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To study the anti-fatigue effect of walnut proteolytic enzymes and to provide scientific basis for the development and utilization of its functional products. Walnut isolated protein (WPI) was extracted from supercritically extracted walnut meal, and the WPI was enzymatically digested by Dregea sinensis Hemsl. protease. The hydrolysis degree (DH) was used as an index to study the optimal conditions for the preparation of walnut peptides, and the effects of different molecular weights of walnut proteins on the alleviation of exercise fatigue in mice were also investigated. The mice were randomly divided into five groups, and the test samples were orally gavaged daily for one month. Finally, weight-bearing and exhaustion swimming experiments were performed to determine the serum urea nitrogen (BUN), lactic acid (LA), hepatic glycogen (HG), myo-glycogen (MG), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) contents. SDS-PAGE gel electrophoresis showed that the WPI was significantly degraded by Dregea sinensis Hemsl. Protease. The one-way combined response surface experiment showed that the DH was up to 30.1% when the material-liquid ratio was 9:100, pH9.6, enzyme addition quality 9.4%, enzyme digestion time 180 min, and enzyme digestion temperature 63 ℃. HE staining showed that the enzyme extracted by the use of Dregea sinensis Hemsl. Protease did not have any toxicity side effects on mice. Compared with other groups, the enzymatic digests with molecular weight less than 3000 Da showed a decrease in LA and BUN content, an increase in HG and MG content, and a more significant prolongation of weight-bearing swimming time (P

During the operation of the Salt Cavern Flow Battery (SCFB) system, the rock surrounding a salt cavern is subjected to erosion by the electrolyte. To study the creep characteristics of electrolyte-bearing salt rock under long-term triaxial cyclic loading in SCFB, a triaxial creep experiment with a cycle period of 1 day was conducted. The results indicated that, when not subjected to failure, the axial stress-strain curve of electrolyte-bearing sample undergoes only two phases of “sparse-dense”, entering dense phase approximately 4 cycles earlier than that of sample without electrolyte. Under the same stress conditions, the strain generated in electrolyte-bearing salt rock surpasses that of sample without electrolyte, demonstrating an initial rapid increase followed by a gradual stabilization trend. The stress-strain curve of electrolyte-bearing sample in a single cycle can be divided into six stages. The number of cycles has almost no effect on the axial strain in stages I, IV, V and VI, and the axial strain in stages IV and VI is basically 0. Additionally, the elastic deformation generated in stage I is basically recovered in stage V. The strain in stage II gradually decreases and disappears in the 4th cycle, which is 13 cycles earlier than that of the sample without electrolyte. The creep rate of electrolyte-bearing sample shows a trend of “gradual decrease—basically stabilization” as the number of cycles increases, and the creep experiment contains only the decay creep stage and steady creep stage. Irreversible deformation of electrolyte-bearing sample exhibits a gradual decrease followed by stabilization with increasing number of cycles. The research findings hold significant implications for the stability analysis of SCFB systems.

BackgroundShoemaking industry workers are prone to work-related musculoskeletal disorders (WMSDs) due to long-term awkward postures during the work process. There is little research on the prevalence and influencing factors of WMSDs in the knee region of this industry, and it should be taken seriously. ObjectiveTo estimate the prevalence of work-related knee pain among shoemaking workers and analyze the related influencing factors. MethodsA total of 6982 shoemaking workers were selected from 26 shoemaking factories in Guangdong, Hubei, Fujian, Chongqing, Shandong, Zhejiang, and Jingxi by convenience sampling. Prevalence of work-related knee pain in past year, demographic characteristics, occupational related factors, and work posture were collected by a cross-sectional survey using the electronic version of Musculoskeletal Disorder Questionnaire. Logistic regression analysis was used to analyze the influencing factors that may lead to work-related knee pain.ResultsThis survey collected 6982 valid questionnaires with a recovery rate of 98.3%. The prevalence of work-related knee pain of shoemaking workers in the past 12 months was 13.0% (908/6982). According to the results of logistic regression analysis, compared with workers with less than 5 years of service, workers with 5-10 years of service (OR=1.21, 95%CI: 1.02, 1.45) and more than 10 years (1.53, 95%CI: 1.27, 1.83) showed a higher risk of knee WMSDs; sometimes, often and very frequent (reference : rarely or never) long-term standing (OR=1.33, 95%CI: 1.08, 1.64; OR=2.67, 95%CI: 2.10, 3.39; OR=2.75, 95%CI: 2.08, 3.63) and sometimes, often and very frequent (reference: rarely or never) long-term squatting or kneeling (OR=1.80, 95%CI: 1.47, 2.21; OR=2.43, 95%CI: 1.58, 3.75; OR=3.22, 95%CI: 1.66, 6.24) increased the risk of knee pain: long-term bending (OR=1.59, 95%CI: 1.34, 1.89) and often repeated movement of lower limbs and ankles (OR=1.48, 95%CI: 1.25, 1.75) were also risk factors for knee WMSDs among shoemaking industry workers (P

Precise pose estimation of textureless objects from RGB images without the use of depth information remains a significant challenge in computer vision. This paper introduces an RGB-based method for 6D pose estimation, designed for robotic grasping in 6 degrees of freedom. We proposed a novel network named the Region-based Keypoint Detection Transformer, which leverages the concept of set prediction. This network generates numerous set points, establishing a fuzzy representation of keypoints. These set points are interpreted as keypoints using a voting mechanism for PnP-based 6D pose solving and refinement, guiding robotic precise grasping actions. To facilitate the training of set points, specialized losses are introduced, including a set-based coordinate loss and a soft index probability loss for multi-label classification. Evaluated on the LineMOD dataset, our method achieved an ADD(-S) accuracy of 92.92 % and a 2D projection accuracy of 98.72 %. Additionally, practical robotic grasping experiments were conducted in real-world environments, covering both static and dynamic grasping, as well as bin-picking tasks. The picking success rate and completion rate reached 93.02 % and 100.00 % respectively, with the success rate surpassing the optimal baseline by 2.11 %. These results demonstrate the accuracy and robustness of our method in cluttered environments. The code is available at https://github.com/Nx1021/RKDT.

Salt cavern flow batteries (SCFBs) are an energy storage technology that utilize salt caverns to store electrolytes of flow batteries with a saturated NaCl solution as the supporting electrolyte. However, the geological characteristics of salt caverns differ significantly from above-ground storage tanks, leading to complex issues in storing electrolytes within salt caverns. Therefore, investigating and summarizing these issues is crucial for the advancement of SCFB technology. This paper’s innovation lies in its comprehensive review of the current state and development trends in SCFBs both domestically and internationally. First, the current development status of SCFB energy storage technology both domestically and internationally is summarized. Then, eight main issues are proposed from the perspectives of salt cavern geological characteristics (tightness, conductivity, ions, and temperature) and electrolyte properties (selection, permeability, corrosion, and concentration). Finally, a novel SCFB system is proposed to address the most critical issue, which is the low concentration and uneven distribution of active materials in the current SCFB system. The review in this paper not only comprehensively summarizes the development status of SCFBs both domestically and internationally, but also points out the direction for the future research focussing on SCFBs.

Oils are important high-density energy sources for increasing the amount of metabolizable energy in poultry diets, and reducing the intake of saturated fatty acids (SFA) and increasing the intake of beneficial unsaturated fatty acids (UFA) in feed are highly important for reducing muscle cholesterol accumulation and improving meat quality and fat composition. The aim of this study was to investigate the effects of walnut oil powder (MC) and hydrogenated palm oil powder (PC) diets on growth performance, meat quality and cecal gut microbes in broiler chickens. Both the MC and PC treatments significantly affected the pH, drip loss rate and cooking loss rate (P

Non-dairy creamer is a class of microencapsulated powdered fats and oils that are widely used in the food industry. However, the oils used in it are hydrogenated vegetable oils, which contain large amounts of saturated fatty acids and are extremely harmful to the human body. This study investigated the effects of replacing hydrogenated vegetable oil with walnut oil to prepare walnut non-dairy creamer on lipid levels and intestinal microorganisms in mice. The results show that low-dose walnut non-dairy creamer significantly decreased the contents of TC and TG in serum and increased the content of HDL-C (p < 0.01). The contents of MDA, ALT, and AST were significantly decreased, while the content of SOD was increased (p < 0.01). The abundance of Firmicutes in the walnut non-dairy creamer group decreased, and the abundance of Bacteroidetes/Firmicutes (B/F) increased, which significantly increased the richness of Lactobacillus and Oscillospira (p < 0.01). Allobaculum richness was significantly decreased (p < 0.01). In conclusion, a low dose of walnut non-dairy creamer can effectively promote the metabolism of blood lipids in vivo, alleviate oxidative stress injury and lipid accumulation damage to mouse hepatocytes, and ameliorate the adverse effects of a high-fat diet on the intestinal microbiota of mice. This study provides a theoretical basis for the replacement of traditional non-dairy creamer and the research and development of walnut deep processing.

Traditional integer-order admittance control is widely used in industrial scenarios requiring force control, but integer-order models often struggle to accurately depict fractional-order-controlled objects, leading to precision bottlenecks in the field of precision machining. For robotic precision polishing scenarios, to enhance the stability of the control process, we propose a more physically accurate five-parameter fractional-order admittance control model. To reduce contact impact, we introduce a method combining the rear fastest tracking differential with fractional-order admittance control. The optimal parameter identification for the fractional-order system is completed through Pareto optimality and a time–frequency domain fusion analysis of the control system. We completed the optimal parameter identification in a simulation, which is applied to the robotic precision polishing scenario. This method significantly enhanced the force control precision, reducing the error margin from 15% to 5%.

IntroductionWith the increasing demand for protein utilization, exploring new protein resources has become a research hotspot. Sacha Inchi Protein (SIP) is a high-quality plant protein extracted from Sacha Inchi meal. This study aimed to investigate the impact of SIP on mouse metabolomics and gut microbiota diversity and explore the underlying pathways responsible for its health benefits.MethodsIn this study, the structural composition of SIP was investigated, and the effects of SIP on fecal metabolomics and intestinal microorganisms in mice were explored by LC–MS metabolomics technology analysis and 16S rRNA gene sequencing.ResultsThe results showed that SIP was rich in amino acids, with the highest Manuscript Click here to view linked References content of arginine, which accounted for 22.98% of the total amino acid content; the potential fecal metabolites of mice in the SIP group involved lipid metabolism, sphingolipid metabolism, arginine biosynthesis, and amino acid metabolism; SIP altered the microbial composition of the cecum in mice, decreased the Firmicutes/Bacteroidetes value, and It decreased the abundance of the harmful intestinal bacteria Actinobacteriota and Desulfobacterota, and increased the abundance of the beneficial intestinal bacteria Faecalibaculum, Dubosiella.DiscussionIn conclusion, SIP is a high-quality plant protein with great potential for development in lipid-lowering, intestinal health, and mental illness, providing valuable clues for further research on its health-promoting mechanisms.

Abstract We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions. The CLS was tested with seven independent datasets and compared with 21 physicians, and the system’s diagnostic ability exceeded 20 physicians by training stage six. The optimal integrated method we developed is expected accurately diagnose breast masses. This method can also be extended to the intelligent diagnosis of masses in other organs. Overall, our findings have potential value in further promoting the application of AI diagnosis in precision medicine.

Bacterial outer membrane vesicles (OMVs) are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine. In this study, OMVs are demonstrated as promising antitumor therapeutics. OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity, but the therapeutic window of OMVs is narrow for its toxicity. We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) into OMVs as a therapeutic platform. We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform, providing combinational photodynamic/chemo-/immunotherapy, eradicates triple-negative breast tumors in mice without side effects. Importantly, this strategy also effectively prevents tumor metastasis to the lung. This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.

Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response via various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation.

In recent years, green and healthy foods have attracted much attention. Plant-based foods have become an alternative to animal-derived foods. In this study, we used walnut and purple rice as the primary raw materials to produce a fermented plant drink. The process included boiling, mixing, grinding, inoculation, fermentation, and sterilization. We then analyzed the similarities and differences between the resulting walnut and purple rice fermented plant drink and an unfermented walnut and purple rice plant drink, as well as dairy-based yoghurt, in terms of physical chemistry, flavor, and sensory characteristics. We also examined the similarities and differences between the walnut and purple rice fermented plant drink and room-temperature yoghurt. The study results revealed that the walnut and purple rice fermented plant drink exhibited greater viscosity than the walnut and purple rice unfermented plant drink and room-temperature yoghurt. Additionally, the former displayed enhanced stability and recovery ability. Notably, distinguishable differences were observed between the three samples in terms of the presence of unknown volatiles and the umami signal, as indicated by electronic nose/tongue and GC-IMS analyses. The umami flavor of the walnut and purple rice fermented plant drink surpasses that of room-temperature yoghurt, while its taste is less salty than that of the walnut and purple rice plant drink. Despite possessing a weaker aroma than dairy-based yogurt, it is more potent than the walnut and purple rice plant drink. Additionally, its relative abundance of olefins, ketones, and alcohols enhances its unique flavor profile, surpassing both other options. Based on sensory analysis, it can be deduced that walnut and purple rice fermented plant drink has the highest overall acceptance rate.

Abstract Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery.

Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. Most asthmatic patients are well-established using standard treatment strategies and advanced biologicals. However, a small group of patients who do not respond to biological treatments or are not effectively controlled by available treatment strategies remain a clinical challenge. Therefore, new therapies are urgently needed for poorly controlled asthma. Mesenchymal stem/stromal cells (MSCs) have shown therapeutic potential in relieving airway inflammation and repairing impaired immune balance in preclinical trials owing to their immunomodulatory abilities. Noteworthy, MSCs exerted a therapeutic effect on steroid-resistant asthma with rare side effects in asthmatic models. Nevertheless, adverse factors such as limited obtained number, nutrient and oxygen deprivation in vitro , and cell senescence or apoptosis affected the survival rate and homing efficiency of MSCs, thus limiting the efficacy of MSCs in asthma. In this review, we elaborate on the roles and underlying mechanisms of MSCs in the treatment of asthma from the perspective of their source, immunogenicity, homing, differentiation, and immunomodulatory capacity and summarize strategies to improve their therapeutic effect.

Background: The expression of TCF20 is the most widespread in brain tissue. TCF20 depletion or mutation can affect the proliferation and differentiation of embryonic neurons, leading to developmental disorder of the central nervous system and subsequent rare syndrome featuring.Case presentation: Here, we report a 3-year-old boy carrying a novel frameshift mutation in TCF20, c.1839_1872del (p.Met613IlefsTer159), resulting in multisystem disease. In addition to symptoms of neurodevelopmental disorder, a large head circumference, special appearance, overgrowth, abnormal testicular descent. Remarkably, previously infrequently reported symptoms of the immune system such as hyperimmunoglobulinemia E (hyper-IgE), immune thrombocytopenic purpura, cows milk protein allergy, and wheezy bronchitis, were observed.Conclusion: This study broadens the mutation spectrum of the TCF20 and the phenotypic spectrum of TCF20-associated disease.

Ferroptosis represents a novel non-apoptotic form of regulated cell death that is driven by iron-dependent lipid peroxidation and plays vital roles in various diseases including cardiovascular diseases, neurodegenerative disorders and cancers. Plenty of iron metabolism-related proteins, regulators of lipid peroxidation, and oxidative stress-related molecules are engaged in ferroptosis and can regulate this complex biological process. Sirtuins have broad functional significance and are targets of many drugs in the clinic. Recently, a growing number of studies have revealed that sirtuins can participate in the occurrence of ferroptosis by affecting many aspects such as redox balance, iron metabolism, and lipid metabolism. This article reviewed the studies on the roles of sirtuins in ferroptosis and the related molecular mechanisms, highlighting valuable targets for the prevention and treatment of ferroptosis-associated diseases.

To increase natural gas storage capacity and further utilize salt mine resources, salt cavern gas storage in the Yunying salt mine, Hubei Province, China, was simultaneously constructed in two different mining layers (K3 and K4). The purpose of this study was to investigate the long-term feasibility of operating salt caverns for gas storage in two mining layers. Based on the geological conditions and sonar test results, the geometric parameters for the salt caverns in the two mining layers were designed, and a 3D geomechanical model was built to predict the cavern stability. The corresponding evaluation index included the displacement, volume shrinkage rate, equivalent strain, and dilatancy factor. The results show that simultaneously operating salt cavern gas storage in two mining layers is feasible, and the operational pressures for the salt caverns in mining layers K3 and K4 should be no less than 4–9 and 7–12 MPa, respectively, to satisfy the stability requirements. The surrounding rock of the salt caverns presents a larger displacement and volume reduction compared with cases in which the salt caverns are operated in a single mining layer. Increasing the injection–withdrawal frequency increases the deformation of the surrounding rock.

Background/purpose: Graft bone maturation and remodeling in the maxillary sinus require adequate angiogenesis and osteoprogenitor cells migration from the surrounding bony walls and Schneiderian membrane. This study aimed to evaluate the influence of anatomical factors related to maxillary sinus on the outcomes of transcrestal sinus floor elevation using cone-beam computed tomography (CBCT). Materials and methods: Forty-five patients (63 elevated sites) were included in this study. CBCT were obtained preoperatively, immediately and 6 months after surgery. The anatomical features of residual bone height, maxillary sinus width, maxillary sinus angle and Schneiderian membrane thickness were measured on preoperative CBCT. Descriptive statistics and correlation analysis were conducted to evaluate the influence of anatomical factors on outcome parameters, including sinus lift height, graft bone resorption and marginal bone loss. Results: The results showed that there was a positive correlation between sinus width and graft bone resorption. A significantly positive correlation between sinus angle and graft bone resorption was also found. Conclusion: Our findings indicate that the anatomical factors of maxillary sinus (sinus width and sinus angle) have influence on the linear change of bone grafts after transcrestal sinus floor elevation.

Abstract Targeted drug delivery to the glioblastoma (GBM) overcoming blood–brain barrier (BBB) has been challenging. Exosomes are promising vehicles for brain tumor drug delivery, but the production and purification hinder its application for nanomedicine. Besides, the formation of protein corona (PC) may affect the behaviour of nanocarriers. Here, multifunctional exosomes-mimetics (EM) are developed and decorated with angiopep-2 (Ang) for enhancing GBM drug delivery by manipulating PC. Docetaxel (DTX)-loaded EM with Ang modification (DTX@Ang-EM) show less absorption of serum proteins and phagocytosis by macrophages. Ang-EM show enhanced BBB penetration ability and targeting ability to the GBM. Ang-EM-mediated delivery increase the concentration of DTX in the tumor area. The multifunctional DTX@Ang-EM exhibits significant inhibition effects on orthotopic GBM growth with reduced side effects of the chemotherapeutic. Findings from this study indicate that the developed DTX@Ang-EM provide a new strategy for targeted brain drug delivery and GBM therapy. Graphical abstract

BackgroundThe published findings on the link between the resistin (RETN) gene polymorphism and type 2 diabetes mellitus (T2DM) risk are still contradictory. Here, through a meta-analysis, we summarized a more precise evaluation of their connection by synthesizing existing research.MethodsPubMed, Google Scholar, and Web of Science were electronically searched, and all cited sources were manually searched. The heterogeneity of effects was tested and all statistical analyses were performed in Stata 12.0.ResultsA total of 23 studies with 10,651 cases and 14,366 controls on RETN -420C/G polymorphism were included. The overall results showed that the association of RETN -420C/G polymorphism and T2DM susceptibility was not significant [for the allelic model: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.87–1.10, pheterogeneity

Glycogen storage disease type IV (GSD IV), caused by a mutation in the glycogen branching enzyme 1 (GBE1) gene, is a rare metabolic disorder with an autosomal recessive inheritance that involves the liver, neuromuscular, and cardiac systems. Here, we reported a case of familial GSD IV induced by novel compound heterozygous mutations in GBE1. The proband (at age 1) and her younger brother (at age 10 months) manifested hepatosplenomegaly, liver dysfunction, and growth retardation at onset, followed by progressive disease deterioration to liver cirrhosis with liver failure. During the disease course, the proband presented rare intractable asymptomatic hypoglycemia. The liver pathology was in line with GSD IV. Both cases carried pathogenic compound heterozygous mutations in GBE1 mutations, i.e., a missense mutation (c.271T>A, p. W91R) in exon 2 and a deletion mutation in partial exons 3–7. Both mutations are first reported. The internationally pioneered split-liver transplantation was performed during progression to end-stage liver disease, and the patients had normal liver function and blood glucose after. This study broadens the mutation spectrum of the GBE1 gene and the phenotypic spectrum of GSD IV.

Abstract Nonalcoholic fatty liver disease (NAFLD) has become the world's largest chronic liver disease, while there is still no specific drug to treat NAFLD. Traditional Chinese Medicine (TCM) have been widely used in hepatic diseases for centuries in Asia, and TCM’s holistic concept and differentiation treatment of NAFLD show their advantages in the treatment of this complex metabolic disease. However, the multi-compounds and multi-targets are big obstacle for the study of TCM. Here, we summarize the pharmacological actions of active ingredients from frequently used single herbs in TCM compounds. The combined mechanism of herbs in TCM compounds are further discussed to explore their comprehensive effects on NAFLD. This article aims to summarize multiple functions and find the common ground for TCM treatment on NAFLD, thus providing enrichment to the scientific connotation of TCM theories and promotes the exploration of TCM therapies on NAFLD.

Abstract Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include ‘nanovesicles (NVs)’, ‘exosome-mimetic (EM)’ and ‘hybrid exosomes (HEs)’, which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

Graphical Abstract

Extracellular vesicles (EVs) are nanovesicles involved in multiple biological functions. Small EVs (sEVs) are emerging as therapeutics and drug delivery systems for their contents, natural carrier properties, and nanoscale size. Despite various clinical application potentials, little is known about the effects of storage conditions on sEVs for functional analysis and therapeutic use. In this study, we evaluated the stability of sEVs stored at 4 °C, −20 °C, and −80 °C up to 28 days and compared them to fresh sEVs. Also, the effect of freeze-thawing circles on the quantity of sEVs was assessed. We found that different storage temperatures, along with shelf life, impact the stability of sEVs when compared to freshly isolated sEVs. Storage changes the size distribution, decreases quantity and contents, and impacts cellular uptake and biodistribution of sEVs. For functional studies, isolated sEVs are suggested to be analyzed freshly or stored at 4 °C or −20 °C for short-term preservation depending on study design; but −80 °C condition would be more preferable for long-term preservation of sEVs for therapeutic application.

The antiparasitic drug nitazoxanide (NTZ) has received considerable attention for its potential in cancer therapy. In this study, we demonstrate that tizoxanide (TIZ), an active metabolite of NTZ, exhibits antiglioma activity in vitro and in vivo by inducing G2/M cell cycle arrest and apoptosis. In vitro, TIZ dose-dependently inhibited the proliferation of U87, U118, and A172 human glioblastoma (GBM) cells at 48 h with IC50 values of 1.10, 2.31, and 0.73 µM, respectively. Treatment with TIZ (1 and 10 µM) also dose-dependently inhibited the colony formation of these GBM cells and accumulated ROS damage in the nucleus. In silico target fishing combined with network pharmacological disease spectrum analyses of GBM revealed that cycle-dependent kinase 1 (CDK1) is the most compatible target for TIZ and molecular docking by Molecule Operating Environment (MOE) software confirmed it. Mechanistically, TIZ inhibited the phosphorylation of CDK1 at Thr161 and decreased the activity of the CDK1/cyclin B1 complex, arresting the cell cycle at the G2/M phase. TIZ may induce apoptosis via the ROS-mediated apoptotic pathway. In vivo, TIZ suppressed the growth of established subcutaneous and intracranial orthotopic xenograft models of GBM without causing obvious side effects and prolonged the survival of nude mice bearing glioma. Taken together, our results demonstrated that TIZ might be a promising chemotherapy drug in the treatment of GBM.

This study investigates the affecting pattern of cooling rates on the physical and mechanical properties of granite at high temperature. The different cooling rates are realized by cooling the heated granite specimens in the air at room temperature, −60 °C, and −100 °C. Slow cooling in the unplugged furnace is also performed on an additional set of specimens as a reference group. Physical and mechanical tests are performed on the granite specimens after thermal shock treatments. The results indicate a decreasing trend of the dry density, P-wave velocity, strength, and fracture toughness, and an increasing trend of the porosity, as the heating level or the cooling rate ascends. The microscopic observation on the fracture surface of the tested specimens manifests the deteriorating effect of thermal shock with a higher cooling rate, where the transition from trans-granular and intra-granular fracturing to intergranular fracturing serves to explain the variation pattern of the properties obtained in the lab tests.

The kinematics analysis of the 3-PRS+2P hybrid mechanism is carried out. The inverse kinematics equation of the mechanism is established by combining the geometric method with the coordinate transformation，and the analytical solution of the inverse kinematics of the mechanism is obtained. The position of the cutter location is transformed into the three vertex coordinates of the moving platform，and the positive kinematics model of the mechanism is established. At the same time，the two parameter numerical extension homotopy algorithm is used to find the numerical solution of the positive kinematics. The analytic expression of the inverse solution is calculated based on Maple. The structure of the solution is simple and easy to be programmed. The iterative process of the positive solution is realized based on the Matlab programming，and the numerical solution reaches the precision requirement. The correctness of the positive and inverse solutions is verified through the modeling，computation and simulation of UG and Matlab.

Abstract The FeF3·0.33H2O cathode material can exhibit a high capacity and high energy density through transfer of multiple electrons in the conversion reaction and has attracted great attention from researchers. However, the low conductivity of FeF3·0.33H2O greatly restricts its application. Generally, carbon nanotubes (CNTs) and graphene can be used as conductive networks to improve the conductivities of active materials. In this work, the FeF3·0.33H2O cathode material was synthesized via a liquid-phase method, and the FeF3·0.33H2O/CNT + graphene nanocomposite was successfully fabricated by introduction of CNTs and graphene conductive networks. The electrochemical results illustrate that FeF3·0.33H2O/CNT + graphene nanocomposite delivers a high discharge capacity of 234.2 mAh g−1 in the voltage range of 1.8–4.5 V (vs. Li+/Li) at 0.1 C rate, exhibits a prominent cycling performance (193.1 mAh g−1 after 50 cycles at 0.2 C rate), and rate capability (140.4 mAh g−1 at 5 C rate). Therefore, the electronic conductivity and electrochemical performance of the FeF3·0.33H2O cathode material modified with CNTs and graphene composite conductive network can be effectively improved.

Abstract A sol-gel method was adopted to obtain LiNi0.5-xGaxMn1.5O4 (x = 0, 0.04, 0.06, 0.08, 0.1) samples. The effect of Ga doping on LiNi0.5Mn1.5O4 and its optimum content were investigated, and the electrochemical properties at room temperature and at a high temperature were discussed. The structural, morphological, and vibrational features of LiNi0.5-xGaxMn1.5O4 (x = 0, 0.04, 0.06, 0.08, 0.1) compounds were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR). The XRD results demonstrate that all samples have a disordered spinel structure with a space group of Fd3m, and Ga doping restrains the formation of the LixNi1-xO secondary phase. FT-IR analysis reveals that Ga doping increases the degree of cation disorder. The SEM results reveal that all samples possess a fine spinel octahedron crystal. The electrochemical performance of the samples was investigated by galvanostatic charge/discharge tests, dQ/dV plots, and electrochemical impedance spectroscopy (EIS). The LiNi0.44Ga0.06Mn1.5O4 sample with the optimum content shows a superior rate performance and cycle stability after Ga doping, especially at a high discharge rate and high temperature. In addition, the LiNi0.44Ga0.06Mn1.5O4 sample retained 98.3% of its initial capacity of 115.7 mAhg−1 at the 3 C discharge rate after 100 cycles, whereas the pristine sample delivered a discharge capacity of 87.3 mAhg−1 at 3 C with a capacity retention of 80% at the 100th cycle. Compared with the pristine material, the LiNi0.44Ga0.06Mn1.5O4 sample showed a high capacity retention from 74 to 98.4% after 50 cycles at a 1 C discharge rate and 55 °C.

Abstract ᅟ Ag-coated spherical Li4Ti5O12 composite was successfully synthesized via a sol-gel-assisted hydrothermal method using an ethylene glycol and silver nitrate mixture as the precursor, and the influence of the Ag coating contents on the electrochemical properties of its was extensively investigated. X-ray diffraction (XRD) analysis indicated that the Ag coating does not change the spinel structure of Li4Ti5O12. The electrochemical impedance spectroscopy (EIS) analyses demonstrated that the excellent electrical conductivity of the Li4Ti5O12/Ag resulted from the presence of the highly conducting silver coating layer. Additionally, the nano-thick silver layer, which was uniformly coated on the particles, significantly improved this material’s rate capability. As a consequence, the silver-coated micron-sized spherial Li4Ti5O12 exhibited excellent electrochemical performance. Thus, with an appropriate silver content of 5 wt.%, the Li4Ti5O12/Ag delivered the highest capacity of 186.34 mAh g−1 at 0.5C, which is higher than that of other samples, and maintained 92.69% of its initial capacity at 5C after 100 cycles. Even at 10C after 100 cycles, it still had a capacity retention of 89.17%, demonstrating remarkable cycling stability. Trial registration ISRCTN NARL-D-17-00568

Abstract A Cr3+ and F− composite-doped LiNi0.5Mn1.5O4 cathode material was synthesized by the solid-state method, and the influence of the doping amount on the material’s physical and electrochemical properties was investigated. The structure and morphology of the cathode material were characterized by XRD, SEM, TEM, and HRTEM, and the results revealed that the sample exhibited clear spinel features. No Cr3+ and F− impurity phases were found, and the spinel structure became more stable. The results of the charge/discharge tests, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) test results suggested that LiCr0.05Ni0.475Mn1.475O3.95F0.05 in which the Cr3+ and F− doping amounts were both 0.05, had the optimal electrochemical properties, with discharge rates of 0.1, 0.5, 2, 5, and 10 C and specific capacities of 134.18, 128.70, 123.62, 119.63, and 97.68 mAh g−1 , respectively. After 50 cycles at a rate of 2 C, LiCr0.05Ni0.475Mn1.475O3.95F0.05 showed extremely good cycling performance, with a discharge specific capacity of 121.02 mAh g−1 and a capacity retention rate of 97.9%. EIS test revealed that the doping clearly decreased the charge-transfer resistance.

For identifying the operation situations of centrifugal pumps by artificial intelligence, we performed an experiment on multi-flow conditions. The multi-flow conditions were simulated by adjusting an automatic flow-regulating valve installed on outlet pipe, and the vertical vibration signals of 20 flow points at the bearing house were collected by the test system. By time-domain analysis, frequency-domain analysis, information entropy, empirical modal decomposition, and wavelet packet decomposition methods, a comprehensive feature space was constructed. In addition, the optimal features were selected by Fisher discriminant ratio, and the dimensionality of the selected optimal features was reduced with principal component analysis. Finally, support vector machine algorithm was employed to identify the real-time flow condition, and the hyper-parameters of support vector machine classifier model were optimized by a grid search technique. Results show that the vibration test can effectively simulate the operation situation of centrifugal pumps under multi-flow conditions, and the proposed multi-flow conditions identification method has achieved a good identification performance.

In most of the previous fault diagnostic literatures, the fault modes and states are pre-determined (i.e. the model structure (topology) is a priori known). However, in practical situation, the monitoring data, especially for the entire life-cycle data, nothing is known about the nature and the origin of the degradation (i.e. the model structure is unknown). Moreover, there is no consensus, how to determine the optimal model structure. In this condition, the different model structures may lead to different fault diagnosis/prognosis results. To address the optimal structure–selection problem, this article presents an automatic segmentation method based on Laplacian eigenmaps manifold learning and adaptive spectral clustering algorithms. Given an entire lifetime data of turbofan engine, we attempt to automatically segment the data into a sequence of contiguous regions corresponding to the degradation states. Furthermore, intrinsic dimensionality estimation, nonlinear dimension reduction, and the optimal number of degradation state estimation have been implemented. Automatic segmentation is applied for degradation state segmentation of non-label life-cycle data, and the output can be considered as the available information for developing fault diagnosis/prognosis. The experimental verification results indicate that the proposed automatic segmentation method is highly efficient and feasible for automatically determining the optimal model structure.

Liquid ring pump is widely applied in many industry fields due to the advantages of isothermal compression process, simple structure, and liquid-sealing. Based on the actual operating cycle of “suction-compression-discharge-expansion,” a universal theoretical model for performance of liquid ring pump was established in this study, to solve the problem that the theoretical models deviated from the actual performance in operating cycle. With the major geometric parameters and operating conditions of a liquid ring pump, the performance parameters such as the actual capacity for suction and discharge, shaft power, and global efficiency can be conveniently predicted by the proposed theoretical model, without the limitation of empiric range, performance data, or the detailed 3D geometry of pumps. The proposed theoretical model was verified by experimental performances of liquid ring pumps and could provide a feasible tool for the application of liquid ring pump.