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Abstract Depression is a common and heterogeneous mental disorder. Although several antidepressants are available to treat the patients with depression, the factors which could affect and predict the treatment response remain unclear. Here, we characterize the longitudinal changes of microbial composition and function during escitalopram treatment in chronic unpredictable mild stress (CUMS) mice model of depression based on 16 S rRNA sequencing and metabolomics. Consequently, we found that escitalopram (ESC) administration serves to increase the alpha-diversity of the gut microbiome in ESC treatment group. The microbial signatures between responder (R) and non-responder (NR) groups were significantly different. The R group was mainly characterized by increased relative abundances of genus Prevotellaceae_UCG-003, and depleted families Ruminococcaceae and Lactobacillaceae relative to NR group. Moreover, we identified 15 serum metabolites responsible for discriminating R and NR group. Those differential metabolites were mainly involved in phospholipid metabolism. Significantly, the bacterial OTUs belonging to family Lachnospiraceae, Helicobacteraceae, and Muribaculaceae formed strong co-occurring relationships with serum metabolites, indicating alternations of gut microbiome and metabolites as potential mediators in efficiency of ESC treatment. Together, our study demonstrated that the alterations of microbial compositions and metabolic functions might be relevant to the different response to ESC, which shed new light in uncovering the mechanisms of differences in efficacy of antidepressants.

Due to its higher energy and smaller heating area, laser joining technology is widely used in aluminum alloy welding and other industrial fields, which meets the solder sealing requirements for electronic packaging. According to experiments, cracks were prone to occur at the corners and spot-welding positions near the weld. In this paper, the depth and width of the melt pool were measured experimentally, and the results were used to calibrate and validate the heat source model. An empirical relationship between heat source parameters and melt pool morphology is presented. The heat source model of laser deep penetration welding was established under the same experimental conditions. And the results were in agreement with the experimental results. The finite element method was used to numerically simulate the welding process of a 50%SiAl shell and a 27%SiAl cover plate. The effects of different spot-welding sequences and numbers on the residual stress and cracking possibility of laser welded samples were analyzed. The results show that under sequential spot-welding, when the amount of spot-welding is increased, the stress peak value decreases. Compared with sequential spot welding and side-by-side spot welding, the spot-welding sequence of diagonal points first, and then side-by-side spot welding, can effectively reduce the residual stress. This research enables us to provide some guidelines in terms of studying the reliability issues of microwave devices.

With polymerization duration and Au3+ concentration of the electrolyte regulated, a desirable nitrate-doped polypyrrole ion-selective membrane (PPy(NO3−)-ISM) and Au solid contact layer of anticipate surface morphology were obtained, and the performance of nitrate all-solid ion-selective electrodes (NS ISEs) was improved. It was found that the roughest PPy(NO3−)-ISM remarkably increases the actual contact surface area of the PPy(NO3−)-ISMs with nitrate solution, which leads to better adsorption of NO3− ions upon the PPy(NO3−)-ISMs, and produces a larger number of electrons. The most hydrophobic Au solid contact layer avoids the formation of the aqueous layer at the interface between the PPy(NO3−)-ISM and Au solid contact layer, and ensures unimpeded transporting of the produced electrons. The PPy-Au-NS ISE for polymerization duration 1800 s and at Au3+ concentration 2.5 mM of the electrolyte displays an optimal nitrate potential response, including a Nernstian slope of 54.0 mV/dec, LOD of 1.1 × 10−4 M, rapid average response time less than 1.9 s, and long-term stability of more than 5 weeks. This indicates that the PPy-Au-NS ISE is an effective working electrode for the electrochemical determination of NO3− concentration.

Magnetometers based on nitrogen-vacancy (NV) centers in diamonds have promising applications in fields of living systems biology, condensed matter physics, and industry. This paper proposes a portable and flexible all-fiber NV center vector magnetometer by using fibers to substitute all conventional spatial optical elements, realizing laser excitation and fluorescence collection of micro-diamond with multi-mode fibers simultaneously and efficiently. An optical model is established to investigate multi-mode fiber interrogation of micro-diamond to estimate the optical performance of NV center system. A new analysis method is proposed to extract the magnitude and direction of the magnetic field, combining the morphology of the micro-diamond, thus realizing μm-scale vector magnetic field detection at the tip of the fiber probe. Experimental testing shows our fabricated magnetometer has a sensitivity of 0.73 nT/Hz1/2, demonstrating its feasibility and performance in comparison with conventional confocal NV center magnetometers. This research presents a robust and compact magnetic endoscopy and remote-magnetic measurement approach, which will substantially promote the practical application of magnetometers based on NV centers.

Background and PurposeThis study was conducted to explore the plasma drug concentration of propranolol in Chinese Han patients with infantile haemangioma (IH) and the influencing factors, as well as the relationship among plasma drug concentrations of propranolol, β1-AR mutation and CYP2D6 188C>T, efficacy, and safety.Experimental ApproachFrom January 2018 to April 2019, 140 patients with IH who were admitted to the hospital for oral propranolol and agreed to have their plasma concentration of propranolol tested, including 112 patients with β1-AR and CYP2D6 gene tested.Key Results and Conclusions and ImplicationsThe mean peak blood levels of propranolol, 4-hydroxypropranolol (4-OH-P), and N-deisopropylpropranolol (NDP) were 60.35 ± 37.90, 1.90 ± 2.37, and 0.24 ± 0.18 ng/ml, respectively. The mean trough blood levels of propranolol, 4-OH-P, and NDP were 24.98 ± 17.68, 0.45 ± 0.52, and 0.05±0.05 ng/ml, respectively. The higher the dose of propranolol, the higher the plasma concentration of propranolol (p = 0.031). The plasma concentration of propranolol was not related to the treatment efficacy.

Myasthenia gravis (MG) comorbid anxiety seriously affects the progress of MG. However, the exact relationship remains poorly understood. Recently, our preliminary study has revealed that intestinal microbe disturbance is closely related to MG. Therefore, further exploration of whether the microbiome is involved in MG comorbid anxiety is warranted. In this study, gas chromatography-mass spectrometry metabolomics analysis was used to characterize the metabotype of feces, serum, and three brain regions involved in emotion (i.e., the prefrontal cortex, hippocampus, and striatum), which were obtained from mice that were colonized with fecal microbiota from patients with MG (MMb), healthy individuals (HMb), or co-colonization of both patients and healthy individuals (CMb). Functional enrichment analysis was used to explore the correlation between the “microbiota–gut–brain” (MGB) axis and anxiety-like behavior. The behavioral test showed that female MMb exhibited anxiety-like behavior, which could be reversed by co-colonization. Moreover, metabolic characterization analysis of the MGB axis showed that the metabotype of gut-brain communication was significantly different between MMb and HMb, and 146 differential metabolites were jointly identified. Among these, 44 metabolites in feces; 12 metabolites in serum; 7 metabolites in hippocampus; 2 metabolites in prefrontal cortex; and 6 metabolites in striatum were reversed by co-colonization. Furthermore, the reversed gut microbiota mainly belonged to bacteroides and firmicutes, which were highly correlated with the reversed metabolites within the MGB axis. Among three emotional brain regions, hippocampus was more affected. Therefore, disturbances in gut microbiota may be involved in the progress of anxiety-like behavior in MG due to the MGB axis.

Previous studies suggest that in people with major depressive disorder (MDD), there exists a perturbation of the normal balance between the excitatory and inhibitory neurotransmitter systems in the visual cortex, indicating the possibility of altered visual cortical excitability. However, investigations into the neural activities of the visual cortex in MDD patients yielded inconsistent findings. The present study aimed to evaluate the visual cortical excitability utilizing a paired-pulse stimulation paradigm in patients with MDD and to access the paired-pulse behavior of recording visual evoked potentials (VEPs) as a marker of MDD. We analyzed the amplitudes of VEPs and paired-pulse suppression (PPS) at four different stimulus onset asynchronies (SOAs) spanning 93 ms to 133 ms. Further, the relationship between PPS and the symptom severity of depression was investigated using Spearman's correlation. We found that, whereas the first VEP amplitude remained unchanged, the second VEP amplitude was significantly higher in the MDD group compared to the healthy controls. As a result, the amplitude ratio (second VEP amplitude/first VEP amplitude) increased, indicating reduced PPS and thus increased excitability in the visual cortex. Moreover, we found the amplitude ratios had a significantly positive correlation with the symptom severity of depression in MDD, indicating a clinically useful biomarker for MDD. Our findings provide new insights into the changes in the excitation-inhibition balance of visual cortex in MDD, which could pave the way for specific clinical interventions.

Information on comparative drug efficacy is of great importance for drug development as well as clinical practice. Up to now, the relative efficacy of biologics and small targeted molecules for Crohn’s disease (CD) remains unclear. The objective of this study was to quantify the relative efficacy of investigational and approved biological treatments for CD measured in Crohn’s Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and C-reactive protein (CRP). The analysis dataset was composed of summary-level data from 46 trials, containing 12,846 patients, with treatment of 24 drugs. Six mathematical models with non-parametric placebo estimations were developed to describe the time course and dose–response of six efficacy measures. The effects of covariate were further evaluated. Time–response relationships were found in outcomes measured in CDAI. The patients’ age, disease duration, baseline CDAI, and CRP showed an impact on the efficacy. Model simulations were performed to compare the efficacies across different drugs. The most achievement in clinical remission (defined as CDAI less than 150) and clinical response (defined as the reduction in CDAI for 100 or 70) was observed in the simulation for PF-04236921 and infliximab, respectively. The most improvement in IBDQ was shown in tofacitinib. In general, tumor necrosis factor (TNF)-α inhibitors were the most effective biologics, and the highest efficacy of small targeted molecules was observed in janus kinase (JAK) inhibitors. These findings have important implications for clinical practice in CD.

Abstract Background Circulating small extracellular vesicles (sEVs) and its associated proteins are of great interest in the early detection of many diseases. However, there is no gold standard for plasma sEVs isolation, especially for proteomic profiling which could be largely affected by contamination such as lipoproteins and plasma proteins. Previous studies suggested combinations of different sEVs isolation methods could improve the yield and purity of the isolated fractions. Nevertheless, there is no systematic evaluation of size-exclusion chromatography (SEC), ultracentrifugation (UC), and their combination in a proteomic perspective. Results Plasma samples were collected from healthy individuals, and sEVs were separated by one-step SEC, one-step UC, and combining SEC with UC, respectively. Here we exhibited that the purity of sEVs was improved by SEC in contrast to traditional UC. Furthermore, by conducting a SEC procedure followed by UC, we separated sEVs with the highest purity. In the proteomic analysis, 992 protein species were identified in the plasma sEVs isolated by our novel separation method, of which several proteins are sEVs-associated proteins but hitherto never been identified in the previous studies and database, much more than plasma sEVs isolated by UC (453) or SEC (682) alone. As compared to Vesiclepedia and Exocarta databases, plasma sEVs isolated by the new procedure kept 584 previously identified sEVs-associated proteins and 360 other proteins that have not been detected before. Detailed analysis suggested that more kinds of sEVs biomarkers, such as CD9, ALIX, and FLOT1, could be identified in plasma sEVs isolated by the novel isolation method as compared to one-step UC/SEC. Furthermore, the lower abundance ranks of common contaminants, such as lipoproteins and IgG chains, in the sEVs fractions obtained by our new method as compared to one-step UC/SEC also demonstrated the purity of sEVs had been improved. Conclusions Combining SEC with UC could significantly improve the performance of mass spectrometry-based proteomic profiling in analyzing plasma-derived sEVs.

Abstract Background Busulfan (Bu) is a key component of several conditioning regimens used before hematopoietic stem cell transplantation (HSCT). However, the optimum systemic exposure (expressed as the area under the concentration-time curve [AUC]) of Bu for clinical outcome in children is controversial. Methods Research on pertinent literature was carried out at PubMed, EMBASE, Web of science, the Cochrane Library and ClinicalTrials.gov . Observational studies were included, which compared clinical outcomes above and below the area under the concentration-time curve (AUC) cut-off value, which we set as 800, 900, 1000, 1125, 1350, and 1500 μM × min. The primary efficacy outcome was notable in the rate of graft failure. In the safety outcomes, incidents of veno-occlusive disease (VOD) were recorded, as well as other adverse events. Results Thirteen studies involving 548 pediatric patients (aged 0.3–18 years) were included. Pooled results showed that, compared with the mean Bu AUC (i.e., the average value of AUC measured multiple times for each patient) of > 900 μM × min, the mean AUC value of

Abstract Background Executive function (EF) is vital to human beings. It has been linked to many genes and family environmental factors in separate studies, but few studies have examined the potential interactions between gene(s) and environmental factor(s). The current study explored the whole genome to identify SNPs, genes, and pathways that interacted with parental warmth (PW) on EF. Results Nine EF tasks were used to measure its three components (common EF, updating, shifting) based on the model proposed by Miyake et al. (2000). We found that rs111605473, LAMP5, SLC4A7, and LRRK1 interacted significantly with PW to affect the updating component of EF, and the GSE43955 pathway interacted significantly with PW to affect the common EF component. Conclusions The current study is the first to identify genes that interacted with PW to affect EF. Further studies are needed to reveal the underlying mechanism.

BackgroundEvidence suggests that an increased risk of major adverse cardiac events (MACE) and all-cause mortality is associated with obstructive sleep apnea (OSA), particularly in the elderly. Metabolic syndrome (MetS) increases cardiovascular risk in the general population; however, less is known about its influence in patients with OSA. We aimed to assess whether MetS affected the risk of MACE and all-cause mortality in elderly patients with OSA.MethodsFrom January 2015 to October 2017, 1,157 patients with OSA, aged ≥60 years, no myocardial infarction (MI), and hospitalization for unstable angina or heart failure were enrolled at baseline and were followed up prospectively. OSA is defined as an apnea-hypopnea index of ≥5 events per hour, as recorded by polysomnography. Patients were classified on the basis of the presence of MetS, according to the definition of the National Cholesterol Education Program (NCEP). Incidence rates were expressed as cumulative incidence. Cox proportional hazards analysis was used to estimate the risk of all events. The primary outcomes were MACE, which included cardiovascular death, MI, and hospitalization for unstable angina or heart failure. Secondary outcomes were all-cause mortality, components of MACE, and a composite of all events.ResultsMetS was present in 703 out of 1,157 (60.8%) elderly patients with OSA. During the median follow-up of 42 months, 119 (10.3%) patients experienced MACE. MetS conferred a cumulative incidence of MACE in elderly patients with OSA (log-rank, P < 0.001). In addition, there was a trend for MACE incidence risk to gradually increase in individuals with ≥3 MetS components (P = 0.045). Multivariate analysis showed that MetS was associated with an incidence risk for MACE [adjusted hazard ratio (aHR), 1.86; 95% confidence interval (CI), 1.17–2.96; P = 0.009], a composite of all events (aHR, 1.54; 95% CI, 1.03–2.32; P = 0.036), and hospitalization for unstable angina (aHR, 2.01; 95% CI, 1.04–3.90; P = 0.039). No significant differences in the risk of all-cause mortality and other components of MACE between patients with and without MetS (P > 0.05). Subgroup analysis demonstrated that males (aHR, 2.23; 95% CI, 1.28–3.91, P = 0.05), individuals aged

Major depressive disorder is caused by gene–environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the underlying mechanisms remain elusive. Herein, the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) between mice inoculated with gut microbiota from major depressive disorder patients or healthy controls were detected, to identify the effects of gut microbiota-dysbiosis on gene regulation patterns at the transcriptome level, and in further to explore the microbial-regulated pathological mechanisms of depression. As a result, 200 mRNAs, 358 lncRNAs, and 4 miRNAs were differentially expressed between the two groups. Functional analysis of these differential mRNAs indicated dysregulated inflammatory response to be the primary pathological change. Intersecting these differential mRNAs with targets of differentially expressed miRNAs identified 47 intersected mRNAs, which were mainly related to neurodevelopment. Additionally, a microbial-regulated lncRNA–miRNA–mRNA network based on RNA–RNA interactions was constructed. Subsequently, according to the competitive endogenous RNAs (ceRNA) hypothesis and the biological functions of these intersected genes, two neurodevelopmental ceRNA sub-networks implicating in depression were identified, one including two lncRNAs (4930417H01Rik and AI480526), one miRNA (mmu-miR-883b-3p) and two mRNAs (Adcy1 and Nr4a2), and the other including six lncRNAs (5930412G12Rik, 6430628N08Rik, A530013C23Rik, A930007I19Rik, Gm15489, and Gm16251), one miRNA (mmu-miR-377-3p) and three mRNAs (Six4, Stx16, and Ube3a), and these molecules could be recognized as potential genetic and epigenetic biomarkers in microbial-associated depression. This study provides new understanding of the pathogenesis of depression induced by gut microbiota-dysbiosis and may act as a theoretical basis for the development of gut microbiota-based antidepressants.

Abstract Background The cultivated peanut is an important oil and cash crop grown worldwide. To meet the growing demand for peanut production each year, genetic studies and enhanced selection efficiency are essential, including linkage mapping, genome-wide association study, bulked-segregant analysis and marker-assisted selection. Specific locus amplified fragment sequencing (SLAF-seq) is a powerful tool for high density genetic map (HDGM) construction and quantitative trait loci (QTLs) mapping. In this study, a HDGM was constructed using SLAF-seq leading to identification of QTL for seed weight and size in peanut. Results A recombinant inbred line (RIL) population was advanced from a cross between a cultivar ‘Huayu36’ and a germplasm line ‘6–13’ with contrasting seed weight, size and shape. Based on the cultivated peanut genome, a HDGM was constructed with 3866 loci consisting of SLAF-seq and simple sequence repeat (SSR) markers distributed on 20 linkage groups (LGs) covering a total map distance of 1266.87 cM. Phenotypic data of four seed related traits were obtained in four environments, which mostly displayed normal distribution with varied levels of correlation. A total of 27 QTLs for 100 seed weight (100SW), seed length (SL), seed width (SW) and length to width ratio (L/W) were identified on 8 chromosomes, with LOD values of 3.16–31.55 and explaining phenotypic variance (PVE) from 0.74 to 83.23%. Two stable QTL regions were identified on chromosomes 2 and 16, and gene content within these regions provided valuable information for further functional analysis of yield component traits. Conclusions This study represents a new HDGM based on the cultivated peanut genome using SLAF-seq and SSRs. QTL mapping of four seed related traits revealed two stable QTL regions on chromosomes 2 and 16, which not only facilitate fine mapping and cloning these genes, but also provide opportunity for molecular breeding of new peanut cultivars with improved seed weight and size.

Background: Few prospective cohort studies have assessed the relationship between Cystatin C (Cys-C) and risk of stroke in elderly patients with obstructive sleep apnea (OSA). The study sought to examine the association between baseline serum Cys-C and long-term risk of stroke among elderly OSA patients.Methods: A total of 932 patients with OSA, no history of stroke, ≥60 years of age, and complete serum Cys-C records were included in this study. All patients had completed polysomnography (PSG). OSA was defined as an apnea-hypopnea index (AHI) of ≥5 events per hour. Participants were categorized into four groups according to baseline serum Cys-C concentration, split into quartiles. Multivariate Cox regression were used to evaluate the association between Cys-C and the incidence of new-onset stroke.Results: Stroke occurred in 61 patients during the median 42-month follow-up period. The cumulative incidence rate of stroke was 6.5%, which included 54 patients with ischemic stroke and 7 patients with hemorrhagic stroke. The cumulative incidence of stroke was higher among patients with baseline serum Cys-C concentration of ≥1.15 mg/L when compared with other groups (PLog–rank < 0.001). After adjusting for potential confounding factors in the Cox regression model, patients with a serum Cys-C concentration of ≥1.15 mg/L had a 2.16-fold higher risk of developing stroke compared with patients with serum Cys-C ≤ 0.81 mg/L (HR, 2.16, 95%CI, 1.09–6.60; P = 0.017). Additionally, there was a higher risk in those of age ≥70 years (HR, 3.23, 95%CI, 1.05–9.24; P = 0.010). The receiver-operating characteristic curves showed that the capability of Cys-C to identify elderly patients with OSA who had a long-time risk of stroke was moderate (AUC = 0.731, 95% CI: 0.683–0.779, P = 0.001).Conclusion: Increased Cys-C concentration was identified as a risk factor in the incidence of stroke in elderly patients with OSA, independent of gender, BMI, hypertension and other risk factors. Additionally, it conferred a higher risk in patients of age ≥70 years.

Piezoelectric vibration energy harvester (PVEH) is a promising device for sustainable power supply of wireless sensor nodes (WSNs). PVEH is resonant and generates power under constant frequency vibration excitation of mechanical equipment. However, it cannot output high power through off-resonance if it has frequency offset in manufacturing, assembly and use. To address this issue, this paper designs and optimizes a PVEH to harvest power specifically from grid transformer vibration at 100 Hz with high power density of 5.28 μWmm−3g−2. Some resonant frequency modulation methods of PVEH are discussed by theoretical analysis and experiment, such as load impedance, additional mass, glue filling, axial and transverse magnetic force frequency modulation. Finally, efficient energy harvesting of 6.1 V output in 0.0226 g acceleration is tested in grid transformer reactor field application. This research has practical value for the design and optimization process of tunable PVEH for a specific vibration source.

Introduction: Few studies have examined the association between the rate of treatment response and the outcome of pediatric Guillain-Barré syndrome (GBS). Therefore, our study aimed to identify treatment response in relation to the short-term outcomes of GBS. Further, we investigated its potential predictive value for prognosis.Methods: Our retrospective study included children diagnosed with GBS in the Pediatric Neurology Department of the Children's Hospital of Hebei Province from 2016 to 2020. According to the rate of response from the standard intravenous immunoglobulin (IVIg) treatment, patients were divided into two groups: rapid-response GBS (initial response within 7 days) and slow-response (initial response within 8–30 days). The GBS disability score (Hughes Functional Grading Scale) was used to assess the children's functional disability at nadir, 1 month, and 6 months after onset.Results: Among the 36 children included in the study, 18 (50%) and 18 (50%) were rapid and slow responders, respectively. Time from IVIg treatment to the initial response was significantly shorter in the rapid-response group (5 [3–6.25] days vs. 10.5[8.75–15] days in slow-response GBS, p < 0.001). Hughes score at 1 month was worse than the rapid responders (Fisher's exact test, p = 0.006). Survival analysis (Kaplan–Meier) with respect to regaining the ability to walk independently (Hughes Functional Grading Scale of 2) within 1 month after onset was significantly different among the two groups (log-rank test for trend, p = 0.024). The abnormal levels of cerebral spinal fluid proteins and autonomic dysfunction were more frequent in the slow-response group than those in the rapid group (p < 0.05).Conclusion: The rate of response to IVIg treatment was correlated with short-term outcomes in children with GBS and had predictive value for prognosis. The role of patient's initial responses to treatment could be significantly valuable in developing more effective and efficient treatment options.

Abstract Extracellular vesicles (EVs) are emerging as a new source of biomarkers in liquid biopsy because of their wide presence in most body fluids and their ability to load cargoes from disease‐related cells. Owing to the crucial role of EVs in disease diagnosis and treatment, significant efforts have been made to isolate, detect, and analyze EVs with high efficiency. A recent overview of advanced EV detection nanotechnologies is discussed here. First, several key challenges in EV‐based liquid biopsies are introduced. Then, the related pivotal advances in nanotechnologies for EV isolation based on physical features, chemical affinity, and the combination of nanostructures and chemical affinity are summarized. Next, a summary of high‐sensitivity sensors for EV detection and advanced approaches for single EV detection are provided. Later, EV analysis is introduced in practical clinical scenarios, and the application of machine learning in this field is highlighted. Finally, future opportunities for the development of next‐generation nanotechnologies for EV detection are presented.

Background: Schizophrenia is a serious mental disorder with complicated biological mechanisms. Few studies explore the transcriptional features that are shared in brain tissue and peripheral blood. In the present study, we aimed to explore the biological pathways with similar expression patterns in both peripheral blood mononuclear cells (PBMCs) and brain tissues.Methods: The present study used transcriptomics technology to detect mRNA expression of PBMCs of 10 drug-naïve patients with schizophrenia and 20 healthy controls. Transcriptome data sets of brain tissue of patients with schizophrenia downloaded from public databases were also analyzed in our study. The biological pathways with similar expression patterns in the PBMCs and brain tissues were uncovered by differential expression analysis, weighted gene co-expression network analysis (WGCNA), and pathway analysis. Finally, the expression levels of differential expressed genes (DEGs) were validated by real-time fluorescence quantitative polymerase chain reaction (qPCR) in another 12 drug-naïve patients with schizophrenia and 12 healthy controls.Results: We identified 542 DEGs, 51 DEGs, 732 DEGs, and 104 DEGs in PBMCs, dorsolateral prefrontal cortex, anterior cingulate gyrus, and nucleus accumbent, respectively. Five DEG clusters were recognized as having similar gene expression patterns in PBMCs and brain tissues by WGCNA. The pathway analysis illustrates that these DEG clusters are mainly enriched in several biological pathways that are related to phospholipid metabolism, ribosome signal transduction, and mitochondrial oxidative phosphorylation. The differential significance of PLAAT3, PLAAT4, PLD2, RPS29, RPL30, COX7C, COX7A2, NDUFAF2, and ATP5ME were confirmed by qPCR.Conclusions: This study finds that the pathways associated with phospholipid metabolism, ribosome signal transduction, and energy metabolism have similar expression patterns in PBMCs and brain tissues of patients with schizophrenia. Our results supply a novel insight for revealing the pathogenesis of schizophrenia and might offer a new approach to explore potential biological markers of peripheral blood in schizophrenia.

The traditional single degree of freedom linear piezoelectric vibration energy harvester (PVEH), such as the cantilever type, mainly works and resonates in a single direction and at a single frequency. To adapt broadband and bidirectional ambient vibration, this paper designs and compares two PVEHs of L-shaped beam and U-shaped beam through COMSOL simulation and prototype test. FEA modeling is introduced for accurate structure design with modal analysis, voltage frequency response analysis, and proof mass analysis with multiphysics electromechanical coupling simulation. Two PVEH prototypes with different gravity angles and clamping angles are tested at 0.1 g acceleration to find the optimal angle for maximum output power. The best clamping angle of L-PVEH is 135° with RMS power of 0.3 mW at 7.9 Hz, and that of U-PVEH is 45° with RMS power of 0.4 mW at 5.0 Hz. The proposed U-PVEH shows more advantages in low broadband and bidirectional vibration energy harvesting.

Semiconductor-based gas sensors are of great interest in both industrial and research settings, but poor selectivity has hindered their further development. Current efforts including doping, surface modifications and facet controlling have been proved effective. However, the “methods-selectivity” correlation is ambiguous because of uncontrollable defects and surface states during the experiments. Here, as a case study, using a DFT method, we studied the adsorption features of commonly tested gases—CH2O, H2, C2H5OH, CH3COCH3, and NH3—on facets of ZnO(0001¯), ZnO(101¯0) and ZnO(101¯1). The adsorption energies and charge transfers were calculated, and adsorption selectivity was analyzed. The results show ZnO(0001¯) has obvious CH2O adsorption selectivity; ZnO(101¯0) has a slight selectivity to C2H5OH and NH3; and ZnO(101¯1) has a slight selectivity to H2, which agrees with the experimental results. The mechanism of the selective adsorption features was studied in terms of polarity, geometric matching and electronic structure matching. The results show the adsorption selectivity is attributed to a joint effort of electronic structure matching and geometric matching: the former allows for specific gas/slab interactions, the latter decides the strength of the interactions. As the sensing mechanism is probably dominated by gas–lattice interactions, this work is envisioned to be helpful in designing new sensing material with high selectivity.

Background: The response time-course information of biologics and small targeted molecules for the treatment of moderate to severe plaque psoriasis which helps clinicians to understand the onset of action and maintenance of effect are unclear. Quantitative information about the efficacy comparation of different systemic agents are needed.Methods: Model-based meta-analysis was conducted and longitudinal models were developed by applying two clinical end points commonly reported in the clinical trials of psoriasis: the proportion of patients achieving ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI75) and the proportion of patients achieving ≥90% reduction from baseline Psoriasis Area and Severity Index score (PASI90).Results: A total of 80 trials of thirteen biological agents and four small targeted molecules covering 235 treatment arms and 40323 patients with moderate to severe plaque psoriasis were included in this analysis. The drugs were divided into five classes of biologics and three classes of small molecules. Two longitudinal models of PASI75 and PASI90 were used to describe the time-varying drug effect and dose-effect relationship. The typical response-time courses for PASI75 and PASI90 increased over time and finally reached to the platform. For PASI75 end point at week 12, of all the therapeutic drugs, risankizumab administered as 150 mg at week 0, week 4, and q12w showed the most efficacious with PASI75 was 85.95% (95%CI, 75.71–92.60%), followed by ixekizumab administered as 160 mg at week 0, and q4w with PASI75 was 85.9% (95%CI, 76.12–92.79%). As for PASI90 end point at week 12, ixekizumab 160 mg at week 0, and q4w showed the greatest percentage of person achieved PASI90 (67.2%; 95%CI, 49.91–77.2%), followed by risankizumab 150 mg at week 0, week 4, and q12w (65.5%; 95%CI, 47.8–75.7%). What’s more, the risankizumab provided the highest response of PASI90 at week 16 and week 24.Conclusions: This study provided a quantitative efficacy comparation of 17 systemic agents for psoriasis in term of efficacy only and that safety was not considered. Risankizumab and ixekizumab showed superiority for both the two end points.

Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which could result in autophagic cell death (ACD). Though novel combination chemotherapy of autophagy inducers with chemotherapeutic agents is extensively investigated, nanomedicine-based combination therapy for ACD remains in infancy. In attempt to actively trigger ACD for synergistic chemotherapy, here we incorporated autophagy inducer rapamycin (RAP) into 7pep-modified PEG-DSPE polymer micelles (7pep-M-RAP) to specifically target and efficiently priming ACD of MCF-7 human breast cancer cells with high expression of transferrin receptor (TfR). Cytotoxic paclitaxel (PTX)-loaded micelle (7pep-M-PTX) was regarded as chemotherapeutic drug model. We discovered that with superior intracellular uptake in vitro and more tumor accumulation of micelles in vivo, 7pep-M-RAP exhibited excellent autophagy induction and synergistic antitumor efficacy with 7pep-M-PTX. Mechanism study further revealed that 7pep-M-RAP and 7pep-M-PTX used in combination provided enhanced efficacy through induction of both apoptosis- and mitochondria-associated autophagic cell death. Together, our findings suggested that the targeted excess autophagy may provide a rational strategy to improve therapeutic outcome of breast cancer, and simultaneous induction of ACD and apoptosis may be a promising anticancer modality. Key words: Autophagic cell death, Combination therapy, Targeted delivery, Rapamycin, Breast cancer, Transferrin receptor, Mitophagy, Nanomedicines, 7pep

Abstract Background Endothelial progenitor cells (EPCs) play an important role in ischemic stroke. However, there are few studies on the relationship between EPC and nondisabling ischemic cerebrovascular events. Our aim was to investigate the association of EPCs and SDF-1 (serum stromal cell-derived factor-1) with NICE (nondisabling ischemic cerebrovascular events). Methods TIA (transient ischemic attack) and minor stroke patients (153 in total) who had an onset of symptoms within 1 day were consecutively collected. 83 of the patients were categorized into the HR-NICE (high-risk nondisabling ischemic cerebrovascular event) group, and 70 of the patients were in the NHR-NICE (non-high-risk nondisabling ischemic cerebrovascular events) group. Adopted FCM (flow cytometry) was used to measure EPCs, taking double-positive CD34/KDR as EPCs. ELISA was used to measure the concentrations of serum SDF-1 and VEGF (vascular endothelial growth factor). By the sequence of admission time, 15 patients were selected separately from the HR-NICE group and NHR-NICE group, and another 15 healthy volunteers were chosen as the NC (Normal Control) group. The MTT method was used to measure the proliferation of EPCs of peripheral blood in all groups, and the Boyden chamber was used to measure the migration of EPCs. Results Compared with the NHR-NICE group, the HR-NICE group was older and contained more patients with hypertension and diabetes. Triglyceride, total cholesterol, and low-density lipoprotein in the HR-NICE group were also higher. For factors such as smoking, BMI (body mass index), and HCY (homocysteine), there were no significant differences (P > 0.05). Circulating EPCs, SDF-1, and VEGF in the NHR-NICE group were all higher. According to the multifactor regression analysis, age, hypertension, diabetes, total cholesterol, EPCs, and SDF-1 are independent risk factors for HR-NICE. For EPCs of 48-h isolated cultures, proliferation and migration were observed to be weakened compared with those of the NC group (P

In this study, thin-film thermocouples (TFTCs) were combined with a smart bolt to design a smart bolt that can directly test high temperature in service monitoring and parameter calculation for gas turbine structure design. The first-principles calculation was used to analyze the design of the surface properties of nickel-based alloys and insulating layers, and finite element analysis was used to optimize dimension parameters by controlling the thermal stress matching of insulating layers and sensitive layers. The effect of the glass powder with different particle sizes on the microstructure of the ITO and In2O3 films was studied via SEM. The preferred particle size of the additive glass powder is 400 nm. The XRD pattern shows the (222) peak has the highest intensity. The intensities of the (222) and (622) peaks increase after the heat treatment. The calibration results show that the average Seebeck coefficient of the TFTCs can reach 64.9 μV/°C at 1100 °C with a maximum voltage of 71.4 mV. The repeatability error of the cycles of the sensor after heat treatment is ±1.05%. The repeatability of the sensor is up to 98.95%. The smart bolts were tested for application in small aero engines. It can be seen that under the impact of 1000 °C, the thermal response of the prepared smart bolt is better than that of the K-type armored thermocouple, and the thermal balance is achieved faster. The intelligent bolt sensor proposed in this work has better engineering application prospects owing to its convenience of installation in harsh environments.

Fu-you formula (FY), a Traditional Chinese Medicine (TCM) formula composed of 12 herbs, as an in-hospital preparation, has been used treat to precocious puberty (PP) for decades. However, the lack of phytochemical characterization and mechanism of FY remains the main limitation for its spreading. In this study, we analyze the components and mechanisms of FY in PP, based on the integrated pharmacology. Investigated main constituents, targets, pathways of FY by using an integrative pharmacology, and recognized main constituents by HPLC-MS/MS. Then, observed the levels of Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2) in danazol-induced PP in Sprague–Dawley (SD) rats. Lastly, retrospective study analyzed the clinical data of 575 patients who were diagnosed PP, treated by the FY, and followed-up in our hospital from 2014–2020. The result that total of 116 important candidate targets were selected based on pharmacological analysis. Selected the top 10 values key targets such as the estrogen receptor alpha (ESR1) and insulin-like growth factor 1 (IGF1), were localized and the related gene functions were determined. Gene functions were associated with biological regulation, a cellular process, or signaling pathway, such as the Estrogen signaling pathway, MAPK signaling pathway and PI3K-Akt signaling pathway. By recognizing the five compounds related to the ESR1 and IGF1, which are Quercetin, kaempferol, Luteolin, Apigenin, and Emodin. The results of the molecular docking study further showed that the flavonoids had a strong binding affinity for ESR1 and IGF1 after docking into the crystal structure. The results showed that the FY could effectively reduce E2, LH, and FSH levels in SD rats. Furthermore, the results of the retrospective analysis of medical records showed that the FY could remarkably reduce E2 levels in girls with PP.

Smart wearable devices are occupying an increasingly important position in scientific research and people’s life fields. As an indispensable component of smart wearable devices, sensors play a crucial role in their sensing and feedback capabilities. In this paper, we investigate the bending gesture sensing for the most dexterous part of human anatomy, the finger. Based on series-connected fiber Bragg gratings (FBGs), recognition of finger bending posture is achieved by MATLAB modeling and the cubic spline interpolation.

High-entropy alloy particles reinforcements improve the mechanical properties of aluminum matrix composites while increasing its density. Investigating the effects of the reinforcement content is conducive to the fabrication of lightweight and high strength composites. FeCoCrNiAl high-entropy alloy particles (HEAp) reinforced 7075Al matrix composites (HEAp/Al) with different HEAp volume fractions of 5, 10, 15, and 20 vol% were fabricated via a vacuum ball milling and vacuum hot pressing sintering, and then the microstructures, interface, density, and mechanical properties of the HEAp/Al composites were characterized. The results indicated that composites with high relative density can be obtained with a holding time of 10 min at 580 °C, 30 MPa; the HEAp distribution was homogeneous as the increase of reinforcement volume fraction decreases and forms agglomeration, especially when the volume fraction is up to 15 vol% and 20 vol%; the density and hardness of HEAp/Al composites improved with the increase of reinforcements’ volume fraction, whereas the flexural strength and fracture toughness of HEAp/Al composites increased at first and then decreased; the HEAp/Al composites reinforced by 10 vol% HEAp showed the maximum flexural strength and fracture toughness, which were increased by 124.6% and 107% compared with 7075Al, respectively; the improvement of mechanical properties was attributed to the dislocation strengthening behavior and load transfer effect of the HEAp reinforcement.

Reduced graphene oxide (rGO) fiber as a carbon-based fiber sensor has aroused widespread interest in the field of gas sensing. However, the low response value and poor flexibility of the rGO fiber sensor severely limit its application in the field of flexible wearable electronics. In this paper, a flexible and wearable nylon fiber sensor modified by rGO and ZnO quantum dots (QDs) is proposed for wide-range NO2 gas detection at room temperature. The response value of the nylon fiber sensor to 100 ppm NO2 gas is as high as 0.4958, and the response time and recovery time are 216.2 s and 667.9 s, respectively. The relationship between the sensor’s response value and the NO2 concentration value is linear in the range of 20–100 ppm, and the fitting coefficient is 0.998. In addition, the test results show that the sensor also has good repeatability, flexibility, and selectivity. Moreover, an early warning module was also designed and is proposed in this paper to realize the over-limit monitoring of NO2 gas, and the flexible sensor was embedded in a mask, demonstrating its great application potential and value in the field of wearable electronics.

A Mach–Zehnder fiber optic sensor with high refractive index response sensitivity was developed. By fabricating a waist-enlarged bitaper structure on the interference arm of a single mode–multimode–single mode (SMS) Mach–Zehnder interferometer (MZI), the spectral contrast and response sensitivity were improved. Subsequently, the response sensitivity was further improved by etching the interference arm. When a beam of light was introduced into the sensor, due to the structural mismatch between the multimode fiber and the normal transmission light, the difference between the low-order mode and the high-order mode was generated in the fiber core and the fiber cladding. In the process of transmission in the sensing arm, due to the different refractive indices of the core and cladding, the optical path difference of the high-order mode and the low-order mode was different, which eventually generated interference fringes. The experimentally measured response sensitivity of SMS MZI in the range of 1.351 RIU to 1.402 RIU is 57.623 nm/RIU; the response sensitivity of a single mode–multimode–bitaper–multimode–single mode (SMBMS) MZI is 61.607 nm/RIU; and the response sensitivity of the etched SMBMS (ESMBMS) MZI is 287.65 nm/RIU. The response sensitivity of the new ESMBMS MZI is three times higher than that of the original SMS MZI. The sensor has the characteristics of compact structure, high sensitivity, easy manufacture, and a wide range of refractive index measurements, and can be used in food processing, pharmaceutical manufacturing and other fields.

An all-fiber temperature and refractive dual-parameter-sensing Michelson interferometer is designed based on the waist-enlarged bitaper. At 5 mm from the fiber end, the waist-enlarged bitaper is manually spliced and the probe is formed. Since the input light encounters the waist-enlarged bitaper, it will excite high-order modes to transmit in the fiber cladding, and there will be an optical path difference between the basic mode and the higher-order mode. The light transmitted in the core and cladding is reflected upon encountering the fiber end face and the interference occurs due to the optical path difference between basic mode and higher-order mode. Changes in temperature and refractive index at the fiber probe can be detected by monitoring the interference fringes. The refractive response sensitivity is −191.06 dBm/RIU from 1.351 RIU to 1.4027 RIU, and the temperature response sensitivity is 0.12 nm/°C from 11 °C to 98 °C. Through the sensitivity matrix equation, the superimposed refractive index and temperature signals can be effectively demodulated. The sensor has the advantages of multi-parameter measurement, compact structure, low cost, easy fabrication and high reliability.

To convert as much vibration energy as possible into electrical energy, the design of a high-performance piezoelectric vibration energy harvester (PVEH) has been studied widely in recent years. To overcome the low energy utilization of a traditional piezoelectric cantilever by inhomogeneous strain, a uniform stress distribution of bimorph by an ARC mechanical stopper structure has been designed for maximum piezoelectric vibration energy harvesting. Deflection equations and their simulation at the first-order modal of two classic bimorph cantilever beam models, with transverse tip force and with equal curvature, are derived based on the Euler–Bernoulli beam assumption. Piezoelectric energy from a beam model with equal curvature is four times that of a cantilever beam model with transverse tip force at the theoretical level. The nonlinear frequency response performance of bimorphs by an ARC mechanical stopper and point stopper model could be observed by the numerical simulations of the lumped parameter electromechanical model. PVEH prototypes were manufactured by 3D printing and tested. To verify the high-power generation capacity, PVEH with an ARC stopper has 1.756 times more voltage than that of a PVEH with a point stopper.

Thin-Film Thermocouples (TFTCs) are characterized by their high spatial resolutions, low cost, high efficiency and low interference on the air flow. However, the thermal stability of TFTCs should be further improved for application since their accuracy is influenced by joule heat and temperature time drift. In this paper, 3D molecular dynamics and finite element analysis are used for structural design. The effects of RF magnetron sputtering power and gas flow rate on conductivity and temperature time drift rate (DT) of high thermal stability tungsten–rhenium (95% W/5% Re vs. 74% W/26% Re) TFTCs were analyzed. According to the experimental results, the average Seebeck coefficient reached 31.1 µV/°C at 900 °C temperature difference (hot junction 1040 °C) with a repeatability error at ±1.37% in 33 h. The conductivity is 17.1 S/m, which is approximately 15.2 times larger than the compared tungsten-rhenium sample we presented, and the DT is 0.92 °C/h (1040 °C for 5 h), which is 9.5% of the old type we presented and 4.5% of compared ITO sample. The lumped capacity method test shows that the response time is 11.5 ms at 300 °C. This indicated an important significance in real-time temperature measurement for narrow spaces, such as the aero-engine combustion chamber.

The efficacy of probiotic strains of Lactobacillus acidophilus to manage acute gastroenteritis in children is still not established. We searched the Cochrane Library, PubMed, EMBASE, and three Chinese literature databases (CNKI, WanFang, and CBM) from their inception to February 2021 for RCTs that compared the use of Lactobacillus acidophilus with no Lactobacillus acidophilus. The grey literature was searched through Google Scholar. Authors of the original papers were contacted for additional data. The study included a total of 15 RCTs involving 1765 patients. Compared with placebo or no treatment, Lactobacillus acidophilus was associated with a reduced duration of diarrhea (moderate quality of evidence), but the effect was not statistically significant when only the individual probiotic strain was provided. Lactobacillus acidophilus was effective when used at a daily dose ≥ 109 CFU. There was no difference in the effect of Lactobacillus acidophilus on diarrhea duration among Asian, European, or American countries. Lactobacillus acidophilus reduced the frequency of diarrhea on day 2 to day 5. However, it was statistically significant on day 3. When administered at a dosage of more than 109 CFU to children with acute gastroenteritis, moderate- to low-quality data showed that Lactobacillus acidophilus reduced the duration of diarrhea and conferred a benefit for frequency of diarrhea.

In electrohydrostatic drive actuators, there is a demand for temperature and pressure monitoring in complex environments. Fiber Bragg grating (FBG) has become a promising sensor for measuring temperature and pressure. However, there is a cross-sensitivity between temperature and pressure. A gold-plated FBG is proposed and manufactured, and an FBG is used as a reference grating to form a parallel all-fiber sensing system, which can realize the simultaneous measurement of pressure and temperature. Based on the simulation software, the mechanical distribution of the pressure diaphragm is analyzed, and the fixation scheme of the sensor is determined. Using the demodulator to monitor the changes in the reflectance spectrum in real-time, the pressure and ambient temperature applied to the sensor are measured. The experimental results show that the temperature sensitivity of gold-plated FBG is 3 times that of quartz FBG, which can effectively distinguish the temperature changes. The pressure response sensitivity of gold-plated FBG is 0.3 nm/MPa, which is same as the quartz FBG. Through the sensitivity matrix equation, the temperature and pressure dual-parameter sensing measurement is realized. The accuracy of the temperature and pressure measurement is 97.7% and 99.0%, and the corresponding response rates are 2.7 ms/°C and 2 ms/MPa, respectively. The sensor has a simple structure and high sensitivity, and it is promising to be applied in health monitoring in complex environments with a high temperature and high pressure.

Early diagnosis of colon cancer (CC) is clinically important, as it can significantly improve patients’ survival rate and quality of life. Although the potential role for small extracellular vesicles (sEVs) in early detection of many diseases has been repeatedly mentioned, systematic screening of plasma sEVs derived early CC specific biomarkers has not yet been reported. In this work, plasma sEVs enriched fractions were derived from 15 early-stage (TisN0M0) CC patients and 10 normal controls (NC). RNA sequencing identified a total number of 95 sEVs enriched fraction derived miRNAs with differential expression between CC and NC, most of which (60/95) was in well accordance with tissue results in the Cancer Genome Atlas (TCGA) dataset. Among those miRNAs, we selected let-7b-3p, miR-139-3p, miR-145-3p, and miR-150-3p for further validation in an independent cohort consisting of 134 participants (58 CC and 76 NC). In the validation cohort, the AUC of 4 individual miRNAs ranged from 0.680 to 0.792. A logistic model combining two miRNAs (i.e. let-7b-3p and miR-145-3p) achieved an AUC of 0.901. Adding the 3rd miRNA into this model can further increase the AUC to 0.927. Side by side comparison revealed that sEVs miRNA profile outperformed cell-free plasma miRNA in the diagnosis of early CC. In conclusion, we suggested that circulating sEVs enriched fractions have a distinct miRNA profile in CC patients, and sEVs derived miRNA could be used as a promising biomarker to detect CC at an early stage.

A micelle system modified with α-Conotoxin ImI (ImI), a potently antagonist for alpha7 nicotinic acetylcholine receptor (α7-nAChR) previously utilized for targeting breast cancer, was constructed. Its targeting efficiency and cytotoxicity against non-small cell lung cancer (NSCLC) highly expressing α7-nAChR was investigated. A549, a non-small cell lung cancer cell line, was selected as the cell model. The cellular uptake study showed that the optimal modification ratio of ImI on micelle surface was 5% and ImI-modification increased intracellular delivery efficiency to A549 cells via receptor-mediated endocytosis. Intracellular Ca2+ transient assay demonstrated that ImI modification led to enhanced molecular interaction between nanocarriers and A549 cells. The in vivo near-infrared fluorescence imaging further revealed that ImI-modified micelles could facilitate the drug accumulation in tumor sites compared with non-modified micelles via α7-nAChR mediation. Moreover, docetaxel (DTX) was loaded in ImI-modified nanomedicines to evaluate its in vitro cytotoxicity. As a result, DTX-loaded ImI-PMs exhibited greater anti-proliferation effect on A549 cells compared with non-modified micelles. Generally, our study proved that ImI-modified micelles had targeting ability to NSCLC in addition to breast cancer and it may provide a promising strategy to deliver drugs to NSCLC overexpressing α7-nAChR.

In the present study, a high-performance n-type temperature sensor was developed by a new and facile synthesis approach, which could apply to ambient temperature applications. As impacted by the low sintering temperature of flexible polyimide substrates, a screen printing technology-based method to prepare thermoelectric materials and a low-temperature heat treatment process applying to polymer substrates were proposed and achieved. By regulating the preparation parameters of the high-performance n-type indium oxide material, the optimal proportioning method and the post-treatment process method were developed. The sensors based on thermoelectric effects exhibited a sensitivity of 162.5 μV/°C, as well as a wide range of temperature measurement from ambient temperature to 223.6 °C. Furthermore, it is expected to conduct temperature monitoring in different scenarios through a sensor prepared in masks and mechanical hands, laying a foundation for the large-scale manufacturing and widespread application of flexible electronic skin and devices.

Piezoelectric bimorph cantilever is a typical structure for vibration energy harvesting. This paper studies the method to improve the accuracy of FEA (finite element analysis) simulation for piezoelectric bimorph cantilever. The COSMOL simulation methods based on 1 D (dimension) model of Euler Bernoulli beam, as well as 2 D and 3 D models of solid mechanics are proposed respectively. Compared with the theory and experiment results given by Erturk A, the influences of 1 D and 3 D piezoelectric material parameters on simulation accuracy in FEA modeling is discussed. The simulation error can be reduced to less than 1.2% by using 1D piezoelectric material parameters in COMSOL simulation, while the maximum simulation error can be up to 28% by using 3D piezoelectric material parameters. Comparing serial and parallel configurations of piezoelectric bimorph cantilever, the output electrical powers, varying with the excitation frequency and load resistance, are also discussed in COMSOL simulation. Performance comparation of three kinds of piezoelectric bimorph cantilevers with tip mass shows that the modelling and simulation in finite element methods by COMSOL are simple and convenient, and are suitable for the electromechanical coupling analysis and optimization of complex topological structures.

In this paper, a novel micro-displacement sensor with double optical fiber probes is proposed and designed, which can realize the highly sensitive sensing of longitudinal or lateral micro-displacements. The optical fiber probes are made through photopolymer formulation, and the effects of reaction time and optical power on the growth length of the probe are illustrated. The relationship between light intensity and longitudinal micro-displacement is a power function in the range of 0–100 μm at room temperature with a correlation coefficient of 98.92%. For lateral micro-displacement, the sensitivity is −2.9697 dBm/μm in the range of 0–6 μm with a linear fit of 99.61%. In addition, the linear correlation coefficient decreases as the initial longitudinal distance increases, and the function of these correlation coefficients is also linear with a linearity of 96.14%. This sensor has a simple manufacturing process, low cost, high sensitivity, and fast response speed. It is suitable for harsh environments such as strong electromagnetic interference and corrosivity, and has a broad application prospect in the field of micro-displacement sensing.

Intracellular micromanipulation assisted by robotic systems has valuable applications in biomedical research, such as genetic diagnosis and genome-editing tasks. However, current studies suffer from a low success rate and a large operation damage because of insufficient information on the operation information of targeted specimens. The complexity of the intracellular environment causes difficulties in visualizing manipulation tools and specimens. This review summarizes and analyzes the current development of advanced biological imaging sampling and computational processing methods in intracellular micromanipulation applications. It also discusses the related limitations and future extension, providing an important reference about this field.

WRe26-In2O3 (WRe26 (tungsten-26% rhenium) and In2O3 thermoelectric materials) thin film thermocouples (TFTCs) have been fabricated based on magnetron sputtering technology, which can be used in temperature measurement. Many annealing processes were studied to promote the sensitivity of WRe26-In2O3 TFTCs. The optimal annealing process of the thermocouple under this kind of RF magnetron sputtering method was proposed after analyzing the properties of In2O3 films and the thermoelectric voltage of TFTCs at different annealing processes. The calibration results showed that the WRe26-In2O3 TFTCs achieved a thermoelectric voltage of 123.6 mV at a temperature difference of 612.9 K, with a sensitivity of up to 201.6 µV/K. Also, TFTC kept a stable thermoelectric voltage output at 973 K for 20 min and at 773 K for two hours. In general, the WRe26-In2O3 TFTCs developed in this work have great potential for practical applications. In future work, we will focus on the thermoelectric stability of TFTCs at higher temperatures.

The ability of electrospun polyvinylidene fluoride (PVDF) fibers to produce piezoelectricity has been demonstrated for a while. Widespread applications of electrospun PVDF as an energy conversion material, however, have not materialized due to the random arrangement of fibers fabricated by traditional electrospinning. In this work, a developed 3D electrospinning technique is utilized to fabricate a PVDF micro wall made up of densely stacked fibers in a fiber-by-fiber manner. Results from X-ray diffraction (XRD) and Fourier transform infrared spectra (FTIR) demonstrate that the crystalline structure of this PVDF wall is predominant in the β phase, revealing the advanced integration capability of structural fabrication and piezoelectric poling with this 3D electrospinning. The piezoelectric response along the radial direction of these PVDF fibers is measured while the toppled micro wall, comprised of 60 fibers, is sandwich assembled with a pair of top/bottom electrodes. The measured electrical output is ca. 0.48 V and 2.7 nA. Moreover, after constant mechanical compression happening over 10,000 times, no obvious reduction in the piezoelectric response has been observed. The combined merits of high-precision 3D fabrication, in situ piezoelectric poling, and high mechanical robust make this novel structure an attractive candidate for applications in piezoelectric energy harvesting and sensing.

Osteoporosis is a highly prevalent disease which has been a major public health problem and considered to be associated with chronic low-grade systemic inflammation and oxidative damage. Taxifolin is a natural flavonoid and possesses many pharmacological activities including antioxidant and anti-inflammatory. Because flavonoids have been confirmed to fight osteoporosis and promote bone health, the aim of this study was to investigate the effects of taxifolin on the formation and function of osteoclast. In this study, we examined the effects of taxifolin on osteoclast using both in vitro and in vivo studies. Taxifolin suppressed the activation of nuclear factor-κB, C-Fos and mitogen-activated protein kinase, and also decreased osteoclast-specific genes expression, including Trap, Mmp-9, Cathepsin K, C-Fos, Nfatc1, and Rank. Taxifolin also prevented reactive oxygen species (ROS) production following RANKL stimulation. In addition, taxifolin alleviated ovariectomized-induced bone loss by repressing osteoclast activity and decreasing serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and receptor activator of nuclear factor-κB ligand (RANKL) in vivo. Our results indicated that taxifolin inhibits osteoclastogenesis via regulation of modulation of several RANKL signaling pathways. Therefore, taxifolin may be considered as a potential alternative therapeutic agent for treating osteoclast-related diseases.

The piezoelectric cantilever with a large proof mass is a classic vibration energy harvesting structure. In this study, in order to harvest much more energy from low frequency vibration in the finite volume, a novel L type mass block is proposed and compared with a traditional rectangular mass block for the piezoelectric cantilever. A theoretical modeling of lumped parameter system is carried out considering the effect of mass block length on mass, stiffness and damping. A series of PZT bimorph cantilevers with brass proof mass prototypes are fabricated for the experimental verification. Their eigenfrequency and maximum piezoelectric power output are analyzed by the experiment and simulation. The piezoelectric cantilever with L type mass block avoids the weakness of decreasing the effective length of piezoelectric cantilever, and has lower eigenfrequency and larger piezoelectric power output than that with rectangular mass block. Its piezoelectric power output of 192 mW/(g2) can be obtained at the low resonant frequency of 18.1 Hz and the optimal load impedance of 5kΩ, and the unit volume power density is as high as 24.6 mW/(cm3×g2).

An improved fuzzy neural network (FNN)/proportion integration differentiation (PID) compound control scheme based on variable universe and back-propagation (BP) algorithms is proposed to improve the ability of disturbance rejection of a three-axis inertially stabilized platform (ISP) for aerial remote sensing applications. In the design of improved FNN/PID compound controller, the variable universe method is firstly used for the design of the fuzzy/PID compound controller; then, the BP algorithm is utilized to finely tune the controller parameters online. In this way, the desired performances with good ability of disturbance rejection and high stabilization accuracy are obtained for the aerial ISP. The simulations and experiments are, respectively, carried out to validate the improved FNN/PID compound control method. The results show that the improved FNN/PID compound control scheme has the excellent capability in disturbance rejection, by which the ISP’s stabilization accuracy under dynamic disturbance is improved significantly.

Dihydromyricetin (DMY), the main flavonoid component of Ampelopsis grossedentata, possesses pharmacological activities useful for treatment of diseases associated with inflammation and oxidative damage. Because osteoclasts are often involved in chronic low-grade systemic inflammation and oxidative damage, we hypothesized that DMY may be an effective treatment for osteoclast-related diseases. The effects of DMY on osteoclast formation and activity were examined in vitro. Female C57BL/6 mice were ovariectomized to mimic menopause-induced bone loss and treated with DMY, and femur samples were subjected to bone structure and histological analysis, serum biochemical indicators were also measured. DMY suppressed the activation of nuclear factor-κB, c-Fos and mitogen-activated protein kinase, and prevented production of reactive oxygen species. DMY decreased expression of osteoclast-specific genes, including Trap, Mmp-9, Cathepsin K, C-Fos, Nfatc1, and Rank. In addition, DMY prevented bone loss and decreased serum levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6, and with a decrease in the ratio between receptor activator of nuclear factor-κB (RANK) ligand (RANKL) and osteoprotegerin (OPG) in vivo. These findings demonstrate that DMY attenuates bone loss and inhibits osteoclast formation and activity through modulation of multiple pathways both upstream and downstream of RANKL signaling. DMY may thus be a useful option for treatment of osteoclast-related diseases such as rheumatoid arthritis and osteoporosis.