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1.
Tissue Cell ; 89: 102414, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38865824

RESUMO

Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan Tongluo Qiangjing recipe (SGTL) on sperm DNA damage and oxidative stress in experimental VC (EVC) rats. EVC model was established by partial ligation of left renal vein. Spermatic vein diameter, testicular weight, sperm DNA fragmentation index (DFI) were evaluated. Telomere reverse transcriptase (TERT) expression, telomere gene transcription, and testicular tissue morphology were determined·H2O2, catalase, SOD, T-AOC were measured with colorimetry. SGTL significantly decreased spermatic vein diameter (P=0.000) and increased testicular weight (P=0.013) of rats compared those of EVC rats. SGTL maintained testicular tissue morphology in EVC rats. SGTL markedly reduced sperm DFI value in sperm of rats compared to EVC rats (P=0.000). SGTL significantly enhanced TERT expression and telomere gene transcription (P=0.028) in testis of rats compared to EVC rats. SGTL reduced H2O2 levels (P=0.001) and promoted CAT activity (P=0.016), SOD activity (P=0.049), and T-AOC activity (P=0.047) of rats, compared to EVC rats. In conclusion, SGTL could reduce pathogenic process of EVC by reducing sperm DNA damage and regulating telomere length in EVC rats, which may be related to oxidative stress regulation.

2.
bioRxiv ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38895209

RESUMO

Alzheimer's disease (AD) has a prolonged latent phase. Sensitive biomarkers of amyloid beta ( A ß ), in the absence of clinical symptoms, offer opportunities for early detection and identification of patients at risk. Current A ß biomarkers, such as CSF and PET biomarkers, are effective but face practical limitations due to high cost and limited availability. Recent blood plasma biomarkers, though accessible, still incur high costs and lack physiological significance in the Alzheimer's process. This study explores the potential of brain functional connectivity (FC) alterations associated with AD pathology as a non-invasive avenue for A ß detection. While current stationary FC measurements lack sensitivity at the single-subject level, our investigation focuses on dynamic FC using resting-state functional MRI (rs-fMRI) and introduces the Generalized Auto-Regressive Conditional Heteroscedastic Dynamic Conditional Correlation (DCC-GARCH) model. Our findings demonstrate the superior sensitivity of DCC-GARCH to CSF A ß status, and offer key insights into dynamic functional connectivity analysis in AD.

3.
Int J Pharm ; 659: 124261, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38782155

RESUMO

The progression of renal fibrosis to end-stage renal disease (ESRD) is significantly influenced by transforming growth factor-beta (TGF-beta) signal pathway. This study aimed to develop nanoparticles (PMVs@PLGA complexes) with platelet membrane camouflage, which can transport interfering RNA to target and regulate the TGF-ß1 pathway in damaged renal tissues. The aim is to reduce the severity of acute kidney injury and to reduce fibrosis in chronic kidney disease. Hence, we formulated PMVs@TGF-ß1-siRNA NP complexes and employed them for both in vitro and in vivo therapy. From the experimental findings we know that the PMVs@siRNA NPs could effectively target the kidneys in unilateral ureteral obstruction (UUO) mice and ischemia/reperfusion injury (I/R) mice. In animal models of treatment, PMVs@siRNA NP complexes effectively decreased the expression of TGF-ß1 and mitigated inflammation and fibrosis in the kidneys by blocking the TGF-ß1/Smad3 pathway. Therefore, these PMVs@siRNA NP complexes can serve as a promising biological delivery system for treating kidney diseases.


Assuntos
Fibrose , Nanopartículas , RNA Interferente Pequeno , Fator de Crescimento Transformador beta1 , Animais , RNA Interferente Pequeno/administração & dosagem , Fator de Crescimento Transformador beta1/metabolismo , Masculino , Camundongos , Plaquetas/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Rim/metabolismo , Rim/patologia , Rim/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Obstrução Ureteral/terapia , Materiais Biomiméticos/administração & dosagem , Materiais Biomiméticos/química , Inflamação/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Proteína Smad3/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Injúria Renal Aguda/prevenção & controle
4.
Int Immunopharmacol ; 134: 112169, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728879

RESUMO

GUANKE is a Lactobacillus plantarum isolated from the feces of healthy volunteer. We have previously shown that GUANKE enhances the efficacy of the SARS-CoV-2 vaccine and prolongs the duration of vaccine protection by upregulating the IFN pathway and T and B lymphocyte functions of the host. The purpose of this study was to evaluate the protective effects and mechanism of oral administration of Lactobacillus plantarum GUANKE in the influenza (A virus A/Puerto Rico/8/34) infection mouse model. In our experiment, oral administration of GUANKE significantly decreased viral load and increased tight junction proteins expression in lung tissues of influenza-infected mice. After GUANKE was co-cultured with mBMDCs in vitro, mBMDCs' maturity and antiviral ability were enhanced, and matured mBMDCs induced polarization of naïve CD4+ T cells into T helper (Th) 1 cells. Adoptive transfer of GUANKE-treated mBMDCs could protect mice from influenza infections. This study suggests that oral administration of Lactobacillus plantarum GUANKE could provide protection against influenza infection in mice, and this protective effect may be mediated, at least in part, by dendritic cells.


Assuntos
Células Dendríticas , Lactobacillus plantarum , Infecções por Orthomyxoviridae , Animais , Lactobacillus plantarum/imunologia , Células Dendríticas/imunologia , Infecções por Orthomyxoviridae/imunologia , Camundongos , Probióticos/administração & dosagem , Feminino , Camundongos Endogâmicos C57BL , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Administração Oral , Carga Viral , Pulmão/imunologia , Pulmão/virologia , Pulmão/microbiologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , SARS-CoV-2/imunologia , Vírus da Influenza A/imunologia
5.
Neurospine ; 21(1): 273-285, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38317559

RESUMO

OBJECTIVE: This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. METHODS: Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. RESULTS: In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4-5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. CONCLUSION: In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.

6.
Math Biosci Eng ; 20(10): 17886-17904, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-38052541

RESUMO

In tobacco production, cigarettes with appearance defects are inevitable and dramatically impact the quality of tobacco products. Currently, available methods do not balance the tension between detection accuracy and speed. To achieve accurate detection on a cigarette production line with the rate of 200 cigarettes per second, we propose a defect detection model for cigarette appearance based on YOLOv5n (You Only Look Once Version 5 Nano), called CJS-YOLOv5n (YOLOv5n with C2F (Cross Stage Partial (CSP) Bottleneck with 2 convolutions-fast), Jump Concat, and SCYLLA-IoU (SIoU)). This model incorporates the C2F module proposed in the state-of-the-art object detection network YOLOv8 (You Only Look Once Version 8). This module optimizes the network by parallelizing additional gradient flow branches, enhancing the model's feature extraction capability and obtaining richer gradient information. Furthermore, this model uses Jump Concat to preserve minor defect feature information during the fusion process in the feature fusion pyramid's P4 layer. Additionally, this model integrates the SIoU localization loss function to improve localization accuracy and detection precision. Experimental results demonstrate that our proposed CJS-YOLOv5n model achieves superior overall performance. It maintains a detection speed of over 500 FPS (frames per second) while increasing the recall rate by 2.3% and mAP (mean average precision)@0.5 by 1.7%. The proposed model is suitable for application in high-speed cigarette production lines.

7.
BMC Oral Health ; 23(1): 484, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452322

RESUMO

BACKGROUND: This study investigated a potential prognostic model based on telomere-related genes (TRGs) for the clinical prediction of oral squamous cell carcinoma (OSCC). METHODS: Gene expression data and associated clinical phenotypes were obtained from online databases. Differentially expressed (DE)-TRGs were identified between OSCC and normal samples, followed by protein-protein interaction and enrichment analyses. Subsequently, the prognostic genes explored based on the DE-TRGs and survival data were applied in the establishment of the current prognostic model, and an integrated analysis was performed between high- and low-risk groups using a prognostic model. The expression of certain prognostic genes identified in the present study was validated using qPCR analysis and/or western blot in OSCC cell lines and clinical samples. RESULTS: 169 DE-TRGs were identified between the OSCC samples and controls. DE-TRGs are mainly involved in functions such as hypoxia response and pathways such as the cell cycle. Eight TRGs (CCNB1, PDK4, PLOD2, RACGAP1, MET, PLK1, KPNA2, and CCNA2) associated with OSCC survival and prognosis were used to construct a prognostic model. qPCR analysis and western blot showed that most of the eight prognostic genes were consistent with the current bioinformatics results. Analysis of the high- and low-risk groups for OSCC determined by the prognostic model showed that the current prognostic model was reliable. CONCLUSIONS: A novel prognostic model for OSCC was constructed by TRGs. PLOD2 and APLK1 may participate in the progression of OSCC via responses to hypoxia and cell cycle pathways, respectively. TRGs, including KPNA2 and CCNA2, may serve as novel prognostic biomarkers for OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Prognóstico , Biomarcadores Tumorais/genética , Neoplasias de Cabeça e Pescoço/genética , Regulação Neoplásica da Expressão Gênica/genética
8.
J Phys Chem B ; 127(28): 6354-6373, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37413969

RESUMO

Environmental regulatory agencies have implemented stringent restrictions on the permissible levels of sulfur compounds in fuel to reduce harmful emissions and improve air quality. Problematically, traditional desulfurization methods have shown low effectiveness in the removal of refractory sulfur compounds, e.g., thiophene (TS), dibenzothiophene (DBT), and 4-methyldibenzothiophene (MDBT). In this work, molecular dynamics (MD) simulations and free energy perturbation (FEP) have been applied to investigate the use of ionic liquids (ILs) and deep eutectic solvents (DESs) as efficient TS/DBT/MDBT extractants. For the IL simulations, the selected cation was 1-butyl-3-methylimidazolium [BMIM] and the anions included chloride [Cl], thiocyanate [SCN], tetrafluoroborate [BF4], hexafluorophosphate [PF6], and bis(trifluoromethylsulfonyl)amide [NTf2]. The DESs were composed of choline chloride with ethylene glycol (CCEtg) or with glycerol (CCGly). Calculation of excess chemical potentials predicted the ILs to be more promising extractants with energies lower by 1-3 kcal/mol compared to DESs. Increasing IL anion size was positively correlated to enhanced solvation of S-compounds, which was influenced by energetically dominant solute-anion interactions and favorable solute-[BMIM] π-π stacking. For the DESs, the solvent components offered a range of synergistic, yet comparatively weaker, electrostatic interactions that included hydrogen bonding and cation-π interactions. An in-depth analysis of the structure of IL and DES systems is presented, along with a discussion of the critical factors behind experimental trends of S-compound extraction efficiency.

9.
World J Clin Cases ; 11(10): 2308-2314, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37122521

RESUMO

BACKGROUND: Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation (LIDH) within a few weeks. CASE SUMMARY: Computed tomography and magnetic resonance imaging (MRI) of the lumbar region of a 25-year-old male diagnosed with LIDH showed prolapse of the L5/S2 disc. The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge. The patient elected a conservative treatment regimen that included traditional Chinese medicine (TCM), acupuncture, and massage. During a follow-up period of more than 12 mo, good improvement in pain was reported without complications. MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation. CONCLUSION: A conservative treatment regimen of TCM, acupuncture, and massage promoted reabsorption of a prolapsed disc.

10.
Heliyon ; 9(3): e14222, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36938437

RESUMO

This paper aims to explore the influence mechanism of powder particle sizes on the microstructure and properties of coatings and identify the effect of powder particle size difference on the coating graphite phase. NbC-reinforced Ni-based coatings were in-situ synthesized by laser cladding to investigate the impact of powder particle sizes on the morphology, structure, and properties of coatings. The results indicate that increasing powder particle size enlarges the coating area and decreases the coating width and dilution ratio. Meanwhile, the defect ratio first increases and then decreases. The XRD test suggests that the coating mainly consists of NbC, solid solution (Fe, Ni), B4C, Cr2C, and CrB2. Different powder particle sizes do not change the phase composition of coatings but affect the graphite phase morphology. The morphology transforms from spherical to flocculent as the powder size varies from micrometer to nanometer. The hardness of coatings gradually increases, and the friction and wear properties decrease with the growth of powder particle size. The dispersed graphite phase in the nano coating plays a self-lubricating role in the friction and wear process. This research provides a reference and theoretical basis for selecting powder particle size in laser cladding.

11.
Materials (Basel) ; 16(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36837333

RESUMO

This paper aims to explore the mechanism of an ultrasonic applied field on the microstructures and properties of coatings, and clarify the evolution of the molten pool under different ultrasonic frequencies. The Taguchi experimental design method was adopted in this paper. NbC-reinforced Ni-based coatings were in situ synthesized by laser cladding to investigate the effects of ultrasonic vibration process parameters on the microstructure, pore area, microhardness, and wear resistance of the cladding layer. The results show that the pore area decreases first and then increases as ultrasonic power increases from 600 to 900 W and ultrasonic frequency from 23 to 40 kHz. On the contrary, the hardness and wear resistance increase at first and then decrease. The pore area is minimized at 800 W ultrasonic power and 32 kHz ultrasonic frequency, and the hardness is maximized at 600 W ultrasonic power and 40 kHz ultrasonic frequency. Meanwhile, the highest wear resistance can be obtained when ultrasonic power is 700 W and ultrasonic frequency is 32 kHz. Based on the phase structure analysis, the cladding layer mainly consists of FeNi3, NbC, B4C, and CrB2. Ultrasonic vibration will not change the phase composition of the layer. Combined with the varying G/R value and cooling rate, the reasons for the change in grain morphology in different areas were analyzed to reveal the evolution mechanism of the molten pool under the influence of ultrasound.

12.
Cell Tissue Res ; 392(2): 413-430, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36737519

RESUMO

Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components.


Assuntos
Neoplasias de Cabeça e Pescoço , Osteorradionecrose , Humanos , Osteorradionecrose/etiologia , Osteorradionecrose/terapia , Osteorradionecrose/patologia , Arcada Osseodentária/patologia , Neoplasias de Cabeça e Pescoço/complicações , Regeneração Óssea , Microambiente Tumoral
13.
Biochemistry ; 62(1): 85-94, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36534405

RESUMO

Bacteria have evolved to utilize alternative organosulfur sources when sulfur is limiting. The SsuE/SsuD and MsuE/MsuD enzymes expressed when sulfur sources are restricted, are responsible for providing specific bacteria with sulfur in the form of alkanesulfonates. In this study, we evaluated why two structurally and functionally similar FMNH2-dependent monooxygenase enzymes (MsuD and SsuD) are needed for the acquisition of alkanesulfonates in some bacteria. In desulfonation assays, MsuD was able to utilize the entire range of alkanesulfonates (C1-C10). However, SsuD was not able to utilize smaller alkanesulfonate substrates. Interestingly, SsuD had a similar binding affinity for methanesulfonate (MES) (15 ± 1 µM) as MsuD (12 ± 1 µM) even though SsuD was not able to catalyze the desulfonation of the MES substrate. SsuD and MsuD showed decreased proteolytic susceptibility in the presence of FMNH2 with MES and octanesulfonate (OCS). Tighter loop closure was observed for the MsuD/FMNH2 complex with MES and OCS compared to SsuD under comparable conditions. Analysis of the SsuD/FMNH2/MES structure using accelerated molecular dynamics simulations found three different conformations for MES, demonstrating the instability of the bound structure. Even when MES was bound in a similar fashion to OCS within the active site, the smaller alkane chain resulted in a shift of FMNH2 so that it was no longer in a position to catalyze the desulfonation of MES. The active site of SsuD requires a longer alkane chain to maintain the appropriate architecture for desulfonation.


Assuntos
Proteínas de Escherichia coli , Domínio Catalítico , Proteínas de Escherichia coli/química , Oxigenases de Função Mista/metabolismo , Alcanossulfonatos/química , Alcanossulfonatos/metabolismo , Enxofre
14.
Cell Chem Biol ; 30(5): 527-539.e5, 2023 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-36351431

RESUMO

Flaviviruses have posed a serious threat to human health in the past decades, and effective therapeutic drugs are lacking; thus, treatment of flavivirus infection is a great challenge. The flavivirus protease NS2B3 is an attractive target for antiviral drug screening. Here, we developed an intracellular Zika virus (ZIKV) NS2AB3 self-cleavage assay to identify inhibitors that interfere with viral polyprotein cleavage and block ZIKV/dengue virus (DENV) replication. Bortezomib was identified as the most potent inhibitor, with a half-maximal effective concentration (EC50) in the nanomolar range. We found that instead of directly inhibiting NS2B3 protease activity, bortezomib dramatically induced the ubiquitination and aggregation of NS3, leading to the attenuation of its protease activity in cells. Two E3 ligases, HRD1 and RNF126, were found to be responsible for NS3 ubiquitination. Our study identifies bortezomib as a potential drug for the treatment of ZIKV/DENV infection and reveals the central role of the ERAD pathway in the inhibition of flaviviruses by bortezomib.


Assuntos
Vírus da Dengue , Flavivirus , Infecção por Zika virus , Zika virus , Humanos , Infecção por Zika virus/tratamento farmacológico , Bortezomib/metabolismo , Degradação Associada com o Retículo Endoplasmático , Ubiquitina-Proteína Ligases/metabolismo
15.
Chinese Journal of Hematology ; (12): 832-837, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012240

RESUMO

Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.


Assuntos
Humanos , Antígenos CD19 , Antígeno de Maturação de Linfócitos B/uso terapêutico , Bilirrubina , Imunoterapia Adotiva , Fígado , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Linfócitos T
16.
Int J Ophthalmol ; 15(8): 1344-1351, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017033

RESUMO

AIM: To assess the retinal vasculature alterations in indirect traumatic optic neuropathy (ITON) patients following craniofacial trauma by optic coherence tomography angiography (OCTA). METHODS: Patients diagnosed of monocular ITON were recruited from August 2016 to May 2020. OCTA was performed using the AngioVue OCT-A system for two cube scans centered at the optic nerve head and fovea. OCTA data included thicknesses of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC), as well as proportion of capillary perfusion and data were analyzed for correlation with post-injury timepoints: within 7, 8-30, 31-90, and 91-365d. RESULTS: A total of 73 ITON patients were studied. Significant thinning of RNFL and GCC layers and attenuation of microvascular perfusion were observed in ITON eyes as compared to contralateral unaffected eyes (for most of the analyzed sectors and quadrants, P<0.05). Without respect to surgical intervention and vision recovery, the decrease in retinal layer thicknesses and microvascular perfusion was time-dependent, and most significant within three months (P<0.001). CONCLUSION: ITON presents with time-dependent thinning of retinal layers and attenuation of microvasculature, indicating possible degeneration of retinal ganglion cells due to reduced retinal blood supply.

17.
J Phys Chem B ; 126(21): 3908-3919, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35594504

RESUMO

OPLS-based force fields (FFs) have been shown to provide accurate bulk-phase properties for a wide variety of imidazolium-based ionic liquids (ILs). However, the ability of OPLS to reproduce an IL solvent structure is not as well-validated given the relative lack of high-level theoretical or experimental data available for comparison. In this study, ab initio molecular dynamics (AIMD) simulations were performed for three widely used ILs: the 1-butyl-3-methylimidazolium cation with chloride, tetrafluoroborate, or hexafluorophosphate anions, that is, [BMIM][Cl], [BMIM][BF4], and [BMIM][PF6], respectively, as a basis for further assessment of two unique IL FFs: the ±0.8 charge-scaled OPLS-2009IL FF and the OPLS-VSIL FF. The OPLS-2009IL FF employs a traditional all-atom functional form, whereas the OPLS-VSIL FF was developed using a virtual site that offloads negative charge to inside the plane of the ring with careful attention given to reproducing hydrogen bonding. Detailed comparisons between AIMD and the OPLS FFs were made based on radial distribution functions (RDFs), combined distribution functions (CDFs), and spatial distribution functions (SDFs) to examine cation-anion interactions and π+-π+ stacking between the imidazolium rings. While both FFs were able to correctly capture the general solvent structure of these popular ILs, the OPLS-VSIL FF quantitatively reproduced interaction distances more accurately. In addition, this work provides further insights into the different short- and long-range structure patterns of these popular ILs.


Assuntos
Líquidos Iônicos , Ânions/química , Cátions , Ligação de Hidrogênio , Líquidos Iônicos/química , Simulação de Dinâmica Molecular , Solventes/química
18.
Biochem Biophys Res Commun ; 601: 129-136, 2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35245742

RESUMO

COVID-19, caused by SARS-CoV-2, has been spreading worldwide for more than two years and has led to immense challenges to human health. Despite the great efforts that have been made, our understanding of SARS-CoV-2 is still limited. The viral helicase, NSP13 is an important enzyme involved in SARS-CoV-2 replication and transcription. Here we highlight the important role of the stalk domain in the enzymatic activity of NSP13. Without the stalk domain, NSP13 loses its dsRNA unwinding ability due to the lack of ATPase activity. The stalk domain of NSP13 also provides a rigid connection between the ZBD and helicase domain. We found that the tight connection between the stalk and helicase is necessary for NSP13-mediated dsRNA unwinding. When a short flexible linker was inserted between the stalk and helicase domains, the helicase activity of NSP13 was impaired, although its ATPase activity remained intact. Further study demonstrated that linker insertion between the stalk and helicase domains attenuated the RNA binding ability and affected the thermal stability of NSP13. In summary, our results suggest the crucial role of the stalk domain in NSP13 enzymatic activity and provide mechanistic insight into dsRNA unwinding by SARS-CoV-2 NSP13.


Assuntos
COVID-19/prevenção & controle , Metiltransferases/metabolismo , RNA Helicases/metabolismo , SARS-CoV-2/metabolismo , Proteínas não Estruturais Virais/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Sítios de Ligação/genética , COVID-19/virologia , Estabilidade Enzimática , Humanos , Metiltransferases/química , Metiltransferases/genética , Modelos Moleculares , Mutação , Conformação Proteica , RNA/química , RNA/genética , RNA/metabolismo , RNA Helicases/química , RNA Helicases/genética , Proteínas Recombinantes/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Temperatura , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética
19.
Molecules ; 27(6)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35335150

RESUMO

The solvent extraction, complexing ability, and basicity of tetradentate N-donor 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-1,10-phenanthroline (CyMe4-BT- Phen) and its derivatives functionalized by Br, hydroxyphenyl, nitryl were discussed and compared. It was demonstrated that four BTPhen ligands are able to selectively extract Am(lll) over Eu(lll). It was notable that the distribution ratio of 5-nitryl-CyMe4-BTPhen for Eu(lll) was suppressed under 0.02, which was much lower compared to DEu(lll) = 1 by CyMe4-BTPhen. The analysis of the effect of the substituent on the affinity to lanthanides was conducted by UV/vis and fluorescence spectroscopic titration. The stability constants of various ligands with Eu(lll) were obtained by fitting titration curve. Additionally, the basicity of various ligands was determined to be 3.1 ± 0.1, 2.3 ± 0.2, 0.9 ± 0.2, 0.5 ± 0.1 by NMR in the media of CD3OD with the addition of DClO4. The basicity of ligands follows the order of L1 > L2 > L3 > L4, indicating the tendency of protonation decreases with the electron-withdrawing ability increase.

20.
Heart Lung Circ ; 31(7): e110-e114, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35341662

RESUMO

Closure of a wide-spaced multi-hole secundum atrial septal defect (MHASD) using a single occluder is difficult to accomplish. Multiple occluder implantation has risks such as incomplete endothelialisation, device embolisation, and residual shunt. Blade or balloon septotomy enables single device occlusion; however, the aforementioned may cause a short circumferential rim with subsequent device instability. This paper describes an inter-defect septal puncture technique for single device closure of different layouts of wide-spaced MHASDs via per-atrial or percutaneous approach under exclusive transoesophageal echocardiographic guidance. This technique combined with anti-tenting puncture equally befits a small caval atrial septal defect and MHASD with a floppy aneurysmal septum.


Assuntos
Comunicação Interatrial , Dispositivo para Oclusão Septal , Cateterismo Cardíaco/métodos , Ecocardiografia Transesofagiana , Átrios do Coração , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/cirurgia , Humanos , Punções , Resultado do Tratamento
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