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Computational thinking (CT) is regarded as the conceptual basis required for identifying and solving real-world problems through algorithmic approaches to achieve transferable solutions. Developing students' CT in primary school stages is essential and has received considerable attention. Meanwhile, researchers incorporated digital badges into classrooms to improve students' learning motivation in computer science (CS). However, few solid empirical studies analyze the effects of the digital badges approach in CS education to develop students' CT. Therefore, to bridge this gap, this study designed and implemented a block-based programming course in a primary school and examined the impact of the digital badges approach on pupils' CT skills and self-efficacy and learning motivation in CS. A quasi-experimental design was conducted among 99 third-grade students across three classes. The results revealed that the adapted digital badges in primary school (1) significantly improved the students' CT skills, (2) had no significant positive impact on their CT self-efficacy or learning motivation in CS, and (3) showed no mediating effect of learning motivation on the relationship between CT skills and CT self-efficacy. In addition, we found that whether students could see only their own digital badges or also those of others had no impact on CT skills, self-efficacy, or learning motivation in CS. These findings have implications for the design of digital badge educational interventions intended to promote students' CT and learning motivation.

Abstract Background Hundreds of millions of tons coal fly ash are produced annually to support economic development and industrial production. However, directly applying coal fly ash to agricultural production can decrease the land productivity and pose a threat to the ecosystem due to the poor physicochemical properties and seriously heavy metal pollution. Methods In this study, a field experiment to investigate the effects of coal fly ash as a soil amendment was conducted in Hebei province, China. The coal fly ash (CFA) soil field was mixed with the carrier soil (CS, without containing coal fly ash) at different rates (0–40% mass content) in the 0–20 cm layer of top soil and then mixed with a rotovator. The soil was then amended with 0.45–1.80 kg·m− 2 of G1 soil amendment for planting corn. Purpose The purpose of this study is to investigate the response mechanism of soil microbial community activities, and soil physicochemical properties to soil amendment and carrier soil in coal fly ash soil. Key results The study found that the G1 amendment, which consisted of humic acid, polyacrylamide, zeolite powder, and FeSO4·7H2O, improved the soil chemical properties and physical structure by increasing soil bulk density and macroaggregates. The highest corn yield was observed in B5 (20% CS and 1.3500 kg·m− 2 G1). Meanwhile, the abundance of microorganisms that facilitate the circulation of soil nutrients such as Acidobacteria (77.05%), Sphingomonas (25.60%), Nitrospira (20.78%), Streptomyces (11.32%), and Gaiella (10.20%) was increased. Conclusions Overall, our results indicate that the use of coal fly ash soil as a amendment can enhance soil sustainability by improving soil microbial functions. These findings provide a reference for the development and application of coal fly ash soil amendments.

Abstract Histone lactylation is a metabolic stress‐related histone modification. However, the role of histone lactylation in the development of sepsis‐associated acute kidney injury (SA‐AKI) remains unclear. Here, histone H3K18 lactylation (H3K18la) is elevated in SA‐AKI, which is reported in this study. Furthermore, this lactate‐dependent histone modification is enriched at the promoter of Ras homolog gene family member A (RhoA) and positively correlated with the transcription. Correction of abnormal lactate levels resulted in a reversal of abnormal histone lactylation at the promoter of RhoA. Examination of related mechanism revealed that histone lactylation promoted the RhoA/Rho‐associated protein kinase (ROCK) /Ezrin signaling, the activation of nuclear factor‐κB (NF‐κB), inflammation, cell apoptosis, and aggravated renal dysfunction. In addition, Ezrin can undergo lactylation modification. Multiple lactylation sites are identified in Ezrin and confirmed that lactylation mainly occurred at the K263 site. The role of histone lactylation is revealed in SA‐AKI and reportes a novel post‐translational modification in Ezrin. Its potential role in regulating inflammatory metabolic adaptation of renal proximal tubule epithelial cells is also elucidated. The results provide novel insights into the epigenetic regulation of the onset of SA‐AKI.

Sodium-ion batteries (SIBs) with low cost and high safety are considered as an electrochemical energy storage technology suitable for large-scale energy storage. Hard carbon, which is inexpensive and has both high capacity and low sodium storage potential, is regarded as the most promising anode for commercial SIBs. However, the commercialization of hard carbon still faces technical issues of low initial Coulombic efficiency, poor rate performance, and insufficient cycling stability, due to the intrinsically irregular microstructure of hard carbon. To address these challenges, the rational design of the hard carbon microstructure is crucial for achieving high-performance SIBs, via gaining an in-depth understanding of its structure–performance correlations. In this context, our review firstly describes the sodium storage mechanism from the perspective of the hard carbon microstructure's formation. We then summarize the state-of-art development of hard carbon, providing a critical overview of emergence of hard carbon in terms of precursor selection, microstructure design, and electrolyte regulation to optimize strategies for addressing practical problems. Finally, we highlight directions for the future development of hard carbon to achieve the commercialization of high-performance SIBs. We believe this review will serve as basic guidance for the rational design of hard carbon and stimulate more exciting research into other types of energy storage devices.

Abstract Antiphospholipid syndrome (APS) is characterized by thrombus formation, poor pregnancy outcomes, and a proinflammatory response. H3K4me3‐related monocytes activation are key regulators of APS pathogenesis. Therefore, H3K4me3 CUT&Tag and ATAC‐seq are performed to examine the epigenetic profiles. The results indicate that the H3K4me3 signal and chromatin accessibility at the FOXJ2 promoter are enhanced in an in vitro monocyte model by stimulation with β2GPI/anti‐β2GPI, which mimics APS, and decreases after OICR‐9429 administration. Furthermore, FOXJ2 is highly expressed in patients with primary APS (PAPS) and is the highest in patients with triple‐positive antiphospholipid antibodies (aPLs). Mechanistically, FOXJ2 directly binds to the SLAMF8 promoter and activates SLAMF8 transcription. SLAMF8 further interacts with TREM1 to stimulate TLR4/NF‐κB signaling and prohibit autophagy. Knockdown of FOXJ2, SLAMF8, or TREM1 blocks TLR4/NF‐κB and provokes autophagy, subsequently inhibiting the release of inflammatory and thrombotic indicators. A mouse model of vascular APS is established via β2GPI intraperitoneal injection, and the results suggest that OICR‐9429 administration attenuates the inflammatory response and thrombus formation by inactivating FOXJ2/SLAMF8/TREM1 signaling. These findings highlight the overexpression of H3K4me3‐mediated FOXJ2 in APS, which consequently accelerates APS pathogenesis by triggering inflammation and thrombosis via boosting the SLAMF8/TREM1 axis. Therefore, OICR‐9429 is a promising candidate drug for APS therapy.

Exploring the complex relationship between the freeze–thaw cycle and the surface energy budget (SEB) is crucial for deepening our comprehension of climate change. Drawing upon extensive field monitoring data of the Qinghai-Tibet Plateau, this study examines how surface energy accumulation influences the thawing depth. Combined with Community Land Model 5.0 (CLM5.0), a sensitivity test was designed to explore the interplay between the freeze–thaw cycle and the SEB. It is found that the freeze–thaw cycle process significantly alters the distribution of surface energy fluxes, intensifying energy exchange between the surface and atmosphere during phase transitions. In particular, an increase of 65.6% is observed in the ground heat flux during the freezing phase, which subsequently influences the sensible and latent heat fluxes. However, it should be noted that CLM5.0 has limitations in capturing the minor changes in soil moisture content and thermal conductivity during localized freezing events, resulting in an imprecise representation of the complex freeze–thaw dynamics in cold regions. Nevertheless, these results offer valuable insights and suggestions for improving the parameterization schemes of land surface models, enhancing the accuracy and applicability of remote sensing applications and climate research.

Despite the significant advancements in cancer treatment brought by immune checkpoint inhibitors (ICIs), their effectiveness in treating glioblastoma (GBM) remains highly dissatisfactory. Immunotherapy relies on the fundamental concept of T cell-mediated tumor killing (TTK). Nevertheless, additional investigation is required to explore its potential in prognostic prediction and regulation of tumor microenvironment (TME) in GBM. TTK sensitivity related genes (referred to as GSTTKs) were obtained from the TISIDB. The training cohort was available from the TCGA-GBM, while the independent validation group was gathered from GEO database. Firstly, we examined differentially expressed GSTTKs (DEGs) with limma package. Afterwards, the prognostic DEGs were identified and the TTK signature was established with univariate and LASSO Cox analyses. Next, we examined the correlation between the TTK signature and outcome of GBM as well as immune phenotypes of TME. Furthermore, the evaluation of TTK signature in predicting the effectiveness of immunotherapy has also been conducted. We successfully developed a TTK signature with an independent predictive value. Patients who had a high score experienced a worse prognosis compared to patients with low scores. The TTK signature showed a strong positive association with the infiltration degree of immunocyte and the presence of various immune checkpoints. Moreover, individuals with a lower score exhibited increased responsiveness to ICIs and experienced improved prognosis. In conclusions, we successfully developed and verified a TTK signature that has the ability to predict the outcome and immune characteristics of GBM. Furthermore, the TTK signature has the potential to direct the personalized immunotherapy for GBM.

Studies have shown that vehicle trajectory data are effective for calibrating microsimulation models. Light Detection and Ranging (LiDAR) technology offers high-resolution 3D data, allowing for detailed mapping of the surrounding environment, including road geometry, roadside infrastructures, and moving objects such as vehicles, cyclists, and pedestrians. Unlike other traditional methods of trajectory data collection, LiDAR’s high-speed data processing, fine angular resolution, high measurement accuracy, and high performance in adverse weather and low-light conditions make it well suited for applications requiring real-time response, such as autonomous vehicles. This research presents a comprehensive framework for integrating LiDAR sensor data into simulation models and their accurate calibration strategies for proactive safety analysis. Vehicle trajectory data were extracted from LiDAR point clouds collected at six urban signalized intersections in Lubbock, Texas, in the USA. Each study intersection was modeled with PTV VISSIM and calibrated to replicate the observed field scenarios. The Directed Brute Force method was used to calibrate two car-following and two lane-change parameters of the Wiedemann 1999 model in VISSIM, resulting in an average accuracy of 92.7%. Rear-end conflicts extracted from the calibrated models combined with a ten-year historical crash dataset were fitted into a Negative Binomial (NB) model to estimate the model’s parameters. In all the six intersections, rear-end conflict count is a statistically significant predictor (p-value < 0.05) of observed rear-end crash frequency. The outcome of this study provides a framework for the combined use of LiDAR-based vehicle trajectory data, microsimulation, and surrogate safety assessment tools to transportation professionals. This integration allows for more accurate and proactive safety evaluations, which are essential for designing safer transportation systems, effective traffic control strategies, and predicting future congestion problems.

Abstract Background Alterations of the trimethylation of histone 3 lysine 4 (H3K4me3) mark in monocytes are implicated in the development of autoimmune diseases. Therefore, the purpose of our study was to elucidate the role of H3K4me3‐mediated epigenetics in the pathogenesis of antiphospholipid syndrome (APS). Methods H3K4me3 Cleavage Under Targets and Tagmentation and Assay for Transposase‐Accessible Chromatin were performed to determine the epigenetic profiles. Luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, co‐immunoprecipitation and chromatin immunoprecipitation were performed for mechanistic studies. Transmission electron microscopy and propidium iodide staining confirmed cell pyroptosis. Primary monocytes from patients with primary APS (PAPS) and healthy donors were utilised to test the levels of key molecules. A mouse model mimicked APS was constructed with beta2‐glycoprotein I (β2GPI) injection. Blood velocity was detected using murine Doppler ultrasound. Results H3K4me3 signal and open chromatin at the ARID5B promoter were increased in an in vitro model of APS. The epigenetic factor ARID5B directly activated LINC01128 transcription at its promoter. LINC01128 promoted the formation of the BTF3/STAT3 complex to enhance STAT3 phosphorylation. Activated STAT3 interacted with the NLRP3 promoter and subsequently stimulated pyroptosis and apoptosis. ARID5B or BTF3 depletion compensated for LINC01128‐induced pyroptosis and apoptosis by inhibiting STAT3 phosphorylation. In mice with APS, β2GPI exposure elevated the levels of key proteins of pyroptosis and apoptosis pathways in bone marrow‐derived monocytes, reduced the blood velocity of the ascending aorta, increased the thrombus size of the carotid artery, and promoted the release of interleukin (IL)‐18, IL‐1β and tissue factor. Patients with PAPS had the high‐expressed ARID5B and LINC01128, especially those with triple positivity for antiphospholipid antibodies. Moreover, there was a positive correlation between ARID5B and LINC01128 expression. Conclusion This study indicated that ARID5B/LINC01128 was synergistically upregulated in APS, and they aggravated disease pathogenesis by enhancing the formation of the BTF3/STAT3 complex and boosting p‐STAT3‐mediated pyroptosis and apoptosis, thereby providing candidate therapeutic targets for APS. Highlights The H3K4me3 mark and chromatin accessibility at the ARID5B promoter are increased in vitro model mimicked APS. ARID5B‐mediated LINC01128 induces pyroptosis and apoptosis via p‐STAT3 by binding to BTF3. ARID5B is high‐ expressed in patients with primary APS and positively correlated with LINC01128 expression. OICR‐9429 treatment mitigates pyroptosis and related inflammation in vivo and in vitro models mimicked APS.

The crosslinking network structure is a crucial factor influencing the properties of natural rubber. Therefore, investigating the impact of different vulcanization bond types on the strain-induced crystallization behavior and properties of natural rubber can provide a theoretical foundation for producing high-performance natural rubber. In this study, diverse curing systems were employed to produce vulcanized natural rubbers with varying crosslink types. The crosslinking network structures of the vulcanized rubbers were analyzed using the tube model theory. Additionally, the effects of vulcanization bonds on strain-induced crystallization behavior and tensile properties were examined through in-situ X-ray diffraction and a tensile testing machine. The results revealed that the vulcanizate with monosulfidic bonds, formed under the effective vulcanization (EV) system, primarily comprised chemical crosslinking networks, resulting in a high tensile modulus, low elongation at break, and low tensile strength. Conversely, the vulcanizate under the conventional vulcanization (CV) system exhibited a distinct entanglement network impact compared to the chemical crosslinking network, resulting in a smaller tensile modulus but the highest elongation at break and the largest tensile strength. These differences stemmed from the distinct roles of vulcanization bonds within the crosslinking network. Specifically, the relatively short monosulfidic bond quickly reached the critical degree of orientation for crystallization during stretching, leading to higher crystallinity under the same strain. However, its shorter length caused earlier fracture during stretching, resulting in network heterogeneity, reduced elongation at break, and lower tensile strength. On the other hand, the longer polysulfidic bond underwent fracture recombination during stretching, with slower orientation and delayed crystallization. Nonetheless, this recombination improved network uniformity and integrity due to stress dissipation from the initial fracture, enhancing crystallinity, elongation at break, and tensile strength. This study elucidated the influence of vulcanization crosslinking on the tensile properties of vulcanizates.

Glioblastoma is the most frequent form of malignant brain tumor. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is overexpressed and involved in the tumorigenesis and metastasis of glioblastoma. miR-130a-3p has been revealed to be aberrantly expressed in tumors and has aroused wide attention. In present study, we would like to investigate the effect and potential mechanism of miR-130a-3p on the proliferation and migration in glioblastoma. The relative expression levels of miR-130a-3p and CPEB4 in glioblastoma cell lines were detected by real-time quantitative polymerase chain reaction. Cell viability and migration were detected by methylthiazolyl tetrazolium assay and transwell assay, and cell cycle analysis was detected by flow cytometry. The expression of CPEB4 protein and epithelial-mesenchymal transition associated markers were detected by western blot. Bioinformatics and luciferase activity analysis were used to verify the targeting relationship between miR-130a-3p and CPEB4. We observed that the expression of CPEB4 was upregulated while that of miR-130a-3p was downregulated in glioblastoma cell lines. CPEB4 was validated as a target of miR-130a-3p by luciferase activity assay. Increased levels of miR-130a-3p inhibited the proliferation and migration of the glioblastoma cells and the overexpression of miR-130a-3p inhibited epithelial-mesenchymal transition. However, CPEB4 overexpression resisted the inhibitory effects of miR-130a-3p. Our study elucidates CPEB4 is upregulated because of the downregulated miR-130a-3p in glioblastoma, which enhances the glioblastoma growth and migration, suggesting a potential therapeutic target for the disease.

Abstract Isoforms of a gene may contribute to diverse biological functions. In the cochlea, the repertoire of alternative isoforms remains unexplored. We integrated single-cell short-read and long-read RNA sequencing techniques and identified 236,012 transcripts, 126,612 of which were unannotated in the GENCODE database. Then we analyzed and verified the unannotated transcripts using RNA-seq, RT-PCR, Sanger sequencing, and MS-based proteomics approaches. To illustrate the importance of identifying spliced isoforms, we investigated otoferlin, a key protein involved in synaptic transmission in inner hair cells (IHCs). Upon deletion of the canonical otoferlin isoform, the identified short isoform is able to support normal hearing thresholds but with reduced sustained exocytosis of IHCs, and further revealed otoferlin functions in endocytic membrane retrieval that was not well-addressed previously. Furthermore, we found that otoferlin isoforms are associated with IHC functions and auditory phenotypes. This work expands our mechanistic understanding of auditory functions at the level of isoform resolution.

The surface energy budget over the Qinghai-Tibet Plateau (QTP) and the Arctic significantly influences the climate system with global consequences. The performances of 30 selected Coupled Model Intercomparison Project Phase 6 (CMIP6) models were evaluated based on six sites in the QTP and Arctic. The simulation results for latent heat flux (LE) were more accurate in the QTP, where the correlation coefficient and root mean square error (RMSE) were 0.9 and 30 W m−2, respectively. The results for sensible heat flux (H) were more accurate in the Arctic, the correlation coefficient and RMSE were 0.8 and 24 W m−2, respectively. Furthermore, the multiple models mean results revealed that the surface energy flux had seasonal variation and regional differences over the QTP and the Arctic. In the QTP, H was the lowest in winter, increased in spring, and reached the maximum in summer. However, the transitional changes in spring and autumn were not apparent in the Arctic, mainly due to seasonal net radiation difference between the two places. LE was affected by precipitation and surface soil moisture content. This work is important for understanding land-atmosphere interactions and useful for improving the accuracy of land surface models simulations.

BackgroundTransforming growth factor-β (TGF-β) is a multifunctional cytokine with an important role in tissue development and tumorigenesis. TGF-β can inhibit the function of many immune cells, prevent T cells from penetrating into the tumor center, so that the tumor cells escape from immune surveillance and lead to low sensitivity to immunotherapy. However, its potential roles in predicting clinical prognosis and tumor microenvironment (TME) immune features need to be deeply investigated in glioblastoma (GBM).MethodsThe TCGA-GBM dataset was obtained from the Cancer Genome Atlas, and the validation dataset was downloaded from Gene Expression Omnibus. Firstly, differentially expressed TGF-β genes (DEGs) were screened between GBM and normal samples. Then, univariate and multivariate Cox analyses were used to identify prognostic genes and develop the TGF-β risk model. Subsequently, the roles of TGF-β risk score in predicting clinical prognosis and immune characteristics were investigated.ResultsThe TGF-β risk score signature with an independent prognostic value was successfully developed. The TGF-β risk score was positively correlated with the infiltration levels of tumor-infiltrating immune cells, and the activities of anticancer immunity steps. In addition, the TGF-β risk score was positively related to the expression of immune checkpoints. Besides, the high score indicated higher sensitivity to immune checkpoint inhibitors.ConclusionsWe first developed and validated a TGF-β risk signature that could predict the clinical prognosis and TME immune features for GBM. In addition, the TGF-β signature could guide a more personalized therapeutic approach for GBM.

Abstract Background Clinical research publications have become the dominant source and basis of clinical evidence-based decision-making. Exploring the type and quantity of clinical research publications in the PubMed database is useful for clarifying the changing trends of clinical research development in recent years. Therefore, a longitudinal analysis of the type and quantity of clinical research publications in the PubMed database over three decades was conducted. Methods The PubMed database was searched to retrieve clinical research according to the type and year of publication from January 1, 1991 to December 31, 2020. The research types were classified as primary and secondary literature. Results A total of 1,078,404 primary literatures were retrieved and the constituent proportions were ranked from high to low as case report/series (27.54%), randomized clinical trials (RCTs) (23.62%), cohort studies (21.05%), cross-sectional studies (17.49%), case control studies (9.15%), non-RCTs (1.01%), and pragmatic clinical trials (PCTs) (0.15%). Correspondingly, 1,302,173 secondary literatures were retrieved and ranked as narrative review (70.88%), systematic review (15.02%), systematic review and meta-analyses (13.89%), traditional meta-analyses (4.48%), expert consensus (2.31%), guidelines (1.49%), scoping reviews (0.68%), net meta-analyses (0.40%), and umbrella reviews (0.04%). The average annual growth rate for the primary literature was 10.28%, and ranked from high to low as PCTs (83.68%), cohort studies (17.74%), cross-sectional studies (17.61%), non-RCTs (12.11%), case control studies (8.86%), RCTs (7.68%), case report/series (7.51%); while that for the secondary literature was 10.57%, and ranked from high to low as net meta-analyses (48.97%), umbrella reviews (47.09%), scoping reviews (41.92%), systematic reviews and meta-analyses (33.44%), systematic reviews (33.05%), traditional meta-analyses (12.49%), expert consensuses (9.22%), narrative review (8.72%), and guidelines (2.82%). Conclusion Both the composition and number of clinical studies changed significantly from 1991 to 2020. Based on the trend, the case report/series, case control study, and narrative review are on the decline, while cohort study, cross-sectional study, systematic reviews, and systematic review and meta-analysis literature have increased. To improve the quality of clinical evidence, we recommend RCT and cohort study give priority to access to allocated research resources in future.

Object detection is the fundamental task of vision-based sensors in environmental perception and sensing. To leverage the full potential of roadside 4D MMW radars, an innovative traffic detection method is proposed based on their distinctive data characteristics. First, velocity-based filtering and region of interest (ROI) extraction were employed to filter and associate point data by merging the point cloud frames to enhance the point relationship. Then, the Louvain algorithm was used to divide the graph into modularity by converting the point cloud data into graph structure and amplifying the differences with the Gaussian kernel function. Finally, a detection augmentation method is introduced to address the problems of over-clustering and under-clustering based on the object ID characteristics of 4D MMW radar data. The experimental results showed that the proposed method obtained the highest average precision and F1 score: 98.15% and 98.58%, respectively. In addition, the proposed method showcased the lowest over-clustering and under-clustering errors in various traffic scenarios compared with the other detection methods.

Multispectral (MS) pansharpening is defined as the fusion of spatial information in panchromatic (PAN) image and spectral information in MS image. In this work, we propose an MS pansharpening based on multisequence convolutional recurrent neural network (MCRNN). The proposed MCRNN contains two subnetworks (shallow feature extraction subnetwork and deep feature fusion subnetwork). In the shallow feature extraction subnetwork, PAN and MS images are superimposed in the spectral dimension as multisequence data. A convolutional neural network based on residual learning is then used to obtain the feature maps from multisequence data. In the deep feature fusion subnetwork, since MS and PAN images are highly correlated, a convolutional recurrent neural network belonging to recurrent neural network is used to model adjacent and across-band relationships between these feature maps to capture the local and global correlations of the features in different bands. The global average pooling is then performed on the output results to yield the pansharpening result. Several datasets are tested at reduced and full-resolution experiments, the experimental results show that the performance of the proposed MCRNN is superior to the traditional pansharpening methods.

The realization of mid-infrared thermal radiation based on metamaterials insensitive to angle and polarization plays an important role in various thermal photonic applications. However, the challenges include the following: most previously designed thermal emitters usually contain metal components with unsatisfied physicochemical stability, accompanied with complex manufacturing technology. The present study proposes a mid-infrared thermal emitter at 3–6 μm wavelength range based on Fibonacci quasi-periodic structure, and a flat one-dimensional structure based on Fibonacci geometry resorting to ITO is designed. The proposed thermal emitter is, theoretically and experimentally, proven to possess good angular and polarization-independent selective thermal emission performance in a relatively wide infrared wavelength range. Furthermore, the good optical and high-temperature thermal stability of the designed thermal emitter is verified in the present experimental research. The thermal emitters proposed have advantages in polarization-independence without scale restraint and low cost but with wide vision. In summary, the present study provides a new tactics for obtaining non-metal spectral selective thermal emitters in a relatively wide wavelength range and thermal photonic applications under harsh conditions.

Lalin River is a first-level tributary of the right bank of Songhua River. High-quality corn production bases irrigated by the Lalin River are famous throughout the country. However, in the last few decades, the hydrological regimes changed severely due to expansion of the irrigation area, leading to more water used for irrigation. To investigate the variation of the hydrological situation, we analyzed the daily runoff data at the Caijiagou Hydrological Station from 1954 to 2015 by using the Indicators of Hydrologic Alteration (IHA) and the range of variability approach (RVA). The results showed a severe decreasing trend of the average monthly flow during the water level with regular and high periods, with a negative slope of −2.924 in August and −2.518 in September. The increasing trend of low pulse and fall rate of flow and the decreasing trend of the rising rate of flow demonstrate that water resources are drying up. Regarding the flow rate, the annual maximum value decreased significantly in slopes of −7.9, −7.6, −6.09, −5.28, and −2.98 on the 1-day, 3-day, 7-day, 30-day, and 90-day, respectively. The flow reversals’ average value is 65 to 50 times/year from 1954 to 2015. From RVA analysis, the hydrological alteration of the basin decreased 50% after 1978. To investigate the influencing factors for the hydrological alteration, we analyzed the variation in land cover and land use between 1978 and 2015. The results showed that the area of paddy fields in 2015 was 1.5 times that of 1978, and the water consumption in paddy fields accounts for 80.8% of the total water resources. Consequently, the wetland area of the basin in 2015 was only 53% of 1978, and the wetland area of the two wetland nature reserves at the mouth of the Lalin River in 2015 was about 53% of 1978. Furthermore, the meteorological condition in the LRB shows a warming and drying tendency. The air temperature has shown an intensively increased tendency, and precipitation decreased in the last 50 years. This indicates that the hydrological situation in the Lalin River Basin has changed considerably under the dual influence of human activities and global warming.

PURPOSEWe aimed to evaluate whether bronchial artery can supply a percutaneously inoculated canine transmissible venereal tumor (CTVT) in a lung tumor model.METHODSFresh CTVT tissue blocks were percutaneously inoculated into unilateral or bilateral lungs of six immunosuppressed dogs at the mid zone of the middle or lower lobe. Tumor growth was monitored by computed tomography (CT). Ten weeks after inoculation, pulmonary arterial digital subtraction angiography (DSA), bronchial arterial DSA, transpulmonary arterial contrast-enhanced multislice CT, transbronchial arterial contrast-enhanced multislice CT (BA-MSCT), and transpulmonary arterial lipiodol multislice CT were performed.RESULTSTumor growth was seen in all 10 inoculated sites, with a maximum diameter of 2.734±0.138 cm at 10th week. Bronchial arterial blood supply was evident in 9 nodules on DSA, and was equivocal in one which was later demonstrated on BA-MSCT. No obvious pulmonary arterial blood supply was observed in any of the nodules. Lipiodol deposition was displayed in two of the small distant metastases, which indicated that pulmonary artery was involved in the supply of the metastases.CONCLUSIONOur results demonstrated bronchial arterial blood supply in this new lung cancer model. This model may be used in further research on transbronchial arterial intervention for lung cancer.

Objectives: The role of asymptomatic infections in the transmission of COVID-19 have drawn considerable attention. Here, we performed a meta-analysis to summarize the epidemiological and radiographical characteristics of asymptomatic infections associated with COVID-19. Methods: Data on the epidemiological and radiographical characteristics of asymptomatic infections were extracted from the existing literature. Pooled proportions with 95% confidence intervals were then calculated using a random effects model. Results: A total of 104 studies involving 20,152 cases were included. The proportion of asymptomatic individuals among those with COVID-19 was 13.34% (10.86%–16.29%), among which presymptomatic and covert infections accounted for 7.64% (4.02%–14.04%) and 8.44% (5.12%–13.62%), respectively. The proportions of asymptomatic infections among infected children and healthcare workers were 32.24% (23.08%–42.13%) and 36.96% (18.51%–60.21%), respectively. The proportion of asymptomatic infections was significantly higher after 2020/02/29 than before (33.53% vs 10.19%) and in non-Asian regions than in Asia (28.76% vs 11.54%). The median viral shedding duration of asymptomatic infections was 14.14 days (11.25–17.04). A total of 47.62% (31.13%–72.87%) of asymptomatic infections showed lung abnormalities, especially ground-glass opacity (41.11% 19.7%–85.79%). Conclusions: Asymptomatic infections were more commonly found in infected children and healthcare workers and increased after 2020/02/29 and in non-Asian regions. Chest radiographical imaging could be conducive to the early identification of asymptomatic infections.

Mutations in a number of genes encoding mitochondrial aminoacyl-tRNA synthetases lead to non-syndromic and/or syndromic sensorineural hearing loss in humans, while their cellular and physiological pathology in cochlea has rarely been investigated in vivo. In this study, we showed that histidyl-tRNA synthetase HARS2, whose deficiency is associated with Perrault syndrome 2 (PRLTS2), is robustly expressed in postnatal mouse cochlea including the outer and inner hair cells. Targeted knockout of Hars2 in mouse hair cells resulted in delayed onset (P30), rapidly progressive hearing loss similar to the PRLTS2 hearing phenotype. Significant hair cell loss was observed starting from P45 following elevated reactive oxygen species (ROS) level and activated mitochondrial apoptotic pathway. Despite of normal ribbon synapse formation, whole-cell patch clamp of the inner hair cells revealed reduced calcium influx and compromised sustained synaptic exocytosis prior to the hair cell loss at P30, consistent with the decreased supra-threshold wave I amplitudes of the auditory brainstem response. Starting from P14, increasing proportion of morphologically abnormal mitochondria was observed by transmission electron microscope, exhibiting swelling, deformation, loss of cristae and emergence of large intrinsic vacuoles that are associated with mitochondrial dysfunction. Though the mitochondrial abnormalities are more prominent in inner hair cells, it is the outer hair cells suffering more severe cell loss. Taken together, our results suggest that conditional knockout of Hars2 in mouse cochlear hair cells leads to accumulating mitochondrial dysfunction and ROS stress, triggers progressive hearing loss highlighted by hair cell synaptopathy and apoptosis, and is differentially perceived by inner and outer hair cells.

The Asian tropopause aerosol layer (ATAL) is an enhanced aerosol concentration layer in the upper troposphere and lower stratosphere over Asia, and it has important effects on radiation balance, atmospheric circulation, regional climate, and atmospheric chemical processes. However, despite its importance, the specific structure and long-term variation trend of the ATAL have been rarely analyzed, which is critical for assessing the impact of ATAL on climate change and evaluating the performance of climate models. This study compared and analyzed the three-dimensional spatial distribution characteristics and temporal variability using CALIPSO, SAGEII, and MERRA-2 data and discussed the possible causes of the variation. The results showed that the ATAL began to appear in the mid-to-late 1990s and then strengthened rapidly until 2010, after which this trend was no longer observed. Moreover, significant heterogeneity existed in the distribution of aerosol concentration in the ATAL, showing north–south differences (NSDs) in both time and space. In addition, it was found that besides surface emissions, atmospheric circulation, the strength of convective transport, and stratosphere–troposphere exchange processes also contribute to this pattern. This study has important implications for quantifying the climate consequences of the ATAL.

Abstract Toll-like receptor 4 (TLR4) is a crucial receptor in neuroinflammation and apoptotic neuronal death, and increasing evidences indicated that β2-microglobulin (B2M) is thought to be a major contributor to age-related cognitive decline. In present study, we designed to investigate the effects of TLR4 on B2M-induced age-related cognitive decline. Wild-type (WT) C57BL/6, TLR4 knockout (TLR4 -KO) mice and hippocampal neurons from the two type mice were respectively divided into two groups: (1) Veh group; (2) B2M-treated group. The behavioral responses of mice were measured using Morris Water Maze. Hippocampal neurogenesis and neuronal damage, inflammatory response, apoptosis, synaptic proteins and neurotrophic factors, and TLR4/MyD88/NF-κB signaling pathway proteins were examined using molecular biological or histopathological methods. The results showed that WT mice received B2M in the DG exhibited age-related cognitive declines, increased TLR4 mRNA expression and high levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and apoptotic neuronal death in the hippocampus, which were partially attenuated in TLR4-KO mice. Moreover, in absence of TLR4, B2M treatment improved hippocampus neurogenesis and increased synaptic related proteins. Our cell experiments further demonstrated that deletion of TLR4 could significantly increase synaptic related protein, decrease neuroinflammatory fators, inhibited apoptotic neuronal death, and regulated MyD88/NF-κB signal pathway after B2M treatment. In summary, our results support the TLR4 contributes to B2M-induced age-related cognitive decline due to neuroinflammation and apoptosis through TLR4/MyD88/NF-κB signaling pathway via a modulation of hippocampal neurogenesis and synaptic function. This may provide an important neuroprotective mechanism for improving age-related cognitive decline.

We proposed a method for driving metal nanoparticles in the focal field by cylindrical metalens with phase gradient. It was found that the introduced gradient phase would not affect the formation of the focal line, where metal nanoparticles can be trapped. While being driven along the direction with the phase gradient, Ag nanoparticles with different sizes, and nanoparticles with different materials (Au and Ag) were successfully separated, respectively. The induced driving force has an approximately linear relationship with the phase gradient. This kind of planar thin structure can be combined with a microfluidic chip to form a miniaturized system for label-free and non-contact sorting of particles or biological cells, and it may find potential applications in biomedicine.

The effect of crystal size of HMOR from micro size to 50 nm, with the apparent similar acid site density, on catalytic performance for the dimethyl ether (DME) carbonylation was investigated. The crystal size of HMOR is sensitive to the deactivation rate of DME carbonylation reaction, and the higher stability around 200 nm can be achieved. The characterization studies reveal that the diffusions of MA product play a key role during the induction and deactivation period in DME carbonylation. These will be helpful for guiding the large-scale synthesis of mordenite zeolites catalysts with high efficiencies for DME carbonylation.

Noise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exposure may vary, thereby impact outcomes of noise exposure. In this study, we investigate the consequences of noise exposure in the two commonly used animal models in hearing research, CBA/CaJ (CBA) and C57BL/6J (B6) mice, focusing on the functional changes of cochlear IHCs. In the CBA mice, moderate noise exposure resulted in a typical fully recovered audiometric threshold but a reduced wave I amplitude of auditory brainstem responses. In contrast, both auditory brainstem response threshold and wave I amplitude fully recovered in B6 mice at 2 weeks after noise exposure. Confocal microscopy observations found that ribbon synapses of IHCs recovered in B6 mice but not in CBA mice. To further characterize the molecular mechanism underlying these different phenotypes in synaptopathy, we compared the ratio of Bax/Bcl-2 with the expression of cytochrome-C and found increased activity in CBA mice after noise exposure. Under whole-cell patch clamped IHCs, we acquired two-photon calcium imaging around the active zone to evaluate the Ca2+ clearance rate and found that CBA mice have a slower calcium clearance rate. Our results indicated that excessive accumulation of calcium due to acoustic overexposure and slow clearance around the presynaptic ribbon might lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of IHCs that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice.

Pedestrians are vulnerable road users that need proactive protection. While both autonomous and connected vehicle technologies aim to deliver greater safety benefits, current designs heavily rely on vehicle-based or on-board sensors and lack strategic real-time interactions with pedestrians who do not have any communication means. As pedestrians are passively protected by the system, they might be put into hazardous situations when vehicle-mounted sensors fail to detect their presence. This paper is part of ongoing research that uses roadside light detection and ranging (LiDAR) sensors to develop a human-in-the-loop system that brings pedestrians into the connected environment. To proactively protect pedestrians, accurate prediction of their intention for crossings at locations, such as unsignalized intersections and street mid-blocks is critical, and this paper presents a modified Naïve Bayes approach for this purpose. It features a probabilistic approach to overcoming the common deficiencies in deterministic methods and provides valuable comparisons between feature-based data processing methods, such as artificial neural network (ANN) and model-based Naïve Bayes approach. A case study was conducted by using a low-cost 16-line LiDAR sensor installed at the roadside. Pedestrians' crossing intention was predicted at a range of 0.5-3 s before actual crossings. The results satisfactorily demonstrated the properties of the modified Naïve Bayes model, as well as its higher flexibility, compared with the ANN approaches in practice.

Distributional Semantic Models (DSMs) established themselves as a standard for the representation of word and sentence meaning. However, DSMs provide quantitative measurement of how strongly two linguistic expressions are related, without being able to automatically classify different semantic relations. Hence the notion of semantic similarity is underspecified in DSMs. We introduce Evalution-MAN in this paper as an effort to address this underspecification problem. Following the EVALution 1.0 dataset for English, we present a dataset for evaluating DSMs on the task of the identification of semantic relations in Mandarin Chinese. Moreover, we test different types of word vectors on the automatic learning of these semantic relations, and we evaluate them both in a unsupervised and in a supervised setting, finding that distributional models tend, in general, to assign higher similarity scores to synonyms and that deep learning classifiers are the best performing ones in the identification of semantic relations.

Nodal lines are 1D band crossings forming a ring in the Brillouin zone which can spawn Weyl points. Here, using a cut-wire metacrystal designed for gigahertz frequencies, Gao et al. observe photonic nodal line degeneracies as well as the photonic Weyl points arising from them.

A pulse waveform profiling algorithm is introduced for processing real-time photoplethysmography (PPG) data in mobile applications. The real PPG waveform is discriminated from artifacts based on rules of probability distribution and physiological significance. The swift background is removed through a two-step method to minimize its effect on the final waveform analysis: interpolating the midpoint of the amplitude of the PPG AC part and then interpolating the minimum of each pulse period. The pulse waveform features are extracted from the stratified PPG wave data. The implementation of the proposed algorithm in a real-time mobile application demonstrated its high efficiency and robustness with a sensitivity of around 96% and a positive specificity of 100%. The potential applications of these extracted features are discussed in terms of long-term trends in physiology such as circadian and arrhythmia real-time monitoring.

Topological effects known from condensed matter physics have recently also been explored in photonic systems. Here, the authors directly observe topological surface-state arcs in momentum space by near-field scanning the surface of a chiral hyperbolic metamaterial.

Origin-destination- (O-D-) based travel time reliability (TTR) is fundamental to next-generation navigation tools aiming to provide both travel time and reliability information. While previous works are mostly focused on route-based TTR and use either ad hoc data or simulation in the analyses, this study uses open-source Uber Movement and Weather Underground data to systematically analyze the impact of rainfall intensity on O-D-based travel time reliability. The authors classified three years of travel time data in downtown Boston into one hundred origin-destination pairs and integrated them with the weather data (rain). A lognormal mixture model was applied to fit travel time distributions and calculate the buffer index. The median, trimmed mean, interquartile range, and one-way analysis of variance were used for quantification of the characteristics. The study found some results that tended to agree with the previous findings in the literature, such that, in general, rain reduces the O-D-based travel time reliability, and some seemed to be unique and worthy of discussion: firstly, although in general the reduction in travel time reliability gets larger as the intensity of rainfall increases, it appears that the change is more significant when rainfall intensity changes from light to moderate but becomes fairly marginal when it changes from normal to light or from moderate to extremely intensive; secondly, regardless of normal or rainy weather, the O-D-based travel time reliability and its consistency in different O-D pairs with similar average travel time always tend to improve along with the increase of average travel time. In addition to the technical findings, this study also contributes to the state of the art by promoting the application of real-world and publicly available data in TTR analyses.

Abstract Background Adrenomyeloneuropathy (AMN) is a rare genetic disease. In this study, a case of AMN was uncovered in a Chinese family. Methods Clinical manifestations were collected and observed through medical records, physical examination, laboratory tests, and magnetic resonance imaging (MRI). Generation sequencing of the ABCD1 gene was performed, and the pedigree of the family was analyzed. Results The proband suffered from adrenocortical insufficiency at 8 years old and presented with a slowly progressive gait disorder at 21 years old. Physical examination, laboratory tests, and MRI showed that he had adult‐onset AMN manifestations, including spasticity and hyperactive tendon reflexes with Hoffman and Babinski signs in the limbs, difficulty in performing the heel‐to‐shin test, hyperpigmentation, increased levels of adrenocorticotropic hormone and very long‐chain fatty acids, decreased levels of corticosteroid and serum gesterol, and salient atrophy of the cervical and thoracic spinal cord. DNA analysis revealed a missense variant, c.290A>C (p.His97Pro) in exon 1 of the ABCD1 gene, in the proband. Sanger sequencing confirmed that the proband's mother was heterozygous for the same variant. The ABCD1 gene mutation transmitted in an X‐linked inheritance manner. Conclusion A novel missense mutation in the ABCD1 gene was identified in a Chinese family, which caused an unusual manifestation of adult‐onset AMN. This discovery is beneficial for the genetic counseling of patients with X‐linked adrenoleukodystrophy.

Crashes among young and inexperienced drives are a major safety problem in the United States, especially in an area with large rural road networks, such as West Texas. Rural roads present many unique safety concerns that are not fully explored. This study presents a complete machine leaning pipeline to find the patterns of crashes involved with teen drivers no older than 20 on rural roads in West Texas, identify factors that affect injury levels, and build four machine learning predictive models on crash severity. The analysis indicates that the major causes of teen driver crashes in West Texas are teen drivers who failed to control speed or travel at an unsafe speed when they merged from rural roads to highways or approached intersections. They also failed to yield on the undivided roads with four or more lanes, leading to serious injuries. Road class, speed limit, and the first harmful event are the top three factors affecting crash severity. The predictive machine learning model, based on Label Encoder and XGBoost, seems the best option when considering both accuracy and computational cost. The results of this work should be useful to improve rural teen driver traffic safety in West Texas and other rural areas with similar issues.

Materials with topologically non-trivial band structures promise applications exploiting exotic electronic transport behaviour. Here, the authors observe a large negative magnetoresistance in Cd3As2nanoribbons, evidence for a chiral transport anomaly required for its status as a Dirac semi metal.

The graft copolymer with semi-interpenetrating polymer networks (semi-IPNs) from 2-hydroxyethyl methacrylate (HEMA) and natural rubber (NR) latex was prepared using cumene hydroperoxide and tetraethylene pentamine redox initiator system. The changes of grafting ratios and grafting efficiency with the reaction time and temperature, the concentration of crosslinking agent, initiator and monomer were investigated. The appropriate amounts of crosslinking agent (0.1phr), initiator (0.2phr) and monomer (20phr) and the optimum reaction conditions of 16ºC×8h were determined. The swelling temperature and times of monomers against NR latex particles were found to be significant for the grafting copolymerization and the appropriate swelling conditions were 16ºC×20h. The water contact angle measurement and platelet adhesion evaluation indicated that the hydrophilicity and blood compatibility of NR latex could be improved by grafting copolymerization with HEMA.

Evacuation planning involves modeling, operation, and management of evacuation routes before and during emergency evacuation. This paper presents the development and examination of a route optimization model which considers the operational cost as a constraint. The study is focused on the situation when the backbone evacuation route, usually the interstate highway system, is over congested and some traffic need to be directed to local street networks. As intersections are the key control components of a street network, traffic operations at intersections cannot be neglected in route selection. In order to consider the operational cost in the modeling process, a street network is first presented by an extended graph network which has cost information associated with each node. Then, a system optimal traffic assignment approach is used to select and optimize the evacuation routes. The property of the approach is examined by a numerical test which includes a network composed of a backbone interstate highway and a grid network with over 30 intersections.

Traffic congestion is a significant problem in many major cities. Getting stuck in traffic, the mileage per unit time that a taxicab travels will decline significantly. Congestion premium (or so-called low-speed fare) has become an increasingly important income source for taxi drivers. However, the impact of congestion premium on the taxicab market is not widely understood yet. In particular, modeling and analyzing of the taxi fare structure with congestion premium are extremely limited. In this paper, we developed a taxi price equilibrium model, in which the adjustment mechanism of congestion premium on optimizing the taxi driver’s income, balancing the supply and demand, and eventually improving the level of service in the whole taxicab market was investigated. In the final part, we provided a case study to demonstrate the feasibility of the proposed model. The results indicated that the current taxi fare scheme in Beijing is suboptimal, since the gain from the raise of congestion premium cannot compensate for the loss from the demand reduction. Conversely, the optimal fare scheme suggested by our model can effectively reduce the excessive demand and reach the supply-demand equilibrium, while keeping the stability of the driver’s income to the maximum extent.

Autosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration.To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥ 30 ml/min/1.73 m(2). Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI). Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). A linear regression model was developed to analyze the factors which determine eGFR and TKV changes.The age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3 ± 10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline log10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (r = 0.222) and higher TKV (r = 0.134).This large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression.