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2.
Anal Chim Acta ; 1189: 339224, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815036

RESUMO

Psoralen ultraviolet A (PUVA) therapy has thrived as a promising treatment for psoriasis. However, overdose of PUVA treatment will cause side-effects, such as melanoma formation. And these side-effects are often ignored during PUVA therapy. Hence, in situ monitoring therapeutic response of PUVA therapy is important to minimize side-effects. Aberrant expression of tyrosinase (TYR) has been proved to be associated with melanoma, indicating that TYR is a potential target for evaluation of PUVA therapy. Herein, we reported a strategy for in situ monitoring TYR activity during PUVA therapy by using a cell-array chip-based SERS platform. The cell-array chip was used to simulate cell survival environment for cell culture. Capture of single cells and living cell analysis were realized in the isolated microchambers. An enzyme-induced core-shell self-assembly substrate was used to evaluate TYR activity in living cells during PUVA therapy. The gold nanoparticle modified with a SERS reporter, 4-mercaptobenzonitrile (4-MBN), was used as the core. In the presence of oxygen and TYR, hydroxylation of l-tyrosine occurred, leading to the reduction of silver ion on the surface of gold cores. The growth of silver shells was accompanied by the increased SERS intensity of the reporter, which is related directly to TYR activity. The detection limit for TYR activity is 0.45 U/mL. Upregulation of TYR activity was successfully monitored after PUVA therapy. Notably, real-time and in situ information of therapeutic response can be obtained through monitoring PUVA therapy by using a cell-array chip-based SERS platform, which has great potential to guide the clinical application of PUVA therapy.


Assuntos
Ouro , Nanopartículas Metálicas , Terapia PUVA , Animais , Linhagem Celular , Camundongos , Prata , Análise Espectral Raman
4.
Infect Drug Resist ; 14: 5131-5136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880637

RESUMO

Purpose: Neisseria gonorrhoeae, resistant to the first-line treatment option ceftriaxone, is widespread in China from 2016. Nowadays, diverse reagents of disks and strips for rapid gonococcal antimicrobial susceptibility tests used in clinics are culture-based disks diffusion and gradient strips methods. This study aimed to evaluate the accuracy, quality, and availability of almost all disks and strips acquired in the Chinese market and serve as a reference for clinical selection. Methods: We tested the performance of 15 commercial disks and 9 commercial gradient strips acquired in China, compared with traditional agar dilution method. The overall performance was evaluated by the categorical agreement. The reagent accuracy of gradient strips was assessed by the essential agreement. Results: A total of 167 gonococcal isolates were used to evaluate antimicrobial disks from three brands. The overall categorical agreements were 71.7% to 81.8% for ceftriaxone, less than 58% for cefixime, 100% for spectinomycin, over 98% for ciprofloxacin, below 70.5% for penicillin, and 73.3% to 81.8% for tetracycline. A total of 81 isolates were tested for different gradient strips. Categorical agreements were over 96% for ceftriaxone, 86.2% for azithromycin, 62.3% to 67.1% for penicillin, 41.9% to 67.5% for tetracycline, and 95% for ciprofloxacin. Essential agreements were 57.7% to 87.3% for ceftriaxone, 70% for azithromycin, 64.9% to 68.4% for penicillin, 51.8% to 71.2% for tetracycline, and 91.3% for ciprofloxacin. Conclusion: Rapid test reagents of disks and strips based on gonococcal culture have suboptimal performance. Disk diffusion for spectinomycin or ciprofloxacin can be recommended for clinical individualized prescription. The gradient strips are of great value to identify ceftriaxone-resistant gonococcal strains. Furthermore, abundant improvements are required for many reagents to further optimize their accuracy till the fulfillment of molecular detection.

5.
BMC Cancer ; 21(1): 1323, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893037

RESUMO

BACKGROUND: Numerous studies have examined catastrophic health expenditures (CHE) worldwide, mostly focusing on general or common chronic populations, rather than particularly vulnerable groups. This study assessed the medical expenditure and compensation of lung cancer, and explored the extent and influencing factors of CHE among households with lung cancer patients in China. METHODS: During 2018-2019, a hospital-based multicenter retrospective survey was conducted in seven provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. CHE was measured according to the proportion of out-of-pocket (OOP) health payments of households on non-food expenditures. Chi-square tests and logistic regression analysis was adjusted to determine the factors that significantly influenced the likelihood of a household with lung cancer patient to incur in CHE. RESULTS: In total, 470 households with lung cancer patients were included in the analysis. Health insurance was shown to protect some households from the impact of CHE. Nonetheless, CHE incidence (78.1%) and intensity (14.02% for average distance and 22.56% for relative distance) were still relatively high among households with lung cancer patients. The incidence was lower in households covered by the Urban Employee Basic Medical Insurance (UEMBI) insurance, with higher income level and shorter disease course. CONCLUSION: More attention is needed for CHE incidence among vulnerable populations in China. Households with lung cancer patients were shown to be more likely to develop CHE. Therefore, policy makers should focus on improving the financial protection and reducing the economic burden of this disease.

6.
Infect Drug Resist ; 14: 5335-5349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34934329

RESUMO

Herpes simplex viruses (HSVs) often cause latent infection for a lifetime, leading to repeated recurrence. HSVs have been engineered as oncolytic HSVs. The mechanism of the latent infection and recurrence remains largely unknown, which brings great challenges and limitations to eliminate HSVs in clinic and engineer safe oHSVs. Here, we systematically reviewed the latest development of the multi-step complex process of HSV latency and reactivation. Significantly, we first summarized the three HSV latent infection pathways, analyzed the structure and expression of the LAT1 and LAT2 of HSV-1 and HSV-2, proposed the regulation of LAT expression by four pathways, and dissected the function of LAT mediated by five LAT products of miRNAs, sRNAs, lncRNAs, sncRNAs and ORFs. We further analyzed that application of HSV LAT deletion mutants in HSV vaccines and oHSVs. Our review showed that deleting LAT significantly reduced the latency and reactivation of HSV, providing new ideas for the future development of safe and effective HSV therapeutics, vaccines and oHSVs. In addition, we proposed that RNA silencing or RNA interference may play an important role in HSV latency and reactivation, which is worth validating in future.

9.
Placenta ; 118: 1-9, 2021 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-34972066

RESUMO

INTRODUCTION: Fetal growth and development depend on metabolic energy from placental mitochondria. However, the impact of placental mitochondria on the occurrence of macrosomia remains unclear. We aimed to explore the association between macrosomia without gestational diabetes mellitus (non-GDM) and changes in placental mitochondrial DNA (mtDNA) copy number and methylation. METHODS: Fifty-four newborns with macrosomia and 54 normal birthweight controls were enrolled in this study. Placental mtDNA copy number and mRNA expression of nuclear genes related to mitochondrial replication or ATP synthesis-related genes were measured by real-time quantitative polymerase chain reaction (qPCR). Methylation levels of the non-coding regulatory region D-loop and ATP synthesis-related genes were detected by targeted bisulfite sequencing. RESULTS: Newborns with macrosomia had lower placental mtDNA copy number and higher methylation rates of the CpG15 site in the D-loop region (D-CpG15) and CpG6 site in the cytochrome C oxidase III (COX3) gene (COX3-CpG6) than normal birth weight newborns. After adjusting for potential covariates (gestational age, prepregnancy BMI, and infant sex), decreased placental mtDNA copy number (adjusted odds ratio [aOR] = 2.09, 95% confidence interval [CI] 1.03-4.25), elevated methylation rate of D-CpG15 (aOR = 2.06, 95% CI 1.03-4.09) and COX3-CpG6 (aOR = 2.13, 95% CI 1.08-4.20) remained significantly associated with a higher risk of macrosomia. DISCUSSION: Reduced mtDNA copy number and increased methylation levels of specific loci at mtDNA would increase the risk of macrosomia. However, the detailed molecular mechanism needs further identification.

10.
BMJ Open ; 11(12): e054681, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34916327

RESUMO

INTRODUCTION: Postoperative pain remains incompletely controlled for decades. Recently, multimodal analgesia is emerging as a potential approach in the management of postoperative pain. Therein, S(+)-ketamine is appealing as an adjuvant drug in multimodal analgesia due to its unique pharmacological advantages. This pragmatic clinical trial (SAFE-SK-A trial) is designed to investigate the analgesic effect and safety of S(+)-ketamine for acute postoperative pain in adults and explore the optimal strategy of perioperative intravenous S(+)-ketamine in a real-world setting. METHODS AND ANALYSIS: This multicentre, randomised, open-label, positive-controlled, pragmatic clinical trial (SAFE-SK-A study) is planned to conduct in 80 centres from China and recruit a total of 12 000 adult participants undergoing a surgical procedure under general anaesthesia. Patient recruitment started in June 2021 and will end in June 2022. Participants will be randomised in a ratio of 2:1 to either receive perioperative intravenous S(+)-ketamine plus conventional anaesthesia or conventional anaesthesia only. Given the pragmatic nature of the study, no specific restriction as to the administration dosage, route, time, synergistic regimen or basic analgesics. Primary endpoints are the area under the broken line of Numerical Rating Scale (NRS) scores for pain intensity and the total opioid consumption within 48 hours postoperative. Secondary endpoints are postoperative NRS scores, the anaesthesia recovery time, time of first rescue analgesia, the incidence of rescue analgesia, the incidence of postoperative delirium, patient questionnaire for effect, changes from baseline in cognitive function and anxiety and depression, as well as the adverse events and pharmacoeconomic outcomes. The general linear model will be used for the primary endpoint, and appropriate methods will be used for the secondary endpoints. ETHICS AND DISSEMINATION: This trial has been approved by the local Institutional Review Board (S2021-026-02) and conducted following the Declaration of Helsinki. Results of this trial will be publicly disclosed and published in scientific journals. TRIAL REGISTRATION NUMBER: NCT04837170; Pre-results.

11.
J Mol Med (Berl) ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837498

RESUMO

Neurogenetic diseases are neurological conditions with a genetic cause (s). There are thousands of neurogenetic diseases, and most of them are incurable. The development of bioinformatics and elucidation of the mechanism of pathogenesis have allowed the development of gene therapy approaches, which show great potential in treating neurogenetic diseases. Viral vectors delivery, antisense oligonucleotides, gene editing, RNA interference, and burgeoning viroid delivery technique are promising gene therapy strategies, and commendable therapeutic effects in the treatment of neurogenetic diseases have been achieved (Fig. 1). This review highlights a sampling of advances in gene therapies for neurogenetic disorders. Fig. 1 Examples of gene therapy strategies used in the treatment of neurogenetic diseases. The schematic diagram shows different gene therapy approaches used for treating a sampling of neurogenetic disorders, such as ASO therapy, gene editing, gene augmentation, and RNA interference.

12.
Am J Transl Res ; 13(10): 11501-11512, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786076

RESUMO

Charcot-Marie-Tooth (CMT) 2A disease, a genetic axonal nervous lesion, results from MFN2 pathogenic variation, and this gene plays a pivotal role in mitochondrial dynamics and calcium signaling. However, the underlying mechanism linking MFN2 defect to progressive dying-back of peripheral nerves is still unclear. The present work focused on analyzing one CMT2A patient from multiple perspectives. Clinical and pathologic evaluation was initially conducted on the recruited case. Subsequently, Sanger sequencing and whole-exome sequencing (WES) were performed for genetic detection. To reveal the cell metabolic alteration caused by the identified variant, this study also established and transfected plasmid vectors in HEK293 cells and analyzed cell metabolites through liquid chromatography in combination with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS). Additionally, we completed structural modeling and molecular dynamic (MD) simulation to investigate the intramolecular impact of the variant. According to our results, the clinical and neuropathologic manifestations of the proband matched with the diagnosis of CMT. The causative variant MFN2: c.638T>C: (p.Ile213Thr) was identified through genetic analysis. Moreover, metabolic pathway enrichment results demonstrated that this variant significantly affected the metabolism of sphingolipids and glycerophospholipids. MD analysis indicated that this variant crippled the binding ability of MFN2 to GTP. Taken together, our study deduced preliminary clues for the underlying mechanism by which mutant MFN2 affects cell metabolism and provided a novel perspective to understand the cellular and molecular impacts of MFN2 variants.

13.
Phys Chem Chem Phys ; 23(45): 25994-26003, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34783808

RESUMO

To easily synthesize a piezoelectric quantum anomalous Hall insulator (PQAHI), the Janus monolayer Fe2IBr (FeI0.5Br0.5) as a representative PQAHI, is generalized to monolayer FeI1-xBrx (x = 0.25 and 0.75) with α and ß phases. By first-principles calculations, it is proved that monolayer FeI1-xBrx (x = 0.25 and 0.75) are dynamically, mechanically and thermally stable. They are excellent room-temperature PQAHIs with high Curie temperatures, sizable gaps and high Chern number (C = 2). Because the considered crystal structures of α and ß phases possess Mx and My mirror symmetries, the topological properties of monolayer FeI1-xBrx (x = 0.25 and 0.75) are maintained. Namely, if the constructed structures have Mx and My mirror symmetries, the mixing ratio of Br and I atoms can be generalized for other proportions. It is also found that different crystal phases have important effects on the out-of-plane piezoelectric response, and the piezoelectric strain coefficient, d32, of the ß phase is higher than or comparable with those of other known two-dimensional (2D) materials. To further confirm this idea, the physical and chemical properties of monolayer LiFeSe0.75S0.25 with α and ß phases, as a generalization of PQAHI LiFeSe0.5S0.5, is investigated, as it has a similar electronic structure, magnetic and topological properties as LiFeSe0.5S0.5. Our work provides a practical guide to achieve PQAHIs experimentally, and the combination of piezoelectricity, topological and ferromagnetic (FM) orders makes Fe2I2-based monolayers a potential platform for multi-functional spintronics and piezoelectric electronics.

14.
Zookeys ; 1063: 1-21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720622

RESUMO

The Chinese species of subgenus Koreonialoe Park & Kwon, 1996 of the genus Pterostichus are revised, including four species from the eastern part of Jilin and Liaoning provinces. Two new species are described: Pterostichus (Koreonialoe) micropoidessp. nov. (type locality: Jilin, Changbai county), and Pterostichus (Koreonialoe) tetralobatussp. nov. (type locality: Liaoning, Xiuyan county). Pterostichus (Koreonialoe) bellatrix (Tschitschérine) is newly recorded from China (Jilin). The subgenus Koreonialoe is classified into two groups on account of their differences on the endophallus, and all Chinese species accord with the microps group defined herein. A key to all six species in the microps group is provided.

15.
Front Neurol ; 12: 734570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764928

RESUMO

Objective: To objective of the study was to investigate whether serum brain-derived neurotrophic factor (BDNF) levels are associated with the severity of restless legs syndrome (RLS) in Parkinson's disease (PD). Methods: A total of 249 PD patients with (n = 53) and without RLS (n = 196) and 326 age-matched controls were included in this study. All the serum BDNF levels of the participants were measured. The International Restless Legs Syndrome Study Group Rating Scale (IRLSSG-RS) was administered for the severity of RLS. The severity of PD patients were assessed by the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr (H-Y) stage. Results: The prevalence of RLS was significantly higher in PD patients (21.3%) than in the controls group (7.4%) (p < 0.05). The IRLSSG-RS score in PD patients with RLS (16.25 ± 5.24) was significantly increased than in controls with RLS (12.08 ± 3.99) (p < 0.01). The serum BDNF levels were significantly decreased in PD patients with RLS than in PD patients without RLS, controls without RLS, and controls with RLS (p < 0.001). BDNF levels were negatively associated with IRLSSG-RS in both PD patients with RLS and controls with RLS group (both p < 0.01). Multiple regression analysis confirmed that in either PD with RLS or controls with RLS group, BDNF was an independent contributor to IRLSSG-RS (both p < 0.01). Conclusions: Decreased serum BDNF levels may be involved in the pathophysiology of RLS in PD, suggesting that it may serve as a potential blood biomarker of diagnostic value for RLS in PD.

16.
Drug Alcohol Depend ; 229(Pt A): 109132, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34768052

RESUMO

BACKGROUND: Substance use disorder (SUD) has become increasingly prevalent worldwide, this study investigated the associations of SUD and alcohol, cannabis, opioid, or stimulant use disorder with cardiovascular disease (CVD) and 11 major CVD subtypes. METHODS: This study was based on a 20% random sample of residents in British Columbia, Canada, who were aged 18 - 80 years at baseline on January 1, 2015. Using linked administrative health data during 2010 - 2014, we identified people with various SUDs and prevalent CVDs at baseline, and examined the cross-sectional associations between SUDs and CVDs. After excluding people with CVDs at baseline, we followed the cohort for 4 years to identify people who developed incident CVDs, and examined the longitudinal associations between SUDs and CVDs. RESULTS: The cross-sectional analysis at baseline included 778,771 people (mean age 45 years, 50% male), 13,279 (1.7%) had SUD, and 41,573 (5.3%) had prevalent CVD. After adjusting for covariates, people with SUD were 2.7 (95% confidence interval [CI], 2.5 - 2.8) times more likely than people without SUD to have prevalent CVD. The longitudinal analysis included 617,863 people, 17,360 (2.8%) developed incident CVD during the follow-up period. After adjusting for covariates, people with SUD were 1.7 (95% CI, 1.6 - 1.9) times more likely than people without SUD to develop incident CVD. The cross-sectional and longitudinal associations were more pronounced for people with opioid or stimulant use disorder. CONCLUSIONS: People with SUD are more likely to have prevalent CVD and develop incident CVD compared with people without SUD.

17.
Langmuir ; 37(46): 13787-13797, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34779209

RESUMO

Nanomaterials for biological applications would inevitably encounter and interact with biomolecules, which have a profound impact on the properties, functions, and even fates of both nanomaterials and biomolecules. Among the biomolecules, lysozyme (Lys) is of great importance in defending the bacterial intruder and maintaining health. Here, the interactions between fluorescent gold nanoclusters (AuNCs) (∼2 nm) capped with different surface ligands and Lys were thoroughly investigated. Fluorescence spectroscopic studies showed that dihydrolipoic acid (DHLA)-capped and glutathione (GSH)-capped AuNCs both quenched the intrinsic fluorescence of Lys by different quenching mechanisms. Agarose gel electrophoresis and zeta-potential assays showed that statistically one DHLA-AuNC could bind one Lys, while one GSH-AuNC could bind 3-4 Lys, providing new examples for the concept of a "protein complex". Activity assays indicated that DHLA-AuNCs heavily inhibited the enzymatic activity of Lys, while GSH-AuNCs had little effect. By synchronous fluorescence and circular dichroism spectroscopic studies, it was deduced that both AuNCs would interact with Lys by electrostatic attractions due to the distinct surface charges, and then DHLA-AuNCs would further interact with Lys by hydrophobic interactions, probably due to the hydrophobic carbon chain of DHLA and the hydrophobic side chains of amino acid residues in Lys, which was proved by the significant secondary structure changes caused by DHLA-AuNCs. Meanwhile, conformational changes induced by GSH-AuNCs with zwitterionic ligands were neglectable. Therefore, this work provided a comprehensive study of the consequences and mechanisms of the interactions between Lys and AuNCs, which was essential for the design and better use of nanomaterials as biological agents.

18.
Phys Rev E ; 104(4-2): 045209, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34781465

RESUMO

An electron heating mechanism based on a resonance between the cyclotron motion of electrons and the radio frequency sheath oscillations is reported in weakly magnetized capacitively coupled plasmas at low pressure. If half of the electron cyclotron period coincides with the radio frequency period, then electrons will coherently collide with the expanding sheath and gain substantial energy, which enhances the plasma density. A relation between the magnetic field and the driving frequency is found to characterize this resonance effect and the kinetics of electrons are revealed at resonance conditions for various driving frequencies.

19.
Opt Lett ; 46(21): 5525-5528, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724517

RESUMO

The realization of monolithic integration of a stable III-V laser on a standard silicon-on-insulator (SOI) substrate has been regarded as a challenging technology for silicon-based photonic integration circuits (PICs). Here, we successfully demonstrated the electrically pumped P-doped 1300 nm InAs/GaAs quantum dot (QD) laser epitaxially grown on {111}-faceted SOI hollow substrates. These III-V QD lasers, which are epitaxially grown on an SOI substrate, generally exhibit strong thermal accumulation due to the oxide layer underneath. By applying a double-side heat dissipation design, the maximum operation temperature of the SOI-based InAs/GaAs QD laser under a continuous-wave (CW) operation mode is ramped up to 35°C from 20°C. Moreover, the thermal profile simulation of three different structures has also been carried out to show the effectiveness of the top heat sink design in order to improve laser performance. An integrated thermal shunt design is proposed to improve heat dissipation without using the external top heat sink. The successful realization of room-temperature SOI-based InAs/GaAs QD lasers pave a viable way for integrating light sources in PICs.

20.
World J Clin Cases ; 9(25): 7311-7318, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34616797

RESUMO

Extracellular vesicles (EVs) are cystic vesicles naturally released by most mammalian cells and bacteria. EV contents include proteins, lipids, and nucleic acids. EVs can act as messengers to transmit a variety of molecules to recipient cells and thus play important regulatory roles in intercellular signal transduction. EVs, released by either a host cell or a pathogen, can carry pathogen-associated antigens and thus act as modulators of immune responses. EVs derived from Mycobacterium tuberculosis (Mtb)-infected cells can regulate the innate immune response through various pathways, such as regulating the release of inflammatory cytokines. In addition, EVs can mediate antigen presentation and regulate the adaptive immune response by transmitting immunoregulatory molecules to T helper cells. In this review, we summarize the regulatory roles of EVs in the immune response against Mtb.

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