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The photonics-assisted millimeter-wave (MMW) communication technology is attractive to facilitate the MMW application in the upcoming B5G and 6G networks. However, its generated MMW signal by optical heterodyne detection usually suffers from serious laser phase noise, which will severely deteriorate the system performance. In this paper, based on a single dual-drive Mach-Zehnder modulator and a single-end photodetector, we first present a simple and spectrally efficient hybrid fiber-wireless double-sideband transmission by employing an overlapping frequency multiplexing scheme. That is, two independent wireless signals with an identical carrier frequency can be simultaneously transmitted in the hybrid fiber-wireless links. To recover the above two overlapped signals, and cancel the concomitant laser phase noise at the same time, a novel digital signal processing method for carrier extraction and signal recovery is further proposed. A proof-of-concept experiment using two independent 3-GBd quadrature phase shift keying (QPSK) signals at W band (92.5 GHz) is performed. After up to 80-km fiber and 3-m wireless transmission, the two QPSK signals can be successfully demodulated, without using the traditional carrier phase estimation algorithm. The proposed scheme not only can double the spectral efficiency of conventional double sideband transmission scheme, but also is immune to its power fading phenomenon induced by chromatic dispersion and robust to the laser phase noise resulting from two free-running lasers in the photonics-assisted MMW communication link.

Abstract Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

ObjectivesMatrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a potent tool for detecting drug resistance in tuberculosis (TB); however, concerns about its reliability have been raised. In this study, we assessed the reliability of MassARRAY (Sequenom, Inc.), which is a MALDI-TOF MS-based method, by comparing it to the well-established GeneXpert assay (Cepheid) as a reference method.MethodsA retrospective study was conducted using laboratory data retrieved from Henan Chest Hospital (Zhengzhou, China). To ensure a rigorous evaluation, we adopted a comprehensive assessment approach by integrating multiple outcomes of the Xpert assay across various specimen types.ResultsAmong the 170 enrolled TB cases, MassARRAY demonstrated significantly higher sensitivity (85.88%, 146 of 170) compared to the Xpert assay (76.62%, 118 of 154) in TB diagnosis (p

China is the largest steel producer in the world. Effective methods to alleviate the contradiction between water supply and water demand of the iron and steel industry in China are to implement the recycling of wastewater from the iron and steel industry and develop unconventional water resources. This paper reviews the development of wastewater recycling in the iron and steel industry in China in the past 40 years (1980–2020). During this period, steel output has increased from 36 to 1,053 million tons, freshwater consumption per ton of steel has decreased from 35.9 to 2.45 tons, and water resources reuse has soared from 61.2 to 98.02%. Four typical cases, including the Anyang Steel Group, the Tangshan Steel Group, the Tianjin Steel Group, and the Taihang Steel Group, were analyzed. In addition, a water efficiency research project of iron and steel enterprises in China was carried out in 2019. Statistical analyses on wastewater recycling rate, reuse rate, direct cooling water circulation rate, and other indicators were performed. The recycling of wastewater in the iron and steel industry would be continuously improved by policy drivers, economic drivers, and technical drivers. HIGHLIGHTS History of steel wastewater reuse and typical projects in China were presented.; Effective methods to alleviate the contradiction between water supply and demand were introduced.; Comparisons of the water use efficiency of steel industries in China were conducted.; Perspectives and challenges of future development of the steel industry were proposed.;

With the explosive growth in demand for lithium (Li) resources, the Mufushan area has been a hotspot for Li deposit exploration in China in recent years. Geochemical maps and geochemical anomaly maps are basic maps in the geochemical exploration of mineral resources. A fixed-value method to contour a Li geochemical map is presented here, in which Li concentrations are divided into 19 levels on 18 fixed values, ranging from 5 μg/g (corresponding to the detection limit) to 1858 μg/g (corresponding to the cut-off grade of Li deposit in hard-rock type) and illustrated in six color tones corresponding to Li areas of low background, high background, low anomaly, high anomaly, mineralization in clay-type, and mineralization in hard-rock type. The geochemical map of Li in the Mufushan area using the new fixed-value method indicates that the study area belongs to the high background area, and the known Li deposits are located in the high anomaly areas. In addition, the geochemical anomaly map of the Mufushan area is drawn using the method of seven levels of classification, and indicates that the known Li deposits are all in the anomaly areas, with anomaly levels not lower than the second level. Furthermore, four other areas are recognized for Li resource potential based on the geochemical map and geochemical anomaly map in the Mufushan area.

Changing film thickness to manipulate microstructural properties has been considered as a potential method in practical application. Here, we report that atomic-scale structural properties are regulated by film thickness in an NiCO2O4(NCO)/CuFe2O4(CFO) bilayer heterostructure prepared on (001)-MgAl2O4 (MAO) substrate by means of aberration-corrected scanning transmission electron microscopy (STEM). The misfit dislocations at the NCO/CFO interface and antiphase boundaries (APBs) bound to dislocations within the films are both found in NCO (40 nm)/CFO (40 nm)/MAO heterostructures, contributing to the relaxation of mismatch lattice strain. In addition, the non-overlapping a/4[101]-APB is found and the structural transformation of this kind of APB is resolved at the atomic scale. In contrast, only the interfacial dislocations form at the interface without the formation of APBs within the films in NCO (10 nm)/CFO (40 nm)/MAO heterostructures. Our results provide evidence that the formation of microstructural defects can be regulated by changing film thickness to tune the magnetic properties of epitaxial bilayer spinel oxide films.

In our previous multicenter study, we delineated the inherent metabolic features of colorectal cancer (CRC). Therein, we identified a member of the ectonucleotide pyrophosphatase/ phosphodiesterase family (ENPP2) as a significant differential metabolite of CRC. In this study, the role of ENPP2 in CRC has been demonstrated using established in vitro and in vivo models including ENPP2 gene knockdown, and use of the ENPP2 inhibitor, GLPG1690. We found that CRC proliferation was decreased after either ENPP2 gene knockdown or use of ENPP2 inhibitors. We further evaluated the role of GLPG1690 in AOM/DSS-induced CRC mice via intestinal barrier function, macrophage polarization, inflammatory response and microbial homeostasis. Results of immunofluorescence staining and Western blotting showed that GLPG1690 can restore gut-barrier function by increasing the expression of tight junction proteins, claudin-1, occludin and ZO-1. M2 tumor-associated macrophage polarization and colonic inflammation were attenuated after treatment with GLPG1690 using the Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) model. Moreover, 16 S rDNA pyrosequencing and metagenomic analysis showed that GLPG1690 could alleviate gut dysbiosis in mice. Furthermore, administration of GLPG1690 with antibiotics as well as fecal microbiota transplantation assays demonstrated a close link between the efficacy of GLPG1690 and the gut microbiota composition. Finally, results of metabolomic analysis implicated mainly the gut microbiota-derived metabolites of aromatic amino acids in CRC progression. These findings may provide novel insights into the development of small-molecule ENPP2 inhibitors for the treatment of CRC.

Laser direct joining enables non-destructive and lightweight joining of carbon fiber reinforced thermoplastic (CFRTP) composites and aluminum alloys. The interfacial bonding process determines the joint performance and is influenced by the time-varying temperature distribution. However, the interfacial bonding process occurs inside the joint, making it difficult to study the effect of temperature distribution. To resolve this issue, a novel online observation device for the interfacial bonding process between CFRTP composites and aluminum alloys is design, and the polymer melting, flowing, and bonding with metal during laser direct joining are observed. Further, temperature field simulation models for laser direct joining are established, and temperature distribution and gradient are calculated. The results show that the temperature distribution determines the melting of CFRTP composites, and bubbles generated by the thermal decomposition of the polymer hinder the melting. The temperature gradient is related to the movement of the molten matrix and fibers, and the movement towards the aluminum alloy induces cracking and delamination. Once the interface is filled with polymer, the motion changes to along the laser scanning direction and the joining defects are reduced. The study can provide a foundation for promoting interfacial bonding and reducing the defects of laser direct joining.

Sivelestat sodium (SIV), a neutrophil elastase inhibitor, is mainly used for the clinical treatment of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). However, studies investigating the effects of SIV treatment of ALI are limited. Therefore, this study investigated the potential molecular mechanism of the protective effects of SIV against ALI. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with tumor necrosis factor α (TNF-α), and male Sprague-Dawley rats were intratracheally injected with Klebsiella pneumoniae (KP) and treated with SIV, ML385, and anisomycin (ANI) to mimic the pathogenetic process of ALI in vitro and in vivo, respectively. The levels of inflammatory cytokines and indicators of oxidative stress were assessed in vitro and in vivo. The wet/dry (W/D) ratio of lung tissues, histopathological changes, inflammatory cells levels in bronchoalveolar lavage fluid (BALF), and survival rates of rats were analyzed. The JNK/NF-κB (p65) and Nrf2/HO-1 levels in the HPMECs and lung tissues were analyzed by western blot and immunofluorescence analyses. Administration of SIV reduced the inflammatory factors levels, intracellular reactive oxygen species (ROS) production, and malondialdehyde (MDA) levels and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues. Meanwhile, SIV alleviated pathological injuries, decreased the W/D ratio, and inflammatory cell infiltration in lung tissue. In addition, SIV also inhibited the activation of JNK/NF-κB signaling pathway, promoted nuclear translocation of Nrf2, and upregulated the expression of heme oxygenase 1 (HO-1). However, ANI or ML385 significantly reversed these changes. SIV effectively attenuated the inflammatory response and oxidative stress. Its potential molecular mechanism was related to the JNK/NF-κB activation and Nrf2/HO-1 signaling pathway inhibition. This further deepened the understanding of the protective effects of SIV against ALI.

Abstract This paper attempts to address the trajectory following control problem of nonholonomic mobile AGV by proposing an improved sliding mode control approach in which, based on the kinematics and attitude deviations established for AGV, the motion characteristics are analyzed and a backstepping sliding mode control with a novel reaching law is designed. This reaching law integrates the merits of the power and exponential reaching laws and promotes the convergence rates of tracking errors. Moreover, with the improved sliding mode controller, the asymptotic stability of tracking deviations can be strictly guaranteed. The simulations have demonstrated the effectiveness and superiority of the proposed approach for mobile AGV.

ObjectiveGamma-glutamyl dipeptides are bioactive peptides involved in inflammation, oxidative stress, and glucose regulation. Gamma-glutamyl-leucine (Gamma-Glu-Leu) has been extensively reported to be associated with the risk of cardio-metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes. However, the causality remains to be uncovered. The aim of this study was to explore the causal-effect relationships between Gamma-Glu-Leu and metabolic risk.Materials and methodsIn this study, 1,289 subjects were included from a cross-sectional survey on metabolic syndrome (MetS) in eastern China. Serum Gamma-Glu-Leu levels were measured by untargeted metabolomics. Using linear regressions, a two-stage genome-wide association study (GWAS) for Gamma-Glu-Leu was conducted to seek its instrumental single nucleotide polymorphisms (SNPs). One-sample Mendelian randomization (MR) analyses were performed to evaluate the causality between Gamma-Glu-Leu and the metabolic risk.ResultsFour SNPs are associated with serum Gamma-Glu-Leu levels, including rs12476238, rs56146133, rs2479714, and rs12229654. Out of them, rs12476238 exhibits the strongest association (Beta = −0.38, S.E. = 0.07 in discovery stage, Beta = −0.29, S.E. = 0.14 in validation stage, combined P-value = 1.04 × 10–8). Each of the four SNPs has a nominal association with at least one metabolic risk factor. Both rs12229654 and rs56146133 are associated with body mass index, waist circumference (WC), the ratio of WC to hip circumference, blood pressure, and triglyceride (5 × 10–5 < P < 0.05). rs56146133 also has nominal associations with fasting insulin, glucose, and insulin resistance index (5 × 10–5 < P < 0.05). Using the four SNPs serving as the instrumental SNPs of Gamma-Glu-Leu, the MR analyses revealed that higher Gamma-Glu-Leu levels are causally associated with elevated risks of multiple cardio-metabolic factors except for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (P > 0.05).ConclusionFour SNPs (rs12476238, rs56146133, rs2479714, and rs12229654) may regulate the levels of serum Gamma-Glu-Leu. Higher Gamma-Glu-Leu levels are causally linked to cardio-metabolic risks. Future prospective studies on Gamma-Glu-Leu are required to explain its role in metabolic disorders.

The introduction of the Sepsis 3.0 guidelines in 2016 improved our understanding of sepsis diagnosis and therapy. Personalized treatment strategies and nursing methods for sepsis patients are recommended in the “Save Sepsis Campaign” in 2021. However, mortality in sepsis patients remains high. Patients with sepsis-related acute respiratory distress syndrome account for around 30% of them, with fatality rates ranging from 30 to 40%. Pathological specimens from individuals with sepsis-related ARDS frequently demonstrate widespread alveolar damage, and investigations have revealed that pulmonary epithelial and pulmonary endothelial injury is the underlying cause. As a result, the purpose of this work is to evaluate the mechanism and research progress of pulmonary epithelial and pulmonary endothelial damage in sepsis-related ARDS, which may provide new directions for future research, diagnosis, and therapy.

Acute skin injuries require timely and effective treatment. Injectable self-healing hydrogels are a very promising approach, but they face many challenges because of the complex microenvironments of skin wound. Although hydrogels have been extensively studied for multifunction, injectable self-healing hydrogels with both hemostatic and antioxidant properties are rare. In this paper, gelatin grafted protocatechuic acid (GT-PCA) and oxidized-dextran (Odex) were used to engineer GT-PCA/Odex composite hydrogels via Schiff base reaction. The in vitro experimental results show that the hydrogels not only are injectable, self-healing, hemostatic, antioxidant, but also have good degradability, adhesion and biocompatibility. Further, the hydrogels can promote wound healing in full-thickness mouse skin defect models by reducing inflammation and increasing angiogenesis, collagen deposition and granulation tissue formation. Notably, the preparation method of GT-PCA/Odex hydrogels is gentle and simple, the hydrogel system has bright prospects in the treatment of acute skin injury and is expected to be applied in clinical trials.

2-hydroxybutyric acid (2HB) serves as an important regulatory factor in a variety of diseases. The circulating level of 2HB in serum is significantly higher in multiple diseases, such as cancer and type 2 diabetes (T2D). However, there is currently no systematic study on 2HB-producing bacteria that demonstrates whether gut bacteria contribute to the circulating 2HB pool. To address this question, we used BLASTP to reveal the taxonomic profiling of 2HB-producing bacteria in the human microbiome, which are mainly distributed in the phylum Proteobacteria and Firmicutes. In vitro experiments showed that most gut bacteria (21/32) have at least one path to produce 2HB, which includes Aspartic acid, methionine, threonine, and 2-aminobutyric acid. Particularly, Fusobacterium nucleatum has the strongest ability to synthesize 2HB, which is sufficient to alter colon 2HB concentration in mice. Nevertheless, neither antibiotic (ABX) nor Fusobacterium nucleatum gavage significantly affected mouse serum 2HB levels during the time course of this study. Taken together, our study presents the profiles of 2HB-producing bacteria and demonstrates that gut microbiota was a major contributor to 2HB concentration in the intestinal lumen but a relatively minor contributor to serum 2HB concentration.

The No. 5 pegmatite vein is the most evolved and well mineralized vein in the Renli deposit, with beryl being the most important beryllium mineral. The vein represents one of the most important gem-quality aquamarine mines at Renli. In this study, beryl crystals from the No. 5 pegmatite vein were examined by EMPA (electron microprobe analysis), ICP-MS (inductively coupled plasma-mass spectrometry), XRD (diffraction of X-rays), FTIR (fourier transform infrared spectrometer), and Raman analyses. Field and petrographic observations showed that most beryl crystals are euhedral to subhedral with light to medium blue color. EMPA analyses indicated that the main chemical compositions of beryl are close to the ideal values, with relatively low Fe (0.222–0.690 wt%) and alkali metal (0.280–0.820 wt%) contents. Geochemical and spectroscopic analyses indicated that cations replacement in beryl is relatively simple. The substituting cations of beryl in the octahedral Al site include mainly: Mg2+, Fe2+, Fe3+, Mn2+, Cr3+, Ti4+, and the excess Si. The tetrahedral Be site is mainly replaced by Li. Alkali metals in channel (esp. Na) serve as a charge compensator. According to the Fe-Mg-alkali and Li-Cs contents, the beryls from No. 5 pegmatite belong to the low Li-Cs and low Fe-Mg-medium alkali beryl groups. Field and geochemical data indicated that the No. 5 pegmatite vein formed by the multistage Mufushan granitic pluton emplacement and the magma source was less evolved.

Injectable Hydrogels with adhesive, antioxidant and hemostatic properties are highly desired for promoting skin injury repair. In this study, we prepared a multi-functional carboxymethyl chitosan/hyaluronic acid-dopamine (CMC/HA-DA) hydrogel, which can be crosslinked by horseradish peroxidase and hydrogen peroxide. The antioxidation, gelation time, degradability, rheology and antihemorrhagic properties of hydrogels can be finely tuned by varying composition ratio. The cytocompatibility test and hemolysis test confirmed that the designed hydrogel holds good biocompatibility. More importantly, the repair effect of the hydrogel on full-thickness skin injury model in mice was studied. The results of wound healing, collagen deposition, immunohistochemistry and immunofluorescence showed that CMC/HA-DA hydrogel could significantly promote angiogenesis and cell proliferation at the injured site. Notably, the inflammatory response can also be regulated to promote the repair of full-thickness skin defect in mice. Results indicate that this injectable CMC/HA-DA hydrogel holds high application prospect for promising wound healing.

The human retina, located in the innermost layer of the eye, plays a decisive role in visual perception. Dissecting the heterogeneity of retinal cells is essential for understanding the mechanism of visual development. Here, we performed single-cell RNA-seq to analyze 194,967 cells from the donors of infants and young children, resulting in 17 distinct clusters representing major cell types in the retina: rod photoreceptors (PRs), cone PRs, bipolar cells (BCs), horizontal cells (HCs), amacrine cells (ACs), retinal ganglion cells (RGCs), Müller glial cells (MGs), microglia, and astrocytes (ASTs). Through reclustering, we identified known subtypes of cone PRs as well as additional unreported subpopulations and corresponding markers in BCs. Additionally, we linked inherited retinal diseases (IRDs) to certain cell subtypes or subpopulations through enrichment analysis. We next constructed extensive intercellular communication networks and identified ligand-receptor interactions that play crucial roles in regulating neural cell development and immune homeostasis in the retina. Intriguingly, we found that the status and functions of PRs changed drastically between the young children and adult retina. Overall, our study offers the first retinal cell atlas in infants and young children dissecting the heterogeneity of the retina and identifying the key molecules in the developmental process, which provides an important resource that will pave the way for research on retinal development mechanisms and advancements in regenerative medicine concerning retinal biology.

Abstract The level of microRNA-9-5p (miRNA-9-5p) in brain tissues is significantly changed in the chronic phase after traumatic brain injury (TBI). However, the effect of miRNA-9-5p on brain function after TBI has not been elucidated. In this study, we used a controlled cortical impact (CCI) model to induce TBI in Sprague–Dawley rats. Brain microvascular endothelial cells (BMECs), astrocytes, and neurons were extracted from immature Sprague–Dawley rats and cocultured to reconstruct the neurovascular unit (NVU) in vitro. The results showed that downregulation of miRNA-9-5p in the chronic phase contributed to neurological function recovery by promoting astrocyte proliferation and increasing the release of astrocyte-derived neurotrophic factors around injured brain tissues after TBI. A dual-luciferase reporter assay validated that miRNA-9-5p was a post-transcriptional modulator of thrombospondin 2 (Thbs-2), and downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes. Furthermore, we verified that Thbs-2 can promote Notch pathway activation by directly binding to Jagged and Notch. Through in vitro experiments, we found that the expression of synaptic proteins and the number of synaptic bodies were increased in neurons in the NVU, which was constructed using astrocytes pretreated with miRNA-9-5p inhibitor. Moreover, we also found that downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes, which activated the Notch/cylindromatosis/transforming growth factor-β-activated kinase 1 pathway in neurons and promoted the expression of synaptic proteins, including post-synaptic density protein 95 and synaptotagmin. Based on these results, miRNA-9-5p may be a new promising prognostic marker and treatment target for TBI.

Background: Metabolic syndrome (MetS) is a cluster of multiple cardiometabolic risk factors that increase the risk of type 2 diabetes and cardiovascular diseases. Identifying novel biomarkers of MetS and their genetic associations could provide insights into the mechanisms of cardiometabolic diseases. Methods: Potential MetS-associated metabolites were screened and internally validated by untargeted metabolomics analyses among 693 patients with MetS and 705 controls. External validation was conducted using two well-established targeted metabolomic methods among 149 patients with MetS and 253 controls. The genetic associations of metabolites were determined by linear regression using our previous genome-wide SNP data. Causal relationships were assessed using a one-sample Mendelian Randomization (MR) approach. Findings: Nine metabolites were ultimately found to be associated with MetS or its components. Five metabolites, including LysoPC(14:0), LysoPC(15:0), propionyl carnitine, phenylalanine, and docosapentaenoic acid (DPA) were selected to construct a metabolite risk score (MRS), which was found to have a dose-response relationship with MetS and metabolic abnormalities. Moreover, MRS displayed a good ability to differentiate MetS and metabolic abnormalities. Three SNPs (rs11635491, rs7067822, and rs1952458) were associated with LysoPC(15:0). Two SNPs, rs1952458 and rs11635491 were found to be marginally correlated with several MetS components. MR analyses showed that a higher LysoPC(15:0) level was causally associated with the risk of overweight/obesity, dyslipidaemia, high uric acid, high insulin and high HOMA-IR. Interpretation: We identified five metabolite biomarkers of MetS and three SNPs associated with LysoPC(15:0). MR analyses revealed that abnormal LysoPC metabolism may be causally linked the metabolic risk. Funding: This work was supported by grants from the National Key Research and Development Program of China (2017YFC0907004).

To address the problems in remote sensing image change detection such as missed detection of features at different scales and incomplete region detection, this paper proposes a high-resolution remote sensing image change detection model (Multi-scale Attention Siamese Network, MASNet) based on a Siamese network and multi-scale attention mechanism. The MASNet model took the Siamese structure of the ResNet-50 network to extract features of different simultaneous images and then applied the attention module to feature maps of different scales to generate multi-scale feature representations. Meanwhile, an improved contrastive loss function was adopted to enhance the learning of change features and improving the imbalance problem between unchanged and changed samples. Furthermore, to address the current time-consuming and laborious phenomenon of manually annotating datasets, we provided a change detection dataset from Yunnan Province in China (YNCD) that contains 1540 pairs of 256 × 256 bi-temporal images with a spatial resolution of 1 m. Then, model training and change detection applications were studied by expanding a small number of experimental area samples into the existing public datasets. The results showed that the overall accuracy of the MASNet model for change detection in the experimental area is 95.34%, precision rate is 79.78%, recall rate is 81.52%, and F1 score is 80.64%, which are better than those of six comparative models (FC-EF, FC-Siam-Diff, FC-Siam-Conc, PAN, MANet, and STANet). This verifies the effectiveness of the MASNet model as well as the feasibility of change detection by expanding existing public datasets.

Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and enlargement and dysfunction of the kidneys. The Consortium of Radiologic Imaging Studies of the Polycystic Kidney Disease (CRISP) cohort revealed that 89.1% had either a PKD1 or PKD2 mutation. Of the CRISP patients with a genetic cause detected, mutations in PKD1 accounted for 85%, while mutations in the PKD2 accounted for the remaining 15%. Here, we report exome sequencing of 16 Saudi patients diagnosed with ADPKD and 16 ethnically matched controls. Methods: Exome sequencing was performed using combinatorial probe-anchor synthesis and improved DNA Nanoballs technology on BGISEQ-500 sequencers (BGI, China) using the BGI Exome V4 (59 Mb) Kit. Identified variants were validated with Sanger sequencing. Results: With the exception of GC-rich exon 1, we obtained excellent coverage of PKD1 (mean read depth = 88) including both duplicated and non-duplicated regions. Of nine patients with typical ADPKD presentations (bilateral symmetrical kidney involvement, positive family history, concordant imaging, and kidney function), four had protein truncating PKD1 mutations, one had a PKD1 missense mutation, and one had a PKD2 mutation. These variants have not been previously observed in the Saudi population. In seven clinically diagnosed ADPKD cases but with atypical features, no PKD1 or PKD2 mutations were identified, but rare predicted pathogenic heterozygous variants were found in cystogenic candidate genes including PKHD1, PKD1L3, EGF, CFTR, and TSC2. Conclusions: Mutations in PKD1 and PKD2 are the most common cause of ADPKD in Saudi patients with typical ADPKD. Abbreviations: ADPKD: Autosomal dominant polycystic kidney disease; CFTR: Cystic fibrosis transmembrane conductance regulator; EGF: Epidermal growth factor; MCIC: Mayo Clinic Imaging Classification; PKD: Polycystic kidney disease; TSC2: Tuberous sclerosis complex 2

The Jiajika rare-metal deposit located in western Sichuan Province (China) is renowned as the largest lithium deposit in Asia, and the No. 134 pegmatite dike is the largest lithium pegmatite under mining conditions in the area. On the basis of a detailed characterization of textures and minerals in the Jiajika No. 134 pegmatite, two zones (the barren Zone I and the spodumene Zone II) and three subzones (Zone II was subdivided into microcrystalline, medium-fine grained and coarse-grained spodumene zones) have been identified. The detailed mineralogical characteristics of lithium minerals and other indicator minerals from each zone were evaluated by EPMA for illustrating the magmatic–hydrothermal evolution and the cooling path of the Jiajika No. 134 pegmatite. From the outer zone inwards, grain size gradually increased, the typical graphic pegmatite zone was absent, and spodumene randomly crystallized throughout nearly the whole pegmatite body. This evidence indicated a Li-saturated melt prior to pegmatite crystallization, which could be the main cause of the super-large-scale Li mineralization of the Jiajika No. 134 pegmatite. A comparison of the Cs content between primary beryl in the Jiajika No. 134 pegmatite and other important Li-Cs-Ta pegmatites in the world indicates that No. 134 pegmatite shows a high degree of fractional crystallization. The evolution of mica species from muscovite to Li-micas from Zone I to Zone II marks the transition from the magmatic to the hydrothermal stage in pegmatite evolution. The absence of individual lepidolite and the relatively limited scale of alteration of spodumene (

A correction to this paper has been published: https://doi.org/10.1038/s41419-021-03429-w

Abstract Background Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous retinal disorder characterized with failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. The purpose of this study was to investigate the molecular mechanisms by which the start codon mutation of the TSPAN12 causes difference in clinical manifestations between individuals in the same family. Methods Next‐generation sequencing (NGS)‐based target capture sequencing was performed in proband with a diagnosis of FEVR and their normal visual acuity family members. Cosegregation analysis of the candidate causative variant was performed in additional family members by using Sanger sequencing. Complete fundus examination, fundus fluorescein angiography (FFA), and family history collection were performed in all family members. Potential candidate causative variants were verified with reference to guidelines and standards from the American College of Medical Genetics and Genomics. Results We identified a novel heterozygous missense mutation (c.1A>G, p.M1V) localized in the start codon of the TSPAN12 and was detected as a potentially disease‐causing variant for the proband. Retrospective analysis of clinical data, fundus examination, and FFA showed that the mutant carrier presented peripheral retinal vascular anomalies in early stages, and visual acuity did not show significant effects. However, the proband who carried this mutation and his cousin showed typical high‐stage FEVR fundus changes coupled with a sharp decline in vision. Conclusions We report a novel start codon mutation (c.1A>G, p.M1V) in the TSPAN12 that causes clinically heterogeneous manifestations. Our results expand the mutation spectrums of TSPAN12, and will be valuable for disease diagnosis, prognosis, genetic counseling, and enriching our understanding of the role of the tetraspanin‐12 protein in the pathogenesis of FEVR.

Abstract Background Alzheimer’s disease (AD) is an important, progressive neurodegenerative disease, with a complex genetic architecture. A key goal of biomedical research is to seek out disease risk genes, and to elucidate the function of these risk genes in the development of disease. For this purpose, expanding the AD-associated gene set is necessary. In past research, the prediction methods for AD related genes has been limited in their exploration of the target genome regions. We here present a genome-wide method for AD candidate genes predictions. Methods We present a machine learning approach (SVM), based upon integrating gene expression data with human brain-specific gene network data, to discover the full spectrum of AD genes across the whole genome. Results We classified AD candidate genes with an accuracy and the area under the receiver operating characteristic (ROC) curve of 84.56% and 94%. Our approach provides a supplement for the spectrum of AD-associated genes extracted from more than 20,000 genes in a genome wide scale. Conclusions In this study, we have elucidated the whole-genome spectrum of AD, using a machine learning approach. Through this method, we expect for the candidate gene catalogue to provide a more comprehensive annotation of AD for researchers.

(1) Background: Considering the serious damage caused by castration and the extremely high outcrossing rate in nature, we hypothesized that artificial controlled pollination of black locust without castration could be conducted for hybridization breeding. (2) Methods: The study conducted controlled pollination on 20 mating combinations of black locust without castration using a single or mixed male parent. Offspring of different developmental stages and the leaves of parents were collected to extract DNA and perform paternity analysis using SSR molecular markers. (3) Results: The contribution rate of each male parent differed according to developmental stage after pollination using different pollens mixed in equal proportions. There were significant correlations between the genetic similarity between each male parent and female parent and contribution rate of each male parent at three different developmental stages after pollination. (4) Conclusions: The composition of offspring pollen donors showed no bias toward selfing or outcrossing when artificially pollinated without castration. Hybrid breeding of black locust by artificially controlled pollination without castration may not be feasible, given that our manual method resulted in a large number of abortive and abnormal offspring. Introduction of honeybees in a limited space to conduct controlled pollination of black locust for hybrid breeding may be feasible.

Weak interfacial interactions remain a bottleneck for composite materials due to their weakened performance and restricted applications. The development of core–shell engineering shed light on the preparation of compact and intact composites with improved interfacial interactions. This review addresses how core–shell engineering has been applied to energetic materials, with emphasis upon how micro-energetic materials, the most widely used particles in the military field, can be generated in a rational way. The preparation methods of core–shell structured explosives (CSEs) developed in the past few decades are summarized herein. Case studies on polymer-, explosive- and novel materials-based CSEs are presented in terms of their compositions and physical properties (e.g., thermal stability, mechanical properties and sensitivity). The mechanisms behind the dramatic and divergent properties of CSEs are also clarified. A glimpse of the future in this area is given to show the potential for CSEs and some suggestions regarding the future research directions are proposed.

Wounds have become one of the causes of death worldwide. The metabolic disorder of the wound microenvironment can lead to a series of serious symptoms, especially chronic wounds that bring great pain to patients, and there is currently no effective and widely used wound dressing. Therefore, it is important to develop new multifunctional wound dressings. Hydrogel is an ideal dressing candidate because of its 3D structure, good permeability, excellent biocompatibility, and ability to provide a moist environment for wound repair, which overcomes the shortcomings of traditional dressings. This article first briefly introduces the skin wound healing process, then the preparation methods of hydrogel dressings and the characteristics of hydrogel wound dressings made of natural biomaterials and synthetic materials are introduced. Finally, the development prospects and challenges of hydrogel wound dressings are discussed.

In this paper, a new method for manufacturing flexible and repeatable sensors made of silicon solar cells is reported. The method involves depositing the noble metal film directly onto the Si template and stripping out the substrate with a pyramid morphology by using an adhesive polymer. In order to evaluate the enhancement ability of the substrate, Rhodamine 6G (R6G) were used as surface-enhanced Raman scattering (SERS) probe molecules, and the results showed a high sensitivity and stability. The limit of detection was down to 10−12 M for R6G. The finite-difference time domain (FDTD) was used to reflect the distribution of the electromagnetic field, and the electric field was greatly enhanced on the surface of the inverted pyramidal substrate, especially in pits. The mechanism of Raman enhancement of two types of pyramidal SERS substrate, before and after stripping of the noble metal film, is discussed. By detecting low concentrations of plasmid DNA, the identification of seven characteristic peaks was successfully realized using a noble metallic pyramidal substrate.

Purpose: Norrie disease (ND) is a rare X-linked genetic disorder, the main symptoms of which are congenital blindness and white pupils. It has been reported that ND is caused by mutations in the NDP gene. Although many mutations in NDP have been reported, the genetic cause for many patients remains unknown. In this study, the aim is to investigate the genetic defect in a five-generation family with typical symptoms of ND. Methods: To identify the causative gene, next-generation sequencing based target capture sequencing was performed. Segregation analysis of the candidate variant was performed in additional family members using Sanger sequencing. Results: We identified a novel missense variant (c.314C>A) located within the NDP gene. The mutation cosegregated within all affected individuals in the family and was not found in unaffected members. By happenstance, in this family, we also detected a known pathogenic variant of retinitis pigmentosa in a healthy individual. Conclusion: c.314C>A mutation of NDP gene is a novel mutation and broadens the genetic spectrum of ND.

Background: Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this study, the aim is to identify the genetic cause of a five-generation Chinese autosomal dominant congenital cataract family. Methods: Whole exome sequencing (WES) was performed on three affected and one unaffected member of the family, known causative genes were scanned first. Sanger sequencing was used to validate co-segregation of the candidate variant in the family. The impact on the transcript and amino acid sequences of the variant was further analyzed. Results: We identified a novel splice donor site mutation c. 2825+1G >A in EPHA2 that was absent in public and in-house databases and showed co-segregation in the family. This variant resulted in an altered splice that led to protein truncation. Conclusions: The mutation we identified was responsible for congenital cataract in our studied family. Our findings broaden the spectrum of causative mutations in EPHA2 gene for congenital cataract and suggest that WES is an efficient strategy to scan variants in known causative genes for genetically heterogeneous diseases.

Oxidative stress plays an important role in Parkinson’s disease and other neurodegenerative disorders. Lycium barbarum polysaccharides (LBP), the main active ingredients extracted from the fruits of Lycium barbarum L., have been shown to be a potent antioxidant. In the present study, we investigated the protective effects, and the possible mechanism of action of LBP against 6-hydroxydopamine (6-OHDA)-induced apoptosis in PC12 cells. Our data demonstrated that LBP significantly reversed the 6-OHDA-induced decrease in cell viability, prevented 6-OHDA-induced changes in condensed nuclei and decreased the percentage of apoptotic cells in a dose-dependent manner. Furthermore, LBP also slowed the accumulation of reactive oxygen species (ROS) and nitric oxide (NO), decreased the level of protein-bound 3-nitrotyrosine (3-NT) and intracellular free Ca2+, and inhibiting the overexpression of nuclear factor κB (NF-κB), neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS). These results demonstrate that LBP prevents 6-OHDA-induced apoptosis in PC12 cells, at least in part through the ROS-NO pathway.

Extensive studies of the crystal-rich inclusions (CIs) hosted in minerals in pegmatite have resulted in substantially different models for the formation mechanism of the pegmatite. In order to evaluate these previously proposed formation mechanisms, the total homogenization processes of CIs hosted in spodumene from the Jiajika pegmatite deposit in Sichuan, China, were observed in situ under external H2O pressures in a new type of hydrothermal diamond-anvil cell (HDAC). The CIs in a spodumene chip were loaded in the sample chamber of HDAC with water, such that the CIs were under preset external H2O pressures during heating to avoid possible decrepitation. Our in situ observations showed that the crystals within the CIs were dissolved in carbonic-rich aqueous fluid during heating and that cristobalite was usually the first mineral being dissolved, followed by zabuyelite and silicate minerals until their total dissolution at temperatures between 500 and 720°C. These observations indicated that the minerals within the CIs were daughter minerals crystallized from an entrapped carbonate- and silica-rich aqueous solution and therefore provided useful information for evaluating the formation models of granitic pegmatites.

Granitic pegmatite deposits, which are usually products of orogenic processes during plate convergence, can be used to demonstrate regional tectonic evolution processes. In the eastern Tibetan Plateau in China, the Jiajika, Dahongliutan, Xuebaoding, Zhawulong, and Ke’eryin rare metal pegmatite deposits are located in the southern, western, northern, midwestern, and central areas of the Songpan−Ganzê orogenic belt, respectively. In this study, we dated two muscovite Ar−Ar ages of 189.4 ± 1.1 Ma and 187.0 ± 1.1 Ma from spodumene pegmatites of the Dahongliutan deposit. We also dated one zircon U-Pb age of 211.6 ± 5.2 Ma from muscovite granite, two muscovite Ar−Ar ages of 179.6 ± 1.0 Ma and 174.3 ± 0.9 Ma, and one columbite−tantalite U-Pb age of 204.5 ± 1.8 Ma from spodumene pegmatites of the Zhawulong deposit. In addition, we dated one muscovite Ar−Ar age of 159.0 ± 1.4 Ma from spodumene pegmatite of the Ke’eryin deposit. Combining these ages and previous studies in chronology, we concluded that the granitic magma in the Jiajika, Xuebaoding, Dahongliutan, Zhawulong, and Ke’eryin deposits intruded into Triassic metaturbidites at approximately 223, 221, 220−217, 212, and 207−205 Ma, respectively, and that the crystallization of the corresponding pegmatite ceased at approximately 199−196, 195−190, 189−187, 180−174, and 159 Ma, respectively. In this study, we demonstrated that the peak in magmatic activity and the final crystallization age of the pegmatite lagged behind one another from the outer areas of the orogeny belt to the inner areas. The pegmatite−parented granitic magmas were sourced from Triassic metaturbidites that were melted by shear heating along the large-scale decollement resulting from Indosinian collisions along the North China block, Qiangtang−Changdu block, and Yangtze block. As a result, the above temporal and spatial regularities indicated that the tectonic−thermal stress resulting from the collisions of three blocks was transferred from the outer areas of the orogenic belt to the inner areas. A large amount of heat and a slow cooling rate at the convergent center of thermal stress in two directions will lead to crystallization and differentiation of magma in the Songpan−Ganzê orogenic belt, forming additional rare metal deposits.

This paper reports the development and validation of an assay for ifenprodil based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) and its application to a pharmacokinetic study involving single and multiple intravenous infusions to healthy Chinese volunteers. After sample preparation of plasma by liquid–liquid extraction with ethyl acetate, the analyte and internal standard, urapidil, were separated by reversed phase chromatography in a run time of 4 min and detected by positive ion electrospray ionization followed by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 326.2→308.1 for ifenprodil and m/z 388.4→205.3 for IS. The assay was linear in the concentration range 0.2–50.0 ng/mL with recovery >76.4%. In the pharmacokinetic study of single intravenous infusions of 5, 10 and 15 mg ifenprodil, peak plasma concentrations and areas under the plasma concentration–time curve were both linearly related to dose. In the pharmacokinetic study of multiple once daily intravenous infusions of 10 mg ifenprodil for 7 days, pharmacokinetic parameters were similar to those after the single dose showing that ifenprodil does not accumulate on repeated administration.

This study aimed to identify the genetics underlying dominant forms of inherited retinal dystrophies using whole exome sequencing (WES) in six families extensively screened for known mutations or genes. Thirty-eight individuals were subjected to WES. Causative variants were searched among single nucleotide variants (SNVs) and insertion/deletion variants (indels) and whenever no potential candidate emerged, copy number variant (CNV) analysis was performed. Variants or regions harboring a candidate variant were prioritized and segregation of the variant with the disease was further assessed using Sanger sequencing in case of SNVs and indels, and quantitative PCR (qPCR) for CNVs. SNV and indel analysis led to the identification of a previously reported mutation in PRPH2. Two additional mutations linked to different forms of retinal dystrophies were identified in two families: a known frameshift deletion in RPGR, a gene responsible for X-linked retinitis pigmentosa and p.Ser163Arg in C1QTNF5 associated with Late-Onset Retinal Degeneration. A novel heterozygous deletion spanning the entire region of PRPF31 was also identified in the affected members of a fourth family, which was confirmed with qPCR. This study allowed the identification of the genetic cause of the retinal dystrophy and the establishment of a correct diagnosis in four families, including a large heterozygous deletion in PRPF31, typically considered one of the pitfalls of this method. Since all findings in this study are restricted to known genes, we propose that targeted sequencing using gene-panel is an optimal first approach for the genetic screening and that once known genetic causes are ruled out, WES might be used to uncover new genes involved in inherited retinal dystrophies.

Euodia rutaecarpa is a common traditional Chinese medicine (TCM) in clinical practice, having the ability to suppress pain and cease coughing; however, with the increasing reports showing that it is toxic, particularly hepatotoxic, the concerns raised by what cause its toxicity is growing. In the current study, an analysis method based on the spectrum effect has been employed to screen the major hepatotoxic components in Euodia rutaecarpa so that the toxic material’s basis would be elucidated. A fingerprinting method of the Euodia rutaecarpa extracts (which were petroleum ether, chloroform, ethyl acetate, n-butanol, and water) using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF/MS) has been developed. Orthogonal partial least squares (OPLS) was used to establish the spectrum-toxicity relationship with the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice serum as evaluation indices for liver injury. The UHPLC-MS fingerprint was established and the OPLS analytical results suggested that coniferin, 1-methyl-2-undecyl-4(1H)-quinolone, 1-methyl-2-[(6Z,9Z,12E)-pentadeca triene]-4(1H)-quinolone, evocarpine, 1-methyl-2-[(Z)-7-tridecenyl]-4(1H)-quinolone, dihydroevocarpine, and 1-methyl-2-tetradecy-4-(1H)-quinolone probably associated with the hepatotoxicity of Euodia rutaecarpa. This paper offered considerable methods and insight for the fundamental research of the toxic material basis of similar toxic TCMs.