While exercise-based cardiac rehabilitation has a beneficial effect on heart failure hospitalization and mortality, it is limited by the presence of chronotropic incompetence (CI) in some patients. This study explored the feasibility of using wearable devices to assess impaired chronotropic response in heart failure patients.

Ischemic stroke is an increasingly important public health problem, and no effective treatments are approved. Xijiao Dihuang Decoction (XDD), a famous herbal formula for treating hemorrhagic fever syndromes, has been shown to exert powerful neuroprotective property. The aim of this study was to identify the chemical constituents in XDD, observe the neuroprotective effect of XDD against acute ischemic stroke, and explore the specific mechanisms by which these effects were mediated. With UHPLC-Q/TOF-MS, 47 components in XDD were detected and 25 of them were identified. In rats subjected to MCAO, XDD ameliorated neurological deficit, histopathology changes, and infarction volume. In addition, levels of TNF-ɑ, IL-6, and IL-1β in XDD-treated group were significantly lower compared to the model group. Mechanistic studies showed that XDD inhibited MCAO-induced NF-κB activation, presenting as downregulating the expression of phospho-NF-κB p65 and preventing IκBɑ degradation. Besides, BDNF, GDNF, VEGF, bFGF, and CD34 levels were significantly increased by XDD, suggesting that the protective effects of XDD may also be associated with the promotion of neurogenesis and angiogenesis. In conclusion, these findings provided a novel regulatory pathway of the neuroprotective effect of XDD that helped rehabilitate patients with stroke.

Patients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD.

Accumulating evidence has suggested that receptor for advanced glycation end products (RAGE) is involved in the development and progression of human abdominal aortic aneurysms (AAAs). However, the association between RAGE gene polymorphisms and AAA has not yet been determined. The present study was aimed at analyzing the potential association between the RAGE gene polymorphisms and AAAs. A cohort of 381 patients and 436 age-matched healthy controls were genotyped to detect the three RAGE polymorphisms (-374 T/A, -429 T/C, and G82S) using SNaPshot. Our study demonstrated a significant difference in the genotype and allele frequencies of the RAGE G82S polymorphism between the AAA patients and the controls. Further stratification by gender and smoking status revealed that the presence of the RAGE 82S allele confers a higher risk for developing AAA in men and smokers. Moreover, AAA patients with the variant 82S allele of RAGE presented with reduced serum soluble RAGE (sRAGE) production, and this decrease was more significant in men and smokers with AAA. Our study provides preliminary evidence that the 82S allele of RAGE is a risk factor for AAA. This new piece of knowledge regarding RAGE may be clinically important for the prevention and therapy of AAAs.

Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652) between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.

Disordered calcium homeostasis can lead to endoplasmic reticulum (ER) stress. Our previous data showed that time course activation of ER stress contributes to time-related increase in ischemia-reperfusion (I/R) injury. However, it has not been tested whether PI3K/Akt and JAK2/STAT3 pathways play differential roles in reducing ER stress to protect the heart. In the present study, using fasudil which is a specific inhibitor of ROCK, we aimed to investigate whether improved SERCA expression and activity accounts for reduced ER stress by ROCK inhibition, specifically whether PI3K/Akt and JAK2/STAT3 pathways are differentially involved in modulating SERCA activity to reduce ER stress and hence I/R injury. The results showed that during the reperfusion period following 45 min of coronary ligation the infarct size (IS) increased from 3 h of reperfusion (45.4±5.57%) to 24 h reperfusion (64.21±5.43, P<0.05), which was associated with ER stress dependent apoptosis signaling activation including CHOP, Caspase-12 and JNK (P<0.05, respectively).The dynamic ER stress activation was also related to impaired SERCA activity at 24 h of reperfusion. Administration of fasudil at 10 mg/Kg significantly attenuated ROCK activation during reperfusion and resulted in an improved SERCA activity which was closely associated with decreases in temporal activation of ER stress and IS changes. Interestingly, while both PI3K/Akt and JAK2/STAT3 signaling pathways played equal role in the protection offered by ROCK inhibition at 3 h of reperfusion, the rescued SERCA expression and activity at 24 h of reperfusion by fasudil was mainly due to JAK2/STAT3 activation, in which PI3K/Akt signaling shared much less roles.

Substrate inhibition of enzymes can be a major obstacle to the production of valuable chemicals in engineered microorganisms. Here, we show substrate inhibition of lycopene cyclase as the main limitation in carotenoid biosynthesis in Yarrowia lipolytica. To overcome this bottleneck, we exploit two independent approaches. Structure-guided protein engineering yields a variant, Y27R, characterized by complete loss of substrate inhibition without reduction of enzymatic activity. Alternatively, establishing a geranylgeranyl pyrophosphate synthase-mediated flux flow restrictor also prevents the onset of substrate inhibition by diverting metabolic flux away from the inhibitory metabolite while maintaining sufficient flux towards product formation. Both approaches result in high levels of near-exclusive β-carotene production. Ultimately, we construct strains capable of producing 39.5 g/L β-carotene at a productivity of 0.165 g/L/h in bioreactor fermentations (a 1441-fold improvement over the initial strain). Our findings provide effective approaches for removing substrate inhibition in engineering pathways for efficient synthesis of natural products.

Background: The effect of transient electromagnetic fields on the function of pacemakers is not well-evaluated. There is a lack of effective methods for clinicians to reduce electromagnetic susceptibility (EMS) during implantation of pacemakers. This study aimed to evaluate whether a novel method of handling the excess leads in the pocket can lower the EMS of pacemakers and consequently reduce the effect of electromagnetic interference caused by transient electromagnetic fields on pacemakers. Methods: An in vitro chest model was established to simulate the clinical condition of dual-chamber pacemaker implantation. Three different intertwining patterns of excess leads were examined: parallel, twisted once, and multiple twisted-pair. Oscillated currents were injected into a copper electrical wire set horizontally above the model to create a radiated magnetic field to simulate the transient daily electromagnetic exposure of pacemakers. The electromagnetic induction of current was measured. The occurrence of EMS-related adverse events was evaluated when the induced pulsed voltage was applied. Results: Transient electromagnetic fields can induce electromagnetic noise in the pacing loop and inhibit the release of pacing pulses. The multiple twisted-pair intertwining pattern of excess leads was associated with a lower induced voltage amplitude than both the parallel and once-twisted patterns (P < 0.001). Even once twisted could significantly reduce induced voltage amplitude compared to not twisted (P < 0.001). A lower incidence of pacing inhibition was also observed in the multiple twisted-pair group than in the other two groups (P < 0.001). Conclusions: Transient electromagnetic fields can cause pacing inhibition. Twisting the excess leads for multiple turns in the pocket is an effective method to reduce the EMS of the dual-chamber pacemaker.

In this study, pretilachlor was encapsulated into polyurea microcapsules prepared by water-initiated polymerization of polyaryl polymethylene isocyanate and eventually made into pretilachlor microcapsules suspension (PMS). We used response surface methodology (RSM) combined with the Box-Behnken design (BBD) model to optimize the formulation of PMS. The encapsulation efficiency (EE) of PMS was investigated with respect to three independent variables including wall material dosage (X1), emulsifier dosage (X2), and polymerization stirring speed (X3). The results showed that the regression equation model had a satisfactory accuracy in predicting the EE of PMS. To achieve an optimal condition for PMS preparation, the dose of wall material was set to 5%, the dose of emulsifier was set to 3.5% and the polymerization stirring speed was set to 200 rpm. The EE of PMS was up to 95.68% under the optimized condition, and the spherical shape with smooth surface morphology was observed. PMS was also proven to have delayed release capability and in vivo herbicidal activity against barnyard grass [Echinochloa crusgalli (L.) Beauv.] with an LC50 value of 274 mg/L. Furthermore, PMS had efficient weed management compared to commercially available 30% pretilachlor emulsifier (PE), showing a promising potential application for weeding paddy fields.

Due to the increase in computing power, it is possible to improve the feature extraction and data fitting capabilities of DNN networks by increasing their depth and model complexity. However, the big data and complex models greatly increase the training overhead of DNN, so accelerating their training process becomes a key task. The Tianhe-3 peak speed is designed to target E-class, and the huge computing power provides a potential opportunity for DNN training. We implement and extend LeNet, AlexNet, VGG, and ResNet model training for a single MT-2000+ and FT-2000+ compute nodes, as well as extended multi-node clusters, and propose an improved gradient synchronization process for Dynamic Allreduce communication optimization strategy for the gradient synchronization process base on the ARM architecture features of the Tianhe-3 prototype, providing experimental data and theoretical basis for further enhancing and improving the performance of the Tianhe-3 prototype in large-scale distributed training of neural networks.

Subarachnoid hemorrhage (SAH) is a life-threatening disease worldwide, and effective pharmaceutical treatment is still lacking. Celastrol is a plant-derived triterpene which showed neuroprotective potential in several types of brain insults. This study aimed to investigate the effects of celastrol on early brain injury (EBI) after SAH.

The number of wheat ears is an essential indicator for wheat production and yield estimation, but accurately obtaining wheat ears requires expensive manual cost and labor time. Meanwhile, the characteristics of wheat ears provide less information, and the color is consistent with the background, which can be challenging to obtain the number of wheat ears required. In this paper, the performance of Faster regions with convolutional neural networks (Faster R-CNN) and RetinaNet to predict the number of wheat ears for wheat at different growth stages under different conditions is investigated. The results show that using the Global WHEAT dataset for recognition, the RetinaNet method, and the Faster R-CNN method achieve an average accuracy of 0.82 and 0.72, with the RetinaNet method obtaining the highest recognition accuracy. Secondly, using the collected image data for recognition, the R2 of RetinaNet and Faster R-CNN after transfer learning is 0.9722 and 0.8702, respectively, indicating that the recognition accuracy of the RetinaNet method is higher on different data sets. We also tested wheat ears at both the filling and maturity stages; our proposed method has proven to be very robust (the R2 is above 90). This study provides technical support and a reference for automatic wheat ear recognition and yield estimation.

Ferroptosis is a type of lipid peroxidation-dependent cell death that is emerging as a therapeutic target for cancer. However, the mechanisms of ferroptosis during the generation and detoxification of lipid peroxidation products remain rather poorly defined. Here, we report an unexpected role for the eukaryotic translation initiation factor EIF4E as a determinant of ferroptotic sensitivity by controlling lipid peroxidation. A drug screening identified 4EGI-1 and 4E1RCat (previously known as EIF4E-EIF4G1 interaction inhibitors) as powerful inhibitors of ferroptosis. Genetic and functional studies showed that EIF4E (but not EIF4G1) promotes ferroptosis in a translation-independent manner. Using mass spectrometry and subsequent protein-protein interaction analysis, we identified EIF4E as an endogenous repressor of ALDH1B1 in mitochondria. ALDH1B1 belongs to the family of aldehyde dehydrogenases and may metabolize the aldehyde substrate 4-hydroxynonenal (4HNE) at high concentrations. Supraphysiological levels of 4HNE triggered ferroptosis, while low concentrations of 4HNE increased the cell susceptibility to classical ferroptosis inducers by activating the NOX1 pathway. Accordingly, EIF4E-dependent ALDH1B1 inhibition enhanced the anticancer activity of ferroptosis inducers in vitro and in vivo. Our results support a key function of EIF4E in orchestrating lipid peroxidation to ignite ferroptosis.

A considerable number of non-ischemic dilated cardiomyopathy (NDCM) patients had been found to have normalized left ventricular (LV) size and systolic function with tailored medical treatments. Accordingly, we aimed to evaluate if strain parameters assessed by cardiovascular magnetic resonance (CMR) feature tracking (FT) analysis could predict the NDCM recovery.

Parkinson's disease (PD) is characterized by pathological changes within several deep structures of the brain, including the substantia nigra and caudate nucleus. However, changes in interstitial fluid (ISF) flow and the microstructure of the interstitial space (ISS) in the caudate nucleus in PD have not been reported. In this study, we used tracer-based magnetic resonance imaging (MRI) to quantitatively investigate the alterations in ISS and visualize ISF flow in the caudate nucleus in a rotenone-induced rat model of PD treated with and without madopar. In the rotenone-induced rat model, the ISF flow was slowed and the tortuosity of the ISS was significantly decreased. Administration of madopar partially prevented these changes of ISS and ISF. Therefore, our data suggest that tracer-based MRI can be used to monitor the parameters related to ISF flow and ISS microstructure. It is a promising technique to investigate the microstructure and functional changes in the deep brain regions of PD.

Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically. In this report, we present a simple, robust, and cost-effective method to isolate a large quantity of NK EVs. After propagating and activating NK cells ex vivo and then incubating them in exosome-free medium for 48 h, EVs were isolated using a polymer precipitation method. The isolated vesicles contain the tetraspanin CD63, an EV marker, and associated proteins (fibronectin), but are devoid of cytochrome C, a cytoplasmic marker. Nanoparticle tracking analysis showed a size distribution between 100 and 200 nm while transmission electron microscopy imaging displayed vesicles with an oval shape and comparable sizes, fulfilling the definition of EV. Importantly, isolated EV fractions were cytotoxic against cancer cells. Furthermore, our results demonstrate for the first time that isolated activated NK (aNK) cell EVs contain the cytotoxic proteins perforin, granulysin, and granzymes A and B, incorporated from the aNK cells. Activation of caspase -3, -7 and -9 was detected in cancer cells incubated with aNK EVs, and caspase inhibitors blocked aNK EV-induced cytotoxicity, suggesting that aNK EVs activate caspase pathways in target cells. The ability to isolate functional aNK EVs on a large scale may lead to new clinical applications. Abbreviations: NK: natural killer cells; activated NK (aNK) cells; EVs: extracellular vesicles; ALL: acute lymphoblastic leukaemia; aAPC: artificial antigen-presenting cell; TEM: transmission electron microscope; PBMC: peripheral blood mononuclear cells; FBS: foetal bovine serum.

Available data show that approximately 8%-18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy.

The preparation of thermochromic vanadium dioxide (VO2) films in an economical way is of interest to realizing the application of smart windows. Here, we reported a successful preparation of self-assembly VO2 nanoplate films on TiO2-buffered glass by a facile hydrothermal process. The VO2 films composed of triangle-shaped plates standing on substrates exhibit a self-generated porous structure, which favors the transmission of solar light. The porosity of films is easily controlled by changing the concentration of precursor solutions. Excellent thermochromic properties are observed with visible light transmittance as high as 70.3% and solar modulating efficiency up to 9.3% in a VO2 film with porosity of ~35.9%. This work demonstrates a promising technique to promote the commercial utilization of VO2 in smart windows.

Adverse ventricular remodeling is a maladaptive response to acute loss of myocardium and an important risk factor for heart failure following myocardial infarction (MI). Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene‑related peptide family, which may possess potent cardioprotective properties. The aim of the present study was to determine whether IMD1‑53, a mature bioactive form of IMD, may promote therapeutic angiogenesis within the infarcted myocardium, therefore attenuating adverse ventricular remodeling post‑MI. The present study observed that treatment with IMD1‑53 promoted proliferation, migration and tube formation of primary cultured myocardial microvascular endothelial cells (MMVECs). In a rat model of MI, chronic administration of IMD1‑53 increased capillary density in the peri‑infarct zone, attenuated ventricular remodeling and improved cardiac performance post‑MI. Treatment with IMD1‑53 also significantly increased the expression levels of phosphorylated‑AMP‑activated protein kinase (AMPK) and the subsequent activation of endothelial nitric oxide synthase in MMVECs and post‑MI rat myocardium, without a significant influence on the expression of vascular endothelial growth factor. Notably, the in vitro effects of IMD1‑53 on angiogenesis and the in vivo effects of IMD1‑53 on post‑MI ventricular remodeling were largely abrogated by the co‑administration of compound C, an AMPK inhibitor. In conclusion, the present study demonstrated that IMD1‑53 could attenuate adverse ventricular remodeling post‑MI via the promotion of therapeutic angiogenesis, possibly through the activation of AMPK signaling.

To study associations between type 2 diabetes (T2DM) candidate genes and microvascular complications of diabetes (MVCDs), we performed case-control association studies for both T2DM and MVCDs in Han Chinese subjects. We recruited 1,939 unrelated Han Chinese T2DM patients and 918 individuals with normal blood glucose levels as nondiabetic controls. Among T2DM patients, 1116 have MVCDs, 266 have a history of T2DM of >10 years but never developed MVCDs. Eighty-two single-nucleotide polymorphisms (SNPs) in 54 candidate genes were genotyped. Discrete association studies were performed by the PLINK program for T2DM and MVCDs. Significant associations were found among candidate gene SNPs and T2DM, including rs1526167 of the TOX gene (allele A, P = 2.85 × 10(-9), OR = 1.44). The SNP rs10811661 of the CDKN2A/B gene was also associated with T2DM (allele T, P = 4.09 × 10(-7), OR = 1.36). When we used control patients with >10 years of T2DM history without MVCD, we found that the G allele of SNP rs1526167 of the TOX gene was associated with MVCD (nominal P = 4.33 × 10(-4)). In our study, significant associations were found between TOX and CDKN2A/B gene SNPs and T2DM. The TOX polymorphism might account for the higher risk of T2DM and the lower risk of MVCDs in the Han Chinese population.