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Abstract Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson’s disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive. Here, we provide compelling evidence that the compensatory expression of synaptotagmin-11 (Syt11) plays a key role in concealing PD-associated phenotypes in parkin knockout (KO) mouse models. Unlike the normal dopamine (DA) release and motor behaviors observed in parkin KO mice, parkin knockdown (KD) in the substantia nigra pars compacta (SNpc) in adult mice led to both the impaired DA release and the pronounced motor deficits. Interestingly, Syt11, a well-established parkin substrate involved in PD, was specifically upregulated in parkin KD mice and in parkin KO mice during the suckling stage, but not in adult parkin KO mice. Importantly, the overexpression of Syt11 alone is capable of inducing PD-like motor and non-motor impairments, as well as the impaired DA release and reuptake, which is essential for parkin-associated pathogenesis of PD. Therefore, this work not only elucidate a compensatory mechanism that accounts for the absence of overt PD phenotypes in parkin KO mice, but also contribute to the comprehensive understanding of the progression of PD, opening new avenues for the therapeutic treatment of PD.

Abstract Schizophrenia is a severe neuropsychiatric disease, but the initiation mechanisms are unclear. Although antipsychotics are effective against positive symptoms, therapeutic interventions for negative symptoms are limited due to the lack of pathophysiological mechanisms. Here we identify synaptotagmin-11 (Syt11) as a potential genetic risk factor and dopamine over-transmission as a mechanism in the development of schizophrenia. Syt11 expression is reduced in individuals with schizophrenia but restored following the treatment with antipsychotics. Syt11 deficiency in dopamine neurons in early adolescence, but not in adults, leads to persistent social deficits and other schizophrenia-like behaviors by mediating dopamine over-transmission in mice. Accordingly, dopamine neuron over-excitation before late adolescence induces persistent schizophrenia-associated behavioral deficits, along with the structural and functional alternations in the mPFC. Notably, local intervention of D2R with clinical drugs presynaptically or postsynaptically exhibits both acute and long-lasting therapeutic effects on social deficits in schizophrenia mice models. These findings not only define Syt11 as a risk factor and DA over-transmission as a potential risk factor initiating schizophrenia, but also propose two D2R-targeting strategies for the comprehensive and long-term recovery of schizophrenia-associated social withdrawal.

Abstract Background This study aimed to investigate the knowledge, attitude and practice (KAP) of pediatric healthcare staff towards the therapy for patients with congenital heart disease (CHD). CHD is a major global health concern, posing significant risks to health and life despite advancements in early detection and treatment. Methods This web-based cross-sectional study was conducted from May 04, 2023 to August 12, 2023 in the Bengbu area (three counties and one city) for pediatric healthcare staff. Correlations between knowledge, attitude and practice scores were evaluated by Pearson correlation analysis. Factors associated with knowledge, attitude and practice scores were identified by multivariate logistic regression. Results A total of 332 valid questionnaires were enrolled, including 258 (77.7%) females, and 161 (48.5%) were pediatrician. The median (25% quartile, 75% quintile) of knowledge, attitude, and practice scores were 38 (36, 40) (possible range: 10—49), 28 (27, 31) (possible range: 7—35), and 35 (32, 39) (possible range: 9—45), respectively. Correlation analysis showed that significant positive correlations were found between knowledge and attitude (r = 0.528, P

Abstract Currently, the global prevalence of myopia is high and on the rise, seriously affecting the health of students. Studies have suggested that dietary factors may be associated with the occurrence and development of myopia, but the results are inconsistent. This survey aims to analyze the correlation between dietary factors and myopia while controlling for more confounding factors. A multi-stage stratified cluster sampling method was performed to select 10,619 primary and secondary school students in Shenyang for visual examination, and questionnaires were administered to 6974 of them. Logistic regression was performed with myopia as the dependent variable and the variables with p

The luteolin in Schisandra chinensis [Schisandraceae Schisandra (Turcz.) Baill.] were extracted by ultrasonic extraction assisted by an ionic liquid–enzyme composite system, and the content of luteolins was determined using high-performance liquid chromatography (HPLC). This process was initially conducted through a one-factor experiment and a Box–Behnken combinatorial design of response surface method. The extraction process was optimized, and the results demonstrated that the optimal extraction conditions were 13.31% enzyme addition, 0.53 mol/L ionic liquid concentration, 173.47 min ultrasonic shaking, and 0.2266 mg/g, which was 4.88 times higher than that of the traditional reflux extraction. Secondly, the antioxidant function of luteolins was studied based on network pharmacology. For the study of the antioxidant mechanism of luteolin, the herb group identification database, SwissTargetPrediction on luteolins target prediction, and GeneCards database to achieve the antioxidant target were used. For the analysis of the intersection of the target protein interactions, GO bioanalysis and KEGG signaling pathway enrichment analysis were used. There were 57 overlapping targets of luteolin and antioxidants, including AKT1, MMP9, ESR1, EGFR, and SRC. GO function and KEGG pathway enrichment analysis showed that luteolin antioxidants were related to zoerythromycin metabolic process, adriamycin metabolic process, negative regulation of apoptotic process, endocrine resistance and oxidoreductase. The key targets in the pathways, such as luteolin AKT1 and MMP9, exert antioxidant effects. The antioxidant activity of luteolins was investigated by determining the scavenging ability of luteolins against two types of free radicals: 2,2-bipyridine-bis(3-ethyl-benzothiazole-6-sulfonic acid) diammonium salt (ABTS+) free radicals and 1,1-diphenyl-2-trinitrophenylhydrazine free radicals (DPPH-). The results of the antioxidant test demonstrated that the ABTS radical scavenging rate was 87.26%, and the DPPH radical scavenging rate was 93.85% when the quality concentration of Schisandra luteolins was 0.1 mg/g, indicating the potential of this natural antioxidant. This method of extracting Schisandra chinensis luteolins is highly productive, environmentally friendly, and practical, and it facilitates the development and utilization of industrial Schisandra chinensis.

IntroductionWhen a distributed photovoltaic (PV) system has access to a large urban distribution network, the active balance is primarily borne by the main network gas unit; when the scale of the distributed PV system is very large, the main network can only provide limited regulation capacity, and the distribution network must determine the active optimal scheduling strategy.MethodsThis work proposes an active optimization scheduling model for the distribution network by considering the regulation capacity of the main network. In terms of the optimisation objectives, the maximum consumption of the distributed PVs and minimum power fluctuation at the demarcation point of the main distribution network are proposed as the main objectives, while the minimum total exchanged power in a cycle at the main distribution demarcation point and minimum distribution network loss are considered as the secondary objectives. In terms of constraints, it is proposed that the main network’s regulation capacity be characterized by the main network’s gas-fired unit creep constraints. A fast solution method for active optimization of the distribution network is designed herein to formulate the priority control order of the adjustable units according to the dispatch economic performances of various types of adjustable resources in the distribution network; this reduces the number of variables involved in the optimization at each step and improves the optimized solution speed.ResultsFinally, Simulation verification by IEEE 33-node distribution network arithmetic example based on Matlab simulation platform.DiscussionSimulation results show the effectiveness of the method in achieving maximum PV consumption and reflecting the limited regulation capacity of the main grid.

Abstract Background Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis. Methods Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis. Results The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301–3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252–5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity. Conclusion This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.

Demand response (DR) can ensure electricity supply security by shifting or shedding loads, which plays an important role in a power system with a high proportion of renewable energy sources. Industrial loads are vital participants in DR, but it is difficult to assess DR potential because of many complex factors. In this paper, a new method based on fuzzy control is given to assess the DR potential of industrial loads. A complete assessment framework including four steps is presented. Firstly, the industrial load data are preprocessed to mitigate the influence of noisy and transmission losses, and then the K-means algorithm considering the optimal cluster number is used to calculate baseline load of industrial load. Subsequently, an open-loop fuzzy controller is designed to predict the response factor of different industrial loads. Three strongly correlated indicators, namely peak load rate, electricity intensity, and load flexibility, are selected as the input of fuzzy control, which represents response willingness. Finally, the baseline load of diverse clustering scenarios and the response factor are used to calculate the DR potential of different industrial loads. The proposed method takes into account both economic and technical factors comprehensively, and thus, the results better represent the available DR potential in real-world situations. To demonstrate the effectiveness of the proposed method, the case of a medium-sized city in China is studied. The simulation focuses on the top eight industrial types, and the results show they can contribute about 189 MW available DR potential.

IntroductionThe uridine diphosphate (UDP)-glycosyltransferase (UGT) family is the largest glycosyltransferase family, which is involved in the biosynthesis of natural plant products and response to abiotic stress. UGT has been studied in many medicinal plants, but there are few reports on Platycodon grandiflorus. This study is devoted to genome-wide analysis of UGT family and identification of UGT genes involved in drought stress of Platycodon grandiflorus (PgUGTs).MethodsThe genome data of Platycodon grandiflorus was used for genome-wide identification of PgUGTs, online website and bioinformatics analysis software was used to conduct bioinformatics analysis of PgUGT genes and the genes highly responsive to drought stress were screened out by qRT-PCR, these genes were cloned and conducted bioinformatics analysis.ResultsA total of 75 PgUGT genes were identified in P.grandiflorus genome and clustered into 14 subgroups. The PgUGTs were distributed on nine chromosomes, containing multiple cis-acting elements and 22 pairs of duplicate genes were identified. Protein-protein interaction analysis was performed to predict the interaction between PgUGT proteins. Additionally, six genes were upregulated after 3d under drought stress and three genes (PGrchr09G0563, PGrchr06G0523, PGrchr06G1266) responded significantly to drought stress, as confirmed by qRT-PCR. This was especially true for PGrchr06G1266, the expression of which increased 16.21-fold after 3d of treatment. We cloned and conducted bioinformatics analysis of three candidate genes, both of which contained conserved motifs and several cis-acting elements related to stress response, PGrchr06G1266 contained the most elements.DiscussionPgGT1 was confirmed to catalyze the C-3 position of platycodin D and only eight amino acids showed differences between gene PGr008G1527 and PgGT1, which means PGr008G1527 may be able to catalyze the C-3 position of platycodin D in the same manner as PgGT1. Seven genes were highly expressed in the roots, stems, and leaves, these genes may play important roles in the development of the roots, stems, and leaves of P. grandiflorus. Three genes were highly responsive to drought stress, among which the expression of PGrchr06G1266 was increased 16.21-fold after 3d of drought stress treatment, indicating that PGrchr06G1266 plays an important role in drought stress tolerance. To summarize, this study laied the foundation to better understand the molecular bases of responses to drought stress and the biosynthesis of platycodin.

Abstract Background and aim DRP1 and OPA1 play important roles in mitochondrial fusion and fission. However, the role of DRP1 and OPA1 amplification in mitochondrial cognitive impairment has not been reported. This study aimed to investigate the relationship between DRP1 and OPA1 and the risk of cognitive impairment. Methods In this study, 45 elderly patients with diabetes admitted to the Lianyungang Second People’s Hospital from September 2020 to January 2021 were included. The patients were divided into normal group, mild cognitive impairment group and dementia group by using MMSE score, and the clinical characteristics of the three groups were compared. The amplification multiples of the two genes’ DNA were calculated by ΔΔCT and defined as 2− K. Spearman rank correlation was used to analyze the correlation between the DNA amplification multiples of patients’ DRP1 and OPA1 and AD8 and MoCA scores. The sensitivity and specificity of DNA amplification multiples of DRP1 and OPA1 to predict clinical outcomes of diabetic cognitive impairment were evaluated using Receiver operator characteristic (ROC) curves. Multiple logistic regression was used to evaluate the relationship between DNA amplification factor of DRP1 and OPA1 and cognitive function. Results DRP1(2− K) and OPA1(2− K) significantly increased and decreased in dementia and MCI groups compared with the normal group (P ≤ 0.001). The DNA amplification factor of DRP1 was positively correlated with AD8 score and negatively correlated with MoCA score (P

BackgroundThe infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas.MethodsDoxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining.ResultsDoxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8+ T cells and tissue-resident memory T cells (TRM) and an increase in the secretion of interferon-γ, granzyme B, and perforin in CD8+ T subsets and activation of B cells and dendritic cells. Doxorubicin alone and in combination with gemcitabine decreased regulatory T cells in the TIME. Moreover, doxorubicin treatment promoted the formation of HEV and TLS. Doxorubicin treatment also upregulated the expression of programmed cell death protein (PD)-1 in CD8+ T cells and programmed cell death protein ligand (PD-L)1 in tumor cells.ConclusionsThese results indicate that doxorubicin with an ICD reaction promotes TLS formation and increases PD-1/PD-L1 expression in tumor tissues. The results demonstrate the development of a therapeutic avenue using combined immune checkpoint therapy.

The localization of electromagnetic radiation leakage through cabin gaps is a critical and challenging aspect of electromagnetic compatibility (EMC) design for spacecraft with complex electromagnetic environments. This paper proposes a localization method based on synthetic aperture interferometric passive radiometry imaging. Electromagnetic radiation signals are measured at a certain distance from the spacecraft surface to form visibility samples. A Fourier transform pair between the visibility sample and the corrected brightness temperature for electromagnetic radiation leakage is established. The spacecraft surface electromagnetic leakage location image is obtained through the inverse Fourier transform. A sparse sampling method based on ant colony optimization was proposed to improve testing efficiency. The impacts of various factors, including positional parameters, positioning accuracy of the test antenna, scanning parameters, and measurement receiver amplitude/phase errors on the imaging results are analyzed. Experiments were conducted on a 1 m × 1 m × 1 m cabin with 51 holes on one surface, and the algorithm proposed in this paper was validated to effectively image and locate electromagnetic leakage points at different frequencies. The effectiveness of sparse sampling was also verified, with a localization accuracy of 90.2% and a testing time savings of 81.9%.

Abstract Background and purpose Cerebral small vessel disease (CSVD) is a common cause of stroke and senile vascular cognitive impairment, imposing a heavy burden on public health care systems worldwide. Hypertension and 24-hour blood pressure variability (BPV), known to be significant risk factors for cognitive dysfunction, have been found to be associated with cognitive function in CSVD patients in previous studies. However, as a derived part of BPV, there are few studies on the relationship between circadian rhythm of blood pressure and cognitive dysfunction in CSVD patients, and the relationship between them is still unclear. Thus, this study aimed to investigate whether the disturbance of circadian rhythm of blood pressure can affect the cognitive function of patients with CSVD. Methods A total of 383 CSVD patients hospitalized in the Geriatrics Department of the Lianyungang Second People’s Hospital between May 2018 and June 2022 were enrolled in this study. The clinical information and parameters of 24-hour ambulatory blood pressure monitoring were compared between the cognitive dysfunction group (n = 224) and the normal group (n = 159). Finally, a binary logistic regression model was used to assess the relationship between circadian rhythm of blood pressure and cognitive dysfunction in patients with CSVD. Results (1) Patients in the cognitive dysfunction group were older, had lower blood pressure on admission, and had a greater number of previous cardiovascular and cerebrovascular diseases (P

Abstract With the rapid increase of the penetration rate of renewable energy sources in power system, the decrease of system inertia will threaten the frequency stability, and the dispersion of frequency response cannot be ignored. This paper proposes a method to estimate area inertia of power system containing wind power considering dispersion of frequency response. Firstly, the impact of inertia distribution between areas on the frequency stability and the inter‐area oscillation are analysed. Secondly, the system is divided based on the spectral clustering algorithm and the frequency similarity index is defined according to the Pearson correlation coefficient to determine the measurement locations for area frequency. Thirdly, the measured tie‐line power and frequency deviation are used to estimate the area inertia based on the numerical integration method. Finally, the case study is conducted based on the modified IEEE 39‐bus system. The simulation results revealed that the proposed method is accurate and reliable in different scenarios.

Wind power forecast is becoming more and more important as the ever-increasing penetration of renewable energies brings uncertainties to the power systems. Although the numerical weather prediction (NWP) has already been widely applied on wind power forecast, it involves high computational burden with complex meteorological models, which has great uncertainty in real environment, so machine learning methods are the significant supplement for accurate wind power forecast. This paper proposes a deep learning model to improve the prediction accuracy based on the NWP data. Variational Mode Decomposition (VMD) is applied to extract time-series information. Furthermore, an encoder–decoder structure consisting of a dual attention-long short term memory (LSTM) neural network is constructed to enhance the forecasting accuracy. The comparison between the proposed model and several benchmark models, show the superiority of proposed model in effectively enhancing the prediction performance.

Abstract Objective To investigate the impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on CTP infarct core volume and poor 90-day functional outcomes in acute ischemic stroke (AIS). Methods A total of 403 hospitalized patients with AIS in the Stroke Center of the First Hospital Affiliated to Soochow University were enrolled from March 2018 to January 2021. The association between NT-proBNP and clinical outcomes in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Also, subgroup analyses were conducted based on treatment decisions. Results NT-proBNP was positively correlated with CTP ischemic volume (p

BackgroundAlthough many efforts have been devoted to identify biomarkers to predict the responsiveness of immune checkpoint inhibitors, including expression of programmed death-ligand 1 (PD-L1) and major histocompatibility complex (MHC) I, microsatellite instability (MSI), mismatch repair (MMR) defect, tumor mutation burden (TMB), tertiary lymphoid structures (TLSs), and several transcriptional signatures, the sensitivity of these indicators remains to be further improved.Materials and methodsHere, we integrated T-cell spatial distribution and intratumor transcriptional signals in predicting the response to immune checkpoint therapy in MMR-deficient tumors including tumors of Lynch syndrome (LS).ResultsIn both cohorts, MMR-deficient tumors displayed personalized tumor immune signatures, including inflamed, immune excluded, and immune desert, which were not only individual-specific but also organ-specific. Furthermore, the immune desert tumor exhibited a more malignant phenotype characterized by low differentiation adenocarcinoma, larger tumor sizes, and higher metastasis rate. Moreover, the tumor immune signatures associated with distinct populations of infiltrating immune cells were comparable to TLSs and more sensitive than transcriptional signature gene expression profiles (GEPs) in immunotherapy prediction. Surprisingly, the tumor immune signatures might arise from the somatic mutations. Notably, patients with MMR deficiency had benefited from the typing of immune signatures and later immune checkpoint inhibition.ConclusionOur findings suggest that compared to PD-L1 expression, MMR, TMB, and GEPs, characterization of the tumor immune signatures in MMR-deficient tumors improves the efficiency of predicting the responsiveness of immune checkpoint inhibition.

With wind power integrated into the power system on a large scale, the system has become vulnerable to the frequency stability issue. The battery energy storage system (BESS) is considered the key solution to improving the system frequency regulation performance due to its fast response ability. Furthermore, the construction of wind-storage combined frequency regulation systems has been developed for many years, in which the optimal capacity configuration of the wind-storage system is getting more attention. However, the secondary frequency drop (SFD) caused by wind turbines (WTs) participating in primary frequency regulation (PFR) is neglected in most existing capacity configurations, which is worthy of further study. In this paper, the optimal capacity of the wind-storage combined frequency regulation system is studied from the perspective of SFD. The time-domain expressions of two-stage system frequency response considering SFD are derived based on the wind-storage combined frequency regulation model. Next, considering the technical and economic characteristics of wind-storage combined frequency regulation, an optimization model of the energy storage capacity configuration is established with the objective of minimizing the sum of the maximum frequency deviations in two stages and the energy storage cost. The optimization model is solved by the multi-objective salp swarm algorithm (MSSA) to obtain the setting value of wind-storage combined frequency regulation parameters and the optimal energy storage capacity. The effectiveness of the proposed method is verified in MATLAB. The simulation results show that the proposed model can effectively improve the frequency regulation effect of the system and ensure the optimal capacity configuration with better economy.

Platycodon grandiflorus, a perennial flowering plant widely distributed in China and South Korea, is an excellent resource for both food and medicine. The main active compounds of P. grandiflorus are triterpenoid saponins. WRKY transcription factors (TFs) are among the largest gene families in plants and play an important role in regulating plant terpenoid accumulation, physiological metabolism, and stress response. Numerous studies have been reported on other medicinal plants; however, little is known about WRKY genes in P. grandiflorus. In this study, 27 PgWRKYs were identified in the P. grandiflorus transcriptome. Phylogenetic analysis showed that PgWRKY genes were clustered into three main groups and five subgroups. Transcriptome analysis showed that the PgWRKY gene expression patterns in different tissues differed between those in Tongcheng City (Southern Anhui) and Taihe County (Northern Anhui). Gene expression analysis based on RNA sequencing and qRT-PCR analysis showed that most PgWRKY genes were expressed after induction with methyl jasmonate (MeJA). Co-expressing PgWRKY genes with triterpenoid biosynthesis pathway genes revealed four PgWRKY genes that may have functions in triterpenoid biosynthesis. Additionally, functional annotation and protein-protein interaction analysis of PgWRKY proteins were performed to predict their roles in potential regulatory networks. Thus, we systematically analyzed the structure, evolution, and expression patterns of PgWRKY genes to provide an important theoretical basis for further exploring the molecular basis and regulatory mechanism of WRKY TFs in triterpenoid biosynthesis.

We utilized a first-principle density functional theory for a comprehensive analysis of CsPbX3 (X = F, Cl, Br, I) to explore its physical and chemical properties, including its mechanical behavior, electronic structure and optical properties. Calculations show that all four materials have good stability, modulus of elasticity, hardness and wear resistance. Additionally, CsPbX3 demonstrates a vertical electron leap and serves as a semiconductor material with direct band gaps of 3.600 eV, 3.111 eV, 2.538 eV and 2.085 eV. In examining its optical properties, we observed that the real and imaginary components of the dielectric function exhibit peaks within the low-energy range. Furthermore, the dielectric function gradually decreases as the photon energy increases. The absorption spectrum reveals that the CsPbX3 material exhibits the highest UV light absorption, and as X changes (with the increase in atomic radius within the halogen group of elements), the light absorption undergoes a red shift, becoming stronger and enhancing light utilization. These properties underscore the material’s potential for application in microelectronic and optoelectronic device production. Moreover, they provide a theoretical reference for future investigations into CsPbX3 materials.

The acid-induced gelation of pectin in potato cell walls has been gradually recognized to be related to the improvement in the cell wall integrity after heat processing. The aim of this study was to characterize the acid-induced gelation of original pectin from a potato cell wall (OPP). Rheological analyses showed a typical solution–sol–gel transition process of OPP with different additions of gluconic acid-δ-lactone (GDL). The gelation time (Gt) of OPP was significantly shortened from 7424 s to 2286 s. The complex viscosity (η*) of OPP gradually increased after 4000 s when the pH was lower than 3.13 and increased from 0.15 to a range of 0.20~6.3 Pa·s at 9000 s. The increase in shear rate caused a decrease in η, indicating that OPP belongs to a typical non-Newtonian fluid. Furthermore, a decrease in ζ-potential (from −21.5 mV to −11.3 mV) and an increase in particle size distribution (from a nano to micro scale) was observed in OPP after gelation, as well as a more complex (fractal dimension increased from 1.78 to 1.86) and compact (cores observed by cryo-SEM became smaller and denser) structure. The crystallinity of OPP also increased from 8.61% to 26.44%~38.11% with the addition of GDL. The above results call for an investigation of the role of acid-induced OPP gelation on potato cell walls after heat processing.

BackgroundWe aimed to investigate the biological mechanism and feature genes of Duchenne muscular dystrophy (DMD) by multi-omics and experimental verification strategy.MethodsWe integrated the transcriptomic and proteomic methods to find the differentially expressed mRNAs (DEMs) and proteins (DEPs) between DMD and Control groups. Weighted gene co-expression network analysis (WGCNA) was then used to identify modules of highly correlated genes and hub genes. In the following steps, the immune and stromal cells infiltrations were accomplished by xCELL algorithm. Furthermore, TF and miRNA prediction were performed with Networkanalyst. ELISA, western blot and external datasets were performed to verify the key proteins/mRNAs in DMD patient and mouse. Finally, a nomogram model was established based on the potential biomarkers.Results4515 DEMs and 56 DEPs were obtained from the transcriptomic and proteomic study respectively. 14 common genes were identified, which is enriched in muscle contraction and inflammation-related pathways. Meanwhile, we observed 33 significant differences in the infiltration of cells in DMD. Afterwards, a total of 22 miRNAs and 23 TF genes interacted with the common genes, including TFAP2C, MAX, MYC, NFKB1, RELA, hsa-miR-1255a, hsa-miR-130a, hsa-miR-130b, hsa-miR-152, and hsa-miR-17. In addition, three genes (ATP6AP2, CTSS, and VIM) showed excellent diagnostic performance on discriminating DMD in GSE1004, GSE3307, GSE6011 and GSE38417 datasets (all AUC > 0.8), which is validated in patients (10 DMD vs. 10 controls), DMD with exon 55 mutations, mdx mouse, and nomogram model.ConclusionTaken together, ATP6AP2, CTSS, and VIM play important roles in the inflammatory response in DMD, which may serve as diagnostic biomarkers and therapeutic targets.

Ataxia with oculomotor apraxia type 1 (AOA1) is a rare genetic disorder and is inherited in an autosomal recessive manner. It is mainly characterized by childhood-onset progressive cerebellar ataxia, with dysarthria and gait disturbance being the two most common and typical manifestations. Axonal sensorimotor peripheral neuropathy, dystonia, chorea, and cognitive impairment are common associated symptoms, as are hypoalbuminemia and hypercholesterolemia. Oculomotor apraxia (OMA)has been reported to be a feature often, although not exclusively, associated with AOA1. The Aprataxin gene, APTX, is ubiquitously expressed, and numerous APTX mutations are associated with different clinical phenotypes have been found. In the present study, we enrolled a 14-year-old boy who developed ataxia with staggering gait from the age of 4 years. Early-onset cerebellar ataxia, peripheral axonal neuropathy, cognitive impairment and hypoalbuminemia, hypercholesterolemia were presented in this patient, except for OMA. We applied ataxia-related genes filtering strategies and whole-exome sequencing (WES) to discover the genetic factors in a Chinese family. Sanger sequencing was used in the co segregation analysis in the family members. A compound heterozygous mutation in APTX gene (c.739C>T and c.501dupG) was identified. This is the first description of a genetically confirmed patient of AOA1 in a Chinese family in addition to a novel mutation of c.501dupG in APTX.

Abstract Background Middle-aged females, especially perimenopausal females, are vulnerable to depression, but the potential mechanism remains unclear. Dopaminergic and GABAergic system dysfunction is involved in the pathophysiology of depression. In the current study, we used 2-month-old and 11-month-old C57BL/6 mice as young and middle-aged mice, respectively. Chronic immobilization stress (CIS) was used to induce depressive-like behaviour, and the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess these behaviours. We then measured the mRNA levels of dopamine receptor D1 (DRD1) and the GABAA receptors GABRA1, GABRB2 and GABRG2 in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Results We found that immobility time in the FST was significantly increased in the middle-aged mice compared with the middle-aged control mice and the young mice. In addition, the preference for sucrose water was reduced in the middle-aged mice compared with the middle-aged control mice. However, CIS did not induce obvious changes in the performance of the young mice in our behavioural tests. Moreover, the middle-aged mice exhibited equal immobility times as the young mice in the absence of stress. Decreases in the mRNA levels of DRD1, GABRA1, and GABRB2 but not GABRG2 were found in the NAc and PFC in the middle-aged mice in the absence of stress. Further decreases in the mRNA levels of DRD1 in the NAc and GABRG2 in the NAc and PFC were found in the middle-aged mice subjected to CIS. Conclusions Our results suggested that ageing could not directly induce depression in the absence of stress. However, ageing could induce susceptibility to depression in middle-aged mice in the presence of stress. CIS-induced decreases in DRD1 and GABRG2 levels might be involved in the increase in susceptibility to depression in this context.

17a-Hydroxylase/17,20-lyase deficiency (17OHD) is caused by pathogenic mutations in CYP17A1. Female patients present with hypertension, hypokalemia, and sexual infantilism while males present with sex development disorder. Moyamoya disease (MMD) is a chronic cerebrovascular disease that frequently results in intracranial ischemia or hemorrhage. The present study describes a case of 17OHD and MMD in a 27-year-old phenotypically female (46, XY) patient and discusses the clinical features and characteristics of her genetic defect. Clinical, hormonal, radiological, and genetic analyses were performed and blood samples were collected for whole-exome sequencing (WES). The results of the WES revealed a homozygous intronic mutation (c.297+2T>C) in CYP17A1, which led to combined 17a-hydroxylase/17,20-lyase deficiency, as well as novel variants in PCNT and CNOT3 that might lead to MMD. To our knowledge, this study is the first to describe 17OHD accompanied by MMD. While several cases have previously described patients with 17OHD with histories of cerebral hemorrhage or cerebral ischemia, a correlation in genetic levels between 17OHD and MMD was not found. The risk of cerebrovascular accidents should be considered in patients with 17OHD and hypertension. Cerebrovascular examination in patients with 17OHD may be beneficial for the prevention of life-threatening intracranial vascular disease.

Understanding building metabolism is critical for guiding urban resource management and addressing challenges in urban sustainable development. Key attributes of buildings, including geolocation, footprint, height, and vintage, are crucial to characterizing spatiotemporal patterns of building metabolism. However, these attributes are usually challenging to obtain broadly and automatically, which obscures a comprehensive understanding and accurate assessment of urban metabolism. Moreover, the lack of a finer spatial pattern of these attributes shadows a spatially explicit characterization of material stock and flow in cities. In this study, we took Shenzhen—whose urbanization over the past three decades has been unprecedented in China and even around the world— has been taken as an example to develop a city-level building dataset based on a random-forest model and quantify the spatiotemporal patterns of material metabolism at relatively high spatial resolution (in 500 m × 500 m grids) by combing material flow analysis (MFA) with geographic information system (GIS). The results show that Shenzhen grew from a small town with 281.02 × 106 m3 of buildings in the 1990s to a mega-city with 3585.5 × 106 m3 of buildings in 2018 and expanded both outward and upward from downtown to suburban areas. The urban “weight” (material stock) increased from 92.69 Mt in the 1990s to 1667.8 Mt in 2018 and tended to be saturated, with an average growth rate of 9.5% per year. Spatially, the south-central areas were the largest container of material stocks and generated the most demolition waste. The spatially explicit maps of building three-dimensional (3-D) form and vintage provide detailed information for architectural conservation and could support the decision-making for urban renewal planning. The spatiotemporal patterns of in-use material stocks and potential generation of construction and demolition waste (CDW) provide a benchmark of environmental risk assessment and potential secondary resources to reduce “original” material consumption, which could help alter urban renewal to an environmental-friendly and sustainable trajectory.

The deleterious effects of methamphetamine (METH) exposure extend beyond abusers, and may potentially impact the vulnerability of their offspring in developing addictive behaviors. Epigenetic signatures have been implicated in addiction, yet the characteristics to identify prenatal METH abuse to offspring addiction risk remains elusive. Here, we used escalating doses of METH-exposed mouse model in F0 female mice before and during pregnancy to simulate the human pattern of drug abuse and generated METH-induced behavioral sensitization to investigate the addictive behavior in offspring mice. We then utilized whole genome-bisulfite sequencing (WGBS) to investigate the methylation signature of nucleus accumbens (NAc) in male METH-sensitized mice. Interestingly, male but not female offspring exhibited an enhanced response to METH-induced behavioral sensitization. Additionally, the METH-exposed group of male mice underwent a more comprehensive wave of epigenome remodeling over all genomic elements compared with unexposed groups due to drug exposure history. 104,219 DMCs (METH-SAL vs. SAL-SAL) induced by prenatal METH-exposure were positively correlated with that of postnatal METH-exposure (38,570, SAL-METH vs. SAL-SAL). Moreover, 4,983 DMCs induced by pre- and postnatal METH exposure (METH-METH vs. SAL-METH) were negatively correlated with that of postnatal METH exposure, and 371 commonly changed DMCs between the two comparison groups also showed a significantly negative correlation and 86 annotated genes functionally enriched in the pathways of neurodevelopment and addiction. Key annotated genes included Kirrel3, Lrpprc, and Peg3, implicated in neurodevelopmental processes, were down-regulated in METH-METH group mice compared with the SAL-METH group. Taken together, we render novel insights into the epigenetic correlation of drug exposure and provide evidence for epigenetic characteristics that link maternal METH exposure to the intensity of the same drug-induced behavioral sensitization in adult offspring.

Objective: Patients with cancer pain are highly dependent on morphine analgesia, but studies have shown a negative correlation between morphine demand and patient outcomes. The long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide (M3G) levels. Hence, the effects of M3G on tumor progression are worth studying. Methods: The effects of M3G on PD-L1 expressions in human non-small cell lung cancer (NSCLC) cell lines were first evaluated. Activation of TLR4 downstream pathways after M3G treatment was then determined by Western blot. The effects of M3G on human cytotoxic T lymphocytes (CTL) cytotoxicity and INF-γ release was also detected. Finally, the LLC murine lung adenocarcinoma cell line were used to establish a murine lung cancer model, and the effects of M3G on tumor growth and metastasis were determined. Results: M3G promoted the expressions of PD-L1 in the A549 and H1299 cell lines in a TLR4-dependent manner (P < 0.05). M3G activated the PI3K and the NFκB signaling pathways, and this effect was antagonized by a TLR4 pathway inhibitor. A PI3K pathway inhibitor reversed the M3G-mediated PD-L1 upregulation. M3G inhibited the cytotoxicity of CTL on A549 cells and decreased the level of INF-γ. Repeated M3G intraperitoneal injections promoted LLC tumor growth and lung metastasis through the upregulation of tumor expressed PD-L1 and the reduction of CTL in the tumor microenvironment. Conclusions: M3G specifically activated TLR4 in NSCLC cells and upregulated PD-L1 expression through the PI3K signaling pathway, thereby inhibiting CTL cytotoxicity and finally promoting tumor immune escape.

Non-Intrusive Load Monitoring (NILM) is particularly important for demand response. This paper proposes an innovative method based on a deep learning model to recognize the working state of electrical appliances using low frequency load data. The approach includes a data processing step, a deep learning model and a new accuracy calculation method. The data processing step consists of a multi-feature and high-dimensional method (MFHDM) and a pre-training process. The deep learning model consists of a convolutional neural network (CNN), a long-term short-term memory network (LSTM) and a random-forest (RF) algorithm. The proposed method addresses the label correlation problem and the class-imbalance problem. To test the proposed method, the Reference Energy Disaggregation Dataset (REDD) and the Pecan Street dataset (PSD) are used. A comparative analysis with several models shows that the proposed method can effectively improve electrical appliance recognition accuracy and realize NILM.

ROS1 gene rearrangements have been reported in diverse cancer types including non‐small‐cell lung cancer (NSCLC), and with a notably higher prevalence in lung adenocarcinoma. The tyrosine kinase inhibitors, crizotinib, lorlatinib, and entrectinib, have demonstrated favorable efficacy in treating ROS1‐rearranged NSCLCs. Herein, we retrospectively reviewed 17 158 NSCLC patients whose tumor specimen and/or circulating cell‐free DNA underwent comprehensive genomic profiling. A total of 258 unique patients were identified with ROS1 rearrangements, representing an overall prevalence of approximately 1.5% of ROS1 fusions in newly diagnosed and relapsed NSCLC patients. CD74 (38%) was the most common fusion partner of ROS1, followed by EZR (13%), SDC4 (13%), SLC34A2 (10%), and other recurrent fusion partners with lower frequencies, including TPM3, MYH9, and CCDC6. Variant breakpoints occurred in ROS1 introns 33 (37%), 31 (25%), 32 (17%), and 34 (11%) with no obvious hotspots. CD74 (63%) and EZR (50%) were more frequently fused to ROS1 intron 33 than other introns, while ROS1 intron 31 was most frequently fused with SDC4 (79%) and SLC34A2 (81%). Crizotinib progression‐free survival (PFS) was not significantly different between fusion variants involving breakpoints in different ROS1 introns, nor was there a significant difference in PFS between CD74‐ROS1 and non‐CD74‐ROS1 groups of patients. Furthermore, TP53 was most frequently mutated in patients who progressed on crizotinib, and TP53 mutations were significantly associated with shorter crizotinib PFS. ROS1 mutations, including G2032R, were observed in approximately 33% of post‐crizotinib samples. Collectively, we report the prevalence of ROS1 fusions in a large‐scale NSCLC population and the efficacy of crizotinib in treating patients with ROS1‐rearranged NSCLC.

BackgroundRhino-orbital cerebral mucormycosis (ROCM) is a rare, invasive, and fatal fungal disease. Due to the lack of specific clinical manifestations and adequate auxiliary examinations, patients are easily misdiagnosed in the early stage. Early diagnosis and timely therapy are essential for successful treatment.Case ReportWe report a 68-year-old man with diabetic ketoacidosis, presented with orbital apex syndrome (OAS), fever, and pansinusitis, which progressively worsened to death only 4 days after admission. It was finally confirmed as a fungal Rhizopus arrhizus infection by metagenomics cell-free DNA next-generation sequencing (mNGS) testing.ConclusionOrbital apex syndrome could be the initial presentation for mucormycosis. Thus, it is necessary to evaluate the presence of mucormycosis in patients with OAS, especially in diabetic or immunosuppressed hosts, and mNGS testing and timely antifungal therapy should be strongly recommended in highly suspected cases.

BackgroundThe incidence of atrial fibrillation (AF)-related stroke increases with aging. Natriuretic peptides (NPs) family, including Corin-B type natriuretic peptide (BNP)-neprilysin (NEP) protein levels increased with age and are risk markers of cardiovascular and cerebrovascular diseases, such as AF and cardioembolic stroke. Aging is also linked to epigenetics, specifically DNA methylation. However, only a few studies have investigated the effect of DNA methylation on the NP system. Thus, the present study aimed to investigate whether the Corin-BNP-NEP protein pathway is involved in the pathogenesis of AF-stroke and CpG methylation in the promoter region of the Corin protein gene has an effect on AF-related ischemic stroke.MethodsA total of 82 patients hospitalized with acute ischemic strokes were enrolled in this study. The differences in clinical information were compared between the AF-stroke (n = 37) and no AF-stroke groups (n = 45). Plasma-soluble Corin and NEP were detected using an ELISA kit. CpG methylation in the promoter region of the gene was assessed by a next-generation sequencing-based bisulfite sequencing polymerase chain reaction (BSP).Results(1) Patients in AF-stroke were older, had higher initial NIHSS score, 90-day mRs, higher D2-dimer, INR, and APTT, and low TG, TC, and HbA1c (all p < 0.05). (2) Serum levels of Corin and BNP in the AF-stroke group were significantly higher than that in the no AF-stroke group (p < 0.05). No significant difference was detected in the serum levels of NEP between the two groups. (3) The levels of CpG methylation in the promoter region of the Corin protein gene in the AF-stroke group was significantly lower than that in the no AF-stroke group (p < 0.05). The CpG sites with maximal methylation differences between the two groups were CORIN:678, CORIN:682, CORIN:694, and CORIN:700.ConclusionThe current findings raise the possibility that the Corin–BNP–NEP protein pathway may be involved in the pathogenesis of AF-related ischemic stroke. Deficient CpG methylation in the promoter region of the Corin protein gene is associated with AF-related ischemic stroke.

In austenitic steels, the co-segregation of C and Cr at grain boundaries can result in the formation of Cr23C6. However, the addition of B to steels can effectively reduce the amount of Cr23C6 formed and inhibit its ripening in experiments, simultaneously transforming it into Cr23(BC)6. Therefore, the effect of B on the co-segregation of C and Cr at the Σ5(210), Σ9(221) and Σ11(113) grain boundaries in austenitic steels was investigated using density functional theory. The results indicate that B, C, and Cr all tend to segregate at the three grain boundaries, with B and C showing a stronger segregation tendency. Furthermore, co-segregation of C and Cr with short distances occurs readily at the Σ5(210), Σ9(221) and Σ11(113) grain boundaries. The presence of B at grain boundaries can impede the segregation of Cr, particularly at the Σ9(221) and Σ11(113) grain boundaries. When B is pre-segregating at the Σ5(210) grain boundary, B, C, and Cr tend to co-segregate at the grain boundary. The grain boundary B hinders the accumulation of Cr near it for most grain boundaries, thereby inhibiting the co-segregation of Cr and C, making it difficult for B, C, and Cr to aggregate at most grain boundaries. This is beneficial for controlling the nucleation of Cr23(BC)6.

ObjectiveAdmission hyperglycemia is an established risk factor for functional outcome in patients with acute ischemic stroke. However, the association between glycated hemoglobin (HbA1c) and prognosis in patients with acute anterior circulation ischemic stroke (AACIS) remains controversial. This study aimed to explore whether elevated HbA1c levels are associated with functional outcome in AACIS patients.Participants and MethodsWe enrolled patients with AACIS hospitalized in the First Hospital Affiliated to Soochow University from March 2018 to January 2021. Patients were categorized into three groups based on baseline HbA1c: HbA1c ≤ 6.5%, 6.5% < HbA1c ≤ 8.0%, and HbA1c > 8.0%. Ninety-day modified Rankin Scale scores of 0–1 and 0–2 were defined as excellent and favorable functional outcome, respectively. Early neurological improvement was regarded as a reduction in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points compared with that on admission, or an NIHSS score of 0–1 at discharge. The association between HbA1c and clinical outcome in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Subgroup analyses by TOAST classification were also conducted.ResultsThe study included 326 patients. The proportion with favorable outcome was significantly lower in the HbA1c > 8.0% group than the HbA1c ≤ 6.5% group (30.4 vs. 55.2%; p < 0.01). Binary logistic regression analysis demonstrated that increasing HbA1c levels (as a continuous variable) were associated with reduced functional independence (adjusted OR = 0.739; 95% CI: 0.605–0.904; p = 0.003). In subgroup analyses, higher HbA1c was also associated with favorable outcome in large-artery atherosclerosis (LAA)-type patients (adjusted OR = 0.776; 95% CI: 0.614–0.981; p = 0.034), but not in LAA group.ConclusionsHbA1c level was an independent predictor of worse functional outcome in patients with AACIS, particularly in those with LAA. For patients with anterior circulation atherosclerosis, strict adherence to a target HbA1c < 6.5% may be required.

Abstract Background Glioblastoma (GBM) cells with stem cell-like properties are called glioma stem cells (GSCs). GSCs display highly treatment resistance and are responsible for tumor recurrence. Napabucasin (BBI608), a novel small molecule inhibitor of STAT3, has been identified to eliminate stemness-like tumor cells in some cancers. However, the influence of Napabucasin on GBM cells, especially on GSCs, is currently unclear. In this study, we explored the influence and underlying mechanisms of Napabucasin on GBM cells. Methods STAT3 expression and its correlation with the glioma grade and patient survival were analyzed using CGGA and TCGA glioma databases. The influence of Napabucasin on proliferation, stemness, the cell cycle, apoptosis, and invasion of human GBM cell lines U87MG and LN229 was tested by CCK8, EdU incorporation, colony formation, Transwell invasion, and three-dimensional spheroid assays as well as flow cytometry, qPCR, and western blot analysis. The ability of Napabucasin to inhibit cell proliferation of U87MG tumor xenografts in mice was assessed using a live animal bioluminescence imaging system and immunohistochemistry. Results Napabucasin suppressed the proliferation, colony formation, and invasion of U87MG and LN229 cells. Furthermore, Napabucasin induced cell cycle arrest and apoptosis. More importantly, Napabucasin treatment obviously inhibited expression of stemness-associated genes including STAT3 and suppressed the spheroid formation of glioma cells in vitro. Napabucasin also disrupted the NF-κB signaling pathway via downregulation of RelA (p65). Finally, glioma growth was effectively impaired by Napabucasin in nude mice bearing intracranial glioma xenografts. Conclusions Napabucasin treatment may be a novel approach for the treatment of GBM, particularly GSCs.

In this paper, molecular dynamics (MD) simulations are used to investigate the effects of machining parameters on the nanomachining and subsurface defect evolution of single crystal γ-TiAl alloys with water medium. The changes of cutting force and cutting temperature with water medium were analyzed in the nano-cutting process, and the subsurface defects and crystal structure changes of the workpiece were studied by common neighbor analysis (CNA) method. The results show that increasing the cutting speed appropriately can reduce the friction between the workpiece and the tool, and improve the machining efficiency. With the increase in cutting depth, the temperature of the Newtonian layer increases gradually, and the cooling of the water medium reduces the temperature of the workpiece. The defect evolution becomes severe and the number of BCC atoms increases with the increase in cutting depth. With the increase in cutting distance, the number of HCP atoms decreases and the number of BCC atoms basically remains stable. In addition, as the cutting speed increases, the internal stress of the workpiece gradually extends to the inside of the workpiece along the depth direction. There is more compressive stress in the unmachined area and the shear zone between the tool and the workpiece.

S is a common corrosion medium for austenitic stainless steels. The severe intergranular fracture of austenitic stainless steels occurs in sulfur environments. In this paper, the permeation of S at different atomic positions for three symmetric tilt grain boundary types, i.e., Σ5(210), Σ5(310), and Σ9(114) have been computed using first-principles calculations. S has the strongest segregation tendency in the Σ5(210) grain boundary. A high content of S at the grain boundary indicates harm to the grain boundary. Sulfur segregation in the grain boundaries can weaken the strength of the metallic bond. When Mo and Cr are present at the Σ5(210) grain boundary, the sulfur-induced embrittlement is inhibited. With increased S concentration at the grain boundary, the coexistence of Mo and Cr can suppress the intergranular fracture of S on the grain boundary. The reason why high-Mo stainless steel has excellent sulfur-induced intergranular corrosion resistance is explained at the atomic level.

Abstract Background Characterizing the synchronous changes of epileptic seizures in different stages between different regions is profound to understand the transmission pathways of epileptic brain network and epileptogenic foci. There is currently no adequate quantitative calculation method for describing the propagation pathways of electroencephalogram (EEG) signals in the brain network from the short and long term. The goal of this study is to explore the innovative method to locate epileptic foci, mapping synchronization in the brain networks based on EEG. Methods Mutual information was used to analyze the short-term synchronization in the full electrodes; while nonlinear dynamics quantifies the statistical independencies in the long –term among all electrodes. Then graph theory based on the complex network was employed to construct a dynamic brain network for epilepsy patients when they were awake, asleep and in seizure, analyzing the changing topology indexes. Results Epileptic network achieved a high degree of nonlinear synchronization compared to awake time. and the main path of epileptiform activity was revealed by searching core nodes. The core nodes of the brain network were in connection with the onset zone. Seizures always happened with a high degree of distribution. Conclusions This study indicated the path of EEG synchronous propagation in seizures, and core nodes could locate the epileptic foci accurately in some epileptic patients.

Lentinula edodes (L. edodes) is a type of edible mushroom which is known to beneficially support the immune system. In this study, three polysaccharide fractions (F1, F2 and F3) were isolated from L. edodes water extracts. Their molecular weights distribution (F1 > F2 > F3) and their immunomodulatory properties were investigated. Thymus index, thickness of footpad, proliferation of splenocytes, immunoglobulin (Ig) content and cytotoxicity of natural killer (NK) cells were measured to evaluate the immunomodulatory effects of the polysaccharides. All three polysaccharide fractions protected host from immunosuppression. F1 had significant effects in enhancing cellular immunity only, while F2 and F3 improved cellular immunity, humoral immunity and innate immunity. The immunomodulatory effects became more significant in the order F1

The transmission of a large amount of video and picture content brings more challenges to wireless communication networks. Unmanned aerial vehicle (UAV)-aided small cells with active content caching deployed on cellular networks are recognized as a promising way to alleviate wireless backhaul and support flexible coverage. However, a UAV cannot operate for a long time due to limited battery life, and its caching capacity is also limited. For this, a multi-UAV content-caching strategy and cooperative, complementary content transmission among UAVs are jointly studied in this paper. Firstly, a user-clustering-based caching strategy is designed, where user clustering is based on user similarity, concurrently taking into consideration similarities in content preference and location. Then, cooperative, complementary content transmission between multiple UAVs is modeled as a coalition formation game (CFG) to maximize the utility of the whole network. Finally, the effectiveness of the proposed algorithms is demonstrated through numerical simulations.

Abstract A combined experimental and first-principle study on the oxidation mechanism of super austenitic stainless steel S32654 at 900 °C for a short time period (1, 3, and 5 h) in air is presented. The samples exhibit excellent oxidation resistance because of the initial and gradual formation of the denser Fe- and Cr-rich layer with increasing oxidation time. Meanwhile, the Mo-rich layer gradually forms because of the Mo diffusion, which results in the formation of the oxide layer with two distinct regions: an inner Fe- and Cr-rich layer and an outer Mo-rich layer. Density functional theory is applied to investigate the diffusion behaviour of Mo atom in the Fe-Cr-Ni/Cr2O3 interface and the effects of alloying elements (Fe, Ni, and Mn) on the Mo diffusion. The Mo originating from the alloy matrix tends to diffuse into the Cr2O3 part, thereby resulting in the formation of the continuous Mo-rich layer, which is consistent with the experimental behaviour. Moreover, the introduction of Ni to the Cr2O3 part can promote the Mo diffusion and the formation of the Mo-rich oxide layer, whereas Fe and Mn can hinder the Mo diffusion. The calculated results provide a microcosmic explanation of the experimental results.

A novel monohydroxycucurbit[7]uril-based stationary phase for capillary gas chromatography (GC) has been produced. For this, a capillary column coating was made using a sol–gel technique, incorporating synthesized monohydroxycucurbit[7]uril [(OH)Q[7]] and hydroxy-terminated poly(dimethylsiloxane) (OH-PDMS) into the sol–gel network through hydrolysis and polycondensation and chemical sol–gel grafting to the inner wall of a fused-silica tube. The preparation method may produce a coating with greater integrity, which gives the prepared column a higher separation efficiency and better selectivity toward analytes than a reported stationary phase based on neat cucurbit[n]urils (Q[n]s). The prepared (OH)Q[7]/PDMS column had 3,225 theoretical plates per meter determined using naphthalene at 120°C and exhibited a weakly polar nature. The (OH)Q[7]/PDMS column has high resolution over a broad spectrum of analytes with symmetrical peak shapes and exhibited better separation performance than commercial capillary columns and reported columns based on neat Q[n]s that failed to resolve some critical analytes. Moreover, the column also showed good thermal stability up to 300°C and separation repeatability with relative standard deviation values in the range of 0.01–0.11% for intraday, 0.11–0.32% for interday and 0.29–0.58% for column-to-column. In addition, the energy effect on the retention of analytes on the (OH)Q[7]/PDMS stationary phase was investigated. The results indicated that retention on the column was determined mainly by the enthalpy change. As demonstrated, the proposed coating method can address some disadvantages that exist with the reported Q[n]s columns and combine the full advantages of (OH)Q[7] with the sol–gel coating method while achieving outstanding GC separation performance.

Background/Aims: A combination sevoflurane postconditioning (SPC) and remote ischemic preconditioning (RIPC) is proved effective in an ex vivo rat heart perfusion model. However, the combined effect of those two interventions is not tested in rat myocardial ischemia/reperfusion (I/R) model, and the underlying mechanisms remain to be elucidated. This study aimed to investigate the effect in vivo using a rat myocardial I/R model and illuminate the related mechanisms. Methods: Forty male Sprague-Dawley rats were randomly divided into the following 5 groups: i) sham-operated control; ii) I/R; iii) I/R + RIPC; iv) I/R + SPC; v) I/R + RIPC + SPC. The hemodynamic parameters were recorded at the end of reperfusion. The histological changes including the infarct size were assessed using Triphenyltetrazolium chloride (TTC) staining and H&E staining. In addition, the circulating levels of cardiac enzymes (CK-MB, hs-cTnT, and cTnT) inflammatory cytokines (IL-6, IL-8, and TNF-α) were detected. The expression levels of apoptosis-related proteins (C-Caspase 3, PARP, Bax, and Bcl-2), proinflammatory factors (TLR4, HMGB-1, MyD88, and p65), and IKB-α were measured by Western blot analysis. Real-time PCR was performed to detect mRNA levels of the proinflammatory factors. Results: Both SPC and RIPC significantly reduced the infarct size, cardiac enzyme release, inflammatory cytokine secretion, and proinflammatory factor expression, and increased IKB-α expression compared to I/R group. Furthermore, the combination of those two strategies had synergic infarct size limiting and anti-inflammatory effects. Conclusions: The finding of this study suggested that the combination of SPC and RIPC had a potentially cardioprotective effect through inhibiting TLR4/MyD88/NF-κB signaling.

Sanicro 25 austenitic heat-resistant steel is expected to be used in superheaters and reheaters for ultra-supercritical power plants above 600 °C due to its excellent structural stability and high temperature mechanical properties. In this paper, the effects of Co and W on the structural stability, thermodynamic stability and mechanical properties of Sanicro 25 steel are analyzed by calculating the formation energy, binding energy, Gibbs free energy, elastic constant, Peierls stress and generalized stacking fault energy (GSFE) with first-principles calculation method. By calculating the formation energy, binding energy and Gibbs free energy, it concludes that alloying elements Co and W in Sanicro 25 steel can improve the structural stability and thermodynamic stability. It indicates that W and a small amount of Co can improve the plasticity and ductility of Sanicro 25 steel by calculating the bulk modulus (B), shear modulus (G), Young’s modulus (E), the B/G ratio, Poisson’s ratio and Peierls stress. It is found that when Co and W are far from the stacking fault region, it will promote the formation of partial dislocations and twins in the system, thereby improving its plastic deformation ability and mechanical properties.

The addition of B can inhibit the precipitation of σ phases at the grain boundary to improve the hot workability and corrosion resistance for super austenitic stainless steel with high Cr and Mo content. This study focused on the interaction between B and Mo at the Fe–Cr(111)/Cr2O3(0001) interface and its effect on interfacial adhesion by employing the first-principles method, especially the effect of B on the segregation behavior of Mo. The most stable O-terminated Fe/Cr2O3 interface was chosen as the basic configuration. The segregation energy and the work of separation were calculated for the metal/chromia interface with Fe–Cr as the substrate. It has been demonstrated that B can promote the diffusion of Mo atoms into the oxide layer to increase the content of Mo in the passive film. In addition, the interfacial adhesion is higher at the most segregated sites. However, it is more difficult for two or more Mo atoms than a single Mo atom to diffuse into the oxide part with the effect of B, indicating that B can only improve the Mo content of the passive film to a small extent. The electronic properties were also further discussed to analyze the interactions and the binding characters between doped atoms and their surrounding atoms and to explain the underlying reasons for the variation of interfacial adhesion.

To improve fuel use and energy-conversion efficiency and reduce the emission of pollutants, oxygenation is now deemed an effective chemical treatment of water in supercritical and ultra-supercritical power plants. Supercritical water with dissolved oxygen significantly enhances the oxidation rate of steels in the main steam pipeline and super-heater header. However, at the atomic scale, the mechanism of metal oxidation in supercritical water containing dissolved oxygen is unknown and has not been investigated by simulation. In this work, the oxidation of iron in supercritical water containing dissolved oxygen is studied by ab initio molecular dynamics and first principles calculations. The results indicate that dissolved oxygen in supercritical water dramatically accelerates the oxidation of iron. With the help of oxygen, the decomposition of water occurs on the iron surface, thereby producing more iron oxides and iron hydroxides. Additionally, hydrogen peroxide (H2O2) forms as an intermediate product, instantaneously decomposing to form iron hydroxides, and this is another reason for the enhancement in the oxidation of steel by supercritical water containing dissolved oxygen. Based on the results from ab initio molecular dynamics, we develop herein typical models of water molecules and oxygen molecules reacting directly on the iron surface and then carry out first-principles calculations. The results show that water decomposes on the iron surface only with the assistance of adjacent oxygen molecules and in the absence of surrounding water molecules. This investigation deepens our understanding of the oxidation mechanism of metal in supercritical water containing dissolved oxygen. The ideas and methods implemented in this work can also be used to study other materials exposed to supercritical water involving oxygen.

In order to promote the development of ultra-supercritical technology, the optimum composition design of three new alumina-forming austenitic heat-resistant steels, based on Fe−22Cr−25Ni (wt. %), with low cost and excellent performance, and used for 700 °C ultra-supercritical unit was carried out using Thermo-Calc software. A comparison of the mechanical properties presented that with increasing Al content, the plasticity of the system was further improved. Based on the composition system, a systematic investigation regarding the structure stability, thermodynamic properties, and mechanical properties of these new steels was carried out to reveal possible strengthening and toughening mechanisms by employing the first-principles method. Calculation results showed that when Al existed in the Fe−Cr−Ni alloy system as a solid solution, the new structures were stable, especially under high temperature. The solution of Al and Al + Si could increase the value of B/G, namely improving the plasticity of the system, particularly in case of alloying with Al + Si. The inclusion of Si in the Fe−Cr−Ni−Al system was conducive to further improving the plasticity without affecting the strength, which provided references for the subsequent optimum composition design and performance regulation of alumina-forming austenitic heat-resistant steels.

As an excellent means of improving students' effective learning, knowledge tracking can assess the level of knowledge mastery and discover latent learning patterns based on students' historical learning evaluation of related questions. The advantage of knowledge tracking is that it can better organize and adjust students' learning plans, provide personalized guidance, and thus, achieve the purpose of artificial intelligence-assisted education. However, existing methods, for instance, convolutional knowledge tracing, lacking consideration of graph structure and multivariate time-series prediction, result in poor prediction accuracy. Inspired by recent successes of the graph neural network (GNN), we present a novel multivariate graph knowledge tracking (MVGKT) framework to address these limitations. Specifically, a multivariate time-series knowledge tracking system based on spatio-temporal GNN is designed to model student learning trajectories in different spatial and temporal dimensions and capture both temporal dependencies and interstudent correlations. MVGKT incorporates a gate recurrent unit attentive mechanism and graph Fourier transform, discrete Fourier transform, and graph convolution network to increase the predictive accuracy of the student performances. In addition, we design a question difficulty extraction system to obtain information on the difficulty of the questions, and thus, enhance the data features. Numerous experiments on the ASSISTments dataset have demonstrated that MVGKT is superior to existing knowledge-tracking methods on four metrics and has shown that our approach can enhance the predictive accuracy of student performance.