Search

Abstract Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). However, the blood physiological indicators for this eye disease are less reported. Here, we systemically investigated healthy controls, DR patients and DM patients from 2014 to 2022 in Sichuan Provincial People’s Hospital (Chengdu, China). We found the leukocyte count, urea, and direct bilirubin in the DR patients were significantly increased (P

Based on the geochemical parameters and analytical data, the heat conservation equation, mass balance law, Rayleigh fractionation model and other methods were used to quantify the in-situ yield and external flux of crust-derived helium, and the initial He concentration and thermal driving mechanism of mantle-derived helium, in the Ledong Diapir area, the Yinggehai Basin, in order to understand the genetic source, migration and accumulation mechanisms of helium under deep thermal fluid activities. The average content of mantle-derived He is only 0.001 4%, the 3He/4He value is (0.002–2.190)×10−6, and the R/Ra value ranges from 0.01 to 1.52, indicating the contribution of mantle-derived He is 0.09%–19.84%, while the proportion of crust-derived helium can reach over 80%. Quantitative analysis indicates that the crust-derived helium is dominated by external input, followed by in-situ production, in the Ledong diapir area. The crust- derived helium exhibits an in-situ 4He yield rate of (7.66– 7.95)×10−13 cm3/(a·g), an in-situ 4He yield of (4.10–4.25)× 10−4 cm3/g, and an external 4He influx of (5.84–9.06)×10−2 cm3/g. These results may be related to atmospheric recharge into formation fluid and deep rock-water interactions. The ratio of initial mole volume of 3He to enthalpy (W) is (0.004–0.018) ×10−11 cm3/J, and the heat contribution from the deep mantle (XM) accounts for 7.63%–36.18%, indicating that deep hot fluid activities drive the migration of mantle-derived 3He. The primary helium migration depends on advection, while the secondary migration is controlled by hydrothermal degassing and gas-liquid separation. From deep to shallow layers, the CO2/3He value rises from 1.34×109 to 486×109, indicating large amount of CO2 has escaped. Under the influence of deep thermal fluid, helium migration and accumulation mechanisms include: deep heat driven diffusion, advection release, vertical hydrothermal degassing, shallow lateral migration, accumulation in traps far from faults, partial pressure balance and sealing capability.

Marine shales from the Niutitang Formation and marine–continental transitional shales from the Longtan Formation are two sets of extremely important hydrocarbon source rocks in South China. In order to quantitatively compare the pore complexity characteristics between marine and marine–continental transitional shales, the shale and kerogen of the Niutitang Formation and the Longtan Formation are taken as our research subjects. Based on organic petrology, geochemistry, and low-temperature gas adsorption analyses, the fractal dimension of their pores is calculated by the Frenkel–Halsey–Hill (FHH) and Sierpinski models, and the influences of total organic carbon (TOC), vitrinite reflectance (Ro), and mineral composition on the pore fractals of the shale and kerogen are discussed. Our results show the following: (1) Marine shale predominantly has wedge-shaped and slit pores, while marine–continental transitional shale has inkpot-shaped and slit pores. (2) Cylindrical pores are common in organic matter of both shale types, with marine shale having a greater gas storage space (CRV) from organic matter pores, while marine–continental transitional shale relies more on inorganic pores, especially interlayer clay mineral pores, for gas storage due to their large specific surface area and high adsorption capacity (CRA). (3) The fractal characteristics of marine and marine–continental transitional shale pores are influenced differently. In marine shale, TOC positively correlates with fractal dimensions, while in marine–continental shale, Ro and clay minerals have a stronger influence. Ro is the primary factor affecting organic matter pore complexity. (4) Our two pore fractal models show that the complexity of the shale in the Longtan Formation surpasses that of the shale in the Niutitang Formation, and type I kerogen has more complex organic matter pores than type III, aiding in evaluating pore connectivity and flow effectiveness in shale reservoirs.

Background: TP53 is frequently mutated in solid tumors, but its basic mutation mapping is mixed, particularly in aggressive-stage lung cancer. Experimental Design: We curated a total of 139 advanced non-small cell lung cancer (NSCLC) patients who harbored wild-type TP53 (TP53wt) or mutated TP53 (TP53mut) based on next-generation sequencing (NGS) to analyze multiple-dimensional data types, including tumor mutation burden (TMB), programmed death receptor ligand 1 (PD-L1) expression, co-mutant alterations, hotspot mutations distribution, and therapy response. Results: TP53 was evident in 125 mutations and significantly associated with male sex, adenocarcinoma differentiation, smoking history, PD-L1 tumor proportion score, and TMB level. The most frequent mutations were distributed on exon 8, but there were no distinct hotspot mutations. After outlining the co-mutation genes, it is interesting to note that DNA damage repair (DDR) genes were frequent alterations in the mutated TP53 cohort. Even though there was no significant difference between the TP53wt and TP53mut cohorts on therapy response, patients with nucleotide variation in G>T achieved a relatively higher durable clinical benefit (DCB) rate. Conclusions: This real-world retrospective study suggests that molecular stratification on the basis of TP53 mutations should be deeply explored for NSCLC to optimize and modify clinical therapy choices.

BackgroundThe pathophysiological processes linked to an acute ischemic stroke (IS) can be reflected in the circulating metabolome. Amino acids (AAs) have been demonstrated to be one of the most significant metabolites that can undergo significant alteration after a stroke.MethodsWe sought to identify the potential biomarkers for the early detection of IS using an extensive targeted technique for reliable quantification of 27 different AAs based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A cohort with 216 participants was enrolled, including 70 mild to moderate ischemic stroke patients (National Institutes of Health Stroke Scale < 15, MB group), 76 stroke mimics (MM group) and 70 healthy controls (NC group).ResultsIt was found that upon comparing MB and MM to control patients, AAs shifts were detected via partial least squares discrimination analysis (PLS-DA) and pathway analysis. Interestingly, MB and MM exhibited similar AAs pattern. Moreover, ornithine, asparagine, valine, citrulline, and cysteine were identified for inclusion in a biomarker panel for early-stage stroke detection based upon an AUC of 0.968 (95% CI 0.924–0.998). Levels of ornithine were positively associated with infract volume, 3 months mRS score, and National Institutes of Health Stroke Scale (NIHSS) score in MB. In addition, a metabolites biomarker panel, including ornithine, taurine, phenylalanine, citrulline, cysteine, yielded an AUC of 0.99 (95% CI 0.966–1) which can be employed to effectively discriminate MM patients from control.ConclusionOverall, alternations in serum AAs are characteristic metabolic features of MB and MM. AAs could serve as promising biomarkers for the early diagnosis of MB patients since mild to moderate IS patients were enrolled in the study. The metabolism of AAs can be considered as a key indicator for both the prevention and treatment of IS.

Fog computing has been applied to the data processing for the Internet of Things (IoT) based on distributed high-precision Global Navigation Satellite Systems (GNSS). However, the space-time adaptive processing (STAP) interference suppression technology in the system will cause fog computing data deviation that includes carrier phase bias and pseudocode offset. An unbiased STAP technique is proposed to eliminate these deviations. First, it is analyzed that the carrier phase bias and pseudocode offset are caused by the non-linear phase response of the STAP equivalent filter. Then, a coefficient-constrained method based on practical engineering processing is proposed, which can eliminate these deviations by restricting the tap coefficients to be symmetrically equal around the center-tap. Moreover, by analyzing the coherent integral function of the pseudocode after filtering, the tap structure of STAP is modified to eliminate the group offset of the pseudocode without increasing the computational complexity and hardware resources. Finally, the unbiased performance and anti-interference performance of the system are verified by numerical and real data simulations.

Single sodium-ion solid electrolyte that meets the requirements of practical applications is difficult to design. Here, the authors show how kinetic stability via the creation of a self-passivating solid electrolyte interphase allows a homogenous glass solid electrolyte to exhibit remarkable electrochemical stability with sodium metal.

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

Telocytes (TCs), a novel type of interstitial cells, have been found to participate in tissue protection and repair. In this study, we investigated the antioxidative effects of TCs in inflamed lungs of mice. Acute respiratory distress syndrome (ARDS) mice were used as models of inflamed lungs of mice. Gene sequencing was used to screen the differentially expressed miRNAs in TCs after lipopolysaccharide (LPS) stimulation. AntagomiR-146a-5p-pretreated TCs were first injected into mice, and antioxidant activity of TCs was estimated. TCs, RAW264.7 cells, and MLE-12 cells were collected for the detection of expressions of NOX1–4, DUOX1–2, SOD1–3, GPX1–2, CAT, Nrf2, miR-146a-5p, and miR-21a-3p after LPS stimulation. Silencing miRNAs were delivered to examine the involved signaling pathways. Oxidative stress was examined by measuring malondialdehyde (MDA) levels. We found that microRNA-146a-5p and microRNA-21a-3p were upregulated in TCs after LPS stimulation. ARDS mice that were preinfused with TCs had lower lung tissue injury scores, lung wet-dry ratios, white blood cell counts in alveolar lavage fluid and lower MDA concentrations in lung tissue. However, in antagomiR-146a-5p-pretreated ARDS mice, the infusion of TCs caused no corresponding changes. After LPS stimulation, DUOX2 and MDA concentrations were downregulated in TCs, while DUOX2 was restored by antagomiR-146a-5p in TCs. Dual-luciferase reporter assay confirmed that CREB1 was downregulated by miR-146a-5p, while DUOX2 was downregulated by CREB1, which was confirmed by treating TCs with a specific CREB1 inhibitor. This study demonstrates that LPS stimulation upregulates miR-146a-5p in TCs, which downregulates the CREB1/DUOX2 pathway, resulting in a decrease in oxidative stress in cultured TCs. TCs reduce LPS-induced oxidative stress by decreasing DUOX2 in inflamed lungs of mice.

Calcite cement is a common diagenetic mineral in carbonate rocks and plays an important role on rock quality as hydrocarbon reservoirs. Traditionally, oxygen isotopic compositions (δ18O) of the diagenetic calcites tend to decrease with increasing depths due to temperature-dependent isotope fractionation. In this study, the stable isotope compositions of the calcite cements in the Changxing and Feixianguan formations from the Puguang, Yuanba, Jiannan and Fuling carbonate fields in the Sichuan Basin were analyzed. The results show that some calcite cements have δ18O values similar to those of their host carbonates, despite the fact that these calcites formed at elevated temperatures (>∼100°C). Based on petrographic and geochemical analyses, the 18O-enriched calcites commonly occur with solid bitumens and have lower δ13C values compared with host rocks, suggesting thermochemical sulfate reduction (TSR) provided organic carbon for these calcite precipitation. During TSR, thermal oxidation of hydrocarbons generated the light carbon, and simultaneously the reduced sulfate ions provided the oxygen. Comparison of our study with the TSR calcites worldwide, a model for oxygen isotope behavior during TSR was established. Oxygen isotope compositions of TSR-related calcites are a function of isotope compositions and amounts of the initial anhydrite and pore waters. TSR shows two opposing effects on the δ18O values of calcites, depending on the δ18O ratios of the initial anhydrite. The reduction of anhydrite with relatively low δ18O values causes the calcite δ18O lower than theoretical values of calcites directly precipitated from pore waters. The heavy δ18O ratios of calcites formed during TSR are not only attributed to the 18O-enriched pore water resulting from extensive water-rock interaction, but also probably due to the involvement of anhydrite with high δ18O values.

Background: Preliminary investigation revealed that Low-density lipoprotein receptor-related protein 1b (LRP1B) and FAT atypical cadherin (FAT) family mutation might serve as immune regulators under certain tumor microenvironment. Experimental design: We curated a total of 70 non-small cell lung cancer (NSCLC) patients who harbored alterations in LRP1B and/or FAT family (FAT1/2/3/4) based on next-generation sequencing (NGS) to analyze multiple-dimensional data types, including comutant status, tumor mutation burden (TMB), programmed death receptor ligand 1 (PD-L1) expression, T cell-inflamed gene expression profiling (GEP) and therapy response. Results: 20 patients with co-occurring mutations in LRP1B and FAT1/2/3/4 revealed a relatively higher TMB level of 17.05 mut/Mb compared with 7.60 mut/Mb and 8.80 mut/Mb in single LRP1B and FAT mutation groups, respectively. LRP1B and FAT members showed specifically enriched T cell-inflamed genes and the co-occurring mutant TP53 status in NSCLC patients who harbor LRP1B/FAT comutations. Conclusions: This work provides evidence that co-occurring mutations of LRP1B and FAT in NSCLC may serve as a group of potential predictive factors in guiding immunotherapy on the basis of their association with TMB status.

This article discusses how a new APRS service-learning model was implemented in a new service-learning project in the traditional Chinese medicine (TCM) orthopedics curriculums at three Hong Kong institutions. The APRS model adopting flipped learning approach consists of four cyclic stages, including Application, Practice, Reflection and Self-regulated learning. Qualitative and quantitative findings in this study reveal that TCM students gained confidence in applying discipline knowledge/skills and improved in various areas, including cross-cultural competence, communication, problem-solving and collaboration. Drawing evidence from this study, possible factors contributing to positive impacts on student learning in the APRS model are the "strong connectivity" (including clear alignment with programme, profession, institutional missions and traditional Chinese philosophy "xiushen"), "reinforced motivation" (student autonomy and buy in) and "structured organisation" (strong network among participating parties and use of a centralised electronic platform). The APRS service-learning model is a culture-based approach helping students reconnect Confucian "xiushen" to the discipline knowledge and the real-life application in the Hong Kong context. This model may also be applicable to other Asian contexts where the Confucian culture prevails.

Metal–organic frameworks (MOFs) have been utilized with increasing interest in various fields, including gas storage and separation, catalysis, sensing, adsorption, and biomedicine. Recently, the scale‐up production and commercialization of MOFs have paved their way to real‐world applications. However, the accidental and intentional exposures of MOFs to humans and organisms make an increasing concern on their health risks and sustainable development. Thus, toxicity assessment is essential for the application of MOFs. In vitro toxic evaluation based on cell culture is low cost, fast, and high throughput, making it an ideal model in toxicity research. To understand the cytotoxicity of MOFs, a short review on the effect of key physicochemical factors on cytotoxicity is necessary. Herein, the application of MOFs is summarized and the possible exposure routes of MOFs to humans are discussed. Moreover, the key physicochemical factors affecting the cytotoxicity of MOFs such as chemical composition, size, and shape are also elucidated. It is expected that this short review helps to understand the cytotoxicity of MOFs and sheds light on the importance of the toxicity assessment of MOFs.

In this report we detail a comprehensive study on the moisture stability of sulfide solid-state electrolytes in dry room environments. Although sulfide SSEs have many favorable attributes, this class of materials suffers from poor stability with water. Sulfide SSEs react with water to form gaseous H2S and a variety of solid byproducts like Li3PO4 and LiOH, which go on to increase the interfacial impedance of solid-state batteries. Lab-scale research typically utilizes gloveboxes with

Isothermal tensile tests have been performed to study the mechanical evolution of Ti-6Al-2Zr-1Mo-1V titanium alloy under a wide temperature range from −60 ℃ to 900 ℃ and a strain rate of 10−3 s-1. Electron backscatter diffraction (EBSD) tests were used to analyze the evolution of microstructure and deformation mechanisms under different temperatures. The results indicate that deformation mechanisms vary with the deformation conditions. At relatively low temperatures, −60 ℃, 23 ℃, and 400 ℃, dislocation slips mechanism dominates the deformation, even though tensile twinning is detected. While globularization of α laths and dynamic recrystallization (DRX) are dominant at high temperatures, 600 ℃ and 800 ℃, resulting in the flow softening. During the deformation under different temperatures, the β phase plays a crucial role in accommodating deformation between α and β phase by migration of grain boundaries and rotation of grain, leading to a dramatically change in texture of β phase.

The multiple peaks characteristic of binary offset carrier (BOC) autocorrelation function (ACF) makes ambiguity easy to be generated. There are some methods to eliminate ambiguity, but for higher-order BOC Signal, it will sacrifice signal energy or cannot maintain narrow correlation. This paper studies these problems. According to the idea of GRASS algorithm shape code, this paper proposes an unambiguous tracking algorithm, Sub Cross-correlation Shift Technique (SCST), which is suitable for BOC(m,n) signals. The key to this algorithm is to generate a new cross-correlation function between the BOC signal and the PRN code based on the shape code. The new cross-correlation function is linearly combined with the autocorrelation function of the BOC signal to remove sub-peak interference and achieve high-accuracy tracking. The phase discrimination function is given, and the effectiveness of the tracking algorithm is analyzed theoretically. The disadvantage of this method is that it needs multilevel storage, which will bring extra resource consumption to the receiver. For comparison, Unit Correlation, ASPeCT, GRASS, and the algorithm proposed by Yan are proposed. Experiments show that SCST can completely remove the side peak, and the phase discriminator output has only two main peaks, which successfully eliminates the false lock point. The multipath error envelope has only one and the smallest area. In terms of code tracking accuracy, for a BOC(10,5) signal with a received signal-to-noise ratio (SNR) of -28 dB, SCST is less than 45.8%, 67.5%, and 12.2% of the Unit Correlation, GRASS, and Yan proposed algorithms.

In the present work, the adiabatic shear characteristics of our recently designed α + β dual-phase Ti alloy at different strain rates have been investigated by hat shaped specimen. The deformation process is divided into three stages: work hardening stage, steady stage, and unstable thermal softening stage. Along or near the shear deformation paths, the microvoids and the cracks can be captured at the strain rate of 1.8 × 104 s−1, 2.0 × 104 s−1, and 2.3 × 104 s−1, both of which contribute to the stable and unstable softening. It is found that dynamic stored energy of cold work will be significantly improved by the enhanced high strain rate. In the view of coupling analysis of inverse pole figure and grain boundary map, it seems that low angle grain boundaries present a good resistance to the formation of cracks and thermal softening. On the contrary, high angles grain boundaries are typically located in ASBs and their affecting regions, which is in line with the reported results. While the geometrical necessary dislocation (GND) density of adiabatic shear band (ASB) and its surroundings increased significantly, the width of the ASB becomes wider as the strain rate increases, which is consistent with the theory of sub-grain rotation dynamic recrystallization model. The formation of multiple ASBs in the corner position is schematically illustrated and the average elastic modulus and hardness of the ASB region are lower than the α and β phases, combined with the GND analysis, which proves that the ASB is a thermal softening zone in this experiment.

Membranous nephropathy is one of the most prevalent conditions responsible for nephrotic syndrome in adults. It is clinically nonspecific and mainly diagnosed by kidney biopsy pathology, with three prevalent techniques: light microscopy, electron microscopy, and immunofluorescence microscopy. Manual observation of glomeruli one by one under the microscope is very time-consuming, and there are certain differences in the observation results between physicians. This study makes use of whole-slide images scanned by a light microscope as well as immunofluorescence images to classify patients with membranous nephropathy. The framework mainly includes a glomerular segmentation module, a confidence coefficient extraction module, and a multi-modal fusion module. This framework first identifies and segments the glomerulus from whole-slide images and immunofluorescence images, and then a glomerular classifier is trained to extract the features of each glomerulus. The results are then combined to produce the final diagnosis. The results of the experiments show that the F1-score of image classification results obtained by combining two kinds of features, which can reach 97.32%, is higher than those obtained by using only light-microscopy-observed images or immunofluorescent images, which reach 92.76% and 93.20%, respectively. Experiments demonstrate that considering both WSIs and immunofluorescence images is effective in improving the diagnosis of membranous nephropathy.

Protein tyrosine phosphatases (PTPs) are modulators of cellular functions such as differentiation, metabolism, migration, and survival. PTPs antagonize tyrosine kinases by removing phosphate moieties from molecular signaling residues, thus inhibiting signal transduction. Two PTPs, SHP-1 and SHP-2 (SH2 domain-containing phosphatases 1 and 2, respectively) and another inhibitory phosphatase, SH2 domain-containing inositol phosphatase (SHIP), are essential for cell function, which is reflected in the defective phenotype of mutant mice. Interestingly, SHP-1, SHP-2, and SHIP mutations are identified in many cases of human leukemia. However, the impact of these phosphatases and their mutations regarding the onset and progression of leukemia is controversial. The ambiguity of the role of these phosphatases imposes challenges on the development of targeting therapies for leukemia. This fundamental problem, confronted by the expanding investigational field of leukemia, will be addressed in this review, which will include a discussion of the molecular mechanisms of SHP-1, SHP-2, and SHIP in normal hematopoiesis and their role in leukemia. Clinical development of leukemic therapies achieved by targeting these phosphatases will be addressed as well.

A facile procedure for preparing copper and nitrogen co-doped active carbon (Cu-N/OAC) by one-step complexed was reported and applied in liquid-phase hydrogenation of furfural (FAL). The facile procedure resulted in high Cu nanoparticles dispersion on OAC with Cu0 and Cu+ sites and apparently promoted the catalytic activities during furfural hydrogenation reaction. The obtained Cu-N/OAC-800 shows 99.5% FAL conversion with 98.4% selectivity to furfuryl alcohols (FOL) under reaction condition of 150 °C, 2 MPa and 6 h. These results indicated that the excellent catalytic performance of the catalyst was due to the synergic effects of nitrogen doping and Cu metal active sites.

Natural gas generation is the result of organic matter degradation under the effects of biodegradation and thermal degradation. Early Cambrian black shales in the Upper Yangtze Region are rich in organic matter and have shown great shale gas potentiality in recent years. Nevertheless, the enrichment mechanism and distribution of organic matter in these black shales between different sedimentary settings, such as intra-platform basin, slope, and deep basin, are still poorly understood. In this paper, based mainly on elemental geochemistry, a comprehensive study of the marine redox conditions, primary productivity, sedimentation rate, terrigenous input, hydrothermal activity, and water mass restrictions was conducted on the Early Cambrian Niutitang black shale in the Upper Yangtze Region. Our data showed that an intra-platform basin received a higher terrigenous input and that it deposited under more restricted conditions than the slope and deep basin settings. The primary productivity in the slope and deep basin settings was higher than that in the intra-platform basin setting. In the intra-platform basin, the productivity increased from its inner part to its margin. For the slope and deep basin settings, the high paleoproductivity generated large amounts of organic matter and its preservation was synergistically affected by the redox conditions. In contrast to the slope and deep basin, the preservation of organic matter in the inner part of the intra-platform basin was mainly controlled by redox conditions because the paleoproductivity in it was much lower than in the slope and deep basin settings. The intra-platform basin margin was the most favorable area for accumulating organic matter.

Aiming at the problem that a no-reference (NR) image quality assessment algorithm is not accurate enough to predict the image quality at present, we proposed a method of NR image quality assessment based on spatial domain coding (SDC). We extracted the spatial structure features of the image on different bit planes. The extracted features quantify the structural information between pixels, which can more accurately reflect the distortion degree of the image. We used a neural network to establish an image quality assessment model. The experimental results show that the proposed image assessment algorithm is more accurate than the existing mainstream image quality assessment algorithms and highly consistent with subjective perception of human eyes. Finally, the proposed algorithm is applied to the auto focus of the camera verifying the practicability and accuracy of the algorithm.

This study uses the powerful nonparametric cointegration test to examine whether nonlinear cointegration exists between prices of used houses and corresponding stock markets in China and the four Asian Tigers. Then, it uses the smooth transition vector error-correction model (STVECM) to explore the adjustment efficiencies of the short-run house and corresponding stockreturn dynamics when there is disequilibrium between house and stock prices. The empirical results indicate that there is a nonlinear cointegration between the house prices and corresponding stock prices in China, South Korea, Singapore, and Taiwan, and that the speed of price adjustment to equilibrium is always greater for houses than stocks when there are large positive and negative deviations. Moreover, the short-run speed of adjustment of the large negative and positive deviations is equal in China, South Korea, and Taiwan, but unequal in Singapore. With the exception of South Korea, the results of the Granger causality test indicate that stock prices clearly lead used house prices, which means a wealth effect exists in most Asian countries. Our study confirms that the STVECM can be used to analyze the short-run adjustment efficiency of house and stock return dynamics in China, South Korea, Singapore, and Taiwan; thus, supporting models of interaction between noise and arbitrage traders.

Acute myeloid leukemia (AML) is a heterogeneous disease associated with various alterations in T cell phenotype and function leading to an abnormal cell population, ultimately leading to immune exhaustion. However, restoration of T cell function allows for the execution of cytotoxic mechanisms against leukemic cells in AML patients. Therefore, long-term disease control, which requires multiple therapeutic approaches, includes those aimed at the re-establishment of cytotoxic T cell activity. AML treatments that harness the power of T lymphocytes against tumor cells have rapidly evolved over the last 3 to 5 years through various stages of preclinical and clinical development. These include tissue-infiltrated lymphocytes (TILs), bispecific antibodies, immune checkpoint inhibitors (ICIs), chimeric antigen receptor T (CAR-T) cell therapy, and tumor-specific T cell receptor gene-transduced T (TCR-T) cells. In this review, these T cell-based immunotherapies and the potential of TILs as a novel antileukemic therapy will be discussed.

Abstract Pattern formation and self-organization are fascinating phenomena found widely in nature and in laboratory environment such as dielectric barrier discharge (DBD). Significant efforts have been made to explain the dynamic pattern formation. In DBD, the formation of side discharges is generally supposed to be a key factor responsible for diversity and spatial-temporal symmetry breaking of pattern formation. However, it is still not clear how such discharges are induced. Here, we present the observations of side discharges in a filamentary dielectric barrier discharge from both numerical simulations and experiments. Two-dimensional particle-in-cell simulations with Monte Carlo collisions included have revealed formation dynamics of side discharges, suggesting that transverse plasma diffusion and ion induced secondary electron emission play critical roles. Moreover, a novel honeycomb superlattice pattern is observed in experiment, where the side discharges associated with honeycomb superlattice are verified by utilizing a high speed camera. Experimental observations and numerical simulation are in good agreement.

This paper examines whether UK fund managers engage in herding behaviour in the stock market using the dynamic herding measure, whether their herding behaviour is different during bullish and bearish periods, whether most of their herding is informational, which types of informational reasons act as the main drivers of their herding and whether there are non-informational drivers of their herding. Our results reveal that UK fund managers engage in significant herding behaviour and that this behaviour does not differ significantly from bullish to bearish stock markets. Moreover, we confirm that there are weak positive correlations between fund managers’ herding and stock returns within the subsequent year, which indicates that their herding is mainly informational. To improve portfolio performance, other investors could follow UK fund managers and purchase stocks overbought by them with at least 15 traders quarterly in the following one-year period, particularly for growth-type, sectorspecific and international-type funds. Moreover, because they are more likely to herd in large-capitalisation securities, the informational reasons driving managers’ herding behaviour are mainly related to investigative herding. We also find that growth-type and international-type funds are more likely to herd with similar- type funds. This finding may result from reputational and characteristic herding, which illustrates that non-informational reasons for managers’ herding still exist.

Nonsyndromic orofacial cleft (NSOFC) is a severe birth defect that occurs early in embryonic development and includes the subtypes cleft palate only (CPO), cleft lip only (CLO) and cleft lip with cleft palate (CLP). Given a lack of specific genetic factor analysis for CPO and CLO, the present study aimed to dissect the landscape of genetic factors underlying the pathogenesis of these two subtypes using 6,986 cases and 10,165 controls. By combining a genome-wide association study (GWAS) for specific subtypes of CPO and CLO, as well as functional gene network and ontology pathway analysis, we identified 18 genes/loci that surpassed genome-wide significance (P < 5 × 10-8) responsible for NSOFC, including nine for CPO, seven for CLO, two for both conditions and four that contribute to the CLP subtype. Among these 18 genes/loci, 14 are novel and identified in this study and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. Interestingly, we observed an opposite effect of the genetic variants in the IRF6 gene for CPO and CLO. Moreover, the gene expression dosage effect of IRF6 with two different alleles at the same single-nucleotide polymorphism (SNP) plays important roles in driving CPO or CLO. In addition, PAX9 is a key TF for CPO. Our findings define subtypes of NSOFC using genetic factors and their functional ontologies and provide a clue to improve their diagnosis and treatment in the future.

We examined the impact of statins on Yes-associated Protein (YAP) localization, phosphorylation and transcriptional activity in human and mouse pancreatic ductal adenocarcinoma (PDAC) cells. Exposure of sparse cultures of PANC-1 and MiaPaCa-2 cells to cerivastatin or simvastatin induced a striking re-localization of YAP from the nucleus to the cytoplasm and inhibited the expression of the YAP/TEAD-regulated genes Connective Tissue Growth Factor (CTGF) and Cysteine-rich angiogenic inducer 61 (CYR61). Statins also prevented YAP nuclear import and expression of CTGF and CYR61 stimulated by the mitogenic combination of insulin and neurotensin in dense culture of these PDAC cells. Cerivastatin, simvastatin, atorvastatin and fluvastatin also inhibited colony formation by PANC-1 and MiaPaCa-2 cells in a dose-dependent manner. In contrast, the hydrophilic statin pravastatin did not exert any inhibitory effect even at a high concentration (10 μM). Mechanistically, cerivastatin did not alter the phosphorylation of YAP at Ser127 in either PANC-1 or MiaPaCa-2 cells incubated without or with neurotensin and insulin but blunted the assembly of actin stress fiber in these cells. We extended these findings with human PDAC cells using primary KC and KPC cells, (expressing KrasG12D or both KrasG12D and mutant p53, respectively) isolated from KC or KPC mice. Using cultures of these murine cells, we show that lipophilic statins induced striking YAP translocation from the nucleus to the cytoplasm, inhibited the expression of Ctgf, Cyr61 and Birc5 and profoundly inhibited colony formation of these cells. Administration of simvastatin to KC mice subjected to diet-induced obesity prevented early pancreatic acini depletion and PanIN formation. Collectively, our results show that lipophilic statins restrain YAP activity and proliferation in pancreatic cancer cell models in vitro and attenuates early lesions leading to PDAC in vivo.

Thermal sulfate reduction (TSR) occurred throughout the Permian Changxing (P2c) and Triassic Feixianguan (T1f) dolostone reservoirs in the western and eastern parts of the Kaijiang-Liangping (K-L) trough in the northeastern part of the Sichuan Basin. To determine the sulfate sources of this TSR, fourteen solid bitumen samples and eight anhydrite samples were collected from the northeastern part of the Sichuan Basin. These samples were analyzed to determine their sulfur isotopes. In addition, untreated, HNO3-treated, and CrCl2-treated solid bitumen samples were analyzed to determine their sulfur isotopes in order to obtain reliable δ34S data for the TSR solid bitumen. The results show that the HNO3 method is more effective at removing pyrite from solid bitumen than the method using CrCl2 thrice because the HNO3-treated solid bitumen has lower sulfur contents and higher δ34S. The δ34S of the T1f solid bitumen samples from the Puguang gas field (in the eastern part of the K-L trough, 12.0-24.0‰) is significantly lower than that of the samples from the Yuanba gas field (in the western part of the K-L trough, 24.1-34.2‰). The δ34S of the T1f1–2 anhydrite is 18.1-26.6‰, which is lower than that of the T1f3–4 anhydrite samples (29.9-39.6‰). The TSR sulfates from the Puguang gas field were most likely from the coeval T1f1–2 evaporating seawater and were enriched during the reflux-seepage dolomitization process. The TSR sulfates from the Yuanba gas field were primarily caused by the evaporation of seawater during the T1f4. First, the evaporating seawater would flow vertically into the P2c reservoirs in the adjacent area, and then, it would flow laterally into the P2c reservoirs in the Yuanba gas field. Considering the fact that the sulfate sources of TSR and the δ34S values of the TSR sulfates are different in the Puguang and Yuanba gas fields, the δ34S of TSR solid bitumen cannot be simply used to show the extent of TSR.

Abstract Background Recommender systems have shown tremendous value for the prediction of personalized item recommendations for individuals in a variety of settings (e.g., marketing, e-commerce, etc.). User-based collaborative filtering is a popular recommender system, which leverages an individuals’ prior satisfaction with items, as well as the satisfaction of individuals that are “similar”. Recently, there have been applications of collaborative filtering based recommender systems for clinical risk prediction. In these applications, individuals represent patients, and items represent clinical data, which includes an outcome. Methods Application of recommender systems to a problem of this type requires the recasting a supervised learning problem as unsupervised. The rationale is that patients with similar clinical features carry a similar disease risk. As the “Big Data” era progresses, it is likely that approaches of this type will be reached for as biomedical data continues to grow in both size and complexity (e.g., electronic health records). In the present study, we set out to understand and assess the performance of recommender systems in a controlled yet realistic setting. User-based collaborative filtering recommender systems are compared to logistic regression and random forests with different types of imputation and varying amounts of missingness on four different publicly available medical data sets: National Health and Nutrition Examination Survey (NHANES, 2011-2012 on Obesity), Study to Understand Prognoses Preferences Outcomes and Risks of Treatment (SUPPORT), chronic kidney disease, and dermatology data. We also examined performance using simulated data with observations that are Missing At Random (MAR) or Missing Completely At Random (MCAR) under various degrees of missingness and levels of class imbalance in the response variable. Results Our results demonstrate that user-based collaborative filtering is consistently inferior to logistic regression and random forests with different imputations on real and simulated data. The results warrant caution for the collaborative filtering for the purpose of clinical risk prediction when traditional classification is feasible and practical. Conclusions CF may not be desirable in datasets where classification is an acceptable alternative. We describe some natural applications related to “Big Data” where CF would be preferred and conclude with some insights as to why caution may be warranted in this context.

In this paper, the microstructure evolution and mechanical properties fluctuation of Ti-6Al-2Zr-1Mo-1V forging state bar after the first stage heat treatment at 950℃~955℃ and the second stage heat treatment at 760℃~840℃ were studied. In the first stage of heat treatment, the content of primary α and the tensile strength decreases with the increase of temperature, and the high temperature duration time is obviously prolonged. During the second stage of heat treatment, the metastable β phase precipitates third α phase, and with the increase of temperature, the tensile strength increases and the high temperature duration time prolongs.

In this paper, the author studied the effects of different stress ratios（R） and stress concentration factors(Kt) on the fatigue properties of WSTi6211 titanium alloy.Through S-N curve, the author obtained the fatigue ultimate strength of the material under different conditions and analyzed characteristics of fatigue fractures, including the crack source sourse, the crack growth region and the final rupture region. The results show that when Kt=1, R=0.5, the fatigue ultimate strength σD is 626MPa; when Kt = 1, R=0.06, the fatigue ultimate strength σD is 527.5MPa; when Kt=3, R=0.06, the ultimate fatigue strength σD is 267MPa. Fatigue performance is very sensitive to R and Kt. The larger R is, the larger the fatigue ultimate strength is. The larger Kt is, the smaller the fatigue limit strength is. The fracture morphology shows typical fatigue fracture morphology. Most of the cracks originate on the surface of specimens and have typical fatigue bands. With the decrease of stress, the area of crack growth zone increases.

The autocorrelation function (ACF) of the Binary Offset Carrier modulation (BOC) signal for Global Navigation Satellite System (GNSS) has multiple peaks, ambiguity is easily generated during the synchronization of the baseband signal. Some methods have been proposed to remove the ambiguity, but the performance is not suitable for high-order BOC signals or does not maintain narrow correlation characteristics. This paper proposes a sub-function reconstruction synchronization algorithm to solve this problem, of which the key is to design a new local auxiliary code: the local Pseudo-Random Noise (PRN) code is divided into several new codes with different delays. The auxiliary code performs a coherent integration operation with the received signal. Then, a correlation function without any positive side peaks is obtained by multiplying the two correlation results to make the acquisition/tracking completely unambiguous. The paper gives a design scheme of navigation signal acquisition/tracking and deduces the theoretical analysis of detection performance. The phase discrimination function is provided. The performance of the method is analyzed from both theoretical and simulation aspects. Compared with the Binary phase shift keying-like (BPSK-LIKE) method, Subcarrier Phase Cancellation (SCPC) method and the Autocorrelation Side-Peak Cancellation Technique (ASPeCT) method, the proposed method has the best detection probability for the acquisition, which is 0.5 dB-Hz better than ASPeCT. For tracking, the proposed method performs best in terms of phase-detection curve, anti-multipath performance, and anti-noise performance. For high-order BOC signals, the SRSA technique successfully removes the false lock points, and there is only one multipath error envelope, and the code tracking error is almost the same as the ASPeCT method.

This paper aims to evaluate the applicability of volcanic mud as the fine aggregate for controlled low-strength material (CLSM) by the experimental method. Two types of binder were selected, including cement and alkali-activated slag binders (without cement). The study mainly explored the effects of different addition rates of volcanic mud and different concentrations of alkaline agents (sodium hydroxide) on the engineering properties of CLSM. The test results show that the CLSMs with cement and volcanic mud have better workability and less water bleeding. However, the compressive strength of CLSM decreases as the replacement rate of volcanic mud increases, and the setting time also increases. The replacement rate of volcanic mud is recommended to be 20%. The volcanic mud mixed with the alkali-activated slag binder (without cement) can be successfully made into CLSM. When the concentration of sodium oxide in CLSM is 5%, although the compressive strength is highest at 7 days or 28 days, it cannot be hardened at the early age (before four days) and without compressive strength. CLSM with 20% sodium oxide concentration has poor workability. Its compressive strength is slightly lower than that of the 10% group. Therefore, the amount of calcium hydroxide recommended is 10%.

This study uses a panel KSS test by Nuri Ucar and Tolga Omay (2009), with a Fourier function based on the sequential panel selection method (SPSM) procedure proposed by Georgios Chortareas and George Kapetanios (2009) to test the efficiency of REIT markets in 16 countries from 28 March 2008 to 27 June 2011. A Fourier approximation often captures the behavior of an unknown break, and testing for a unit root increases its power to do so. Moreover, SPSM can determine the mix of I(0) and I(1) series in a panel setting to clarify how many and which are random walk processes. Our empirical results demonstrate that REIT markets are efficient in all sampled countries except the UK. Our results imply that investors in countries with efficient REIT markets can adopt more passive portfolio strategies.

We investigated changes in the financial performance of representatives of the world’s top 200 commercial banks after the global subprime financial crisis. Our empirical results show that following the subprime-crisis disclosure, all commercial banks exhibited worse performance in asset quality, profitability, liquidity, and growth index, accompanied by risk increases in asset adequacy, managerial ability, profitability, and growth index. Developed markets have suffered a greater negative influence than emerging markets, causing downward pressure on asset adequacy, asset quality, and profitability since the subprime crisis. Commercial banks within developed nations suffered more direct pronounced effects from the subprime crisis than did those in emerging markets. Our results prove that larger commercial banks, particularly those with larger capitalization, have the economies-of-scale advantage to resist the negative effects of economic downturns.

Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples. After the whole exome sequencing data were filtered through a series of existing variation databases, a heterozygous mutation c.499T