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1.
Artigo em Inglês | MEDLINE | ID: mdl-34855366

RESUMO

Despite the unique ability of lanthanide-doped upconversion nanoparticles (UCNPs) to convert near-infrared (NIR) light to high-energy UV-vis radiation, low quantum efficiency has rendered their application unpractical in biomedical fields. Here, we report anatase titania-coated plasmonic gold nanorods decorated with UCNPs (Au NR@aTiO2@UCNPs) for combinational photothermal and photodynamic therapy to treat cancer. Our novel architecture employs the incorporation of an anatase titanium dioxide (aTiO2) photosensitizer as a spacer and exploits the localized surface plasmon resonance (LSPR) properties of the Au core. The LSPR-derived near-field enhancement induces a threefold boost of upconversion emissions, which are re-absorbed by neighboring aTiO2 and Au nanocomponents. Photocatalytic experiments strongly infer that LSPR-induced hot electrons are injected into the conduction band of aTiO2, generating reactive oxygen species. As phototherapeutic agents, our hybrid nanostructures show remarkable in vitro anticancer effect under NIR light [28.0% cancer cell viability against Au NR@aTiO2 (77.3%) and UCNP@aTiO2 (98.8%)] ascribed to the efficient radical formation and LSPR-induced heat generation, with cancer cell death primarily following an apoptotic pathway. In vivo animal studies further confirm the tumor suppression ability of Au NR@aTiO2@UCNPs through combinatorial photothermal and photodynamic effect. Our hybrid nanomaterials emerge as excellent multifunctional phototherapy agents, providing a valuable addition to light-triggered cancer treatments in deep tissue.

2.
Math Biosci Eng ; 18(6): 9148-9162, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34814340

RESUMO

Estimating the binding affinity between proteins and drugs is very important in the application of structure-based drug design. Currently, applying machine learning to build the protein-ligand binding affinity prediction model, which is helpful to improve the performance of classical scoring functions, has attracted many scientists' attention. In this paper, we have developed an affinity prediction model called GAT-Score based on graph attention network (GAT). The protein-ligand complex is represented by a graph structure, and the atoms of protein and ligand are treated in the same manner. Two improvements are made to the original graph attention network. Firstly, a dynamic feature mechanism is designed to enable the model to deal with bond features. Secondly, a virtual super node is introduced to aggregate node-level features into graph-level features, so that the model can be used in the graph-level regression problems. PDBbind database v.2018 is used to train the model. Finally, the performance of GAT-Score was tested by the scheme $C_s$ (Core set as the test set) and CV (Cross-Validation). It has been found that our results are better than most methods from machine learning models with traditional molecular descriptors.

3.
Cancer Med ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34816622

RESUMO

BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare malignant tumor with increasing incidence. The goal of our study was to analyze the treatment outcome and prognostic factors of ASCC in South China in the past half-century. METHODS: This study retrospectively included 59 patients with ASCC admitted from 1975 to 2018 in Sun Yat-sen University cancer center. The clinical records and follow-up information of all patients were collected. Survival analysis and univariate and multivariate regression analyses were performed using the "survival" and "survminer" packages of R software. RESULTS: In 59 patients, 5 patients had distant metastasis at diagnosis. Among 54 M0 stage patients, 33 patients received chemoradiotherapy (CRT), 19 patients received local surgery, and 2 patients refused curative treatment and received the best supportive treatment (BST). The most common grade 3-4 acute toxicities during treatment were myelosuppression and radiation dermatitis. The median follow-up time was 32 months. For the whole group, the 3-year and 5-year overall survival (OS) rates and disease-free survival (DFS) were 71.1% and 63.6%, and 73.4% and 69.0%, respectively. Multivariate regression analysis showed that the T3-4 stage was an independent prognostic risk factor for OS, progression-free survival (PFS), and DFS. And M1 was an independent prognostic risk factor for PFS and DFS. Patients in stage M0 mainly treated with CRT had better local control than those mainly treated with surgery (p = 0.027). For M0 patients, induction chemotherapy combined with CRT tends to prolong OS compared with CRT alone (p = 0.26). The 3-year colostomy-free survival for the whole group was 81.1%. CONCLUSIONS: CRT is recommended as the first choice for the treatment of M0 stage ASCC. Induction chemotherapy may bring better survival benefits for some patients. Patients with ASCC in China seem to have a better local control rate, which suggested different treatment strategies may be needed in China.

4.
World J Clin Cases ; 9(28): 8504-8508, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754860

RESUMO

BACKGROUND: Congenital coronary artery fistula can lead to symptoms of chest tightness, chest pain, or exertional dyspnea, which is a congenital vascular malformation that should not be ignored. Patients who have such malformations are frequently observed with different concurrent abnormal anatomic structures. Collateral circulation may have a positive effect on improving the patients' symptoms. CASE SUMMARY: A 53-year-old female experienced episodic chest discomfort for the past month with symptoms manifesting when she was agitated or overexerted. After a positive treadmill test, the patient underwent coronary angiography. "Ghostlike" intermittent appearance of coronary ventricular fistula and collateral branching were observed. The patient was diagnosed with a right coronary ventricular fistula and collateral circulation. CONCLUSION: This case shows the likelihood of collateral circulation in patients with coronary artery fistula. This may provide medical staff with novel solutions to treat insufficiency of myocardial blood supply induced by cardiovascular malformations.

5.
World J Clin Cases ; 9(28): 8545-8551, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754866

RESUMO

BACKGROUND: Lumbar facet joint syndrome (LFJS) is a pain condition arising from lumbar facet joint diseases. Treatments of LFJS includes patient education, oral medication, bed rest, physical therapy, and procedural interventions. For some refractory cases that fail conservative therapies, dorsal ramus medial brunch radiofrequency ablation is warranted. However, as nerve fibers can regenerate, their efficacy is impermanent, and the recurrence rate is relatively high. Considering synovial impingement is a paramount pathogenesis of LFJS, in this case, we removed the culprit hyperplastic articular capsule and the articular process partially through a spinal endoscope. As the culprit hyperplastic joint capsule was excised, it is supposed to generate more prolonged efficacy and a lower recurrence rate than radiofrequency treatment. CASE SUMMARY: A 40-year-old female patient was diagnosed with LFJS. She complained of low back pain and right buttock pain for half a year. The patient was placed in the prone position. After disinfection and draping, a 25-cm 18-gauge needle was inserted into the dorsal surface of the right L5 articular process. Subsequently, a guidewire, dilating tubes, and a working cannula was inserted successively. The spinal endoscope was positioned in the working cannula. Under the endoscope, the microvascular tissue, muscle tissue attached on the L5 inferior articular process and S1 superior articular process, as well as the capsule and minor portion of the inferior articular process were removed. After the joint space was clear and no bleeding points existed, the endoscope and working cannula were shifted, and the incision was sutured. After treatment, the symptoms were completely relieved. The patient was pain-free during the follow-up period of 6 mo. CONCLUSION: The endoscopic partial joint capsule and articular process excision is an effective procedure for LFJS, especially for cases caused by synovial impingement.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34804183

RESUMO

Objective: To identify the biological function and metabolic pathway of differential metabolites in follicular fluid of senile patients with kidney qi deficiency undergoing in vitro fertilization-embryo transfer (IVF-ET) and observe the effect of kidney-invigorating herbs on IVF outcomes in senile patients. Methods: A total of 95 women undergoing IVF treatment were recruited and divided into three groups, including 34 cases in the treatment group (the senile patients with kidney qi deficiency after the intervention of Chinese medicine), 31 cases in the experiment group (the senile patients with kidney qi deficiency of no intervention of Chinese medicine), and 30 cases in the control group (young women with infertility due to male factor). The three groups of women were treated with long protocol ovarian hyperstimulation; the treatment group was given Qi-Zi-Yu-Si decoction on the day of HCG downregulation. Their IVF clinical outcomes were observed. The metabolites changes of kidney qi deficiency syndrome were analyzed in follicular fluid metabolomics using liquid chromatography-mass spectrometry (UPLC-MS/MS). Results: The syndrome score of kidney qi deficiency syndrome in the treatment group was significantly improved after treatment (P < 0.01). Compared with the experiment group, the available embryo rate and implantation rate were increased, and the difference was statistically significant (P < 0.05). Progesterone, indoleacrylic acid, 2-propenyl 1-(1-propenylsulfinyl) propyl disulfide, N-acetyltryptophan, decanoylcarnitine, 20a-dihydroprogesterone, testosterone acetate, eicosatrienoic acid, 1H-indole-3-carboxaldehyde, choline, phosphorylcholine, and tryptophan were downregulated in the treatment group. Through pathway analysis, glycerophospholipid metabolism and steroid hormone biosynthesis were regulated in senile patients with kidney qi deficiency after Qi-Zi-Yu-Si decoction intervention. Conclusion: Qi-Zi-Yu-Si decoction can effectively improve the IVF outcome and clinical symptoms of senile patients. Follicular fluid metabolites were significantly changed in senile infertile women with kidney qi deficiency, and the mechanism by which kidney-invigorating herbs improve IVF treatment outcomes may be related to glycerophospholipid metabolism and steroid hormone biosynthesis. This study was registered in the Chinese Clinical Trials Registry Platform (ChiCTR1800014422).

7.
Int J Cardiol ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34838680

RESUMO

BACKGROUND: Previous studies have shown that optimal blood pressure (BP) control is necessary to outcomes in patients with acute myocardial infarction (AMI). Acute left ventricular MI is a prevalent type of AMI with poor prognosis. We aimed to analyze the associations between BP control in the first 7 days of hospitalization and long-term mortality specific to patients with isolated left ventricular MI. METHODS: A total of 3108 acute left ventricular MI patients were included in this analysis. The average BP on the first seven days of hospitalization was categorized into 10-mmHg increments. The primary and secondary outcomes were all-cause death and cardiac death, respectively. Cox models were used to assess the association of outcomes with BP during hospitalization. RESULTS: The median length-of-stay was 7 (IQR 6-10) days. The relationship between systolic BP (SBP) or diastolic BP (DBP) followed a U-shaped curve association with outcomes. All-cause mortality was higher in patients with lower SBP (≤90 mmHg) (adjusted hazard ratios (HRs) 7.12, 95% confidence interval (CI) 3.13-16.19; p < 0.001) and DBP (<60 mmHg) (HR 1.76, 95% CI 1.14-2.71; p = 0.011) [reference: 110 < SBP ≤120 mmHg; 70 < DBP ≤ 80 mmHg], respectively. Furthermore, primary outcome was higher in patients with higher SBP (>130 mmHg) (HR 1.51, 95% CI 1.12-2.03; p = 0.007) and DBP (>80 mmHg) (HR 1.61, 95% CI 1.20-2.18; p = 0.002), respectively. CONCLUSION: Maintaining a SBP from 90 to 130 mmHg and a DBP from 60 to 80 mmHg may be beneficial to patients with acute left ventricular MI in the long run.

8.
Tzu Chi Med J ; 33(4): 345-349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760629

RESUMO

Underactive bladder (UAB) is a symptom complex suggestive of detrusor underactivity (DU). Although it implies a primary dysfunction of the detrusor muscle, many other conditions such as advanced age, neurogenic factors, and bladder outlet obstruction also lead to UAB. The current understanding of the pathophysiology directly leading to UAB is limited. We believe that by identifying the morphological changes associated with UAB might shed light on this. Therefore, we searched literature with keywords of electron microscopy, ultrastructure, UAB, and DU to review current ultrastructural evidence concerning UAB.

9.
Tzu Chi Med J ; 33(4): 419-420, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760641
10.
Adv Sci (Weinh) ; : e2103910, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784102

RESUMO

Lithium-sulfur (Li-S) battery is identified as one of the most promising next-generation energy storage systems due to its ultra-high theoretical energy density up to 2600 Wh kg-1 . However, Li metal anode suffers from dramatic volume change during cycling, continuous corrosion by polysulfide electrolyte, and dendrite formation, rendering limited cycling lifespan. Considering Li metal anode as a double-edged sword that contributes to ultrahigh energy density as well as limited cycling lifespan, it is necessary to evaluate Li-based alloy as anode materials to substitute Li metal for high-performance Li-S batteries. In this contribution, the authors systematically evaluate the potential and feasibility of using Li metal or Li-based alloys to construct Li-S batteries with an actual energy density of 500 Wh kg-1 . A quantitative analysis method is proposed by evaluating the required amount of electrolyte for a targeted energy density. Based on a three-level (ideal material level, practical electrode level, and pouch cell level) analysis, highly lithiated lithium-magnesium (Li-Mg) alloy is capable to achieve 500 Wh kg-1 Li-S batteries besides Li metal. Accordingly, research on Li-Mg and other Li-based alloys are reviewed to inspire a promising pathway to realize high-energy-density and long-cycling Li-S batteries.

11.
PLoS One ; 16(11): e0259798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34780519

RESUMO

Protein posttranslational modifications (PTMs) regulate the biological processes of human diseases by genetic code expansion and cellular pathophysiology regulation; however, system-wide changes in PTM levels in the intracerebral hemorrhage (ICH) brain remain poorly understood. Succinylation refers to a major PTM during the regulation of multiple biological processes. In this study, according to the methods of quantitative succinyllysine proteomics based on high-resolution mass spectrometry, we investigated ICH-associated brain protein succinyllysine modifications and obtained 3,680 succinylated sites and quantified around 3,530 sites. Among them, 25 succinyllysine sites on 23 proteins were upregulated (hypersuccinylated), whereas 13 succinyllysine sites on 12 proteins were downregulated (hyposuccinylated) following ICH. The cell component enrichment analysis of these succinylproteins with significant changes showed that 58.3% of the hyposuccinylated proteins were observed in the mitochondria, while the hyper-succinylproteins located in mitochondria decreased in the percentage to about 35% in ICH brains with a concomitant increase in the percentage of cytoplasm to 30.4%. Further bioinformatic analysis showed that the succinylproteins were mostly mitochondria and synapse-related subcellular located and involved in many pathophysiological processes, like metabolism, synapse working, and ferroptosis. Moreover, the integrative analysis of our succinylproteomics data and previously published transcriptome data showed that the mRNAs matched by most differentially succinylated proteins were especially highly expressed in neurons, endothelial cells, and astrocytes. Our study uncovers some succinylation-affected processes and pathways in response to ICH brains and gives us novel insights into understanding pathophysiological processes of brain injury caused by ICH.

12.
J Mol Med (Berl) ; 99(12): 1797-1813, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34628513

RESUMO

Spinal muscular atrophy (SMA), a degenerative motor neuron disease and a leading cause of infant mortality, is caused by loss of functional survival motor neuron (SMN) protein due to SMN1 gene mutation. Here, using mouse and cell models for behavioral and histological studies, we found that SENP2 (SUMO/sentrin-specific protease 2)-deficient mice developed a notable SMA-like pathology phenotype with significantly decreased muscle fibers and motor neurons. At the molecular level, SENP2 deficiency in mice did not affect transcription but decreased SMN protein levels by promoting the SUMOylation of SMN. SMN was modified by SUMO2 with the E3 PIAS2α and deconjugated by SENP2. SUMOylation of SMN accelerated its degradation by the ubiquitin-proteasome degradation pathway with the ubiquitin E1 UBA1 (ubiquitin-like modifier activating enzyme 1) and E3 ITCH. SUMOylation of SMN increased its acetylation to inhibit the formation of Cajal bodies (CBs). These results showed that SENP2 deficiency induced hyper-SUMOylation of the SMN protein, which further affected the stability and functions of the SMN protein, eventually leading to the SMA-like phenotype. Thus, we uncovered the important roles for hyper-SUMOylation of SMN induced by SENP2 deficiency in motor neurons and provided a novel targeted therapeutic strategy for SMA. KEY MESSAGES: SENP2 deficiency enhanced the hyper-SUMOylation of SMN and promoted the degradation of SMN by the ubiquitin-proteasome pathway. SUMOylation increased the acetylation of SMN to inhibit CB formation. SENP2 deficiency caused hyper-SUMOylation of SMN protein, which further affected the stability and functions of SMN protein and eventually led to the occurrence of SMA-like pathology.

13.
Anticancer Res ; 41(10): 4761-4769, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593425

RESUMO

BACKGROUND/AIM: The early stage of atherosclerosis (AS) demonstrates a lipid-driven inflammatory cytokine increase. In the present study, we aimed to use ultrasound-targeted microbubble delivery (UTMD) therapy with the Endostar-loaded target microbubbles (MBs) to reduce AS-related inflammatory response. MATERIALS AND METHODS: Normal and lipopolysaccharide (LPS) induced human umbilical vein endothelial cells (HUVECs) were placed in a parallel-plate flow chamber. MBs were perfused through the parallel-plate flow chamber to mimic physiological blood flow. Five groups were set up: G1: Negative control (normal HUVECs); G2: LPS control (LPS induced HUVECs); G3: ICAM-1-loaded-MBs (MBi); G4: Endostar-loaded-MBs (MBe) and G5: Endostar-ICAM-1-loaded-MBs (MBei). mRNA expression of inflammatory factors and release of inflammatory cytokines were detected by RT-PCR and ELISA, respectively. RESULTS: After treatment with MBei, the mRNA expression of cell adhesion molecule-1 (CD31) (p=0.004), endothelin-1 (ET-1) (p=0.010), von willebrand factor (vWF) (p=0.018), extracellular regulated protein kinases (ERK) (p=0.046) and nuclear factor kappa B (NF-κB) (p=0.003) were significantly reduced compared to LPS-induced HUVECs. Release of inflammatory cytokines including tissue factor (TF) (p=0.033), tissue factor pathway inhibitor (TF-PI) (p=0.019), ET-1 (p=0.014), vWF (p=0.030) and blood-coagulation factor VIIα (FVIIα) (p=0.000) were also significantly reduced compared to LPS-induced HUVECs. CONCLUSION: UTMD therapy can inhibit the inflammatory response by reducing atherosclerotic-related inflammatory factors, suggesting a potential treatment at the early-stage of AS.


Assuntos
Anti-Inflamatórios/farmacologia , Fibrinolíticos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Microbolhas , Anti-Inflamatórios/química , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/terapia , Adesão Celular , Endostatinas/química , Endostatinas/farmacologia , Fibrinolíticos/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/toxicidade , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Ultrassom
14.
Biomaterials ; 278: 121140, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34634661

RESUMO

The in vivo fate of nanoformulated drugs is governed by the physicochemical properties of the drug and the functionality of nanocarriers. Nanoformulations such as polymeric micelles, which physically encapsulate poorly soluble drugs, release their payload into the bloodstream during systemic circulation. This results in three distinct fractions of the drug-nanomedicine: encapsulated, protein-bound, and free drug. Having a thorough understanding of the pharmacokinetic (PK) profiles of each fraction is essential to elucidate mechanisms of nanomedicine-driven changes in drug exposure and PK/PD relationships pharmacodynamic activity. Here, we present a comprehensive preclinical assessment of the poly (2-oxazoline)-based polymeric micelle of paclitaxel (PTX) (POXOL hl-PM), including bioequivalence comparison to the clinically approved paclitaxel nanomedicine, Abraxane®. Physicochemical characterization and toxicity analysis of POXOL hl-PM was conducted using standardized protocols by the Nanotechnology Characterization Laboratory (NCL). The bioequivalence of POXOL hl-PM to Abraxane® was evaluated in rats and rhesus macaques using the NCL's established stable isotope tracer ultrafiltration assay (SITUA) to delineate the plasma PK of each PTX fraction. The SITUA study revealed that POXOL hl-PM and Abraxane® had comparable PK profiles not only for total PTX but also for the distinct drug fractions, suggesting bioequivalence in given animal models. The comprehensive preclinical evaluation of POXOL hl-PM in this study showcases a series of widely applicable standardized studies by NCL for assessing nanoformulations prior to clinical investigation.


Assuntos
Antineoplásicos Fitogênicos , Paclitaxel , Paclitaxel Ligado a Albumina , Animais , Linhagem Celular Tumoral , Portadores de Fármacos , Isótopos , Macaca mulatta , Micelas , Ratos , Roedores , Equivalência Terapêutica
15.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638970

RESUMO

Cardiovascular disease (CVD) is a common disease caused by many factors, including atherosclerosis, congenital heart disease, heart failure, and ischemic cardiomyopathy. CVD has been regarded as one of the most common diseases and has a severe impact on the life quality of patients. The main features of CVD include high morbidity and mortality, which seriously threaten human health. SUMO proteins covalently conjugate lysine residues with a large number of substrate proteins, and SUMOylation regulates the function of target proteins and participates in cellular activities. Under certain pathological conditions, SUMOylation of proteins related to cardiovascular development and function are greatly changed. Numerous studies have suggested that SUMOylation of substrates plays critical roles in normal cardiovascular development and function. We reviewed the research progress of SUMOylation in cardiovascular development and function, and the regulation of protein SUMOylation may be applied as a potential therapeutic strategy for CVD treatment.


Assuntos
Doenças Cardiovasculares/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Sumoilação , Animais , Doenças Cardiovasculares/tratamento farmacológico , Cisteína Endopeptidases/metabolismo , Coração/embriologia , Humanos , Lisina/metabolismo , Terapia de Alvo Molecular/métodos , Organogênese , Transdução de Sinais/efeitos dos fármacos , Sumoilação/efeitos dos fármacos , Enzimas de Conjugação de Ubiquitina/metabolismo
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(4): 529-536, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34704414

RESUMO

: To establish a high performance liquid chromatography method to simultaneously quantify eight related substances in entecavir film-coated tablets.According to USP40 and YBH33292005 standards, a high performance liquid chromatography (HPLC) method for simultaneous determination of 8 related substance in entecavir film-coated tablets was established and validated. The column was WATERS C18 (250 mm the mobile phase A was water-acetonitrile-trifluoroacetic acid (990∶10∶1), the mobile phase B was water-acetonitrile-trifluoroacetic acid (700∶300∶1) with gradient elution and ultraviolet-visible light detector, detection wavelength at 254 nm and column temperature of The resolution between entecavir and each impurity peak was more than 1.5, and each impurity had a good linear relationship with the peak area in the linear range. The limits of detection and quantification, precision, stability, durability, specificity, met the verification requirements. The HPLC method established in this study can be used for simultaneous determination of 8 related substance in entecavir film-coated tablets.


Assuntos
Guanina , Cromatografia Líquida de Alta Pressão , Guanina/análogos & derivados , Reprodutibilidade dos Testes , Comprimidos
17.
Biochemistry ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665595

RESUMO

The design of functional metalloenzymes is attractive for the biosynthesis of biologically important compounds, such as phenoxazinones and phenazines catalyzed by native phenoxazinone synthase (PHS). To design functional heme enzymes, we used myoglobin (Mb) as a model protein and introduced an artificial CXXC motif into the heme distal pocket by F46C and L49C mutations, which forms a de novo disulfide bond, as confirmed by the X-ray crystal structure. We further introduced a catalytic Tyr43 into the heme distal pocket and found that the F43Y/F46C/L49C Mb triple mutant and the previously designed F43Y/F46S Mb exhibit PHS-like activity (80-98% yields in 5-15 min), with the catalytic efficiency exceeding those of natural metalloenzymes, including o-aminophenol oxidase, laccase, and dye-decolorizing peroxidase. Moreover, we showed that the oxidative coupling product of 1,6-disulfonic-2,7-diaminophenazine is a potential pH indicator, with the orange-magenta color change at pH 4-5 (pKa = 4.40). Therefore, this study indicates that functional heme enzymes can be rationally designed by structural modifications of Mb, exhibiting the functionality of the native PHS for green biosynthesis.

18.
Brain Sci ; 11(10)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34679394

RESUMO

Mind-wandering (MW) is a common phenomenon, defined as task-unrelated thoughts. This study is based on event-related potentials (ERPs), using modified sustained attention to response task (modified SART, mSART) to discuss the neural patterns of different types of MW. In the current study, we defined the MW realized by participants as self-caught MW, and the MW measurement acquired by probes as probe-caught MW. The behavioral results showed that the reaction times (RTs) during self-caught MW were greater than those during non-self-caught MW. The ERP results showed that during self-caught MW, the mean amplitudes of N1 decreased significantly, indicating that the participants' attention had deviated from the current task. The increase in the mean amplitudes of P2 during self-caught MW indicated lower vigilance. We also found that the mean amplitudes of N300 reduced during self-caught MW, which indicated that cognitive control or monitoring might be affected by self-caught MW. The average amplitudes of P300 were significantly lower during probe-caught MW than during on-task, indicating the impact on high-level cognitive processing. In addition, the amplitudes of N1, P2, and N300 in anterior regions were greater than those in posterior regions. P300 amplitudes during probe-caught MW in the right hemisphere were greater than those of the left hemisphere. In summary, our research results demonstrated that alertness and cognitive processing decreased during both self-caught MW and probe-caught MW. ERPs were statistically different under the conditions of self-caught MW and probe-caught MW. The current study provided new insights into the relationship between MW and neural markers. It was the first study exploring the ERP correlates between self-caught MW and probe-caught MW based on mSART.

19.
Biomedicines ; 9(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34680422

RESUMO

This study aimed to evaluate the clinical significance of urinary bladder wall thickening on computed tomography (CT) among patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Patients with IC/BPS were prospectively enrolled and classified into three groups according to bladder CT finding: smooth bladder wall, focal bladder thickening, and diffuse bladder thickening. Among the 100 patients with IC/BPS, 49, 36, and 15 had smooth bladder wall, focal bladder thickening, and diffuse bladder thickening on CT, respectively. Patients with Hunner's lesion showed a higher proportion of diffuse and focal bladder thickening compared to those without the same (p < 0.001). Patients with diffuse bladder thickening displayed smaller first sensation of filling, cystometric bladder capacity, and voided volume compared to the rest (all p < 0.001). Patients with focal and diffuse thickening had a higher proportion of inflammatory cell infiltration, uroepithelial cell denudation, and granulation tissue compared to those with smooth bladder wall (p = 0.045, 0.002, and 0.005, respectively). Bladder wall thickening on CT was correlated with clinical phenotypes of IC/BPS, including histopathological findings. Focal or diffuse bladder wall thickening on CT might indicate the presence of chronic bladder wall inflammation and fibrosis and could be used to differentiate bladder-centered IC/BPS.

20.
Front Oncol ; 11: 731460, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671556

RESUMO

Purpose: This study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy. Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches. Results: Among the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p <0.001). Conclusions: Minimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further prospective studies are needed to validate our findings.

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