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Abstract Background Hepatoid adenocarcinoma of the lung (HAL) is a distinctly uncommon subtype of lung adenocarcinoma (LAC), characterized by hepatoid features and an alarmingly low 5-year survival rate of approximately 8%. The scarcity of information on this condition has contributed to the absence of standardized treatment protocols, and the molecular underpinnings of its pathogenesis remain largely unexplored. To bridge these gaps, this study compiled data from 191 primary HAL patients to delineate treatment patterns, prognostic factors, and potential pathogenic mechanisms. Methods This study was divided into two cohorts: cohort 1, comprising 110 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and cohort 2, consisting of 70 patients identified through a comprehensive literature review via the PubMed, Web of Science, and Scopus databases, in addition to 11 patients from Tongji Hospital. The Cox proportional hazards regression model was employed to identify independent prognostic factors. Kaplan-Meier survival curves were generated to assess the impact of treatment modalities centered around surgery and chemotherapy. Moreover, this study evaluated the efficacy of first-line treatment regimens and conducted Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses on identified mutated genes. Results The demographic and clinical profile of HAL patients typically comprises older individuals who are smokers, with a predisposition for diagnosis at advanced disease stages, culminating in a high mortality rate. Key prognostic indicators identified included disease stage, chemotherapy and surgical interventions. The study suggests a treatment strategy that advocates chemotherapy for patients with stage IV HAL and surgery for those with non-stage IV disease. The combination of paclitaxel and platinum-based chemotherapy emerged as an efficacious first-line treatment, with the integration of immunotherapy and targeted therapies showing potential benefits. Genetic analysis underscored similarities between HAL and LAC, particularly highlighting aberrant kinase activity (serine, threonine, and tyrosine) and the activation of PI3K-Akt and MAPK signaling pathways as contributing factors to HAL pathogenesis. Conclusion Despite its relatively rare occurrence, this study underscores the significance of treatment strategies and concludes probable prognostic factors. Due to limited reports, a deeper understanding of the molecular mechanisms driving tumorigenesis and progression in HAL is needed.

Abstract Background Dihydroxyacetone (DHA) stands as a crucial chemical material extensively utilized in the cosmetics industry. DHA production through the dephosphorylation of dihydroxyacetone phosphate, an intermediate product of the glycolysis pathway in Escherichia coli, presents a prospective alternative for industrial production. However, insights into the pivotal enzyme, dihydroxyacetone phosphate dephosphorylase (HdpA), remain limited for informed engineering. Consequently, the development of an efficient tool for high-throughput screening of HdpA hypermutants becomes imperative. Results This study introduces a methylglyoxal biosensor, based on the formaldehyde-responding regulator FrmR, for the selection of HdpA. Initial modifications involved the insertion of the FrmR binding site upstream of the −35 region and into the spacer region between the −10 and −35 regions of the constitutive promoter J23110. Although the hybrid promoter retained constitutive expression, expression of FrmR led to complete repression. The addition of 350 μM methylglyoxal promptly alleviated FrmR inhibition, enhancing promoter activity by more than 40-fold. The methylglyoxal biosensor system exhibited a gradual increase in fluorescence intensity with methylglyoxal concentrations ranging from 10 to 500 μM. Notably, the biosensor system responded to methylglyoxal spontaneously converted from added DHA, facilitating the separation of DHA producing and non-producing strains through flow cytometry sorting. Subsequently, the methylglyoxal biosensor was successfully applied to screen a library of HdpA mutants, identifying two strains harboring specific mutants 267G > T and D110G/G151C that showed improved DHA production by 68% and 114%, respectively. Expressing of these two HdpA mutants directly in a DHA-producing strain also increased DHA production from 1.45 to 1.92 and 2.29 g/L, respectively, demonstrating the enhanced enzyme properties of the HdpA mutants. Conclusions The methylglyoxal biosensor offers a novel strategy for constructing genetically encoded biosensors and serves as a robust platform for indirectly determining DHA levels by responding to methylglyoxal. This property enables efficiently screening of HdpA hypermutants to enhance DHA production.

Since the approval for the treatment of melanoma in 2014, immune checkpoint inhibitors (ICIs) have revolutionized the therapy pattern across various malignancies. Coinciding with their frequent usage, their adverse effects, including fever, cannot be neglected. In the context of cancer diseases and cancer treatments, fever of unknown origin (FUO), which has long posed a challenge for clinicians in terms of diagnosis and management, brings forth new connotation and significance. In this paper review, we present the concept of ICIs-associated FUO, consider activated immune system and elevated cytokines as common mechanisms by which ICIs induce fever and various immune-related adverse events (irAEs), summarize and compare the primary etiologies of ICI-associated FUO, and compare it with conventional types of FUO.

The issue of continuous observer design for integer order nonlinear systems has been widely studied in existing works. Yet, there are few works that closely related to granular computing theory and discrete signal to better estimate system states. In this paper, by using the granular function description, we propose a novel impulsive observer design algorithm to ensure the cognitive convergence of error dynamic systems. Especially, the resulting criterion reflects well the relationship between the fractional order and the pulse signal. A numerical simulation is provided to illustrate effectiveness of the given method.

Geological storage of CO2 is an effective measure to reduce carbon emission and mitigate greenhouse effect. Through geothermal exploration and comprehensive research，it is found that the sandstone stratified strata of the Third and Fourth Member of the Quantou Formation，the Qingshankou Formation and the Yaojia Formation of the Cretaceous age in the Lindian area of Heilongjiang Province，with the burial depth of about 940−2062 m，contain rich saline water with TDS of 2000−9000 mg/L，and are of well-developed pores and slow groundwater flow. The caprock is dominated by pelite stratified strata of the Nenjiang Formation，Sifangtai Formation and Mingshui Formation of the Cretaceous age，with a thickness of about 800−1300 m. It has not been penetrated by major fault zones and is well closed，which determines that it can be used as a good geological reservoir for CO2 storage. At the same time, Lindian is close to the city of Daqing, with numerous chemical enterprises, concentrated and sufficient carbon sources, and large scale and short distance, providing favorable conditions for CO2 geological storage in the study area. Due to the lack of oil and gas resources and oil wells in the Lindian area, this work uses geothermal exploration wells for the first time. According to the mechanism of CO2 geological storage technology and the international authoritative potential assessment formula, the potential assessment of CO2 geological storage of deep saline aquifers in this area is carried out. The results show that the theoretical CO2 storage in the deep salt aquifers is 478.91×108 t，the effective CO2 storage is 11.49×108 t, which is of large storage potential. In the future, it can provide geological storage sites for carbon reduction in Daqing, Qiqihar and other neighboring cities. The implementation of this work provides technical support for the next implementation of CO2 geological storage suitability evaluation, objective target area and site selection and demonstration projects in the Lindian area.

Marine ecosystems are dominated by microbial communities. Inspired by the photoelectric conversion feature of the marine ecosystems, the authors design a four-species microbial community to mimic primary producer, primary degrader, and ultimate consumers, and show its ability to convert light into electricity for over one month.

Due to the worldwide attention of fossil fuel consumption and environment pollution, geothermal is recognized to be amongst the prospering alternative energy. Previous researches mainly focused on the shallow-depth geothermal heat pump systems (SD-GHPs), while medium-depth geothermal heat pump system (MD-GHPs) lacked of the experimental support especially in severely cold region. A field test of MD-GHPs using deep borehole heat exchanger (DBHE) was conducted and verified in terms of temperature variation, heat exchange and COP. The indoor temperature remained 20 °C around even though the outdoor temperature was as low as −25.10 °C. The water supply and return water temperature on the customer side performed steadfast heating characteristics that the averages were 35.13 °C and 30.97 °C. Moreover, flow rate and borehole depth are the essential influencing factors on DBHE outlet temperatures. This suggests that lifting flow rates is a fantastic option when only considering the enhancement of the thermal extraction. The DBHE average heat exchange per meter is 1000/1200 m for 61.1/84.9 W/m and 2000 m is 152.6 W/m respectively. Besides, the average heat exchange of DBHEs for working days was 485.4 kW while during Chinese New Year Holidays was 388.6 kW. Correspondingly, the average COPs for MD-GHPs ground side were 4.5 and 5.2, respectively. Results show that MD-GHPs can be extended to severely cold regions and obtain superior performance.

Anterior inferior cerebellar artery (AICA) occlusion is a subtype of posterior circulation stroke. Confirmation of its angiomorphology and etiology is challenging because of the complex mechanisms underlying small-artery thrombogenesis. In addition to conventional factors, physicians frequently overlook hemorheological changes. In this case report, we describe right AICA occlusion in a 50-year-old man. He presented with an unsteady walk, tinnitus, dizziness, and left-sided peripheral facial palsy observed over 36 hours, accompanied by increased blood viscosity on hemorheological evaluation. Magnetic resonance imaging revealed acute infarction in the left cerebellar hemisphere and middle cerebellar peduncles. Magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) failed to detect AICA occlusion, which was later confirmed using digital subtraction angiography. Repeat routine blood examinations showed elevated erythrocyte and leukocyte counts and serum hemoglobin concentrations that persisted over many days. Hemorheological evaluation revealed increased whole blood viscosity at a low shear rate. AICA occlusion should thus be diagnosed based on its initial characteristic manifestations; notably, MRA and CTA may fail to detect arterial occlusion. The importance of hemorheological change as a factor of stroke is frequently neglected. We therefore report this case hoping to emphasize its relevance, especially in small-artery occlusion.

Land type survey is an important task of land resources survey and the basis of scientific management of land resources. With the increasingly prominent problems of population, resources, and environment, there is an urgent need for a fast and accurate classification method of large-scale land use and land cover based on remote sensing data. Traditional machine learning classification methods based on pixel classification achieved sufficient results and are widely used, such as maximum likelihood classification and random forests method. However, with the development of the novel technology of deep learning, in practical application, for multi-classified land resources, how to use the fast and effective classification method of low and medium resolution RS images needs further research. This paper takes the land resource classification of the Tonghe medium resolution RS dataset of the third land survey in China as an example to screen and compare traditional machine learning classification methods and semantic segmentation models FC-DenseNet56, GCN, BiSeNet, U-Net, DeepLabV3, AdapNet, and PSPNet, which aim to select the optimal feature extraction model. The results show that the classification accuracy of the U-Net model can reach 93.62%, which is more accurate and effective than traditional machine learning methods and other semantic segmentation models. It is suitable for multi-classification tasks of land cover resources in low and medium resolution RS images and shows a superior effect in practical application. Besides, the conclusion of this study can provide a demonstration for large-scale land cover resources investigation using low and medium resolution RS images.

Abstract Chlorination converts an efficient isoindigo (IID)‐based electron donor material to an effective electron acceptor material, which could pair with different donor materials. The polymer PAZ could work as the donor and achieve moderate power conversion efficiency of 3.56%, but organic solar cells based on the blend of PC71BM and the chlorinated analogue PAZ‐Cl fail. On the contrary, only PAZ‐Cl could be used as the acceptor material matching with typical donor polymers, such as PTB7‐Th, J52 and J52‐2Cl. Simulation based on density functional theory suggests that the main reason for this transform might be attributed to the change in the electrostatic potential of the polymers. This research paves a new way to design novel electron acceptors for organic solar cells.

This study constructs a preliminary inventory of landslides triggered by the MS 6.8 Luding earthquake based on field investigation and human-computer interaction visual interpretation on optical satellite images. The results show that this earthquake triggered at least 5 007 landslides, with a total landslide area of 17.36 ​km2, of which the smallest landslide area is 65 ​m2 and the largest landslide area reaches 120 747 ​m2, with an average landslide area of about 3 500 ​m2. The obtained landslides are concentrated in the IX intensity zone and the northeast side of the seismogenic fault, and the area density and point density of landslides are 13.8%, and 35.73 ​km−2 peaks with 2 ​km as the search radius. It should be noted that the number of landslides obtained in this paper will be lower than the actual situation because some areas are covered by clouds and there are no available post-earthquake remote sensing images. Based on the available post-earthquake remote sensing images, the number of landslides triggered by this earthquake is roughly estimated to be up to 10 000. This study can be used to support further research on the distribution pattern and risk evaluation of the coseismic landslides in the region, and the prevention and control of landslide hazards in the seismic area.

Emerging holographic optical elements and lithography-based devices are enhancing the performances of augmented reality and virtual reality displays with glasses-like form factor.

The mechanical properties of rock can be weakened under the influence of high temperatures. To describe the mechanical behavior of rock under the action of high temperature more accurately, based on the Zienkiewicz–Pande yield criterion, the damage variable Dc which accounts for the coupling between high temperature and load is introduced. According to plastic potential theory and plastic flow law, the iterative incremental method for a high-temperature and load-coupled damage constitutive model in Flac3D is deduced in detail and compiled into the corresponding dynamic link library file (.dll file). By modifying the shape function to degenerate into the Mohr–Coulomb constitutive model, an elastic–plastic analysis of an ideal circular tunnel is performed, and a comparison is made between calculation results obtained from the built-in Mohr–Coulomb constitutive model in Flac3D, proving the correctness of the secondary development program. Finally, numerical simulations are conducted to study the effects of high-temperature damage using rock uniaxial compression tests, and the model’s validity is established by comparing it with previous experimental results.

Summary The unconventional yeast Pichia kudriavzevii is renowned for its ability to survive at low pH and has been exploited for the industrial production of various organic acids, especially succinic acid (SA). However, P. kudriavzevii can also utilize the di‐ and tricarboxylate intermediates of the Krebs cycle as the sole carbon sources for cell growth, which may adversely affect the extracellular accumulation of SA. Because the carboxylic acid transport machinery of P. kudriavzevii remains poorly understood, here, we focused on studying its SA transportation process from the perspective of mining and characterization of dicarboxylate transporters in a newly isolated acid‐tolerant P. kudriavzevii strain CY902. Through genome sequencing and transcriptome analysis, two JEN family carboxylate transporters (PkJEN2‐1 and PkJEN2‐2) were found to be involved in SA transport. Substrate specificity analysis revealed that both PkJEN proteins are active dicarboxylate transporters, that can effectively import succinate, fumarate and L‐malate into the cell. In addition, PkJEN2‐1 can transport α‐ketoglutarate, while PkJEN2‐2 cannot. Since PkJEN2‐1 shows higher transcript abundance than PkJEN2‐2, its role in dicarboxylate transport is more important than PkJEN2‐2. In addition, PKJEN2‐2 is also responsible for the uptake of citrate. To our best knowledge, this is the first study to show that a JEN2 subfamily transporter is involved in tricarboxylate transport in yeast. A combination of model‐based structure analysis and rational mutagenesis further proved that amino acid residues 392‐403 of the tenth transmembrane span (TMS‐X) of PkJEN2‐2 play an important role in determining the specificity of the tricarboxylate substrate. Moreover, these two PkJEN transporters only exhibited inward transport activity for SA, and simultaneous inactivation of both PkJEN transporters reduced the SA influx, resulting in enhanced extracellular accumulation of SA in the late stage of fermentation. This work provides useful information on the mechanism of di‐/tricarboxylic acid utilization in P. kudriavzevii, which will help improve the organic acid production performance of this microbial chassis.

Hyperspectral imaging (HSI) is widely used in various fields owing to its rich spectral information. Nonetheless, the high dimensionality of HSI and the limited number of labeled data remain significant obstacles to HSI classification technology. To alleviate the above problems, we propose an attention-embedded triple-branch fusion convolutional neural network (AETF-Net) for an HSI classification. The network consists of a spectral attention branch, a spatial attention branch, and a multi-attention fusion branch (MAFB). The spectral branch introduces the cross-channel attention to alleviate the band redundancy problem in high dimensions, while the spatial branch preserves the location information of features and eliminates interfering image elements by a bi-directional spatial attention module. These pre-extracted spectral and spatial attention features are then embedded into a novel MAFB with large kernel decomposition technique. The proposed AETF-Net achieves multi-attention features reuse and extracts more representative and discriminative features. Experimental results on three well-known datasets demonstrate the superiority of the method AETF-Net.

In our previous work, a two-phase multiobjective sparse unmixing (Tp-MoSU) approach has been proposed, which settled the regularization parameter issues of the regularization unmixing methods. However, Tp-MoSU has limited performance in identifying the real end-members from the highly noisy data in the first phase and cannot effectively exploit the spatial-contextual information in the second phase because of the similarity measure it used. To settle these two problems, a composite spectral similarity measure is first constructed by fusing the spectral correlation angle and the Euclidean distance. It is used instead of the Frobenius norm to measure the unmixing residuals in the first phase because it considers both the shape and amplitude discrepancy between two spectra simultaneously. Then, the L2,∞ norm is used instead of the l2 norm to measure the unmixing residuals in the second phase, and the initialization, recombination, mutation, and local search strategies are also elaborately redesigned to help reduce this new objective, based on which the unmixing tasks of all pixels in a hyperspectral image can be completed at once. Therefore, this new measure facilitates the estimation of the abundances as a whole, and thus, the spatial-contextual information can be better exploited to improve the estimated abundances. Besides, the time efficiency for abundance estimation is also greatly improved. Experimental results demonstrate that the proposed method (termed as TpMoSU+) outperforms Tp-MoSU in both of the two phases under heavy noise and outperforms the tested regularization algorithms in estimating the abundances.

AbstractHeinrich (H) events are significant millennial climatic events that occurred during the last glacial period. Their footprints exited most parts of the global world, including the Asian monsoon (AM) region. However, the internal hydroclimatic characteristics of the AM system and their link to the external forcing during the H stadials are not fully understood. This study reconstructed monsoon precipitation changes during 33,000-12,500 a BP using grain size characteristics, elementary ratios, and pollen percentages from sediments of a crater lake (Tianchi Lake) in northeastern China. The H1 ~ H3 events are identified by high values of median grain size (MGS) and low values of Fe/Mn ratios and pollen percentages. By comparison with other records in the AM region, we found that H events in monsoon precipitation records were more obvious in the relatively higher-latitude region than in the lower-latitude sites. These inconsistent responses within the AM region during the H stadials might be attributed to both the high- and low-latitude climate processes.

Abstract Escherichia coli BL21 is arguably the most popular host for industrial production of proteins, and industrial fermentations are often plagued by phage infections. The CRISPR/Cas system is guided by a gRNA to cleave a specific DNA cassette, which can be developed into a highly efficient programable phage defense system. In this work, we constructed a CRISPR/Cas system targeting multiple positions on the genome of T7 phage and found that the system increased the BL21’s defense ability against phage infection. Furthermore, the targeted loci on phage genome played a critical role. For better control of expression of CRISPR/Cas9, various modes were tested, and the OD of the optimized strain BL21(pT7cas9, pT7-3gRNA, prfp) after 4 h of phage infection was significantly improved, reaching 2.0, which was similar to the control culture without phage infection. Although at later time points, the defensive ability of CRISPR/Cas9 systems were not as obvious as that at early time points. The viable cell count of the engineered strain in the presence of phage was only one order of magnitude lower than that of the strain with no infection, which further demonstrated the effectiveness of the CRISPR/Cas9 phage defense system. Finally, the engineered BL21 strain under phage attack expressed RFP protein at about 60% of the un-infected control, which was significantly higher than the parent BL21. In this work, we successfully constructed a programable CRISPR/Cas9 system to increase the ability of E. coli BL21’s to defend against phage infection, and created a resistant protein expression host. This work provides a simple and feasible strategy for protecting industrial E. coli strains against phage infection.

Abstract Background LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angiogenesis of HUVECs and whether the linc-OIP5 regulations are involved in angiogenesis-related Notch and Hippo signaling pathways. Methods A trans-well system co-cultured HUVECs with linc-OIP5 knockdown breast cancer cell MDA-MB-231 was utilized to study the proliferation, migration and tube formation abilities of HUVECs and alterations of related signaling indicators in breast cancer cells and their conditioned medium through a series of cell and molecular experiments. Results Overexpressed linc-OIP5, YAP1, and JAG1 were found in breast cancer cell lines MCF7 and MDA-MB-231 and the expression levels of YAP1 and JAG1 were proportional to the breast cancer tissue grades. MDA-MB-231 cells with linc-OIP5 knockdown led to weakened proliferation, migration, and tube formation capacity of co-cultured HUVECs. Besides, linc-OIP5 knockdown in co-cultured MDA-MB-231 cells showed downregulated YAP1 and JAG1 expression, combined with a reduced JAG1 level in conditioned medium. Furthermore, a disrupted DLL4/Notch/NRP1 signaling in co-cultured HUVECs were also discovered under this condition. Conclusion Hence, linc-OIP5 in MDA-MB-231 breast cancer cells may act on the upstream of the YAP1/Notch/NRP1 signaling circuit to affect proliferation, migration, and tube formation of co-cultured HUVECs in a non-cellular direct contact way through JAG1 in conditioned medium. These findings at least partially provide a new angiogenic signaling circuit in breast cancers and suggest linc-OIP5 could be considered as a therapeutic target in angiogenesis of breast cancers.

The parallel seismic method is an effective method to detect the length of pile. In the paper, based on the ray theory of Snell’s law, the two methods of determining the pile length by the first transmission P-wave in the side hole are discussed and modified. The error influencing factors of both two methods are then analysed. Finally, the finite element software ABAQUS was used to simulate the inspection of pile foundations by the parallel seismic method. The numerical simulation results were compared with the results of the error calculation theory to verify the applicability of the error calculation theory. The error calculation theory was then tested and applied in an engineering example. The results show that (1) in order to reduce errors, unreasonable data points need to be removed when fitting the inspection data points and (2) the larger the pile slenderness ratio, the smaller the distance between the side holes and the pile, and the more accurate the pile length results obtained.

To realize parameter feedback optimization of tunnel construction in water-rich areas, a feedback analysis method for tunnel parameters under fluid–solid coupling conditions was established based on an intelligent optimization algorithm. Firstly, the numerical calculation model was established and solved using the fluid–solid coupling model. In orthogonal design analysis, the displacement of surrounding rock and pore water pressure distribution in different rock mass parameter combinations were obtained, and the learning samples needed for machine learning were established. The input group was surrounding rock displacement and pore water pressure, and the output was rock mass parameters. Then, the Gaussian process algorithm was used to obtain the nonlinear mapping relationship contained in the learning samples. A differential evolution algorithm was used to optimize the critical parameters involved in this process. Furthermore, according to the established regression model and the measured displacement and pore water pressure in the research area, differential evolution was used again to optimize the rock mass parameters and obtain the parameter feedback analysis results. Finally, the inversion values were compared with the actual measured values, and the reliability of the surrounding rock parameters obtained from the feedback analysis was verified, providing an effective method for obtaining surrounding rock parameters for similar projects.

As one of the most complete archaic human fossils, the Harbin cranium provides critical evidence for studying the diversification of the Homo genus and the origin of Homo sapiens. However, the unsystematic recovery of this cranium and a long and confused history since the discovery impede its accurate dating. Here, we carried out a series of geochemical analyses, including non-destructive X-ray fluorescence (XRF), rare earth elements (REE), and the Sr isotopes, to test the reported provenance of the Harbin cranium and get better stratigraphic constraints. The results show that the Harbin cranium has very similar XRF element distribution patterns, REE concentration patterns, and Sr isotopic compositions to those of the Middle Pleistocene-Holocene mammalian and human fossils recently recovered from the Harbin area. The sediments adhered in the nasal cavity of the Harbin cranium have a 87Sr/86Sr ratio of 0.711898, falling in the variation range measured in a core drilled near the Dongjiang Bridge, where the cranium was discovered during its reconstruction. The regional stratigraphic correlations indicate that the Harbin cranium was probably from the upper part of the Upper Huangshan Formation of the Harbin area, which has an optically stimulated luminescence dating constraint between 138 and 309 ka. U-series disequilibrium dating (n = 10) directly on the cranium suggests that the cranium is older than 146 ka. The multiple lines of evidence from our experiments consistently support the theory that the Harbin cranium is from the late Middle Pleistocene of the Harbin area. Our study also shows that geochemical approaches can provide reliable evidence for locating and dating unsystematically recovered human fossils, and potentially can be applied to other human fossils without clear provenance and stratigraphy records. Public summary: • Unsystematic recovery of the Harbin fossil cranium and a long history since the discovery impede its accurate dating • Geochemical analyses, including non-destructive X-ray fluorescence, rare earth elements, and the strontium isotopes, suggest that the fossil cranium was from a bed of lacustrine sediments aged between 138 and 309 thousand years ago in the Harbin region • Uranium-series disequilibrium dating directly on the cranium suggests that the cranium is older than 146 thousand years

Augmented reality (AR) displays are attracting significant attention and efforts. In this paper, we review the adopted device configurations of see-through displays, summarize the current development status and highlight future challenges in micro-displays. A brief introduction to optical gratings is presented to help understand the challenging design of grating-based waveguide for AR displays. Finally, we discuss the most recent progress in diffraction grating and its implications. Keywords: Near-eye displays, See-through display, Augmented reality, Micro-displays, Bragg gratings

The track fasteners may be damaged by fatigue and impact load during long-term subway operation, resulting in the failure of the connecting components between the rail and the track plate, and the spacing of rail support becomes larger, resulting in an increase in its dynamic deformation, affecting the subway vehicle’s running performance, and, in severe cases, endangering the vehicle’s running safety. A vehicle-subway track system model was created to study the running performance of subway vehicles when fasteners failed. A multi-rigid, body spring damping system is used to describe the vehicle system. The model for the track system is created using the finite element method (FEM), and the vehicle dynamic performances under various fastener failure scenarios are calculated, as well as the vehicle’s running comfort and safety in various scenarios. The findings show that fastener failure has little impact on the vehicle’s running comfort but it has a significant impact on the vehicle’s wheel unloading ratio.

Objective This study aimed to investigate the role of sex hormones in postmenopausal women with vestibular migraine. Methods This observational study included 242 female patients with vestibular migraine who were postmenopausal during April 2017 to December 2019. Serum levels of sex hormones, including estradiol, progesterone, testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin, were determined by radioimmunoassay. The duration and frequency (every month) of onset of vestibular migraine were recorded. The degree of vestibular migraine was measured by the visual analogue scale. Results Serum levels of estradiol, progesterone, and testosterone were significantly lower, while serum prolactin levels were significantly higher in postmenopausal patients with vestibular migraine compared with healthy controls. Serum estradiol levels were negatively correlated with the duration, frequency, and severity of onset of vestibular migraine. Patients with higher serum estradiol levels showed a longer disease-free survival time. Conclusion Sex hormones are correlated with vestibular migraine in postmenopausal women. Additionally, estradiol levels are correlated with the duration, frequency, and severity of onset of vestibular migraine, as well as the disease-free survival time.

Shengmai Formula (SMF) is one of the traditional Chinese medicine representative formulas and is widely used for the treatment of cardio- and cerebrovascular disease. Previous studies demonstrated that the major effective ingredients in SMF can interact with each other based on some uptake transporters. However, the role of the efflux transporter breast cancer resistance protein (BCRP) in these interactions involving SMF remains unclear. The purpose of this study was to investigate the interactions of the major active components of SMF with BCRP and the compatibility mechanism of these complex components in SMF based on BCRP. We selected 4 main fractions, including ginseng total saponins (GTS), ophiopogon total saponins (OTS), ophiopogon total flavonoids (OTF), and fructus schisandrae total lignans (STL), and 12 bioactive components, including ginsenosides Re, Rd, Rb1, and Rg1, ophiopogonins D and Dˊ, methylophiopogonanones A and B, schizandrins A and B, and schizandrols A and B to explore the interactions of SMF with BCRP in LLC-PK1 and LLC-PK1/BCRP cells and BCRP membrane vesicles. The results showed that ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A can be transported by BCRP into LLC-PK1/BCRP cells. Schisandrol B exhibited a markedly inhibitory effect on the transport function of BCRP and can significantly inhibit the uptake of methylophiopogonanone B and schizandrin A into LLC-PK1/BCRP cells. In “Inside-Out” BCRP membrane vesicles, BCRP mediated the transport of ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A, with Km values of 111.9 ± 31.26 μM, 82.01 ± 16.72 μM, 57.06 ± 8.789 μM, and 37.19 ± 6.512 μM, respectively. GTS, STL, ginsenosides Rd and Rb1, and schisandrol B were potent inhibitors of BCRP and showed different degrees of inhibition on the transport of ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A via BCRP. In conclusion, GTS, STL, ginsenosides Rd and Rb1, and schizandrol B are potential inhibitors of BCRP. Ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A are potential substrates of BCRP, and their transport, which is mediated by BCRP, may be inhibited by potential inhibitors in SMF. There are potential interactions of these main effective components of SMF at the cellular and vesicular levels that are mediated by BCRP. The interplay of these bioactive components based on BCRP may be an important compatibility mechanism in SMF.

While promoting a business or activity in geo-social networks, the geographical distance between its location and users is critical. Therefore, the problem of Distance-Aware Influence Maximization (DAIM) has been investigated recently. The efficiency of DAIM heavily relies on the sample location selection. Specifically, the online seeding performance is sensitive to the distance between the promoted location and its nearest sample location, and the offline precomputation performance is sensitive to the number of sample locations. However, there is no work to fully study the problem of sample location selection for DAIM in geo-social networks. To do this, we first formalize the problem under a reasonable assumption that a promoted location always adheres to the distribution of users (query zone). Then, we propose two efficient location sampling approaches based on facility location analysis, which is one of the most well-studied areas of operations research, and these two approaches are denoted by Facility Location based Sampling (FLS) and Conditional Facility Location Based Sampling (CFLS), respectively. FLS conducts one-time sample location selection, and CFLS extends the one-time sample location selection to a continuous process, so that an online advertising service can be started immediately without sampling a lot of locations. Our experimental results on two real datasets demonstrate the effectiveness and efficiency of the proposed methods. Specifically, both FLS and CFLS can achieve better performance than the existing sampling methods for the DAIM problem, and CFLS can initialize the online advertising service in a matter of seconds and achieve better objective distance than FLS after sampling a large number of sample locations.

Cataracts are a serious complication of diabetes. In long-term hyperglycemia, intracellular Ca2+ concentration ([Ca2+]i) and reactive oxygen species (ROS) are increased. The apoptosis of lens epithelial cells plays a key role in the development of cataract. We investigated a potential role for transient receptor potential vanilloid 2 (TRPV2) in the development of diabetic cataracts. Immunohistochemical and Western blotting analyses showed that TRPV2 expression levels were significantly increased in the lens epithelial cells of patients with diabetic cataracts as compared with senile cataract, as well as in both a human lens epithelial cell line (HLEpiC) and primary rat lens epithelial cells (RLEpiCs) cultured under high-glucose conditions. The [Ca2+]i increase evoked by a TRPV2 channel agonist was significantly enhanced in both HLEpiCs and RLEpiCs cultured in high-glucose media. This enhancement was blocked by the TRPV2 nonspecific inhibitor ruthenium red and by TRPV2-specific small interfering (si)RNA transfection. Culturing HLEpiCs or RLEpiCs for seven days in high glucose significantly increased apoptosis, which was inhibited by TRPV2-specific siRNA transfection. In addition, ROS inhibitor significantly suppressed the ROS-induced increase of TRPV2-mediated Ca2+ signal and apoptosis under high-glucose conditions. These findings suggest a mechanism underlying high-glucose–induced apoptosis of lens epithelial cells, and offer a potential target for developing new therapeutic options for diabetes-related cataracts.

Recently, a frequency diverse array (FDA) has been employed in an orthogonal frequency division multiplexing (OFDM) transmitter to achieve secure wireless communication without mathematical encryption. However, an insecure coupling effect arises if the frequency increments are linearly assigned to all antenna elements. To solve this problem, random subcarrier-selection methods are proposed; however, the challenge lies in the random selection of subcarriers. Inspired by the randomness of index modulation (IM), this paper proposes a low complexity random subcarrier-selection method based on index modulation (RSCS-IM). Specifically, this work conducted analysis on the spectral efficiency (SE) of our system and the computational complexity of RSCS-IM, which works out a closed-form expression of the BER performance of a desired position and validates the theoretical outcomes through simulation.

Summary: As one of the most promising candidates for next-generation mobile platform, augmented reality (AR) and virtual reality (VR) have potential to revolutionize the ways we perceive and interact with various digital information. In the meantime, recent advances in display and optical technologies, together with the rapidly developing digital processers, offer new development directions to advancing the near-eye display systems further. In this perspective paper, we start by analyzing the optical requirements in near-eye displays poised by the human visual system and then compare it against the specifications of state-of-the-art devices, which reasonably shows the main challenges in near-eye displays at the present stage. Afterward, potential solutions to address these challenges in both AR and VR displays are presented case by case, including the most recent optical research and development, which are already or have the potential to be industrialized for extended reality displays.

At about 20:40 on 23 July 2019, a high-level and long-runout landslide occurred in Jichang Town, Shuicheng County, Guizhou Province (hereafter called the Shuicheng landslide). This slope failure was highly devastating, and most of the local residents were severely affected, including 52 dead or missing. Based on the information provided by field investigations, drilling boreholes, and Google Earth, we describe the landform and stratigraphy characteristics of the Shuicheng landslide in this study. Additionally, the dataset of 1158 ancient landslides near the Shuicheng landslide is obtained by Google Earth and ArcGIS, including their morphological scales and spatial distribution characteristics, to analyze the landslide development preference in this region. Furthermore, the causes of the Shuicheng landslide are discussed by analyzing the effects of active tectonic activities on the broken basalt and the steep terrain, as well as the trigger action of continuous heavy rainfall. Finally, a previous empirical prediction formula of sliding distance is verified by the Shuicheng landslide parameters and is applied into the width range calculation of the ancient landslide risk zones, which is a kind of risk source for future landslides. The result indicates the area up to ≈3500 m away from the landslide risk source should be concerned during engineering construction in the study area. This study provides significant scientific guidance for the risk management of potential landslide hazards in this area.

Geothermal systems represent discrete and relatively homogenous habitats for extremophiles; investigation into the microbial community is key to revealing the geochemical environment and the geochemical evolution of fluids in geothermal reservoirs. The reservoir of the Lindian geothermal field in Northeast China, is highly reducing and rich in methane, but the pathways of methane generation and the related microbial community structure are still unclear. In this research, five thermal water samples were collected and tested, and the microbial community structure and diversity were analyzed. The results show that in the sandstone reservoir belonging to the low-temperature (reservoir temperature < 90°C) brackish water (total dissolved solids concentration between 1000 and 10,000 mg/L) environment, the richness of the microbial community is relatively high. The microbial community structure is different from other geothermal systems reported but similar to that of oilfields, which may be related to the highly reducing geochemical environment with abundant organic matter. According to the analysis of archaeal function, the biogas production in the Lindian geothermal field is dominated by hydrogen nutrition type methane production, while the H2 reducing methylamine type methane production is secondary, and results of Pearson correlation show that the archaeal communities are more strongly correlated to physicochemical factors than the bacterial communities.

Background: Oleanolic acid (OA) and its isomer ursolic acid (UA) have recently emerged as research foci based on their biologic activities. We previously demonstrated that UA can inhibit the activities of UGT1A3 and UGT1A4, and OA inhibits UGT1A3 activity in liver microsomes. However, whether OA and UA affect the expression of UGT1As in HepG2 cells and the underlying regulatory mechanism remain unclear.Purpose: The present study aimed to explore the effect of OA and UA on the expression of UGT1As in HepG2 cells and the regulatory mechanisms on UGT1A1 based on the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) signaling pathways.Methods: We analyzed the effect of OA and UA on UGT1A expression and on the PXR/CAR regulatory pathway in HepG2 cells, hPXR-silenced HepG2 cells, and hCAR-silenced HepG2 cells by Q-PCR, Western blotting, and dual-luciferase reporter gene assays.Results: In HepG2 cells, OA and UA both significantly induced the expression of UGT1A1, UGT1A3, UGT1A4, and UGT1A9 and upregulated the expression of PXR. However, OA and UA did not affect CAR expression. A dual-luciferase reporter assay showed that OA and UA could markedly promote PXR-mediated UGT1A1 luciferase activity, whereas OA and UA did not affect CAR-mediated UGT1A1 luciferase activity. In hPXR-silenced HepG2 cells, OA and UA did not elevate UGT1A1 activity compared to the control group. However, the expression of UGT1A1 in hCAR-silenced HepG2 cells was markedly elevated compared to the control group or with non-silenced HepG2 cells treated with OA (10, 20, and 40 μM) or UA (10, 20, and 40 μM).Conclusions: OA and UA significantly induce the expression of UGT1A1, UGT1A3, UGT1A4, and UGT1A9 in HepG2 cells, and their induction on UGT1A1 is mediated by PXR activation, not CAR.

We demonstrate a light efficient virtual reality (VR) near-eye display (NED) design based on a directional display panel and a diffractive deflection film (DDF). The DDF was essentially a high-efficiency Pancharatnam-Berry phase optical element made of liquid crystal polymer. The essence of this design is directing most of the display light into the eyebox. The proposed method is applicable for both catadioptric and dioptric VR lenses. A proof-of-concept experiment was conducted with off-the-shelf optical parts, where the light efficiency was enhanced by more than 2 times.

Color-converted micro-light-emitting diode (micro-LED) displays with wide color gamut, high ambient contrast ratio, and fast response time are emerging as a potentially disruptive technology. However, due to limited optical density and thickness of the color-conversion film, the blue light leakage and low color-conversion efficiency still hinder their widespread applications. In this paper, we demonstrate a patterned cholesteric liquid crystal (CLC) polymer film with two special optical functionalities. On the green and red sub-pixels, the corresponding planar CLC texture acts as a distributed Bragg reflector for the blue light, which in turn improves the color conversion efficiency and expands the color gamut. On the blue sub-pixels, the corresponding focal-conic CLC texture acts as light scattering medium, which helps to reduce the angular color shift. Further analysis reveals that the patterned CLC film can alleviate the crosstalk between green and blue color filters. Therefore, compared to the display system without such a CLC film, our proposed device structure increases the color conversion efficiency by 143% (at ~90% Rec. 2020) and reduces average angular color shift Δu’v’ from 0.03 to 0.018 at the viewing angle with the most severe color shift. Such a patterned CLC film is applicable to all kinds of color-conversion display systems, including organic and inorganic phosphors.

Background: Glycine oxidase (GO), a type of d-amino acid oxidase, is of biotechnological interest for its potential in several fields. In our previous study, we have characterized a new glycine oxidase (BceGO) from Bacillus cereus HYC-7. Here, a variant of N336K with increased the affinity against all the tested substrate was obtained by screening a random mutant library of BceGO. It is observed that the residue N336 is invariable between its homogeneous enzymes. This work was aimed to explore the role of the residue N336 in glycine oxidase by site-directed mutagenesis, kinetic assay, structure modeling and substrate docking. Results: The results showed that the affinity of N336H, N336K and N336R increased gradually toward all the substrates, with increase in positive charge on side chain, while N336A and N336G have not shown a little significant effect on substrate affinity. The structure modeling studies indicated that the residue Asn336 is located in a random coil between β-18 and α-10. Also, far-UV CD spectra-analysis showed that the mutations at Asn336 do not affect the secondary structure of enzyme. Conclusion: Asn336 site was located in a conserved GHYRNG loop which adjoining to substrate and the isoalloxazine ring of FAD, and involved in the substrate affinity of glycine oxidase. This might provide new insight into the structure–function relationship of GO, and valuable clue to redesign its substrate specificity for some biotechnological application.

Liquid crystal-based reflective polarization volume grating (PVG), also known as a linear Bragg–Berry phase optical element or a member of volume Bragg gratings (VBGs), is a functional planar structure with patterned orientation of optical axis. Due to the strong polarization selectivity, nearly 100% diffraction efficiency, large diffraction angle, and simple fabrication process, PVGs have found potential applications in novel photonic devices and emerging near-eye displays. In this review paper, we describe the operation principles, discuss the optical properties, present the fabrication methods, and provide promising applications of PVGs for near-eye displays and novel photonic devices.

Continuous, wide field-of-view, high-efficiency, and fast-response beam steering devices are desirable in a plethora of applications. Liquid crystals (LCs)—soft, bi-refringent, and self-assembled materials which respond to various external stimuli—are especially promising for fulfilling these demands. In this paper, we review recent advances in LC beam steering devices. We first describe the general operation principles of LC beam steering techniques. Next, we delve into different kinds of beam steering devices, compare their pros and cons, and propose a new LC-cladding waveguide beam steerer using resistive electrodes and present our simulation results. Finally, two future development challenges are addressed: Fast response time for mid-wave infrared (MWIR) beam steering, and device hybridization for large-angle, high-efficiency, and continuous beam steering. To achieve fast response times for MWIR beam steering using a transmission-type optical phased array, we develop a low-loss polymer-network liquid crystal and characterize its electro-optical properties.

Glyphosate, a broad spectrum herbicide widely used in agriculture all over the world, inhibits 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, and glycine oxidase (GO) has been reported to be able to catalyze the oxidative deamination of various amines and cleave the C-N bond in glyphosate (Pedotti et al., 2009). Here, in an effort to improve the catalytic activity of the glycine oxidase that was cloned from a glyphosate-degrading marine strain of Bacillus cereus (BceGO), we used a bacteriophage T7 lysis-based method for high-throughput screening of oxidase activity and engineered the gene encoding BceGO by directed evolution.

Glyphosate, a broad spectrum herbicide widely used in agriculture all over the world, inhibits 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, and glycine oxidase (GO) has been reported to be able to catalyze the oxidative deamination of various amines and cleave the C-N bond in glyphosate. Here, in an effort to improve the catalytic activity of the glycine oxidase that was cloned from a glyphosate-degrading marine strain of Bacillus cereus (BceGO), we used a bacteriophage T7 lysis-based method for high-throughput screening of oxidase activity and engineered the gene encoding BceGO by directed evolution. Six mutants exhibiting enhanced activity toward glyphosate were screened from two rounds of error-prone PCR combined with site directed mutagenesis, and the beneficial mutations of the six evolved variants were recombined by DNA shuffling. Four recombinants were generated and, when compared with the wild-type BceGO, the most active mutant B3S1 showed the highest activity, exhibiting a 160-fold increase in substrate affinity, a 326-fold enhancement in catalytic efficiency against glyphosate, with little difference between their pH and temperature stabilities. The role of these mutations was explored through structure modeling and molecular docking, revealing that the Arg(51) mutation is near the active site and could be an important residue contributing to the stabilization of glyphosate binding, while the role of the remaining mutations is unclear. These results provide insight into the application of directed evolution in optimizing glycine oxidase function and have laid a foundation for the development of glyphosate-tolerant crops.

In 2000, Biehl et al. proposed a fault-based attack on elliptic curve cryptography. In this paper, we refined the fault attack method. An elliptic curve E is defined over prime field 𝔽p with base point P∈E(𝔽p). Applying the fault attack on these curves, the discrete logarithm on the curve can be computed in subexponential time of Lp(1/2,1+o(1)). The runtime bound relies on heuristics conjecture about smooth numbers similar to the ones used by Lenstra, 1987.