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Objective: To explore the value of flow cytometry (FCM) in detecting the level of exfoliated cells in pleural effusion in the differential diagnosis of non-small cell lung cancer and benign lung diseases. Methods: Clinical data of patients with non-small cell lung cancer who were hospitalized in Hebei hospital from June 2019 to March 2022 were collected. A total of 98 patients were included, and 63 patients with alveolar lung disease were screened during the same period, and the two groups of patients were analyzed. Results: Compared with alveolar lung disease group, FCM detection and analysis showed that the level of exfoliated cells in the pleural effusion of non-small cell lung cancer (NSCLC) patients was 99 (3-969)/100,000, and patients with alveolar lung disease was 4 (0 ~ 19)/100,000. Additionally, compared with the alveolar lung disease group, the level of exfoliated cells in the pleural effusion of patients with non-small cell lung cancer (NSCLC) was significantly increased (P

Objective: To investigate the effect of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), cancer antigen 125 (CA125), and neuron-specific enolase (NSE) in patients with lung cancer by fluorescence flow cytometry. Methods: From August 2019 to July 2022, 200 patients with lung cancer diagnosed by pathology in our hospital were retrospectively analyzed. 2 mL venous blood was collected in a fasting state and centrifuged to separate the serum (containing human chorionic gonadotropin antibody [anti-hCG antibody], hepatitis B surface antibody [anti-HBs antibody], and CEA). Results: The sensitivities of CEA and CYFRA21-1 detected via enzyme-linked immunosorbent assay (ELISA) were 100%, and the detection limits were 0.5 ng/mL and 0.1 ng/mL, respectively; the sensitivities of CA125 and NSE detected via flow cytometry were 100%, and the detection limits were 10 U/mL and 2 ng/mL, respectively. Compared with ELISA, the sensitivities of CA125 and NSE detected via flow cytometry were higher. When the concentration of CEA was 10–40 ng/mL, the sensitivities of the three markers CYFRA21-1, CA125, and NSE showed no significant changes (P > 0.05); when the concentration of CEA was 40–80 ng/mL, the sensitivity of CEA significantly decreased (P < 0.01), but the sensitivities of the three markers CYFRA21-1, CA125, and NSE showed no significant changes (P > 0.05); when the concentration of CEA was 80–200 ng/mL, the sensitivities of all four markers showed no significant changes (P > 0.05). Conclusion: Compared with the double-antibody sandwich ELISA, fluorescence flow cytometry has certain advantages, including high sensitivity, good precision, short detection time, low sample usage, and low medical cost; thus, it is worthy of clinical promotion.

In recent years, obesity is a growing pandemic in the world and has likely contributed to increasing the incidence of obesity-related diseases. Fat mass and obesity-associated gene (FTO) is the first gene discovered which has a close connection with fat. Recent studies suggested that FTO gene has played an important role in the molecular mechanisms of many diseases. Obesity is considered to be a hereditary disease and can evoke many kinds of diseases, including polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), cancer, etc., whose exact possible molecular mechanisms responsible for the effect of FTO on obesity and obesity-related diseases remain largely unknown. In this review, we comprehensively discuss the correlation between FTO gene and obesity, cancer, PCOS, T2DM, as well as the molecular mechanism involved in these diseases.

Atherosclerosis is identified as the most common reason of numerous cardiovascular diseases (CVD), which is a chronic disease caused by the low-density lipoprotein (LDL) accumulate together and form a plaque. One of the factors contributing to that is the inflammatory response which is related to various signaling pathways. Both innate immune cells and adaptive immune cells participate in inflammatory responses, which lead to atherosclerosis. Their specific roles in the disease are explained in detail respectively in this project. In order to mitigate overactivated inflammatory responses in atherosclerosis, lots of research and studies have been made to find the potential treatment. Various antagonists which target interleukin 6 (IL-6) or interleukin-1 (IL-1) have been evaluated and applied in clinical treatment for atherosclerosis. In addition, monoclonal antibodies are also developed to target oxidized LDL. Despite the progress on the current therapy for atherosclerosis, more research on the field is needed due to the limit efficiency and adverse effects.

Until now, relatively little is known about marine-derived fungal polysaccharides and their activities. Exopolysaccharide AVP141-A was isolated from the broth of marine-derived fungus Aspergillus versicolor SCAU141 and purified by Diethylaminoethyl-Sepharose Fast Flow and Sephadex G-100. The structural characteristics of AVP141-A was studied by chemical analysis together with high-performance gel permeation chromatography, ion chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The results showed that AVP141-A with the molecular weight of 5.10 kDa was mainly composed of →4)-α-D-Glcp-(1→, branched by α-D-Glcp-(1→ and →6)-α-D-Glcp-(1→ at C-6 positions of the glucan backbone. In particular, sulfate ester (approximately 3.62 %) was found in AVP141-A, which was frequently considered to occur in marine-derived microbial polysaccharides rather than other microbial polysaccharides. Furthermore, AVP141-A significantly enhanced the activity of the inflammatory factors NO, COX-2 and TNF-α in RAW264.7 macrophages by activating the MAPK/p38 and NF-κB/p65 pathways. In addition, metabolomic analysis revealed that most of the pathways with significant changes in RAW264.7 macrophages treated with AVP141-A were amino acid-related pathways, and arginine was the characteristic metabolite. In conclusion, this study identified AVP141-A as a marine fungus-derived sulfated exopolysaccharide with potential for development as an immune activator.

CoS2/NC@1T MoS2 synthesized by a one-step hydrothermal method forms a unique hierarchical configuration with simultaneous internal and external modifications. A lithium–sulfur battery with a CoS2/NC@1T MoS2-PP separator shows superior cycling performance.

Selective assembly of monolayered MoS2 (A) and In2Se3 (B) in solution gives a controllable atomic AB-type layer stacking. A new class of photocatalysts can be tailor-made with high activity using this simple but inexpensive bottom-up solution method.

Methicillin-resistant

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.

Background The long-term complications of gestational diabetes mellitus (GDM) may be associated with the development of arthritis, particularly rheumatoid arthritis (RA) and osteoarthritis (OA). However, the possible relationship between these two conditions remains unclear, hindering our understanding of both diseases. We conducted a novel study using bidirectional two-sample Mendelian randomization to explore the potential causal bidirectional relationship between GDM and arthritis. Methods In this study, we extracted single nucleotide polymorphisms closely associated with GDM and arthritis (RA, OA) from published genome-wide association studies (GWAS) data in open databases as instrumental variables (IVs). We employed inverse variance-weighted as the main evaluation criterion, the weighted median method as a possible alternative criterion, and multiple methods as supplements to assess causal relationships. Results were presented as odds ratios (ORs). Additionally, leave-one-out sensitivity analysis, horizontal pleiotropy, and heterogeneity tests were used to verify the reliability and stability of the results. Result Our results indicate a causal association between GDM and an increased risk of arthritis (RA: OR = 4.34, 95% CI = 3.49–5.41, P = 1.96 × 10–39, OA: OR = 1.05, 95% CI = 1.02–1.07, P = 5.27 × 10− 05). In reverse MR analysis, our findings supported the promoting effect of RA on the development of GDM (OR = 1.15, 95% CI = 1.11–1.20, P = 4.44 × 10–14), while the evidence is insufficient to support the conclusion that OA affects the development of GDM (P = 0.757). The heterogeneity test, horizontal pleiotropy test, and leave-one-out sensitivity analysis demonstrated the reliability and stability of our study's results. Conclusion Our study suggests that genetically predisposed GDM increases the risk of developing arthritis (OA, RA). Additionally, genetically predisposed RA is causally associated with an increased risk of GDM. However, we did not find evidence for a causal association between genetically predisposed OA and GDM. These results contribute to a better understanding of the underlying mechanisms of GDM and arthritis. Furthermore, our study has significant potential to guide clinical management and the prevention of complications in patients with GDM and arthritis.

Background： The relationship between ankylosing spondylitis (AS) and mechanical complications of prosthesis after arthroplasty has garnered increasing attention in the medical community. However, the causal relationship between them remains unclear. We conducted a novel study utilizing a two-sample Mendelian randomization analysis to investigate the relationship between these two diseases. Methods: In this study, we obtained single-nucleotide polymorphisms (SNPs) strongly associated with AS and mechanical complications of prosthesis from summary data from genome-wide association studies (GWAS). AS was used as exposure and SNPs as instrumental variables (IVs). The causality was assessed using inverse variance weighted method, and the results were presented as odds ratios (OR). In addition, we conducted heterogeneity tests, horizontal pleiotropy tests, and sensitivity analysis to investigate the potential existence of any bias that may impact the causal relationship. Results: Our results indicate that AS has a causal effect that promotes mechanical complications of prosthesis, as assessed by the inverse variance weighted (IVW) method (OR= 1.037, 95% CI = 1.011, 1.062; P = 0.00366). Although the results of other methods such as MR Egger, weighted median, simple mode， and weighted mode showed no significant causal relationship between the two diseases (P > 0.05), the IVW results should be considered the primary criterion of causality, indicating that AS is a facilitator of mechanical complications of prosthesis. Heterogeneity tests, horizontal pleiotropy tests, and sensitivity analysis showed that these results are reliable and stable. Conclusion: In a word, the results of this Mendelian randomized study suggest that ankylosing spondylitis is associated with an increased risk of mechanical complications of prosthesis after arthroplasty. Therefore, it is recommended that AS patients undergo careful assessment and monitoring during the surgical process to minimize the risk of such complications.

Background Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease that is characterized by the interruption of blood supply to the femoral head. This leads to ischemia of the internal tissues, subchondral bone fractures, necrosis, and ultimately, the collapse of the weight-bearing portion of the femoral head, resulting in severe functional impairment, pain, and even disability of the hip joint. Currently, available animal models of ONFH are limited in their ability to accurately replicate the natural progression of the disease. Therefore, there is a need for the development of a new animal model that can better simulate the localized pressure on the human femoral head to facilitate research related to ONFH.Method In this study, we have developed a novel method for modeling ONFH that incorporates stress factors into the modeling process using 3D printing technology and principles of biomechanics. 36 animals were randomly assigned to six groups and received either a novel modeling technique or traditional hormone induction. Following an 8-week treatment period, Micro CT scans and histological evaluations were conducted to assess tissue outcomes.Results The new model effectively replicates the pathological features of ONFH, including femoral head collapse, with a large number of empty bone lacunae observed, cartilage defects, and subchondral bone fractures in the subchondral bone region. Furthermore, the new model shows the ability to simulate the progression of the disease, making it a valuable tool for research in this field.Conclusion In conclusion, our study provides evidence that the new ONFH model is a useful tool for simulating the disease and can contribute to the development of better treatment strategies for this debilitating condition. It holds great promise for advancing our understanding of the pathogenesis of ONFH and the potential therapeutic interventions for this challenging clinical problem.

Study design Meta-analysis and systematic review. Background Robot-assisted pedicle screw placement technique offers greater accuracy than the traditional freehand screw placement technique. However, it is controversial whether there is a difference between the two procedures in terms of improved clinical outcomes. Materials and methods We systematically searched PubMed, EMBASE, Cochrane, and Web of Science to identify potentially eligible articles. Indispensable data such as the year of publication, study type, age, number of patients, sex distribution, and outcomes were extracted. The outcome indicators of interest included Oswestry disability index (ODI), visual analog scale (VAS) score, operative time, intraoperative blood loss, and post-operative length of stay. RevMan 5.4.1 was used for the meta-analysis. Results A total of eight studies with 508 participants were included. Eight were related to ΔVAS, six were related to ΔODI, seven were related to operative time, five were related to intraoperative blood loss, and seven were related to the length of hospitalization. The results showed that, in terms of ΔVAS (95% CI, −1.20 to −0.36, P = 0.0003) and ΔODI (95% CI, −2.50 to −0.48, P = 0.004), robot-assisted pedicle screw placement technique scored higher than traditional freehand technique. Additionally, the intraoperative blood loss (95% CI, −140.34 to −10.94, P = 0.02) and the length of hospitalization (95% CI, −2.59 to −0.31, P = 0.01) for patients who underwent robotic-assisted pedicle screw placement were less than that of those who underwent the conventional freehand screw placement. No significant difference was found between robot-assisted techniques and conventional freehand techniques in pedicle screw placement in surgical time (95% CI, −2.24 to 26.32, P = 0.10). Conclusions Robot-assisted technique helps improve short-term clinical outcomes, reduce intraoperative blood loss and patient suffering, and shorten recovery time compared to the freehand technique.

Salt stress is a major adverse environmental factor limiting plant growth. Nitrogen (N) application is an effective strategy to alleviate the negative effects of salt stress on plants. To improve the knowledge of the mechanism of N application on alleviating salt stress on rapeseed seedlings, a pot experiment was conducted with four N application treatments (0, 0.1, 0.2, and 0.3 g N kg−1 soil, referred to as N0, N1, N2, and N3, respectively) and exposed to non-salt stress (0 g NaCl kg−1 soil, referred to as S0) and salt stress (3 g NaCl kg−1 soil, referred to as S1) conditions. The results indicated that in comparison with non-salt stress, salt stress increased the Na content (236.53%) and reactive oxygen species (ROS) production such as hydrogen peroxide (H2O2) (30.26%), resulting in cell membrane lipid peroxidation characterized by an increased content of malondialdehyde (MDA) (122.32%) and suppressed photosynthetic rate (15.59%), finally leading to inhibited plant growth such as shorter plant height, thinner root neck, lower leaf area, and decreased dry weight. N application improved the plant growth, and the improvement by N application under salt stress was stronger than that under non-salt stress, suggesting that rapeseed seedlings exposed to salt stress are more sensitive to N application and require N to support their growth. Moreover, seedlings exposed to salt stress under N application showed lower ROS accumulation; increased photosynthesis; higher antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and ascorbic acid (AsA); and greater accumulation of osmotic substances including soluble protein, soluble sugar, and proline, as compared with seedlings without N application. In particular, the best improvement by N application under salt stress occurred at the N2 level, while too high N application could weaken the improvement due to inhibited N metabolism. In summary, this study suggests that moderate N application can improve photosynthesis, antioxidants, and osmoregulation to alleviate the adverse effects of salt stress in rapeseed seedlings.

Open Set Domain Adaptation (OSDA) aims to reduce the variation across domains while distinguishing between known samples and unknown samples. However, existing OSDA methods are based on deep neural network classifiers to separate unknown samples, which leads the network to produce overconfident predictions and fails to establish the boundary between the known and the unknown. We propose an Energy-based Open Set Domain Adaptation method (EOS). Specifically, EOS is a new two-stage approach of separation followed by alignment. We use an energy-based anomaly detection strategy as a separation method for unknown samples, transforming the traditional K-way classification task into a K+1-dimensional classifier that uses an additional dimension to model the uncertainty of Out-of-distribution (OOD) samples. Then, we use a coarse-to-fine separation method to continuously adjust the separation results and add the exact separation results as weights in the alignment process, weighing their importance to the feature distribution alignment. In the alignment phase we also optimize our separation network module at the same time, so that the module can be better adapted with invariant features. We have done experiments on the standard ground Office-31, Office-Home, and VisDA-2017 benchmarks, and the results show that our approach outperforms our competitors in most cases.

The travel patterns of urban inhabitants are not optimized and require improvement. By utilizing big data visualization, the optimization of urban residents' travel structure can be efficiently achieved, resulting in the reduction of urban traffic and the promotion of a healthier lifestyle for individuals. Through the utilization of big data visualization, the optimization of urban residents' travel structure can be comprehended by means of a mathematical model and the implementation of effective policies aimed at enhancing human settlement. This can also serve as a significant point of reference for exploring future studies in this field. The focus of this paper is to examine the influence of big data visualization technologies that offer insights into the routes of transportation and the movements of pedestrians, as captured by public cameras situated worldwide. In the course of transportation planning, conventional statistical methodologies and extensive data analysis techniques are employed to optimize the travel patterns of urban residents using a basic programming language such as Python. The research has confirmed the efficiency of big data visualization technologies in ameliorating the transportation framework of city dwellers.

Polycrystalline Li(Ni,Mn,Co)O2 (NMC) secondary particles are the most common cathode materials for Li-ion batteries. During electrochemical (dis)charge, lithium is believed to diffuse through the bulk and enter (leave) the secondary particle at the surface. Based on this model, smaller particles would cycle faster due to shorter diffusion lengths and larger surface-area-to-volume ratios. In this work, we evaluate this widespread assumption by developing a new high-throughput single-particle electrochemistry platform using the multi-electrode array from neuroscience. By measuring the reaction and diffusion times for 21 individual particles in liquid electrolytes, we find no correlation between the particle size and either the reaction or diffusion times, which is in stark contrast to the prevailing lithium transport model. We propose that electrochemical reactions occur inside secondary particles, possibly due to electrolyte penetration into cracks. Our high-throughput, single-particle electrochemical platform further opens new frontiers for robust, statistical quantification of individual particles in electrochemical systems.

Due to sudden loss of cerebral blood circulation, acute ischemic stroke (IS) causes neuronal energy attenuation or even exhaustion by mitochondrial dysfunction resulting in aggravation of neurological injury. In this study, we investigated if Notoginsenoside R1 ameliorated cerebral energy metabolism by limiting neuronal mitochondrial dysfunction in acute IS. Male Sprague-Dawley rats (260-280 g) were selected and performed by permanent middle cerebral artery occlusion model. In vitro, the oxygen glucose deprivation (OGD) model of Neuro2a (N2a) cells was established. We found Notoginsenoside R1 treatment reduced rats' cerebral infarct volume and neurological deficits, with increased Adenosine triphosphate (ATP) level together with upregulated expression of glucose transporter 1/3, monocarboxylate transporter 1 and citrate synthase in brain peri-ischemic tissue. In vitro, OGD-induced N2a cell death was inhibited, cell mitochondrial morphology was improved. Mitochondrial amount, mitochondrial membrane potential, and mitochondrial DNA copy number were increased by Notoginsenoside R1 administration. Furthermore, mitochondrial energy metabolism-related mRNA array found Atp12a and Atp6v1g3 gene expression were upregulated more than twofold, which were also verified in rat ischemic tissue by quantitative polymerase chain reaction (qPCR) assay. Therefore, Notoginsenoside R1 administration increases cerebral glucose and lactate transportation and ATP levels, ameliorates neuronal mitochondrial function after IS. Notoginsenoside R1 may be a novel protective agent for neuronal mitochondria poststroke.

Co-detection of multiplex cancer subtypes and bacteria subtypes in situ is crucial for understanding tumor microbiome interactions in tumor microenvironment. Current standard techniques such as immunohistochemical staining and immunofluorescence staining are limited for their multiplicity. Simultaneously visualizing detailed cell subtypes and bacteria distribution across the same pathological section remains a major technical challenge. Herein, we developed a rapid semi-quantitative method for in situ imaging of bacteria and multiplex cell phenotypes on the same solid tumor tissue sections. We designed a panel of antibody probes labeled with mass tags, namely prokaryotic and eukaryotic cell hybrid probes for in situ imaging (PEHPSI). For application demonstration, PEHPSI stained two bacteria subtypes (lipopolysaccharides (LPS) for Gram-negative bacteria and lipoteichoic acid (LTA) for Gram-positive bacteria) simultaneously with four types of immune cells (leukocytes, CD8 + T-cells, B-cells and macrophages) and four breast cancer subtypes (classified by a panel of 12 human proteins) on the same tissue section. We unveiled that breast cancer cells are commonly enriched with Gram-negative bacteria and almost absent of Gram-positive bacteria, regardless of the cancer subtypes (triple-negative breast cancer [TNBC], HER2+, Luminal A and Luminal B). Further analysis revealed that on the single-cell level, Gram-negative bacteria have a significant correlation with CD8 + T-cells only in HER2+ breast cancer, while PKCD, ER, PR and Ki67 are correlated with Gram-negative bacteria in the other three subtypes of breast cancers. On the cell population level, in TNBC, CD19 expression intensity is up-regulated by approximately 25% in bacteria-enriched cells, while for HER2+, Luminal A and Luminal B breast cancers, the intensity of biomarkers associated with the malignancy, metastasis and proliferation of cancer cells (PKCD, ISG15 and IFI6) is down-regulated by 29%-38%. The flexible and expandable PEHPSI system permits intuitive multiplex co-visualization of bacteria and mammalian cells, which facilitates future research on tumor microbiome and tumor pathogenesis.

Utilization of lignocellulosic biomass is receiving increasing attention lately. In this study, Jasminum nudiflorum Lindl. (JNL) wood were extracted using methanol, ethanol, and benzene/ethanol (2:1, v:v) separately. Fourier transform-infrared spectroscopy (FTIR) and gas chromatography-mass spectroscopy (GC-MS) were used to study the chemical components of extracts. A thermogravimetric (TG) analyzer and pyrolysis (Py)-GC-MS investigated the characteristics of thermal loss law and pyrolyzates of JNL wood, respectively. The FTIR results showed that many functional groups were detected from the extracts of JNL wood, which were consistent with the chemical structures in the components detected by GC-MS. There were two obvious stages of thermal loss for removing moisture and decomposition of the organic constituents. The components of the extracts and pyrolyzates were esters, acids, aldehydes, alcohols, inositol, furfural, alkanes, phenols, ketones, antibiotics, saccharides, and glycosides. Among them, some components, such as ethyl iso-allocholate, scopoletin, isosorbide dinitrate, and idebenone, have high medicinal value. This study revealed the chemical component characterization and potential medicinal utilization of JNL wood. It provides the scientific basis for enhancing the utilization value of JNL wood.

Juvenile hormone (JH) and 20-hydroxyecdysone (20E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant (Met) and germ-cell expressed (Gce), have been identified in the fruit fly Drosophila melanogaster. To investigate JH membrane signaling pathway without the interference from JH intracellular signaling, we characterized phosphoproteome profiles of the Met gce double mutant in the absence or presence of JH in both chronic and acute phases. Functioning through a potential receptor tyrosine kinase and phospholipase C pathway, JH membrane signaling activated protein kinase C (PKC) which phosphorylated ultraspiracle (USP) at Ser35, the PKC phosphorylation site required for the maximal action of 20E through its nuclear receptor complex EcR-USP. The uspS35A mutant, in which Ser was replaced with Ala at position 35 by genome editing, showed decreased expression of Halloween genes that are responsible for ecdysone biosynthesis and thus attenuated 20E signaling that delayed developmental timing. The uspS35A mutant also showed lower Yorkie activity that reduced body size. Altogether, JH membrane signaling phosphorylates USP at Ser35 and thus potentiates 20E action that regulates the normal fly development. This study helps better understand the complex JH signaling network.

Background Blood–brain barrier (BBB) disruption is a major adverse event after ischemic stroke (IS). Caveolin-1 (Cav-1), a scaffolding protein, played multiple roles in BBB permeability after IS, while the pros and cons of Cav-1 on BBB permeability remain controversial. Numerous studies revealed that extracellular vesicles (EVs), especially stem cells derived EVs, exerted therapeutic efficacy on IS; however, the mechanisms of BBB permeability needed to be clearly illustrated. Herein, we compared the protective efficacy on BBB integrity between bone marrow mesenchymal stem cells derived extracellular vesicles (BMSC-EVs) and EVs from brain endothelial cells (BEC-EVs) after acute IS and investigated whether the mechanism was associated with EVs antagonizing Cav-1-dependent tight junction proteins endocytosis. Methods BMSC-EVs and BEC-EVs were isolated and characterized by nanoparticle tracking analysis, western blotting, and transmission electron microscope. Oxygen and glucose deprivation (OGD) treated b. End3 cells were utilized to evaluate brain endothelial cell leakage. CCK-8 and TRITC-dextran leakage assays were used to measure cell viability and transwell monolayer permeability. Permanent middle cerebral artery occlusion (pMCAo) model was established, and EVs were intravenously administered in rats. Animal neurological function tests were applied, and microvessels were isolated from the ischemic cortex. BBB leakage and tight junction proteins were analyzed by Evans Blue (EB) staining and western blotting, respectively. Co-IP assay and Cav-1 siRNA/pcDNA 3.1 vector transfection were employed to verify the endocytosis efficacy of Cav-1 on tight junction proteins. Results Both kinds of EVs exerted similar efficacies in reducing the cerebral infarction volume and BBB leakage and enhancing the expressions of ZO-1 and Claudin-5 after 24 h pMCAo in rats. At the same time, BMSC-EVs were outstanding in ameliorating neurological function. Simultaneously, both EVs treatments suppressed the highly expressed Cav-1 in OGD-exposed b. End3 cells and ischemic cerebral microvessels, and this efficacy was more prominent after BMSC-EVs administration. Cav-1 knockdown reduced OGD-treated b. End3 cells monolayer permeability and recovered ZO-1 and Claudin-5 expressions, whereas Cav-1 overexpression aggravated permeability and enhanced the colocalization of Cav-1 with ZO-1 and Claudin-5. Furthermore, Cav-1 overexpression partly reversed the lower cell leakage by BMSC-EVs and BEC-EVs administrations in OGD-treated b. End3 cells. Conclusions Our results demonstrated that Cav-1 aggravated BBB permeability in acute ischemic stroke, and BMSC-EVs exerted similar antagonistic efficacy to BEC-EVs on Cav-1-dependent ZO-1 and Claudin-5 endocytosis. BMSC-EVs treatment was superior in Cav-1 suppression and neurological function amelioration. Graphical Abstract

Background: Oral submucous fibrosis (OSF) is a chronic disease with carcinogenic tendency that poses a non-negligible threat to human health. Exosomes derived from human adipose mesenchymal stem cells (ADSC-Exo) reduces visceral and cutaneous fibroses, but theirrole in OSF has received little attention. The aim of this studywas to investigate the effects of ADSC-Exo on OSFand elucidate the mechanism. Methods: In brief, ADSCs were extracted from adipose tissues and subjected to flow cytometry and induction culture. Fibroblasts were isolated from human buccal mucosa and subjected to immunofluorescence. Myofibroblasts were obtained from fibroblasts induced by arecoline and identified. Immunofluorescence assay confirmed that myofibroblasts could take up ADSC-Exo. The effects of ADSC-Exo on the proliferative and migratory capacities of myofibroblasts were examined using the Cell Counting Kit-8 and scratch assay. Real-time quantitative polymerase chain reaction (qPCR) was performed to evaluate mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad7, collagen type 1 (Col1),Col3, alpha smooth muscle actin (α-SMA), fibronectin, and vimentin. Western blotting was performed to detect phospho (p)-Smad2, Smad2, p-Smad2/3, Smad2/3, Smad7, Col1, Col3, α-SMA, fibronectin, and vimentin. Furthermore, the dual-luciferase reporter assay was performed to prove that miR-181a-5p in ADSC-Exo directly inhibited the expression of Smad2mRNA to regulate the transforming growth factor beta (TGF-β)pathway. We also performed qPCR and western blotting to verify the results. Results: ADSC-Exo could promote the proliferation and migration of myofibroblasts, reduce the expressions of p-smad2, Smad2, p-smad2/3, Smad2/3, Col1, αSMA, fibronectin, and vimentin and elevated the levels of Smad7 and Col3. In addition, miR-181a-5p was highly expressed in ADSC-Exo and bound to the 3'-untranslated region of Smad2. ADSC-Exo enriched with miR-181a-5p reduced collagen production in myofibroblasts and modulated the TGF-β pathway. Conclusions: ADSC-Exo promoted the proliferative and migratory capacities of myofibroblasts and inhibited collagen deposition and trans-differentiation of myofibroblasts in vitro. miR-181a-5p in exosomes targets Smad2 to regulate the TGF-β pathway in myofibroblasts. ADSC-Exo perform antifibrotic actions through the miR-181a-5p/Smad2 axis and may be a promising clinical treatment for OSF. Trial registration: Not applicable

Electronic switches based on the migration of high-density point defects, or memristors, are poised to revolutionize post-digital electronics. Despite significant research, key mechanisms for filament formation and oxygen transport remain unresolved, thus hindering our ability to predict and design crucial device properties. For example, predicted retention times based on current models can be 10 orders of magnitude lower than ones experimentally realized. Here, using electrical measurements, chemical spectroscopy, and first-principles calculations on tantalum oxide memristors, we reveal that the formation and stability of conductive filaments crucially depend on the stability of the amorphous oxygen-rich and oxygen-poor compounds, which undergo composition phase separation. Including the previously neglected effects of this amorphous phase separation reconciles unexplained discrepancies and enables predictive design of key performance indicators such as retention stability. This result emphasizes non-ideal thermodynamic interactions as key design criteria in post-digital devices with defect densities substantially exceeding those of today’s covalent semiconductors.

Accelerating the repair of a bone defect is crucial clinically due to the increased prevalence of trauma, tumor, and infections in bone. Studies have found that excess acute and chronic inflammation attenuate osteogenic differentiation of BMSCs (bone marrow mesenchymal stem cells). Moreover, TNF-α and NF-κB could inhibit osteoblasts differentiation of BMSCs and promote osteoclastogenesis via multiple mechanisms, such as increasing osteoclast precursor cells and acting synergistically with cell cytokines. However, melatonin could inhibit the expression of TNFα/NF-κB and promote bone formation by activating the Wnt/β-catenin signaling pathway. However, there has been no evidence regarding the effect of melatonin on TNFα/NF-κB-inhibited osteoblastogenesis and bone formation. This study aimed to investigate the role of melatonin on TNFα/NF-κB-inhibited osteoblastogenesis and bone formation. Micro-CT, high-throughput screening, overexpression, and other methods were used, and we found that the number of osteoblasts was elevated with melatonin treatment. Additionally, TNFα/NF-κB signaling was inhibited, while miR-335-5p expression increased markedly following treatment with melatonin. Furthermore, miR-335-5p negatively regulated TNFα/NF-κB signaling, while miR-335-5p inhibitor ameliorated the effects of melatonin on TNFα/NF-κB. In conclusion, melatonin facilitates osteogenesis in bone defect healing by enhancing miR-335-5p expression and inhibiting the TNFα/NF-κB pathway.

Energy is indispensable in human life and social development, but this has led to an overconsumption of non-renewable energy. Sustainable energy is needed to maintain the global energy balance. Lignocellulose from agriculture or forestry is often discarded or directly incinerated. It is abundantly available to be discovered and studied as a biomass energy source. Therefore, this research uses

Electrochemical random-access memory (ECRAM) is a recently developed and highly promising analog resistive memory element for in-memory computing. One longstanding challenge of ECRAM is attaining retention time beyond a few hours. This short retention has precluded ECRAM from being considered for inference classification in deep neural networks, which is likely the largest opportunity for in-memory computing. In this work, we develop an ECRAM cell with orders of magnitude longer retention than previously achieved, and which we anticipate to exceed 10 years at 85C. We hypothesize that the origin of this exceptional retention is phase separation, which enables the formation of multiple effectively equilibrium resistance states. This work highlights the promises and opportunities to use phase separation to yield ECRAM cells with exceptionally long, and potentially permanent, retention times., 14 pages, 4 figures

Robot-assisted total knee arthroplasty (RA-TKA) requires a lot of training from surgeons to master it. The purpose of the present study was to determine the learning curve for a novel seven-axis RA-TKA system, and to explore whether it could provide superior short-term clinical and radiological outcomes compared with conventional surgery. In the present retrospective study, 180 patients from our hospital with primary unilateral TKA were included, from January 2021 to June 2022. Of these, 90 patients underwent RA-TKA and were included in robot-assisted system (RAS) group, while the remaining 90 patients underwent conventional TKA and were included in the conventional group. The learning curve for the RA-TKA system was evaluated by cumulative sum (CUSUM) and risk-adjusted cumulative sum (RA-CUSUM) methods. Depending on the learning curve data, the RAS group patients were categorized as either in a learning or proficiency group. In addition, the proficiency group was compared with the conventional group using propensity score matching. There was no significant difference in postoperative Hip–Knee–Ankle (HKA) angle, or deviations in the postoperative HKA angle, component tibial coronal angle (CTCA), component femoral coronal angle (CFCA), sagittal tibial component angle (STCA), or sagittal femoral component angle (SFCA) between the learning and proficiency phases in RA-TKA group patients. A total of 49 patients in the proficiency group were matched with 49 patients from the conventional group. The indicators representing the accuracy of the prosthetic installation differ between the proficiency group and conventional group. (P

Network embedding has attracted a lot of attention in different fields recently. It represents nodes in a network into a low-dimensional and dense space while preserving the structural properties of the network. Some methods (e.g. motif2Vec, RUM, and MODEL) have been proposed to preserve the higher-order structures, i.e., motifs in embedding space, and they have obtained better results in some downstream network analysis tasks. However, there still exists a significant challenge because original motifs may include redundant noise edges, and embedding entire motifs into embedding space may adversely affect the performance in downstream tasks. To overcome this problem, we propose a motifs enhancement framework for network embedding, based on edge reweighting. Through edge reweighting, the weight of redundant noise edges between motifs is decreased. Therefore, the effect of redundant noise edges will be reduced in the embedding space. We apply the edge reweighting as a preprocessing phase in network embedding, and construct the motifs enhanced network by incorporating enhanced motifs structures with the original network. By doing this, the embedding vectors from the motifs enhanced network can achieve better performance in downstream network analysis tasks. Extensive experiments are performed on two network analysis tasks (community detection and node classification) with synthetic and real-world datasets. The results show that our framework outperforms state-of-the-art network embedding methods.

Biomass rapid pyrolysis technology is easy to implement in continuous production and industrial application, and has become one of the leading technologies in the field of world renewable energy development. Agricultural and forestry waste is an important resource of renewable energy in China. In general, abandoned leaves in forest areas cause serious waste of resources. Its utilization may help to settle the problems of energy deficiency and environment pollution. In this study

Biomass has been recognized as the most common source of renewable energy. In recent years, researchers have paved the way for a search for suitable biomass resources to replace traditional fossil fuel energy and provide high energy output. Although there are plenty of studies of biomass as good biomaterials, there is little detailed information about