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The reverse time migration (RTM) of ground penetrating radar (GPR) is usually implemented in its two-dimensional (2D) form, due to huge computational cost. However, 2D RTM algorithm is difficult to focus the scattering signal and produce a high precision subsurface image when the object is buried in a complicated subsurface environment. To better handle the multi-offset GPR data, we propose a three-dimensional (3D) prestack RTM algorithm. The high-order finite difference time domian (FDTD) method, with the accuracy of eighth-order in space and second-order in time, is applied to simulate the forward and backward extrapolation electromagnetic fields. In addition, we use the normalized correlation imaging condition to obtain pre-stack RTM result and the Laplace filter to suppress the low frequency noise generated during the correlation process. The numerical test of 3D simulated GPR data demonstrated that 3D RTM image shows excellent coincidence with the true model. Compared with 2D RTM image, the 3D RTM image can more clearly and accurately reflect the 3D spatial distribution of the target, and the resolution of the imaging results is far better. Furthermore, the application of observed GPR data further validates the effectiveness of the proposed 3D GPR RTM algorithm, and its final image can more reliably guide the subsequent interpretation.

Altered behavioural responses to sensory stimuli, including both hypo- and hyper-reactivity, have been found in individuals with schizophrenia. However, how specific sensory responsiveness patterns are associated with symptomatology of schizophrenia remains largely unknown. The present study aimed to examine sensory responsiveness in typically-developing (TD) adolescents (n = 98) and adolescents with early-onset schizophrenia (EOS) (n = 29) and investigate the relationship between schizotypal traits and sensory responsiveness patterns. All participants completed the Adult/Adolescent Sensory Profile (AASP), the Schizotypal Personality Questionnaire (SPQ) and the Autism Spectrum Quotient (AQ). Results showed that higher levels of hypersensitivity and hyposensitivity coexisted in EOS patients and were correlated with positive and negative symptoms of schizophrenia. Atypical sensory experiences except for sensory seeking were found to be positively correlated with higher levels of schizotypal traits regardless of diagnostic status. Moreover, the strength and pattern of such correlations were comparable in both EOS and TD groups. This study also provided evidence that higher levels of autistic traits would intensify the positive correlation between schizotypal traits and sensory responsiveness abnormalities, suggesting an additive effect of co-occurring schizotypal and autistic traits on atypical sensory experiences. These findings extend previous research by depicting sensory responsiveness patterns in younger populations with schizophrenia, and may have implications for future development of sensory-related interventions in clinical settings.

Glioma is one of the most commonly diagnosed brain malignancies with a high cancer-related death rate in humans. The prognosis of glioma patients is still unsatisfactory. In the present study, we attempted to identify lncRNAs and miRNAs that might be related to NF-κB-mediated epithelial-mesenchymal transition in glioma cells based on online microarray expression profiles, and investigate the specific effects of lncRNA-miRNA-mRNA axes on glioma cell phenotypes. Herein, we identified lncRNA DGCR5 as a downregulated lncRNA in glioma that was negatively regulated by NF-κB1 in an NF-κB1 RE-dependent manner. LncRNA DGCR5 overexpression significantly inhibited the capacity of glioma cells to proliferate, migrate, and invade, whereas promoted the apoptosis of glioma cells. Moreover, lncRNA DGCR5 overexpression upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker VIM, as well as Snai2 and TWIST. Regarding the underlying molecular mechanisms, lncRNA DGCR5 could inhibit miR-21 and miR-23a expression, and miR-21 or miR-23a overexpression significantly reversed the tumor-suppressive effects of lncRNA DGCR5 overexpression. LncRNA DGCR5 exerted its tumor-suppressive effects through the DGCR5/miR-21/Smad7 and DGCR5/miR-23a/PTEN axes. In conclusion, lncRNA DGCR5 suppresses the capacity of glioma cells to migrate and invade via miR-21/Smad7, whereas it inhibits the proliferation and enhances the apoptosis of glioma cells through miR-23a/PTEN.

Stable quantum memories that capable of storing quantum information for long time scales are an essential building block for an array of potential applications. The long memory time are usually achieved via dynamical decoupling technique involving decoupling of the memory states from its local environment. However, because this process is strongly limited by the errors in the pulses, an noise-protected scheme remains challenging in the field of quantum memories. Here we propose a scheme to design a noise-resisted \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pi$$\end{document}π pulse, which features high fidelity exceeding \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$99.9\%$$\end{document}99.9% under realistic situations. Using this \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pi$$\end{document}π pulse we can generate different dynamical decoupling sequences that preserve high fidelity for long time scales. The versatility, robustness, and potential scalability of this method may allow for various applications in quantum memories technology.

Retinitis pigmentosa (RP) is a complex group of hereditary retinal dystrophies. Although >60 genes have been identified to be associated with non-syndromic RP, the exact genetic variant remains elusive in numerous cases of RP. In the present study, a Chinese pedigree affected by RP with autosomal recessive inheritance, including a total of seven members with one affected patient and six unaffected individuals, was recruited. Comprehensive ophthalmic examinations were performed on the proband and the proband's unaffected daughter. Genomic DNA was extracted from peripheral blood. Whole-exome sequencing (WES) was performed for the affected individual. The candidate pathogenic variant was verified by direct Sanger sequencing. The affected individual presented with classical clinical symptoms of RP. A novel homozygous variant, c.265delC (p.L89Ffs*3) in the cyclic nucleotide-gated channel subunit α 1 gene was identified in the affected patient. This homozygous variant was absent in other unaffected family members and 600 ethnicity-matched healthy controls. The variant was co-segregated with the disease phenotype in an autosomal recessive manner.

Correctly locating the tunnel lining cavity is extremely important tunnel quality inspection. High-accuracy imaging results are hard to obtain because conventional one-way wave migration is greatly affected by lateral velocity change and inclination limitation and because the diffracted wave cannot be accurately returned to the real spatial position of the lining cavity. This paper presents a tunnel lining cavity imaging method based on the ground-penetrating radar (GPR) reverse-time migration (RTM) algorithm. The principle of GPR RTM is described in detail using the electromagnetic wave equation. The finite-difference timedomain method is employed to calculate the backward extrapolation electromagnetic fields, and the zero-time imaging condition based on the exploding-reflector concept is used to obtain the RTM results. On this basis, the GPR RTM program is compiled and applied to the simulated and observed GPR data of a typical tunnel lining cavity GPR model and a physical lining cavity model. Comparison of RTM and Kirchhoff migration results reveals that the RTM can better converge the diffracted waves of steel bar and cavity to their true position and have higher resolution and better suppress the effect of multiple interference and clutter scattering waves. In addition, comparison of RTM results of different degrees of noise shows that RTM has strong anti-interference ability and can be used for the accurate interpretation of radar profile in a strong interference environment.

A large genome-wide association study showed that five new variants, {A total 799 POAG patients and 799 controls are enrolled in this case-control study. All individuals were genotyped for the five single-nucleotide polymorphisms (SNPs) using ABI SNaPshot method. Four genetic models (homozygous, heterozygous, dominant, and recessive) were applied to further evaluate the possible correlation between the five SNPs and POAG.In our study, rs736893 in theOur findings indicated that

Accurate, rapid, and reliable quantification of saccharides is essential for understanding their behaviors and roles in environmental processes. However, the conventional colorimetric method for saccharide quantification fails to discriminate between fructose and glucose, resulting in the misestimation of total saccharides. To solve this problem, a fluorescence approach, that is, parallel factor framework-linear regression analysis, was developed in this work to quantify the specific fluorescence signatures of the fluorescent products generated from the reaction between saccharides and sulfuric acid. The fluorescent derivatives of saccharides were recognized and the simultaneous quantification of glucose and fructose was achieved with a detection limit of 2.9 μg/mL and 1.3 μg/mL, respectively. Furthermore, 200 μg/mL of the treated sorbitol and gluconic acid only, respectively, equaled to 6 μg/mL and 3 μg/mL of the treated glucose, indicating their negligible interference for the saccharide quantification using this method. In addition, the feasibility and robustness of this method in environmental applications were validated with the recovery tests using spiked real water samples. This fluorescence-based approach offers a new tool to monitor saccharides in complex environments.

Objectives This paper is aimed to explore the value of double source CT angiography (DS-CTA) for diagnosing in-stent restenosis in lower limb artery. Methods From January 2016 to October 2018, all patients with stent in lower limb artery in our hospital were investigated by both DS-CTA and digital subtraction angiography. We measured the minimum lumen diameter and the diameter of the proximal normal vessels under each stent placement. The in-stent restenosis is defined as restenosis when the lumen area decreased by more than 50%. Digital subtraction angiography was performed within 1 week after DS-CT scan. Relationship between DS-CTA and digital subtraction angiography for diagnosing in-stent restenosis in lower limb artery was analyzed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DS-CTA for diagnosis of in-stent restenosis were analyzed with digital subtraction angiography as the reference standard. A total of 68 stents were placed in 51 patients. Among these patients, 27 cases were diagnosed as in-stent restenosis, presenting as endovascular contrast agent bias or crescent filling defect with the lumen area reducing over 50%, 6 cases of which had no significant in-stent restenosis by digital subtraction angiography analysis. Furthermore, 12 cases were occlusion, in which there was no high density contrast agent in stents; the remaining 41 stents were unobstructed and the contrast agent was filled well, 8 cases of which had significant in-stent restenosis by digital subtraction angiography analysis. In addition, four stents were deformed or distorted. Statistical analysis demonstrated the concentrations of DS-CTA and digital subtraction angiography in diagnosing in-stent restenosis for lower limb artery were closely related, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DS-CTA were 72.4%, 84.6%, 77.8%, 80.5%, and 79.4%, respectively. Conclusion DS-CTA has a potential reliability for diagnosis of in-stent restenosis in lower limb artery, which may be further improved to be used for clinical interventional treatment of vascular diseases.

Fatigue driving is one of the main factors which affect the safety of drivers and passengers in mountain freeway. To improve the driving safety, the application of fatigue driving detection system is a crucial measure. Accuracy, speed and robustness are key performances of fatigue detection system. However, most researches pay attention to one of them, instead of taking care of them all. It has limitation in practical application. This paper proposes a novel three-layered framework, named Real-time and Robust Detection System. Specifically, the framework includes three modules, called facial feature extraction, eyes regions extraction and fatigue detection. In the facial feature extraction module, the paper designs a deep cascaded convolutional neural network to detect the face and locate eye key points. Then, a face tracking sub-module is constructed to increase the speed of the algorithm, and a face validation submodule is applied to improve the stability of detection. Furthermore, to ensure the orderly operation of each sub-module, we designed a recognition loop based on the finite state machine. It can extract facial feature of the driver. In the second module, eyes regions of the driver were captured according to the geometric feature of face and eyes. In the fatigue detection module, the ellipse fitting method is applied to obtain the shape of driver's pupils. According to the relationship between the long and short axes of the ellipse, eyes state (opening or closed) can be decided. Lastly, the PERCLOS, which is defined by calculating the number of closed eyes in a period, is used to determine whether fatigue driving or not. The experimental results show that the comprehensive accuracy of fatigue detection is 95.87%. The average algorithm rate is 32.29 ms/f in an image of 640×480 pixels. The research results can serve the design of a new generation of driver fatigue detection system to mountain freeway.

Background Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. Method FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/β-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. Result Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P Conclusion FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/βcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.

We propose a scheme to generate ultra-strong four-wave mixing (FWM) signal based on a suspended monolayer graphene nanoribbon nanomechanical resonator (NR) coupled to an Au nanoparticle (NP). It is shown that, the FWM spectrum can switch among two-peaked, three-peaked, four-peaked or five-peaked via the modulation of exciton-phonon and exciton-plasmon couplings. This is mainly attributed to the vibrational properties of NR related to the exciton-phonon coupling, and the energy-level splitting of the localized exciton correlated to three classes of resonances consisting of three-photon resonance, Rayleigh Resonance, and AC-Stark atomic resonance. Especially, in a dual-strong coupling regime, the gains for these peaks can be as high as nine orders of magnitude (∼ 109) around the lower bistable threshold due to a combined effect of two couplings. Our findings not only offer an efficient way to measure the vibrational frequency of NR and the exciton-phonon coupling strength but also provide a possibility to fabricate high-performance optoelectronic nanodevices.

Objectives: To investigate intra-specialty citation patterns of radiology articles, compared with another medical specialty: gastroenterology/hepatology. Methods: Four radiology journals ( Radiology, European Radiology, Diagnostic and Interventional Imaging, Canadian Association of Radiologists Journal) and four gastroenterology/hepatology journals ( Journal of Hepatology, Journal of Gastroenterology, World Journal of Gastroenterology, Journal of Clinical Gastroenterology) with similar Web of Science in-category 2020 IF ranking were selected. The original research, review, letter, and editorial articles published in these journals in 2021 were identified. The average number of intra-specialty citations per article (intra-specialty citation count) and percentage of intra-specialty citations out of total citations per article (intra-specialty citation rate) were compared between radiology and gastroenterology/hepatology articles using Student’s t-test. Results: The radiology articles demonstrated a lower total citation count per article (radiology: 29.7 ± .4 (mean ± SEM), n = 2063; gastroenterology/hepatology: 50.1 ± 1.4, n = 1335). The intra-specialty citation count was also lower in radiology articles than gastroenterology/hepatology articles (radiology: 12.9 ± .2, gastroenterology/hepatology: 19.6 ± .7; P < .001), both overall and in all article types. Additionally, the overall intra-specialty citation rate was not significantly different between the two specialties (radiology: 48.8% ± .5%; gastroenterology/hepatology: 47.1 ± .8%; P = .057), although the intra-specialty citation rates were higher in radiology original research and editorial article types. Conclusions: The significantly lower per-article intra-specialty citation counts in all radiology article types, a measurement that directly links to specialty IFs, may contribute to the lower impact factors of radiology journals compared with gastroenterology/hepatology ones.

Given the failure of reverse cut-off seal performance in the test process of the check valve, the fault location and mechanism analysis were carried out, and the improvement measures were proposed and verified by the test. It is analyzed that the main reason for the failure is the unreasonable design of the moving pair and the welding position of the check valve, which makes the sealing pair cannot fit effectively after the welding of the check valve, leading to the failure of the reverse cut-off seal. By controlling the ratio of the length of the guide surface to the diameter of the guide surface to 1.25, and controlling the distance between the welding position and the sealing pair to 10mm, the failure problem of the reverse cut-off seal of the check valve caused by the unreasonable design of the moving pair and the weld position is successfully solved. The effectiveness of the improved scheme of the check valve is verified by the test.

Multiple myeloma (MM), characterized by high intratumour heterogeneity, accounts for ∼10% of all haematologic malignancies. Stratified by the Revised International Staging System (R-ISS), little is known about R-ISS-related plasma cell (PC) heterogeneity, gene expression modules in cytotoxic T/NK cells and immunoregulatory ligands and receptors. Herein, we constructed a single-cell transcriptome atlas of bone marrow in normal and R-ISS-staged MM patients. Focusing on PCs, we identified and validated a subset of GZMA+ cytotoxic PCs. In addition, a malignant PC population with high proliferation capability (proliferating PCs) was associated with unfavourable prognosis and EBV infection in our collected samples. Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), a specific marker of proliferating PCs, was shown to induce MM cell line proliferation and serve as a detrimental marker in MM. Subsequently, three R-ISS-dependent gene modules in cytotoxic CD8+ T and NKT cells were identified and functionally analysed. Finally, cell-cell communication between neutrophils and proliferating PCs with cytotoxic CD8+ T and NKT cells was investigated, which identified intercellular ligand receptors and potential immunotargets such as SIRPA-CD47 and TIGIT-NECTIN3. Collectively, this study provides an R-ISS-related single-cell MM atlas and reveals the clinical significance of two PC clusters, as well as potential immunotargets in MM progression.

Retinitis pigmentosa (RP) belongs to a family of retinal disorders that is characterized by the progressive degeneration of rod and cone photoreceptors. The aim of the present study was to screen for possible disease-causing genetic variants in a non-consanguineous Chinese family with non-syndromic autosomal recessive RP. Whole-exome sequencing (WES) was performed in samples from the affected individual (the proband) and those from the two children of the proband. A novel compound heterozygous variant of c.C958T (p.R320X) and c.G1355A (p.R452H) in the

Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant PC population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, ribonucleotide reductase regulatory subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8Multiple myeloma is a type of bone cancer. It affects the immune cells that make antibodies, known as plasma cells. These immune cells live in the bone marrow. As with many types of cancer, the chance of survival is highest when multiple myeloma is diagnosed early. It has three stages, labelled I, II, and III. People with stage I or II disease have better outcomes than those with stage III, but the exact reasons are unclear. Bone marrow contains lots of different types of cells, which can affect the growth of a tumour. These include cancer-targeting cells, called killer T-cells, and cancer-supporting cells called myeloid cells. Understanding these cells and how they interact could shed light on the different stages of multiple myeloma. One way to do this is to use single cell sequencing, which looks at the genes in use inside each cell at any one time. Zhong, Hao, Zhang, Jiang et al. examined the bone marrow of two healthy donors and nine people with different stages of multiple myeloma. This revealed two new groups of plasma cells. One group, highest in stage II patients, was protective, with the potential to kill cancer cells. The other, highest in people with more aggressive disease, was harmful, with the potential to divide rapidly. The sequencing also identified molecules that might be useful drug targets for the future. These included a gene that drove growth in the dangerous plasma cells, and several that might help tumours escape from the immune system. It is becoming increasingly clear that the environment around a tumour has a huge role to play in its progression. Understanding how this environment changes over time could aid in the development of more targeted treatments. The next step is to find out more about the molecules identified here.

Windblown sand two-phase flow characteristics become an essential factor in evaluating the windblown sand load on infrastructures and civil structures. Based on the measured wind characteristics in arid desert regions, windblown sand flow fields with three kinds of sand beds are simulated in the wind tunnel, respectively. The results indicate that the characteristic saltation height of sand particles increases with the wind speed and particle size in the windblown sand flow field. As the sand concentration increases, the wind speed decreases, and the turbulence intensity increases. The concentration, energy, and impact pressure of sand particles increase with increasing wind speed and decrease exponentially with increasing height. At the same wind speed, the concentration, energy, and impact pressure of the coarse sand, fine sand, and mixed sand increases, in turn. Moreover, the variation of kinetic energy with height is similar to that of total energy with height and the proportion of potential energy to total energy is quite small.

An understanding of the excited-state process and the sensing mechanism for specific anions can be helpful for the design and synthesis of fluorescent sensors in analytical chemistry and biotechnology. Here, we theoretically investigated the fluorescent response mechanism of a reported acylhydrazone-based fluorescent sensor (Soft Matter, 2019, 15, 6690) for fluoride recognition using the time-dependent density functional theory approach. At the M06/TZVP/SCM level, the vertical excitation energies, which were calculated based on the ground state and first singlet-state geometries of the sensor molecule, agreed well with the experimental ultraviolet-visible and fluorescence spectra. Therefore, the time-dependent density functional theory method was considered reasonable and effective. According to the frontier orbital analysis and an excited-state potential energy scan, we proposed an excited-state proton transfer mechanism for the sensor-fluorine complex, where the steric hindrance leads to a high potential barrier. The excited-state proton transfer process facilitates sensor molecule deprotonation, alleviates its steric hindrance effect and expands its conjugated system. As a result, the fluorescence emission band of the sensor molecule was red-shifted significantly with the addition of fluoride anion. Based on this fluorescence difference, the sensor could be used for fluoride anion identification. This work provides a strategy to study sensor-analyte interactions in the excited state and offers an approach to tune the fluorescence emission wavelength of sensor molecules in anionic environments.

Nuclear pore complexes (NPCs) are channels for nucleocytoplasmic transport of proteins and RNAs. However, it remains unclear whether composition, structure, and permeability of NPCs dynamically change during the cleavage period of vertebrate embryos and affect embryonic development. Here, we report that the comprehensive NPC maturity (CNM) controls the onset of zygotic genome activation (ZGA) during zebrafish early embryogenesis. We show that more nucleoporin proteins are recruited to and assembled into NPCs with development, resulting in progressive increase of NPCs in size and complexity. Maternal transcription factors (TFs) transport into nuclei more efficiently with increasing CNM. Deficiency or dysfunction of Nup133 or Ahctf1/Elys impairs NPC assembly, maternal TFs nuclear transport, and ZGA onset, while nup133 overexpression promotes these processes. Therefore, CNM may act as a molecular timer for ZGA by controlling nuclear transport of maternal TFs that reach nuclear concentration thresholds at a given time to initiate ZGA.

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10−15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10−3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10−16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Immune checkpoint therapy targeting the PD-1/PD-L1 axis is a potentially novel development in anticancer therapy and has been applied to clinical medicine. However, there are still some problems, including a relatively low response rate, innate mechanisms of resistance against immune checkpoint blockades, and the absence of reliable biomarkers to predict responsiveness. In this study of in vitro and in vivo models, we demonstrate that PD-L1–vInt4, a splicing variant of PD-L1, plays a role as a decoy in anti–PD-L1 antibody treatment. First, we showed that PD-L1–vInt4 was detectable in clinical samples and that it was possible to visualize the secreting variants with IHC. By overexpressing the PD-L1–secreted splicing variant on MC38 cells, we observed that an immune-suppressing effect was not induced by their secretion alone. We then demonstrated that PD-L1–vInt4 secretion resisted anti–PD-L1 antibody treatment, compared with WT PD-L1, which was explicable by the PD-L1–vInt4’s decoying of the anti–PD-L1 antibody. The decoying function of PD-L1 splicing variants may be one of the reasons for cancers being resistant to anti–PD-L1 therapy. Measuring serum PD-L1 levels might be helpful in deciding the therapeutic strategy.

Histone recognition constitutes a key epigenetic mechanism in gene regulation and cell fate decision. PHF14 is a conserved multi-PHD finger protein that has been implicated in organ development, tissue homeostasis, and tumorigenesis. Here we show that PHF14 reads unmodified histone H3(1–34) through an integrated PHD1-ZnK-PHD2 cassette (PHF14PZP). Our binding, structural and HDX-MS analyses revealed a feature of bipartite recognition, in which PHF14PZP utilizes two distinct surfaces for concurrent yet separable engagement of segments H3-Nter (e.g. 1–15) and H3-middle (e.g. 14–34) of H3(1–34). Structural studies revealed a novel histone H3 binding mode by PHD1 of PHF14PZP, in which a PHF14-unique insertion loop but not the core β-strands of a PHD finger dominates H3K4 readout. Binding studies showed that H3-PHF14PZP engagement is sensitive to modifications occurring to H3 R2, T3, K4, R8 and K23 but not K9 and K27, suggesting multiple layers of modification switch. Collectively, our work calls attention to PHF14 as a ‘ground’ state (unmodified) H3(1–34) reader that can be negatively regulated by active marks, thus providing molecular insights into a repressive function of PHF14 and its derepression.

Genetic factors have been studied to be associated with diabetic retinopathy (DR). This study aimed to investigate the association between the polymorphisms in theThere were 475 patients with diabetic retinopathy (DR), 478 type 2 diabetes mellitus without retinopathy (DNR) and 469 healthy controls collected in this study.There was a statistically significant difference forThis study showed that

Closed-loop deep brain stimulation (DBS) paradigm is gaining tremendous favor due to its potential capability of further and more efficient improvements in neurological diseases. Preclinical validation of closed-loop controller is quite necessary in order to minimize injury risks of clinical trials to patients, which can greatly benefit from real-time computational models and thus potentially reduce research and development costs and time. Here we developed an embedded multi-core real-time simulation platform (EMC-RTP) for a biological-faithful computational network model of basal ganglia (BG). The single neuron model is implemented in a highly real-time manner using a reasonable simplification. A modular mapping architecture with hierarchical routing organization was constructed to mimic the pathological neural activities of BG observed in parkinsonian conditions. A closed-loop simulation testbed for DBS validation was then set up using a host computer as the DBS controller. The availability of EMC-RTP and the testbed system was validated by comparing the performance of open-loop and proportional-integral (PI) controllers. Our experimental results showed that the proposed EMC-RTP reproduces abnormal beta bursts of BG in parkinsonian conditions while meets requirements of both real-time and computational accuracy as well. Closed-loop DBS experiments using the EMC-RTP suggested that the platform could perform reasonable output under different kinds of DBS strategies, indicating the usability of the platform.

In many cultures, rice is let to cool for a while after cooking before being consumed, which results in some retrogradation of the starch. The in vitro digestibility of 16 cooked rice starches after extended cold (4 °C) storage, which leads to extensive retrogradation, was investigated from the perspective of their starch molecular fine structure. Size-exclusion chromatography (SEC) and fluorophore-assisted carbohydrate electrophoresis (FACE) were used to characterize the starch chain-length distributions (CLDs) and whole molecular size distributions. The retrograded starch gel network was studied by differential scanning calorimetry and scanning electron microscopy. Pearson correlation analysis with in vitro digestibility revealed that the starch digestion rate was positively correlated with cell size and cell wall thickness within the formed gel network, which was mainly derived from the interactions of amylose short-medium chains and not strongly related to amylopectin molecular structure. This suggests that rather than just altering amylose content, modification of amylose fine molecular structure (e.g. increasing the amount of short-medium amylose chains) can also slow rice starch digestibility.

Chromium (Cr(VI)) is highly toxic and carcinogenic. Cr(VI) water pollution has become more and more serious. This article reports on a study in which lotus seed pods (LSP), an agricultural waste product, was used to efficiently remove Cr(VI) from an aqueous solution, and the carbonization product of LSP after the removal of Cr(VI) (CPLSP) can be regarded as a resource containing Cr. Cr(VI) removed by LSP fits a pseudo-second-order model. pH levels greatly influence the amount of Cr removed. The maximum removal of Cr(VI) by LSP in aqueous solution was 153.85 mg/g. The possible removal mechanism is absorption, redox, and reabsorption based upon SEM/EDS, FT-IR, and XPS spectra results. The Cr content of CPLSP was 42.95% by ammonium persulfate oxidation titrimetric method. These results suggest that LSP can be an excellent, low cost, biomaterial for removing and enriching Cr(VI) from an aqueous solution. PRACTITIONER POINTS: Lotus seed pods are an efficient adsorbent for Cr(VI) from aqueous solutions. The Cr removal by lotus seed pods occurs via absorption, redox, and reabsorption. Cr can be captured after the pods are carbonized. Lotus seed pods can be applied to the removal and enrichment of Cr(VI) from waste water.

Electrical Impedance Tomography (EIT), an imaging technique which operates non-invasively and without radiation exposure, provides information about ventilation- and cardiac-synchronous (pulsatile) changes in the lung. It is well known, that perfusion within the thorax is influenced by lung volume or intrathoracic pressure. In this observational study, it shall be investigated if this phenomenon can be monitored by EIT. Therefore, the impact of the amount of air within the lung on the pulsatile EIT signal was evaluated by carrying out EIT measurements with a spontaneously breathing lung healthy subject holding the breath at three different inspiratory and three various expiratory volume levels during normal tidal breathing. For EIT data analysis, a region of interest was defined by including lung tissue and excluding the heart region. The EIT data revealed, that the shape and the amplitude of the pulsatile EIT signal (evaluated per heartbeat) during the phases of breath holding were dependent on the enclosed lung volume. For lung volumes > 4 L, the amplitude of the pulsatile EIT signal increased with rising inspiratory level and the shape remained almost unchanged. For lung volumes < 4 L, a change in shape was visible but the amplitude remained more or less the same with decreasing expiratory level. Since the results of this observational study show that the pulsatile EIT signal is influenced by the lung volume, it might be used in future to draw conclusions of cardiacpulmonary interactions or intrathoracic pressure states, benefitting the treatment of intensive care patients.

As a type of moderate- and high-temperature thermoelectric materials, half-Heusler thermoelectric materials have a unique advantage in terms of their power factors and mechanical properties, and the figure of merit (ZT) of FeNb0.88Hf0.12Sb reaches 1.0 at 600°C. In this paper, after taking into account factors such as electrical conductivity, thermal conductivity, melting point, and metal activity, silver (Ag) was selected as the barrier layer material. The barrier layer and thermoelectric materials were welded together by atomic diffusion using spark plasma sintering. There was no obvious elemental diffusion on the connection surface after sintering, indicating that Ag did not impact the performance of FeNb0.88Hf0.12Sb. However, many cracks appeared on the joint surface during the aging process. In further experiments, we added a small amount of nickel (Ni) into the Ag to achieve a close connection between the barrier layer and FeNb0.88Hf0.12Sb. Moreover, we analyzed the interface of the intermetallic compounds after aging for 192 h, which showed that Ni3Nb and Ni6Nb7 compounds formed at the interface. The contact resistance was tested by a scanning probe method, and the resistivity of the barrier layer was determined to be 0.4 μΩ cm2, which is far less than that of other barrier layers. Moreover, the connection strength was greater than 40 MPa. When Ag0.9Ni0.1 was used as the barrier layer to compose the half-Heusler thermoelectric module, the thermoelectric conversion efficiency reached 7.33%, and there was no significant decrease in efficiency during the cyclic test.

Cross-linked biopolymer networks are widespread in the cytoskeleton of cells and biological gels, which are responsible for maintaining the structural integrity of the cells/materials as well as generating forces to drive cellular movement. Microscopically, these networks are composed of randomly distributed semi-flexible filaments along with the associated cross-linking and motor proteins that are under constant external and internal stresses. In the present study, we developed a computational model based on Langevin dynamics to examine the mechanical response of such networks where the bending and stretching of individual biopolymers, deformation and breakage of cross-linkers and the active role of molecular motors have all been considered. It was found that pronounced strain stiffening took place with increasing imposed shear deformation. However, such stiffening effect under shear was attenuated by the successive rupture of cross-linkers. Interestingly, the appearance of motor-induced contractile forces within the networks significantly increased their apparent modulus in the entropy-dominated regime (i.e., at small strains). In addition, considerable bundling and re-alignment of filaments were also observed under the contraction by motor proteins, in agreement with experimental observations. Finally, the fluctuating forces generated by active motors were found to contribute to the enhanced diffusion of nanometer-sized particles within the network.

Indomethacin (Indo) and naproxen (Nap) belong to Biopharmaceutical Classification System (BCS) class II drugs, which permeate membranes well but are poorly soluble. Two pharmaceutical salts hydrate of Indo and Nap with (1R,2R)-1,2-diphenylethylenediamine (DPEN) were obtained using solution crystallization. Both salts, (DPEN)2·(Indo)2·(H2O)2 and (DPEN)1·(Nap)1·(H2O)0.5, were characterised using various solid-state characterisation techniques such as single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Raman spectra. The structure analysis shows that DPEN is monocation as only one amine is protonated into ammonium. The Indo, DPEN and water molecules form one-dimensional hydrogen bond chains through extensive N H⋯O, N H⋯N and O H⋯N interactions. The solubility study shows that the two salts are more soluble in pH 1.2, 4.5 and 6.8 buffer mediums compared with pure raw materials. Solubility thermodynamics calculation was carried out to further understand the solubility properties of two salts.

Background: It has been shown that genetic factors play an important role in the pathogenesis of primary open-angle glaucoma (POAG). This study was conducted to investigate the association between the polymorphism rs11656696 located in the growth arrest-specific 7 gene (GAS7) and POAG. Methods: A cohort of 799 unrelated POAG patients and 799 unrelated control subjects was enrolled in this case-control association study. The polymorphism rs11656696 was genotyped using the SNaPshot method. The genotype and allele frequencies were evaluated using the χ2 tests. Results: The allele frequency distribution of rs11656696 in the GAS7 gene showed that there was significant difference between POAG cases and controls (P= .006448, OR = 0.82, 95%CI = (0.72-0.95). The minor "A" allele frequency of this polymorphism was 0.477 in the POAG cases, whereas it was 0.526 in controls, suggesting a protective effect for POAG. Significant associations were detected under the homozygous model (p = .006425, OR = 0.68, 95%CI = 0.51-0.90) and recessive model (p = .0003432, OR = 0.66, 95%CI = 0.52-0.84), indicating that subjects carrying rs11656696 AA genotype were less likely to suffer from POAG than those carrying AC/CC genotypes. Conclusion: This case-control association study showed that polymorphism rs11656696 in GAS7 is related to POAG and might be a protective factor against POAG.