Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases.

Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. In 2022, the CVDs contributed to 19.8 million deaths globally, accounting for one-third of all global deaths. With an aging population and changing lifestyles, CVDs pose a major threat to human health. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are communication platforms between cellular organelles and regulate cellular physiological functions, including apoptosis, autophagy, and programmed necrosis. Further research has shown that MAMs play a critical role in the pathogenesis of CVDs, including myocardial ischemia and reperfusion injury, heart failure, pulmonary hypertension, and coronary atherosclerosis. This suggests that MAMs could be an important therapeutic target for managing CVDs. The goal of this study is to summarize the protein complex of MAMs, discuss its role in the pathological mechanisms of CVDs in terms of its functions such as Ca2+ transport, apoptotic signaling, and lipid metabolism, and suggest the possibility of MAMs as a potential therapeutic approach.

MAGPIE: accurate pathogenic prediction for multiple variant types using machine learning approach.

Identifying pathogenic variants from the vast majority of nucleotide variation remains a challenge. We present a method named Multimodal Annotation Generated Pathogenic Impact Evaluator (MAGPIE) that predicts the pathogenicity of multi-type variants. MAGPIE uses the ClinVar dataset for training and demonstrates superior performance in both the independent test set and multiple orthogonal validation datasets, accurately predicting variant pathogenicity. Notably, MAGPIE performs best in predicting the pathogenicity of rare variants and highly imbalanced datasets. Overall, results underline the robustness of MAGPIE as a valuable tool for predicting pathogenicity in various types of human genome variations. MAGPIE is available at https://github.com/shenlab-genomics/magpie .

Multidimensional Interactive Cascading Nanochips for Detection of Multiple Liver Diseases via Precise Metabolite Profiling.

It is challenging to detect and differentiate multiple diseases with high complexity/similarity from the same organ. Metabolic analysis based on nanomatrix-assisted laser desorption/ionization mass spectrometry (NMALDI-MS) is a promising platform for disease diagnosis, while the enhanced property of its core nanomatrix materials has plenty of room for improvement. Herein, a multidimensional interactive cascade nanochip composed of iron oxide nanoparticles (FeNPs)/MXene/gold nanoparticles (AuNPs), IMG, is reported for serum metabolic profiling to achieve high-throughput detection of multiple liver diseases. MXene serves as a multi-binding site and an electron-hole source for ionization during NMALDI-MS analysis. Introduction of AuNPs with surface plasmon resonance (SPR) properties facilitates surface charge accumulation and rapid energy conversion. FeNPs are integrated into the MXene/Au nanocomposite to sharply reduce the thermal conductivity of the nanochip with negligible heat loss for strong thermally-driven desorption, and construct a multi-interaction proton transport pathway with MXene and AuNPs for strong ionization. Analysis of these enhanced serum fingerprint signals detected from the IMG nanochip through a neural network model results in differentiation of multiple liver diseases via a single pass and revelation of potential metabolic biomarkers. The promising method can rapidly and accurately screen various liver diseases, thus allowing timely treatment of liver diseases.

Application of 3D printing in ear reconstruction with autogenous costal cartilage: A systematic review.

PURPOSE: In recent years, 3D printing technology has been employed as a production method that builds materials layer upon layer, providing notable advantages in terms of individual customization and production efficiency. Autologous costal cartilage ear reconstruction has seen substantial changes due to 3D printing technology. In this context, this research evaluated the prospects and applications of 3D printing in ear reconstruction education, preoperative planning and simulation, the production of intraoperative guide plates, and other related areas. METHODOLOGY: All articles eligible for consideration were sourced through a comprehensive search of PubMed, the Cochrane Library, EMBASE, and Web of Science from inception to May 22, 2023. Two reviewers extracted data on the manufacturing process and interventions. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the research. Database searching yielded 283 records, of which 24 articles were selected for qualitative analysis. RESULTS: The utilization of 3D printing is becoming increasingly widespread in autogenous costal cartilage ear reconstruction, from education to the application of preoperative design and intraoperative guide plates production, possessing a substantial influence on surgical training, the enhancement of surgical effects, complications reduction, and so forth. CONCLUSION: This study sought to determine the application value and further development potential of 3D printing in autologous costal cartilage ear reconstruction. However, there is a lack of conclusive evidence on its effectiveness when compared to conventional strategies because of the limited number of cohort studies and randomized controlled trials. Simultaneously, the evaluation of the effect lacks objective and quantitative evaluation criteria, with most of them being emotional sentiments and ratings, making it difficult to execute a quantitative synthetic analysis. It is hoped that more large-scale comparative studies will be undertaken, and an objective and standard effect evaluation system will be implemented in the future.

A novel electrospun nanofiber system with PEGylated paclitaxel nanocrystals enhancing the transmucus permeability and in situ retention for an efficient cervicovaginal cancer therapy.

Overcoming the vaginal barrier to achieve sufficient drug penetration and retention is a huge obstacle for drug delivery in chemotherapeutics for cervical cancer. In this study, we investigate the feasibility of a novel composite nanocrystal/nanofiber system for improving the transmucus penetration and, thus, enhancing retention and drug delivery to the lesion of a cervicovaginal tumor. Herein, paclitaxel (PTX) was sequentially formulated in the form of nanocrystals, coated with polydopamine (PDA), and modified with PEG. The nanocrystals (NCs@PDA-PEG) were creatively fabricated to create a composite nanofibrous membrane (NCs@PDA-PEG NFs) by using an electrospinning technique. The morphology, size distribution, drug loading, encapsulation efficiency, X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectra, in vitro release, in vivo vaginal retention, apoptosis index, anti-tumor efficacy in a murine cervicovaginal tumor model, and local irritation were characterized. The NCs@PDA-PEG were formulated in a cube-like shape with an average size of 385.6 ± 35.47 nm; they were dispersed in electrospun nanofibers, and the drug loading was 7.94 %. The XRD curves indicated that the phase state of PTX changed after the creation of the nanocrystals. The FTIR spectra showed that the drug and the excipients were compatible with each other. In vitro delivery showed that the dissolution of PTX in the electrospun nanofibers was significantly faster than that when using bulk PTX. Compared with the PTX NC NFs, the NC@PDA-PEG NFs exhibited prolonged vaginal residence, superior transmucus penetration, minimal mucosal irritation, and significant tumor inhibition efficacy after the intravaginal administration of the NFs in tumor-bearing mice. In conclusion, by acting as novel pharmaceutical repositories, NCs@PDA-PEG NFs can be promising candidates for non-invasive local treatment, leading to efficient tumor inhibition in cervicovaginal cancer.

Polyurethane Foam Skeleton-Based Phase Change Hydrogel for Efficient Battery Thermal Management with Favorable Antivibration Performance.

Efficient thermal management is critical to ensure the safe and reliable operation of lithium-ion batteries (LIBs) as they are highly sensitive to temperature changes. Meanwhile, LIBs are exposed to various external forces during operation, such as vibration, shock, and oscillation, which may disrupt the physical and chemical processes inside the battery and lead to a decreased performance and shortened life. Here, we designed a phase change hydrogel (PCH) pad based on the polyurethane (PU) foam skeleton and demonstrated its effectiveness in efficient thermal management and improving antivibration performance. The thermal conductivity of the prepared composite is 0.65 W/(m·K), while the thermal contact resistance could decrease to ∼20 K·cm2/W under 60 °C. It exhibits a flexible contact transformation during the phase transition, resulting in enhanced interfacial heat transfer and storage rate, as well as improved resistance against external impacts. The temperature of the battery module wrapped with a composite plate decreases by 11.4 °C during the 6C discharge. Moreover, the additional heat generated by external vibration is only half that of the bare battery, and the temperature difference could reach 5.2 °C, demonstrating the effective buffering effect of PCH@PU in mitigating long-term discharge-induced increases in internal resistance. The developed PCH@PU, known for its exceptional thermal management and favorable antivibration performance, holds promising potential for widespread utilization in the field of power battery heat dissipation.

Genome Mining of Linaridins Provides Insights into the Widely Distributed LinC Oxidoreductases.

Linaridins are a family of underexplored ribosomally synthesized and post-translationally modified peptides despite the prevalence of their biosynthetic gene clusters (BGCs) in microbial genomes, as shown by bioinformatic studies. Our genome mining efforts reveal that 96 putative oxidoreductase genes, namely, LinC, are encoded in linaridin BGCs. We heterologously expressed two such LinC-containing linaridin BGCs, yan and ydn, from Streptomyces yunnanensis and obtained three new linaridins, named yunnanaridins A-C (1-3). Their structures are characterized by Z-configurations of the dehydrobutyrines and the presence of a variety of epimerized amino acid residues. Yunnanaridin A (1) is the sixth member of the family of type-B linaridins, whereas yunnanaridins B (2) and C (3) represent the first examples of expressed type-C linaridins. Interestingly, heterologous expression of the same BGCs with LinC in-frame knockouts produced the same compounds. This work expands the structural diversity of linaridins and provides evidence for the notion that the widespread LinCs may not be involved in linaridin biosynthesis.

The Clinical Efficacy Evaluation of Thigh Liposuction Based on 3-Dimensional Digital Technology: A Quantitative Study.

BACKGROUND: There is a lack of convenient and accurate objective methods to evaluate the clinical efficacy of thigh liposuction. METHODS: This retrospective study involved the 3-dimensional images of 19 patients who underwent bilateral thigh liposuction. Data such as volume change and volume change rate before and after surgery, circumference change, and circumference change rate of 3 planes (upper, middle, and lower) were analyzed. The correlation between body mass index and volume change rate and between preoperative circumference and circumference change rate of different planes were determined. RESULTS: There were significant differences between the preoperative and postoperative volume and circumference of 3 planes of 19 patients (38 thighs). The rate of change in total volume (16.90 ± 5.55%) correlated with the circumference change rate at the top of the thigh. There was also a linear relationship between body mass index and volume change rate, but not between preoperative circumference and circumference change rate. CONCLUSIONS: Three-dimensional imaging technology can accurately quantify the volume and circumference change of the thigh to objectively evaluate the clinical efficacy of thigh liposuction.

Suppression of apoptosis in osteocytes, the potential way of natural medicine in the treatment of osteonecrosis of the femoral head.

OBJECTIVES: In the field of orthopedics, osteonecrosis of the femoral head (ONFH) is a common and refractory condition sometimes known as "immortal cancer" due to its complicated etiology, difficult treatment, and high disability rate. This paper's main goal is to examine the most recent literature on the pro-apoptotic effects of traditional Chinese medicine TCM monomers or compounds on osteocytes and to provide a summary of the potential signal routes. METHODS: The last ten years' worth of literature on ONFH as well as the anti-ONFH effects of aqueous extracts and monomers from traditional Chinese medicine were compiled. CONCLUSIONS: When all the relevant signal pathways are considered, the key apoptotic routes include those mediated by the mitochondrial pathway, the MAPK signaling pathway, the PI3K/Akt signaling pathway, the Wnt/-catenin signaling pathway, the HIF-1 signaling network, etc. As a result, we anticipate that this study will shed light on the value of TCM and its constituent parts for treating ONFH by inducing apoptosis in osteocytes and offer some guidance for the future development of innovative medications as anti-ONFH medications in clinical settings.

Deep Double Incomplete Multi-View Multi-Label Learning With Incomplete Labels and Missing Views.

View missing and label missing are two challenging problems in the applications of multi-view multi-label classification scenery. In the past years, many efforts have been made to address the incomplete multi-view learning or incomplete multi-label learning problem. However, few works can simultaneously handle the challenging case with both the incomplete issues. In this article, we propose a new incomplete multi-view multi-label learning network to address this challenging issue. The proposed method is composed of four major parts: view-specific deep feature extraction network, weighted representation fusion module, classification module, and view-specific deep decoder network. By, respectively, integrating the view missing information and label missing information into the weighted fusion module and classification module, the proposed method can effectively reduce the negative influence caused by two such incomplete issues and sufficiently explore the available data and label information to obtain the most discriminative feature extractor and classifier. Furthermore, our method can be trained in both supervised and semi-supervised manners, which has important implications for flexible deployment. Experimental results on five benchmarks in supervised and semi-supervised cases demonstrate that the proposed method can greatly enhance the classification performance on the difficult incomplete multi-view multi-label classification tasks with missing labels and missing views.

Safety Helmet Detection Based on YOLOv5 Driven by Super-Resolution Reconstruction.

High-resolution image transmission is required in safety helmet detection problems in the construction industry, which makes it difficult for existing image detection methods to achieve high-speed detection. To overcome this problem, a novel super-resolution (SR) reconstruction module is designed to improve the resolution of images before the detection module. In the super-resolution reconstruction module, the multichannel attention mechanism module is used to improve the breadth of feature capture. Furthermore, a novel CSP (Cross Stage Partial) module of YOLO (You Only Look Once) v5 is presented to reduce information loss and gradient confusion. Experiments are performed to validate the proposed algorithm. The PSNR (peak signal-to-noise ratio) of the proposed module is 29.420, and the SSIM (structural similarity) reaches 0.855. These results show that the proposed model works well for safety helmet detection in construction industries.

Potential Mechanisms Between HF and COPD: New Insights From Bioinformatics.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are closely related in clinical practice. This study aimed to investigate the co-genetic characteristics and potential molecular mechanisms of HF and COPD. HF and COPD datasets were downloaded from gene expression omnibus database. After identifying common differentially expressed genes (DEGs), the functional analysis highlighted the critical role of extracellular matrix and ribosomal signaling pathways in both diseases. In addition, GeneMANIA's results suggested that the 2 diseases were related to immune infiltration, and CIBERSORT suggested the role of macrophages. We also discovered 4 TFs and 1408 miRNAs linked to both diseases, and salbutamol may positively affect them.

Finite-time and fixed-time stabilization of multiple memristive neural networks with nonlinear coupling.

This brief presents the finite-time stabilization and fixed-time stabilization of multiple memristor-based neural networks (MMNNs) with nonlinear coupling. Under the retarded memristive theory, the generalized Lyapunov functional method, extended Filippov-framework and Laplacian matrix theory, we can realize both the finite-time stabilization and fixed-time stabilization problem of MMNNs by designing novel state-feedback controller and the corresponding adaptive controller with regulate parameters. Moreover, we assess the bounds of settling time for the both two kinds of stabilization respectively, and we deeply analyze the influence of initial desiring values and the linear growth condition of the controller on the system. Finally, the benefits of the proposed approach and the experimental analysis are demonstrated by numerical examples.

Function of Perceived Corporate Social Responsibility in Safety of Sports Activities and Home Aerobic Equipment in the Late Period of COVID-19.

The pandemic has impacted various industries, including the sports industry. However, corporate social responsibility (CSR) can mitigate the adverse effects of the crisis and promote the sports industry. To analyze the effect of CSR, the study examined the impact of perceived corporate social responsibility on injury prevention expectation, injury risk perception, and health up-gradation with the mediation of sports safety measures. There are 259 sportsmen of local sports bodies provided the data through a self-administered survey. Data analysis was conducted through Smart-PLS and SEM techniques. The outcome of the analysis showed that perceived corporate social responsibility leads to injury prevention expectation, injury risk perception, and health up-gradation. Also, the study found that sports safety measure mediates the relationship between perceived corporate social responsibility and injury prevention expectation, between perceived corporate social responsibility and injury risk perception, and between perceived corporate social responsibility and health up-gradation among sportsmen of local sports bodies. The theoretical implications were presented related to the significance of CSR and sports safety measure and their impact on sportsmen injury prevention expectation, health, and risk perception. The practical implications were related to the management of local sports bodies and how they can induce CSR initiatives and programs. Some limitations related to sample size, incorporating other variables, examining the model in other contexts, and using different study designs, have also been mentioned in the study.

Regulating the Spin State of FeIII Enhances the Magnetic Effect of the Molecular Catalysis Mechanism.

Aqueous-phase oxygen evolution reaction (OER) is the bottleneck of water splitting. The formation of the O-O bond involves the generation of paramagnetic oxygen molecules from the diamagnetic hydroxides. The spin configurations might play an important role in aqueous-phase molecular electrocatalysis. However, spintronic electrocatalysis is almost an uncultivated land for the exploration of the oxygen molecular catalysis process. Herein, we present a novel magnetic FeIII site spin-splitting strategy, wherein the electronic structure and spin states of the FeIII sites are effectively induced and optimized by the Jahn-Teller effect of Cu2+. The theoretical calculations and operando attenuated total reflectance-infrared Fourier transform infrared (ATR FT-IR) reveal the facilitation for the O-O bond formation, which accelerates the production of O2 from OH- and improves the OER activity. The Cu1-Ni6Fe2-LDH catalyst exhibits a low overpotential of 210 mV at 10 mA cm-2 and a low Tafel slope (33.7 mV dec-1), better than those of the initial Cu0-Ni6Fe2-LDHs (278 mV, 101.6 mV dec-1). With the Cu2+ regulation, we have realized the transformation of NiFe-LDHs from ferrimagnets to ferromagnets and showcase that the OER performance of Cu-NiFe-LDHs significantly increases compared with that of NiFe-LDHs under the effect of a magnetic field for the first time. The magnetic-field-assisted Cu1-Ni6Fe2-LDHs provide an ultralow overpotential of 180 mV at 10 mA cm-2, which is currently one of the best OER performances. The combination of the magnetic field and spin configuration provides new principles for the development of high-performance catalysts and understandings of the catalytic mechanism from the spintronic level.

[Effects of ankle exoskeleton assistance during human walking on lower limb muscle contractions and coordination patterns].

Lower limb ankle exoskeletons have been used to improve walking efficiency and assist the elderly and patients with motor dysfunction in daily activities or rehabilitation training, while the assistance patterns may influence the wearer's lower limb muscle activities and coordination patterns. In this paper, we aim to evaluate the effects of different ankle exoskeleton assistance patterns on wearer's lower limb muscle activities and coordination patterns. A tethered ankle exoskeleton with nine assistance patterns that combined with differenet actuation timing values and torque magnitude levels was used to assist human walking. Lower limb muscle surface electromyography signals were collected from 7 participants walking on a treadmill at a speed of 1.25 m/s. Results showed that the soleus muscle activities were significantly reduced during assisted walking. In one assistance pattern with peak time in 49% of stride and peak torque at 0.7 N·m/kg, the soleus muscle activity was decreased by (38.5 ± 10.8)%. Compared with actuation timing, the assistance torque magnitude had a more significant influence on soleus muscle activity. In all assistance patterns, the eight lower limb muscle activities could be decomposed to five basic muscle synergies. The muscle synergies changed little under assistance with appropriate actuation timing and torque magnitude. Besides, co-contraction indexs of soleus and tibialis anterior, rectus femoris and semitendinosus under exoskeleton assistance were higher than normal walking. Our results are expected to help to understand how healthy wearers adjust their neuromuscular control mechanisms to adapt to different exoskeleton assistance patterns, and provide reference to select appropriate assistance to improve walking efficiency.

Induction of PI3K/Akt-Mediated Apoptosis in Osteoclasts Is a Key Approach for Buxue Tongluo Pills to Treat Osteonecrosis of the Femoral Head.

The Buxue Tongluo pill (BTP) is a self-made pill with the functions of nourishing blood, promoting blood circulation, dredging collaterals, and relieving pain. It consists of Angelica sinensis (Oliv.) Diels, Pheretima aspergillum (E.Perrier), Panax notoginseng (Burk.) F. H. Chen, Astragalus membranaceus (Fisch.) Bge, and Glycyrrhiza uralensis Fisch. Various clinical practices have confirmed the therapeutic effect of BTP on osteonecrosis of the femoral head (ONFH), but little attention has been paid to the study of its bioactive ingredients and related mechanisms of action. In this study, UPLC/MS-MS combined with GEO data mining was used to construct a bioactive ingredient library of BTP and a differentially expressed gene (DEG) library for ONFH. Subsequently, Cytoscape (3.7.2) software was used to analyze the protein-protein interaction between BTP and DEGs of ONFH to screen the key targets, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 34 bioactive compounds were screened, which acted on 1,232 targets. A total of 178 DEGs were collected, and 17 key genes were obtained after two screenings. By bioinformatics annotation on these key genes, a total of 354 gene ontology (GO) functional annotation analyses and 42 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. The present study found that GO and KEGG enrichment were mainly related to apoptosis, suggesting that BTP may exert an anti-ONFH effect by promoting osteoclast apoptosis. Experiments in vitro demonstrated that BTP could increase the mitochondrial membrane potential (MMP) and induce remarkable apoptosis in osteoclasts. Furthermore, we determined the apoptosis marker of cleaved(C)-caspase-3, bcl-2, and bax and found that BTP could upregulate the C-caspase-3 and bax expression in osteoclasts and decrease the expression of bcl-2, p-Akt, and p-PI3K in a dose-dependent manner, indicating that BTP could induce PI3K/Akt-mediated apoptosis in osteoclasts to treat ONFH. This study explored the pharmacodynamic basis and mechanism of BTP against ONFH from the perspective of systemic pharmacology, laying a foundation for further elucidating the therapeutic effects of BTP against ONFH.

In Situ Controllable Fabrication of Two-Dimensional Magnetic Fe3O4/TiO2@Ti3C2Tx Composites for Highly Efficient Phosphopeptides Enrichment.

Highly efficient enrichment of phosphopeptides is of great significance for phosphoproteomics-related biological and pathological processes research, but it remains challenging due to the lack of affinity materials which hold high enrichment efficiency and capacity. Ti3C2Tx MXene, a novel two-dimensional material with outstanding physicochemical properties, has attracted wide research interests for application in various fields. However, there are few reports on the use of MXene-derived materials for phosphopeptides separation in the biomedical field. In this work, we proposed a facile one-pot method that in situ oxidation and modification of Ti3C2Tx MXene, to prepare two-dimensional (2D) magnetic Fe3O4/TiO2@Ti3C2Tx composites for potential application in phosphopeptides enrichment. Benefiting from the outstanding magnetic responsiveness and multiaffinity sites (Ti-O, Fe-O, and NH2 groups), the Fe3O4/TiO2@Ti3C2Tx composites possessed excellent enrichment performance with high sensitivity (0.1 fmol µL-1), excellent selectivity (ß-casein: bovine serum albumin = 1:5000, molar ratio), good repeatability (5 times), and high enrichment capacity (200 mg g-1). Moreover, the results of selective enrichment of phosphopeptides from nonfat milk, human saliva, human serum, and rat brain lysates indicated the great potential of Fe3O4/TiO2@Ti3C2Tx composites in low-abundance phosphopeptides enrichment from complex biological samples. This work has put forward a versatile method to prepare magnetic MXene composites and promoted the use of MXene composites in phosphoproteome in biomedicine.

Horizontally arranged zinc platelet electrodeposits modulated by fluorinated covalent organic framework film for high-rate and durable aqueous zinc ion batteries.

Rechargeable aqueous zinc-ion batteries (RZIBs) provide a promising complementarity to the existing lithium-ion batteries due to their low cost, non-toxicity and intrinsic safety. However, Zn anodes suffer from zinc dendrite growth and electrolyte corrosion, resulting in poor reversibility. Here, we develop an ultrathin, fluorinated two-dimensional porous covalent organic framework (FCOF) film as a protective layer on the Zn surface. The strong interaction between fluorine (F) in FCOF and Zn reduces the surface energy of the Zn (002) crystal plane, enabling the preferred growth of (002) planes during the electrodeposition process. As a result, Zn deposits show horizontally arranged platelet morphology with (002) orientations preferred. Furthermore, F-containing nanochannels facilitate ion transport and prevent electrolyte penetration for improving corrosion resistance. The FCOF@Zn symmetric cells achieve stability for over 750 h at an ultrahigh current density of 40 mA cm-2. The high-areal-capacity full cells demonstrate hundreds of cycles under high Zn utilization conditions.