Cistite , Hidronefrose , Malacoplasia , Ureter , Humanos , Malacoplasia/diagnóstico , Pessoa de Meia-Idade
4.
Nanomicro Lett ; 13(1): 213, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674052

RESUMO

Detecting and quantifying intracellular microRNAs (miRNAs) are a critical step in resolving a cancer diagnostic and resolving the ensemble of gene products that orchestrate the living state of cells. However, the nanoprobe for detecting low abundance miRNAs in cell cytosol is restricted by either the "one-to-one" signal-trigger model or difficulty for cytosol delivery. To address these challenges, we designed a light-harvesting nanoantenna-based nanoprobe, which directs excitation energy to a single molecule to sensitively detect cytosolic miRNA. With light irradiation, the light-harvesting nanoantenna effectively disrupted lysosomal structures by generation of reactive oxygen species, substantially achieved cytosol delivery. The nanoantenna containing > 4000 donor dyes can efficiently transfer excitation energy to one or two acceptors with 99% efficiency, leading to unprecedented signal amplification and biosensing sensitivity. The designed nanoantenna can quantify cytosolic miR-210 at zeptomolar level. The fluorescence lifetime of the donor exhibited good relationship with miR-210 concentration in the range of 0.032 to 2.97 amol/ngRNA. The zeptomole sensitivity of nanoantenna provides accurate bioimaging of miR-210 both in multiple cell lines and in vivo assay, which creates a pathway for the creation of miRNA toolbox for quantitative epigenetics and personalized medicine.

5.
J Dermatol ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487567

RESUMO

Topical Janus kinase (JAK) and phosphodiesterase-4 (PDE4) inhibitors are novel treatment approaches for atopic dermatitis (AD). This study aimed to compare the efficacy and safety of JAK and PDE4 inhibitors for AD treatment. The databases of PubMed, EMBASE, Web of Science, and Cochrane Library were searched until June 2021 for eligible studies of AD patients treated with topical JAK and PDE4 inhibitors. Baseline and follow-up data were extracted. Efficacy of JAK inhibitors was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear", with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA response"). A Bayesian multiple treatment network meta-analysis with fixed effects was performed. Odds ratio (OR) with 95% credibility interval (CrI) were used for comparing the efficacy of JAK and PDE4 inhibitors with placebo for AD. A total of 10 randomized controlled trials of topical JAK and PDE4 inhibitors with 4689 patients were included for analysis. A total of three topical JAK inhibitors and two topical PDE4 inhibitors were included. Compared with placebo, all JAK and PDE4 inhibitors had higher IGA response at 4 weeks of treatment. Notably, with similar safety profile, tofacitinib 2% b.i.d., ruxolitinib 1.5% b.i.d., and delgocitinib 3% b.i.d. showed favorable IGA response compared with topical tacrolimus and corticosteroids. Ranking analysis suggested that among all included JAK and PDE4 inhibitors, tofacitinib 2% b.i.d. had the highest probability of achieving IGA response (SUCRA = 0.880). Besides, JAK and PDE4 inhibitors showed non-inferior safety profile with placebo. This study confirmed that topical JAK and PDE4 inhibitors had promising treatment efficacy and safety for AD patients. Tofacitinib 2% b.i.d., ruxolitinib 1.5% b.i.d. and delgocitinib 3% b.i.d. showed superior efficacy over other JAK and PDE4 inhibitors.

6.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4175-4186, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467730

RESUMO

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1ß(IL-1ß), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.


Assuntos
Neuralgia , Receptores de N-Metil-D-Aspartato , Animais , Sensibilização do Sistema Nervoso Central , Neuralgia/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo
7.
Anal Chem ; 93(40): 13658-13666, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34591463

RESUMO

Currently, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-MS (LC-MS) are the primary methods used to detect pesticides and their metabolites for biomonitoring of exposure. Although GC-MS and LC-MS can provide accurate and sensitive measurements, these techniques are not suitable for point-of-care or in-field biomonitoring applications. The objective of this work is to develop a smartphone-based dual-channel immunochromatographic test strip (ICTS) for on-site biomonitoring of exposure to cypermethrin by simultaneous detection of cypermethrin and its metabolite, 3-phenoxybenzoic acid (3-PBA). Polymer carbon dots (PCDs) with ultrahigh fluorescent brightness were synthesized and used as a signal amplifier in ICTS assay. Cypermethrin (a representative pyrethroid pesticide) and its major metabolite 3-PBA were simultaneously detected to provide more comprehensive analysis of cypermethrin exposure. After competitive immunoreactions between the target sample and the coating antigens preloaded on the test line, the tracer antibody (PCD-conjugated antibody) was quantitatively captured on the test lines. The captured PCDs were inversely proportional to the amount of the target compound in the sample. The red fluorescence on the test line was then recorded using a smartphone-based device capable of conducting image analysis and recording. Under optimal conditions, the sensor showed excellent linear responses for detecting cypermethrin and 3-PBA ranging from 1 to 100 ng/mL and from 0.1 to 100 ng/mL, respectively, and the limits of detection were calculated to be ∼0.35 ng/mL for cypermethrin and ∼0.04 ng/mL for 3-PBA. The results demonstrate that the ICTS device is promising for accurate point-of-care biomonitoring of pesticide exposure.


Assuntos
Piretrinas , Pontos Quânticos , Benzoatos , Polímeros , Smartphone
8.
PLoS One ; 16(9): e0257974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582500

RESUMO

Sichuan, China, has abundant genetic resources of sheep (Ovis aries). However, their genetic diversity and population structure have been less studied, especially at the genome-wide level. In the present study, we employed the specific-locus amplified fragment sequencing for identifying genome-wide single nucleotide polymorphisms (SNPs) among five breeds of sheep distributed in Sichuan, including three local pure breeds, one composite breed, and one exotic breed of White Suffolk. From 494 million clean paired-end reads, we obtained a total of 327,845 high-quality SNPs that were evenly distributed among all 27 chromosomes, with a transition/transversion ratio of 2.56. Based on this SNP panel, we found that the overall nucleotide diversity was 0.2284 for all five breeds, with the highest and lowest diversity observed in Mage sheep (0.2125) and Butuo Black (0.1963) sheep, respectively. Both Wright's fixation index and Identity-by-State distance revealed that all individuals of Liangshan Semifine-wool, White Suffolk, and Butuo Black sheep were respectively clustered together, and the breeds could be separated from each other, whereas Jialuo and Mage sheep had the closest genetic relationship and could not be distinguished from each other. In conclusion, we provide a reference panel of genome-wide and high-quality SNPs in five sheep breeds in Sichuan, by which their genetic diversity and population structures were investigated.


Assuntos
Variação Genética/genética , Carneiro Doméstico/genética , Ovinos/genética , Animais , China , Cromossomos de Mamíferos/genética , Feminino , Frequência do Gene/genética , Heterozigoto , Masculino , Polimorfismo de Nucleotídeo Único/genética , Especificidade da Espécie
10.
Acta Pharmacol Sin ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462562

RESUMO

Large amounts of tumor-associated macrophages (TAM), which are predominately localized in hypoxia area of the tumor tissue, are associated with the malignant progression of the tumor. In the present study, we investigated the inhibitory effects of modified citrus pectin (MCP), a natural dietary polysaccharide, on the survival and polarization of TAM in relation to its inhibition on the growth and migration of breast cancer. M2 macrophages polarized from human monocyte THP-1 were chosen as a model for TAM. We showed that MCP (0.06%-1%) concentration-dependently suppressed the survival of TAM through inhibiting glucose uptake with a greater extent in hypoxia than in normoxia. Furthermore, MCP treatment decreased ROS level in TAM through its reducibility and inhibiting galectin-3 expression, leading to inhibition of glucose transporter-1 expression and glucose uptake. In addition, MCP suppressed M2-like polarization via inhibiting STAT3 phosphorylation. Moreover, the tumor-promoting effect of TAM could be restrained by MCP treatment as shown in human breast cancer MDA-MB-231 cells in vitro and in mouse breast cancer 4T1-luc orthotopic and metastasis models. In both tumor tissue and lung tissue of the mouse tumor models, the number of TAM was significantly decreased after MCP treatment. Taken together, MCP may be a promising agent for targeting TAM in tumor hypoxic microenvironment for breast cancer treatment.

11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 706-710, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323053

RESUMO

Objective: To assess the efficacy of 595 nm pulsed dye laser (PDL) in the treatment of facial and neck port-wine stains (PWSs), and to explore the main factors affecting the efficacy. Methods: A total of 259 PWS cases who were treated with 595 nm PDL were retrospectively enrolled and their clinical information was analyzed in the study. Before- and after-treatment comparison of individual patient was done by comparing patient photographs taken before and after PDL treatment of the PWSs in order to assess the treatment efficacy, using mild purpura as the endpoint of the PDL treatment. A total of 82 male and 177 female cases were included, with patient age ranging between 1 month and 63 years. Univariate analysis was done to select factors influencing the treatment efficacy. Then, ordered multivariate logistic regression analysis was performed to evaluate the main factors affecting the efficacy. Statistics of adverse reaction of patients were also collected. Results: Of the 259 patients covered in the study, 57 (22%) had achieved complete clearing of PWS, 106 (40.9%) showed significant improvement, and 68 (26.3%) showed moderate improvement, amounting to a total of 231 effective treatment cases, indicating a 89.2% overall rate of effective treatment. There were 28 ineffective treatment cases (10.8%). Ordered multivariate logistic regression analysis showed that the color of PWS, the area of PWS, anatomical sites of PWS and the number of treatment sessions were the main factors affecting the therapeutic efficacy, while proliferation did not affect the therapeutic efficacy. Red-type PWS had better treatment efficacy than that of the purple-type PWS (odds ratio [ OR]=2.748, P<0.05). Patients with PWS≤10 cm 2 showed better treatment efficacy than those with PWS>10 cm 2 ( OR=2.094, P<0.05). Treatment efficacy of PWS located in the central section of the face was not as good as those located on the neck ( OR=0.190, P<0.05), and the treatment efficacy of PWS located in the central and lateral section of the face was not as good as those located on the neck ( OR=0.243, P<0.05). Patients who had more than 3 treatment sessions showed better efficacy than those who had 1-3 sessions of treatment ( OR=0.508, P<0.05). No patients incurred any serious adverse reactions. Conclusion: Patients with PWS located on the neck, red-type PWS and area ≤10 cm 2 are suitable for treatment with 595 nm PDL and there should be more than three sessions of treatment. Patient sex, age, or proliferation do not affect the treatment effect.


Assuntos
Lasers de Corante , Mancha Vinho do Porto , Face , Feminino , Humanos , Lactente , Lasers de Corante/uso terapêutico , Masculino , Mancha Vinho do Porto/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
12.
Biosens Bioelectron ; 191: 113434, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34225056

RESUMO

An electrochemical sensor based on molecularly imprinted polypyrrole nanotubes (MIPNs) has been developed for the detection of glyphosate (Gly) with high sensitivity and specificity. Herein, the MIPNs are prepared by imprinting Gly sites on the surface of polypyrrole (PPy) nanotubes. The synthesized MIPNs have high electrical conductivity and exhibit rapid adsorption rate, enhanced affinity and specificity to Gly. An electrochemical sensor for Gly detection is fabricated by assembling MIPNs-modified screen-printed electrodes with a 3D-printed electrode holder, which is highly portable and suitable for real-time detection. The results demonstrate that the MIPNs-based electrochemical sensor for Gly exhibits a wide detection range of 2.5-350 ng/mL with a limit of detection (LOD) of 1.94 ng/mL. Besides, the Gly sensor possessed good stability, reproducibility, and excellent selectivity against other interferents. The practicability of the sensor is verified by detecting Gly in orange juice and rice beverages, indicating that the sensor is suitable for monitoring pesticides in actual food and environmental samples.


Assuntos
Técnicas Biossensoriais , Impressão Molecular , Nanotubos de Carbono , Técnicas Eletroquímicas , Eletrodos , Glicina/análogos & derivados , Limite de Detecção , Polímeros , Pirróis , Reprodutibilidade dos Testes
13.
Nanomicro Lett ; 13(1): 146, 2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34146178

RESUMO

Fe-based single-atomic site catalysts (SASCs), with the natural metalloproteases-like active site structure, have attracted widespread attention in biocatalysis and biosensing. Precisely, controlling the isolated single-atom Fe-N-C active site structure is crucial to improve the SASCs' performance. In this work, we use a facile ion-imprinting method (IIM) to synthesize isolated Fe-N-C single-atomic site catalysts (IIM-Fe-SASC). With this method, the ion-imprinting process can precisely control ion at the atomic level and form numerous well-defined single-atomic Fe-N-C sites. The IIM-Fe-SASC shows better peroxidase-like activities than that of non-imprinted references. Due to its excellent properties, IIM-Fe-SASC is an ideal nanoprobe used in the colorimetric biosensing of hydrogen peroxide (H2O2). Using IIM-Fe-SASC as the nanoprobe, in situ detection of H2O2 generated from MDA-MB-231 cells has been successfully demonstrated with satisfactory sensitivity and specificity. This work opens a novel and easy route in designing advanced SASC and provides a sensitive tool for intracellular H2O2 detection.

14.
Research (Wash D C) ; 2021: 9861384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104892

RESUMO

Near-infrared (NIR) laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy. However, insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen (1O2) distribution over tumors from phototherapy results in tumor recurrence and inferior outcomes. To achieve high tumor killing efficacy, one of the solutions is to employ the combinational treatment of phototherapy with other modalities, especially with chemotherapeutic agents. In this paper, a simple and effective multimodal therapeutic system was designed via combining chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) to achieve the polytherapy of malignant glioma which is one of the most aggressive tumors in the brain. IR-780 (IR780) dye-labeled tube-forming peptoids (PepIR) were synthesized and self-assembled into crystalline nanotubes (PepIR nanotubes). These PepIR nanotubes showed an excellent efficacy for PDT/PTT because the IR780 photosensitizers were effectively packed and separated from each other within crystalline nanotubes by tuning IR780 density; thus, a self-quenching of these IR780 molecules was significantly reduced. Moreover, the efficient DOX loading achieved due to the nanotube large surface area contributed to an efficient and synergistic chemotherapy against glioma cells. Given the unique properties of peptoids and peptoid nanotubes, we believe that the developed multimodal DOX-loaded PepIR nanotubes in this work offer great promises for future glioma therapy in clinic.

15.
Small ; 17(25): e2100664, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34028983

RESUMO

Heme enzymes, with the pentacoordinate heme iron active sites, possess high catalytic activity and selectivity in biosensing applications. However, they are still subject to limited catalytic stability in the complex environment and high cost for broad applications in electrochemical sensing. It is meaningful to develop a novel substitute that has a similar structure to some heme enzymes and mimics their enzyme activities. One emerging strategy is to design the Fe-N-C based single-atomic site catalysts (SASCs). The obtained atomically dispersed Fe-Nx active sites can mimic the active sites of heme enzymes effectively. In this work, a SASC (Fe-SASC/NW) is synthesized by doping single iron atoms in polypyrrole (PPy) derived carbon nanowire via a zinc-atom-assisted method. The proposed Fe-SASC/NW shows high heme enzyme-like catalytic performance for hydrogen peroxide (H2 O2 ) with a specific activity of 42.8 U mg-1 . An electrochemical sensor based on Fe-SASC/NW is developed for the detection of H2 O2 . This sensor exhibits a wide detection concentration range from 5.0 × 10-10 m to 0.5 m and an excellent limit of detection (LOD) of 46.35 × 10-9 m. Such excellent catalytic activity and electrochemical sensing sensitivity are attributed to the isolated Fe-Nx active sites and their structural similarity with natural metalloproteases.


Assuntos
Heme , Peróxido de Hidrogênio , Domínio Catalítico , Polímeros , Pirróis
16.
Dig Dis Sci ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33939149

RESUMO

BACKGROUND/AIMS: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients. METHODS: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared. RESULTS: There were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4-14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7-34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone. CONCLUSIONS: This study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes.

17.
Bioorg Med Chem ; 38: 116138, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33857737

RESUMO

A series of novel pleuromutilin derivatives were designed and synthesized with 1,2,4-triazole as the linker connected to benzoyl chloride analogues under mild conditions. The in vitro antibacterial activities of the synthesized derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, ATCC 29213, AD3 and 144) were tested by the broth dilution method. Most of the synthesized derivatives displayed potent activities, and 22-(3-amino-2-(4-methyl-benzoyl)-1,2,4-triazole-5-yl)-thioacetyl)-22-deoxypleuromutilin (compound 12) was found to be the most active antibacterial derivative against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed compound 12 had a certain inhibitory effect against MRSA in vitro. The in vivo antibacterial activity of compound 12 was further evaluated using MRSA infected murine thigh model. Compound 12 exhibited superior antibacterial efficacy than tiamulin. It was also found that compound 12 had no significant inhibitory effect on the proliferation of RAW264.7 cells. Compound 12 was further evaluated in CYP450 inhibition assay and showed moderate inhibitory effect on CYP3A4 (IC50 = 3.95 µM). Moreover, seven candidate compounds showed different affinities with the 50S ribosome by SPR measurement. Subsequently, binding of compound 12 and 20 to the 50S ribosome was further investigated by molecular modeling. Three strong hydrogen bonds were formed through the interaction of compound 12 and 20 with 50S ribosome. The binding free energy of compound 12 and 20 with the ribosome was calculated to be -10.7 kcal/mol and -11.66 kcal/mol, respectively.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Desenho de Fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Compostos Policíclicos/farmacologia , Subunidades Ribossômicas Maiores de Bactérias/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/síntese química , Diterpenos/química , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Compostos Policíclicos/síntese química , Compostos Policíclicos/química , Células RAW 264.7 , Relação Estrutura-Atividade
18.
Biosens Bioelectron ; 184: 113238, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33878594

RESUMO

The widespread use of herbicides in agriculture and gardening causes environmental and safety issues such as water pollution. Thus, efficient and convenient analysis of the levels of herbicide residues is of significant importance. Here, we employed 3D-printing to design a multiplex immunosensor for simultaneous detection of two widely used herbicides, atrazine and acetochlor. Multiplexing was achieved through customization of a lateral flow immunoassay, and then integrated with an electrochemical analyzer for ultrasensitive detection. Quantification of herbicide residues was realized through the detection of a novel nanomaterial label, the mesoporous core-shell palladium@platium nanoparticle (Pd@Pt NP), for its outstanding peroxidase-like property. During the electrochemical analysis, the catalytic activity of Pd@Pt NPs on the redox reaction between thionin acetate and hydrogen peroxide provided an electrochemically driven signal that accurately indicated the level of herbicide residues. Using this Nanomaterial-enhanced multiplex electrochemical immunosensing (NEMEIS) system, simultaneous detection of atrazine and acetochlor was realized with a limit of detection of 0.24 ppb and 3.2 ppb, respectively. To further evaluate the feasibility, the optimized NEMEIS was employed for detection in atrazine and acetochlor residue-containing spiked samples, and an overall recovery with 90.8% - 117% range was obtained. The NEMEIS constructed with the aid of 3D-printing provides a rapid, precise, economical, and portable detection device for herbicides, and its success suggests potential broad applications in chemical analysis, biosensors and point-of-care monitoring.


Assuntos
Atrazina , Técnicas Biossensoriais , Herbicidas , Nanoestruturas , Herbicidas/análise , Imunoensaio , Impressão Tridimensional , Toluidinas
19.
Vaccine ; 39(20): 2746-2754, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33875266

RESUMO

BACKGROUND: This study examined the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine. METHOD: In a phase I randomized, double-blinded, placebo-controlled trial involving 192 healthy adults 18-59 years old, two injections of three doses (50 EU, 100 EU, 150 EU) of an inactivated SARS-CoV-2 vaccine or placebo were administered intramuscularly at a 2- or 4-week interval. The safety and immunogenicity of the vaccine were evaluated. RESULTS: Vaccination was completed in 191 subjects. Forty-four adverse reactions occurred within 28 days, most commonly mild pain and redness at the injection site or slight fatigue. At days 14 and 28, the seroconversion rates were 87.5% and 79.2% (50 EU), 100% and 95.8% (100 EU), and 95.8% and 87.5% (150 EU), respectively, with geometric mean titers (GMTs) of 18.1 and 10.6, 54.5 and 15.4, and 37.1 and 18.5, respectively, for the schedules with 2-week and 4-week intervals. Seroconversion was associated with synchronous upregulation of antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. No cytokines and immune cells related to immunopathology were observed. Transcriptome analysis revealed the genetic diversity of immune responses induced by the vaccine. INTERPRETATION: In a population aged 18-59 years in this trial, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. TRIAL REGISTRATION: CTR20200943 and NCT04412538.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas , Adolescente , Adulto , Anticorpos Antivirais , China , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina , Pessoa de Meia-Idade , SARS-CoV-2 , Adulto Jovem
20.
Gait Posture ; 87: 19-26, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33878509

RESUMO

BACKGROUND: Depth sensors could be a portable, affordable, marker-less alternative to three-dimension motion capture systems for gait analysis, but the effects of camera viewing angles on their joint angle tracking performance have not been fully investigated. RESEARCH QUESTIONS: This study evaluated the accuracies of three depth sensors [Azure Kinect (AK); Kinect v2 (K2); Orbbec Astra (OA)] for tracking kinematic gait patterns during treadmill walking at five camera viewing angles (0°/22.5°/45°/67.5°/90°). METHODS: Ten healthy subjects performed fifteen treadmill walking trials (3 speeds × 5 viewing angles) using the three depth sensors to measure joint angles in sagittal hip, frontal hip, sagittal knee, and sagittal ankle. Ten walking steps were recorded and averaged for each walking trial. Range of motion in terms of maximum and minimum joint angles measured by the depth sensors were compared with the Vicon motion capture system as the gold standard. Depth sensors tracking accuracies were compared against the Vicon reference using root-mean-square error (RMSE) on the joint angle time series. Effects of different walking speeds, viewing angles, and depth sensors on the tracking accuracy were observed using three-way repeated-measure analysis of variance (ANOVA). RESULTS: ANOVA results on RMSE showed significant interaction effects between viewing angles and depth sensors for sagittal hip [F(8,72) = 4.404, p = 0.005] and for sagittal knee [F(8,72)=13.211, p < 0.001] joint angles. AK had better tracking performance when subjects walked at non-frontal camera viewing angles (22.5°/45°/67.5°/90°); while K2 performed better at frontal viewing angle (0°). The superior tracking performance of AK compared with K2/OA might be attributed to the improved depth sensor resolution and body tracking algorithm. SIGNIFICANCE: Researchers should be cautious about camera viewing angle when using depth sensors for kinematic gait measurements. Our results demonstrated Azure Kinect had good tracking performance of sagittal hip and sagittal knee joint angles during treadmill walking tests at non-frontal camera viewing angles.


Assuntos
Marcha , Fenômenos Biomecânicos , Análise da Marcha , Humanos , Reprodutibilidade dos Testes
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