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1.
J Phys Chem Lett ; 12(40): 9783-9790, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34596405

RESUMO

Narrow bandgap donor-acceptor organic semiconductors are generally considered to show a closed-shell singlet ground state, and their radicals are reported as impurities, defects, polarons, and charge transfer monoradicals. Herein, we systematically investigated the open-shell singlet diradical electronic ground state of two diketopyrrolopyrrole-based compounds via the combination of electron spin resonance (ESR), nuclear magnetic resonance, superconducting quantum interference device magnetometry, and theoretical calculations. It is widely known that the quinoidal character will be significantly enhanced in the aggregation state accompanied by improved planarity and enhanced delocalization. We proposed an aggregation-induced radical and captodative effect as the driving force for the formation and stabilization of the open-shell quinoid diradical based on the ESR test in different proportions of mixed solvents. Our results provided a novel view for understanding the intrinsic chemical structure of donor-acceptor organic semiconductors, the open-shell singlet and thermally excited triplet electronic states, and the unexpected physical processes between the ground state and the excited state.

2.
Front Microbiol ; 12: 700008, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603226

RESUMO

Numerous studies have shown that droplet digital PCR (ddPCR) is a promising tool for the diagnosis of pathogens, especially in samples with low concentrations of pathogenic DNA. An early diagnosis of candidemia is critical for the effective treatment of patients. In this study, we evaluated the sensitivity and specificity of ddPCR assay for Candida DNA detection both in vitro by mixing fungal cells with human blood and in vivo by analyzing blood samples from infected mice and patients with suspected candidemia. The results showed that ddPCR assay could detect a minimum of 4.5 DNA copies per reaction in blood samples. ddPCR showed higher sensitivity and specificity for Candida DNA detection than traditional culture and quantitative PCR (qPCR) methods and also exhibited significantly better positive and negative predictive values than the culture and qPCR methods that were commonly used in clinical practice. Hence, our study demonstrates that ddPCR assay is a promising method for the timely diagnosis of candidemia and could be useful for monitoring the treatment of candidemia.

3.
Front Genet ; 12: 740134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650599

RESUMO

Anxiety disorders are common mental disorders that often result in disability. Recently, large-scale genome-wide association studies (GWASs) have identified several novel risk variants and loci for anxiety disorders (or anxiety traits). Nevertheless, how the reported risk variants confer risk of anxiety remains unknown. To identify genes whose cis-regulated expression levels are associated with risk of anxiety traits, we conducted a transcriptome-wide association study (TWAS) by integrating genome-wide associations from a large-scale GWAS (N = 175,163) (which evaluated anxiety traits based on Generalized Anxiety Disorder 2-item scale (GAD-2) score) and brain expression quantitative trait loci (eQTL) data (from the PsychENCODE and GTEx). We identified 19 and 17 transcriptome-wide significant (TWS) genes in the PsychENCODE and GTEx, respectively. Intriguingly, 10 genes showed significant associations with anxiety in both datasets, strongly suggesting that genetic risk variants may confer risk of anxiety traits by regulating the expression of these genes. Top TWS genes included RNF123, KANSL1-AS1, GLYCTK, CRHR1, DND1P1, MAPT and ARHGAP27. Of note, 25 TWS genes were not implicated in the original GWAS. Our TWAS identified 26 risk genes whose cis-regulated expression were significantly associated with anxiety, providing important insights into the genetic component of gene expression in anxiety disorders/traits and new clues for future drug development.

4.
Int J Biol Macromol ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34655590

RESUMO

The BTB (broad-complex, tram track, and bric-abrac) proteins are involved in germination, biotic, and abiotic stress responses in various plants, but the molecular basis of protein interactions has been not elucidated in rice yet. In this study, the identified BTB proteins were divided into BTB-TAZ, MATH-BTB, BTB-NPH, BTB-ANK, BTB-Skp, BTB-DUF, and BTB-TPR subfamilies based on the additional functional domains found together with the BTB domain at N- and C-terminal as well, suggesting that the extension region at both terminal sites could play a vital role in the BTB gene family expansion in plants. The yeast two-hybrid system, firefly luciferase complementation imaging (LCI) assay and bimolecular fluorescence complementation (BiFC) assay further confirmed that BTB proteins interact with several other proteins to perform a certain developmental process in plants. The overexpression of BTB genes of each subfamily in Arabidopsis revealed that BTB genes including OsBTB4, OsBTB8, OsBTB64, OsBTB62, OsBTB138, and OsBTB147, which contain certain additional functional domains, could play a potential role in the early flowering, branching, leaf, and silique development. Moreover, we concluded that the presence of other functional domains such as TAZ, SKP, DUF, ANK, NPH, BACK, PQQ, and MATH could diversify the function of BTB protein in plant growth and development.

5.
Nat Commun ; 12(1): 5889, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620849

RESUMO

Most organic semiconductors have closed-shell electronic structures, however, studies have revealed open-shell character emanating from design paradigms such as narrowing the bandgap and controlling the quinoidal-aromatic resonance of the π-system. A fundamental challenge is understanding and identifying the molecular and electronic basis for the transition from a closed- to open-shell electronic structure and connecting the physicochemical properties with (opto)electronic functionality. Here, we report donor-acceptor organic semiconductors comprised of diketopyrrolopyrrole and naphthobisthiadiazole acceptors and various electron-rich donors commonly utilized in constructing high-performance organic semiconductors. Nuclear magnetic resonance, electron spin resonance, magnetic susceptibility measurements, single-crystal X-ray studies, and computational investigations connect the bandgap, π-extension, structural, and electronic features with the emergence of various degrees of diradical character. This work systematically demonstrates the widespread diradical character in the classical donor-acceptor organic semiconductors and provides distinctive insights into their ground state structure-property relationship.

6.
BMC Cancer ; 21(1): 1119, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663268

RESUMO

BACKGROUND: Previous studies have observed a close association between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) as well as extrahepatic cancers. However, research concerning the effect of HBV infection on the risk of colorectal cancer (CRC) is rare and inconsistent. This study aims to determine the relationship between HBV infection and new-onset CRC. METHODS: We prospectively examined the relationship between HBV infection and new-onset CRC among 93,390 participants from Kailuan Cohort study. Cox proportional hazards regression models, subgroup analyses and competing risk analyses were used to evaluate the association between HBV infection and the risk of new-onset CRC. RESULTS: During a median follow-up of 11.28 years, 448 incident CRC cases were identified. The adjusted HR (95%confidence interval (CI)) for the association of HBsAg Seropositive with CRC was 1.85(1.15 ~ 2.96) in the Cox regression. Subgroup analyses showed that the HBsAg seropositive group was associated with increased risk of new-onset CRC among male, middle-aged, normal weight, smokers and non-drinker participants, respectively. A positive association of HBV infection with the risk of CRC was observed in the adjusted sub-distribution proportional hazards (SD) models (HRSD = 1.77, 95% CI:1.11-2.84) and cause-specific hazards (CS) models (HRCS = 1.79, 95% CI: 1.13-2.91). CONCLUSIONS: Our results have found a significant association between HBV infection and the risk of incident CRC among Chinese participants. TRIAL REGISTRATION: Kailuan study, ChiCTR-TNRC-11001489. Registered 24 August 2011 - Retrospectively registered, http:// http://www.chictr.org.cn/showprojen.aspx?proj=8050.

7.
Opt Express ; 29(20): 32271-32284, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615302

RESUMO

This paper presents a method to directly calibrate the position of a trapped micro-sphere in optical tweezers utilizing its interference pattern formed at the back focal plane (BFP). Through finite difference time domain (FDTD) and scalar diffraction theorem, the scattering field complex amplitude of the near and far fields can be simulated after interference between the trapped sphere and focus Gaussian beam. The position of the trapped sphere can be recovered and calibrated based on a back focal plane interferometry (BFPI) algorithm. Theoretical results demonstrate that optical tweezers with a larger numerical aperture (NA) Gaussian beam will yield a better detection sensitivity but with a smaller linear range. These results were experimentally validated by trapping a microsphere in a single beam optical tweezer. We used an extra focused laser to manipulate the trapped sphere and then compared its position in the images and that obtained using the BFP method. The interference pattern from simulation and experiments showed good agreement, implying that the calibration factor can be deduced from simulation and requires no intermediate calculation process. These results provide a pathway to obtain the calibration factor, enable a faster and direct measurement of the sphere position, and show possibilities for adjusting the crosstalk and nonlinearity inside an optical trap.

8.
Ecotoxicol Environ Saf ; 225: 112806, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555716

RESUMO

Ionic liquids (ILs) are widely used for their physical and chemical properties. Toxicological assessments of ILs could help to avoid their threat to human health, but these are rarely reported, and no assessments of IL neurotoxicity in mammals have been performed. Here, we aimed to evaluate the neurotoxicity of chronic 1-octyl-3-methylimidazolium hexafluorophosphate ([C8mim][PF6]) (0, 1 mg/kg) exposure during development on rats. Our results indicated that chronic exposure to low-dose ([C8mim][PF6]) induces behavioural abnormalities, including cognitive deficits, social communication disorders, and sensory gating function impairment. Moreover, rats subjected to chronic ([C8mim][PF6]) exposure showed hypofunction of glutamatergic excitatory synapses, including increased expression of NMDA receptor subunits, increased density and immaturity of dendritic spines, and increased expression of PSD95. Additionally, ([C8mim][PF6]) exposure resulted in hippocampal-specific inflammatory activation, indicated by increased levels of proinflammatory factors, elevated nuclear localisation of NF-κB, and activation of microglia and astrocytes. In conclusion, chronic exposure to low-dose ([C8mim][PF6]) induced neurotoxicity, including damage to glutamatergic excitatory synapses and inflammatory activation, which may illuminate the associated behavioural abnormalities. The results presented here may be helpful for the safe use of ILs in the future.


Assuntos
Disfunção Cognitiva , Síndromes Neurotóxicas , Animais , Astrócitos , Microglia , NF-kappa B , Síndromes Neurotóxicas/etiologia , Ratos
9.
J Biomech ; 128: 110734, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34509913

RESUMO

Knee osteoarthritis (KOA) is a common and severe disease characterized by articular cartilage degeneration, subchondral bone remodeling and inflammation. The purpose of this study was to investigate the therapeutic effects of high fibular osteotomy (HFO) in a KOA rabbit model and to examine the molecular mechanisms involved in medial compartment KOA protective effects. Our data showed that HFO delayed the progression of articular cartilage damage and suppressed subchondral bone remodeling in destabilization of the medial meniscus (DMM)-induced KOA model. HFO also decreased MMP-1, MMP-3, MMP-13 and ADAMTS-5 expression, and increased Col2 and aggrecan expression. In parallel, HFO attenuated the expression of IL-1ß, IL-6 and TNF-α. Furthermore, HFO suppressed DMM-mediated NFκB activation, which suggested that the molecular mechanism underlying the protective effect of HFO in medial compartment KOA may be related to the NFκB signaling pathway. Collectively, our data indicated that HFO may be a therapeutic approach to treating medial compartment KOA.

10.
J Colloid Interface Sci ; 607(Pt 1): 281-289, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34507000

RESUMO

Exploring innovation strategies has huge potential to significantly improving both activity and stability of current catalysts. Here, a chainmail design is proposed to enable the electronic interaction of ultrathin nitrogen-doped carbon shell with Ni2P nanorod core arrayed on nickel foam (Ni2P@NC/NF) for simultaneously promoting the activity and stability in both alkaline and neutral hydrogen evolution reaction (HER). The easy penetration of valence electrons from active Ni2P core to NC shell enables the obvious improvement of HER performance compared to pure Ni2P. In 1 M KOH and 1 M PBS solution, the resultant Ni2P@NC/NF requires the ultralow overpotentials of only 93 and 96 mV to drive the current density of 10 mA cm-2 with the Faradaic efficiency of 96% and 94%, respectively. Remarkably, such a chainmail design also reveals an obviously improved stability with almost negligible performance degradation under the current density of 20 mA cm-2 for 30 h. Theoretical calculations confirm that the nitrogen-doped carbon shell improves the durability of transition metal phosphides by increasing the dissolution resistance of Ni atoms. The proposed concept may create a new pathway for synchronizing high activity and robust stability in manipulating heterogeneous catalytic properties.

11.
Front Bioeng Biotechnol ; 9: 709679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589471

RESUMO

To accelerate serious skin burn wound healing in a convenient manner, an interpenetrating network of hydrogel consisting of gellan gum and polyacrylamide was synthesized by chemical crosslinking and Mg2+ ion immersion techniques. The prepared Mg2+@PAM/GG hydrogel was characterized by morphology, water vapor loss, swelling ratio, rheological properties, tensile mechanical, biocompatibility, and flow cytometry study. The results show that Mg2+@PAM/GG hydrogel's mechanical strength could be enhanced by the dual network structure and physical crosslinking agent Mg2+ ions. In addition, the tension strength of Mg2+@PAM/GG hydrogel is obviously increased from 86 to 392 kPa, the elongation at break increased from 84 to 231%, and crosslinking density N increased from 4.3 to 7.2 mol/m3 compared with pure GG hydrogel. The cumulative release curve of Mg2+ ions shows that the multiple release mechanism of Mg2+ ions belong to non-Fick's diffusion. Meanwhile, in vitro experiments show that Mg2+@PAM/GG double network hydrogel has favorable proliferation and an NF-κB pathway inhibition property for fibroblast cells. Finally, the healing effect of the Mg2+@PAM/GG was evaluated in a rat full-thickness burn model. The animal study demonstrates that Mg2+@PAM/GG could accelerate the healing efficiency in case of the sustained-released Mg2+ ions in wound beds. Considering this excellent performance, this convenient prepared hydrogel has great potential as a commercial application for skin full-thickness burn healing materials.

12.
BMC Biotechnol ; 21(1): 55, 2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563172

RESUMO

BACKGROUND: The unnatural amino acid, L-2-aminobutyric acid (L-ABA) is an essential chiral building block for various pharmaceutical drugs, such as the antiepileptic drug levetiracetam and the antituberculosis drug ethambutol. The present study aims at obtaining variants of ω-transaminase from Ochrobactrum anthropi (OATA) with high catalytic activity to α-ketobutyric acid through protein engineering. RESULTS: Based on the docking model using α-ketobutyric acid as the ligand, 6 amino acid residues, consisting of Y20, L57, W58, G229, A230 and M419, were chosen for saturation mutagenesis. The results indicated that L57C, M419I, and A230S substitutions demonstrated the highest elevation of enzymatic activity among 114 variants. Subsequently, double substitutions combining L57C and M419I caused a further increase of the catalytic efficiency to 3.2-fold. This variant was applied for threonine deaminase/OATA coupled reaction in a 50-mL reaction system with 300 mM L-threonine as the substrate. The reaction was finished in 12 h and the conversion efficiency of L-threonine into L-ABA was 94%. The purity of L-ABA is 75%, > 99% ee. The yield of L-ABA was 1.15 g. CONCLUSION: This study provides a basis for further engineering of ω-transaminase for producing chiral amines from keto acids substrates.

13.
Stroke ; : STROKEAHA120032989, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34538087

RESUMO

BACKGROUND AND PURPOSE: This study tests whether patients with unruptured intracranial aneurysm who underwent stent placement benefitted from platelet function monitoring-guided adjustment of antiplatelet therapy. METHODS: We conducted a randomized, open-label, parallel group, assessor-blinded trial. Patients with unruptured intracranial aneurysm who underwent stent placement were assigned in a 1:1 ratio to receive either drug adjustment (patients who had high on-treatment platelet reactivity to antiplatelet therapy on the basis of platelet function monitoring [monitoring group]) or conventional therapy (without monitoring and drug adjustment [conventional group]). The second monitoring was performed 14 days after randomization in patients with drug adjustment. The primary outcome was the composite frequency of ischemic stroke, transient ischemic attack, stent thrombosis, urgent revascularization, and cerebrovascular death within 7 days after stent implantation. The safety outcome was the composite frequency of major, minor, or minimal bleeding within 1 month after stent implantation. RESULTS: In total, 314 patients were included (n=157 per group). The primary combined outcome occurred in 19 patients (12.1%) in the conventional group and 8 patients (5.1%) in the monitoring group (hazard ratio, 0.39 [95% CI, 0.17-0.92]; P=0.03). Ischemic stroke occurred at a lower frequency in the monitoring group compared with that in the conventional group (4.5% versus 12.1%; hazard ratio, 0.34 [95% CI, 0.14-0.83]; P=0.01), which drove the overall primary combined outcome. The safety outcome occurred in the monitoring group (7.0%) and in the conventional group (1.9%; hazard ratio, 3.87 [95% CI, 1.06-14.14]; P=0.03). A significant difference was observed in the frequency of minor or minimal bleeding events between the two groups (monitoring group versus conventional group, 6.4% versus 1.3%; P=0.02) but not in the frequency of major bleeding events between the two groups. CONCLUSIONS: Platelet function monitoring-guided antiplatelet therapy reduces thromboembolic events in patients with unruptured intracranial aneurysm after stent placement, significantly enhancing minor or minimal bleeding events but not major bleeding events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03989557.

14.
BMC Med ; 19(1): 177, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34380480

RESUMO

BACKGROUND: Over 200 schizophrenia risk loci have been identified by genome-wide association studies (GWASs). However, the majority of risk loci were identified in populations of European ancestry (EUR), potentially missing important biological insights. It is important to perform 5 GWASs in non-European populations. METHODS: To identify novel schizophrenia risk loci, we conducted a GWAS in Han Chinese population (3493 cases and 4709 controls). We then performed a large-scale meta-analysis (a total of 143,438 subjects) through combining our results with previous GWASs conducted in EAS and EUR. In addition, we also carried out comprehensive post-GWAS analysis, including heritability partitioning, enrichment of schizophrenia associations in tissues and cell types, trancscriptome-wide association study (TWAS), expression quantitative trait loci (eQTL) and differential expression analysis. RESULTS: We identified two new schizophrenia risk loci, including associations in SHISA9 (rs7192086, P = 4.92 × 10-08) and PES1 (rs57016637, P = 2.33 × 10-11) in Han Chinese population. A fixed-effect meta-analysis (a total of 143,438 subjects) with summary statistics from EAS and EUR identifies 15 novel genome-wide significant risk loci. Heritability partitioning with linkage disequilibrium score regression (LDSC) reveals a significant enrichment of schizophrenia heritability in conserved genomic regions, promoters, and enhancers. Tissue and cell-type enrichment analyses show that schizophrenia associations are significantly enriched in human brain tissues and several types of neurons, including cerebellum neurons, telencephalon inhibitory, and excitatory neurons. Polygenic risk score profiling reveals that GWAS summary statistics from trans-ancestry meta-analysis (EAS + EUR) improves prediction performance in predicting the case/control status of our sample. Finally, transcriptome-wide association study (TWAS) identifies risk genes whose cis-regulated expression change may have a role in schizophrenia. CONCLUSIONS: Our study identifies 17 novel schizophrenia risk loci and highlights the importance and necessity of conducting genetic study in different populations. These findings not only provide new insights into genetic etiology of schizophrenia, but also facilitate to delineate the pathophysiology of schizophrenia and develop new therapeutic targets.


Assuntos
Estudo de Associação Genômica Ampla , Esquizofrenia , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Proteínas de Ligação a RNA , Esquizofrenia/genética , Transcriptoma
15.
Front Neurosci ; 15: 722592, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456681

RESUMO

Epilepsy (affects about 70 million people worldwide) is one of the most prevalent brain disorders and imposes a huge economic burden on society. Epilepsy has a strong genetic component. In this study, we perform the largest genome-wide meta-analysis of epilepsy (N = 8,00,869 subjects) by integrating four large-scale genome-wide association studies (GWASs) of epilepsy. We identified three genome-wide significant (GWS) (p < 5 × 10-8) risk loci for epilepsy. The risk loci on 7q21.11 [lead single nucleotide polymorphism (SNP) rs11978015, p = 9.26 × 10-9] and 8p23.1 (lead SNP rs28634186, p = 4.39 × 10-8) are newly identified in the present study. Of note, rs11978015 resides in upstream of GRM3, which encodes glutamate metabotropic receptor 3. GRM3 has pivotal roles in neurotransmission and is involved in most aspects of normal brain function. In addition, we also identified three genes (TTC21B, RP11-375N15.2, and TNKS) whose cis-regulated expression level are associated with epilepsy, indicating that risk variants may confer epilepsy risk through regulating the expression of these genes. Our study not only provides new insights into genetic architecture of epilepsy but also prioritizes potential molecular targets (including GRM3 and TTC21B) for development of new drugs and therapeutics for epilepsy.

16.
Chin Neurosurg J ; 7(1): 38, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425918

RESUMO

BACKGROUND: The aim of this study was to comprehensively evaluate the risk factors of periprocedural ischemic stroke associated with endovascular treatment of intracranial aneurysms using a real-world database. METHODS: From August 2016 to March 2017, 167 patients were enrolled. Univariate analysis and multivariate logistic regression analysis were used to examine the risk factors for periprocedural ischemic stroke. RESULTS: Among the 167 cases, periprocedural ischemic stroke occurred in 20 cases (11.98%). After univariate analysis, the ischemic group had a higher proportion of large (≥ 10 mm) aneurysms than the control group (45.0% vs. 23.1%, p = 0.036). The incidence of periprocedural ischemic stroke was higher in cases treated by flow diverter (21.6%) or stent-assisted coiling (11.8%) than in cases treated by coiling only (2.7%), and the differences were statistically significant (p = 0.043). After multivariate logistic regression analysis, treatment modality was the independent risk factor for periprocedural ischemic stroke. Compared with the coiling-only procedure, flow diverter therapy was associated with a significantly higher rate of periprocedural ischemic stroke (OR 9.931; 95% CI 1.174-84.038; p = 0.035). CONCLUSIONS: Aneurysm size and treatment modality were associated with periprocedural ischemic stroke. Larger aneurysms were associated with increased risk of periprocedural ischemic stroke. Flow diverter therapy was associated with significantly more periprocedural ischemic stroke than the coiling procedure alone.

17.
Front Pharmacol ; 12: 679580, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194330

RESUMO

Overexpression of reactive oxygen species (ROS) can lead to chronic inflammation, which limits skin wound healing. Therefore, it is of great significance to develop materials that can locally control the adverse reactions caused by excessive ROS. In this research, an ROS-sensitive hydrogel with strong free radical scavenging ability was prepared by introducing the thione (Tk) group into carboxymethyl chitosan (CMCTS) hydrogel. CMCTS hydrogel was cross-linked by NH2-Tk-NH2 agent and loaded curcumin (Cur), which possessed favorable nontoxicity, water absorption, mechanical property, biodegradability, drug release behavior, the M2 phenotype, and inflammatory factor regulating the capacity of macrophages. It is worth noting that Cur@CMCTS-Tk hydrogel can significantly inhibit oxidative damage of human fibroblasts in the H2O2-induced microenvironment and protect their viability by reducing the production of intracellular ROS. In vivo, ROS-removing hydrogel effectively accelerated the process of wound healing and possessed good regenerative properties, including hair follicle formation, promotion of new blood vessel formation, and highly orderly arrangement of collagen fibers in the full-thickness skin burn defect rat model. Hence, we expect that the Cur@CMCTS-Tk hydrogel could be used for wound treatment and tissue regeneration due to the ability to scavenge excess ROS.

18.
Front Neurosci ; 15: 677153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234640

RESUMO

Objectives: Schizophrenia (SZ) is a complex psychiatric disorder with high heritability, and genetic components are thought to be pivotal risk factors for this illness. The glutamate decarboxylase 1 gene (GAD1) was hypothesized to be a candidate risk locus for SZ given its crucial role in the GABAergic neurotransmission system, and previous studies have examined the associations of single nucleotide polymorphisms (SNPs) spanning the GAD1 gene with SZ. However, inconsistent results were obtained. We hence examined the associations between GAD1 SNPs and SZ in two independent case-control samples of Han Chinese ancestry. Materials and Methods: Two Han Chinese SZ case-control samples, referred as the discovery sample and the replication sample, respectively, were recruited for the current study. The discovery sample comprised of 528 paranoid SZ cases (with age of first onset ≥ 18) and 528 healthy controls; the independent replication sample contained 1,256 early onset SZ cases (with age of first onset < 18) and 2,661 healthy controls. Logistic regression analysis was performed to examine the associations between GAD1 SNPs and SZ. Results: Ten SNPs covering GAD1 gene were analyzed in the discovery sample, and two SNPs showed nominal associations with SZ (rs2241165, P = 0.0181, OR = 1.261; rs2241164, P = 0.0225, OR = 1.219). SNP rs2241164 was also nominally significant in the independent replication sample (P = 0.0462, OR = 1.110), and the significance became stronger in a subsequent meta-analysis combining both discovery and replication samples (P = 0.00398, OR = 1.138). Nevertheless, such association could not survive multiple corrections, although the effect size of rs2241164 was comparable with other SZ risk loci identified in genome-wide association studies (GWAS) in Han Chinese population. We also examined the associations between GAD1 SNPs and SZ in published datasets of SZ GWAS in East Asians and Europeans, and no significant associations were observed. Conclusion: We observed weak associations between GAD1 SNPs and risk of SZ in Han Chinese populations. Further analyses in larger Han Chinese samples with more detailed phenotyping are necessary to elucidate the genetic correlation between GAD1 SNPs and SZ.

19.
Front Neurol ; 12: 625652, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149588

RESUMO

Background: Flow diverters and conventional coiling are established modalities for the retreatment of intracranial recurrent aneurysms after initial endovascular treatment. We aimed to compare the efficacy of these techniques. Methods: We retrospectively analyzed data for patients with recurrent aneurysms after initial endovascular treatment retreated in our center with either a pipeline embolization device (PED) or conventional coil embolization from January 2012 to July 2020. We performed 1:2 propensity score matching (PSM) using the nearest neighbor method. We controlled for: initial treatment strategy, aneurysm size, neck diameter, symptom presentation, history of aneurysm rupture, age, sex, fusiform-dissecting aneurysm, bifurcation aneurysm, and aneurysm location. The clinical and morphological factors of all patients at initial treatment and the angiographic and clinical results at the second treatment were collected and compared between the propensity-matched pairs. Results: A total of 105 intracranial aneurysms were identified; 18 patients (17.1%) were treated with a PED, and 87 (82.9%) were treated via conventional coil embolization. PSM resulted in 12 matched pairs (12 patients in the PED group and 24 in the coiling group). There was no significant difference of ischemic and hemorrhagic complications between the groups, the obliteration rate of branches covered by stent, or modified Rankin Scale scores at the last clinical follow-up. Importantly, the retreatment strategy in the PED group provided significantly different results vs. the coiling group (P < 0.001), with a lower recurrence rate (0.0 vs. 29.2%, respectively; P = 0.037). However, the procedural failure rate and the parent artery stenosis were more frequently in PED group compared with coiling group (both were 16.7 vs. 0.0%; P = 0.040). Conclusions: Endovascular retreatment for recurrent aneurysms after initial endovascular treatment might be safe and effective. Flow diverters might be associated with reduced risk of recanalization and an increased risk of procedural failure and mild parent artery stenosis.

20.
BMC Musculoskelet Disord ; 22(1): 573, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162362

RESUMO

BACKGROUND: Post-traumatic tibial osteomyelitis is considered as complex clinical problem due to its unique characteristics such as prolonged course, multi-staged treatment and high recurrence rate. The purpose of this study is to identify and analyze the causes and risk factors associated with infection recurrence of tibial osteomyelitis treated with Ilizarov technique. METHODS: From January 2011 to January 2019, a total of 149 patients with post-traumatic tibial osteomyelitis treated with Ilizarov bone transport technique were included in this study. Demographic and clinical data were collected and analyzed. Univariate analysis and logistic regression analysis were used to analyze the factors that may affect the recurrence or reinfection of post-traumatic tibial osteomyelitis after treated with Ilizarov bone transport technique. RESULTS: All included patients were successfully followed up with an average of 37.5 month (18-78 month), among them, 17 patients (11.4%) occurred with recurrence or reinfection of tibial osteomyelitis in which 2 cases were in distraction area and 15 cases in docking site. Among them, 5 patients were treated successfully with appropriate intravenous antibiotic, the remaining 12 patients were intervened by surgical debridement or bone grafting after debridement. Univariate analysis showed that Pseudomonas aeruginosa infection, bone exposure, number of previous operations (> 3 times), blood transfusion during bone transport surgery, course of osteomyelitis > 3 months, diabetes was associated with recurrence or reinfection of postoperative tibial osteomyelitis. According to the results of logistic regression analysis, Pseudomonas aeruginosa infection, bone exposure, and the number of previous operations (> 3 times) are risk factors for recurrence or reinfection of posttraumatic tibial osteomyelitis treated with Ilizarov bone transport technique, with odds ratios (OR) of 6.055, 7.413, and 1.753, respectively. CONCLUSION: The number of previous operations (> 3 times), bone exposure, and Pseudomonas aeruginosa infection are risk factors for infection recurrence of posttraumatic tibial osteomyelitis treated with Ilizarov bone transport technique.


Assuntos
Técnica de Ilizarov , Osteomielite , Fraturas da Tíbia , Humanos , Osteomielite/epidemiologia , Osteomielite/etiologia , Osteomielite/cirurgia , Estudos Retrospectivos , Fatores de Risco , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Fraturas da Tíbia/complicações , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
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