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Abstract Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.

Liver fibrosis, a common characteristic in various chronic liver diseases, is largely influenced by glycolysis. Quercetin (QE), a natural flavonoid known to regulate glycolysis, was studied for its effects on liver fibrosis and its underlying mechanism. Results showed that QE effectively improved liver injury and fibrosis caused by carbon tetrachloride (CCl4). This was supported by evidence of improved pathological features and reduced levels of serum markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), hyaluronic acid (HA), laminin (LN), and procollagen type III. QE also decreased lactate production and downregulated the expression of glycolysis-related enzymes – pyruvate kinase M2 (PKM2), phosphofructokinase platelet (PFKP), and hexokinase 2 (HK2) – at both the mRNA and protein levels. In liver sinusoidal endothelial cells (LSECs), QE reduced the expression and activity of these enzymes, resulting in reduced glucose consumption, ATP production, and lactate generation. Further analysis revealed that QE inhibited the production of chemokine (C-X-C motif) ligand 1 (CXCL1) and suppressed neutrophil recruitment. Overall, QE showed promising therapeutic potential for liver fibrosis by targeting LSEC glycolysis and reducing neutrophil infiltration.

Abstract Background Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that affects infants and young children but is extremely rare in neonates, especially afebrile KD. We present a case of KD without fever in a neonate and review the literature on KD in neonates. Case presentation A newborn female was hospitalized because her peripheral blood leukocytes increased for half a day. The admission diagnosis was considered neonatal sepsis and bacterial meningitis. She had no fever since the admission, but a rash appeared on her face by the 7th day. On day 11 after admission, there was a desquamation on the distal extremities. On day 15 after admission, ultrasound showed non-suppurative cervical lymphadenopathy. Echocardiogram revealed coronary artery aneurysms in both sides. Finally, the patient was diagnosed with incomplete KD (IKD). The follow-up echocardiogram showed that the internal diameter of both coronary arteries returned to normal three months after birth. Conclusions Fever, rash, and distal extremity desquamation during the recovery phase are the most common symptoms of IKD. When newborns present with clinical manifestations such as rash, distal extremity desquamation and cervical lymph adenitis and with an increased peripheral blood leukocyte count and progressive increase in platelets simultaneously, the medical staff should be highly alert to the possibility of KD even without fever. The echocardiogram needs to be performed promptly. The incidence of coronary artery lesions is significantly higher if neonatal KD patients miss timely diagnosis and treatment.

To enhance the resistance of SiCf/SiC to hydrothermal corrosion in the pressurized water reactor (PWR) environment, structurally tunable Ti3SiC2-based corrosion mitigation coatings for SiCf/SiC were prepared using molten salt synthesis. The influence of various process parameters, such as Si/Ti molar ratio in raw materials, annealing time, and annealing temperature, on the phase composition and the structure of the coatings was explored. Through the process control, the fabricated coatings can be either Ti3SiC2 monolithic structure or TiC/Ti3SiC2 and TiC/Ti3SiC2/Ti5Si3Cx multi-layered structures. The coatings demonstrate strong bonding to the substrate due to in-situ reaction, exhibiting tensile and shear strength of at least 26.9 and 30.8 MPa, respectively. Incorporating TiC as a transition layer further enhances the tensile and shear strength to 41.3 and 51.4 MPa, respectively. Monolithic Ti3SiC2 coatings enhance the thermal conductivity of SiCf/SiC by 10%–12%. Notably, Ti3SiC2 coatings effectively protect SiCf/SiC from hydrothermal corrosion, demonstrating an 83% strength retention rate compared to 71% in the control group after corrosion. However, the Ti5Si3Cx layer exhibits unsatisfactory corrosion mitigation. The Ti3SiC2 monolithic coating has higher thermal conductivity, TiC/Ti3SiC2 multi-layered coating has higher bonding strength, and both have desirable resistance to the hydrothermal corrosion.

In this work, the effects of carbon nanotubes (CNTs) on the microstructure evolution, thermal conductivity, and mechanical properties of Cf/SiC composites during chemical vapor infiltration (CVI) densification were investigated in detail. Compared with composites without CNTs, the thermal conductivity, flexural strength, flexural modulus, fracture toughness, interfacial shear strength, and proportional limit stress of specimens with CNTs of 4.94 wt% were improved by 117%, 21.8%, 67.4%, 10.3%, 36.4%, and 71.1%, respectively. This improvement was attributed to the role of CNTs in the division of inter-layer pores, which provided abundant vapor growth sites for the ceramic matrix and promoted densification of the whole composite. In addition, the high thermal conductivity network formed by the overlap of CNTs and the rivet strengthening effect of CNTs were beneficial for synergistic improvement of thermal conductivity and mechanical properties of the composites. Therefore, this study has practical significance for the development of thermal protection composite components with enhanced thermal conductivity and mechanical characteristics.

Abstract Background Displaced lateral malleolus fractures are typically stabilised through open reduction and internal fixation. The biomechanically and clinically efficacy of locking plates and lag screws, particularly in Weber A and B distal fibular fractures remains a subject of contention. This study examines two locking plate designs for lateral malleolus fractures, evaluating their performance with and without interfragmentary screws using finite element models. Methods Utilising CT images of a healthy adult male volunteer, a three-dimensional finite element model was constructed. The Fibula-specific Flank Multiaxial Locking Anatomic Plate (FMLP) and the Conventional Locking Plate (CLP) were subjected to stabilisation, both with and without an interfragmentary screw, mimicking the Danis-Weber A and B lateral malleolus oblique fracture fixation. Loads of 140 N and 70 N, equivalent to 20% of the body weight, were applied to simulate the single-leg and two-leg standing conditions in the axial direction. The von Mises stress (VMS) distributions and element displacements were subsequently analyzed. Results In the Danis-Weber A fracture model group, the FMLP with an interfragmentary screw fixation exhibited the lowest peak VMS values: 51.9 MPa in the fibula, 89.0 MPa in the plate, and 61.3 MPa in the screws for simulating single-leg conditions. Under two-leg standing conditions, these peak VMS values decreased to 25.9 MPa in the fibula, 44.5 MPa in the plate, and 30.6 MPa in the screws, respectively. Furthermore, the overall structural peak displacements during single-leg standing for both Weber-A and B fractures with different implants ranged from 1.61 to 2.54 mm. While standing on two feet, the ranged was from 0.80 to 1.27 mm. An interfragmentary screw at the oblique fracture site resulted in reduced the peak value of VMS in the fibula, plate, screws, consequently decreased the overall structural displacement for FMLP and CLP fixation in lateral malleolus fractures. Conclusions The current finite element analysis (FEA) demonstrates that FMLP exhibits superior mechanical characteristics in Danis-Weber A and B lateral malleolus fractures compared to CLP. The inclusion of an interfragmentary screw, combined with locking plate design, enhances stability for simple oblique distal fibular fractures. The FMLP presents itself as potential as an alternative for lateral malleolus fractures from a biomechanical perspective. Nevertheless, further verification of these results is imperative through subsequent clinical studies.

ObjectiveThis study aims to explore the association between outdoor artificial light at night (ALAN) exposure and gestational diabetes mellitus (GDM).MethodsThis study is a retrospective case–control study. According with quantiles, ALAN has been classified into three categories (Q1-Q3). GDM was diagnosed through oral glucose tolerance tests. Conditional logistic regression models were used to evaluate the association between ALAN exposure and GDM risk. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Restricted cubic spline analysis (RCS) was utilized to investigate the no liner association between ALAN and GDM.ResultsA total of 5,720 participants were included, comprising 1,430 individuals with GDM and 4,290 matched controls. Pregnant women exposed to higher levels of ALAN during the first trimester exhibited an elevated risk of GDM compared to those with lower exposure levels (Q2 OR = 1.39, 95% CI 1.20–1.63, p

Summary: The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers.

BackgroundAnxiety and depression are prevalent mental disorders. As modern society continues to face mounting pressures, the incidence of anxiety and depression is on the rise. In recent years, there has been an increasing breadth of research exploring the relationship between anxiety, depression, and physical activity (PA). However, the current research progress and future development trends are unclear. The purpose of this study is to explore the research hotspots and development trends in this field, and to provide guidance for future studies and to provide some reference for clinicians.MethodsWe searched the relevant literature of Web of Science Core Collection from the establishment of the database to August 15, 2023. CiteSpace, VOSviewer and Bibliometrix Packages based on the R language were used to analyze the number of publications, countries, institutions, journals, authors, references, and keywords.ResultsA total of 1,591 studies were included in the analysis, and the research in the field of PA on anxiety or depression has consistently expanded. The USA (304 publications), Harvard University (93 publications), and the journal of affective disorders (97 publications) were the countries, institutions, and journals that published the highest number of articles, respectively. According to the keywords, students and pregnant women, adult neurogenesis, and Tai Chi were the groups of concern, physiological and pathological mechanisms, and the type of PA of interest, respectively.ConclusionThe study of PA on anxiety or depression is experiencing ongoing expansion. Clinicians can consider advising patients to take mind–body exercise to improve mood. In addition, future researchers can explore the mind–body exercise and its impact on anxiety or depression, PA and anxiety or depression in specific populations, and adult neurogenesis of various exercise in anxiety or depression.

Abstract Hydroxycarboxylic acid receptor 2 (HCAR2) belongs to the family of class A G protein-coupled receptors with key roles in regulating lipolysis and free fatty acid formation in humans. It is deeply involved in many pathophysiological processes and serves as an attractive target for the treatment of cardiovascular, neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases. Here, we report four cryo-EM structures of human HCAR2–Gi1 complexes with or without agonists, including the drugs niacin (2.69 Å) and acipimox (3.23 Å), the highly subtype-specific agonist MK-6892 (3.25 Å), and apo form (3.28 Å). Combined with molecular dynamics simulation and functional analysis, we have revealed the recognition mechanism of HCAR2 for different agonists and summarized the general pharmacophore features of HCAR2 agonists, which are based on three key residues R1113.36, S17945.52, and Y2847.43. Notably, the MK-6892–HCAR2 structure shows an extended binding pocket relative to other agonist-bound HCAR2 complexes. In addition, the key residues that determine the ligand selectivity between the HCAR2 and HCAR3 are also illuminated. Our findings provide structural insights into the ligand recognition, selectivity, activation, and G protein coupling mechanism of HCAR2, which shed light on the design of new HCAR2-targeting drugs for greater efficacy, higher selectivity, and fewer or no side effects.

As one of the most advanced film forming technologies, the surface-initiated controlled/living radical polymerization provides an effective method for in-situ fabricating functional films on material surface. In this paper, the triazole film of polymerized (1-tosyl-1H-1,2,3-triazol-4-yl) methyl acrylate (P-TTMA) is in-situ prepared on copper surface via Cu catalyzed surface-initiated atom transfer radical polymerization (SI-ATRP) method. The P-TTMA film with different degree of polymerization (DP) is obtained by varying its molecular weight, which is achieved via regulating the polymerization time of SI-ATRP reaction. When the polymerization time is within 48 h, the SI-ATRP system can achieve a regular chain growth of P-TTMA film, the DP value of P-TTMA film shows an S-shaped variation as the polymerization time increasing. The electrochemical test is performed to evaluate the anticorrosion performance of different P-TTMA films for copper. The result demonstrates that the P-TTMA films exhibit good anticorrosion performance for Cu in 3.5 wt% NaCl solution. The P-TTMA obtained by 48 h polymerization time, with the DP value of 105, exhibits the stable and good protection performance. The anticorrosion performance of P-TTMA film can be optimized via regulating the SI-ATRP reaction. This paper provides a new idea for preparing inhibition film with a certain degree of polymerization and protection performance on metal surface. It is expected to be a theoretical guidance for fabricating triazole polymer film using ATRP with lower catalyst loading or metal-free ATRP in the coming future.

Aiming at the problem of the difficult segmentation of adherent images due to the not fully convex shape of peanut pods, their complex surface texture, and their diverse structures, a multimodal fusion algorithm is proposed to achieve a 2D segmentation of adherent peanut images with the assistance of 3D point clouds. Firstly, the point cloud of a running peanut is captured line by line using a line structured light imaging system, and its three-dimensional shape is obtained through splicing and combining it with a local surface-fitting algorithm to calculate a normal vector and curvature. Seed points are selected based on the principle of minimum curvature, and neighboring points are searched using the KD-Tree algorithm. The point cloud is filtered and segmented according to the normal angle and the curvature threshold until achieving the completion of the point cloud segmentation of the individual peanut, and then the two-dimensional contour of the individual peanut model is extracted by using the rolling method. The search template is established, multiscale feature matching is implemented on the adherent image to achieve the region localization, and finally, the segmentation region is optimized by an opening operation. The experimental results show that the algorithm improves the segmentation accuracy, and the segmentation accuracy reaches 96.8%.

Abstract Recent advancements in single‐cell technologies have led to rapid developments in the construction of cell atlases. These atlases have the potential to provide detailed information about every cell type in different organisms, enabling the characterization of cellular diversity at the single‐cell level. Global efforts in developing comprehensive cell atlases have profound implications for both basic research and clinical applications. This review provides a broad overview of the cellular diversity and dynamics across various biological systems. In addition, the incorporation of machine learning techniques into cell atlas analyses opens up exciting prospects for the field of integrative biology.

BackgroundThis study aimed to investigate the association between outdoor artificial light at night (ALAN) exposure during pregnancy and the risk of preterm birth (PTB).MethodsA retrospective case–control study was conducted, and data were collected from pregnant women residing in Beijing, China. The level of ALAN exposure during pregnancy was estimated using remote sensing satellite data. Propensity score matching was utilized to match the control group. Logistic and multivariate linear regression were used to analyze the association between ALAN and the risk of PTB. The odds ratio (OR) and partial regression coefficient (β) with 95% confidence interval (CI) were utilized to assess the association.ResultsA total of 2,850 pregnant women were enrolled in this study. ALAN (nW/cm2/sr) exposure was higher in the PTB group than in the control group during first trimester (mean ± standard deviation: 25.30 ± 17.91 vs. 17.56 ± 14.74, p

The thermos-structural materials with high strength and high temperature water-oxygen corrosion resistance are urgently needed in aero-space fields. SiC whisker reinforced SiC matrix (SiCw/SiC) composites are the ideal candidate materials for their excellent mechanical properties and thermostability. However, the poor resistance to water-oxygen corrosion ability of SiC matrix limits their further application. In this work, a novel SiCw/SiC–Si–Y composites were first prepared by infiltrating silicon-yttrium (Si–Y) alloy into SiCw/C preform via reactive melt infiltration method. The as-obtained composites not only show the excellent mechanical properties (σF = 363 MPa, KⅠC = 9.14 MPa m1/2), and more importantly after water-oxygen corrosion of 20 h at such temperature as high as 1500 °C, the strength and toughness retention of the composites can reach 106.1% and 103.6%, respectively. The SiCw/SiC–Si–Y composites developed in this paper have a great potential as a new high-performance thermos-structural material for aero-space applications.

Abstract Background This study aimed to examine the prevalence and clinical findings of the vacuum phenomenon (VP) in closed pelvic fractures. Methods We retrospectively reviewed 352 patients with closed pelvic fractures who presented to our institution from January 2017 to December 2020. Pelvic fractures were diagnosed by plain radiography and computed tomography (CT). The default “bone window” was used for inspection in the cross section. Electronic medical records were consulted by two orthopedic physicians to obtain patient information. The VP of pelvic fracture, fracture classification, injury mechanism, and image data were evaluated, and the demographic parameter data were statistically analyzed. The follow-up time was 12–18 months. Results Among them, 169 were males and 183 were females with ages ranging from 3 to 100 years, with an average of 49.6 ± 19.3 years. VP in pelvic fractures was detected by CT in 109 (31%) of the 352 patients with pelvic fractures. Patients were divided into the high-energy trauma group (278 cases) and fragility fractures of the pelvis (FFP) group (74 cases) according to the injury mechanism. In the high-energy trauma group, 227 cases were treated surgically and 201 cases had bony healing. The healing time was 9.8 ± 5.3 weeks. In the FFP group, 54 cases were treated surgically and 49 cases had bone healing. The healing time was 9.3 ± 3.8 weeks. Fractures progressed in nine patients. VP was mostly located in the sacroiliac joint in our study. Conclusions The incidence of VP in pelvic fractures is statistically high and is affected by many factors, such as examination technique, joint position, population composition, etc. Therefore, the VP is not a reliable sign of pelvic injury. Clinically, we need to determine the nature of VP in conjunction with gas patterns, laboratory tests, history, and physical examination.

An ultralight and high-strength Silicon nitride (Si3N4) foam ceramic with highly efficient wave-transparent and heat insulation properties was successfully prepared using the organic foam impregnation technique combined with chemical vapor infiltration (CVI) process. The microstructure of Si3N4 foam ceramic inherits the pore structure characteristics of the template, and the ceramic skeleton is formed by coupling the Si3N4 whiskers with the CVI Si3N4 matrix. The use of CVI process avoids the volume shrinkage problem during the ceramic formation process by traditional sintering method at high temperature, and ensures the near-net-shape preparation of ceramic. Meanwhile, CVI Si3N4 matrix has pure components without impurities like low melting point metal oxides by sintering method or free carbon by polymer-derived ceramic method, which is beneficial to the improvement of wave-transparent ability and thermal stability. The addition of whisker reinforcement greatly increases the compressive strength of ceramic through whisker pulling out, crack deflection and other strengthening and toughening mechanisms. Moreover, we discuss in detail the relationship between the structural parameters of Si3N4 foam ceramic, such as whiskers-matrix solid content ratio, open-closed porosity ratio, pore size and mechanical, wave-transparent as well as heat insulation properties. In this study, the compressive strength of 40PPI Si3N4 foam ceramic with total porosity of 91.97% is 1.06 MPa, the thermal conductivity is only 0.624 W/(m·K) at 25 °C and the dielectric constant and loss tangent are 1.40 (10 GHz) and 6.35 × 10−3 (10 GHz), respectively.

The fabrication of silicon nitride (Si3N4) fiber-reinforced boron nitride (BN) and Si3N4 matrix (Si3N4f/BN/Si3N4) composites with BN interphase through precursor infiltration and pyrolysis (PIP) process is reported. The effects of heating rate during PIP process on mechanical and dielectric properties of composites are analyzed. When the heating rate is 5 °C/min, the overall performance of Si3N4f/BN/Si3N4 composites is optimal, and the flexural strength and fracture toughness attain 138 MPa and 5.7 MPa m1/2, and the dielectric constant and dielectric loss are 3.90 and 0.008, respectively. The composites achieve a synergy combining structural with functional properties. The influence mechanism of the heating rate during PIP process on the Si3N4f/BN/Si3N4 composites disclose the following. First, the heating rate makes an effect on the carbon content in the Si3N4 matrix, and consequently the dielectric properties of the composites are changed. Second, at 8 °C/min, the modulus of Si3N4 matrix is the lowest due to the existence of nanopores. At 2 °C/min, the strong axial tensile stress results in severe cracking of the Si3N4 matrix, so the matrix modulus decrease. Third, the heating rate strongly affects the radial stress state at the interphase, which affects the interfacial shear strength of the composites. The matrix modulus and interfacial shear strength can be optimized at 5 °C/min to improve the mechanical properties of the composites.

BackgroundAmnestic mild cognitive impairment (aMCI) is a pre-dementia condition associated with declined cognitive function dominated by memory impairment. The occurrence of aMCI is associated with the gut-brain axis. Previous studies have shown cognitive improvements in MCI after acupuncture treatment. This study evaluates whether acupuncture can produce a therapeutic effect in patients with aMCI by modulating the gut-brain axis.Methods and designThis is a prospective, parallel, multicenter randomized controlled trial. A total of 40 patients with aMCI will be randomly assigned to an acupuncture group (AG) or a waiting-list group (WG), participants in both groups will receive health education on improving cognitive function at each visit, and acupuncture will be conducted twice a week for 12 weeks in the AG. Another 20 matched healthy volunteers will be enrolled as normal control. The primary outcome will be the change in Alzheimer’s Disease Assessment Scale-cognitive scale score before and after treatment. Additionally, functional magnetic resonance imaging data, faeces, and blood will be collected from each participant to characterize the brain function, gut microbiota, and inflammatory cytokines, respectively. The differences between patients with aMCI and healthy participants, and the changes in the AG and WG groups before and after treatment will be observed. Ultimately, the correlation among brain function, gut microbiota, inflammatory cytokines, and clinical efficacy evaluation in patients with aMCI will be analyzed.DiscussionThis study will identify the efficacy and provide preliminary data on the possible mechanism of acupuncture in treating aMCI. Furthermore, it will also identify biomarkers of the gut microbiota, inflammatory cytokines, and brain function correlated with therapeutic effects. The results of this study will be published in peer-reviewed journals.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2200062084.

Abstract Three strategies were proposed to prolong the service life of continuous fiber-reinforced silicon carbide ceramic matrix composite (CMC-SiC), which served as thermal-structure components of aeroengine at thermo-mechanical-oxygenic coupling environment. As for some thermal-structure components with low working stress, improving the degree of densification was crucial to prolong the service life, and the related process approaches were recited. If the thermal-structure components worked under moderate stress, the matrix cracking stress (σ mc) should be improved as far as possible. The fiber preform architecture, interface shear strength, residual thermal stress, and matrix strengthening were associated with σ mc in this review. Introducing self-healing components was quite significant with the appearance of matrix microcracks when CMC-SiC worked at more severe environment for hundreds of hours. The damage can be sealed by glass phase originating from the reaction between self-healing components and oxygen. The effective self-healing temperature range of different self-healing components was first summarized and distinguished. The structure, composition, and preparation process of CMC-SiC should be systematically designed and optimized to achieve long duration target.

The Mexican axolotl is a well-established tetrapod model for regeneration and development. Here the authors report a scRNA-seq method to profile neotenic, metamorphic and limb development stages, highlighting unique perturbation patterns of cell type-related gene expression throughout metamorphosis.

In order to promote the virtuous cycle of development and protection of marine ecological resources in China, and guarantee the sustainable supply of marine ecological products, this paper analyzed the evolution of marine ecological product value implementation logic based on the definition and characteristics of marine ecological products, combined with the typical model to explore marine ecological product value realization and marine products in China, put forward the value realization of mechanism design. The results showed that the marine ecological products were direct or indirect tangible and intangible products provided by marine ecosystem, to meet people′s growing needs of beautiful marine ecological environment, and had the characteristics of overall externality, non-exclusivity, non-competition and irreversibility. The evolutionary logic of realizing the value of marine ecological products could be divided into 4 stages: marine ecological resources capitalization of marine ecological assets productization of marine ecological capital and monetization of marine ecological products. The value of public and quasi-public marine ecological products corresponded to the realization path of government-led market-oriented and government-market hybrid respectively. In the future, China should strengthen mechanism construction in marine ecological resource property right management, marine ecological product value accounting, marine ecological product value-added, marine ecological resource trade and marine ecological protection compensation.

Abstract Background Tumor microenvironment plays pivotal roles in carcinogenesis, cancer development and metastasis. Composition of cancer immune cell subsets can be inferred by deconvolution of gene expression profile accurately. Compositions of the cell types in cancer microenvironment including cancer infiltrating immune and stromal cells have been reported to be associated with the cancer outcomes markers for cancer prognosis. However, rare studies have been reported on their association with the response to preoperative radiotherapy for rectal cancer. Methods In this paper, we deconvoluted the immune/stromal cell composition from the gene expression profiles. We compared the composition of immune/stromal cell types in the RT responsive versus nonresponsive for rectal cancer. We also compared the peripheral blood immune cell subset composition in the stable diseases versus progressive diseases of rectal cancer patients with fluorescence-activated cell sorting from our institution. Results Compared with the non-responsive group, the responsive group showed higher proportions of CD4+ T cell (0.1378 ± 0.0368 vs. 0.1071 ± 0.0373, p = 0.0215), adipocytes, T cells CD4 memory resting, and lower proportions of CD8+ T cell (0.1798 ± 0.0217 vs. 0.2104 ± 0.0415, p = 0.0239), macrophages M2, and preadipocytes in their cancer tissue. The responsive patients showed a higher ratio of CD4+/CD8+ T cell proportions (mean 0.7869 vs. 0.5564, p = 0.0210). Consistently, the peripheral blood dataset showed higher proportion of CD4+ T cells and higher ratio of CD4+/CD8+ T cells, and lower proportion of CD8+ T cells for favorable prognosis. We validated these results with a pooled dataset of GSE3493 and GSE35452, and more peripheral blood data, respectively. Finally, we imported these eight cell features including eosinophils and macrophage M1 to Support Vector Machines and could predict the pre-radiotherapy responsive versus non-responsive with an accuracy of 76%, ROC AUC 0.77, 95% confidential interval of 0.632–0.857, better than the gene signatures. Conclusions Our results showed that the proportions of tumor-infiltrating subsets and peripheral blood immune cell subsets can be important immune cell markers and treatment targets for outcomes of radiotherapy for rectal cancer.

ObjectiveAlzheimer’s disease (AD) as the most frequent neurodegenerative disease is featured by gradual decline of cognition and social function in the elderly. However, there have been few studies focusing on AD heterogeneity which exists both genetically and clinically, leading to the difficulties of AD researches. As one major kind of clinical heterogeneity, the lifespan of AD patients varies significantly. Aiming to investigate the potential driving factors, the current research identified the differentially expressed genes (DEGs) between longer-lived AD patients and shorter-lived ones via bioinformatics analyses.MethodsQualified datasets of gene expression profiles were identified in National Center of Biotechnology Information Gene Expression Omnibus (NCBI-GEO). The data of the temporal lobes of patients above 60 years old were used. Two groups were divided according to the lifespan: the group ≥85 years old and the group

Aim: The aim of this review was to determine whether the caregivers of breast cancer patients who undergo psychosocial interventions report improvements in quality of life (QOL), depression, and anxiety. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. A systematic search was conducted in the CINAHL, Embase, PsycINFO, PubMed, Web of Science, CNKI and Wanfang databases from inception until March 1, 2022. Randomized controlled trials (RCTs) and quasiexperimental studies involving psychosocial interventions for caregivers of breast cancer patients were included. Cochrane's risk of bias tool and the Joanna Briggs Institute checklist were used to assess the risk of bias. Results: This systematic review included eight original studies involving 528 caregivers of breast cancer patients. According to the meta-analyses, psychosocial interventions contributed significantly to improvements in QOL (SMD = 1.00, 95% CI [0.47, 1.54], p

Abstract GPR21 belongs to class A orphan G protein‐coupled receptor (GPCR). The endogenous ligands for human GPR21 remain unidentified. GPR21 expression is associated with developing type 2 diabetes (T2DM), a multifactorial metabolic disease caused by pancreatic β‐cell dysfunction, decreasing insulin production, insulin resistance, and obesity. Animal studies suggested that GPR21 is a potential therapeutic target for T2DM treatment. The underlying mechanisms leading to GPR21 self‐activation remain unknown. In our co‐expression analysis, we noted that GPR21 could also form a stable complex with an unreported Gα protein subtype, Gαs. To gain further insights into the structural mechanisms of GPR21 activation, we employed cryo‐electron microscopy (cryo‐EM) and single‐particle analysis to resolve the high‐resolution structure of GPR21‐Gαs complexes. The clear electron density map of the GPR21‐Gαs provided direct evidence that GPR21 could couple to Gαs protein at physiological conditions. Thus, GPR21 might mediate previously unexplored pathways in normal or pathological conditions, which warrants further investigation. Structure‐guided mutagenesis and biochemical analysis revealed that extracellular loop 2 (ECL2) of GPR21 is essential for the receptor transducing intracellular signal via cAMP. Together, the new structure data reveal a novel signaling cascade of human GPR21 mediated by ECL2 and provide fundamental information for future structure‐based drug development.

Clothing textiles could protect our human skin against external factors, but the microbial population, including conditional pathogens, in clothing, would cause unpleasant odor, Skin inflammation, and textile deterioration. Several studies have reported that microbiomes on clothes are affected by skin microorganisms of individuals, the local environment and the types of textile fabrics, but little is known about how the textile microbial community is shaped in the Chinese population. In this study, 10 healthy young students were recruited to successfully wear the T-shirts made with 3 different fabrics (polyester, cotton, and blending fabrics of polyester and cotton) during physical exercise. Total deoxyribonucleic acid (DNA) was extracted from 30 T-shirts and 16s rRNA gene amplicon sequencing was applied to estimate the absolute abundances of bacteria in the samples. The main bacteria on wore T-shirts were Staphylococcus (21.66%) Enhydrobacter (13.81%), Pantoea (8.14%), Acinetobacter (7.81%), Pseudomonas (6.18%), Cutibacterium (4.99%). However, no difference of α and β diversity was observed among the three textile fabrics. Further analysis found that Pantoea and Pseudomonas, mainly from the environment, enriched on the polyester, but not on cotton, while Enhydrobacter, from human skin, has the growth advantage on cotton, and the blending fabric in between. Collectively, our study preliminary explored the clothes microbiome in Chinese young students, contributing to helping understand the role of clothing microorganisms on human health.

Abstract GPR17 is a class A orphan G protein‐coupled receptor (GPCR) expressed in neurons and oligodendrocyte progenitors of the central nervous system (CNS). The signalling of GPR17 occurs through the heterotrimeric Gi, but its activation mechanism is unclear. Here, we employed cryo‐electron microscopy (cryo‐EM) technology to elucidate the structure of activated GPR17‐Gi complex. The 3.02 Å resolution structure, together with mutagenesis studies, revealed that the extracellular loop2 of GPR17 occupied the orthosteric binding pocket to promote its self‐activation. The active GPR17 carried several typical microswitches like other class A GPCRs. Moreover, the Gi interacted with the key residues of transmembrane helix 3 (TM3), the amphipathic helix 8 (Helix8), and intracellular loops 3 (ICL3) in GPR17 to engage in the receptor core. In summary, our results highlight the activation mechanism of GPR17 from the structural basis. Elucidating the structural and activation mechanism of GPR17 may facilitate the pharmacological intervention for acute/chronic CNS injury.

Broadband seismographs are used to collect seismic data over an extended period. Temperature, pressure, and humidity are field variables that can have an impact on the broadband seismograph’s performance as well as the accuracy of observational data. Variations in performance, geological structure, and noise source will cause the cross-correlation function of seismic ambient noise to alter. To evaluate the effectiveness of seismographs, we propose to use the whole cross-correlation function as well as the positive and negative time waveforms for feature extraction. The cross-correlation function is decomposed to evaluate the phase variations using Local Mean Decomposition (LMD) and Variational Mode Decomposition (VMD). This is followed by the calculation of the Multivariate Multiscale Fuzzy Entropy Partial Mean (MMFEPM). Wavelet Packet Decomposition (WPD) and MMFEPM are used to evaluate phase variations in the positive and negative time waveforms. WPD combined with Wavelet Feature Scale Entropy (WFSE) is chosen to evaluate the amplitude variations of the cross-correlation function and its positive and negative waveforms. The results show that the proposed methods can identify time offsets within 0.025-2.5s and amplitude variations of 10−16, which provide a new direction for evaluating the performance of seismographs using ambient noise.

Abstract Oxidation behaviors of carbon fiber reinforced SiC matrix composites (C/SiC) are one of the most noteworthy properties. For C/SiC, the oxidation behavior was controlled by matrix microcracks caused by the mismatch of coefficients of thermal expansion (CTEs) and elastic modulus between carbon fiber and SiC matrix. In order to improve the oxidation resistance, multilayer SiC-Si3N4 matrices were fabricated by chemical vapor infiltration (CVI) to alleviate the above two kinds of mismatch and change the local stress distribution. For the oxidation of C/SiC with multilayer matrices, matrix microcracks would be deflected at the transition layer between different layers of multilayer SiC-Si3N4 matrix to lengthen the oxygen diffusion channels, thereby improving the oxidation resistance of C/SiC, especially at 800 and 1000 °C. The strength retention ratio was increased from 61.9% (C/SiC-SiC/SiC) to 75.7% (C/SiC-Si3N4/SiC/SiC) and 67.8% (C/SiC-SiC/Si3N4/SiC) after oxidation at 800 °C for 10 h.

Objective: This study aimed to identify the clinical significance of TP53 and common cytogenetic abnormalities. Materials and Methods: A total of 114 patients with newly diagnosed multiple myeloma (MM) and TP53 abnormalities were selected from two large patient cohorts of collaborating hospitals from 2010 to 2017. The characteristics and outcomes of these patients were analyzed. TP53 and other common mutations in MM patients were quantified by fluorescence in situ hybridization. Kaplan-Meier curves and logrank tests were applied for survival analysis. A Cox proportional hazard model for covariate analysis was used to determine the prognostic factors. Results: By extensive data analysis, we found that TP53 amplification is a strong positive predictor for complete response (CR) to therapy and positively correlated with patient survival. The number of simultaneous genomic abnormalities with TP53 mutation has a modest impact on patient survival. Among these mutations, 1q21 amplification is associated with decreased CR (odds ratio: 4.209) and FGFR3 levels are positively correlated with progression-free and overall survival. Conclusion: TP53 abnormalities at the diagnosis of MM are of great clinical significance in predicting patient response to therapy and survival. Furthermore, 1q21 and FGFR3 mutations could potentially be used in combination with TP53 status to better predict patient survival and guide the selection of high-risk patients to advance patient treatment strategies.

Abstract We provide a novel explanation to the muon g − 2 excess with new physics contributions at the two-loop level. In this scenario, light millicharged particles are introduced to modify the photon vacuum polarization that contributes to muon g − 2 at one additional loop. The muon g − 2 excess can be explained with the millicharged particle mass m χ around 10 MeV and the product of the multiplicity factor and millicharge squared of N χ ε 2 ∼ 10 −3. The minimal model faces severe constraints from direct searches at fixed-target experiments and astrophysical observables. However, if the millicharged particles are also charged under a hidden confining gauge group SU(N χ ) with a confinement scale of MeV, hidden-sector hadrons are unstable and can decay into neutrinos, which makes this scenario consistent with existing constraints. This explanation can be well tested at low-energy lepton colliders such as BESIII and Belle II as well as other proposed fixed-target experiments.

ObjectivesThis meta-analysis aimed to test the association of angiotensin-converting enzyme (ACE) gene I/D polymorphism with asthma risk and circulating ACE changes.MethodsPublic literature retrieval, publication selection, and information extraction were completed independently by two investigators. Effect-size values are expressed as odds ratios (ORs) or standardized mean differences (SMDs) with a 95% confidence interval (95% CI).ResultsNineteen studies (2,888 patients and 9,549 controls) fulfilled the eligibility criteria. Overall investigations demonstrated that ACE gene I/D polymorphism was significantly associated with asthma risk under allelic (OR, 95% CI: 1.26, 1.08 to 1.48), homozygous genotypic (1.50, 1.09 to 2.06), and recessive (1.53, 1.24 to 1.89) models with moderate heterogeneity (I2 statistic: 64% to 79%). Subsidiary investigations recorded that race, matched status, asthma diagnosis, sample size, and age possibly accounted for the existence of significant heterogeneity. Relative to carriers with the II genotype, those with the DD genotype, ID genotype, and the combination of DD and ID genotypes had significantly higher concentrations of circulating ACE (WMD: 3.13, 2.07, and 2.83 U/L, respectively, p < 0.05). Adoption of Mendelian randomization analyses revealed that one unit increment in circulating ACE concentrations was found to be significantly associated with a 1.14-fold increased risk of asthma (95% CI: 1.02 to 4.24).ConclusionWe provided strong meta-analytical evidence supporting the causal implication of high circulating ACE concentrations in the development of asthma.

IntroductionPseudocontinuous Arterial Spin Labeling (pCASL) perfusion imaging allows non-invasive quantification of regional cerebral blood flow (CBF) as part of a multimodal magnetic resonance imaging (MRI) protocol. This study aimed to compare regional CBF in autism spectrum disorders (ASD) individuals with their age-matched typically developing (TD) children using pCASL perfusion imaging.Materials and methodsThis cross-sectional study enrolled 17 individuals with ASD and 13 TD children. All participants underwent pCASL examination on a 3.0 T MRI scanner. Children in two groups were assessed for clinical characteristics and developmental profiles using Autism Behavior Checklist (ABC) and Gesell development diagnosis scale (GDDS), respectively. We compared CBF in different cerebral regions of ASD and TD children. We also assessed the association between CBF and clinical characteristics/developmental profile.ResultsCompared with TD children, individuals with ASD demonstrated a reduction in CBF in the left frontal lobe, the bilateral parietal lobes, and the bilateral temporal lobes. Within the ASD group, CBF was significantly higher in the right parietal lobe than in the left side. Correlation analysis of behavior characteristics and CBF in different regions showed a positive correlation between body and object domain scores on the ABC and CBF of the bilateral occipital lobes, and separately, between language domain scores and CBF of the left frontal lobe. The score of the social and self-help domain was negatively correlated with the CBF of the left frontal lobe, the left parietal lobe, and the left temporal lobe.ConclusionCerebral blood flow was found to be negatively correlated with scores in the social and self-help domain, and positively correlated with those in the body and object domain, indicating that CBF values are a potential MRI-based biomarker of disease severity in ASD patients. The findings may provide novel insight into the pathophysiological mechanisms of ASD.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly around the world as well as in China. The sporadic AD (sAD) accounts for over 95% among AD. The pathogenesis of sAD remains unclear, which leads to current failures of disease-modifying therapies. In this report, the peripheral blood mononuclear cells (PBMCs) of two clinical sAD patients in Southwestern China were reprogrammed into hiPSC lines by an episomal and non– integrating Sendai virus system. The induced sAD-hiPSC lines, SPPHIi003-A and SPPHIi004-A, were further expanded and validated for stem cell-like pluripotency, normal karyotyping, and capability of in vitro differentiation into three germ-layers. Importantly, the point mutation on microtubule associated protein tau (MAPT) gene, which encodes the tau protein and is the pivotal and hallmark lesion of AD, was discovered and confirmed in both patient’s PBMCs and hiPSCs. These newly generated sAD-hiPSC lines can sever as disease model for discovering and developing potential therapeutic targets for sAD and relevant hyperphosphorylated Tauopathies.

As an important strategic decision for enterprise sustainability, the green entrepreneurial orientation can facilitate boundary-spanning search for external knowledge and resources to achieve triadic sustainable economic, environmental, and social performance. Based on organizational search theory and dynamic capability theory, this study introduces environmental dynamism into the model of the relationship between green entrepreneurial orientation, boundary-spanning search and enterprise triadic sustainable performance. By analyzing the questionnaire data from 202 managers of manufacturing SMEs, the study explores the internal and external influences of green entrepreneurial orientation on the enterprise sustainable performance. The results show that: green entrepreneurial orientation has a positive impact on enterprise economic, environmental and social performance; boundary-spanning search plays a fully mediating role between green entrepreneurial orientation and enterprise economic, environmental and social performance; environmental dynamism, as a key external environmental factor, positively regulates the relationship between boundary-spanning search and enterprise economic performance and environmental performance, and negatively regulates the relationship between boundary-spanning search and social performance. This study clearly demonstrates how green entrepreneurial orientation in the environmental era can drive triadic sustainable performance improvement of enterprises. In addition, this study argues that boundary-spanning search is an important tool that enables manufacturing SMEs to achieve a triad of coordinated sustainable development of economic, environmental and social benefits in a dynamic environment.

The evidence linking sleep duration and metabolic body size phenotypes is limited, especially in young adulthood. In this study, we aimed to examine the association between sleep duration and metabolic body size phenotypes among Chinese young workers and investigate whether discrepancies exist among shift and non-shift workers. A cross-sectional study was performed between 2018 and 2019 in Wuhan, China and 7,376 young adults aged 20–35 years were included. Self-reported sleep duration was coded into four groups:

Abstract The SiBCN matrix via chemical vapor infiltration (CVI) or/and polymer infiltration pyrolysis (PIP) technologies was orderly introduced to SiCf/SiC composites to optimize the mechanical property and electromagnetic (EM) shielding effectiveness simultaneously. The BN interface with the thickness of 350 nm was designed to obtain a little stronger interface bonding. The flexural strength of SiCf/SiC-SiBCN composites reached 545.45±29.59 MPa thanks to the crack deflection between the CVI SiC and CVI SiBCN, as well as CVI SiBCN and PIP SiBCN matrix because of the modulus difference between them. The fracture toughness (K IC) with the value of 16.02±0.94 MPa·m1/2 was obtained owing to the extension of crack propagation path. The adverse effect of stronger interface bonding was eliminated by the design of matrix microstructure for SiCf/SiC-SiBCN composites. The thermal conductivity in the thickness direction was 7.64 W·(m·K)−1 at 1200 °C and the electric resistivity decreased to 1.53×103 Ω·m. The tunable dielectric property was obtained with the coordination of wave-absorption CVI SiBCN matrix and impedance matching PIP SiBCN matrix, and the total shielding effectiveness (SE T) attained 30.01 dB. It indicates that the SiCf/SiC-SiBCN composites have great potential to be applied as structural and functional materials.

Abstract Although the Higgs potential in the Standard Model (SM) contains only a simple electroweak symmetry breaking vacuum in the small field region, additional metastable or global vacua could exist in models beyond the SM. In this paper, we study one intriguing scenario with an additional electroweak symmetric vacuum that could be the global one. For the thermal universe ending at the current metastable vacuum, the electroweak symmetry should stay non-restored at high temperatures. We realize the scenario in a model with Higgs-portal couplings to SM singlet scalars with approximately global O(N) symmetries with a large N. For a large portion of model parameter space, both the quantum and thermal tunneling rates are suppressed such that our current metastable vacuum is long-lived enough. Our scenario predicts order-one changes for the Higgs self-couplings and a large contribution to the signal of the off-shell Higgs invisible decay. It can be partly probed at the LHC Run 3 and well tested at the high luminosity LHC. We also discuss the subcritical (anti-de Sitter) bubbles from the thermal tunneling that could have a large population and interesting cosmological implications.

Background: Autism spectrum disorders (ASDs) are a set of complex neurobiological disorders. Growing evidence has shown that the microbiota that resides in the gut can modulate brain development via the gut–brain axis. However, direct clinical evidence of the role of the microbiota–gut–brain axis in ASD is relatively limited. Methods: A case-control study of 71 boys with ASD and 18 neurotypical controls was conducted at China-Japan Friendship Hospital. Demographic information and fecal samples were collected, and the gut microbiome was evaluated and compared by 16S ribosomal RNA gene sequencing and metagenomic sequencing. Results: A higher abundance of operational taxonomic units (OTUs) based on fecal bacterial profiling was observed in the ASD group. Significantly different microbiome profiles were observed between the two groups. At the genus level, we observed a decrease in the relative abundance of Escherichia, Shigella, Veillonella, Akkermansia, Provindencia, Dialister, Bifidobacterium, Streptococcus, Ruminococcaceae UCG_002, Megasphaera, Eubacterium_coprostanol, Citrobacter, Ruminiclostridium_5, and Ruminiclostridium_6 in the ASD cohort, while Eisenbergiella, Klebsiella, Faecalibacterium, and Blautia were significantly increased. Ten bacterial strains were selected for clinical discrimination between those with ASD and the neurotypical controls. The highest AUC value of the model was 0.947. Conclusion: Significant differences were observed in the composition of the gut microbiome between boys with ASD and neurotypical controls. These findings contribute to the knowledge of the alteration of the gut microbiome in ASD patients, which opens the possibility for early identification of this disease.

Water-based electromagnetic wave absorbers have attracted significant attention due to their potential applications for conformal absorbing structures. In this paper, a flexible broadband electromagnetic wave metamaterial absorber (MMA) based on sandwiched cylindrical water resonators is designed and prepared via the 3D printing, which realizes a low and high frequency cooperative electromagnetic absorption in 4–40 GHz. Additionally, the proposed absorber shows a comprehensive performance with temperature insensitivity and broad absorption characteristics at wide incidence angles. The broadband perfection electromagnetic absorption is discussed based on the improved impedance matching induced by the sandwiched water resonators, and the enhanced electromagnetic wave loss introduced by connected water resonators would further improve the absorption efficiency. Particularly, the radar cross section (RCS) of the designed flexible MMA with different curvature also shows excellent conformal absorption in the evaluated frequency range. Therefore, the proposed flexible ultra-broadband MMA based optimized 3D patterned cylindrical water resonators shows excellent comprehensive performances, which could be widely utilized in electromagnetic protection applications for conformal devices.

BackgroundAlthough children with COVID-19 account for fewer hospitalizations than adults, many develop severe disease requiring intensive care treatment. Critical illness due to COVID-19 has been associated with lymphopenia and functional immune suppression. Myeloid-derived suppressor cells (MDSCs) potently suppress T cells and are significantly increased in adults with severe COVID-19. The role of MDSCs in the immune response of children with COVID-19 is unknown.AimsWe hypothesized that children with severe COVID-19 will have expansion of MDSC populations compared to those with milder disease, and that higher proportions of MDSCs will correlate with clinical outcomes.MethodsWe conducted a prospective, observational study on a convenience sample of children hospitalized with PCR-confirmed COVID-19 and pre-pandemic, uninfected healthy controls (HC). Blood samples were obtained within 48 h of admission and analyzed for MDSCs, T cells, and natural killer (NK) cells by flow cytometry. Demographic information and clinical outcomes were obtained from the electronic medical record and a dedicated survey built for this study.ResultsFifty children admitted to the hospital were enrolled; 28 diagnosed with symptomatic COVID-19 (10 requiring ICU admission) and 22 detected by universal screening (6 requiring ICU admission). We found that children with severe COVID-19 had a significantly higher percentage of MDSCs than those admitted to the ward and uninfected healthy controls. Increased percentages of MDSCs in peripheral blood mononuclear cells (PBMC) were associated with CD4+ T cell lymphopenia. MDSC expansion was associated with longer hospitalizations and need for respiratory support in children admitted with acute COVID-19.ConclusionThese findings suggest that MDSCs are part of the dysregulated immune responses observed in children with severe COVID-19 and may play a role in disease pathogenesis. Future mechanistic studies are required to further understand the function of MDSCs in the setting of SARS-CoV-2 infection in children.

Unmanned Aerial Vehicles (UAVs) can be an important component in the Internet of Things (IoT) ecosystem due to their ability to collect and transmit data from remote and hard-to-reach areas. Ensuring collision-free navigation for these UAVs is crucial in achieving this goal. However, existing UAV collision-avoidance methods face two challenges: conventional path-planning methods are energy-intensive and computationally demanding, while deep reinforcement learning (DRL)-based motion-planning methods are prone to make UAVs trapped in complex environments—especially for long trajectories with unpredictable obstacles—due to UAVs’ limited sensing ability. To address these challenges, we propose a hybrid collision-avoidance method for the real-time navigation of UAVs in complex environments with unpredictable obstacles. We firstly develop a Human-in-the-Loop DRL (HL-DRL) training module for mapless obstacle avoidance and secondly establish a global-planning module that generates a few points as waypoint guidance. Moreover, a novel goal-updating algorithm is proposed to integrate the HL-DRL training module with the global-planning module by adaptively determining the to-be-reached waypoint. The proposed method is evaluated in different simulated environments. Results demonstrate that our approach can rapidly adapt to changes in environments with short replanning time and prevent the UAV from getting stuck in maze-like environments.

Abstract Heterogeneous interface design to boost interfacial polarization has become a feasible way to realize high electromagnetic wave absorbing (EMA) performance of dielectric materials. However, interfacial polarization in simple structures such as particles, rods, and flakes is weak and usually plays a secondary role. In order to enhance the interfacial polarization and simultaneously reduce the electronic conductivity to avoid reflection of electromagnetic wave, a more rational geometric structure for dielectric materials is desired. Herein, a Ti3C2Tx/MoS2 self‐rolling rod‐based foam is proposed to realize excellent interfacial polarization and achieve high EMA performance at ultralow density. Different surface tensions of Ti3C2Tx and ammonium tetrathiomolybdate are utilized to induce the self‐rolling of Ti3C2Tx sheets. The rods with a high aspect ratio not only remarkably improve the polarization loss but also are beneficial to the construction of Ti3C2Tx/MoS2 foam, leading to enhanced EMA capability. As a result, the effective absorption bandwidth of Ti3C2Tx/MoS2 foam covers the whole X band (8.2–12.4 GHz) with a density of only 0.009 g cm−3, at a thickness of 3.3 mm. The advantages of rod structures are verified through simulations in the CST microwave studio. This work inspires the rational geometric design of micro/nanostructures for new‐generation EMA materials.

BackgroundRecent evidence of genetics and metabonomics indicated a potential role of apolipoprotein M (ApoM) in the pathogenesis of Alzheimer’s disease (AD). Here, we aimed to investigate the association between plasma ApoM with AD.MethodsA multicenter, cross-sectional study recruited patients with AD (n = 67), age- and sex-matched cognitively normal (CN) controls (n = 73). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, we examined and compared the plasma levels of ApoM, tau phosphorylated at threonine 217 (p-tau217) and neurofilament light (NfL). Multivariate logistic regression analysis was applied to determine the association of plasma ApoM with the presence of AD. The correlation analysis was used to explore the correlations between plasma ApoM with cognitive function [Mini–Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)], activities of daily living (ADL), and the representative blood-based biomarkers (plasma p-tau217 and NfL). Receiver operating characteristic (ROC) analysis and Delong’s test were used to determine the diagnostic power of plasma ApoM.ResultsPlasma ApoM and its derived indicators (ratios of ApoM/TC, ApoM/TG, ApoM/HDL-C, and ApoM/LDL-C) were significantly higher in AD group than those in CN group (each p < 0.0001). After adjusted for the risk factors of AD, the plasma ApoM and its derived indicators were significantly associated with the presence of AD, respectively. ApoM (OR = 1.058, 95% CI: 1.027–1.090, p < 0.0001), ApoM/TC ratio (OR = 1.239, 95% CI: 1.120–1.372, p < 0.0001), ApoM/TG ratio (OR = 1.064, 95% CI: 1.035–1.095, p < 0.0001), ApoM/HDL-C ratio (OR = 1.069, 95% CI: 1.037–1.102, p < 0.0001), and ApoM/LDL-C ratio (OR = 1.064, 95% CI:1.023–1.106, p = 0.002). In total participants, plasma ApoM was significantly positively correlated with plasma p-tau217, plasma NfL, and ADL (each p < 0.0001) and significantly negatively correlated with MMSE and MoCA (each p < 0.0001), respectively. In further subgroup analyses, these associations remained in different APOEϵ 4 status participants and sex subgroups. ApoM/TC ratio (ΔAUC = 0.056, p = 0.044) and ApoM/TG ratio (ΔAUC = 0.097, p = 0.011) had a statistically remarkably larger AUC than ApoM, respectively. The independent addition of ApoM and its derived indicators to the basic model [combining age, sex, APOEϵ 4, and body mass index (BMI)] led to the significant improvement in diagnostic power, respectively (each p < 0.05).ConclusionAll the findings preliminarily uncovered the association between plasma ApoM and AD and provided more evidence of the potential of ApoM as a candidate biomarker of AD.

Abstract Background Astrocyte Connexin 43 (Cx43) is essential for the trophic and protective support of neurons during brain ischemia reperfusion (I/R) injury. It is believed that dexmedetomidine participates in Cx43-mediated effects. However, its mechanisms remained unclear. This study aims to address the relationship and regulation among them. Methods Adult male Sprague-Dawley rats were allocated to the 90-min right middle cerebral arterial occlusion with or without dexmedetomidine pretreatment (5 μg/kg). Neurological functions were evaluated and brain lesions, as well as inflammatory factors (IL-1β, IL-6, TNF-α), were assessed. Ischemic penumbral cortex was harvested to determine the expression of astrocyte Cx43. Primary astrocytes were cultured to evaluate the effect of dexmedetomidine on Cx43 after oxygen-glucose deprivation. Results Dexmedetomidine pretreatment attenuated neurological injury, brain lesions and expression of inflammatory factors (IL-1β, IL-6, TNF-α) after brain ischemia (P

Nowadays, the contradiction between strict construction land supply restriction and excessive construction land demand is extremely prominent. Construction land reduction (CLR) is a policy innovation for economically developed regions designed to solve the tight constraints of the construction land quota as urban development continues in China, however, it leads to a lack of spatial justice. In this study, we address a gap in land use regulation literature regarding regional economic development in fast-developing nations by presenting a quantitative investigation of spatial justice in Shanghai, China. We theoretically analyze the connotation of spatial justice in CLR and its influence on residents’ policy acceptance of CLR. Based on theoretical analysis and using household questionnaires from JJ Town in W District, Shanghai, China, we investigate how spatial justice affects residents’ policy acceptance of CLR through an ordered probit model. The results show that (1) spatial justice strengthens residents’ policy acceptance of CLR; (2) both policy familiarity and participation are important influencing factors that contribute to residents’ policy acceptance of CLR; (3) age, education, household income, the contracting land scale and household population structure also affect residents’ policy acceptance of CLR. (4) Robustness tests support the above findings. Thus, in the process of CLR, it is essential to fully consider the realization of spatial justice to ensure the development of remote suburbs, especially the regions experiencing a net reduction in their construction land.

Abstract Background Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes. Methods Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells. Results From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic “cancer attractor” that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape. Conclusions We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor.

Background: Recent observational studies have reported a negative association between physical activity and chronic back pain (CBP), but the causality of the association remains unknown. We introduce bidirectional Mendelian randomization (MR) to assess potential causal inference between physical activity and CBP.Materials and Methods: This two-sample MR used independent genetic variants associated with physical activity and CBP as genetic instruments from large genome-wide association studies (GWASs). The effects of both directions (physical activity to CBP and CBP to physical activity) were examined. Inverse variance-weighted meta-analysis and alternate methods (weighted median and MR-Egger) were used to combine the MR estimates of the genetic instruments. Multiple sensitivity analyses were conducted to examine the robustness of the results.Results: The MR set parallel GWAS cohorts, among which, those involved in the primary analysis were comprised of 337,234 participants for physical activity and 158,025 participants (29,531 cases) for CBP. No evidence of a causal relationship was found in the direction of physical activity to CBP [odds ratio (OR), 0.98; 95% CI, 0.85–1.13; p = 0.81]. In contrast, a negative causal relationship in the direction of CBP to physical activity was detected (β = −0.07; 95% CI, −0.12 to −0.01; p = 0.02), implying a reduction in moderate-vigorous physical activity (approximately 146 MET-minutes/week) for participants with CBP relative to controls.Conclusion: The negative relationship between physical activity and CBP is probably derived from the reduced physical activity of patients experiencing CBP rather than the protective effect of physical activity on CBP.