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The coronavirus SARS-CoV-2 is the causative pathogen of the COVID-19 pandemic that has been causing global upheaval since 2019. The widespread administration of vaccines has partially deterred the spread of SARS-CoV-2, yet the virus is mutating its genome to reduce its antigenicity and evade the human herd immunity. It seems that SARS-CoV-2 will co-exist with the human population for many decades to come. While most infected individuals only experience mild to moderate symptoms, some develop severe pulmonary and systemic disease that can result in hospitalization or even death. The natural history model of SARS-CoV-2 infection has been proposed which includes three sequential stages: the early infection stage, pulmonary stage, and hyper-inflammatory stage. Recently, it has been observed that many people who recovered from an acute infection still experience persistent symptoms for weeks or months, a condition known as long COVID. Furthermore, some COVID-19 patients display escalated rates of both macro- and micro-thrombosis due to endotheliopathy. Hence, we added the thrombosis and convalescent stages to the natural history model, encompassing the entire period from early infection to long COVID. The early infection stage is characterized by symptomatic or asymptomatic elevation of viral titers. Some patients progress to the pulmonary stage characterized by opacities in chest X-rays and computed tomography. The thrombosis stage is characterized by heightened rates of pulmonary thrombosis and consistently elevated D-dimer levels. The hyper-inflammatory stage is characterized by storms of cytokines, such as IL-6, IL-17, and interferons, which is a systemic effect. In the convalescent stage, some people recover completely, while others suffer from long COVID with persistent symptoms such as fatigue, shortness of breath, or brain fog. The natural history model of SARS-CoV-2 infection can be used to elucidate treatment and care. [ABSTRACT FROM AUTHOR]

Tidal flats in northern China are essential parts of the East Asian-Australasian Flyway, the densest pathway for migratory waterbirds, and are of great ecological and economic importance. They are threatened by human activities and climate change, raising the urgency surrounding tracking the spatiotemporal dynamics of tidal flats. However, there is no cost-effective way to map morphological changes on a large spatial scale due to the inaccessibility of the mudflats. In this study, we proposed a pixel-based multi-indices tidal flat mapping algorithm that precisely characterizes 2D/3D morphological changes in tidal flats in northern China using time-series remote sensing data. An overall accuracy of 0.95 in delineating tidal flats to a 2D extent was achieved, with 11,716 verification points. Our results demonstrate that the reduction in sediment discharge from rivers along the coastlines of the Yellow and Bohai Seas has resulted in an overall decline in the area of tidal flats, from 4856.40 km2 to 4778.32 km2. Specifically, 3D analysis showed that significant losses were observed in the mid-to-high-tidal flat zones, while low-elevation tidal flats experienced an increase in area due to the transformations in mid-to-high-tidal flats. Our results indicate that the sediment inputs from rivers and the succession of native vegetation are the primary drivers leading to 2D/3D morphological changes of tidal flats following the cessation of extensive land reclamation in northern China. [ABSTRACT FROM AUTHOR]

Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (n = 7) or endoglin (n = 7) deleted in the endothelial cells or brain focally (n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage. [ABSTRACT FROM AUTHOR]

Simple Summary: Although SARS-CoV-2 primarily affects the upper respiratory system and the lungs, it can also affect vasculature, leading to the impairment of endothelial and multi-organ function. SARS-CoV-2 can trigger the release of pro-inflammatory cytokines, leading to disruption of tight junction proteins between endothelial cells and impairment of the blood-brain barrier (BBB). This process further allows the infiltration of immune cells and other particles into the brain, worsening brain injury. Prolonged neuro-inflammation and disruption of the BBB have been postulated as the potential primary causes of both acute and chronic cognitive dysfunction in COVID-19 patients. This review explores the effects of COVID-19 on vascular dysfunction and consequent cognitive impairment in patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another very common but debilitating complication caused by SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized COVID-19 patients and range from shortness of concentration and overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and "brain fog" are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra-pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully and their underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients. [ABSTRACT FROM AUTHOR]

The reverse inter-shaft gas film seal is a gas path seal used in the intermediate bearing cavity of an aero-engine, which is challenging to implement due to its special installation and usage conditions. This paper proposes a C/C (Carbon/Carbon) composite cylindrical reverse inter-shaft seal structure and carries out a performance simulation analysis based on bidirectional fluid–solid coupling technology. The results show that the cylindrical reverse inter-shaft gas film seal with double-layer C/C composite sealing rings with different material mesoscopic parameters can balance seal leakage and friction power consumption and is beneficial to improving the comprehensive performance of the seal. As the mesoscopic parameters of the inner sealing ring material increase in warp and weft density, the sealing leakage rate decreases, and the gas film force and gas friction power consumption all increase. As the pressure difference increases, the sealing leakage rate and gas film force increase. As the rotation speed of the inner and outer rotors increases, the seal leakage rate increases, and the gas film force decreases. A C/C composite sealing ring cylindrical reverse inter-shaft gas film seal has a lower leakage rate and larger gas film force than a graphite sealing ring cylindrical reverse inter-shaft seal, which confers certain performance advantages. The work in this paper can provide a reference for the design of reverse inter-shaft seals. [ABSTRACT FROM AUTHOR]

The cylinder gas film seal between dual-rotor reverse shafts is a new method for sealing aircraft engines that has excellent developmental prospects. We propose a novel method for determining if the sealing ring is fully fluid-lubricated using the average Reynolds equation. Considering surface roughness and centrifugal expansion, we calculated the dynamic pressure, gas film force and friction power consumption with and without inlet pressure differences for each of the four rotation modes. The gas film's dynamic pressure effects were weakest when the dual rotors rotated in a reverse direction (Mode 3), with or without differences in inlet pressure, since solid contact is most likely to occur under counter-rotation. When the dual rotors were in counter-rotation with an inlet differential pressure of 80 kPa and fixed inner and outer rotor speeds (e.g., 3000 rpm), we calculated the minimum sealing ring film thickness, leakage rate, friction power consumption and gas film force. Changes in outer rotor speed greatly influenced the minimum film thickness and the sealing ring's performance. Meanwhile, changes in the inner rotor speed had little influence on the minimum film thickness and sealing ring's lubrication performance. When the speed difference was fixed and the sealing ring was fully fluid-lubricated, lubrication performance changes were mainly affected by changes in centrifugal expansion caused by the outer rotor speed. Given a fixed rotor speed and under dual-rotor counter-rotation, we calculated the effects of inlet differential pressure changes on minimum gas film thickness, leakage rate, friction power consumption, gas film force and other sealing performance variables. Leakage rate and the friction power consumption increase as inlet differential pressure increases. Our results provide a theoretical reference for avoiding solid contact of the cylinder seal between dual-rotor reverse shafts. [ABSTRACT FROM AUTHOR]

As the most relevant indicator of global warming, the ocean heat content (OHC) change is tightly linked to the Earth's energy imbalance. Therefore, it is vital to study the OHC and heat absorption and redistribution. Here we analyzed the characteristics of global OHC variations based on a previously reconstructed OHC dataset (named OPEN) with four other gridded OHC datasets from 1993 to 2021. Different from the other four datasets, the OPEN dataset directly obtains OHC through remote sensing, which is reliable and superior in OHC reconstruction, further verified by the Clouds and the Earth's Radiant Energy System (CERES) radiation flux data. We quantitatively analyzed the changes in the upper 2000 m OHC of the oceans over the past three decades from a multisource and multilayer perspective. Meanwhile, we calculated the global ocean heat uptake to quantify and track the global ocean warming rate and combined it with the Oceanic Niño Index to analyze the global evolution of OHC associated with El Niño–Southern Oscillation variability. The results show that different datasets reveal a continuously increasing and non-decaying global ocean warming from multiple perspectives, with more heat being absorbed by the subsurface and deeper ocean over the past 29 years. The global OHC heating trend from 1993 to 2021 is 7.48 ± 0.17, 7.89 ± 0.1, 10.11 ± 0.16, 7.78 ± 0.17, and 12.8 ± 0.26 × 1022 J/decade according to OPEN, IAP, EN4, Ishii, and ORAS5, respectively, which shows that the trends of the OPEN, IAP, and Ishii datasets are generally consistent, while those of EN4 and ORAS5 datasets are much higher. In addition, the ocean warming characteristics revealed by different datasets are somewhat different. The OPEN OHC dataset from remote sensing reconstruction shows a unique remote sensing mapping advantage, presenting a distinctive warming pattern in the East Indian Ocean. Meanwhile, the OPEN dataset had the largest statistically significant area, with 85.6% of the ocean covered by significant positive trends. The significant and continuous increase in global ocean warming over the past three decades, revealed from remote sensing reconstruction, can provide an important reference for projecting ocean warming in the context of global climate change toward the United Nations Sustainable Development Goals. [ABSTRACT FROM AUTHOR]

Considering grid requirements of high Reynolds flow, wall-modeled large eddy simulation (WMLES) and detached eddy simulation (DES) have become the main methods to deal with near-wall turbulence. However, the flow separation phenomenon is a challenge. Three typical separated flows, including flow over a cylinder at R e D = 3900 based on the cylinder diameter, flow over a wall-mounted hump at R e c = 9.36 × 105 based on the hump length, and transonic flow over an axisymmetric bump with shock-induced separation at R e c = 2.763 × 106 based on the bump length, are used to verify WMLES, shear stress transport k- ω DES (SST-DES), and Spalart–Allmaras DES (SA-DES) methods in OpenFOAM. The three flows are increasingly challenging, namely laminar boundary layer separation, turbulent boundary layer separation, and turbulent boundary layer separation under shock interference. The results show that WMLES, SST-DES, and SA-DES methods in OpenFOAM can easily predict the separation position and wake characteristics in the flow around the cylinder, but they rely on the grid scale and turbulent inflow to accurately simulate the latter two flows. The grid requirements of Larsson et al. ( δ / Δ x , δ / Δ y , δ / Δ z ≈ (12 , 50 , 20) ) are the basis for simulating turbulent boundary layers upstream of flow separation. A finer mesh ( δ / Δ x , δ / Δ y , δ / Δ z ≈ (40 , 75 , 40) ) is required to accurately predict the separation and reattachment. The WMLES method is more sensitive to grid scales than the SA-DES method and fails to obtain flow separation under a coarser grid, while SST-DES method can only describe the vortices generated by the separating shear layer, but not within the turbulent boundary layer, and overestimates the separation-reattachment zone based on the grid system in this paper. [ABSTRACT FROM AUTHOR]

Simple Summary: Human Cub and Sushi Multiple Domains 1 (CSMD1) is a novel candidate tumor-suppressor gene. We investigated CSMD1 in esophageal squamous cell carcinoma (ESCC) by performing an integrated analysis of somatic DNA alterations (i.e., copy number alteration, allelic imbalance, and loss of heterozygosity) with RNA expressions (mRNA and target miRNAs) on specimens from the same ESCC patients, using data from SNP, miRNA, and RT-PCR arrays. Our results indicate that the CSMD1 gene may play a role in the development of ESCC through complex patterns involving somatic alterations and mRNA expression. Furthermore, somatic copy number alterations in SNPs located in non-coding regions of CSMD1 appear to influence expression of both this gene and its target miRNAs. Background: Human Cub and Sushi Multiple Domains 1 (CSMD1) is a novel candidate tumor-suppressor gene that codes for multiple domains, including complement regulatory and adhesion proteins, and has recently been shown to have alterations in multiple cancers. We investigated CSMD1 in esophageal squamous cell carcinoma (ESCC) by performing an integrated analysis on somatic copy number alterations (CNAs), including copy-number gain or loss, allelic imbalance (AI), loss of heterozygosity (LOH), and the expressions of mRNA and its target miRNAs on specimens from the same patients with ESCC. Results: (i) Two-thirds of ESCC patients had all three types of alterations studied—somatic DNA alterations in 70%, and abnormal expressions of CSMD1 RNA in 69% and in target miRNAs in 66%; patterns among these alterations were complex. (ii) In total, 97% of 888 CSMD1 SNPs studied showed somatic DNA alterations, with most located near exons 4–11, 24–25, 39–40, 55–56, and 69–70. (iii) In total, 68% of SNPs with a CNA were correlated with expression of CSMD1. (iv) A total of 33 correlations between non-coding SNPs and expression of CSMD1 target miRs were found. Conclusions: Our results indicate that the CSMD1 gene may play a role in ESCC through complex patterns of DNA alterations and RNA and miRNA expressions. Alterations in some somatic SNPs in non-coding regions of CSMD1 appear to influence expression of this gene and its target miRNAs. [ABSTRACT FROM AUTHOR]

Nursing home residents often have impaired faculties, which limit their evacuation responses in light of accidents. Specifically, fire accidents can pose significant risks to both residents and property. In this study, we designed a water film cooling system to enhance the heat and smoke resistance of a fire retardant curtain without a fire resistance rating. The experimental results on a full-scale door/wall refractory furnace and smoke-barrier system showed that the proposed curtain had 1.5-h heat resistance properties, while the smoke control performance could meet the ISO 5925-1 requirement. Finally, we used Fire Dynamics Simulator (FDS) 6.0 to simulate an existing nursing home with this type of fireproof curtain setup for horizontal evacuation waiting space. The results show that our proposed water film cooling system can effectively inhibit the diffusion of smoke during the initial stage of a fire, creating a safe evacuation waiting zone for disadvantaged evacuees. [ABSTRACT FROM AUTHOR]

The rapid development of marine ranching in recent years provides a new way of tackling the global food crisis. However, the uncontrolled expansion of coastal aquaculture has raised a series of environmental problems. The fast and accurate detection of raft will facilitate scientific planning and the precise management of coastal aquaculture. A new deep learning-based approach called RaftNet is proposed in this study to extract the coastal raft aquaculture in Sansha Bay using Landsat 8 OLI images accurately. To overcome the issues of turbid water environments and varying raft scales in aquaculture areas, we constructed the RaftNet by modifying the UNet network with dual-channel and residual hybrid dilated convolution blocks to improve the extraction accuracy. Meanwhile, we adopted the well-known semantic segmentation networks (FCN, SegNet, UNet, UNet++, and ResUNet) as the contrastive approaches for the extraction. The results suggested that the proposed RaftNet model achieves the best accuracy with a precision of 84.5%, recall of 88.1%, F1-score of 86.30%, overall accuracy (OA) of 95.7%, and intersection over union (IoU) of 75.9%. We then utilized our RaftNet to accurately extract a raft aquaculture area in Sansha Bay from 2014 to 2018 and quantitatively analyzed the change in the raft area over this period. The results demonstrated that our RaftNet is robust and suitable for the precise extraction of raft aquaculture with varying scales in turbid coastal waters, and the Kappa coefficient and OA can reach as high as 88% and 97%, respectively. Moreover, the proposed RaftNet will unleash a remarkable potential for long time-series and large-scale raft aquaculture mapping. [ABSTRACT FROM AUTHOR]

Formulated as a group effort of the stroke community, the transforming concept of the neurovascular unit (NVU) depicts the structural and functional relationship between brain cells and the vascular structure. Composed of both neural and vascular elements, the NVU forms the blood–brain barrier that regulates cerebral blood flow to meet the oxygen demand of the brain in normal physiology and maintain brain homeostasis. Conversely, the dysregulation and dysfunction of the NVU is an essential pathological feature that underlies neurological disorders spanning from chronic neurodegeneration to acute cerebrovascular events such as ischemic stroke and cerebral hemorrhage, which were the focus of this review. We also discussed how common vascular risk factors of stroke predispose the NVU to pathological changes. We synthesized existing literature and first provided an overview of the basic structure and function of NVU, followed by knowledge of how these components remodel in response to ischemic stroke and brain hemorrhage. A greater understanding of the NVU dysfunction and remodeling will enable the design of targeted therapies and provide a valuable foundation for relevant research in this area. [ABSTRACT FROM AUTHOR]

The reconstruction of the ocean's 3D thermal structure is essential to the study of ocean interior processes and global climate change. Satellite remote sensing technology can collect large-scale, high-resolution ocean observation data, but only at the surface layer. Based on empirical statistical and artificial intelligence models, deep ocean remote sensing techniques allow us to retrieve and reconstruct the 3D ocean temperature structure by combining surface remote sensing observations with in situ float observations. This study proposed a new deep learning method, Convolutional Long Short-Term Memory (ConvLSTM) neural networks, which combines multisource remote sensing observations and Argo gridded data to reconstruct and produce a new long-time-series global ocean subsurface temperature (ST) dataset for the upper 2000 m from 1993 to 2020, which is named the Deep Ocean Remote Sensing (DORS) product. The data-driven ConvLSTM model can learn the spatiotemporal features of ocean observation data, significantly improves the model's robustness and generalization ability, and outperforms the LighGBM model for the data reconstruction. The validation results show our DORS dataset has high accuracy with an average R2 and RMSE of 0.99/0.34 °C compared to the Argo gridded dataset, and the average R2 and NRMSE validated by the EN4-Profile dataset over the time series are 0.94/0.05 °C. Furthermore, the ST structure between DORS and Argo has good consistency in the 3D spatial morphology and distribution pattern, indicating that the DORS dataset has high quality and strong reliability, and well fills the pre-Argo data gaps. We effectively track the global ocean warming in the upper 2000 m from 1993 to 2020 based on the DORS dataset, and we further examine and understand the spatial patterns, evolution trends, and vertical characteristics of global ST changes. From 1993 to 2020, the average global ocean temperature warming trend is 0.063 °C/decade for the upper 2000 m. The 3D temperature trends revealed significant spatial heterogeneity across different ocean basins. Since 2005, the warming signal has become more significant in the subsurface and deeper ocean. From a remote sensing standpoint, the DORS product can provide new and robust data support for ocean interior process and climate change studies. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a positive-sense single-stranded RNA virus in the Flaviviridae, which is classified into two different lineages Asian and African. The outbreak of ZIKV Asian lineage isolates in 2015–2016 is associated with the increase in cases with prenatal microcephaly and Guillain–Barré syndrome, and has sparked attention throughout the world. Genome sequence alignment and the analysis of Asian and African lineage isolates indicate that amino acid changes, particular in positively charged amino acid substitutions in the pr region of prM protein might involve a phenotypic change that links with the global outbreak of ZIKV Asian-lineage. The study generated and characterized the virological properties of wild type and mutants of single-round infectious particles (SRIPs) and infectious clones (i.c.s) of ZIKV Asian-lineage Natal RGN strain, and then identified the function of amino acid substitutions at the positions 139 [Asn139→Ser139 (N139S)] and 143 [Glu143→Lys143 (E143K)] in ZIKV polyproteins (located within the pr region of prM protein) in the infectivity and cytopathogenicity. The E143K SRIP and i.c. of Natal RGN strain exhibited relatively higher levels of cytopathic effect, EGFP reporter, viral RNA and protein synthesis, and virus yield in three types of human cell lines, TE617, SF268 and HMC3, compared to wild type (WT), N139S SRIPs and i.c.s, which displayed more efficiency in replication kinetics. Additionally, E143K Natal RGN i.c. had greater activities of virus attachment and entry, yielded higher titers of intracellular and extracellular virions, and assembled the E proteins near to the plasma membrane in infected cells than the other i.c.s. The results indicate that the positively charged amino acid residue Lys143, a conserved residue in the pr region of prM of ZIKV African lineages, plays a crucial role in viral replication kinetics, including viral attachment, entry, assembly and egress. Thus, the negatively charged amino acid residue Glu143 within the pr region of prM leads to an alteration of the phenotypes, in particular, a lower replication efficiency of ZIKV Asian-lineage isolates with the attenuation of infectivity and cytopathicity. [ABSTRACT FROM AUTHOR]

The coastline plays an important role in indicating the conditions of social-economic development in the coastal zone. In this study, an integrated assessment framework was proposed to address the provincial and county-level spatiotemporal dynamics of continental coastlines from the perspectives of length, position, composition, and anthropogenic utilization quantitatively, and to explore the exact impacts of urbanization on coastline changes in the Fujian Province over the period from 1985 to 2020. Results showed that the total length of coastlines decreased first and then increased due to the different patterns of economic development. The proportion of artificial coastlines and the index of coastal utilization degree increased rapidly during the same period. Moreover, the seaward movement of coastlines due to the coastal reclamation projects resulted in a considerable increment in land areas. The pressure brought by the continuous concentration of population, built-up areas, and industrial districts under the rapid urbanization was the primary factor that increased the degree of anthropogenic disturbances in the coastal zone. Furthermore, the policies issued by the local or central government can be critical tipping points for coastline changes in different periods. [ABSTRACT FROM AUTHOR]

Protists are a dominant group in marine microplankton communities and play important roles in energy flux and nutrient cycling in marine ecosystems. Environmental sequences produced by high-throughput sequencing (HTS) methods are increasingly used for inferring the diversity and distribution patterns of protists. However, studies testing whether methods disentangling biological variants affect the diversity and distribution patterns of protists using field samples are insufficient. Oligotrich (s.l.) ciliates are one group of the abundant and dominant planktonic protists in coastal waters and open oceans. Using oligotrich (s.l.) ciliates in field samples as an example, the present study indicates that DADA2 performs better than SWARM, UNOISE, UPARSE, and UCLUST for inferring diversity patterns of oligotrich (s.l.) ciliates in the Pearl River Estuary and surrounding regions. UPARSE and UNOISE might underestimate species richness. SWARM might not be suitable for the resolution of alpha diversity owing to its rigorous clustering and sensitivity to sequence variations. UCLUST with 99% clustering threshold overestimates species richness, and the beta diversity pattern inferred by DADA2 is more reasonable than that of the other methods. Additionally, salinity is shown to be one of the key factors responsible for variations in the community distribution of ciliates, but infrequent marine–freshwater transitions occurred during evolutionary terms of this group. [ABSTRACT FROM AUTHOR]

Simple Summary: We applied an integrated approach to analyze expression, genotyping and somatic DNA alterations to find genetic markers (genes and SNPs) related to esophageal squamous cell carcinoma (ESCC). We extended the expression-quantitative trait loci (eQTL) analysis by using tumor vs. normal fold change data. By analyzing both RNA and DNA data from multiple platforms and focusing on the genes in three pathways: inflammation, DNA repair, and immunity, we have found results more relevant to ESCC. We integrated ESCC expression and GWAS genotyping, to investigate eQTL and somatic DNA segment alterations, including somatic copy number alteration, allelic imbalance (AI), and loss of heterozygosity (LOH) in ESCC. First, in eQTL analysis, we used a classical approach based on genotype data from GWAS and expression signals in normal tissue samples, and then used a modified approach based on fold change in the tumor vs. normal samples. We focused on the genes in three pathways: inflammation, DNA repair, and immunity. Among the significant (p < 0.05) SNP-probe pairs from classical and modified eQTL analyses, 24 genes were shared by the two approaches, including 18 genes that showed the same numbers of SNPs and probes and 6 genes that had the different numbers of SNPs and probes. For these 18 genes, we found 28 SNP–probe pairs were correlated in opposite directions in the two approaches, indicating an intriguing difference between the classical and modified eQTL approaches. Second, we analyzed the somatic DNA segment alterations. Across the 24 genes, abnormal gene expression on mRNA arrays was seen in 19–95% of cases and 26–78% showed somatic DNA segment alterations on Affymetrix GeneChip Human Mapping Arrays. The results suggested that this strategy could identify gene expression and somatic DNA segment alterations for biological markers (genes) by combining classical and modified eQTLs and somatic DNA evaluation on SNP arrays. Thus, this study approach may allow us to understand functionality indicative of potentially relevant biomarkers in ESCC. [ABSTRACT FROM AUTHOR]

In this report, quantum dots of hexagonal boron nitride (h-BN) were fabricated on the surface of polycrystalline Ni film at low growth temperatures (700, 750, and 800 °C) by plasma-assisted molecular beam epitaxy. Reflection high-energy electron diffraction could trace the surface condition during the growth and perform the formation of BN. The observation of surface morphology by scanning electron microscopy and atomic force microscopy showed the nanodots of BN on Ni films. The existence of crystal h-BN quantum dots was determined by the analysis of Raman spectra and Kevin probe force microscopy. The cathodoluminescence of h-BN quantum dots performed at the wavelength of 546 and 610 nm, attributed to the trapping centers involving impurities and vacancies. Moreover, the influence of temperatures for the substrate and boron source cell was also investigated in the report. When the k-cell temperature of boron and growth temperature of substrate increased, the emission intensity of cathodoluminescence spectra increased, indicating the better growth parameters for h-BN quantum dots. [ABSTRACT FROM AUTHOR]

Featured Application: Two-stage finger seal is a novel and revolutionary compliant seal, which has the characteristics of high speed, pressure and temperature capacity, low leakage, low cost, and long life time. It can be used in the secondary flow system of aeroengines. To solve the high leakage and high wear problems faced by sealing devices in aeroengines under the condition of high axial pressure difference, the two-stage finger seal is proposed in this paper. The finite element method and computational fluid dynamics (FEM/CFD) coupling iterative algorithm of the two-stage finger seal is developed and validated. Then the performance advantages of two-stage finger seal compared to the one-stage finger seal are studied, as well as the leakage and the inter-stage pressure drop characteristics of two-stage finger seal are investigated. Finally, the measure to improve the inter-stage imbalance of pressure drop of two-stage finger seal is proposed. The results show that the two-stage finger seal has lower leakage and lower contact pressure than the one-stage finger seal at high axial pressure difference, but there exists an inter-stage imbalance of pressure drop. Increasing the axial pressure difference and the root mean square (RMS) roughness of finger element can aggravate the imbalance of pressure drop, while the radial displacement excitation of rotor has little influence on it. The results also indicate that the inter-stage imbalance of pressure drop of the two-stage finger seal can be improved by increasing the number of finger elements of the 1st finger seal and decreasing the number of finger elements of the 2nd finger seal. [ABSTRACT FROM AUTHOR]

Japanese encephalitis virus (JEV), a neurotropic flavivirus, annually causes over 30,000 Japanese Encephalitis (JE) cases in East and Southeast Asia. Histone deacetylases (HDACs) modulate lysine acetylation of histones and non-histone proteins, regulating many processes including inflammation and antiviral immune response. This study investigated antiviral activity of pan- and selective-HDAC inhibitors as host-targeting agents against JEV. Among HDAC inhibitors, selective HDAC6 inhibitors (tubastatin-A (TBSA) and tubacin) concentration-dependently inhibited JEV-induced cytopathic effect and apoptosis, as well as reduced virus yield in human cerebellar medulloblastoma cells. The 50% inhibitory concentration (IC50) values of virus yield was 0.26 μM for tubacin and 1.75 μM for TBSA, respectively. Tubacin (IC50 of 1.52 μM), but not TBSA, meaningfully blocked the production of intracellular infectious virus particles. In time-of-addition assays, the greatest potency of antiviral activity was observed in the mode of pre-treatment with tubacin (IC50 of 1.89 μM) compared to simultaneous (IC50 of 4.88 μM) and post-treatment (IC50 of 2.05 μM) modes. Interestingly, tubacin induced the hyperacetylation of a HDAC6 substrate Hsp90 and reduced the interaction of Hsp90 with JEV NS5 protein. Novobiocin, an Hsp90 inhibitor, diminished the NS5 protein amount and virus replication in JEV-infected cells. Meantime, tubacin suppressed the NS5 expression and antisense RNA genome synthesis in infected cells. Tubacin-induced Hsp90 hyperacetylation was suggested to influence the NS5 activity in JEV replication. Therefore, tubacin had a high potential of a host-targeting agent against JEV, exhibiting preventive and therapeutic activities against JEV infection. [ABSTRACT FROM AUTHOR]

Japanese Encephalitis virus (JEV) is a mosquito-borne flavivirus with a positive-sense single-stranded RNA genome that contains a big open reading frame (ORF) flanked by 50- and 30- untranslated regions (UTRs). Nearly 30,000 JE cases with 10,000 deaths are still annually reported in East Asia. Although the JEV genotype III vaccine has been licensed, it elicits a lower protection against other genotypes. Moreover, no effective treatment for a JE case is developed. This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. Genetic instability of JEV genome cDNA in the pBR322 plasmid was associated with the prokaryotic promoter at 50 end of the JEV genome that triggers the expression of the structural proteins in E. coli. JEV structural proteins were toxic E. coli, thus the encoding region for structural proteins was replaced by a reporter gene (enhanced green fluorescent protein, EGFP) that was in-frame fused with the first eight amino acids of the C protein at N-terminus and the foot-and-mouth disease virus (FMDV) 2A peptide at C-terminus in a pBR322-based JEV-EGFP replicon. JEV-EGFP SRIPs generated from JEV-EGFP replicon-transfected packaging cells displayed the infectivity with cytopathic effect induction, self-replication of viral genomes, and the expression of EGFP and viral proteins. Moreover, the combination of JEV-EGFP SRIP plus flow cytometry was used to determine the half maximal inhibitory concentration (IC50) values of antiviral agents according to fluorescent intensity and positivity of SRIP-infected packaging cells post treatment. MJ-47, a quinazolinone derivative, significantly inhibited JEV-induced cytopathic effect, reducing the replication and expression of JEV-EGFP replicon in vitro. The IC50 value of 6.28 M for MJ-47 against JEV was determined by the assay of JEV-EGFP SRIP infection in packaging cells plus flow cytometry that was more sensitive, effective, and efficient compared to the traditional plaque assay. Therefore, the system of JEV-EGFP SRIPs plus flow cytometry was a rapid and reliable platform for screening antiviral agents and evaluating antiviral potency. [ABSTRACT FROM AUTHOR]

Calorimetric biochemical measurements offer various advantages such as low waste, low cost, low sample consumption, short operating time, and labor-savings. Multichannel calorimeters can enhance the possibility of performing higher-throughput biochemical measurements. An enthalpy sensor (ES) array is a key device in multichannel calorimeters. Most ES arrays use Wheatstone bridge amplifiers to condition the sensor signals, but such an approach is only suitable for null detection and low resistance sensors. To overcome these limitations, we have developed a multichannel calorimetric simultaneous assay (MCSA) platform. An adjustable microampere constant-current (AMCC) source was designed for exciting the ES array using a microampere current loop measurement circuit topology. The MCSA platform comprises a measurement unit, which contains a multichannel calorimeter and an automatic simultaneous injector, and a signal processing unit, which contains multiple ES signal conditioners and a data processor. This study focused on the construction of the MCSA platform; in particular, construction of the measurement circuit and calorimeter array in a single block. The performance of the platform, including current stability, temperature sensitivity and heat sensitivity, was evaluated. The sensor response time and calorimeter constants were given. The capability of the platform to detect relative enzyme activity was also demonstrated. The experimental results show that the proposed MCSA is a flexible and powerful biochemical measurement device with higher throughput than existing alternatives. [ABSTRACT FROM AUTHOR]

The effect of Eu2O3 concentration on the luminescence properties of double perovskite (cubic) Sr2-xEuxZnMoO6 phosphors was thoroughly investigated using different synthesizing temperatures. Phosphors with the composition Sr2-xEuxZnMoO6, where Eu2O3 was substituted for SrO and x was changed from 0 to 0.12, were synthesized by the solid-state method at temperatures of 900-1200 °C, respectively. Analysis of the X-ray diffraction (XRD) patterns showed that even when the synthesizing temperature was 1100 °C, secondary or unknown phases were observed in Sr2-xEuxZnMoO6 ceramic powders. The effect of the concentration of Eu3+ ions on the luminescence properties of the Sr2-xEuxZnMoO6 phosphors was readily observable because no characteristic emission peak was observed in the Sr2ZnMoO6 phosphor. Two characteristic emission peaks at 597 and 616 nm were observed, which correspond to the 5D0-7F1 and 5D0-7F2 transitions of Eu3+ ions, respectively. The two characteristic emission peaks of the Sr2-xEuxZnMoO6 phosphors were apparently influenced by the synthesizing temperature and the concentration of Eu3+ ions. When x was larger than 0.08, a concentration quenching effect of Eu3+ ions in the Sr2-xEuxZnMoO6 phosphors could be observed. The lifetime of the Sr2-xEuxZnMoO6 phosphors decreased as the synthesizing temperature increased. A linear relation between temperature and lifetime was obtained by using a fitting curve of t = -0.0016 × T + 3.543, where t was lifetime and T was synthesizing temperature. [ABSTRACT FROM AUTHOR]

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has five genotypes (I, II, III, IV, and V). JEV genotype I circulates widely in some Asian countries. However, current JEV vaccines based on genotype III strains show low neutralizing capacities against genotype I variants. In addition, JE has no specific treatment, except a few supportive treatments. Compound CW-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against JEV in this study. CW-33 exhibited the less cytotoxicity to Syrian baby hamster kidney (BHK-21) and human medulloblastoma (TE761) cells. CW-33 dose-dependently reduced the cytopathic effect and apoptosis of JEV-infected cells. Supernatant virus yield assay pinpointed CW-33 as having potential anti-JEV activity with IC50 values ranging from 12.7 to 38.5 μM. Time-of-addition assay with CW-33 indicated that simultaneous and post-treatment had no plaque reduction activity, but continuous and simultaneous treatments proved to have highly effective antiviral activity, with IC50 values of 32.7 and 48.5 μM, respectively. CW-33 significantly moderated JEV-triggered Ca2+ overload, which correlated with the recovery of mitochondria membrane potential as well as the activation of Akt/mTOR and Jak/STAT1 signals in treated infected cells. Phosphopeptide profiling by LC-MS/MS revealed that CW-33 upregulated proteins from the enzyme modulator category, such as protein phosphatase inhibitor 2 (I-2), Rho GTPase-activating protein 35, ARF GTPase-activating protein GIT2, and putative 3-phosphoinositide-dependent protein kinase 2. These enzyme modulators identified were associated with the activation of Akt/mTOR and Jak/STAT1 signals. Meanwhile, I-2 treatment substantially inhibited the apoptosis of JEV-infected cells. The results demonstrated that CW-33 exhibited a significant potential in the development of anti-JEV agents. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals. [ABSTRACT FROM AUTHOR]

γ-Bisabolene has demonstrated antiproliferative activities against several human cancer cell lines. This study first discloses the antiproliferative and apoptosis induction activities of γ-bisabolene to human neuroblastoma TE671 cells. A CC50 value of γ-bisabolene was 8.2 μMto TE671 cells. Cell cycle analysis with PI staining showed γ-bisabolene elevating the sub-G1 fractions in a time-dependent manner. In addition, annexin V-FITC/PI staining showed γ-bisabolene significantly triggering early (annexin-V positive/PI negative) and late (annexin-V positive/PI positive) apoptosis in dose-dependent manners. γ-Bisabolene induced caspase 3/8/9 activation, intracellular ROS increase, and mitochondrial membrane potential decrease in apoptosis of human neuro-blastoma cells. Moreover, γ-bisabolene increased p53 phosphorylation and up-regulated p53-mediated apoptotic genes Bim and PUMA, as well as decreased the mRNA and protein levels of CK2α. Notably, the results indicated the involvement of CK2α-p53 pathways in mitochondria-mediated apoptosis of human neuroblastoma cells treated with γ-bisabolene. This study elucidated the apoptosis induction pathways of γ-bisabolene-treated neuroblastoma cells, in which could be useful for developing anti-neuroblastoma drugs. [ABSTRACT FROM AUTHOR]

Regular monitoring of blood α-fetoprotein (AFP) and/or carcino-embryonic antigen (CEA) levels is important for the routine screening of liver cancer. However, AFP and CEA have a much lower specificity than des-γ-carboxyprothrombin (DCP) to detect liver cancer. Therefore, the study reported here was designed, to develop a screen-printed DCP immunosensor incorporating zinc oxide nanoparticles, for accurate determination of DCP. The designed immunosensor shows low detection limits for the detection of DCP: 0.440 ng/mL (based on impedance measurement), 0.081 ng/mL (based on real part of impedance measurement) and 0.078 ng/mL (based on imaginary part of impedance measurement), within the range of 3.125 ng/mL to 2000 ng/mL. In addition, there was little interference to DCP determination by molecules such as Na+, K+, Ca2+, Cl-, glucose, urea, and uric acid. It is therefore concluded that the DCP immunosensor developed and reported here is simple, inexpensive and effective, and shows promise in the rapid screening of early-stage liver cancer at home with a point-of-care approach. [ABSTRACT FROM AUTHOR]

Enterovirus A71 (EV-A71) in the Picornaviridae family causes hand-foot-and-mouth disease, aseptic meningitis, severe central nervous system disease, even death. EV-A71 2A protease cleaves Type I interferon (IFN)-α/β receptor 1 (IFNAR1) to block IFN-induced Jak/STAT signaling. This study investigated anti-EV-A7l activity and synergistic mechanism(s) of a novel furoquinoline alkaloid compound CW-33 alone and in combination with IFN-β. Anti-EV-A71 activities of CW-33 alone and in combination with IFN-β were evaluated by inhibitory assays of virus-induced apoptosis, plaque formation, and virus yield. CW-33 showed antiviral activities with an IC50 of near 200 µM in EV-A71 plaque reduction and virus yield inhibition assays. While, anti-EV-A71 activities of CW-33 combined with 100 U/mL IFN-β exhibited a synergistic potency with an IC50 of approximate 1 µM in plaque reduction and virus yield inhibition assays. Molecular docking revealed CW-33 binding to EV-A71 2A protease active sites, correlating with an inhibitory effect of CW33 on in vitro enzymatic activity of recombinant 2A protease (IC50 = 53.1 µM). Western blotting demonstrated CW-33 specifically inhibiting 2A protease-mediated cleavage of IFNAR1. CW-33 also recovered Type I IFN-induced Tyk2 and STAT1 phosphorylation as well as 2',5'-OAS upregulation in EV-A71 infected cells. The results demonstrated CW-33 inhibiting viral 2A protease activity to reduce Type I IFN antagonism of EV-A71. Therefore, CW-33 combined with a low-dose of Type I IFN could be applied in developing alternative approaches to treat EV-A71 infection. [ABSTRACT FROM AUTHOR]

Chalcone derivatives (£)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one and (£)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one (Compounds 1 and 2) have been demonstrated to be potent anti-inflammatory agents in our previous study. In light of the relationship of intracellular mechanisms between anti-inflammatories and antioxidants, we further designed and synthesized a series of chalcone derivatives based on 1 and 2, to explore their antioxidant efficacy. The majority of the derivatives exhibited strong protective effects on PC12 (PC12 rat pheochromocytoma) cells exposed to H2O2, and all compounds were nontoxic. A preliminary structure-activity relationship was proposed. Compounds 1 and 1d ((£)-2-methoxy-4-(3-(4-methoxyphenyl)-3-oxoprop-1-en-1-yl) phenyl acrylate) exerted the action in a good dose-dependent manner. Quantitative RT-PCR (qRT-PCR) and western blot analysis showed that 1 and 1d significantly improve the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant genes g-Glutamylcysteine Ligase Catalytic Subunit (GCLC) and heme oxygenase-1 (HO-1) and their corresponding proteins (y-glutamyl cysteine synthase (y-GCS) and HO-1) in PC12 cells. Inhibition of GCLC and HO-1 by specific inhibitors, L-buthionine-S-sulfoximine (BSO) and zinc protoporphyrin (ZnPP), respectively, partially reduce the protective effect of 1 and 1d. These data present a series of novel chalcone analogs, especially compounds 1 and 1d, as candidates for treating oxidative stress-related disease by activating the Nrf2-antioxidant responsive element (ARE) pathway. [ABSTRACT FROM AUTHOR]

In this paper, a 3D numerical simulation was completed to explore the thermal characteristics in a water flow window in-depth. CFD was used to carry out the analysis on top of successful validation. By changing the solar intensity, water supply temperature and velocity, the temperature distribution and flow field in the window cavity, as well as the water heat gain, were analyzed and compared. This is meaningful for improving the energy-conserving performance in building applications. Simulation results reveal that the variation of solar intensity and water supply temperature affects directly the temperature distribution and the water heat gain but has little impact on the overall velocity field. Local vortices are generated in the window cavity, and their formation and location are largely affected by the varied temperature rise in the water layer. The water heat gain increases and then decreases with the increase in water supply velocity. In addition, a large-enough water supply velocity can disorder the uniform upward flow. These are detrimental to effective thermal extraction. Therefore, in practical application, the vortex should be eliminated, and the flow velocity should be determined properly to maximize the water heat gain. [ABSTRACT FROM AUTHOR]

During the pandemic era, quarantines might potentially have negative effects and disproportionately exacerbate health condition problems. We conducted this cross-sectional, national study to ascertain the prevalence of constant pain symptoms and how quarantines impacted the pain symptoms and identify the factors associated with constant pain to further guide reducing the prevalence of chronic pain for vulnerable people under the pandemic. The sociodemographic data, quarantine conditions, mental health situations and pain symptoms of the general population were collected. After adjusting for potential confounders, long-term quarantine (≥15 days) exposures were associated with an increased risk of constant pain complaints compared to those not under a quarantine (Odds Ratio (OR): 1.26; 95% Confidence Interval (CI): 1.03, 1.54; p = 0.026). Risk factors including unemployment (OR: 1.55), chronic disease history (OR: 2.38) and infection with COVID-19 (OR: 2.15), and any of mental health symptoms including depression, anxiety, insomnia and PTSD (OR: 5.44) were identified by a multivariable logistic regression. Additionally, mediation analysis revealed that the effects of the quarantine duration on pain symptoms were mediated by mental health symptoms (indirect effects: 0.075, p < 0.001). These results advocated that long-term quarantine measures were associated with an increased risk of experiencing pain, especially for vulnerable groups with COVID-19 infection and with mental health symptoms. The findings also suggest that reducing mental distress during the pandemic might contribute to reducing the burden of pain symptoms and prioritizing interventions for those experiencing a long-term quarantine. [ABSTRACT FROM AUTHOR]

The removal of boron (B) from water by co-precipitation with hydroxyapatite (HAP) has been extensively studied due to its low cost, ease of use and high efficiency. However, there is no explicit mechanism to express how resolved B was trapped by HAP. Thus, in this work, the process of removing B from water was studied using a low-cost calcium (Ca) precipitation agent derived from used waste oyster shells. The results showed that the removal rate of B in the simulated wastewater by calcined oyster shell (COS) in the presence of phosphorus (P) is up to more than 90%, as opposed to virtually no removal without phosphate. For B removal, the treated water needs to be an alkaline solution with a high pH above 12, where B is removed as [CaB(OH)4]+ but is not molecular. Finally, the synergistic mechanism of co-precipitation between HAP and dissolved B, occlusion co-precipitation, was explained in detail. The proposed method discovered the relationship between Ca, P and B, and was aimed at removing B without secondary pollution through co-precipitation. [ABSTRACT FROM AUTHOR]

Interest in edible beans as nutraceuticals is increasing. In the present study, the individual phenolic acids, the total phenolic content (TPC), the total flavonoid content (TFC), and the antioxidant and antidiabetic potential of 13 varieties of rice beans from China were investigated. Eight phenolic compounds (catechin, epicatechin, p-coumaric acid, ferulic acid, vitexin, isovitexin, sinapic acid, quercetin) were analyzed on an ultra-performance liquid chromatography (UPLC) mass spectrometry (MS) system. The rice bean varieties had significant differences in total phenolic compounds (ranging from 123.09 ± 10.35 to 843.75 ± 30.15 µg/g), in TPC (ranging from 3.27 ± 0.04 to 6.43 ± 0.25 mg gallic acid equivalents (GAE)/g), in TFC (ranging from 55.95 ± 11.16 to 320.39 ± 31.77 mg catechin (CE)/g), in antioxidant activity (ranging from 39.87 ± 1.37 to 46.40 ± 2.18 µM⋅TE/g), in α-glucosidase inhibition activity (ranging from 44.32 ± 2.12 to 68.71 ± 2.19) and in advanced glycation end products formation inhibition activity (ranging from 34.11 ± 0.59 to 75.75 ± 0.33). This study is the first report on phytochemistry and biological activities in rice beans. [ABSTRACT FROM AUTHOR]

The potential energy curves (PECs) of X2Σ+, A2Πr and B2Σ+ states of BeF radical have been investigated using the complete active space self-consistent-field (CASSCF) method, followed by the highly accurate valence internally contracted multireference configuration interaction (MRCI) approach at the correlation-consistent basis sets, cc-pV5Z for Be and aug-cc-pV6Z for F. Based on the PECs of X2Σ+, A2Πr and B2Σ+ states, the spectroscopic parameters (De, Re, ωe, ωeχe, αe and Be) have also been determined in the present work. With the PECs determined at the present level of theory, vibrational states have been predicted for each state when the rotational quantum number J equals zero (J = 0). The vibrational levels, inertial rotation and centrifugal distortion constants are determined for the three states, and the classical turning points are also calculated for the X2Σ+ state. Compared with the available experiments and other theories, it can be seen that the present spectroscopic parameter and molecular constant results are more fully in agreement with the experimental findings. [ABSTRACT FROM AUTHOR]

Global ocean heat content (OHC) is generally estimated using gridded, model and reanalysis data; its change is crucial to understanding climate anomalies and ocean warming phenomena. However, Argo gridded data have short temporal coverage (from 2005 to the present), inhibiting understanding of long-term OHC variabilities at decadal to multidecadal scales. In this study, we utilized multisource remote sensing and Argo gridded data based on the long short-term memory (LSTM) neural network method, which considers long temporal dependence to reconstruct a new long time-series OHC dataset (1993–2020) and fill the pre-Argo data gaps. Moreover, we adopted a new machine learning method, i.e., the Light Gradient Boosting Machine (LightGBM), and applied the well-known Random Forests (RFs) method for comparison. The model performance was measured using determination coefficients (R2) and root-mean-square error (RMSE). The results showed that LSTM can effectively improve the OHC prediction accuracy compared with the LightGBM and RFs methods, especially in long-term and deep-sea predictions. The LSTM-estimated result also outperformed the Ocean Projection and Extension neural Network (OPEN) dataset, with an R2 of 0.9590 and an RMSE of 4.45 × 1019 in general in the upper 2000 m for 28 years (1993–2020). The new reconstructed dataset (named OPEN-LSTM) correlated reasonably well with other validated products, showing consistency with similar time-series trends and spatial patterns. The spatiotemporal error distribution between the OPEN-LSTM and IAP datasets was smaller on the global scale, especially in the Atlantic, Southern and Pacific Oceans. The relative error for OPEN-LSTM was the smallest for all ocean basins compared with Argo gridded data. The average global warming trends are 3.26 × 108 J/m2/decade for the pre-Argo (1993–2004) period and 2.67 × 108 J/m2/decade for the time-series (1993–2020) period. This study demonstrates the advantages of LSTM in the time-series reconstruction of OHC, and provides a new dataset for a deeper understanding of ocean and climate events. [ABSTRACT FROM AUTHOR]

The exploration of nonhazardous nanoparticles to fabricate a template-driven superhydrophobic surface is of great ecological importance for oil/water separation in practice. In this work, nano-hydroxyapatite (nano-HAp) with good biocompatibility was easily developed from discarded oyster shells and well incorporated with polydimethylsiloxane (PDMS) to create a superhydrophobic surface on a polyurethane (PU) sponge using a facile solution–immersion method. The obtained nano-HAp coated PU (nano-HAp/PU) sponge exhibited both excellent oil/water selectivity with water contact angles of over 150° and higher absorption capacity for various organic solvents and oils than the original PU sponge, which can be assigned to the nano-HAp coating surface with rough microstructures. Moreover, the superhydrophobic nano-HAp/PU sponge was found to be mechanically stable with no obvious decrease of oil recovery capacity from water in 10 cycles. This work presented that the oyster shell could be a promising alternative to superhydrophobic coatings, which was not only beneficial to oil-containing wastewater treatment, but also favorable for sustainable aquaculture. [ABSTRACT FROM AUTHOR]

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the "tail approach" and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors. [ABSTRACT FROM AUTHOR]

Chlorophyll-a (chl-a) is an important parameter of water quality and its concentration can be directly retrieved from satellite observations. The Ocean and Land Color Instrument (OLCI), a new-generation water-color sensor onboard Sentinel-3A and Sentinel-3B, is an excellent tool for marine environmental monitoring. In this study, we introduce a new machine learning model, Light Gradient Boosting Machine (LightGBM), for estimating time-series chl-a concentration in Fujian's coastal waters using multitemporal OLCI data and in situ data. We applied the Case 2 Regional CoastColour (C2RCC) processor to obtain OLCI band reflectance and constructed four spectral indices based on OLCI feature bands as supplementary input features. We also used root-mean-square error (RMSE), mean absolute error (MAE), median absolute percentage error (MAPE), and R2 as performance indicators. The results indicate that the addition of spectral indices can easily improve the prediction accuracy of the model, and normalized fluorescence height index (NFHI) has the best performance, with an RMSE of 0.38 µg/L, MAE of 0.22 µg/L, MAPE of 28.33%, and R2 of 0.785. Moreover, we used the well-known band ratio and three-band methods for chl-a estimation validation, and another two OLCI chl-a products were adopted for comparison (OC4Me chl-a and Inverse Modelling Technique (IMT) Neural Net chl-a). The results confirmed that the LightGBM model outperforms the traditional methods and OLCI chl-a products. This study provides an effective remote sensing technique for coastal chl-a concentration estimation and promotes the advantage of OLCI data in ocean color remote sensing. [ABSTRACT FROM AUTHOR]

Background: Tibia fracture (BF) before stroke shortly causes long-term post-stroke memory dysfunction in mice. The mechanism is unclear. We hypothesize that BF enhances neuroinflammation and blood brain barrier (BBB) breakdown in the hippocampus and white matter (WM) damage. Methods: Mice were assigned to groups: BF, stroke, BF+stroke (BF 6 h before stroke) and sham. BBB integrity was analyzed 3 days after the surgeries and WM injury was analyzed 3 days and 8 weeks after the surgeries. Results: Stroke and BF+stroke groups had more activated microglia/macrophages and lower levels of claudin-5 in the ipsilateral hippocampi than the BF group. BF+stroke group had the highest number microglia/macrophages and the lowest level of claudin-5 among all groups and had fewer pericytes than BF group. Stroke and BF+stroke groups had smaller WM areas in the ipsilateral basal ganglia than the sham group 8 weeks after the injuries. The BF+stroke group also had smaller WM areas in the ipsilateral than sham and BF groups 3 days after the injuries and in the contralateral basal ganglia than stroke and BF groups 8 weeks after the injuries. Conclusions: BF exacerbates neuroinflammation and BBB leakage in the hippocampus and WM damage in basal ganglia, which could contribute to the long-lasting memory dysfunction in BF+stroke mice. [ABSTRACT FROM AUTHOR]

Retrieving information concerning the interior of the ocean using satellite remote sensing data has a major impact on studies of ocean dynamic and climate changes; however, the lack of information within the ocean limits such studies about the global ocean. In this paper, an artificial neural network, combined with satellite data and gridded Argo product, is used to estimate the ocean heat content (OHC) anomalies over four different depths down to 2000 m covering the near-global ocean, excluding the polar regions. Our method allows for the temporal hindcast of the OHC to other periods beyond the 2005–2018 training period. By applying an ensemble technique, the hindcasting uncertainty could also be estimated by using different 9-year periods for training and then calculating the standard deviation across six ensemble members. This new OHC product is called the Ocean Projection and Extension neural Network (OPEN) product. The accuracy of the product is accessed using the coefficient of determination (R2) and the relative root-mean-square error (RRMSE). The feature combinations and network architecture are optimized via a series of experiments. Overall, intercomparison with several routinely analyzed OHC products shows that the OPEN OHC has an R2 larger than 0.95 and an RRMSE of <0.20 and presents notably accurate trends and variabilities. The OPEN product can therefore provide a valuable complement for studies of global climate changes. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome–associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1β in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3−/− mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents. [ABSTRACT FROM AUTHOR]

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae), is an important transmission vector of the citrus greening disease Candidatus Liberibacter asiaticus (CLas). The D. citri midgut exhibits an important tissue barrier against CLas infection. However, the molecular mechanism of the midgut response to CLas infection has not been comprehensively elucidated. In this study, we identified 778 differentially expressed genes (DEGs) in the midgut upon CLas infection, by comparative transcriptome analyses, including 499 upregulated DEGs and 279 downregulated DEGs. Functional annotation analysis showed that these DEGs were associated with ubiquitination, the immune response, the ribosome, endocytosis, the cytoskeleton and insecticide resistance. KEGG enrichment analysis revealed that most of the DEGs were primarily involved in endocytosis and the ribosome. A total of fourteen DEG functions were further validated by reverse transcription quantitative PCR (RT-qPCR). This study will contribute to our understanding of the molecular interaction between CLas and D. citri. [ABSTRACT FROM AUTHOR]

Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as β-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC50 = 0.64 μg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC50 values against virus yield were 1.52 μM and 2.60 μM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC50 = 0.06 μM) and indigodole B (IC50 = 2.09 μM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection. [ABSTRACT FROM AUTHOR]

Arteriovenous malformations (AVMs) are abnormal connections of vessels that shunt blood directly from arteries into veins. Rupture of brain AVMs (bAVMs) can cause life-threatening intracranial bleeding. Even though the majority of bAVM cases are sporadic without a family history, some cases are familial. Most of the familial cases of bAVMs are associated with a genetic disorder called hereditary hemorrhagic telangiectasia (HHT). The mechanism of bAVM formation is not fully understood. The most important advances in bAVM basic science research is the identification of somatic mutations of genes in RAS-MAPK pathways. However, the mechanisms by which mutations of these genes lead to AVM formation are largely unknown. In this review, we summarized the latest advance in bAVM studies and discussed some pathways that play important roles in bAVM pathogenesis. We also discussed the therapeutic implications of these pathways. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages. ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant. However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated. This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques. The DNA-launched replicon of ZIKV Natal RGN was constructed and contains the EGFP reporter, lacks prM-E genes, and replicates under CMV promoter control. The peak in the ZIKV Natal RGN SRIP titer reached 6.25 × 106 TCID50/mL in the supernatant of prM-E-expressing packaging cells 72 h post-transfection with a ZIKV Natal RGN replicon. The infectivity of ZIKV Natal RGN SRIPs has been demonstrated to correlate with the green florescence intensity of the EGFP reporter, the SRIP-induced cytopathic effect, and ZIKV's non-structural protein expression. Moreover, ZIKV Natal RGN SRIPs effectively self-replicated in rhabdomyosarcoma/muscle, glioblastoma/astrocytoma, and retinal pigmented epithelial cells, displaying unique cell susceptibility with differential attachment activity. Therefore, the recombinant ZIKV Natal RGN strain was rescued as SRIPs that could be used to elucidate the biological features of a neurotropic strain regarding cell tropism and pathogenic components, apply for antiviral agent screening, and develop vaccine candidates. [ABSTRACT FROM AUTHOR]

Sea ice distribution is an important indicator of ice conditions and regional climate change in the Bohai Sea (China). In this study, we monitored the spatiotemporal distribution of the Bohai Sea ice in the winter of 2017–2018 by developing sea ice information indexes using 300 m resolution Sentinel-3 Ocean and Land Color Instrument (OLCI) images. We assessed and validated the index performance using Sentinel-2 MultiSpectral Instrument (MSI) images with higher spatial resolution. The results indicate that the proposed Normalized Difference Sea Ice Information Index (NDSIIIOLCI), which is based on OLCI Bands 20 and 21, can be used to rapidly and effectively detect sea ice but is somewhat affected by the turbidity of the seawater in the southern Bohai Sea. The novel Enhanced Normalized Difference Sea Ice Information Index (ENDSIIIOLCI), which builds on NDSIIIOLCI by also considering OLCI Bands 12 and 16, can monitor sea ice more accurately and effectively than NDSIIIOLCI and suffers less from interference from turbidity. The spatiotemporal evolution of the Bohai Sea ice in the winter of 2017–2018 was successfully monitored by ENDSIIIOLCI. The results show that this sea ice information index based on OLCI data can effectively extract sea ice extent for sediment-laden water and is well suited for monitoring the evolution of Bohai Sea ice in winter. [ABSTRACT FROM AUTHOR]

Chitin synthase is a critical enzyme that catalyzes N-acetylglucosamine to form chitin, which plays an important role in the growth and development of insects. In this study, we identified a chitin synthase gene (CHS) with a complete open reading frame (ORF) of 3180 bp from the genome database of Diaphorina citri, encoding a protein of 1059 amino acid residues with the appropriate signature motifs (EDR and QRRRW). Reverse transcription-quantitative PCR (RT-qPCR) analysis suggested that D. citri CHS (DcCHS) was expressed throughout all developmental stages and all tissues. DcCHS had the highest expression level in the integument and fifth-instar nymph stage. Furthermore, the effects of diflubenzuron (DFB) on D. citri mortality and DcCHS expression level were investigated using fifth-instar nymph through leaf dip bioassay, and the results revealed that the nymph exposed to DFB had the highest mortality compared with control group (Triton-100). Silencing of DcCHS by RNA interference resulted in malformed phenotypes and increased mortality with decreased molting rate. In addition, transmission electron microscopy (TEM) and fluorescence in situ hybridization (FISH) also revealed corresponding ultrastructural defects. Our results suggest that DcCHS might play an important role in the development of D. citri and can be used as a potential target for psyllid control. [ABSTRACT FROM AUTHOR]

Retrieving multi-temporal and large-scale thermohaline structure information of the interior of the global ocean based on surface satellite observations is important for understanding the complex and multidimensional dynamic processes within the ocean. This study proposes a new ensemble learning algorithm, extreme gradient boosting (XGBoost), for retrieving subsurface thermohaline anomalies, including the subsurface temperature anomaly (STA) and the subsurface salinity anomaly (SSA), in the upper 2000 m of the global ocean. The model combines surface satellite observations and in situ Argo data for estimation, and uses root-mean-square error (RMSE), normalized root-mean-square error (NRMSE), and R2 as accuracy evaluations. The results show that the proposed XGBoost model can easily retrieve subsurface thermohaline anomalies and outperforms the gradient boosting decision tree (GBDT) model. The XGBoost model had good performance with average R2 values of 0.69 and 0.54, and average NRMSE values of 0.035 and 0.042, for STA and SSA estimations, respectively. The thermohaline anomaly patterns presented obvious seasonal variation signals in the upper layers (the upper 500 m); however, these signals became weaker as the depth increased. The model performance fluctuated, with the best performance in October (autumn) for both STA and SSA, and the lowest accuracy occurred in January (winter) for STA and April (spring) for SSA. The STA estimation error mainly occurred in the El Niño-Southern Oscillation (ENSO) region in the upper ocean and the boundary of the ocean basins in the deeper ocean; meanwhile, the SSA estimation error presented a relatively even distribution. The wind speed anomalies, including the u and v components, contributed more to the XGBoost model for both STA and SSA estimations than the other surface parameters; however, its importance at deeper layers decreased and the contributions of the other parameters increased. This study provides an effective remote sensing technique for subsurface thermohaline estimations and further promotes long-term remote sensing reconstructions of internal ocean parameters. [ABSTRACT FROM AUTHOR]