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Abstract Objective Socioeconomic status (SES) has been previously associated with children’s early development, health, and nutrition; however, evidence about the potential role of caregiver-child interaction in such associations was limited. This study aimed to explore the effect of caregiver-child interaction on the associations of SES with child developmental outcomes, including early neurodevelopment and social-emotional behavior. Methods A cross-sectional survey was conducted among 2078 children aged 0–6 in a rural county that just lifted out of poverty in 2020 in Central China. The Ages & Stages Questionnaires-Chinese version (ASQ-C) and the Social-Emotional (ASQ: SE) questionnaire were used to assess children's early neurodevelopment and social-emotional behavior, respectively. Caregiver-child interaction was evaluated with the Brigance Parent–Child Interactions Scale. Regression-based statistical mediation and moderation effect were conducted with the PROCESS macro of SPSS. Results Children with low SES had an increased risk of suspected neurodevelopmental delay [OR = 1.92, 95% CI: 1.50, 2.44] and social-emotional developmental delay [OR = 1.31, 95% CI: 1.04, 1.66]. The caregiver-child interaction partially mediated the associations of SES with child developmental outcomes; the proportion of the indirect effect was 14.9% for ASQ-C total score and 32.1% for ASQ: SE score. Moreover, the caregiver-child interaction had a significant moderation effect on the association of SES with ASQ-C total score (P

Highlights LPS-induced ARDS rats and PMVECs have low Fcgr2b level and high Elk1 level; Fcgr2b overexpression mitigates LPS-induced ALI/ARDS in rats and PMVECs; Elk1 knockdown mitigates LPS-induced ALI/ARDS in rats and PMVECs; Elk1 represses Fcgr2b transcription by recruiting H3K9me3; Elk1/Fcgr2b axis aggravates LPS-induced ALI/ARDS in rats and PMVECs.

Abstract Hepatitis C, a particularly dangerous form of viral hepatitis caused by hepatitis C virus (HCV) infection, is a major socio-economic and public health problem. Due to the rapid development of deep learning, it has become a common practice to apply deep learning to the healthcare industry to improve the effectiveness and accuracy of disease identification. In order to improve the effectiveness and accuracy of hepatitis C detection, this study proposes an improved denoising autoencoder (IDAE) and applies it to hepatitis C disease detection. Conventional denoising autoencoder introduces random noise at the input layer of the encoder. However, due to the presence of these features, encoders that directly add random noise may mask certain intrinsic properties of the data, making it challenging to learn deeper features. In this study, the problem of data information loss in traditional denoising autoencoding is addressed by incorporating the concept of residual neural networks into an enhanced denoising autoencoder. In our experimental study, we applied this enhanced denoising autoencoder to the open-source Hepatitis C dataset and the results showed significant results in feature extraction. While existing baseline machine learning methods have less than 90% accuracy and integrated algorithms and traditional autoencoders have only 95% correctness, the improved IDAE achieves 99% accuracy in the downstream hepatitis C classification task, which is a 9% improvement over a single algorithm, and a nearly 4% improvement over integrated algorithms and other autoencoders. The above results demonstrate that IDAE can effectively capture key disease features and improve the accuracy of disease prediction in hepatitis C data. This indicates that IDAE has the potential to be widely used in the detection and management of hepatitis C and similar diseases, especially in the development of early warning systems, progression prediction and personalised treatment strategies.

Abstract Background The excellent efficacy is mitigated by the limited safety profile of microfocused ultrasound procedures. Objective We sought to assess the safety and tightening efficacy of a novel microfocused ultrasound. Methods The randomized middle and lower face and submental region of the participants were treated with the novel device using the following transducers: M4.5, D4.5, M3.0, and D3.0. Improvement in paired comparison of pretreatment and posttreatment photographs, three-dimensional (3D) volumetric assessments, skin thickness measured by B-ultrasonography, and skin photoaging parameters were evaluated. Adverse events and patient satisfaction were also recorded. Results A total of 20 participants (20 female) were enrolled. Fourteen of 20 participants (70%) were judged to show clinically significant facial tightening during 3-month follow-up (P

Abstract Lung cancer (LCa), the most frequent malignancy worldwide, causes millions of mortalities each year. Overexpression of the long noncoding RNA MIR210HG in LCa has been established; however, a more comprehensive investigation into its biological role within LCa is imperative. This study aimed to validate the MIR210H levels in LCa tissues and cells. The expression of indicated genes was evaluated using quantitative real‐time polymerase chain reaction (qRT‐PCR) and/or Western blotting. The viability, proliferation, migration, and invasion of LCa cells were measured using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT), colony formation, wound healing, and transwell assays, respectively. The methylation levels of LCa cells were determined via methylation‐specific PCR; additionally, chromatin immunoprecipitation or RNA immunoprecipitation assays were performed to determine the targeting relationship between DNA methyltransferase 1 (DNMT1) and the SH3‐domain containing CRB2 like 3 (SH3GL3) promoters and the interaction between DNMT1 and MIR210HG, respectively. Our findings revealed the upregulation of MIR210HG, coupled with a diminished expression of SH3GL3 in LCa tissues and cells. Knockdown of MIR210HG or overexpression of SH3GL3 suppressed the proliferative, migratory, and invasive capacities of the cells. DNMT1 bound to the SH3GL3 promoter region, and MIR210HG inhibited the transcription of SH3GL3 by recruiting DNMT1. These findings indicate that MIR210HG facilitates LCa cell growth and metastasis by repressing SH3GL3 transcription via the recruitment of DNMT1 to the SH3GL3 promoter region.

Huangjiu is known for its unique aroma, primarily attributed to its high concentration of β-phenylethanol (ranging from 40 to 130 mg/L). Phenylalanine aminotransferase Aro9p and phenylpyruvate decarboxylase Aro10p are key enzymes in the β-phenylethanol synthetic pathway of Saccharomyces cerevisiae HJ. This study examined the enzymatic properties of these two enzymes derived from S. cerevisiae HJ and S288C. After substrate docking, Aro9pHJ (−24.05 kJ/mol) and Aro10pHJ (−14.33 kJ/mol) exhibited lower binding free energies compared to Aro9pS288C (−21.93 kJ/mol) and Aro10pS288C (−12.84 kJ/mol). ARO9 and ARO10 genes were heterologously expressed in E. coli BL21. Aro9p, which was purified via affinity chromatography, showed inhibition by l-phenylalanine (L-PHE), but the reaction rate Vmax(Aro9pHJ: 23.89 μmol·(min∙g)−1) > Aro9pS288C: 21.3 μmol·(min∙g)−1) and inhibition constant Ki values (Aro9pHJ: 0.28 mol L−1>Aro9pS288C 0.26 mol L−1) indicated that Aro9p from S. cerevisiae HJ was more tolerant to substrate stress during Huangjiu fermentation. In the presence of the same substrate phenylpyruvate (PPY), Aro10pHJ exhibited a stronger affinity than Aro10pS288C. Furthermore, Aro9pHJ and Aro10pHJ were slightly more tolerant to the final metabolites β-phenylethanol and ethanol, respectively, compared to those from S288C. The study suggests that the mutations in Aro9pHJ and Aro10pHJ may contribute to the increased β-phenylethanol concentration in Huangjiu. This is the first study investigating enzyme tolerance mechanisms in terms of substrate and product, providing a theoretical basis for the regulation of the β-phenylethanol metabolic pathway.

Aptamer-based lateral flow analysis (Apt-LFAs) has promising applications in many fields. Nanozymes have demonstrated high potential in improving the performance of Apt-LFAs and have been increasingly utilized in recent studies. In this study, we developed a nanozyme-based Apt-LFA for the rapid and sensitive detection of kanamycin by using a novel dual-functionalized AuNPs@polyA-DNA/GpG-Cu2+ nanozyme as a nanoprobe. In the nanoprobe design, the polyA-cDNA strand can discriminate a kanamycin aptamer from the kanamycin/aptamer complex, and the GpG-Cu2+ complex can amplify the detection signal by catalyzing the chromogenic reaction. The nanozyme Apt-LFA can quantify kanamycin in the range of 1–250 ng/mL with an LOD of 0.08 ng/mL, which demonstrated a 4-fold sensitivity improvement and had a wider linear range than the conventional AuNP-based LFA. The Apt-LFA was successfully applied to the detection of kanamycin in honey with good recoveries. Our dual-functionalized AuNP nanoprobe is easily prepared and can be highly compatible with the conventional AuNP-DNA-based LFA platform; thus, it can be extended to the application of Apt-LFAs for other small molecules.

Abstract Objective Sepsis is an organ malfunction disease that may become fatal and is commonly accompanied by severe complications such as multiorgan dysfunction. Patients who are already hospitalized have a high risk of death due to sepsis. Even though early diagnosis is very important, the technology and clinical approaches that are now available are inadequate. Hence, there is an immediate necessity to investigate biological markers that are sensitive, specific, and reliable for the prompt detection of sepsis to reduce mortality and improve patient prognosis. Mounting research data indicate that ferroptosis contributes to the occurrence, development, and prevention of sepsis. However, the specific regulatory mechanism of ferroptosis remains to be elucidated. This research evaluated the expression profiles of ferroptosis‐related genes (FRGs) and the diagnostic significance of the ferroptosis‐related classifiers in sepsis. Methods and Results We collected three peripheral blood data sets from septic patients, integrated the clinical examination data and mRNA expression profile of these patients, and identified 13 FRGs in sepsis through a co‐expression network and differential analysis. Then, an optimal classifier tool for sepsis was constructed by integrating a variety of machine learning algorithms. Two key genes, ATG16L1 and SRC, were shown to be shared between the algorithms, and thus were identified as the FRG signature of classifier. The tool exhibited satisfactory diagnostic efficiency in the training data set (AUC = 0.711) and two external verification data sets (AUC = 0.961; AUC = 0.913). In the rat cecal ligation puncture sepsis model, in vivo experiments verified the involvement of ATG16L1 and SRC in the early sepsis process. Conclusion These findings confirm that FRGs may participate in the development of sepsis, the ferroptosis related classifiers can provide a basis for the development of new strategies for the early diagnosis of sepsis and the discovery of new potential therapeutic targets for life‐threatening infections.

Abstract Objective To investigate the mechanism of action of Srg3 in acute lung injury caused by sepsis. Methods First, a sepsis-induced acute lung injury rat model was established using cecal ligation and puncture (CLP). RNA sequencing (RNA-seq) was used to screen for highly expressed genes in sepsis-induced acute lung injury (ALI), and the results showed that Srg3 was significantly upregulated. Then, SWI3-related gene 3 (Srg3) was knocked down using AAV9 vector in vivo, and changes in ALI symptoms in rats were analyzed. In vitro experiments were conducted by establishing a cell model using lipopolysaccharide (LPS)-induced BEAS-2B cells and coculturing them with phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells to analyze macrophage polarization. Next, downstream signaling pathways regulated by Srg3 and transcription factors involved in regulating Srg3 expression were analyzed using the KEGG database. Finally, gain-of-loss functional validation experiments were performed to analyze the role of downstream signaling pathways regulated by Srg3 and transcription factors involved in regulating Srg3 expression in sepsis-induced acute lung injury. Results Srg3 was significantly upregulated in sepsis-induced acute lung injury, and knocking down Srg3 significantly improved the symptoms of ALI in rats. Furthermore, in vitro experiments showed that knocking down Srg3 significantly weakened the inhibitory effect of LPS on the viability of BEAS-2B cells and promoted alternative activation phenotype (M2) macrophage polarization. Subsequent experiments showed that Srg3 can regulate the activation of the NF-κB signaling pathway and promote ferroptosis. Specific activation of the NF-κB signaling pathway or ferroptosis significantly weakened the effect of Srg3 knockdown. It was then found that Srg3 can be transcriptionally activated by interferon regulatory factor 7 (Irf7), and specific inhibition of Irf7 significantly improved the symptoms of ALI. Conclusions Irf7 transcriptionally activates the expression of Srg3, which can promote ferroptosis and activate classical activation phenotype (M1) macrophage polarization by regulating the NF-κB signaling pathway, thereby exacerbating the symptoms of septic lung injury.

Abstract Background Herein, the effect of pre-use of Dexmedetomidine(Dex) on the half-effective dose (ED50) and 95%-effective dose (ED95) of Remimazolam tosilate(RT) in inhibiting the positive cardiovascular response(CR) which means blood pressure or heart rate rises above a critical threshold induced by double-lumen bronchial intubation was evaluated. Methods Patients who underwent video-assisted thoracic surgery were divided into groups A (0), B (0.5 µg/kg), and C (1 µg/kg) based on different Dex doses. Group A included subgroups comprising young (A-Y) and elderly (A-O) patients. Neither groups B nor C included elderly patients due of the sedative effect of Dex. Based on the previous subject’s CR, the dose of RT was increased or decreased in the next patient using the sequential method. This trial would be terminated when the seventh crossover occurred, at which point the sample size met the stable estimate of the target dose. Heart rate (HR) and mean arterial pressure (MAP) were monitored throughout the trial, and sedation was assessed using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale. HR and MAP were recorded at baseline (T1), the end of Dex (T2), and the end of RT (T3), the maximum HR and MAP were recorded within 3 min of intubation from beginning to end (T4). There was a positive CR when the T4 levels rose above 15% of the baseline. The ED50/ED95 and corresponding confidence interval were calculated using probability regression. Results In total, 114 patients completed the trial. Without the use of Dex, the ED50/ED95 of TR inhibiting the positive CR caused by double-lumen bronchial intubation was 0.198/0.227 and 0.155/0.181 mg/kg in groups A-Y and A-O, respectively. The changes in vital signs from T1 to T3 were similar in the subgroups, indicating that the elderly patients were more sensitive to the dose of RT. The ED50/ED95 of RT inhibiting the positive CR caused by double-lumen endobronchial intubation was 0.122/0.150 and 0.068/0.084 mg/kg in groups B and C, respectively. And, the fluctuation of blood pressure from T3 to T4 was reduced by using Dex. RT was 100% effective in sedation with no significant inhibition of circulation. Apart from one case of hypotension occurred in group A-Y, two cases of low HR in group B, and one case of low HR in group C, no other adverse events were noted. Conclusions The optimal dose of RT to inhibit positive CR induced by double-lumen bronchial intubation in elderly patients was 0.18 mg/kg and 0.23 mg/kg in younger patients. When the pre-use dose of Dex was 0.5 µg/kg, the optimal dose to inhibit positive CR of RT was 0.15 mg/kg. And, when the pre-use dose of Dex was 1 µg/kg, the optimal dose of RT was 0.9 mg/kg. Clinical trial registration NCT05631028.

Abstract Memory reconsolidation refers to the process by which the consolidated memory was restored after reactivation (RA). Memory trace becomes labile after reactivation and inhibition of memory reconsolidation may disrupt or update the original memory trace, which provided a new strategy for the treatment of several psychiatric diseases, such as drug addiction and post-traumatic stress disorder. Fat mass and obesity-associated gene (FTO) is a novel demethylase of N6-methyladenosine (m6A) and it has been intensively involved in learning and memory. However, the role of FTO in memory reconsolidation has not been determined. In the present study, the function of FTO in memory reconsolidation was investigated in the novel object recognition (NOR) model in mice. The results showed that RA of NOR memory increased hippocampal FTO expression in a time-dependent manner, while FTO inhibitor meclofenamic acid (MA) injected immediately, but not 6 h after RA disrupted NOR memory reconsolidation. MA downregulated BDNF expression during NOR memory reconsolidation in the hippocampus, while the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) reversed the disruptive effects of MA on NOR memory reconsolidation. Furthermore, overexpression of FTO increased BDNF expression via decreasing mRNA m6A in HT22 cells. Taken together, these results indicate that FTO may up-regulate the BDNF-TrkB pathway to promote NOR memory reconsolidation through m6A modification.

Abstract Solutions of a group of conjugate time-varying matrix equations are discussed in this paper. Through mathematical derivation, the solutions to this group of equations are equivalent to the solutions to a class of conjugate time-invariant matrix equations. Further, the related conditions of solvability are obtained and the general explicit solutions are represented by using quasicontrollability and quasiobservability matrices. A detailed algorithm is presented to make the calculation process clear, and the effectiveness of the algorithm is verified by a concrete example. The proposed algorithm can provide complete solutions to the considered equation in explicit parametric form and its main computation includes solving an ordinary linear algebraic equation and some matrix multiplication operations.

Abstract Background Exercise rehabilitation training is an important measure for improving the prognosis of patients with hip fractures. However, the particular program that works effectively and the efficiency of exercise therapy are still controversial. Objective To compare the effects of usual postoperative care combined with rehabilitation based on exercise prescription on motor function and complications in elderly patients who underwent surgery for hip fracture. Methods This was an observational study. A total of 71 elderly patients with hip fractures who were treated with hip arthroplasty and internal fixation of the proximal femur with an intramedullary nail at Suzhou Municipal Hospital from October 2020 to December 2021 were included; 11 cases were excluded (eight cases were excluded due to loss of follow-up, two due to deaths from other causes, and one due to other reasons). Finally, 60 patients (18 males and 42 females) were included. Patients were randomly assigned to the control (n = 30) and experimental (n = 30) groups using a random number generator. Patients in the control group received usual postoperative care, whereas those in the experimental group received usual postoperative care combined with rehabilitation training based on the principles of exercise prescription. We recorded the motor function (Harris hip score), daily living ability (Barthel Index), and complications at discharge and 1, 3, and 6 months postoperatively for statistical analysis. Results The Harris hip score and Barthel Index score were significantly higher at 1, 3, and 6 months postoperatively than at discharge in both groups (p

Through the pendulum mechanism inside the spherical shell, the centroid can be varied circumferentially, enabling the spherical robot to achieve omnidirectional flexible movement. Additionally, the radial variation ability of the centroid enables spherical robots to adopt two distinct driving modes: the traditional lower pendulum driving mode and the inverted pendulum driving mode. There are two manifestations of radial variation in the centroid: having different radial positions of the centroid and achieving radial movement of the centroid. Focusing on these two manifestations, experimental data are obtained through different motion velocities and different motion slopes to conduct research on the influence of radial variation in the centroid on the motion of spherical robots. Based on the experimental data, multiple indicators are analyzed, including response speed, convergence speed, stability, and overshoot, as well as steering ability, climbing ability, and output power. The impact of the radial variation ability of the centroid on the control performance, locomotion capability, and energy consumption of spherical robots is summarized, and the correlation model relating the motion requirements to the radial position of the centroid is established, providing a theoretical basis for the selection of driving modes and centroid positions for spherical robots facing complex task requirements.

Abstract Two-photon absorption (TPA) fluorescence imaging holds great promise in diagnostics and biomedicine owing to its unparalleled spatiotemporal resolution. However, the adaptability and applicability of currently available TPA probes, which act as a critical element for determining the imaging contrast effect, is severely challenged by limited photo-luminescence in vivo. This is particularly a result of uncontrollable aggregation that causes fluorescence quenching, and inevitable photo-oxidation in harsh physiological milieu, which normally leads to bleaching of the dye. Herein, we describe the remarkably enhanced TPA fluorescence imaging capacity of self-assembling near-infrared (NIR) cyanine dye-based nanoprobes (NPs), which can be explained by a photo-oxidation enhanced emission mechanism. Singlet oxygen generated during photo-oxidation enables chromophore dimerization to form TPA intermediates responsible for enhanced TPA fluorescence emission. The resulting NPs possess uniform size distribution, excellent stability, more favorable TPA cross-section and anti-bleaching ability than a popular TPA probe rhodamine B (RhB). These properties of cyanine dye-based TPA NPs promote their applications in visualizing blood circulation and tumoral accumulation in real-time, even to cellular imaging in vivo. The photo-oxidation enhanced emission mechanism observed in these near-infrared cyanine dye-based nanoaggregates opens an avenue for design and development of more advanced TPA fluorescence probes.

Infantile hemangiomas (IHs) are the most common benign soft-tissue tumors in infancy; about 10%–15% of them may result in various complications that require active management. The current first-line treatment for IH is oral propranolol; however, some studies recommend intralesional corticosteroid injections for small, limited, deep, or prominent tumors because of concern regarding serious systemic complications related to propranolol. This review summarizes and analyzes the current clinical studies on corticosteroid injections in IHs, discusses treatment norms, and explores future research directions.

The pore structure and its heterogeneity of tight reservoirs are key factors affecting the storage and percolation of crude oil. The pore system of Chang 7 tight sandstone has multi-scale and multi-type characteristics. However, the contribution of different pore types and pore sizes to the physical properties of Chang 7 tight sandstone is still unclear. In this paper, we collected a suite of Chang 7 tight sandstones to investigate the full-scale pore structure and fractal characteristics by casting thin section, field emission scanning electron microscope, two-dimensional multi-scale backscattered scanning electron microscopy, N2 adsorption (NA) and NMR. The pore diameters of Chang 7 tight sandstone are usually distributed between 0.001 and 20 μm. Intercrystalline pores are mainly distuibuted 300 nm), mesopores (mainly 7–300 nm), and micropores (mainly 12×10−3 mL/g, the continuous percolation network consists entirely of macropores, resulting in higher porosity and permeability of the reservoir. Moreover, reservoir physical properties show excellent correlation with macropore heterogeneity. These results demonstrate that the content and heterogeneity of macropores are key indicators indicating the quality of the Chang 7 tight sandstones.

Abstract Despite decades of genetic studies on late-onset Alzheimer’s disease, the underlying molecular mechanisms remain unclear. To better comprehend its complex etiology, we use an integrative approach to build robust predictive (causal) network models using two large human multi-omics datasets. We delineate bulk-tissue gene expression into single cell-type gene expression and integrate clinical and pathologic traits, single nucleotide variation, and deconvoluted gene expression for the construction of cell type-specific predictive network models. Here, we focus on neuron-specific network models and prioritize 19 predicted key drivers modulating Alzheimer’s pathology, which we then validate by knockdown in human induced pluripotent stem cell-derived neurons. We find that neuronal knockdown of 10 of the 19 targets significantly modulates levels of amyloid-beta and/or phosphorylated tau peptides, most notably JMJD6. We also confirm our network structure by RNA sequencing in the neurons following knockdown of each of the 10 targets, which additionally predicts that they are upstream regulators of REST and VGF. Our work thus identifies robust neuronal key drivers of the Alzheimer’s-associated network state which may represent therapeutic targets with relevance to both amyloid and tau pathology in Alzheimer’s disease.

Distiller’s grains resourcing is a crucial problem for the sustainable development of the Chinese Baijiu industry. In order to improve the protein utilization of distiller’s grains. In this study, distiller’s grains pretreated by wet crushing combined with amylase/cellulase were further hydrolyzed with neutral protease combined with papain at 50 °C for 3 h. The hydrolysates were decolorized by 1% coconut shell activated carbon for 15 min, and separated and purified by macroporous resin and Sephadex gel to yield peptide fractions (F1, F2, F3 and F4). The F3 fraction with the highest radical scavenging activity was analyzed by nano-LC-MS/MS and peptidomics to identify peptides. Three peptides (especially newly discovered AAHVLAAAFL) displayed strong alcohol solubility and antioxidant activity and were stably bound to key regulatory pathway receptors (Keap1-Nrf2) and myeloperoxidase (MPO), further elucidating molecular mechanism of anti-oxidation. These findings provided knowledge for potential functional peptide candidates and facilitates the high-value commercial development of distiller’s grains.

Abstract Introduction The mechanisms of cognitive impairments in Parkinson’s disease (PD) remain unknown. Accumulating evidence revealed that brain neuroinflammatory response mediated by microglial cells contributes to cognitive deficits in neuropathological conditions and macrophage antigen complex-1 (Mac1) is a key factor in controlling microglial activation. Objectives To explore whether Mac1-mediated microglial activation participates in cognitive dysfunction in PD using paraquat and maneb-generated mouse PD model. Methods Cognitive performance was measured in wild type and Mac1−/− mice using Morris water maze test. The role and mechanisms of NADPH oxidase (NOX)–NLRP3 inflammasome axis in Mac1-mediated microglial dysfunction, neuronal damage, synaptic degeneration and phosphorylation (Ser129) of α-synuclein were explored by immunohistochemistry, Western blot and RT-PCR. Results Genetic deletion of Mac1 significantly ameliorated learning and memory impairments, neuronal damage, synaptic loss and α-synuclein phosphorylation (Ser129) caused by paraquat and maneb in mice. Subsequently, blocking Mac1 activation was found to mitigate paraquat and maneb-elicited microglial NLRP3 inflammasome activation in both in vivo and in vitro. Interestingly, stimulating activation of NOX by phorbol myristate acetate abolished the inhibitory effects of Mac1 blocking peptide RGD on paraquat and maneb-provoked NLRP3 inflammasome activation, indicating a key role of NOX in Mac1-mediated NLRP3 inflammasome activation. Furthermore, NOX1 and NOX2, two members of NOX family, and downstream PAK1 and MAPK pathways were recognized to be essential for NOX to regulate NLRP3 inflammasome activation. Finally, a NLRP3 inflammasome inhibitor glybenclamide abrogated microglial M1 activation, neurodegeneration and phosphorylation (Ser129) of α-synuclein elicited by paraquat and maneb, which were accompanied by improved cognitive capacity in mice. Conclusions Mac1 was involved in cognitive dysfunction in a mouse PD model through NOX–NLRP3 inflammasome axis-dependent microglial activation, providing a novel mechanistic basis of cognitive decline in PD.

Abstract Background Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer’s Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level. Methods We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics. The results were compared to human AD and to human patients that suffered from early onset dementia and that carry the P301L Tau mutation. Results Both mouse models accumulate insoluble Tau species during disease. The Tau aggregation is driven by progressive phosphorylation within the proline rich domain and the C-terminus of the protein. This is reflective of early disease stages of human AD and of the pathology of dementia patients carrying the P301L Tau mutation. However, Tau ubiquitination and acetylation, which are important to late-stage human AD are not represented in the mouse models. Conclusion AD mouse models that overexpress human Tau using risk mutations are a suitable tool for testing drug candidates that aim to intervene in the early formation of insoluble Tau species promoted by increased phosphorylation of Tau.

Abstract The problem of solving a class of Sylvester‐conjugate periodic matrix equations is investigated in this paper. Utilising conjugate gradient method, an iterative algorithm is provided, from which a matrix sequence can be generated to approximate the unknown matrix of the equation to be solved. Theoretical derivation proves that the proposed algorithm is convergent starting from any initial value, and simulation examples show the effectiveness of the proposed algorithm.

Abstract Objective To translate and culturally adapt the Profile Fitness Mapping neck questionnaire (ProFitMap-neck) into the Chinese version and evaluate its psychometric properties. Methods The procedure of translation and cross-cultural adaptation was performed according to the recommended guidelines. A total of 220 patients with chronic neck pain (CNP) and 100 individuals without neck pain participated in the study. Internal consistency, test-retest reliability, content validity and construct validity were investigated. Results The Chinese version of ProFitMap-neck (CHN-ProFitMap-neck) showed adequate internal consistency (Cronbach’s α = 0.88–0.95). A good test-retest reliability was proven by the intraclass correlation coefficient (ICC3A,1 = 0.78–0.86). Floor-ceiling effects were absent. Exploratory factor analysis revealed 6 factors for the symptom scale and 4 factors for the function scale. The CHN-ProFitMap-neck showed a moderate to high negative correlation with NDI (r = 0.46–0.60, P 0.05) or the mental health domain of the SF-36 was found (P > 0.05). The CHN-ProFitMap-neck scores were significantly lower in the CNP group than in the non-CNP group (P

With the rapid development of wind power generation， the impact of the construction and operation of utility-scale wind farms on the local climate has attracted extensive attention.In order to study the characteristics of the local climatic response to the deployment of wind farms under different surface conditions， the area from Wulan Chaka to Gonghe Shazhu Yuxiang， which is located in the southwest of Qinghai Lake， was chosen as center， and the mesoscale meteorological numerical model WRF （Weather Research and Forecasting Model） and the Fitch wind turbine model were carried out under the conditions of flat canyons， high-altitude mountains and water body， respectively.The results showed that： Under the ideal situation of the same installed capacity， the averaged wind speed inside the wind farms showed the significant decrease trends under the three sensitivity experiments， and the amplitude and scope of wind speed attenuation was stronger during nighttime than that during the daytime， and the wind speed attenuation in the vertical direction can reached up to 600 m.The 2 m temperature inside the wind farms located in flat canyons or water body mainly decreased， which was possibly related to the negative temperature gradient and the water evaporation enhancement， and the temperature cooling was more significant during nighttime while no significant changes in 2 m temperature were detected over the mountain wind farm.Meanwhile， the changes of 2 m humidity inside the wind farms were not obvious， and the overall decreased trends were mainly weak during nighttime.Due to rotation of the wind turbine， the planetary boundary layer height increased significantly.The characteristics of the local climatic response to the deployment of wind farms under different surface conditions were different， which was mainly related to the different climatic features under different surface conditions， and was also affected by the spatial layout of wind turbines.These results can provide some support for the design of climate-friendly wind farms.

Based on the ground incident radiation data of FY-4A and the radiation data of ground weather station， the nowcasting method based on mean generation function is used to obtain the forecast radiation， as well as its rolling correction.Taking Taiyuan station in Shanxi Province as an example， the experiment in 2019 shows that the high spatial-temporal resolution radiation related products provided by the new generation geostationary meteorological satellite FY-4A can provide relatively reliable initial conditions for nowcasting prediction； The nowcasting forecast based on satellite radiation products captures the impact of weather changes， and the revised nowcasting forecast radiation has been effectively improved； In sunny days， the maximum deviation of nowcasting forecast global radiation is improved from about 120 W·m-2 before correction to about 40 W·m-2 after correction.In cloudy days， the average absolute error decreases to 14 W·m-2.In cloudy days， the average absolute error decreases to 56 W·m-2.According to the comprehensive statistical analysis of 16 prediction time steps without considering temporal variation， the corrected nowcasting global radiation and observed global radiation are coincided very well at each prediction time step， the relative error decreased from 44.7%~66.4% to 21.3%~54.3%， and the RMSE decreased from 166.4~198.8 W·m-2 to 132.2~189.9 W·m-2； From the comprehensive statistical analysis of the whole year， the revised correlation coefficient is generally higher than that before the revision， increased from 0.77~0.84 to 0.79~0.88， only slightly decreased at 15 hour， the RMSE decreased from 162.7~197.1 W·m-2 to 129.3~180.9 W·m-2， and the average absolute relative error decreased from 46.0%~76.8% to 24.0%~46.5%.This method can be used for nowcasting prediction of the whole disk at any time.

Catalytic asymmetric deuterations rely largely on two-electron reaction manifolds and are mostly limited to benzylic positions. Here, a metal-free platform using peptide- or sugar-derived chiral thiols and deuterium oxide allows for asymmetric open-shell deuteration at non-benzylic positions under visible-light irradiation.

Objective: To compare the image quality between the deep learning image reconstruction (DLIR) and iterative reconstruction (IR) algorithms via the dedicated phantom. Method: ACR quality assurance phantom (Gammex 464) was scanned by GE Revolution Apex. The CT value accuracy, low contrast resolution, image uniformity and high contrast resolution of five substances from module 1 to module 4 were measured respectively. Through the above indicators, the image quality of three levels (DL, DM and DH) of Truefedelitytm (TFI) and three levels (30%, 60% and 90%) of adaptive statistical iterative reconstruction-V (asir-V, hereinafter referred to as AV) under high dose (20 mgy) were compared. The comparison between the two algorithms for each parameter was tested by One-Way Anova. Results: The high/low-contrast resolution of the six image series were consistent (high-contrast resolution: 10 lp/cm; low-contrast resolution: 6 mm). The two algorithms both slightly overestimated the CT value of polyethylene, air and acrylic, and no statistically significant difference was found among the difference of CT values of the substances. Both algorithms underestimated the CT value of bone and the solid water; TFI showed better performance in evaluating the solid water which was closer to the real value, though statistical difference was not found between each group of images. Among the 6 groups of images, TFI DH showed the best image uniformity and at the same reconstruction level, TFI showed better uniformity than AV. Conclusion: DLIR can further reduced image noise while maintaining image spatial resolution and CT value accuracy at high dose level.

We experimentally investigate trap-loss spectra of the cesium 6S1/2(F = 4) → 71P3/2 Rydberg transition by combining the cesium atomic magneto-optical trap with the narrow-linewidth, continuously tunable 318.6 nm ultraviolet laser. Specifically, the atoms in the magneto-optical trap are excited to the Rydberg state due to the ultraviolet laser single-step Rydberg excitation, which leads to the reduction of atomic fluorescence. Based on the trap-loss spectroscopy technology, the Autler–Townes (AT) splitting due to a strong cooling laser is observed, and the parameter dependence of the AT splitting interval of trap-loss spectroscopy is investigated. The effective temperature of cold atoms is measured by using simplified time-of-flight fluorescence imaging. In addition, closed-loop feedback power stabilization of 318.6 nm ultraviolet laser is carried out. This lays the foundation for further experimental research related to the Rydberg atoms using ultraviolet lasers, which is of great significance for the development of quantum computing and quantum information.

The maleimides, or 1H-pyrrole-2, 5-diones, are one of the novel types of biological markers existed in both sedimentary organic matter and petroleum, which could be products derived from the degradation of chlorophylls and bacteriochlorophylls. In this study, the maleimides composition was investigated in detail for several crude oils and petroleum source rocks with varying depositional settings, and abundant 2-methyl-3-n-propyl (Me, n-Pr) and 2-methyl-3-isobutyl (Me, i-Bu) maleimide, together with aryl isoprenoids were detected. These pigments-derived products were prominently generated by Chlorobiaceae and are especially abundant in the saline and marine black shales and related oils, indicating that PZE (photic zone euxinia) occurred in the brackish water environment of the Nenjiang Formation in the Songliao Basin, the saline to semi-saline water environment of the Shahejie Formation in the Bohai Bay Basin, and the marine environment of the Napo Formation in the Oriente Basin, showing strong reduction preservation conditions. It can be concluded that PZE is a favorable factor for the enrichment of organic matter and the development of high-quality source layers. In addition, the ratios of Me, i-Bu/Me, Et and Me, n-Pr/Me, when coupled together, could be used to diagnose the depositional conditions such as marine, saline, semi-saline or brackish water column.

Objective: To compare the image quality between virtual monochromatic images (VMI) of dual-source dual-energy CT (DECT) and conventional CT images. Siemens SOMATOM Force dual source dual energy CT was adopted in the scanning of the high contrast resolution CTP 528 component and low contrast resolution CTP 515 component of image quality control phantom catphan 500. Dual-tube dual-energy scanning scheme was used to reconstruct low, medium and high-level VMI (group A: 40 keV, group B: 70 keV, group C: 100 keV) and a single tube scanning scheme was used to reconstruct conventional images (Group D: 120 kVp). Two radiologiss carried out the measurement of high resolution by the smallest line pair one could distinguish and low-contrast sensitivity was measured by the smallest diameter under 1% contrast. Mean noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also evaluated for each group. Results: The image consistency of the two radiologists turned out well (high reolution and low-contrast sensitivity: Kappa coefficient=0.667; noise parameter: Spearman r = 0.920). Among all images, D group performed the best in high resolution (6 lp/cm) and A and B groups showed the best low-contrast sensitivity (diameter of 4 mm). C group had the lowest noise (2.333±0.289) and highest SNR (37.944±3.949). Mean noise and SNR were found significantly difference among the four groups. B group showed the highest CNR (3.361±0.875), but no statistical significance was found among the groups. Conclusion: Compared with conventional CT, VMI images from DECT could improve image quality while retain low-contrast sensitivity; image noise decreases while SNR increases as VMI elevates.

Abstract Background Microglia, the resident immune cells of the brain, play a critical role in numerous diseases, but are a minority cell type and difficult to genetically manipulate in vivo with viral vectors and other approaches. Primary cultures allow a more controlled setting to investigate these cells, but morphological and transcriptional changes upon removal from their normal brain environment raise many caveats from in vitro studies. Methods To investigate whether cultured microglia recapitulate in vivo microglial signatures, we used single-cell RNA sequencing (scRNAseq) to compare microglia freshly isolated from the brain to primary microglial cultures. We performed cell population discovery, differential expression analysis, and gene co-expression module analysis to compare signatures between in vitro and in vivo microglia. We constructed causal predictive network models of transcriptional regulators from the scRNAseq data and identified a set of potential key drivers of the cultured phenotype. To validate this network analysis, we knocked down two of these key drivers, C1qc and Prdx1, in primary cultured microglia and quantified changes in microglial activation markers. Results We found that, although often assumed to be a relatively homogenous population of cells in culture, in vitro microglia are a highly heterogeneous population consisting of distinct subpopulations of cells with transcriptional profiles reminiscent of macrophages and monocytes, and are marked by transcriptional programs active in neurodegeneration and other disease states. We found that microglia in vitro presented transcriptional activation of a set of “culture shock genes” not found in freshly isolated microglia, characterized by strong upregulation of disease-associated genes including Apoe, Lyz2, and Spp1, and downregulation of homeostatic microglial markers, including Cx3cr1, P2ry12, and Tmem119. Finally, we found that cultured microglia prominently alter their transcriptional machinery modulated by key drivers from the homeostatic to activated phenotype. Knockdown of one of these drivers, C1qc, resulted in downregulation of microglial activation genes Lpl, Lyz2, and Ccl4. Conclusions Overall, our data suggest that when removed from their in vivo home environment, microglia suffer a severe case of “culture shock”, drastically modulating their transcriptional regulatory network state from homeostatic to activated through upregulation of modules of culture-specific genes. Consequently, cultured microglia behave as a disparate cell type that does not recapitulate the homeostatic signatures of microglia in vivo. Finally, our predictive network model discovered potential key drivers that may convert activated microglia back to their homeostatic state, allowing for more accurate representation of in vivo states in culture. Knockdown of key driver C1qc partially attenuated microglial activation in vitro, despite C1qc being only weakly upregulated in culture. This suggests that even genes that are not strongly differentially expressed across treatments or preparations may drive downstream transcriptional changes in culture.

Huangjiu is rich in low-molecular-weight peptides and has an umami taste. In order for its umami peptides to be discovered, huangjiu was subjected to ultrafiltration, ethanol precipitation, and macroporous resin purification processes. The target fractions were gathered according to sensory evaluation. Subsequently, we used peptidomics to identify the sum of 4158 peptides in most umami fractions. Finally, six novel umami peptides (DTYNPR, TYNPR, SYNPR, RFRQGD, NFHHGD, and FHHGD) and five umami-enhancing peptides (TYNPR, SYNPR, NFHHGD, FHHGD, and TVDGPSH) were filtered via virtual screening, molecular docking, and sensory verification. Moreover, the structure–activity relationship was discussed using computational approaches. Docking analysis showed that all umami peptides tend to bind with T1R1 through hydrogen bonds and hydrophobic forces, which involve key residues HIS71, ASP147, ARG151, TYR220, SER276, and ALA302. The active site calculation revealed that the positions of the key umami residues D and R in the terminal may cause taste differences in identified peptides.

Abstract A thymoma is a type of thymic tumor which is rarely malignant that is frequently reported in adult patients. A number of thymoma‐related immune disorders are observed including autoimmune diseases, which suggests a strong connection between thymoma development and immunological mechanisms. Characterized by association with humoral and cellular immunodeficiency, thymoma patients are susceptible to opportunistic infections by environmental factors. Recent reports have suggested that viral infection may play a role in the etiological mechanisms of thymoma development associated with dysregulated immunity. In this review, we summarize the case reports and studies related to viral infection, such as CMV, EBV and HSV, that probably play a part in the pathogenesis of thymoma and related diseases. Furthermore, we demonstrate the underlying mechanisms by which viruses may induce the occurrence of thymoma with autoimmune diseases. Lastly, we discuss the potential application of antiviral therapy in the treatment of thymic diseases.

Narrow-linewidth lasers have a high spectral purity, long coherent length, and low phase noise, so they have important applications in atomic clocks, precision measurement, and quantum computing. We inject a transmitted laser from a narrow-linewidth (∼15 kHz) flat-concave Fabry–Perot (F-P) cavity made from ultra-low expansion (ULE) optical glass into an 852 nm distributed Bragg reflector-type laser diode (DBR-LD), of which the comprehensive linewidth is 1.67 MHz for the free running case. With an increase in the self-injection power, the laser linewidth gradually narrows, and the injection locking current range gradually increases. The narrowest linewidth measured by the delayed frequency-shifted self-heterodyne (DFSSH) method is about 365 Hz, which is about 1/4500 of the linewidth for the free running case. Moreover, to characterize the laser phase noise, we use a detuned F-P cavity to measure the conversion signal from the laser phase noise to the intensity noise for both the free running case and the self-injection lock case. The laser phase noise for the self-injection lock case is significantly suppressed in the analysis frequency range of 0.1–10 MHz compared to the free running case. In particular, the phase noise is suppressed by more than 30 dB at an analysis frequency of 100 kHz.

Abstract The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p

Understanding crust–atmosphere interactions on Venus is fundamentally important to interpretations of Venus’ surface spectroscopic data. Olivine, in basaltic crust, is oxidized under a heated CO2 atmosphere. However, the oxidation rates, product assemblages and spectral characteristics of olivine samples with different Fa# values remain largely unclear. Herein, we investigated the oxidation of olivine with different Fa# values (Fa09, Fa29 and Fa71) under CO2 atmosphere at 470 °C and 900 °C and characterized the oxidation products (both microscopically and macroscopically), conversion rates and VNIR spectra. The results showed that the oxidation of olivine produced magnesioferrite, magnetite, laihunite, hematite and maghemite at 470 °C and hematite, magnetite, magnesioferrite and amorphous SiO2 at 900 °C. Both high temperature and high Fa# values accelerated the oxidation rates. The production of oxide coatings on olivine grains (74 μm in size) was estimated to be completed within tens to hundreds of years at 470 °C in natural settings, with even shorter periods under higher temperatures. Thus, CO2 oxidation would quickly eliminate olivine spectral characteristics, and spectral parameters at 850 and 1020 nm, as well as other relevant spectral windows (considering shifts induced by the elevated temperature), could be used to trace olivine oxidation processes. This work presented a case study connecting microscopic features to spectral characteristics for Venus’ surface–atmosphere interactions. Further studies considering more realistic Venus’ surface–atmosphere conditions will be essential to better interpret the measured spectroscopic data and determine the origins of the high emissivity detected on elevated terrain on Venus.

Antitumor immunity is an essential component of cancer therapy and is primarily mediated by the innate immune response, which plays a critical role in initiating and shaping the adaptive immune response. Emerging evidence has identified innate immune checkpoints and pattern recognition receptors, such as CD47 and Toll-like receptor 7 (TLR7), as promising therapeutic targets for cancer treatment. Based on the fusion protein Fc-CV1, which comprises a high-affinity SIRPα variant (CV1), and the Fc fragment of the human IgG1 antibody, we exploited a preparation which coupled Fc-CV1 to imiquimod (TLR7 agonist)-loaded liposomes (CILPs) to actively target CT26. WT syngeneic colon tumor models. In vitro studies revealed that CILPs exhibited superior sustained release properties and cell uptake efficiency compared to free imiquimod. In vivo assays proved that CILPs exhibited more efficient accumulation in tumors, and a more significant tumor suppression effect than the control groups. This immunotherapy preparation possessed the advantages of low doses and low toxicity. These results demonstrated that a combination of immune checkpoint blockade (ICB) therapy and innate immunity agonists, such as the Fc-CV1 and imiquimod-loaded liposome preparation utilized in this study, could represent a highly effective strategy for tumor therapy.

Abstract Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) images of early-stage melanomas. We tested whether automated digital (TIL) analysis (ADTA) improved accuracy of prediction of disease specific survival (DSS) based on current pathology standards. ADTA was applied to a training cohort (n = 80) and a cutoff value was defined based on a Receiver Operating Curve. ADTA was then applied to a validation cohort (n = 145) and the previously determined cutoff value was used to stratify high and low risk patients, as demonstrated by Kaplan–Meier analysis (p ≤ 0.001). Multivariable Cox proportional hazards analysis was performed using ADTA, depth, and ulceration as co-variables and showed that ADTA contributed to DSS prediction (HR: 4.18, CI 1.51–11.58, p = 0.006). ADTA provides an effective and attainable assessment of TILs and should be further evaluated in larger studies for inclusion in staging algorithms.

In recent years, with the continuous development of artificial intelligence and brain-computer interface technology, emotion recognition based on physiological signals, especially electroencephalogram signals, has become a popular research topic and attracted wide attention. However, the imbalance of the data sets themselves, affective features’ extraction from electroencephalogram signals, and the design of classifiers with excellent performance, pose a great challenge to the subject. Motivated by the outstanding performance of deep learning approaches in pattern recognition tasks, we propose a method based on convolutional neural network with data augmentation method Borderline-synthetic minority oversampling technique. First, we obtain 32-channel electroencephalogram signals from DEAP data set, which is the standard data set of emotion recognition. Then, after data pre-processing, we extract features in frequency domain and data augmentation based on the data augmentation algorithm above for getting more balanced data. Finally, we train a one dimensional convolutional neural network for three classification on two emotional dimensions valence and arousal. Meanwhile, the proposed method is compared with some traditional machine learning methods and some existing methods by other researchers, which is proved to be effective in emotion recognition, and the average accuracy rate of 32 subjects on valence and arousal are 97.47% and 97.76% respectively. Compared with other existing methods, the performance of the proposed method with data augmentation algorithm Borderline-SMOTE shows its advantage in affective emotional recognition than that without Borderline-SMOTE.

AbstractHerein, integrated vertical variation characteristic analysis was conducted by measuring total organic carbon (TOC), major and trace elements in Upper Ordovician-Lower Silurian (Wufeng-Longmaxi formations) black shale in Weiyuan, Luzhou, and Changning areas, southern Sichuan Basin to clarify the control of organic matter (OM) enrichment in different sublayers. According to the cycle boundary, it was divided into member 1 (submember 1 and submember 2) and member 2 from early to late Longmaxi formation, while it was divided into 4 sublayers from early to late during submember 1 depositional period. Under the warm and humid paleoclimate, high paleoproductivity, and gradually oxic paleoredox conditions, the TOC content (0.22-3.27 wt% in Luzhou area) in Wufeng formation increased gradually from early to late under the cocontrolling of tectonic framework and stagnant sea. After the glacial period, the warm and humid climate of Wufeng formation continued in Longmaxi formation, and TOC content reached the highest in sublayer 1 (2.02-4.02 wt%, 4.78 wt%, and 6.45 wt% in Weiyuan, Luzhou, and Changning areas, respectively), due to the high paleoproductivity and high sea level caused by melting glaciers, causing the extremely anoxic environment. The OM was preserved best. It remains higher in sublayer 2 (2.39 wt%, 3.69-4.18 wt%, and 3.5-3.86 wt% in three areas, respectively) because of the anoxic environment caused by deep water and the high paleoproductivity, but the temporary hot and dry environment has a certain negative impact on the OM preservation. Under the stable paleoproductivity, sublayer 3 has a character of water decreasing slowly, and the suboxic environment led to the decrease of TOC content (3.82-5.28 wt% and 3.77-4.13 wt% in Luzhou and Changning areas, respectively). Meanwhile, that in the yuan area became deeper and the TOC content became relatively higher (1.92-3.33 wt%). Under the open environment, sublayer 4 was controlled by lower sea level caused by regression, resulting in lower TOC content (1.31-4.57 wt%, 1.64-3.52 wt%, and 3.88-4.49 wt% in three areas, respectively). However, the global regression of the submember 2 period, high terrigenous debris dilution, and oxic environment lead to the no preservation of OM. Generally speaking, the enrichment of OM is not only affected by the changes of global sea level and paleoproductivity to some extent (Longmaxi shale) but also controlled by the tectonic framework in Sichuan Basin (Wufeng shale). The findings of this study can help for a better understanding of the OM enrichment mechanism and provide a theoretical basis for the evaluation of high-quality source rocks.

Drug addiction is a chronic psychiatric disorder characterized by compulsive drug-seeking and drug-using behavior, and a tremendous socioeconomic burden to society. Current pharmacological and psychosocial methods have shown limited treatment effects for substance abuse. Deep Brain Stimulation (DBS) is a novel treatment for psychiatric disease and has gradually gained popularity in the treatment of addiction. Addiction is characterized by neuroplastic changes in the nucleus accumbens (NAc), a key structure in the brain reward system, and DBS in this region has shown promising treatment effects. In this paper, the research progress on DBS for drug addiction has been reviewed. Specifically, we discuss the mechanism of NAc DBS for addiction treatment and summarize the results of clinical trials on DBS treatment for addiction to psychoactive substances such as nicotine, alcohol, cocaine, opioids and methamphetamine/amphetamine. In addition, the treatment effects of DBS in other brain regions, such as the substantia nigra pars reticulata (SNr) and insula are discussed.

Abstract Background To investigate the clinical efficacy and outcomes of skin stretch suturing with self-locking sliding Nice knots in the treatment of small- or medium-sized wounds. Methods From June 2015 to May 2018, 26 patients with small- or medium-sized wounds were included in the present study. Skin stretch suturing with self-locking slide Nice knots was performed to gradually close the soft-tissue defects in these patients. The time of wound closure and healing was recorded. The color and blood supply of the skin, cutaneous sensation, the stretch of skin, and the hair growth situation of the skin wound were observed and recorded. Results There were 17 males and 9 females with an average age of 30.65 years (range, 15–48 years). The areas of the soft-tissue defects were between 3.2 × 7.1 cm and 8.0 × 15.2 cm. All patients underwent stretch suturing with self-locking slide Nice knots to close the soft-tissue defects. All wounds were successfully closed and healed. The mean time of wound closure was 10.69 days (range, 5–20 days), and the mean time of wound healing was 16.85 days (range, 10–24 days). The cutaneous sensation of skin wound recovered normally, and the color of the skin wounds was the same as that of normal skin at the last follow-up. The hair growth situation of the skin wounds also returned to normal. Conclusions This study revealed that Nice knots yielded an accepted clinical result as a new method to close small- or medium-sized wounds that was simple and less minimally invasive, resulted in progressive tension, did not return to previous results, and partially replace flaps or free skin grafts.

Sex and the APOE ε4 genotype are important risk factors for late-onset Alzheimer’s disease. In the current study, the authors investigate how sex and APOE ε4 genotype modify the association between Alzheimer’s disease biomarkers and metabolites in serum.

This article discusses the task allocation decision of single management ability and multiple management ability in view of the operation stage of the specific project of enterprise lean management service supply chain. First of all, the basic process of the management service integrator’s task allocation to the functional management service provider is given. Based on factors such as business satisfaction and other factors, we construct a management task allocation model based on service income price discounts in the case of fuzzy demand. On this basis, we further dig out the external and internal related factors of supply risk, use enterprise research and data mining methods to verify theoretical hypotheses and identify related factors of supply risk, analyze the impact of the characteristics of cooperation with different types of suppliers in data mining to determine the key factors of supply risk for different types of supply and demand cooperation, and determine the focus of supply risk control for different types of suppliers for data mining. In the process of simulation experiment, the method of maximum satisfaction of fuzzy multiobjective programming is adopted, and the influence of factors such as the preference of decision-makers and price discounts on the result of task allocation is analyzed in combination with specific examples. Finally, on the basis of fully considering the characteristics of management services, we build a comprehensive evaluation index system for management service providers in terms of service capabilities, service quality, informatization capabilities, and cooperation risks and comprehensively consider the uncertain factors in the decision-making process. The experimental results show that the proposed interval data mining solution method based on the degree of possibility can realize the ranking of management service providers by combining the subjective wishes of decision-makers with the objective evaluation of data mining.

Adrenomedullin (ADM) is a novel cardiovascular peptide with anti-inflammatory and antioxidant properties. Chronic inflammation, oxidative stress and calcification play pivotal roles in the pathogenesis of vascular dysfunction in obesity-related hypertension (OH). Our study aimed to explore the effects of ADM on the vascular inflammation, oxidative stress and calcification in rats with OH. Eight-week-old Sprague Dawley male rats were fed with either a Control diet or a high fat diet (HFD) for 28 weeks. Next, the OH rats were randomly subdivided into two groups as follows: (1) HFD control group, and (2) HFD with ADM. A 4-week treatment with ADM (7.2 μg/kg/day, ip) not only improved hypertension and vascular remodeling, but also inhibited vascular inflammation, oxidative stress and calcification in aorta of rats with OH. In vitro experiments, ADM (10 nM) in A7r5 cells (rat thoracic aorta smooth muscle cells) attenuated palmitic acid (PA, 200 μM) or angiotensin II (Ang II, 10 nM) alone or their combination treatment-induced inflammation, oxidative stress and calcification, which were effectively inhibited by the ADM receptor antagonist ADM22-52 and AMP-activated protein kinase (AMPK) inhibitor Compound C, respectively. Moreover, ADM treatment significantly inhibited Ang II type 1 receptor (AT1R) protein expression in aorta of rats with OH or in PA-treated A7r5 cells. ADM improved hypertension, vascular remodeling and arterial stiffness, and attenuated inflammation, oxidative stress and calcification in OH state partially via receptor-mediated AMPK pathway. The results also raise the possibility that ADM will be considered for improving hypertension and vascular damage in patients with OH.

Recent studies revealed that circular RNAs (circRNAs) are important in numerous biological process and involved in autoimmune diseases. However, their role in Vogt–Koyanagi–Harada (VKH) disease, a classical autoimmune disease, is not yet known. This research aimed to study the expression profile of mRNAs, microRNAs (miRNAs) and circRNAs and investigate the influence of circRNAs on the pathogenesis of VKH disease. We identified circRNAs, miRNAs, and mRNAs expression profiles in CD4+ T cells between 4 VKH patients and 3 healthy controls using the whole-transcriptome sequencing (RNA-seq) technique. We discovered that a total of 5088 mRNAs, 451 circRNAs and 433 miRNAs were differently expressed. The GO and KEGG pathway enrichment analyses were performed for significantly differentially expressed circRNAs and mRNAs. GSEA was conducted for all mRNAs. The functional enrichment suggested that the inflammatory response, the adaptive immune response, NF-kappa B signaling pathway, Th17 cell differentiation, Th1 and Th2 cell differentiation and T cell receptor signaling pathway were associated with VKH disease. In addition, based on the immune-related genes we screened, the circRNA-miRNA-mRNA ceRNA network was analyzed and constructed. Ten differently expressed mRNAs (LAT, ZAP70, ITK, ICOS, RASGRP1, PAG1, PLCG1, PRKCQ, LCK, CARD11) and 5 differently expressed circRNAs (hsa_circ_0033144, hsa_circ_0000233, hsa_circ_0000396, hsa_circ_0001924, hsa_circ_0001320) were selected to be validated by Real-time qPCR (RT-qPCR). The results of RT-qPCR turned out to be consistent with RNA-seq data. Further analysis showed that hsa_circ_0001320 and hsa_circ_0001924 may serve as crucial candidate marker genes of VKH disease. These results reveal that circRNAs may have a crucial immunomodulatory function in the pathophysiological process of VKH disease.

The space target capturing task using the spacecraft-manipulator system (SMS) has special significance in on-orbit servicing due to its theoretical challenges and practical value. The contact force between the end effector (gripper) and the target exerted by the tumbling motion of the space target destabilizes the spacecraft base. A full-dimensional controllable damping mechanism (FDCDM) with a cross-axis structure was designed to buffer the transient impact force on the end joint. The introduction of a damping mechanism gives the space robot a variable stiffness and damping system, and a stiffness estimation algorithm is proposed to calibrate the system stiffness, as stiffness cannot be measured directly. The full-dimensional controllable damping mechanism (FDCDM) with a cross-axis structure is equivalent to a four-DOF tandem joint, and the whole-body dynamic model of the SMS endowed with a full-dimensional controllable damping mechanism (FDCDM) was established using the Kane equation. Then, an unknown input observer (UIO)-based identification theory is proposed to precisely estimate the internal flexibility torque and the corresponding joint stiffness. A model-based neural learning algorithm is proposed to update the variable parameter matrix of the observer. The simulation experiment results demonstrate that the flexibility torque and joint stiffness could be accurately estimated within the expected error, illustrating the feasibility and effectiveness of the proposed method.

Compliant capture of the space non-cooperative targets is a key technology in on-orbit services. A great challenge is that the multi-dimensional contact force generated by the tumbling space target can destabilize the spacecraft-manipulator system (SMS), which may eventually cause failure of the capture task. A full-dimensional controllable damping mechanism (FDCDM) with gyroscopic structure is introduced into the joint of the SMS to buffer the multi-dimensional contact forces during capture. The six-dimensional damping force outputs by the FDCDM can be equivalent to the actuator outputs in the end joint, which could form a coordinated control system with the torque of base flywheel and active joints. The whole-body dynamic model of SMS with FDCDM is established using the Kane method. Furthermore, a backstepping non-singular sliding mode control is proposed to optimize the momentum distribution and impact absorption. The characteristics of collision process for the above SMS-FDCDM system is analyzed in the ADAMS workspace, and the experiments performed in MATLAB demonstrate that the full-dimensional damping mechanism and coordinated control can greatly reduce the vibration caused by the impact force, and the attitude of SMS is quickly stabilized after capture, which proves the feasibility of its application in non-cooperative target capturing tasks.

Fuchs’ uveitis syndrome (FUS) is one of the most under- or misdiagnosed uveitis entities. Many undiagnosed FUS patients are unnecessarily overtreated with anti-inflammatory drugs, which may lead to serious complications. To offer assistance for ophthalmologists in the screening and diagnosis of FUS, we developed seven deep convolutional neural networks (DCNNs) to detect FUS using slit-lamp images. We also proposed a new optimized model with a mixed “attention” module to improve test accuracy. In the same independent set, we compared the performance between these DCNNs and ophthalmologists in detecting FUS. Seven different network models, including Xception, Resnet50, SE-Resnet50, ResNext50, SE-ResNext50, ST-ResNext50, and SET-ResNext50, were used to predict FUS automatically with the area under the receiver operating characteristic curves (AUCs) that ranged from 0.951 to 0.977. Our proposed SET-ResNext50 model (accuracy = 0.930; Precision = 0.918; Recall = 0.923; F1 measure = 0.920) with an AUC of 0.977 consistently outperformed the other networks and outperformed general ophthalmologists by a large margin. Heat-map visualizations of the SET-ResNext50 were provided to identify the target areas in the slit-lamp images. In conclusion, we confirmed that a trained classification method based on DCNNs achieved high effectiveness in distinguishing FUS from other forms of anterior uveitis. The performance of the DCNNs was better than that of general ophthalmologists and could be of value in the diagnosis of FUS.