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Self-reported effectiveness of electroencephalogram-based neurofeedback (EEG-NF) against the core symptoms of attention-deficit hyperactivity disorder (ADHD) in adolescents/adults remains unclear. We searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to August 2021 for randomized clinical trials (RCTs) of EEG-NF with self-reported ADHD symptom ratings. Comparators included participants on waitlist/treatment as usual (TAU) or receiving other interventions. Of the 279 participants (mean age = 23.48; range: 6–60) in five eligible RCTs, 183 received EEG-NF treatment. Forest plot demonstrated no difference in inattention (SMD = −0.11, 95% CI −0.39–0.18, p = 0.46), total score (SMD = −0.08, 95% CI −0.36–0.2, p = 0.56), and hyperactivity/impulsivity (SMD = 0.01, 95% CI −0.23–0.25, p = 0.91) between EEG-NF and comparison groups. Nevertheless, compared with waitlist/TAU, EEG-NF showed better improvement in inattention (SMD = −0.48, 95% CI −0.9–−0.06, p = 0.03) but not hyperactivity/impulsivity (SMD = −0.03, 95% CI −0.45–0.38, p = 0.87). Follow-up 6–12 months demonstrated no difference in inattention (SMD = −0.01, 95% CI −0.41–0.38, p = 0.94), total score (SMD = 0.22, 95% CI −0.08–0.52, p = 0.15), and hyperactivity/impulsivity (SMD = −0.01, 95% CI −0.27–0.26, p = 0.96) between the two groups. Dropout rate also showed no difference (RR = 1.05, 95% CI 0.82–1.33, p = 0.72). Our results support EEG-NF for improving inattention in adolescents/young adults, although its effectiveness against hyperactivity/impulsivity remains inconclusive.

In this study, we developed a portable smartphone-based diffusometry for analyzing the C-reactive protein (CRP) concentration. An optimized fluorescence microscopic add-on system for a smartphone was used to image the 300 nm fluorescent beads. Sequential nanobead images were recorded for a period and the image data were used for fluorescence correlation spectrometric (FCS) analysis. Through the analysis, the nanobeads’ diffusion coefficient was obtained. Further, the diffusion coefficients of the anti-CRP-coated nanobeads, which were suspended in the samples with various CRP concentrations, were estimated using smartphone-based diffusometry. After 10 min of reaction, the anti-CRP-coated nanobeads in a higher CRP concentration solution led to a lower diffusion coefficient. Based on the experiments, a linear sensing range of 1~8 µg/mL was found.

Studies to examine the impact of end-of-life (EOL) discussions on the utilization of life-sustaining treatments near death are limited and have inconsistent findings. This nationwide population-based cohort study determined the impact of EOL discussions on the utilization of life-sustaining treatments in the last three months of life in Taiwanese cancer patients. From 2012 to 2018, this cohort study included adult cancer patients, which were confirmed by pathohistological reports. Life-sustaining treatments during the last three months of life included cardiopulmonary resuscitation, intubation, and defibrillation. EOL discussions in cancer patients were confirmed by their medical records. Association of EOL discussions with utilization of life-sustaining treatments were assessed using multiple logistic regression. Of 381,207 patients, the mean age was 70.5 years and 19.4% of the subjects received life-sustaining treatments during the last three months of life. After adjusting for other covariates, those who underwent EOL discussions were less likely to receive life-sustaining treatments during the last three months of life compared to those who did not (Adjusted odds ratio [AOR] 0.87; 95% confidence interval [CI] 0.85–0.89). Considering the type of treatments, EOL discussions correlated with a lower likelihood of receiving cardiopulmonary resuscitation (AOR = 0.45, 95% CI 0.43–0.47), endotracheal intubation (AOR = 0.92, 95%CI 0.90–0.95), and defibrillation (AOR = 0.54, 95%CI 0.49–0.59). Since EOL discussions are associated with less aggressive care, our study supports the importance of providing these discussions to cancer patients during the EOL treatment.

Obese men have lower circulating testosterone than men with an optimal body mass index. Elevated fatty acids (FAs) caused by obesity have been reported to suppress the steroidogenesis of Leydig cells. Recent studies have demonstrated that autophagy regulates steroidogenesis in endocrine cells; however, few studies have investigated the molecular mechanisms of FA-impaired steroidogenesis. To study FA regulation in the steroidogenesis of Leydig cells, MA-10 cells were treated with an FA mixture and co-treated with 8-Br-cAMP to stimulate the steroidogenesis capacity. We showed that FAs led to cellular lipid accumulation and decreased steroidogenesis of MA-10 cells, and FA-suppressed steroidogenesis was largely recovered by P5 treatment but not by 22R-OHC treatment, suggesting the primary defect was the deficiency of CYP11A1. To examine the involvement of autophagy in the steroidogenesis of Leydig cells, we treated MA-10 cells with autophagy regulators, including rapamycin, bafilomycin, and chloroquine. Inhibition of late-stage autophagy including FA-upregulated Rubicon suppressed the steroidogenesis of MA-10 cells. More interestingly, Rubicon played a novel regulatory role in the steroidogenesis of MA-10 cells, independent of inhibitors of late-stage autophagy. Collectively, this study provides novel targets to investigate the interaction between FAs and steroidogenesis in steroidogenic cells.

Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs). Moreover, MAT treatment promoted Akt phosphorylation and shifted the Bcl-2/Bax ratio back towards an antiapoptotic one, which could be a mechanism for its therapeutic effect in the ON model. Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.

To characterize rod- and cone-pathway function in the 5xFAD mouse model of Alzheimer’s disease (AD) using the full-field electroretinogram (ERG). Dark-adapted (DA; rod-pathway) and light-adapted (LA; cone-pathway) ERGs were recorded from three-month-old 5xFAD and wild type (WT) mice. ERGs were elicited by achromatic flashes (0.01–25 cd-s-m−2). Amplitude and implicit time (IT) of the a-wave, b-wave, and oscillatory potentials (OPs) were calculated according to convention. In addition, the amplitude and IT of the photopic negative response (PhNR) were measured from the LA recordings. Amplitude and IT differences between the 5xFAD and WT groups were evaluated using quantile regression models. Under DA conditions, there were significant differences between the 5xFAD and WT groups in post-receptor function, whereas photoreceptor function did not differ significantly. Specifically, the DA a-wave amplitude did not differ between groups (p = 0.87), whereas the b-wave amplitude was reduced in the 5xFAD mice (p = 0.003). There were significant OP (p p = 0.04) delays, but the a-wave delay may be attributable to a post-receptor abnormality. Under LA conditions, the only 5xFAD abnormalities were in the PhNR, which was reduced (p = 0.009) and delayed (p = 0.04). The full-field ERG can be abnormal in the 5xFAD model of AD, with the greatest effects on post-receptor rod pathway function. These results indicate that retinal electrophysiology may be a useful tool for evaluating neural dysfunction in AD.

Glypican-3 (GPC3) is a cell surface heparan sulfate proteoglycan that is being evaluated as an emerging therapeutic target in hepatocellular carcinoma (HCC). GPC3 has been shown to interact with several extracellular signaling molecules, including Wnt, HGF, and Hedgehog. Here, we reported a cell surface transmembrane protein (FAT1) as a new GPC3 interacting protein. The GPC3 binding region on FAT1 was initially mapped to the C-terminal region (Q14517, residues 3662-4181), which covered a putative receptor tyrosine phosphatase (RTP)-like domain, a Laminin G-like domain, and five EGF-like domains. Fine mapping by ELISA and flow cytometry showed that the last four EGF-like domains (residues 4013-4181) contained a specific GPC3 binding site, whereas the RTP domain (residues 3662-3788) and the downstream Laminin G-2nd EGF-like region (residues 3829-4050) had non-specific GPC3 binding. In support of their interaction, GPC3 and FAT1 behaved concomitantly or at a similar pattern, e.g. having elevated expression in HCC cells, being up-regulated under hypoxia conditions, and being able to regulate the expression of EMT-related genes Snail, Vimentin, and E-Cadherin and promoting HCC cell migration. Taken together, our study provides the initial evidence for the novel mechanism of GPC3 and FAT1 in promoting HCC cell migration.

A major number of studies have demonstrated Beta-tricalcium phosphate (β-TCP) biocompatibility, bioactivity, and osteoconductivity characteristics in bone regeneration. The aim of this research was to enhance β-TCP's biocompatibility, and evaluate its physicochemical properties by argon glow discharge plasma (GDP) plasma surface treatment without modifying its surface. Treated β-TCP was analyzed by scanning electron microscopy (SEM), energy-dispersive spectrometry, X-ray photoelectron spectroscopy (XPS), X-ray diffraction analysis, and Fourier transform infrared spectroscopy characterization. To evaluate treated β-TCP biocompatibility and osteoblastic differentiation, water-soluble tetrazolium salts-1 (WST-1), immunofluorescence, alkaline phosphatase (ALP) assay, and quantitative real-time polymerase chain reaction (QPCR) were done using human mesenchymal stem cells (hMSCs). The results indicated a slight enhancement of the β-TCP by GDP sputtering, which resulted in a higher Ca/P ratio (2.05) than the control. Furthermore, when compared with control β-TCP, we observed an improvement of WST-1 on all days (p p p

To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

As a key component of various acoustic systems, acoustic beam splitter (BS) finds important application in many scenarios, yet are conventionally based on the assumption that the acoustic waves propagate as easily when incident from either input or output side. It would therefore be intriguing, from the viewpoints of both science and technology, to break through this limit by realizing acoustic BSs supporting asymmetric transmission. Here we propose the concept of one-way acoustic BS capable of splitting acoustic beam incident from the input port into multiple beams while effectively reducing the backward transmission from any of the output ports. Furthermore, our design enables flexibly adjusting the number and angle of output beams by blocking the unused line defects. The numerical results verify the theoretical predictions and demonstrate the phenomenon of one-way acoustic BS at the predesigned frequency. Our design with functionality and flexibility bridges the gap between acoustic diodes and BSs and may enable novel multi-functional devices with great application prospects in diverse fields such as acoustic integrated circuits and acoustic communication.

Previous studies have demonstrated the important role of kisspeptin in impaired glucose-stimulated insulin secretion (GSIS). In addition, it was reported that the activation of autophagy in pancreatic β-cells decreases insulin secretion by selectively degrading insulin granules. However, it is currently unknown whether kisspeptin suppresses GSIS in β-cells by activating autophagy. To investigate the involvement of autophagy in kisspeptin–regulated insulin secretion, we overexpressed Kiss1 in NIT-1 cells to mimic the long-term exposure of pancreatic β-cells to kisspeptin during type 2 diabetes (T2D). Interestingly, our data showed that although kisspeptin potently decreases the intracellular proinsulin and insulin ((pro)insulin) content and insulin secretion of NIT-1 cells, autophagy inhibition using bafilomycin A1 and Atg5 siRNAs only rescues basal insulin secretion, not kisspeptin-impaired GSIS. We also generated a novel in vivo model to investigate the long-term exposure of kisspeptin by osmotic pump. The in vivo data demonstrated that kisspeptin lowers GSIS and (pro)insulin levels and also activated pancreatic autophagy in mice. Collectively, our data demonstrated that kisspeptin suppresses both GSIS and non-glucose-stimulated insulin secretion of pancreatic β-cells, but only non-glucose-stimulated insulin secretion depends on activated autophagic degradation of (pro)insulin. Our study provides novel insights for the development of impaired insulin secretion during T2D progression.

Uncontrolled haemorrhage shock is the highest treatment priority for military trauma surgeons. Injuries to the torso area remain the greatest treatment challenge, since external dressings and compression cannot be used here. Bleeding control strategies may thus offer more effective haemostatic management in these cases. Chitosan, a linear polysaccharide derived from chitin, has been considered as an ideal material for bleeding arrest. This study evaluated the potential of chitosan-based dressings relative to commercial gauze to minimise femoral artery haemorrhage in a swine model. Stable haemostasis was achieved in animals treated with chitosan fibre (CF) or chitosan sponge (CS), resulting in stabilisation of mean arterial pressure and a substantially higher survival rate (100% vs. 0% for gauze). Pigs receiving treatment with CF or CS dressings achieved haemostasis within 3.25 ± 1.26 or 2.67 ± 0.58 min, respectively, significantly more rapidly than with commercial gauze (>100 min). Moreover, the survival of animals treated with chitosan-based dressings was dramatically prolonged (>180 min) relative to controls (60.92 ± 0.69 min). In summary, chitosan-based dressings may be suitable first-line treatments for uncontrolled haemorrhage on the battlefield, and require further investigation into their use as alternatives to traditional dressings in prehospital emergency care.

Molecular recognition plays an important role in biological systems and relates to a wide range of applications in disease diagnostics and therapeutics. Studies based on steady state or ensemble analysis may mask critical dynamic information of single recognition events. Here we report a study of monitoring the transient molecular recognition via single particle motion. We utilized a super-localization imaging methodology, to comprehensively evaluate the rotational Brownian motion of a single nanoparticle in spatial-temporal-frequential domain, with a spatial accuracy ~20 nm and a temporal resolution of ~10 ms. The transient moment of molecular encountering was captured and different binding modes were discriminated. We observed that the transient recognition events were not static states of on or off, but stochastically undergoes dynamical transformation between different binding modes. This study improves our understanding about the dynamic nature of molecular recognition events beyond the ensemble characterization via binding constant.

Electrophoretic display encountered several challenges towards high frame rate applications, such as long response time and high driving voltage. In this study, liquid crystal additive doping can simultaneously increase the response speed by 2.8 times and reduce the driving voltage to half of the initial value of electrophoretic dispersion. The backflow effect of liquid crystal, which induces an inversely electrorheological effect and facilitates the reverse micelles’ dielectrophoretic separation, was suggested to be the main reason for the performance improvement. The proposed method is facile and effective which shows promising potential for fast response and low power consumption e-paper applications.

Renal diseases impose considerable health and economic burdens on health systems worldwide, and there is a lack of efficient methods for the prevention and treatment due to their complexity and heterogeneity. Kidneys are organs with a high demand for energy produced by mitochondria, in which Rrm2b has critical functions as reported. The Rrm2b kidney-specific knockout mice we generated exhibited age-dependent exacerbated features, including mitochondrial dysfunction and increased oxidative stress; additionally, resulted in severe disruption of mitochondria-related metabolism. Rrm2b is vital not only to supply dNTPs for DNA replication and repair, but also to maintain structural integrity and metabolic homeostasis in mitochondria. Thence, Rrm2b deletion might induce chronic kidney defects in mice. This model can facilitate exploration of novel mechanisms and targeted therapies in the kidney diseases and has important translational and clinical implications.

Dense surface registration, commonly used in computer science, could aid the biological sciences in accurate and comprehensive quantification of biological phenotypes. However, few toolboxes exist that are openly available, non-expert friendly, and validated in a way relevant to biologists. Here, we report a customizable toolbox for reproducible high-throughput dense phenotyping of 3D images, specifically geared towards biological use. Given a target image, a template is first oriented, repositioned, and scaled to the target during a scaled rigid registration step, then transformed further to fit the specific shape of the target using a non-rigid transformation. As validation, we use n = 41 3D facial images to demonstrate that the MeshMonk registration is accurate, with 1.26 mm average error, across 19 landmarks, between placements from manual observers and using the MeshMonk toolbox. We also report no variation in landmark position or centroid size significantly attributable to landmarking method used. Though validated using 19 landmarks, the MeshMonk toolbox produces a dense mesh of vertices across the entire surface, thus facilitating more comprehensive investigations of 3D shape variation. This expansion opens up exciting avenues of study in assessing biological shapes to better understand their phenotypic variation, genetic and developmental underpinnings, and evolutionary history. ispartof: Scientific Reports vol:9 issue:11 ispartof: location:England status: published

Open heart surgeries are common for treating ischemic and heart valve disease. During cardiac surgery, cardiopulmonary bypass (CPB) can temporarily take over the function of heart and lungs. However, elevated red blood cell (RBC) aggregation may lead to the common side-effects such as microinfarction. We investigated blood physical properties changes and the correlation between blood microstructure, viscoelastic response and biochemical changes following surgery with CPB. We examined shear-rate dependent blood viscosity, elasticity and RBC aggregate size in the pre-surgery disease state, post-surgery state and long-term recovery state of cardiac surgical patients. Within a week following surgery, the patient hematocrit was significantly lower due to CPB. Despite lower RBC concentration, the RBC aggregate shape became larger and more rounded, which is correlated to the elevated plasma fibrinogen related to systemic inflammatory response. During the same period, the hematocrit-adjusted low shear rate viscosity increased significantly, as did the yield stress, indicating more solid-like behavior for blood. Six months to one year later, all the physical and biochemical properties measured returned to baseline.

Accurate characterization of the mechanical properties of brain tissue is essential for understanding the mechanisms of traumatic brain injuries and developing protective gears or facilities. However, how storage conditions might affect the mechanical properties of brain tissue remains unclear. The objective of this study is to investigate the effect of in vitro storage duration on the mechanical performance of brain tissue since measurements are usually carried out in vitro. Differential Scanning Calorimetry (DSC) measurements and uniaxial compression mechanical experiments are carried out. The results indicate that, for brain tissue stored at 1 °C without any liquid medium, the bio-molecular interactions and the mechanical strength of both white and grey matter deteriorate with prolonged storage duration. Transmission Electron Microscopy (TEM) results reveal the degeneration of myelin sheaths and the vacuolization of cristae with prolonged storage duration, suggesting that the in vitro storage duration should be carefully controlled. The findings from this study might facilitate the development of guidelines and standards for the in vitro storage of brain tissue.

By investigating the uptake of 16 priority polycyclic aromatic hydrocarbons (PAHs) and five heavy metals from soils to maize at the farmlands with industrial wastewater irrigation, this study revealed the effects of heavy metals on PAHs uptake in terms of co-contamination. The results of 15 investigated soils showed medium contamination level and the vertical PAHs distribution in soils indicated that 2–3 rings PAHs with low octanol-water partition coefficient (log Kow ow less than 4.5, while negatively correlated otherwise. Redundancy analysis indicated the unexpected results that, except for soil PAHs concentration, the PAHs translocation by maize was reduced by Pb uptake, but not significantly affected by soil organic matters, pH or the other four heavy metals (Cr, Cu, Ni and Zn). This study for the first time provides the restricted factors of PAHs and heavy metal acropetal translocation by maize when they co-exist at wastewater irrigation sites.