Aim To explore the altered spontaneous cerebral activity patterns and impaired functional regions in patients with diabetic retinopathy (DR) using resting-state functional magnetic resonance imaging ...(rs-fMRI) based on the amplitude of low-frequency fluctuations (ALFF) algorithm. Materials and methods Twenty-one patients with DR (mean age, 54.9±9.9 years; 11 females) and 17 healthy control subjects (54.8±5.7 years; 9 females) were prospectively studied. The DR patients underwent laboratory tests. All individuals underwent a neuropsychological test. The differences in the ALFF values between the two groups were compared. The relationships between ALFF values and clinical measurements were analysed using a multiple-factor analysis. Results Compared to the controls, the DR group showed significantly increased ALFF values in the bilateral occipital gyrus, right lingual gyrus, and precuneus, and decreased values in the right posterior/anterior cerebellar lobe and the parahippocampal, fusiform, superior temporal, inferior parietal, and angular gyrus. Furthermore, the Montreal Cognitive Assessment (MoCA) scores were negatively correlated with decreased ALFF values in the right occipital lobe of the DR group, while increased ALFF values in the right precuneus and lingual gyrus were found to be positively correlated with glycosylated haemoglobin (HbA1c) levels. Conclusions Patients with DR showed spontaneous cerebral activity abnormalities in many cerebral regions that were associated with cognitive impairments. HbA1c levels altered spontaneous cerebral activity in DR patients.
Phase separation of nucleic acids and proteins is a ubiquitous phenomenon regulating subcellular compartment structure and function. While complex coacervation of flexible single-stranded nucleic ...acids is broadly investigated, coacervation of double-stranded DNA (dsDNA) is less studied because of its propensity to generate solid precipitates. Here, we reverse this perspective by showing that short dsDNA and poly-l-lysine coacervates can escape precipitation while displaying a surprisingly complex phase diagram, including the full set of liquid crystal (LC) mesophases observed to date in bulk dsDNA. Short dsDNA supramolecular aggregation and packing in the dense coacervate phase are the main parameters regulating the global LC-coacervate phase behavior. LC-coacervate structure was characterized upon variations in temperature and monovalent salt, DNA, and peptide concentrations, which allow continuous reversible transitions between all accessible phases. A deeper understanding of LC-coacervates can gain insights to decipher structures and phase transition mechanisms within biomolecular condensates, to design stimuli-responsive multiphase synthetic compartments with different degrees of order and to exploit self-assembly driven cooperative prebiotic evolution of nucleic acids and peptides.
We analyzed the seasonal variations of energy balance components over three different surfaces: irrigated cropland (Yingke, YK), alpine meadow (A'rou, AR), and spruce forest (Guantan, GT). The energy ...balance components were measured using eddy covariance (EC) systems and a large aperture scintillometer (LAS) in the Heihe River Basin, China, in 2008 and 2009. We also determined the source areas of the EC and LAS measurements with a footprint model for each site and discussed the differences between the sensible heat fluxes measured with EC and LAS at AR. The results show that the main EC source areas were within a radius of 250 m at all of the sites. The main source area for the LAS (with a path length of 2390 m) stretched along a path line approximately 2000 m long and 700 m wide. The surface characteristics in the source areas changed with the season at each site, and there were characteristic seasonal variations in the energy balance components at all of the sites. The sensible heat flux was the main term of the energy budget during the dormant season. During the growing season, however, the latent heat flux dominated the energy budget, and an obvious "oasis effect" was observed at YK. The sensible heat fluxes measured by LAS at AR were larger than those measured by EC at the same site. This difference seems to be caused by the so-called energy imbalance phenomenon, the heterogeneity of the underlying surfaces, and the difference between the source areas of the LAS and EC measurements.
► ET were measured for three years using EC and LAS at three sites over a basin. ► The seasonal and interannual variations of observed ET at two scales were analyzed. ► ET differences among the years ...and sites, from EC and LAS measurements were analyzed. ► ET measurements were compared to field water balance calculations and MODIS products.
Evapotranspiration (ET) observations were made for 3years (2008–2010), using eddy covariance (EC) systems and large aperture scintillometers (LAS), in typical underlying surfaces across the Hai River Basin: orchards (Miyun, MY), cropland in the suburbs (Daxing, DX), and cropland in the plains (Guantao, GT). Reliable data were obtained after carefully data processing, and the seasonal and interannual variability in ET was quantitatively analyzed. The annual ET during 2008–2010 ranged from 510–730mm for the EC measurements and 430–560mm for the LAS measurements. The differences in ET among the years and sites were connected with differences in soil moisture and crop growing conditions. The difference in the source areas of EC and LAS measurements and the heterogeneity in their source areas are the primary causes of the discrepancy between EC and LAS measurements. The EC and LAS measurements are compared to the field water balance method calculation and MOD16 ET (the MODIS ET product from the MODIS Global Evapotranspiration Project), respectively. The average difference was 0.85% (mean relative error) and 33.80mm (root mean square error) between the EC measurements and field water balance method calculations, and 7.72% and 47.08mm between LAS measurements and MOD16 ET from 2008 to 2010 at the three sites. We found a decreasing tendency for ET in the past 15years across the Hai River Basin, especially after the year of 2005.
The association between infarct location and hemorrhagic transformation of acute ischemic stroke after mechanical thrombectomy is not understood. We aimed to evaluate the association between ...CTP-based ischemic core variables at admission and hemorrhagic transformation after a successful thrombectomy.
We retrospectively analyzed patients who underwent endovascular thrombectomy for acute anterior circulation large-vessel occlusion between October 2019 and June 2021. We enrolled 146 patients with visible ischemic core on pretreatment CTP who had successful reperfusion. The ischemic core infarct territories were classified into the cortical and subcortical areas and then qualitatively and quantitatively analyzed by CTP. Logistic regression and receiver operating characteristic curve analyses were performed to determine the association between ischemic core variables and hemorrhagic transformation.
Of the 146 patients analyzed, 72 (49.3%) had hemorrhagic transformation and 23 (15.8%) had symptomatic intracerebral hemorrhage. Multivariate analysis showed that subcortical infarcts were independently associated with hemorrhagic transformation (OR, 8.06; 95% CI, 2.31-28.10;
= .001) and subcortical infarct volume was independently linked to symptomatic intracerebral hemorrhage (OR, 1.05; 95% CI, 1.01-1.09;
= .039). The receiver operating characteristic curve indicated that subcortical infarcts can predict hemorrhagic transformation accurately (area under the curve = 0.755; 95% CI, 0.68-0.82;
< .001) and subcortical infarct volume can predict symptomatic intracerebral hemorrhage (area under the curve = 0.694; 95% CI, 0.61-0.77;
= .002).
Subcortical infarcts seen on CTP at admission are associated with hemorrhagic transformation in patients after successful thrombectomy, and subcortical infarct volume may influence the risk of symptomatic intracerebral hemorrhage.
The single-nucleotide polymorphism (SNP) rs2235371 (IRF6 V274I) is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Han Chinese and other populations but appears to be ...without a functional effect. To find the common etiologic variant or variants within the haplotype tagged by rs2235371, we carried out targeted sequencing of an interval containing IRF6 in 159 Han Chinese with NSCL/P. This study revealed that the SNP rs12403599, within the IRF6 promoter, is associated with all phenotypes of NSCL/P, especially nonsyndromic cleft lip (NSCLO) and a subphenotype of it, microform cleft lip (MCL). This association was replicated in 2 additional much larger cohorts of cases and controls from the Han Chinese. Conditional logistic analysis indicated that association of rs2235371 with NSCL/P was lost if rs12403599 was excluded. rs12403599 contributes the most risk to MCL: its G allele is responsible for 38.47% of the genetic contribution to MCL, and the odds ratios of G/C and G/G genotypes were 2.91 and 6.58, respectively, for MCL. To test if rs12403599 is functional, we carried out reporter assays in a fetal oral epithelium cells (GMSM-K). Unexpectedly, the risk allele G yielded higher promoter activity in GMSM-K. Consistent with the reporter studies, expression of IRF6 in lip tissues from NSCLO and MCL patients with the G/G phenotype was higher than in those from patients with the C/C phenotype. These results indicate that rs12403599 is tagging the risk haplotype for NSCL/P better than rs2235371 in Han Chinese and supports investigation of the mechanisms by which the allele of rs12403599 affects IRF6 expression and tests of this association in different populations.
Endovascular recanalization has been attempted in patients with symptomatic chronic ICA occlusion, however, the heterogeneity of recanalization outcomes and the perioperative complications present ...challenges for the clinical application. Our aim was to evaluate the safety and efficacy of endovascular recanalization for symptomatic chronic ICA occlusion and identify potential predictors for successful recanalization.
This study included 47 consecutive patients with symptomatic chronic ICA occlusion who underwent endovascular recanalization at our institution. Patients' clinical information, radiologic characteristics, procedural results, and outcomes were recorded. Factors related to technical success were analyzed by univariate and multivariate analyses.
The technical success rate was 74.5% (35/47); 12.8% of patients (6/47) experienced intraoperative complications, but none had permanent neurologic deficits. Three months after recanalization, 21 of the 29 recanalized patients (72.4%) and 3 of the 10 failed patients (30.0%) demonstrated improved mRS scores. Restenosis or re-occlusion occurred in 12.9% of patients (4/31) with successful recanalization. Multivariate analysis showed that tapered or blunt stump (
= .016), distal ICA occlusion segment (below the cavernous segment versus at or above the ophthalmic segment,
= .003; at the cavernous or clinoid segment versus at or above the ophthalmic segment,
= .027), and radiologic occlusion to recanalization of ≤3 months (
= .044) were significantly associated with successful recanalization. Patients were assigned points according to the coefficients of the prediction model, and the technical success rates were 0%, 46.2%, 90.5%, and 100% in patients with 1, 2, 3, and 4 points, respectively.
Endovascular recanalization is a safe and effective treatment for symptomatic chronic ICA occlusion in selected patients. A residual stump, low levels of the distal ICA occlusion segment, and a short radiologic occlusion time were identified as positive predictors of technical success.
SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Although population average structure models of the ...genome were recently reported, there is little experimental data on native structural ensembles, and most structures lack functional characterization. Here we report secondary structure heterogeneity of the entire SARS-CoV-2 genome in two lines of infected cells at single nucleotide resolution. Our results reveal alternative RNA conformations across the genome and at the critical frameshifting stimulation element (FSE) that are drastically different from prevailing population average models. Importantly, we find that this structural ensemble promotes frameshifting rates much higher than the canonical minimal FSE and similar to ribosome profiling studies. Our results highlight the value of studying RNA in its full length and cellular context. The genomic structures detailed here lay groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics.
Literature review.
Spinal cord injury (SCI) remains a major public health issue in developed countries as well as worldwide. The pathophysiology of SCI is characterized by an initial primary injury ...followed by secondary deterioration. Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress have a significant role in the pathophysiology of SCI. Thus, alleviating oxidative stress may be an effective strategy for therapeutic intervention of SCI. The aim of this review was to describe (i) the sources of ROS as well as the major antioxidant defenses with particular attention being paid to lipid peroxidation; (ii) the biomarkers of oxidative stress in SCI and (iii) the neuroprotective effects of various compounds with antioxidative properties in animal models of SCI.
PubMed, one of the most comprehensive biomedical databases, was searched from 1976-2011. All relevant papers were read by title, abstract and full-length article.
Oxidative stress is considered a hallmark of injury of SCI. Thus, alleviating oxidative stress may be an effective way of therapeutic intervention of SCI. Two of these agents, the glucocorticoid steroid methylprednisolone and the non-glucocorticoid 21-aminosteroid tirilazad, have been shown to possess significant antioxidant activities and improve recovery of SCI patients in clinical trials. Other promising botanical compounds and their molecular targets and mechanisms of action with regard to potential protection against SCI were also described. These include carotenoids and phenolic compounds.
ROS and oxidative stress have a significant role in the pathophysiology of SCI. Alleviating oxidative stress is be an effective strategy for therapeutic intervention of SCI. Extensive research over the past several decades has identified numerous bioactive compounds that have antioxidative stress benefits in animal models of SCI. Thus, continued studies on bioactive compounds with ROS-scavenging capacity may lead to the development of effective antioxidant-based modalities for treating SCI in human subjects.
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