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Abstract The development and application of Electrochemical Quartz Crystal Microbalance (EQCM) sensing to study metal electroplating, especially for energy storage purposes, are reviewed. The roles of EQCM in describing electrode/electrolyte interface dynamics, such as the electric double‐layer build‐up, ionic/molecular adsorption, metal nucleation, and growth, are addressed. Modeling of the QCM sensor is introduced and its importance is emphasized. Challenges of metal electrode use, including side reactions and dendrite formation, along with their mitigation strategies are reviewed. Numerous factors affecting the electroplating processes, such as electrolyte composition, additives, temperature, and current density, and their influence on the electroplated metals’ mass, structural, and mechanical characteristics are discussed. Looking forward, the need for deeper fundamental understanding and advancing simulations of the QCM signal response as a result of electroplating metal nanostructures is stressed. Further development and integration of innovative EQCM‐strategies will provide unique future means to fundamentally understand and optimize metal electroplating for energy storage and application alike.

ABSTRACTGlass-based nanochannels have become powerful tools for chemical and biological sensing due to their advantages of easy preparation, flexible modification, and high sensitivity. Lately, research on ion transport behaviors in glass-based nanochannels and their applications in nanofluidic iontronics has gradually become a focus, including various ion transport behaviors such as resistive-pulse, ion rectification, ionic current memory, etc. In this review, we summarize the progress of manufacturing methods for glass-based nanochannels and discuss several typical ion transport behaviors of glass-based nanochannels, as well as the main application scenarios of glass-based nanochannels in terms of biosensing, detection, and neuromorphic functions. The enormous assistance of artificial intelligence in the standardized manufacturing process of glass-based nanochannels was anticipated, and the potential development of glass-based nanochannels in achieving neuromorphic functions was expected.

Membrane separation technology with the ability to regulate gas/liquid transport and separation is critical for environmental fields, such as sewerage treatment, multiphase separation, and desalination. Although numerous membranes can dynamically control liquid-phase fluids transport via external stimuli, the transport and separation of gas-phase fluids remains a challenge. Here, we show a temperature-regulation liquid gating membrane that allows in-situ dynamically controllable gas/liquid transfer and multiphase separation by integrating a thermo-wettability responsive porous membrane with functional gating liquid. Experiments and theoretical analysis have demonstrated the temperature-regulation mechanism of this liquid gating system, which is based on thermo-responsive changes of porous membrane surface polarity, leading to changes in affinity between the porous membrane and the gating liquid. In addition, the sandwich configuration with dense Au-coated surfaces and heterogeneous internal components by a bistable interface design enables the liquid gating system to enhance response sensitivity and maintain working stability. This temperature-regulation gas/liquid transfer strategy expands the application range of liquid gating membranes, which are promising in environmental governance, water treatment and multiphase separation.

BackgroundPatients with heart failure (HF) were compared with non-HF people to explore the relationship between the triglyceride glucose (TyG) index and HF in participants with cardiovascular and cerebrovascular diseases.MethodsTyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate logistic regression models were used to investigate the association between the TyG index and the risk of HF. Restricted cubic spline (RCS) analysis was applied to evaluate the dose–response relationship between the TyG index and the risk of HF.ResultsNational Health and Nutrition Examination Survey (NHANES) (2007–2018) was used to analyze the association between TyG and HF in patients. A total of 13,825 participants who had their TyG index measured were included, involving 435 individuals with HF and 13,390 individuals without HF. Those with HF had higher levels of the TyG index compared with those without HF (8.91 ± 0.74 vs. 8.57 ± 0.66, p < 0.001). The odds ratio (OR) of HF for the TyG index from logistic regression was 1.644 and 1.057 in Model 1 (without adjusting for any variables) and Model 4 (adjusted for all covariates), respectively. Compared with individuals with Q1, a higher TyG index was related to the increased risk of HF. Model 1 showed that there was a linear dose–response relationship between the TyG index and HF (p = 0.686). The TyG index predicted the area of the receiver operating characteristic (ROC) curve of 0.602 (95% CI: 0.575–0.629, p < 0.001) and the optimal cutoff value was 8.91.ConclusionThe TyG index was positively associated with the risk of HF. The TyG index may be a therapeutic target and an important predictor of HF.

Abstract Background and Aims Percutaneous transcatheter left atrial appendage (LAA) closure (LAAC) is an effective approach for preventing ischemic stroke in nonvalvular atrial fibrillation patients. Intracardiac echocardiography (ICE), a new imaging modality, is a promising strategy for guiding LAAC. This review highlights the various strategies for ICE‐guided‐LAAC as an option for clinical policy. Methods A comprehensive literature search was conducted of PubMed, ScienceDirect, Ovid Web of Science, SpringerLink, and other notable databases to identify recent peer‐reviewed clinical trials, reviews, and research articles related to ICE and its application in the guidance of LAAC. Results Various methods are used to evaluate the spatial structure and dimensions of the LAA. The main techniques for guiding LAAC are transesophageal echocardiography (TEE), cardiac computed tomography (CTA), and ICE. Among these techniques, the advantages of ICE typically include (1) multiangle and real‐time assessment of intracardiac structure, (2) a reduction in procedural fluoroscopy, (3) reduced operation time and improved workflow in the catheterization laboratory, and (4) the avoidance of general anesthesia and the early detection of complications. Conclusion ICE is a promising strategy for the guidance of LAAC. Among the most advanced and recent technological innovations in cardiovascular imaging in general and volume imaging in particular, ICE offers greater efficacy and safety.

Background: In this study, we aimed to investigate the performance of GALAD, GALAD-C, and GAAP models in Chinese population in comparison to our newly build statistical model. Methods: In this study, we built the AALP model based on age, α-fetoprotein (AFP), AFP-L3, and prothrombin induced by vitamin K absence-II (PIVKA II) to differentiate between patients with HCC and patients with CLD. We then compared the serum levels of AFP-L3 and PIVKA II in patients with HCC who were defined as remission or progression and showed the prognostic value of combined biomarkers. Results: The AUC value of the AALP model for HCC detection was 0.939 and AALP model exhibited a sensitivity of 81 % and a high specificity of 95 %. AALP model also exhibited good performance in the subgroups of patients with CLD. Furthermore, we demonstrated the consistency between imaging results and serum levels of AFP-L3 and PIVKA II. Conclusions: The AALP model achieved a good diagnostic performance and a high sensitivity for predicting HCC patients. Our research also showed that AFP-L3 and PIVKA II are complementary to each other but irreplaceable in the clinical detection and monitoring of HCC.

Aiming at the problem that short-wave point-to-point communication was not reliable enough to meet the actual needs, a wide area cooperative resource allocation algorithm based on shortwave communication access network was proposed.The reliability of the shortwave communication was improved by invoking multiple stations to coordinately guarantee users from different channels.The resource allocation problem was decomposed into two sub-problems of channel and station matching and station allocation.Firstly, the maximum expected success rate matching model was established to match the channel and the station, and the stations allocated to the channel were combined into different guarantee schemes.Then, the fuzzy analytic hierarchy process and the entropy weight method were used to obtain the subjective and objective scores of the scheme, and the optimal scheme was selected through fusion of evidence reasoning.The results show that the proposed algorithm can effectively improve the success rate of shortwave communication and has good adaptability.

The utilization of Erythritol/xylitol eutectic material for low-temperature thermal energy storage and thermal management holds great promise. However, its inability to undergo spontaneous nucleation and crystallization poses a significant obstacle. This research paper introduces a novel nucleation technique that combines gas injection agitation and seeding to address this issue. The study aims to investigate the impact of gas injection tube diameter, thermal environment, and gas injection duration on the nucleation and crystallization characteristics of the material. Experimental analysis reveals that, under optimal conditions, the solidification enthalpy reaches 203.1 J/g, equivalent to 85% of the melting enthalpy. Additionally, the material exhibits excellent thermal cycle stability, with no observed phase separation or deterioration after 100 heating and cooling cycles. Furthermore, the influence of Multi-Walled Carbon Nanotube (MWCNT) nanoparticle additives on nucleation is explored. Different MWCNT additive mass fractions are compared. The obtained results underscore the significance of understanding the effects of gas injection parameters and nanoparticle additives on nucleation and crystallization processes. The enhanced solidification enthalpy, remarkable thermal cycle stability, and insights into MWCNT effects pave the way for broader applications of this promising phase change material in thermal energy storage and thermal management.

Abstract Solar‐driven evaporation has been a promising desalination method for treating concentrated seawater, since it is cost‐effectiveness, simplicity, and environmentally friendly. However, this method faces an unavoidable long‐term problem that the salt generated in the evaporation processes would affect and hinder its evaporation efficiency. Because the salt inevitably crystallizes on the surface of photothermal evaporation materials, and this crystallization process increases with time to impair the material area of the sunlight absorption and evaporation. Here, we show a ternary hierarchical structure based solar‐driven evaporator that reduces the evaporation material surface coverage of the salt to get long‐lasting concentrated brine treatment capacity. This evaporator is constructed by plugging vertically arranged hollow tube arrays across a porous plate. The top, middle, and bottom of the evaporator respectively serve as the salt crystallization site, the evaporation site, and the light absorption site. Meanwhile, the self‐cleaning of the evaporator can be achieved by back diffusion of the crystallized salts. As a result, this efficient and durable evaporator exhibits freshwater production of 10.21 kg/(m2·day) in outdoor experiment in the treatment of the concentrated natural seawater (21.3 wt%).

The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity (MVPA) time and sedentary (SED) time with a history of cardiovascular disease (CVD) and multifactorial (i.e., blood pressure (BP), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin A1c (HbA1c)) control status among type 2 diabetes mellitus (T2DM) patients in China. A cross-sectional analysis of 9152 people with type 2 diabetes from the Multifactorial Intervention on Type 2 Diabetes (MIDiab) study was performed. Patients were grouped according to their self-reported MVPA time (low, < 150 min·week−1; moderate, 150 to < 450 min·week−1; high, ≥ 450 min·week−1) and SED time (low, < 4 h·d–1; moderate, 4 to < 8 h·d–1; high, ≥ 8 h·d–1). Participants who self-reported a history of CVD were identified as having a CVD risk. Odds ratios (ORs) and 95% confidence intervals (CIs) of CVD risk and multifactorial control status associated with MVPA time and SED time were estimated using mixed-effect logistic regression models, adjusting for China’s geographical region characteristics. The participants had a mean ± standard deviation (SD) age of (60.87 ± 8.44) years, 44.5% were women, and 25.1% had CVD. After adjustment for potential confounding factors, an inverse association between high MVPA time and CVD risk that was independent of SED time was found, whereas this association was not observed in the moderate-MVPA group. A higher MVPA time was more likely to have a positive effect on the control of BMI. Compared with the reference group (i.e., those with MVPA time ≥ 450 min·week−1 and SED time

The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury. Valproate is a histone deacetylase inhibitor and multitarget drug, which has been demonstrated to protect retinal neurons. In this study, we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling. We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope. Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein, phosphorylated eukaryotic translation initiation factor 2α, and caspase-12 in the endoplasmic reticulum of retinal ganglion cells. These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress. These findings represent a newly discovered mechanism that regulates how valproate protects neurons.

Abstract Over the last decades, the treatment of the large quantities of hypersaline wastewater generated by conventional industries, inland desalination, and fossil‐fueled power plants has been an important economic issue and also an inescapable green issue. Here, we developed a versatile interfacial heating membrane with alternating utilization of electricity or solar energy for hypersaline water treatment. This hierarchical membrane functions both as a separation membrane and an interface heater, which can quickly (5 wt%), with a high salt rejection rate of 99.99%. This system shows an efficient desalination strategy that can provide fresh water from brines for agriculture and industry, and even for daily life.

Streaming potential is mainly related to electrokinetic energy conversion, which has been considered to show promising potential for advanced technologies, especially sensing. The inherent property of streaming potential is that the energy conversion process is always a continuous state. However, practical applications include many cases of discontinuous states, such as nonlinear sensing. Here, we report a discontinuous streaming potential electrokinetic energy conversion fluid system. Experiments and theoretical calculations reveal that this system exhibits a discontinuous electrokinetic effect and provides a gating liquid slip in micropores, offering the advantages of gating liquid charge coupling and interfacial drag reduction. Moreover, the system is demonstrated in a wearable fall-down alert application. We expect this liquid gating energy conversion system to open up a platform for the design and application of autonomous health monitoring devices, seismic sea wave warning systems, and beyond.

BackgroundPatients with Prader-Willi syndrome (PWS) have a reduced life expectancy due to inflammation-related disease including cardiovascular disease and diabetes. Abnormal activation of peripheral immune system is postulated as a contributor. However, detailed features of the peripheral immune cells in PWS have not been fully elucidated.MethodsSerum inflammatory cytokines were measured in healthy controls (n=13) and PWS patients (n=10) using a 65- multiplex cytokine assays. Changes of the peripheral immune cells in PWS was assessed by single-cell RNA sequencing (scRNA-seq) and high-dimensional mass cytometry (CyTOF) using peripheral blood mononuclear cells (PBMCs) from PWS patients (n=6) and healthy controls (n=12).ResultsPWS patients exhibited hyper-inflammatory signatures in PBMCs and monocytes were the most pronounced. Most inflammatory serum cytokines were increased in PWS, including IL-1β, IL-2R, IL-12p70, and TNF-α. The characteristics of monocytes evaluated by scRNA-seq and CyTOF showed that CD16+ monocytes were significantly increased in PWS patients. Functional pathway analysis revealed that CD16+ monocytes upregulated pathways in PWS were closely associated with TNF/IL-1β- driven inflammation signaling. The CellChat analysis identified CD16+ monocytes transmitted chemokine and cytokine signaling to drive inflammatory process in other cell types. Finally, we explored the PWS deletion region 15q11–q13 might be responsible for elevated levels of inflammation in the peripheral immune system.ConclusionThe study highlights that CD16+ monocytes contributor to the hyper-inflammatory state of PWS which provides potential targets for immunotherapy in the future and expands our knowledge of peripheral immune cells in PWS at the single cell level for the first time.

In field, visual, chemical detection is of use for a wide range of possible applications. Here, the authors report on the creation of a host-guest liquid gating mechanism where detection of the target host triggers gate opening allowing for gas through the liquid gate, which can be used for visual detection.

ABSTRACT Aims/Introduction To evaluate the effectiveness and safety of the novel sodium–glucose cotransporter inhibitor, ertugliflozin, compared with a placebo or other antihyperglycemic agents for type 2 diabetes patients. Materials and Methods We carried out a meta‐analysis of randomized controlled trials to assess the benefits and harms of ertugliflozin. Online database searches were carried out in PubMed, EMBASE, WEB OF SCIENCE and Cochrane from inception up to 11 March 2021. Our end‐points were glycated hemoglobin, fasting plasma glucose and bodyweight. We analyzed the results using a random effects model, computed weighted mean differences and risk ratios. Result A total of 10 randomized controlled trials with 13,223 patients met the inclusion criteria. Compared with a placebo, the weighted mean differences in glycated hemoglobin were −0.77% (95% confidence interval [CI] −0.86 to −0.68%) for ertugliflozin 5 mg, and −0.82% (95% CI −1.01 to −0.63%) for ertugliflozin 15 mg. Ertugliflozin 5 mg daily was also associated with bodyweight loss (weighted mean difference −1.87 kg, 95% CI −2.12 to −1.6). When compared with a placebo, ertugliflozin significantly reduced fasting plasma glucose by −1.62 mmol/L (weighted mean difference, 95% CI −1.82 to −1.42 for 5 mg ertugliflozin). Yet, we observed a rising risk for genital mycotic infections (risk ratio 4.34, 95% CI 2.78–6.76). The results were similar for the 15 mg ertugliflozin group. Conclusion Ertugliflozin effectively reduces glycated hemoglobin levels and provides extra clinical benefits including bodyweight and fasting plasma glucose. Common adverse effects, including genital mycotic infections and so on, were reviewed.

Abstract There has been a growing interest in oil–water separation due to the massive economic and energy loss caused by world-wide oil spill. In the past decades, a new type of superhydrophobic surface has been developed for the efficient oil–water separation, but its large-scale use is significantly limited by its expensive, sophisticated, and fragile roughness structure. Meanwhile, to handle complex operating conditions, the transparency of the superhydrophobic surface has been more attractive due to its potential visual oil–water separation and optical application scenarios. Herein, we showed a simple and versatile strategy to fabricate superhydrophobic coating with robustness and high transparency. Subsequently, this multifunctional superhydrophobic coating was utilized for oil–water separation and indicated excellent separation efficiency. In this strategy, candle soot composed of carbon nanoparticles was deposited onto the substrate and used as a rough surface template. Then, a filmy and hard silica shell was modified onto this template via chemical vapor deposition to reinforce the roughness structure. Following, this soot-silica coated substrate was calcined in air to remove the candle soot template. Finally, based on a rational surface design, this robust silica coating achieved excellent superhydrophobicity thereby showing inherently oil–water separation benefits. This reinforced superhydrophobic coating presented robust superhydrophobicity even after 410 s sand impacting with the height of 40 cm and 20 cycles of sandpaper abrasion. Also, it retained excellent oil–water separation efficiency even after reuses.

Abstract A smart liquid gating membrane is a responsive structural material as a pressure‐driven system that consists of solid membrane and dynamic liquid, responding to the external field. An accurate prediction of rheological and mechanical properties is important for the designs of liquid gating membranes for various applications. However, high predicted accuracy by the traditional sequential method requires a large amount of experimental data, which is not practical in some situations. To conquer these problems, artificial intelligence has promoted the rapid development of material science in recent years, bringing hope to solve these challenges. Here we propose a Kriging machine learning model with an active candidate region, which can be smartly updated by an expected improvement probability method to increase the local accuracy near the most sensitive search region, to predict the mechanical and rheological performance of liquid gating system with an active minimal size of experimental data. Besides this, this new machine learning model can instruct our experiments with optimal size. The methods are then verified by liquid gating membrane with magnetorheological fluids, which would be of wide interest for the design of potential liquid gating applications in drug release, microfluidic logic, dynamic fluid control, and beyond.

The ability to control multiphase flows is essential for applications such as microvalves, chemical analyses, microreactors, and multiphase separators. Furthermore, more specific controls, including the positional navigation control of fluids under steady-state pressures, will improve the development of these applications. Here, we present a fundamentally new photothermally induced liquid gating system that allows light-controlled contactless fluid transport and gas/liquid separations at designated locations, with seconds response times, under constant pressures. Experiments and theoretical calculations demonstrate the stability of our system and its novel regulation mechanism, which is based on a photothermally induced liquid-reconfigurable gate with a change in the surface/interfacial tension and Marangoni flow redistribution of the gating liquid at the illuminated location. This regulation mechanism with positional navigation properties requires neither mechanical parts nor complex accessories and can further enable the miniaturization and integration of various engineering processes. Our application demonstrations confirm the potential of this system in fields of smart valves, multiphase separations, multiphase microreactors, and beyond.

Abstract Background Tumors are the second most common cause of death in humans worldwide, second only to cardiovascular and cerebrovascular diseases. Although methods and techniques for the treatment of tumors continue to improve, the effect is not satisfactory. These may lack effective therapeutic targets. This study aimed to evaluate the value of SNHG12 as a biomarker in the prognosis and clinical characteristics of various cancer patients. Methods We analyzed SNHG12 expression and plotted the survival curves of all cancer samples in the TCGA database using the GEPIA tool. Then, we searched for eligible papers up to April 1, 2019, in databases. Next, the data were extracted from studies examining SNHG12 expression, overall survival and clinicopathological features in patients with malignant tumors. We used Review Manager 5.3 and Stata 15 software to analyze the statistical data. Results In the TCGA database, abnormally high expression of SNHG12 in tumor samples indicates that the patient has a poor prognosis. Results of meta-analysis is that SNHG12 high expression is related to low overall survival (HR = 2.72, 95% CI = 1.95–3.8, P < 0.00001), high tumor stage (OR = 3.94, 95% CI = 2.80–5.53, P < 0.00001), high grade (OR = 2.04, 95% CI = 1.18–3.51, P = 0.01), distant metastasis (OR = 2.20, 95% CI = 1.40–3.46, P = 0.0006), tumor size (OR = 2.79, 95% CI = 1.89–4.14, P < 0.00001), and lymph node metastasis (OR = 2.66, 95% CI = 1.65–4.29, P < 0.0001). Conclusions Our study confirmed that the high expression level of SNHG12 is closely related to the clinicopathological characteristics and prognosis of patients and is a new predictive biomarker for various cancer patients.

A light-responsive and corrosion resistant gas valve with non-thermal effective liquid gating positional flow control under a constant pressure by incorporating dynamic gating liquid with light-responsiveness of solid porous substrate.

In nature, numerous creatures have evolved exquisite structures, surface wettabilities, and interfacial interactions to manipulate fluids for survival, such as water collection, water feeding, air capture, air exchange, etc. These unique functionalities have become a constant source of inspiration for human beings to explore versatile applications. Recently, the control of gas or liquid transport has attracted more and more attention owing to the great potentiality in various fields. Particularly, the drive that does not rely on gravity is of great significance for applications under micro- or reduced-gravity conditions. This review gives a brief description of the fluid transport control mechanisms in living organisms and the biomimetic interfacial design to create controllable fluid manipulation devices. The recent progress of gravity-independent liquid transport, underwater gas transport, and multiphase fluids transport are classified and summarized. The crucial influence of geometric structures and interfacial wettabilities on fluid dynamic behaviors and the driven mechanisms behind these behaviors, along with emerging applications, opportunities, and challenges, are presented.

Heart failure (HF) remains the leading cause of death, morbidity, and medical expenses worldwide. Treatments for HF with reduced ejection fraction have progressed in recent years; however, acute decompensated heart failure remains difficult to treat. The transient receptor potential (TRP) channel family plays roles in various cardiovascular diseases, responding to neurohormonal and mechanical load stimulation. Thus, TRP channels are promising targets for drug discovery, and many studies have evaluated the roles of TRP channels expressed on pain neurons. The natriuretic peptide (NP) family of proteins regulates blood volume, natriuresis, and vasodilation and can antagonize the renin-angiotensin-aldosterone system and participate in the pathogenesis of major cardiovascular diseases, such as HF, coronary atherosclerotic heart disease, and left ventricular hypertrophy. NPs are degraded by neprilysin, and the blood level of NPs has predictive value in the diagnosis and prognostic stratification of HF. In this review, we discuss the relationships between typical TRP family channels (e.g., transient receptor potential cation channel subfamily V member 1 andTRPV1, transient receptor potential cation channel subfamily C member 6) and the NP system (e.g., atrial NP, B-type NP, and C-type NP) and their respective roles in HF. We also discuss novel drugs introduced for the treatment of HF.

Thermal transfer systems involving temperature control through heating, ventilation, and air conditioning applications have emerged as one of the largest energy issues in buildings. Traditional approaches mainly comprise closed and open systems, both of which have certain advantages and disadvantages in a single heating or cooling process. Here we report a thermal adaptive system with beneficial energy-saving properties, which uses functional liquid to exhibit high metastability, providing durability in a temperature-responsive liquid gating system. With an efficient use of energy, this system achieves smart “breathing” during both heating and cooling processes to dynamically tune the indoor temperature. Theoretical modeling and experiments demonstrate that the adaptive, sandwich-structured, membrane-based system can achieve temperature control, producing obvious advantages of energy saving compared with both closed and open systems through the bistable interfacial design of the liquid gating membrane. Further energy saving evaluation of the system on the basis of simulation with current global greenhouse plantation data shows a reduction of energy consumption of 7.9 × 1013 kJ/year, a percentage change of ∼11.6%. Because the adaptive system can be applied to a variety of thermal transfer processes, we expect it to prove useful in a wide range of real-world applications.

While the role of PbTiO3 in PbTiO3/SrTiO3 superlattices has been widely studied, little attention is paid to possible polar topologies in SrTiO3. Here, the authors create atomic-scale vortex–antivortex pairs in the superlattices, expanding the understanding of topological structures.

Abstract Background There are many continuous blood glucose monitoring (CGM) data-based indicators, and most of these focus on a single characteristic of abnormal blood glucose. An ideal index that integrates and evaluates multiple characteristics of blood glucose has not yet been established. Methods In this study, we proposed the glycemic deviation index (GDI) as a novel integrating characteristic, which mainly incorporates the assessment of the glycemic numerical value and variability. To verify its effectiveness, GDI was applied to the simulated 24 h glycemic profiles and the CGM data of type 2 diabetes (T2D) patients (n = 30). Results Evaluation of the GDI of the 24 h simulated glycemic profiles showed that the occurrence of hypoglycemia was numerically the same as hyperglycemia in increasing GDI. Meanwhile, glycemic variability was added as an independent factor. One-way ANOVA results showed that the application of GDI showed statistically significant differences in clinical glycemic parameters, average glycemic parameters, and glycemic variability parameters among the T2D groups with different glycemic levels. Conclusions In conclusion, GDI integrates the characteristics of the numerical value and the variability in blood glucose levels and may be beneficial for the glycemic management of diabetic patients undergoing CGM treatment.

Abstract High-grade glioma is the most common and aggressive primary brain tumor in adults with poor therapeutic efficiency and survival prognosis. Cell division cycle associated 8 (CDCA8) has been well known as a cell cycle regulator and tumor promotor in various malignant tumors. However, its biological role in glioma still remains unclear. Our results showed that high level of CDCA8 was significantly correlated with advanced WHO grade and poor overall survival and disease-free survival prognosis. In vitro and in vivo investigations demonstrated that CDCA8 promoted the glioma malignancy by promoting cell proliferation, cell migration, and inhibiting cell apoptosis. Moreover, we found its synergetic biological protein—E2F1 by the gene microarray chip. In this study, we revealed that CDCA8 synergized with E2F1 facilitated the proliferation and migration of glioma. In conclusion, our study provides a novel promising therapeutic targets and prognostic biomarkers for malignant glioma treatment.

AIM: To quantitatively measure and evaluate the VEGF-A, platelet derived growth factor(PDGF)and pigment epithelium derired factor(PEDF)in the aqueous humor of patients with neovascular glaucoma(NVG). METHODS: Prospectively clinical study. This study involved 23 eyes of 23 patients with advanced NVG and 23 control subjects with age related cataract. Protein concentrations of VEGF-A, PDGF and PEDF in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay(ELISA)tests. RESULTS: The VEGF-A and PDGF concentrations in aqueous humor from NVG patients were(1130.56±69.32)ng/L and(221.95±56.08)ng/L, respectively. Both of them were significantly higher than control subject(226.45±37.46)ng/L,(36.25±7.12)ng/L(PPP>0.05). The concentrations of VEGF-A were closely positive correlated with levels of PDGF in the aqueous humor of patients with NVG(r=0.502, P=0.015). However, the concentrations of VEGF-A were closely negative correlated with levels of PEDF in the aqueous humor of patients with NVG(r=-0.480, P=0.020). CONCLUSION: There were higher levels of VEGF-A and PDGF, and lower level of PEDF in the aqueous humor of patients with NVG. There was a positive correlation between VEGF-A and PDGF, a negative correlation between VEGF-A and PEDF. The combination of anti-VEGF agent, PDGF inhibitor and PEDF may provide a new idea for the treatment of NVG.

Genome instability is a hallmark of tumors and is involved in proliferation, invasion, migration, and treatment resistance of many tumors. However, the relationship of genome instability with gliomas remains unclear. Here, we constructed genome instability-derived long non-coding RNA (lncRNA)-based gene signatures (GILncSig) using genome instability-related lncRNAs derived from somatic mutations. Multiple platforms were used to confirm that the GILncSig were closely related to patient prognosis and clinical characteristics. We found that GILncSig, the glioma microenvironment, and glioma cell DNA methylation-based stemness index (mDNAsi) interacted with each other to form a complex regulatory network. In summary, this study confirmed that GILncSig was an independent prognostic indicator for patients, distinguished high-risk and low-risk groups, and affected immune-cell infiltration and tumor-cell stemness indicators (mDNAsi) in the tumor microenvironment, resulting in tumor heterogeneity and immunotherapy resistance. GILncSig are expected to provide new molecular targets for the clinical treatment of patients with gliomas.

Quintulene, a quintuple non-graphitic cycloarene, is challenging to synthesize. Here, the authors synthesize and characterize the cone-shaped extended quintulene and its bilayer dimer, and disclose its dimerization as an entropy-driven, second-order reaction with a substantial activation energy.

There is growing interest in non-traditional materials for logic applications. Here, the authors demonstrate a domain device architecture based on ferroelectric LiNbO3 crystals with gate voltage controlled transistor without subthreshold swing and source voltage controlled nonvolatile transistor.

A magnetic skyrmion is a particle-like topological soliton, which is an ideal candidate for developing high-density storage and logic devices due to its nonvolatility and tunability. In view of the particle motion characteristics of skyrmion, different skyrmions in a material inevitably interact in the form of short-range repulsion and long-range attraction. In this work, the dynamic characteristics of skyrmion collision in a ferromagnetic Co thin film are investigated by using micromagnetic simulations. It is found that the dynamic behavior of skyrmion after collision is highly dependent on the size of the strip, the initial velocity of skyrmion and magnetic damping constant. For the collision of two skyrmions, when the strip width exceeds the critical value, the skyrmions form a pair and rotate counterclockwise in the form of spiral and breath. It is interesting that the rotation and breath of skyrmions keep the same periodicity under the negligible damping, and the frequency increases with the increase of the initial velocity of skyrmion. Further, the collision of a system of three skyrmions reveals that they interact in pairs to form closed periodic trajectories. The results of the present work not only give an insight into the multi-skyrmion dynamics, but also provide guidance for the development of spintronic devices based on multi-skyrmion motion.

Cement-based materials with a low water/binder ratio contain a high number of unhydrated cement particles, which implies that a rehydration reaction occurs when they encounter water again. This study aimed to explore how rehydration influences the macroscopic and microscopic properties of cement-based materials. The key study findings included that rehydration could still occur in cement-based materials after one year of hydration, and that the capacity for rehydration-induced repair or damage to cement-based materials depended on whether their internal pores could accommodate rehydration products. During rehydration, the compressive strength and porosity of the specimens were found to first increase and then decrease. The capillary water absorption coefficient decreased continuously over a rehydration period of 120 days. As the water/binder ratio rose, the rehydration rate first increased and then decreased. First, the influence of temperature on the rehydration rate was more noticeable when the water/binder ratio was below 0.3; second, whereas adding large amounts of fly ash and silica fume did not prove to be conducive to repairing and enhancing cement-based materials undergoing rehydration, adding slag and small quantities of silica fume, or alternatively compounding small amounts of silica fume and fly ash could improve the repair and enhancement effects of rehydration.

To access the enhancement effect of the topology optimization and porous foam structure, numerical studies were conducted to investigate the heat conduction enhancement (by metal foam, graphite foam, topologically optimized fins, and combinations of metal foam and topologically optimized fins) of phase change material (PCM (n-octadecane)) based tubular thermal energy storage unit for spacecraft. The results showed that metal foam performed better than topologically optimized fins and a combination of metal foam and topology optimized fins, of which conductive material, unit mass, and volume fraction of PCM were the same. Graphite foam (140 W/(m·K)) had the best heat transfer enhancing effect, making PCM melt much faster than other enhancing methods investigated. A multi-criteria decision-making (MCDM) method integrated with the combined weight and TOPSIS method was introduced to evaluate the preferred alternatives’ performance based on the energy storage time, equivalent density, and energy storage. The evaluation pointed out that 3% topologically optimized aluminum fins with 98% copper foam had the best comprehensive performance. This study guided the optimal design of latent heat thermal energy storage units for spacecraft under microgravity.

Electrocaloric effect (ECE) of ferroelectrics has attracted considerable interest due to its potential application in environmentally friendly solid-state refrigeration. The discovery of giant ECE in ferroelectric thin films has greatly renewed the research activities and significantly stimulated experimental and theoretical investigations. In this review, the recent progress on the theoretical modeling of ECE in ferroelectric and antiferroelectric materials are introduced, which mainly focuses on the phase field modeling and first-principles based effective Hamiltonian method. We firstly provide the theoretical foundation and technique details for each method. Then a comprehensive review on the progress in the application of two methods and the strategies to tune the ECE are presented. Finally, we outline the practical procedure on the development of multi-scale computational method without experiemtal parameters for the screening of optimized electrocaloric materials.

Loss of either PINK1 or PRKN causes an early onset Parkinson’s disease (PD) phenotype. Functionally, PINK1 and PRKN work together to mediate stress-activated mitochondrial quality control. Upon mitochondrial damage, PINK1, a ubiquitin kinase and PRKN, a ubiquitin ligase, decorate damaged organelles with phosphorylated ubiquitin for sequestration and degradation in lysosomes, a process known as mitophagy. While several genetic mutations are established to result in loss of mitophagy function, many others have not been extensively characterized and are of unknown significance. Here, we analyzed a set of twenty variants, ten in each gene, focusing on understudied variants mostly from the Parkinson’s progressive marker initiative, with sensitive assays to define potential functional deficits. Our results nominate specific rare genetic PINK1 and PRKN variants that cause loss of enzymatic function in line with a potential causative role for PD. Additionally, we identify several variants with intermediate phenotypes and follow up on two of them by gene editing midbrain-derived neuronal precursor cells. Thereof derived isogenic neurons show a stability defect of the rare PINK1 D525N mutation, while the common PINK1 Q115L substitution results in reduced kinase activity. Our strategy to analyze variants with sensitive functional readouts will help aid diagnostics and disease treatment in line with current genomic and therapeutic advances.

Although JAM-C is abundantly expressed in the retinae and upregulated in choroidal neovascularization (CNV), it remains thus far poorly understood whether it plays a role in the blood-retinal barrier, which is critical to maintain the normal functions of the eye. Here, we report that JAM-C is highly expressed in retinal capillary endothelial cells (RCECs), and VEGF or PDGF-C treatment induced JAM-C translocation from the cytoplasm to the cytomembrane. Moreover, JAM-C knockdown in RCECs inhibited the adhesion and transmigration of macrophages from wet age-related macular degeneration (wAMD) patients to and through RCECs, whereas JAM-C overexpression in RCECs increased the adhesion and transmigration of macrophages from both wAMD patients and healthy controls. Importantly, the JAM-C overexpression-induced transmigration of macrophages from wAMD patients was abolished by the administration of the protein kinase C (PKC) inhibitor GF109203X. Of note, we found that the serum levels of soluble JAM-C were more than twofold higher in wAMD patients than in healthy controls. Mechanistically, we show that JAM-C overexpression or knockdown in RCECs decreased or increased cytosolic Ca2+ concentrations, respectively. Our findings suggest that the dynamic translocation of JAM-C induced by vasoactive molecules might be one of the mechanisms underlying inner endothelial BRB malfunction, and inhibition of JAM-C or PKC in RCECs may help maintain the normal function of the inner BRB. In addition, increased serum soluble JAM-C levels might serve as a molecular marker for wAMD, and modulating JAM-C activity may have potential therapeutic value for the treatment of BRB malfunction-related ocular diseases.

Summary: Conventional printing is worth revisiting because of its established procedures in meeting the surging demand of manufacturing printed electronics, 3D products, etc. However, one goal in penetrating printing into these is to control pattern transfer with no limitation of wettability. Here we introduce a miscible liquid-liquid transfer printing mechanism that can synchronize material preparation and material patterning with desirable properties including limitless selection of raw materials, corrosion resistance, no wetting constraint, and ability to prepare large-area defect-free materials for multi-function applications. Theoretical modeling and experiments demonstrate that donor liquid could be used to make patterns within the bulk of a receiver material, allowing the obtained intrinsically patterned functional materials to be resistant to harsh conditions. Different from current liquid printing technologies, this printing approach enables stable and defect-free material preparation and is expected to prove useful in flexible display, soft electronics, 4D printing, and beyond. : Interface Science; Surface Property; Materials Property; Materials Design Subject Areas: Interface Science, Surface Property, Materials Property, Materials Design

Abstract In this report, we locally modulate the doping type in the n-AlGaN layer by proposing n-AlGaN/p-AlGaN/n-AlGaN (NPN-AlGaN)-structured current spreading layer for AlGaN-based deep ultraviolet light-emitting diodes (DUV LEDs). After inserting a thin p-AlGaN layer into the n-AlGaN electron supplier layer, a conduction band barrier can be generated in the n-type electron supplier layer, which enables the modulation of the lateral current distribution in the p-type hole supplier layer for DUV LEDs. Additionally, according to our studies, the Mg doping concentration, the thickness, the AlN composition for the p-AlGaN insertion layer and the NPN-AlGaN junction number are found to have a great influence on the current spreading effect. A properly designed NPN-AlGaN current spreading layer can improve the optical output power, external quantum efficiency (EQE), and the wall-plug efficiency (WPE) for DUV LEDs.

Liquid gating membranes with molecular-level smooth liquid lining layers break through the limitations of traditional porous membrane materials in gas transport control. Owing to the stable, self-healing, and reconfigurable properties, liquid gating membranes have shown wide application prospects in microfluidics, intelligent valves, chemical reactions, and beyond. Here, we develop a periodic gas transport control system based on the self-oscillating liquid gating membrane. Under continuous gas injection, the gas–liquid interface is reversibly deformed, enabling self-oscillating behavior for discontinuous and periodic gas transport without the need for any complex external changes to the original system. Meanwhile, our experimental analysis reveals that the periodic time and periodic gas release in the system can be regulated. Based on the cycle stability of the system, we further demonstrate the controllability of the system for periodic droplet manipulation in microfluidics. Looking forward, it will offer new opportunities for various applications, such as pneumatic robots, gas-involved chemical reactions, droplet microfluidics, and beyond.

Parkinson’s disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings. Variants of interest were validated using Sanger sequencing. CTSB p.Gly284Val was genotyped in 2077 PD patients and 615 unrelated healthy controls from the Czech Republic, Ireland, Poland, Ukraine, and the USA. The gene burden analysis was conducted for the CTSB gene in an additional 769 PD probands from Mayo Clinic Florida familial PD cohort. CTSB expression and activity in patient-derived fibroblasts and controls were evaluated by qRT-PCR, western blot, immunocytochemistry, and enzymatic assay. The CTSB p.Gly284Val candidate variant was only identified in affected family members. Functional analysis of CTSB patient-derived fibroblasts under basal conditions did not reveal overt changes in endogenous expression, subcellular localization, or enzymatic activity in the heterozygous carrier of the CTSB variant. The identification of the CTSB p.Gly284Val may support the hypothesis that the CTSB locus harbors variants with differing penetrance that can determine the disease risk.

Background/Aims: Glioblastoma multiforme (GBM) is the most devastating and widespread primary central nervous system tumour in adults, with poor survival rate and high mortality rates. Existing treatments do not provide substantial benefits to patients; therefore, novel treatment strategies are required. Peiminine, a natural bioactive compound extracted from the traditional Chinese medicine Fritillaria thunbergii, has many pharmacological effects, especially anticancer activities. However, its anticancer effects on GBM and the underlying mechanism have not been demonstrated. This study was conducted to investigate the potential antitumour effects of peiminine in human GBM cells and to explore the related molecular signalling mechanisms in vitro and in vivo Methods: Cell viability and proliferation were detected with MTT and colony formation assays. Morphological changes associated with autophagy were assessed by transmission electron microscopy (TEM). The cell cycle rate was measured by flow cytometry. To detect changes in related genes and signalling pathways in vitro and in vivo, RNA-seq, Western blotting and immunohistochemical analyses were employed. Results: Peiminine significantly inhibited the proliferation and colony formation of GBM cells and resulted in changes in many tumour-related genes and transcriptional products. The potential anti-GBM role of peiminine might involve cell cycle arrest and autophagic flux blocking via changes in expression of the cyclin D1/CDK network, p62 and LC3. Changes in Changes in flow cytometry results and TEM findings were also observed. Molecular alterations included downregulation of the expression of not only phospho-Akt and phospho-GSK3β but also phospho-AMPK and phospho-ULK1. Furthermore, overexpression of AKT and inhibition of AKT reversed and augmented peiminine-induced cell cycle arrest in GBM cells, respectively. The cellular activation of AMPK reversed the changes in the levels of protein markers of autophagic flux. These results demonstrated that peiminine mediates cell cycle arrest by suppressing AktGSk3β signalling and blocks autophagic flux by depressing AMPK-ULK1 signalling in GBM cells. Finally, peiminine inhibited the growth of U251 gliomas in vivo. Conclusion: Peiminine inhibits glioblastoma in vitro and in vivo via arresting the cell cycle and blocking autophagic flux, suggesting new avenues for GBM therapy.

BackgroundThe tumor immune microenvironment is closely related to the malignant progression and treatment resistance of glioma. Long non-coding RNA (lncRNA) plays a regulatory role in this process. We investigated the pathological mechanisms within the glioma microenvironment and potential immunotherapy resistance related to lncRNAs.MethodWe downloaded datasets derived from glioma patients and analyzed them by hierarchical clustering. Next, we analyzed the immune microenvironment of glioma, related gene expression, and patient survival. Coexpressed lncRNAs were analyzed to generate a model of lncRNAs and immune-related genes. We analyzed the model using survival and Cox regression. Then, univariate, multivariate, receiver operating characteristic (ROC), and principle component analysis (PCA) methods were used to verify the accuracy of the model. Finally, GSEA was used to evaluate which functions and pathways were associated with the differential genes.ResultsNormal brain tissue maintains a low-medium immune state, and gliomas are clearly divided into three groups (low to high immunity). The stromal, immune, and estimate scores increased along with immunity, while tumor purity decreased. Further, human leukocyte antigen (HLA), programmed cell death-1 (PDL1), T cell immunoglobulin and mucin domain 3 (TIM-3), B7-H3, and cytotoxic T lymphocyte-associated antigen-4 (CTLA4) expression increases concomitantly with immune state, and the patient prognosis worsens. Five immune gene-related lncRNAs (AP001007.1, LBX-AS1, MIR155HG, MAPT-AS1, and LINC00515) were screened to construct risk models. We found that risk scores are related to patient prognosis and clinical characteristics, and are positively correlated with PDL1, TIM-3, and B7-H3 expression. These lncRNAs may regulate the tumor immune microenvironment through cytokine–cytokine receptor interactions, complement, and coagulation cascades, and may promote CD8 + T cell, regulatory T cell, M1 macrophage, and infiltrating neutrophils activity in the high-immunity group. In vitro, the abnormal expression of immune-related lncRNAs and the relationship between risk scores and immune-related indicators (PDL1, CTLA4, CD3, CD8, iNOS) were verified by q-PCR and immunohistochemistry (IHC).ConclusionFor the first time, we constructed immune gene-related lncRNA risk models. The risk score may be a new biomarker for tumor immune subtypes and provide molecular targets for glioma immunotherapy.

Stomata in the plant leaves are channels for gas exchange between the plants and the atmosphere. The gas exchange rate can be regulated by adjusting the opening and closing of stoma under the external stimuli, which plays a vital role in plant survival. Under visible light irradiation, the stomata open for gas exchange with the surroundings, while under intense UV light irradiation, the stomata close to prevent the moisture loss of plants from excessive transpiration. Inspired by this stomatal self-protection behavior, we have constructed a bioinspired photo-responsive liquid gating membrane (BPRLGM) through infusing the photo-responsive gating liquid obtained by dissolving the azobenzene-based photo-responsive surfactant molecules (AzoC8F15) in N,N-Dimethylacetamide (DMAC) into nylon porous substrate, which can reversibly switch the open/closed states under different photo-stimuli. Theoretical analysis and experimental data have demonstrated that the reversible photoisomerization of azobenzene-based surfactant molecules induces a change in surface tension of the photo-responsive gating liquid, which eventually results in the reversible variation of substantial critical pressure for gas through BPRLGM under alternating UV (PCritical (off)) and visible (PCritical (on)) light irradiations. Therefore, driven by a pressure difference ΔP between PCritical (on) and PCritical (off), the reversible switches on the open/closed states of this photo-responsive liquid gating membrane can be realized under photo-stimuli. This bioinspired membrane with switchable open/closed liquid gating performance under photo-stimuli has the opportunity to be used in the precise and contactless control of microfluidics.

In the field of robotics, soft robots have been showing great potential in the areas of medical care, education, service, rescue, exploration, detection, and wearable devices due to their inherently high flexibility, good compliance, excellent adaptability, and natural and safe interactivity. Pneumatic soft robots occupy an essential position among soft robots because of their features such as lightweight, high efficiency, non-pollution, and environmental adaptability. Thanks to its mentioned benefits, increasing research interests have been attracted to the development of novel types of pneumatic soft robots in the last decades. This article aims to investigate the solutions to develop and research the pneumatic soft robot. This paper reviews the status and the main progress of the recent research on pneumatic soft robots. Furthermore, a discussion about the challenges and benefits of the recent advancement of the pneumatic soft robot is provided.

Background/Aims: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. Methods: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo. Results: The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice. Conclusions: The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.

Fouling of solid surfaces is a problem when designing microchannel systems for applications such as bioassays and drug delivery. Here Hou et al. propose a way to overcome this issue by controlling fluid flow by means of an immiscible functional liquid partly infiltrated in a porous solid matrix.

Background/Aims: Glioma is the most devastating cancer in the brain and has a poor prognosis in adults. Therefore, there is a critical need for novel therapeutic strategies for the management of glioma patients. Isogambogenic acid, an active compound extracted from the Chinese herb Garcinia hanburyi, induces autophagic cell death. Methods: Cell viability was detected with MTT assays. Cell proliferation was assessed using the colony formation assay. Morphological changes associated with autophagy and apoptosis were tested by TEM and Hoechst staining, respectively. The apoptosis rate was measured by flow cytometry. Western blot, immunofluorescence and immunohistochemical analyses were used to detect protein expression. U87-derived xenografts were established for the examination of the effect of isogambogenic acid on glioma growth in vivo. Results: Isogambogenic acid induced autophagic death in U87 and U251 cells, and blocking late-stage autophagy markedly enhanced the antiproliferative activities of isogambogenic acid. Moreover, we observed the activation of AMPK-mTOR signalling in isogambogenic acid-treated glioma cells. Furthermore, the activation of AMPK or the inhibition of mTOR augmented isogambogenic acid-induced autophagy. Inhibition of autophagy attenuated apoptosis in isogambogenic acid-treated glioma cells. Finally, isogambogenic acid inhibited the growth of U87 glioma in vivo. Conclusion: Isogambogenic acid inhibits the growth of glioma via activation of the AMPK-mTOR signalling pathway, which may provide evidence for future clinical applications in glioma therapy.

Abstract Background Early onset Parkinson’s disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 and parkin operate in pathways that preserve mitochondrial integrity, but the function of DJ-1 and how it relates to PINK1 and parkin is poorly understood. Methods A series of unbiased high-content screens were used to analyze changes at the protein, RNA, and metabolite level in rodent brains lacking DJ-1. Results were validated using targeted approaches, and cellular assays were performed to probe the mechanisms involved. Results We find that in both rat and mouse brains, DJ-1 knockout results in an age-dependent accumulation of hexokinase 1 in the cytosol, away from its usual location at the mitochondria, with subsequent activation of the polyol pathway of glucose metabolism in vivo. Both in the brain and in cultured cells, DJ-1 deficiency is associated with accumulation of the phosphatase PTEN that antagonizes the kinase AKT. In cells, addition of an inhibitor of AKT (MK2206) or addition of a peptide to dissociate association of hexokinases from mitochondria both inhibit the PINK1/parkin pathway, which works to maintain mitochondrial integrity. Conclusion Hexokinases are an important link between three major genetic causes of early onset Parkinson’s disease. Because aging is associated with deregulated nutrient sensing, these results help explain why DJ-1 is associated with age-dependent disease.

Abstract Gout is a chronic disease resulting from elevated serum urate (SU). Previous genome-wide association studies (GWAS) have identified dozens of susceptibility loci for SU/gout, but few have been conducted for Chinese descent. Here, we try to extensively investigate whether these loci contribute to gout risk in Han Chinese. A total of 2255 variants in linkage disequilibrium (LD) with GWAS identified SU/gout associated variants were analyzed in a Han Chinese cohort of 1255 gout patients and 1848 controls. Cumulative genetic risk score analysis was performed to assess the cumulative effect of multiple “risk” variants on gout incidence. 23 variants (41%) of LD pruned variants set (n = 56) showed nominal association with gout in our sample (p