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A survey was conduct to analyze the usage situation of post-exposure prophylaxis(PEP) and related factors among men who have sex with men(MSM) in 6 cities of Shandong Province. Total of 2 620 subjects, the use ratio was 2.98% (78/2 620). Compared with age≤24 years,monthly income5 000 yuan,non-commercial sex, non-DU,non-STD,role for being insert in the anal intercourse,MSM was more likely to use PEP with age≥45 years(对山东省某6个地市招募的2 620名男男性行为者（MSM）进行调查，分析MSM人群HIV暴露后预防（PEP）的使用状况及相关影响因素。MSM人群整体PEP使用比例为2.98%（78/2 620），不同年龄、月收入水平、商业性行为发生状况、吸食新型毒品状况、性病患病状况、性行为角色的MSM人群其PEP使用比例差异具有统计学意义（

Single-step nonadaptive group testing approaches for reducing the number of tests required to detect a small subset of positive samples from a larger set require solving two algorithmic problems. First, how to design the samples-to-tests measurement matrix, and second, how to decode the results of the tests to uncover positive samples. In this study, we focus on the first challenge. We introduce real-valued group testing, which matches the characteristics of existing PCR testing pipelines more closely than combinatorial group testing or compressed sensing settings. We show a set of conditions that allow measurement matrices to guarantee unambiguous decoding of positives in this new setting. For small matrix sizes, we also propose an algorithm for constructing matrices that meet the proposed condition. On simulated data sets, we show that the matrices resulting from the algorithm can successfully recover positive samples at higher positivity rates than matrices designed for combinatorial group testing setting. We use wet laboratory experiments involving SARS-CoV-2 nasopharyngeal swab samples to further validate the approach.

Decreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS. As part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls. 396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). Cohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1–3 (724.99 ± 32.09 mg/mm3 (p

Neutrino oscillation experiments require a precise measurement of the neutrino energy. However, the kinematic detection of the final-state neutron in the neutrino interaction is missing in current neutrino oscillation experiments. The missing neutron kinematic detection results in a smaller detected neutrino energy than the true neutrino energy. A novel 3D-projection scintillator tracker, which consists of roughly ten million active cubes covered with an optical reflector, is capable of measuring the neutron kinetic energy and direction on an event-by-event basis using the time-of-flight technique thanks to the fast timing, fine granularity, and high light yield. The ν¯μ interactions tend to produce neutrons in the final state. By measuring the neutron kinetic energy, the ν¯μ energy can be reconstructed better, allowing a tighter incoming neutrino flux constraint. This article shows the detector’s ability to reconstruct neutron kinetic energy and the ν¯μ flux constraint achieved by selecting the charged-current interactions without mesons or protons in the final state. Neutrino oscillation experiments require a precise measurement of the neutrino energy. However, the kinematic detection of the final-state neutron in the neutrino interaction is missing in current neutrino oscillation experiments. The missing neutron kinematic detection results in a feed-down of the detected neutrino energy compared to the true neutrino energy. A novel 3D\textcolor{black}{-}projection scintillator tracker, which consists of roughly ten million active cubes covered with an optical reflector, is capable of measuring the neutron kinetic energy and direction on an event-by-event basis using the time-of-flight technique thanks to the fast timing, fine granularity, and high light yield. The $\bar{\nu}_{\mu}$ interactions tend to produce neutrons in the final state. By inferring the neutron kinetic energy, the $\bar{\nu}_{\mu}$ energy can be reconstructed better, allowing a tighter incoming neutrino flux constraint. This paper shows the detector's ability to reconstruct neutron kinetic energy and the $\bar{\nu}_{\mu}$ flux constraint achieved by selecting the charged-current interactions without mesons or protons in the final state.

Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of cataract. This study aimed to explore the effects of TRPM7 on the proliferation and differentiation of human lens epithelial cells. TRPM7 was over-expressed in LECs treated with TGF-β2. Down-regulation of TRPM7 attenuated the increase in cell viability and cell proliferation induced by TGF-β2. The LEC migration induced by TGF-β2 was also repressed by down-regulation of TRPM7. Epithelial-specific protein E-cadherin was up-regulated through knock-down of TRPM7. EMT-specific proteins, α-SMA, fibronectin and vimentin, were down-regulated through knockdown of TRPM7. Moreover, phosphorylation of Smad2 and Smad3 was also prevented by inhibition of TRPM7. Therefore, TRPM7 elicited LEC proliferation and EMT through enhancing activation of the TGF-β/Smad pathways, implying a new therapeutic target for cataract.

This analysis aimed to investigate the candidate biomarkers associated with overall survival (OS) in hepatocellular carcinoma (HCC) patients.In the GSE14520 dataset, candidate parameters were selected and included in the Cox regression and Nomogram models through bioinformatic enrichment methods and LASSO analysis, survivor functions of candidate biomarkers were also assessed.Complement and coagulation cascades including 36 differential expressed genes (DEGs) and ribosome pathway including 27 DEGs were significantly enriched (both p0.05 and adjusted p0.05). LASSO model, Cox regression and nomogram analysis indicated that RPS3, together with BCLC and TNM staging, were significantly associated with OS in HCC patients. Validated in the GEO series, TCGA and Human Protein Atlas (HPA) datasets, RPS3 mRNA and RPS3 protein were significantly upregulated in tumor tissues compared to that in nontumor tissues (all p0.05). Upregulation of RPS3 has been linked to high alpha fetoprotein (AFP), advanced tumor stages and multinodular (all p0.05). After adjusting AFP, tumor stage and multinodular, log rank analysis revealed that HCC patients with high RPS3 had unfavorable OS compared to those with low RPS3 (all p0.05).RPS3 upregulation in tumors might contribute to unfavorable OS in HCC patients.

Golden section is a subtle technology from nature to split space, which is both extensive and mysterious. In recent years, some studies1-4 have begun to focus on metabolic scaling (B∝Mb) at the macroevolutionary scale, and some important trends have been revealed. To further answer the question of "where does b come from and where does it go in evolution", a golden section model of macroevolution was constructed by integrating metabolic scaling and Fibonacci sequence. The results showed that, (1) macroevolution at the boundary level was a highly ordered process from one-dimensional (prokaryotes) to five-dimensional evolution (fungi). Four-dimensional life5 was only the choice of animals. (2) b just was the syndrome of dimension application and metabolism realization of life following Fibonacci sequence; however, it indicated major evolution events in the macroevolution and the directions in secondary macroevolution. The logic and panorama of macroevolution therefore were re-outlined based on the idea of dimensional evolution and metabolic evolution. It was argued that the golden section model of macroevolution established a full-new logic system of dimensional and metabolic evolution, and provided a possible path for the unification of macroevolution and microevolution.

As a type of highly plastic innate immune cells, macrophages may be differentiated into M1 and M2 macrophages upon different stimuli, and M2 macrophages are involved in immune regulation, tissue remodeling and regeneration, and wound healing. Previous epidemiological studies have shown a significant negative correlation between the prevalence of helminth infections and the incidence of inflammatory diseases, such as allergy and autoimmune diseases. As a common type of intestinal helminths, hookworm infection may trigger high levels of type II host immune responses, with alternative activation of macrophages, which are effective to inhibit the development and progression of inflammatory diseases. This review summarizes the advances in alternative activation of macrophages in hookworm therapy for inflammatory diseases.

International audience; ObjectivesThe accurate preoperative segmentation of the uterus and uterine fibroids from magnetic resonance images (MRI) is an essential step for diagnosis and real-time ultrasound guidance during high-intensity focused ultrasound (HIFU) surgery. Conventional supervised methods are effective techniques for image segmentation. Recently, semi-supervised segmentation approaches have been reported in the literature. One popular technique for semi-supervised methods is to use pseudo-labels to artificially annotate unlabeled data. However, many existing pseudo-label generations rely on a fixed threshold used to generate a confidence map, regardless of the proportion of unlabeled and labeled data.Materials and MethodsTo address this issue, we propose a novel semi-supervised framework called Confidence-based Threshold Adaptation Network (CTANet) to improve the quality of pseudo-labels. Specifically, we propose an online pseudo-labels method to automatically adjust the threshold, producing high-confident unlabeled annotations and boosting segmentation accuracy. To further improve the network's generalization to fit the diversity of different patients, we design a novel mixup strategy by regularizing the network on each layer in the decoder part and introducing a consistency regularization loss between the outputs of two sub-networks in CTANet.ResultsWe compare our method with several state-of-the-art semi-supervised segmentation methods on the same uterine fibroids dataset containing 297 patients. The performance is evaluated by the Dice similarity coefficient, the precision, and the recall. The results show that our method outperforms other semi-supervised learning methods. Moreover, for the same training set, our method approaches the segmentation performance of a fully supervised U-Net (100% annotated data) but using 4 times less annotated data (25% annotated data, 75% unannotated data).ConclusionExperimental results are provided to illustrate the effectiveness of the proposed semi-supervised approach. The proposed method can contribute to multi-class segmentation of uterine regions from MRI for HIFU treatment.

Purpose The primary objective was to determine the feasibility of implementing the TrueNTH SHAReClinic as a pan-Canadian sexual health and rehabilitation intervention for patients treated for localized prostate cancer. Methods The feasibility study was designed to evaluate the accessibility and acceptability of the intervention. Participants from five institutions across Canada were enrolled to attend one pre-treatment and five follow-up online clinic visits over 1 year following their prostate cancer (PC) treatment. Results Sixty-five patients were enrolled in the intervention. Website analytics revealed that 71% completed the intervention in its entirety, including the educational modules, with an additional 10% completing more than half of the intervention. Five thousand eighty-three views of the educational modules were made along with 654 views of the health library items. Over 1500 messages were exchanged between participants and their sexual health coaches. At 12 months, the intervention received an overall average participant rating of 4.1 out of 5 on a single item satisfaction measure. Conclusion Results support the TrueNTH SHAReClinic as highly acceptable to participants as defined by intervention adherence and engagement. The TrueNTH SHAReClinic demonstrated promise for being a feasible and potentially resource-efficient approach to effectively improving the sexual well-being of patients after PC treatment.

BACKGROUND The pathophysiological changes in the remote myocardium after acute myocardial infarction (MI) remains less understood. PURPOSE To assess the inflammation in the remote myocardium post-MI and its association with left ventricular (LV) remodeling using T2 mapping. STUDY TYPE Prospective. ANIMAL MODEL AND SUBJECTS Twelve pigs at 3-day post-MI, 6 pigs at 3-month post-MI, 6 healthy pigs; 54 patients at 3-day and 3-month post-MI, 31 healthy volunteers; FIELD STRENGTH/SEQUENCE: A 3 T MRI/ steady-state free-precession sequence for T2 mapping (animals: 0, 30, and 55 msec; human: 0, 25, and 55 msec), phase-sensitive inversion recovery gradient echo for late gadolinium enhancement (LGE), balanced steady free-precession sequence for cine. ASSESSMENT Infarcted myocardium was defined on LGE, remote T2 was measured on T2 maps. LV remodeling was evaluated as LV end-diastolic volume change index between two scans using cine. CD68 staining was conducted to detect monocyte/macrophage. STATISTICAL TESTS Student-t test and one-way ANOVA were used to compare remote T2 with normal controls. The association of remote T2 with LV remodeling was assessed using linear regression. P values of

In this study, the liquefaction behavior and development laws of pore water pressure in fiber-reinforced sand were studied using cyclic triaxial tests, and the effects of cyclic stress ratio, fiber content, and fiber length were investigated. The test results showed that the cycle number leading to liquefaction and liquefaction resistance increased with fiber content and fiber length, whereas the cycle number leading to liquefaction decreased as the cyclic stress ratio increased. The pore water pressure accumulated more slowly in the fiber-reinforced sand than in the unreinforced sand, and the curves of pore water pressure at low cyclic stress ratio (0.195, 0.203, and 0.230) exhibit three stages, namely a rapidly increasing stage, a slowly increasing stage and a sharply increasing stage. The curves of pore water pressure at high cyclic stress ratio (0.258 and 0.282) exhibited a more varied pattern than those at a low cyclic stress ratio. Based on the test results, a three-parameter pore water pressure model was established considering the effect of cyclic stress ratio, fiber content, fiber length, and sand particle diameter. The predictions agreed relatively well with experimental results, demonstrating that the model can be used to predict pore water pressure in fiber-reinforced sands.

Sequence variation in enhancers that control cell-type-specific gene transcription contributes significantly to phenotypic variation within human populations. However, it remains difficult to predict precisely the effect of any given sequence variant on enhancer function due to the complexity of DNA sequence motifs that determine transcription factor (TF) binding to enhancers in their native genomic context. Using Fsub1/sub-hybrid cells derived from crosses between distantly related inbred strains of mice, we identified thousands of enhancers with allele-specific TF binding and/or activity. We find that genetic variants located within the central region of enhancers are most likely to alter TF binding and enhancer activity. We observe that the AP-1 family of TFs (Fos/Jun) are frequently required for binding of TEAD TFs and for enhancer function. However, many sequence variants outside of core motifs for AP-1 and TEAD also impact enhancer function, including sequences flanking core TF motifs and AP-1 half sites. Taken together, these data represent one of the most comprehensive assessments of allele-specific TF binding and enhancer function to date and reveal how sequence changes at enhancers alter their function across evolutionary timescales.There are hundreds of different types of cells in the body. Each one performs a unique role, but they all share the same genes. Sequences of the genetic code called enhancers decide which genes each cell uses. Enhancers work like genetic switches: to turn a gene on, proteins called transcription factors assemble on an enhancer. Each transcription factor recognises a short sequence on the enhancer, and several distinct transcription factors work together to promote the activatation of a gene. The relationship between transcription factors, enhancers, and gene activation is complex. The specific genetic sequences of enhancers differ between species, changing the way these genetic switches work. But scientists are not yet able to reliably predict the effects of small changes in the DNA sequence of an enhancer. One way to tackle this problem is to look at different versions of the same enhancers side by side to see how small mutations change their behaviour. Mammalian cells generally carry two copies of each chromosome (the molecules that contain the genetic code), one inherited from each parent. Each of the two copies carries the same genes and enhancers, but there are many small differences in the DNA sequences of enhancers between the chromosomes inherited from each parent, which can potentially alter their function Yang, Ling et al. generated cells from mice that come from different inbred strains, which are similar to purebred dogs. By breeding two distinct inbred mouse strains together that are very different from one another, they generated a panel of hybrid mouse cell lines that have a relatively large number of differences in their DNA sequence between the maternal and paternal chromosomes. Looking at the different versions of each enhancer side-by-side revealed thousands of single letter changes in the DNA sequence of enhancers that changed how they work. Mutations affecting the binding site of one transcription factor within an enhancer can indirectly affect the binding of other types of transcription factors. Yang, Ling et al. found that if a transcription factor could no longer find its place on an enhancer, it stopped others from binding even if their own places had not changed. Sometimes, mutations on either side of the binding sequences also affected transcription factor binding. This suggests a more complex relationship than previously thought may exist between the DNA sequence of an enhancer and the transcription factors that bind to it. Spotting the differences caused by mutations could help further the efforts of scientists to read and write the genetic code. This could have many benefits. It would allow scientists to control natural or artificial genes, and to predict the effects of genetic changes that are identified in humans with genetic diseases. This might improve genetic experiments, medical screening, gene therapy, and our understanding of evolution.

The crosstalk between Toll-like receptor 4 (TLR-4) and lipopolysaccharide (LPS) accounts for liver fibrosis progression. This study aimed to investigate the predictive performance of altered genes induced by TLR-4 and LPS challenge for advanced liver fibrosis.The overlapping differentially expressed genes (DEGs) of TLR-4 and LPS challenge models from the Gene Expression Omnibus (GEO) database were screened and included in the random forest analysis to identify potential candidates for predicting advanced liver fibrosis in the GSE84044 dataset. The roles of the identified candidates in liver injury development and activation of hepatic stellate cells (HSCs) were also addressed.Among the overlapping DEGs in the GSE30485, GSE33446 and GSE166488 datasets, vimentin (VIM) was the most important gene for predicting advanced liver fibrosis (S ≥ 2) by the random forest model. In the GSE84044 dataset, VIM was positively correlated with liver fibrosis (r = 0.68, 95% CI = 0.57-0.76, p0.0001), and accurately predicted advanced liver fibrosis (AUC = 0.85, 95% CI = 0.78-0.91), both in males (AUC = 0.84, 95% CI = 0.76-0.92) and females (AUC = 0.87, 95% CI = 0.76-0.99). VIM was significantly upregulated in various liver diseases (cirrhosis, liver failure, chronic hepatitis B and fatty liver disease) and liver injury models (ANIT, BDL, CCl4 and DMN). Additionally, VIM was correlated with HSC regulators (TGFβ, PDGF, CTGF and BMP7) and overexpressed in activated HSCs (p0.05). Enrichment analysis indicated that VIM-induced gene alterations were involved in the cytosolic DNA-sensing pathway, Toll-like receptor signaling pathway, etc. CONCLUSIONS: VIM could predict advanced liver fibrosis in CHB patients and is mainly involved in the activation of HSCs and profibrotic signaling pathways.

We use approximately 1800 X-ray active galactic nuclei (AGN) in the eROSITA Final Equatorial-Depth Survey (eFEDS) that span over two orders of magnitude in X-ray luminosity, LX, 2−10 keV ≈ 1043−45 erg s−1, and compare their star-formation rate (SFR) to that of non-AGN star-forming systems, at 0.5 1044.2 erg s−1, the SFR of AGN appears enhanced by ∼30% compared to that of star-forming sources, for systems with stellar mass in the range of 10.5 11.5, present a flat SFRnorm–LX relation up to LX, 2−10 keV ∼ 1044.5 erg s−1, with SFR similar to that of star-forming galaxies. However, at higher LX (LX, 2−10 keV ∼ 1045 erg s−1), we find indications that the SFR of these massive AGN hosts may be enhanced compared to that of non-AGN systems., G.M. acknowledges support by the Agencia Estatal de Investigación, Unidad de Excelencia María de Maeztu, ref. MDM-2017-0765. The project has received funding from Excellence Initiative of Aix-Marseille University – AMIDEX, a French ‘Investissements d’Avenir’ programme. M.B. gratefully acknowledges support by the ANID BASAL project FB210003. K.M. is supported by the Polish National Science Centre grant UMO-2018/30/E/ST9/00082.

OBJECTIVE: To investigate the protective effect of fucoxanthin (FX) against diabetic cardiomyopathy and explore the underlying mechanism. METHODS: Rat models of diabetes mellitus (DM) induced by intraperitoneal injection of streptozotocin (60 mg/kg) were randomized into DM model group, fucoxanthin treatment (DM+FX) group and metformin treatment (DM+ Met) group, and normal rats with normal feeding served as the control group. In the two treatment groups, fucoxanthin and metformin were administered after modeling by gavage at the daily dose of 200 mg/kg and 230 mg/kg, respectively for 12 weeks, and the rats in the DM model group were given saline only. HE staining was used to examine the area of cardiac myocyte hypertrophy in each group. The expression levels of fibrotic proteins TGF-β1 and FN proteins in rat hearts were detected with Western blotting. In the cell experiment, the effect of 1 μmol/L FX on H9C2 cell hypertrophy induced by exposure to high glucose (HG, 45 mmol/L) was evaluated using FITC-labeled phalloidin. The mRNA expression levels of the hypertrophic factors ANP, BNP and β-MHC in H9C2 cells were detected using qRT-PCR. The protein expressions of Nrf2, Keap1, HO-1 and SOD1 proteins in rat heart tissues and H9C2 cells were determined using Western blotting. The DCFH-DA probe was used to detect the intracellular production of reactive oxygen species (ROS). RESULTS: In the diabetic rats, fucoxanthin treatment obviously alleviated cardiomyocyte hypertrophy and myocardial fibrosis, increased the protein expressions of Nrf2 and HO-1, and decreased the protein expressions of Keap1 in the heart tissue (P < 0.05). In H9C2 cells with HG exposure, fucoxanthin significantly inhibited the enlargement of cell surface area, lowered the mRNA expression levels of ANP, BNP and β-MHC (P < 0.05), promoted Nrf2 translocation from the cytoplasm to the nucleus, and up-regulated the protein expressions its downstream targets SOD1 and HO-1 (P < 0.05) to enhance cellular antioxidant capacity and reduce intracellular ROS production. CONCLUSION: Fucoxanthin possesses strong inhibitory activities against diabetic cardiomyocyte hypertrophy and myocardial fibrosis and is capable of up-regulating Nrf2 signaling to promote the expression of its downstream antioxidant proteins SOD1 and HO-1 to reduce the level of ROS.

The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children. This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results. Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = − 3.51 nmol/L; 95% confidence interval (CI): − 5.60 to − 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of − 4.35 nmol/L (95% CI: − 6.64 to − 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%). This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.

Immune checkpoint molecule PD-1, expressed on the cell surface, impairs antigen-driven activation of T cells and thus plays a critical role in tumorigenesis, progression, and the poor prognosis of oral squamous cell carcinoma (OSCC). In addition, increasing evidence indicates that PD-1 carried on small extracellular vesicles (sEVs) also mediates tumor immunity, although their contributions to OSCC are yet unclear. Here, we investigated the biological functions of sEV PD-1 in patients with OSCC. The cell cycle, proliferation, apoptosis, migration, and invasion of CAL27 cell lines treated with or without sEV PD-1 were examined in vitro. We performed mass spectrometry to investigate the underlying biological process, combined with an immunohistochemical study of SCC7-bearing mice models and OSCC patient samples. In vitro data demonstrated that sEV PD-1 induced senescence and subsequent epithelial-mesenchymal transition (EMT) in CAL27 cells by ligating with tumor cell surface PD-L1 and activating the p38 mitogen-activated protein kinase (MAPK) pathway. Comprehensive immunohistochemical analysis of the xenograft mice models and OSCC patient samples revealed a very close correlation between the level of circulating sEV PD-1 and lymph node metastasis. These results demonstrate that circulating sEV PD-1 triggers senescence-initiated EMT in a PD-L1-p38 MAPK-dependent manner, contributing to tumor metastasis. It also suggests that the inhibition of sEV PD-1 may be a promising therapeutic target for the treatment of OSCC.

Redis cluster is the key component to realize device access. In order to improve the access efficiency of Redis cluster, this paper proposes a Redis cluster method with Sentinel mechanism. The core idea of this method is to add sentries to the Redis cluster and use them to monitor the operation of the Redis cluster. When the Redis cluster fails, the sentinel can realize the fault detection and fault recovery of the Redis cluster, so that the Redis cluster can operate normally. The experiment verifies the effectiveness of this method.

Neuronal activity-dependent gene expression is essential for brain development. Although transcriptional and epigenetic effects of neuronal activity have been explored in mice, such an investigation is lacking in humans. Because alterations in GABAergic neuronal circuits are implicated in neurological disorders, we conducted a comprehensive activity-dependent transcriptional and epigenetic profiling of human induced pluripotent stem cell-derived GABAergic neurons similar to those of the early developing striatum. We identified genes whose expression is inducible after membrane depolarization, some of which have specifically evolved in primates and/or are associated with neurological diseases, including schizophrenia and autism spectrum disorder (ASD). We define the genome-wide profile of human neuronal activity-dependent enhancers, promoters and the transcription factors CREB and CRTC1. We found significant heritability enrichment for ASD in the inducible promoters. Our results suggest that sequence variation within activity-inducible promoters of developing human forebrain GABAergic neurons contributes to ASD risk. Boulting et al. profile activity-dependent gene expression and regulatory elements in human induced pluripotent stem cell-derived GABAergic neurons and uncover a possible role for calcium-responsive gene promoters of these neurons in autism risk.

Mitochondrial DNA (mtDNA) damage is a very important molecular event, which has significant effects on living organisms. Therefore, a particularly important challenge for biomaterials research is to develop functionalized nanoparticles that can activate and monitor mtDNA damage and instigate cancer cell apoptosis, and as such eliminate the negative effects on living organisms. Toward that goal, with this research, we have developed a hydroxyapatite ultrathin nanosheet (HAP-PDCns) - a high Ca2+ content biomaterial. HAP-PDCns undergoes proton-triggered decomposition after entering cancer cells via clathrin-mediated endocytosis, and then, it selectively concentrates in the charged mitochondrial membrane. This kind of proton-triggered decomposition phenomenon facilitates mtDNA damage by causing instantaneous local calcium overload in the mitochondria of cancer cells, and inhibits tumor growth. Importantly, at the same time, a real-time green-red-green fluorescence change occurs that correlates with the degree of mtDNA deterioration because of the changes in the highest occupied molecular orbital-lowest unoccupied molecular orbital energy gaps during this process. Significantly, the decomposition and the fluorescence changes cannot be triggered in normal cells. Thus, HAP-PDCns can selectively induce apoptosis and the death of a cancer cell by facilitating mtDNA damage, but does not affect normal cells. In addition, HAP-PDCns can simultaneously monitor the degree of mtDNA damage. We anticipate that this design strategy can be generalized to develop other functionalized biomaterials that can be used to instigate the positive effects of mtDNA damage on living organisms while eliminating any negative effects.

The long non-coding RNA (lncRNA) RUSC1-AS1 has been reported to be dysregulated in the progression of many cancers. Also, RUSC1-AS1 had been detected to be highly expressed in laryngeal squamous cell carcinoma and breast cancer cells, suggesting that RUSC1-AS1 may be a biomarker for cancers. However, the biological role and regulatory mechanism of RUSC1-AS1 in hepatocellular carcinoma (HCC) remain unknown. In this study, we found that RUSC1-AS1 was upregulated in HCC tissues and cells, and predicted unfavorable prognosis of HCC patients. The function assays including colony formation, EdU, TUNEL assay revealed that RUSC1-AS1 facilitated HCC cell proliferation and inhibited HCC cell apoptosis. Furthermore, mechanism assays including luciferase reporter assay and RIP assay demonstrated that RUSC1-AS1 could directly bind to hsa-miR-7-5p. Besides, hsa-miR-7-5p targeted and negatively regulated NOTCH3 expression. Moreover, RUSC1-AS1 sponged hsa-miR-7-5p to upregulate NOTCH3 and to trigger the NOTCH signaling pathway. The rescue assays depicted that RUSC1-AS1 regulated HCC cell proliferation and apoptosis through modulating NOTCH signaling. In conclusion, lncRNA RUSC1-AS1 promoted the proliferation and reduced the apoptosis of HCC cells through activation of NOTCH signaling via hsa-miR-7-5p/NOTCH3 axis.

Adenine containing phthalonitrile (ADCN)/graphene/Fe3O4 composites with excellent EMI performance, outstanding thermal, thermo-oxidative stability, and heat resistance ae introduced. The interactions between ADCN and nanofillers combined with high-energy ball milling-molding sintering processing method ensure the uniform dispersion of nanofillers in the matrix. The EMI shielding effectiveness (EMI SE) of ADCN/G/Fe3O4 is up to 50 dB with only 0.5 mm thickness, which is one of the best EMI performance compared with previous reports on conductive polymer composites (CPCs). The high-performance ADCN polymer introduces outstanding thermal, thermo-oxidative stability and heat resistance into the composites. The T5% in the air of composites could still maintain more than 491 °C, and the EMI value of composites after flame retardancy test could reach 40 dB. The results prove that ADCN/G/Fe3O4 composite is a promising candidate that could be used in the aerospace industry and under extreme working conditions.

During the curing process of thermoset composites, residual stresses inevitably develop in them and lead to their curing deformation after the manufacturing process. This work was aimed at investigating the effect of tool–part interaction and bending stiffness on the curing deformation of L-shaped composite structures. Therefore, a twostep calculation model was developed. It consists of a numerical model to capture the residual stress due to the tool–part interaction and a viscoelastic model considering the anisotropic material properties. Calculation results were compared with experimental data, and a good agreement was found to exist between them.

We study manufacturing firms' asymmetric inventory investment in response to sales changes. Focusing on the costs of resource adjustment and stockout that likely differ in sales‐increasing and sales‐decreasing periods, we predict and find that inventory investment declines less during periods with sales decreases than it rises during periods with sales increases. We validate this claim by showing that managers' expectations of future demand and desire to avoid inventory stockouts are important determinants of this asymmetry. In addition, we find that asymmetric inventory investment provides useful information for predicting future sales growth, and that both managers' and analysts' sales forecasts are positively associated with the asymmetry. Lastly, we document that forecasts of future sales growth that incorporate asymmetric inventory investment are associated with lower absolute forecast errors than benchmark forecasts. Overall, we highlight the importance of inventory information in understanding managers' resource adjustment and utilization decisions that have implications for forecasting future demand. Our findings on asymmetric inventory management provide new insights to fundamental analysis based on inventory signals. Gestion asymetrique des stocks et orientation de la fluctuation des ventes Les auteurs etudient l'investissement asymetrique des entreprises de fabrication dans les stocks en reaction a la fluctuation des ventes. En se penchant plus particulierement sur les couts de l'ajustement des ressources de production et de la rupture des stocks, couts susceptibles de differer en periode de croissance et de decroissance des ventes, les auteurs formulent et confirment l'hypothese selon laquelle l'investissement dans les stocks decline moins durant les periodes de decroissance des ventes qu'il n'augmente durant les periodes de croissance des ventes. Ils valident cette observation en demontrant que les attentes des gestionnaires quant a la demande future et leur desir d’eviter les ruptures de stock sont d'importants determinants de cette asymetrie. Ils constatent egalement que l'investissement asymetrique dans les stocks fournit de l'information utile a la prediction de la croissance future des ventes et que les previsions de ventes, tant celles des gestionnaires que celles des analystes, ont un lien positif avec l'asymetrie. Enfin, les donnees recueillies par les auteurs confirment que les previsions de croissance future des ventes qui incorporent l'investissement asymetrique des entreprises dans les stocks sont associees a des erreurs previsionnelles moins grandes en valeur absolue que les previsions reposant sur des elements de reference. Dans l'ensemble, l’etude met en relief l'importance de l'information relative aux stocks dans la comprehension des decisions d'ajustement et d'utilisation des ressources que prennent les gestionnaires et qui influent sur la prevision de la demande future. L'information livree sur la gestion asymetrique des stocks ouvre de nouvelles perspectives a l'analyse fondamentale basee sur les indicateurs relatifs aux stocks.