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1.
Brain Imaging Behav ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478055

RESUMO

Unilateral temporal lobe epilepsy (TLE) is the most common type of focal epilepsy characterized by foci in the unilateral temporal lobe grey matters of regions such as the hippocampus. However, it remains unclear how the functional features of white matter are altered in TLE. In the current study, resting-state functional magnetic resonance imaging (fMRI) was performed on 71 left TLE (LTLE) patients, 79 right TLE (RTLE) patients and 47 healthy controls (HC). Clustering analysis was used to identify fourteen white matter networks (WMN). The functional connectivity (FC) was calculated among WMNs and between WMNs and grey matter. Furthermore, the FC laterality of hemispheric WMNs was assessed. First, both patient groups showed decreased FCs among WMNs. Specifically, cerebellar white matter illustrated decreased FCs with the cerebral superficial WMNs, implying a dysfunctional interaction between the cerebellum and the cerebral cortex in TLE. Second, the FCs between WMNs and the ipsilateral hippocampus (grey matter foci) were also reduced in patient groups, which may suggest insufficient functional integration in unilateral TLE. Interestingly, RTLE showed more severe abnormalities of white matter FCs, including links to the bilateral hippocampi and temporal white matter, than LTLE. Taken together, these findings provide functional evidence of white matter abnormalities, extending the understanding of the pathological mechanism of white matter impairments in unilateral TLE.

2.
Environ Res ; 204(Pt A): 111979, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34506782

RESUMO

The response of the denitrification community to long-term antibiotic exposure requires further investigation. Here, the significantly altered denitrifying community structure and function were observed by continuous exposure to 1 mg/L sulfamethoxazole (SMZ) or chlortetracycline (CTC) for 180 d in the expanded granular sludge bed reactors. Thaurea, positively correlated with SMZ and NO3- removal efficiency (NrE), was highly enriched in the SMZ-added reactor, while, Comamons and Acinetobacter were largely inhibited. The acute inhibited and then gradual-recovered NrE (87.17-90.38 %) was observed with highly expressed narG, indicating the adaptability of Thaurea to SMZ. However, the abundance of Thaurea and Comamonas greatly decreased, while Melioribacter and Acinetobacter were largely enriched in the CTC-added reactor. CTC created more serious and continuous inhibition of NO3- reduction (NrE of 64.53-66.95 %), with lowly expressed narG. Improved NO2- reduction capacity was observed in both reactors (70.16-95.42 %) with highly expressed nirS and nosZ, revealing the adaptability of NO2- reduction populations to antibiotics.

3.
J Mol Graph Model ; 109: 108030, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34509094

RESUMO

Cell division cycle 25B (CDC25B) was responsible for regulating the various stages of cell division in the cell cycle. R492L was one of the common types of CDC25B mutants. Researches showed that compared to CDC25BWT, CDC25BR492L mutant had a ∼100-fold reduction in the rate constant for forming phosphatase intermediate (k2). However, the molecular basis of how the CDC25BR492L mutant influenced the process of binding between CDC25B and CDK2/CyclinA was not yet known. Therefore, the optimizations of three-dimensional structure of the CDC25BWT-CDK2/CyclinA system and the CDC25BR492L-CDK2/CyclinA system were constructed by ZDOCK and RDOCK, and five methods were employed to verify the reasonability of the docking structure. Then the molecular dynamics simulations on the two systems were performed to explore the reason why CDC25BR492L mutant caused the weak interactions between CDC25BR492L and CDK2/CyclinA, respectively. The remote docking site (Arg488-Tyr497) and the second active site (Lys538-Arg544) of CDC25B were observed to have high fluctuations in the CDC25BR492L-CDK2/CyclinA system with post-analysis, where the high fluctuation of these two regions resulted in weak interactions between CD25B and CDK2. In addition, Asp38-Glu42 and Asp206-Asp210 of CDK2 showed the slightly descending fluctuation, and CDK2 revealed an enhanced the self-interaction, which made CDK2 keep a relatively stable state in the CDC25BR492L-CDK2/CyclinA system. Finally, Leu492 of CDC25B was speculated to be the key residue, which had great effects on the binding between CDC25BR492L and CDK2 in the CDC25BR492L-CDK2/CyclinA system. Consequently, overall analyses appeared in this study ultimately offered a helpful understanding of the weak interactions between CDC25BR492L and CDK2.

4.
J Comput Assist Tomogr ; 45(4): 537-543, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34519452

RESUMO

OBJECTIVE: We explored the feasibility of cardiac computed tomography (CCT) to evaluate postoperative ventricular function in children with congenital heart disease (CHD) and evaluated the accuracy and reproducibility of CCT using cardiac magnetic resonance (CMR) as a reference. METHODS: Thirty-two postoperative children with CHD (20 boys and 12 girls) who underwent CMR and CCT were enrolled. Left and right ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, and cardiac index were measured using cardiac function analysis software. Cardiac function data were compared between CMR and CCT. The agreement between the 2 modalities was assessed using a Bland-Altman analysis. Intraclass correlation coefficients were used to assess intraobserver and interobserver reproducibility in CCT functional measurements. RESULTS: All functional parameters showed no significant difference (P > 0.05) and were well-correlated (r > 0.5, P < 0.05) between CMR and CCT. The mean values of all ventricular function parameters in CCT were higher compared with CMR. As indicated by 95% limits of agreement, left ventricular function parameters showed a better level of agreement compared with right ventricular function parameters between the 2 modalities. Intraobserver and interobserver reproducibility were excellent in CCT measurements for all functional parameters (intraclass correlation coefficient > 0.9). CONCLUSIONS: Compared with the criterion standard of CMR, CCT is feasible for assessing postoperative ventricular function with sufficient diagnostic accuracy and reproducibility in children with CHD. In addition to its important role regarding anatomical characterization, CCT is a suitable alternative and convenient follow-up tool that can be used to functional evaluation in children who are intolerant with CMR or have contraindications to CMR.

5.
Curr Mol Pharmacol ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521336

RESUMO

MiRNA-129-5p belongs to the microRNA-129 (miRNA-129) family. MiRNA-129-5p is expressed in many tissues and organs of the human body, and it regulates a wide range of biological functions. The abnormal expression of miRNA-129-5p is related to the occurrence and development of a variety of malignant tumors. MiRNA-129-5p plays an important role in the tumorigenesis process and functions by promoting or inhibiting tumors. However, the role of miRNA-129-5p in cancer remains controversial. This article reviews the different biological functions of miRNA-129-5p in cancer and provides ideas for research in this field to guide the development of targeted therapies and drugs for malignant tumors.

6.
Theranostics ; 11(18): 8660-8673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522205

RESUMO

Rationale: Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and progressive chronic kidney disease (CKD). Exosome-mediated cell-cell communication has been suggested to be involved in various diseases, including renal fibrosis. However, little is known regarding how exosomes regulate renal fibrosis in obstructed kidneys. Methods: We first examined the secretion of exosomes in UUO (unilateral ureteral obstruction) mouse kidneys and TGF-ß1-stimulated tubular epithelial cells (NRK-52E). Exosomes from NRK-52E cells were subsequently harvested and incubated with fibroblasts (NRK-49F) or injected into UUO mice via the tail vein. We next constructed Rab27a knockout mice to further confirm the role of exosome-mediated epithelial-fibroblast communication relevant to renal fibrosis in UUO mice. High-throughput miRNA sequencing was performed to detect the miRNA profiles of TGFß1-Exos. The roles of candidate miRNAs, their target genes and relevant pathways were predicted and assessed in vitro and in vivo by setting specific miRNA mimic, miRNA inhibitor, siRNA or miRNA LNA groups. Results: Increased renal fibrosis was associated with prolonged UUO days, and the secretion of exosomes was markedly increased in UUO kidneys and TGF-ß1-stimulated NRK-52E cells. Purified exosomes from TGF-ß1-stimulated NRK-52E cells could activate fibroblasts and aggravate renal fibrosis in vitro and in vivo. In addition, the inhibition of exosome secretion by Rab27a knockout or GW4869 treatment abolished fibroblast activation and ameliorated renal fibrosis. Exosomal miR-21 was significantly increased in TGFß1-Exos compared with Ctrl-Exos, and PTEN is a certain target of miR-21. The promotion or inhibition of epithelial exosomal miR-21 correspondingly accelerated or abolished fibroblast activation in vitro, and renal fibrosis after UUO was alleviated by miR-21-deficient exosomes in vivo through the PTEN/Akt pathway. Conclusion: Our findings reveal that exosomal miR-21 from tubular epithelial cells may accelerate the development of renal fibrosis by activating fibroblasts via the miR-21/PTEN/Akt pathway in obstructed kidneys.

7.
Adv Sci (Weinh) ; : e2102666, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523247

RESUMO

Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρsurf. molecule (Nsurf. molecules /(a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross-talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF-α from macrophages. GNRs with small ρsurf. molecule mainly induce apoptosis, while with large ρsurf. molecule they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρsurf. molecule due to the overexpression of key protease caspase 8, which cleaves the RIP1-RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρsurf. molecule greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics.

8.
J Steroid Biochem Mol Biol ; 214: 105993, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34478831

RESUMO

In this research, a series of novel diosgenin-1,4-quinone hybrids were synthesized and evaluated in antiproliferative assays against three human cancer cell lines (MCF-7, HepG2, and HeLa). Structure-activity relationship analysis revealed that the activities depended on the type of 1,4-quinone moiety. Among them, hybrid 11a exhibited significant cytotoxicity against the HepG2 cell line with a IC50 of 1.76 µM, which was 35-fold more potent than diosgenin (IC50 = 43.96 µM). Western blot analysis showed that hybrid 11a upregulated Bax, Cl-caspase-3/9, and Cl-PARP levels, and downregulated Bcl-2 level of HepG2 cell line. Meanwhile, hybrid 11a could increase the generation of intracellular reactive oxygen species. The molecular docking study revealed an interaction between hybrid 11a and NQO1 enzyme. Our present studies suggested that hybrid 11a as a potential substrate for NQO1 enzyme could be a promising anticancer agent for further investigation.

9.
Biosens Bioelectron ; 194: 113602, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34481241

RESUMO

Inhibition of HIV-1 protease (PR) activity is realized by exposure to 60Co γ-radiation. The radiation effects on enzyme kinetics of HIV-1 PR are subsequently monitored using nanopore sensor. Substantial loss of proteolytic efficiency towards GagPol polypeptide is observed due to the radiation treatment. Results shows ~50% of GagPol polypeptide was not involved in HIV-1 PR proteolysis by exposure to ultra-low intensity of γ-radiation (0.1K Gy), and the values reach to over 90% with high γ-ray treatment. Besides, the inactivation effect is also verified in blood samples which contain the virus protease. Our finding provides the potential benefits of γ-radiation to inactivate viral proteinic function, and might be a complementary to the designation of HIV-1 PR inhibitors.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34487495

RESUMO

Sleep stage classification is essential for sleep assessment and disease diagnosis. Although previous attempts to classify sleep stages have achieved high classification performance, several challenges remain open: 1) How to effectively utilize time-varying spatial and temporal features from multi-channel brain signals remains challenging. Prior works have not been able to fully utilize the spatial topological information among brain regions. 2) Due to the many differences found in individual biological signals, how to overcome the differences of subjects and improve the generalization of deep neural networks is important. 3) Most deep learning methods ignore the interpretability of the model to the brain. To address the above challenges, we propose a multi-view spatial-temporal graph convolutional networks (MSTGCN) with domain generalization for sleep stage classification. Specifically, we construct two brain view graphs for MSTGCN based on the functional connectivity and physical distance proximity of the brain regions. The MSTGCN consists of graph convolutions for extracting spatial features and temporal convolutions for capturing the transition rules among sleep stages. In addition, attention mechanism is employed for capturing the most relevant spatial-temporal information for sleep stage classification. Finally, domain generalization and MSTGCN are integrated into a unified framework to extract subject-invariant sleep features. Experiments on two public datasets demonstrate that the proposed model outperforms the state-of-the-art baselines.

11.
Phys Chem Chem Phys ; 23(35): 19394-19401, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34490874

RESUMO

A generalized energy-based fragmentation (GEBF) approach has been combined with a universal solvation model based on solute electron density (SMD) to compute the solvation energies of general large systems (such as protein molecules) in solutions. In the GEBF-SMD method, the solvation energy of a target system could be combined by the corresponding solvation energies of various subsystems, each of which is embedded in the background point charges and surface charges on the surface of solute cavity at the positions of its atoms and neighbouring atoms outside of the subsystem. Our results show that the GEBF-SMD model could reproduce the conventional SMD solvation energies quite well for various proteins in solutions, and could significantly reduce the computational costs for the SMD calculations of large proteins. In addition, the GEBF-SMD approach is almost independent of the basis sets and the types of solvents (including protic, polar, and nonpolar ones). Also, the GEBF-SMD approach could reproduce the relative energies of various conformers of large systems in solutions. Therefore, the GEBF-SMD method is expected to be applicable for computing the solvation energies of a broad range of large systems.

12.
Molecules ; 26(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34500559

RESUMO

Endothelial dysfunction plays key roles in the pathological process of contrast media (CM)-induced acute kidney injury (CI-AKI) in patients undergoing vascular angiography or intervention treatment. Previously, we have demonstrated that an apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, inhibits oxidative stress and improves endothelial dysfunction caused by CM through the AMPK/PKC pathway. However, it is unclear whether CM induce metabolic impairments in endothelial cells and whether D-4F ameliorates these metabolic impairments. In this work, we evaluated vitalities of human umbilical vein endothelial cells (HUVECs) treated with iodixanol and D-4F and performed nuclear magnetic resonance (NMR)-based metabolomic analysis to assess iodixanol-induced metabolic impairments in HUVECs, and to address the metabolic mechanisms underlying the protective effects of D-4F for ameliorating these metabolic impairments. Our results showed that iodixanol treatment distinctly impaired the vitality of HUVECs, and greatly disordered the metabolic pathways related to energy production and oxidative stress. Iodixanol activated glucose metabolism and the TCA cycle but inhibited choline metabolism and glutathione metabolism. Significantly, D-4F pretreatment could improve the iodixanol-impaired vitality of HUVECs and ameliorate the iodixanol-induced impairments in several metabolic pathways including glycolysis, TCA cycle and choline metabolism in HUVECs. Moreover, D-4F upregulated the glutathione level and hence enhanced antioxidative capacity and increased the levels of tyrosine and nicotinamide adenine dinucleotide in HUVECs. These results provided the mechanistic understanding of CM-induced endothelial impairments and the protective effects of D-4F for improving endothelial cell dysfunction. This work is beneficial to further exploring D-4F as a potential pharmacological agent for preventing CM-induced endothelial impairment and acute kidney injury.

13.
Sensors (Basel) ; 21(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502570

RESUMO

A novel wearable button antenna sensor is proposed for the concept of simultaneous wireless information and power transfer (SWIPT). This integrates two working modes for the transfer of power and information, respectively, and optimizes transfer efficiency. An omni-directional radiation pattern is achieved in the 3.5 GHz World Interoperability for Microwave Access (WiMAX) band to support on-body wireless communications, while a circularly polarized broadside radiation pattern is obtained in the 5 GHz wireless local area networks (WLAN) band to harvest power. The measured -10 dB return loss bandwidths are 4.0% (3.47-3.61 GHz) in the lower band, and 25.0% (4.51-5.80 GHz) in the higher band, respectively. An artificial magnetic conductor (AMC) structure with wideband characteristics is applied to obtain a low-profile design and to increase the stability of the antenna sensor. A high radiation efficiency of over 80% in the whole working band is observed. The specific absorption rate (SAR) of the proposed antenna sensor is below 0.509 W/kg at 3.55 GHz, and below 0.0532 W/kg at 5.5 GHz, respectively, which is much lower than the European standard threshold of 2 W/kg. All these characteristics make the designed antenna sensor suitable for on-body information transmission and off-body energy harvesting. The antenna sensor has been prototyped. Simulations and measurements agree well, proving the validity of the new concept.


Assuntos
Dispositivos Eletrônicos Vestíveis , Tecnologia sem Fio , Desenho de Equipamento , Redes Locais , Micro-Ondas
14.
Sci Rep ; 11(1): 18087, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508171

RESUMO

Pulmonary embolism (PE) is a leading cause of mortality in postoperative patients. Numerous PE prevention clinical practice guidelines are available but not consistently implemented. This study aimed to develop and validate a novel risk assessment model to assess the risk of PE in postoperative patients. Patients who underwent Grade IV surgery between September 2012 and January 2020 (n = 26,536) at the Affiliated Dongyang Hospital of Wenzhou Medical University were enrolled in our study. PE was confirmed by an identified filling defect in the pulmonary artery system in CT pulmonary angiography. The PE incidence was evaluated before discharge. All preoperative data containing clinical and laboratory variables were extracted for each participant. A novel risk assessment model (RAM) for PE was developed with multivariate regression analysis. The discrimination ability of the RAM was evaluated by the area under the receiver operating characteristic curve, and model calibration was assessed by the Hosmer-Lemeshow statistic. We included 53 clinical and laboratory variables in this study. Among them, 296 postoperative patients developed PE before discharge, and the incidence rate was 1.04%. The distribution of variables between the training group and the validation group was balanced. After using multivariate stepwise regression, only variable age (OR 1.070 [1.054-1.087], P < 0.001), drinking (OR 0.477 [0.304-0.749], P = 0.001), malignant tumor (OR 2.552 [1.745-3.731], P < 0.001), anticoagulant (OR 3.719 [2.281-6.062], P < 0.001), lymphocyte percentage (OR 2.773 [2.342-3.285], P < 0.001), neutrophil percentage (OR 10.703 [8.337-13.739], P < 0.001), red blood cell (OR 1.872 [1.384-2.532], P < 0.001), total bilirubin (OR 1.038 [1.012-1.064], P < 0.001), direct bilirubin (OR 0.850 [0.779-0.928], P < 0.001), prothrombin time (OR 0.768 [0.636-0.926], P < 0.001) and fibrinogen (OR 0.772 [0.651-0.915], P < 0.001) were selected and significantly associated with PE. The final model included four variables: neutrophil percentage, age, malignant tumor and lymphocyte percentage. The AUC of the model was 0.949 (95% CI 0.932-0.966). The risk prediction model still showed good calibration, with reasonable agreement between the observed and predicted PE outcomes in the validation set (AUC 0.958). The information on sensitivity, specificity and predictive values according to cutoff points of the score in the training set suggested a threshold of 0.012 as the optimal cutoff value to define high-risk individuals. We developed a new approach to select hazard factors for PE in postoperative patients. This tool provided a consistent, accurate, and effective method for risk assessment. This finding may help decision-makers weigh the risk of PE and appropriately select PE prevention strategies.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34509952

RESUMO

Determining the sex and controlling the sex ratio are essential aspects of fish genetics that can assist in developing successful fish breeding programs. High quality genome assembly and annotations are prerequisites to determine sex-specific genes and their expression. In addition, analysis of resequencing data can identify genomic difference between male and female fishes. In this study, we performed chromosome-level genome assembly in female Ancherythroculter nigrocauda fish having low heterozygosity using PacBio reads. High-throughput chromatin conformation capture (HiC) yielded a genome of size 1054.05 Mb, with a contig N50 length of 3.40 Mb and a scaffold N50 length of 42.68 Mb. In addition, we sequenced 5 female and 5 male A. nigrocauda samples and identified sex-specific regions on LG20 Furthermore, diet-specific amino acid mutation were found on 582 genes between herbivorous and carnivorous fishes, with 26 of them exhibiting significantly different expression patterns in the liver tissue of these two types of fishes. The chromosome-level genome assembly of A. nigrocauda provides valuable resources for conducting in-depth comparative genomic studies with immense applications in fish genetic breeding and farming. Similarly, the diet-specific amino acid mutations are useful in the breeding of new strains of carnivorous fishes with an herbivorous diet.

16.
Drug Des Devel Ther ; 15: 3717-3731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511881

RESUMO

Compulsory licensing for drug patents is of great significance to ensure the accessibility of drugs. Although the development of China's compulsory licensing system for drug patents has been gradually improved, there are still problems. For example, the scope of the object is not realistic, the setting of the initiating subject is unreasonable, the reasons for issuance are not clear, the duration and scope of the license are not refined, and the provisions on the exploitation fee are missing. Consequently, in order to improve China's compulsory licensing system for drug patents, it is necessary to expand reasonably the scope of the object, remove the restrictions on the initiating subject, adjust the initiating rights of different subjects, determine the duration and scope of the license and the applicability of the hearing on a case-by-case basis, and determine a reasonable exploitation fee by taking into account the national income, patent cost, market share and other factors, in consideration of the flexibly international norms and the actual situation in China.

17.
Medicine (Baltimore) ; 100(36): e27057, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516495

RESUMO

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most common cause of childhood hearing loss (HL), although the strength of this association remains limited and inconclusive. Thus, the purpose of this study was to summarize evidence regarding the strength of the relationship between cCMV and childhood HL and to determine whether this relationship differs according to patient characteristics. METHODS: The PubMed, EmBase, and Cochrane Library databases were searched for studies evaluating the relationship between cCMV and HL from inception to September 2019. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the investigated outcomes in a random-effects model. Sensitivity, subgroup, and publication bias analyses were also performed. RESULTS: A total of 15 studies involving 235,026 children met the inclusion criteria and were included in the final analysis. The summary results indicated that cCMV infection was associated with an increased risk of HL (odds ratio [OR]: 8.45; 95% confidence interval [CI]: 3.95-18.10; P < .001), irrespective of whether studies reported sensorineural HL (OR: 5.42; 95% CI: 1.98-14.88; P = .001), or did not evaluate HL types among their patients (OR: 11.04; 95% CI: 3.91-31.16; P < .001). However, in studies conducted in the United States (P < 0.001) and published in or after 2000 (P = 0.026), the study populations included <60% males (P < 0.001). Moreover, studies of high quality (P < .001) demonstrated a significantly greater risk of HL with cCMV infection than that in the corresponding subgroups. CONCLUSIONS: The study results suggest that cCMV infection increases the risk of HL. Further studies are required to investigate the association of cCMV infection with the risk of specific subtypes of HL.

18.
Sci Rep ; 11(1): 17963, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504154

RESUMO

Melting is one of the most studied phase transitions important for atomic, molecular, colloidal, and protein systems. However, there is currently no microscopic experimentally accessible criteria that can be used to reliably track a system evolution across the transition, while providing insights into melting nucleation and melting front evolution. To address this, we developed a theoretical mean-field framework with the normalised mean-square displacement between particles in neighbouring Voronoi cells serving as the local order parameter, measurable experimentally. We tested the framework in a number of colloidal and in silico particle-resolved experiments against systems with significantly different (Brownian and Newtonian) dynamic regimes and found that it provides excellent description of system evolution across melting point. This new approach suggests a broad scope for application in diverse areas of science from materials through to biology and beyond. Consequently, the results of this work provide a new guidance for nucleation theory of melting and are of broad interest in condensed matter, chemical physics, physical chemistry, materials science, and soft matter.

19.
Proc Natl Acad Sci U S A ; 118(37)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34507987

RESUMO

The formation of the branched actin networks is essential for cell polarity, but it remains unclear how the debranching activity of actin filaments contributes to this process. Here, we showed that an evolutionarily conserved coronin family protein, the Caenorhabditis elegans POD-1, debranched the Arp2/3-nucleated actin filaments in vitro. By fluorescence live imaging analysis of the endogenous POD-1 protein, we found that POD-1 colocalized with Arp2/3 at the leading edge of the migrating C. elegans neuroblasts. Conditional mutations of POD-1 in neuroblasts caused aberrant actin assembly, disrupted cell polarity, and impaired cell migration. In C. elegans one-cell-stage embryos, POD-1 and Arp2/3, moved together during cell polarity establishment, and inhibition of POD-1 blocked Arp2/3 motility and affected the polarized cortical flow, leading to symmetric segregation of cell fate determinants. Together, these results indicate that F-actin debranching organizes actin network and cell polarity in migrating neuroblasts and asymmetrically dividing embryos.

20.
JACC Heart Fail ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509406

RESUMO

OBJECTIVES: This study aims to examine the association between the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score and the 30-day and 1-year rates of composite events of cardiovascular death and heart failure (HF) rehospitalization in patients with acute HF. BACKGROUND: Few studies reported the prognostic effects of KCCQ in acute HF. METHODS: This study prospectively enrolled adult patients hospitalized for HF from 52 hospitals in China and collected the KCCQ-12 score within 48 hour of index admission. The study used multivariable Cox regression to examine the association between KCCQ-12 score and 30-day and 1-year composite events and was further stratified by new-onset HF and acutely decompensated chronic heart failure (ADCHF). Subgroup analyses were performed to explore the potential heterogeneity. The study evaluated the incremental prognostic value of KCCQ-12 score over N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and established risk scores by C-statistics, net reclassification improvement, and integrated discrimination improvement. RESULTS: Among 4,898 patients, 29.4% had new-onset HF. After adjustment, each 10-point decrease in the KCCQ-12 score was associated with a 13% increase in 30-day risk and a 7% increase in 1-year risk. The associations were consistent regardless of new-onset HF or ADCHF, age, sex, left ventricular ejection fraction, New York Heart Association functional class, NT-proBNP level, comorbidities, and renal function. Adding KCCQ-12 score to NT-proBNP and established risk scores significantly improved prognostic capabilities measured by C-statistics, net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: In acute HF, a poor KCCQ-12 score predicted short- and long-term risks of cardiovascular death and HF rehospitalization. KCCQ-12 could serve as a convenient tool for rapid initial risk stratification and provide additional prognostic value over NT-proBNP and established risk scores.

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