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BackgroundThe causal relationship between cathepsins and neurological diseases remains uncertain. To address this, we utilized a two-sample Mendelian randomization (MR) approach to assess the potential causal effect of cathepsins on the development of neurological diseases.MethodsThis study conducted a two-sample two-way MR study using pooled data from published genome-wide association studies to evaluate the relationship between 10 cathepsins (B, D, E, F, G, H, L2, O, S, and Z) and 7 neurological diseases, which included ischemic stroke, cerebral hemorrhage, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and epilepsy. The analysis employed various methods such as inverse variance weighting (IVW), weighted median, MR Egger regression, MR pleiotropy residual sum and outlier, Cochran Q statistic, and leave-one-out analysis.ResultsWe found a causal relationship between cathepsins and neurological diseases, including Cathepsin B and Parkinson’s disease (IVW odds ratio (OR): 0.89, 95% confidence interval (CI): 0.83, 0.95, p = 0.001); Cathepsin D and Parkinson’s disease (OR: 0.80, 95%CI: 0.68, 0.95, p = 0.012); Cathepsin E and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.09, p = 0.015); Cathepsin O and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.021). Reverse MR analyses revealed that multiple sclerosis and Cathepsin E (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.030). There is currently no significant relationship has been found between other cathepsins and neurological diseases.ConclusionOur study reveals a causal relationship between Cathepsins B, D, E, and O and neurological diseases, offering valuable insights for research aimed at improving the diagnosis and treatment of such conditions.

BackgroundThe global prevalence of stroke has been increasing. Motor dysfunction is observed in approximately 55 to 75% of stroke patients, with upper limb impairment affecting around 85% of them. Following upper limb dysfunction, the body’s recovery time is not only slower compared to the lower limbs, but the restoration of its fine motor skills is significantly more challenging, greatly impacting the daily lives of patients. Consequently, there is an increasing urgency for study on the upper limb function in stroke.MethodsA search was conducted in the Web of Science Core Collection: Science Citation Index Expanded (SCI-Expanded) database for material published from January 1, 2004 to December 31, 2023. We included all relevant literature reports and conducted an analysis of annual publications, countries/regions, institutions, journals, co-cited references, and keywords using the software packages CiteSpace, VOSviewer, and Bibliometrix R. Next, we succinctly outlined the research trends and hotspots in post-stroke upper limb dysfunction.ResultsThis analysis comprised 1,938 articles from 1,897 institutions, 354 journals, and 53 countries or regions. A yearly rise in the production of publications was noted. The United States is the foremost nation on the issue. Northwestern University has the most amounts of papers compared to all other institutions. The journal Neurorehabilitation and Neural Repair is a highly significant publication in this field, with Catherine E. Lang serving as the principal author. The majority of the most-cited references focus on subjects such as the reliability and validity of assessment instruments, RCT of therapies, systematic reviews, and meta-analyses. The intervention measures primarily comprise three types of high-frequency phrases that are related, as determined by keyword analysis: intelligent rehabilitation, physical factor therapy, and occupational therapy. Current areas of focus in research include randomized clinical trials, neurorehabilitation, and robot-assisted therapy.ConclusionCurrent research has shown a growing interest in studying upper limb function assessment, occupational therapy, physical therapy, robot-assisted therapy, virtual reality, brain-computer interface, telerehabilitation, cortical reorganisation, and neural plasticity. These topics have become popular and are expected to be the focus of future research.

The study aims to explore whether internationalization by state-owned enterprises is a curse or blessing in the context of aspirant industrial economies, such as China. What do state-owned enterprises' global production aspirations, such as outward foreign direct investment, bring into their home country? To answer this question, this study proposes a unique, co-evolutionary perspective of the state-driven industrialized economy by leveraging insights from economic discoveries such as Adam Smith's wealth of nations, David Ricardo's comparative advantage, and Michael Porter's competitive advantage. This view suggests that an outward foreign investment strategy may likely provide state-owned enterprises with access to resources and advanced production technologies, enhance innovation capabilities, gain more competitive advantage, and achieve superior performance, thus leading to spillover effects on their home country's wealth, comparative advantage, and competitiveness. This study discusses China's grand policies, economic performance, and successful cross-border industrial acquisitions.

Accurate diabetic retinopathy (DR) grading is crucial for making the proper treatment plan to reduce the damage caused by vision loss. This task is challenging due to the fact that the DR related lesions are often small and subtle in visual differences and intra-class variations. Moreover, relationships between the lesions and the DR levels are complicated. Although many deep learning (DL) DR grading systems have been developed with some success, there are still rooms for grading accuracy improvement. A common issue is that not much medical knowledge was used in these DL DR grading systems. As a result, the grading results are not properly interpreted by ophthalmologists, thus hinder the potential for practical applications. This paper proposes a novel fine-grained attention & knowledge-based collaborative network (FA+KC-Net) to address this concern. The fine-grained attention network dynamically divides the extracted feature maps into smaller patches and effectively captures small image features that are meaningful in the sense of its training from large amount of retinopathy fundus images. The knowledge-based collaborative network extracts a-priori medical knowledge features, i.e., lesions such as the microaneurysms (MAs), soft exudates (SEs), hard exudates (EXs), and hemorrhages (HEs). Finally, decision rules are developed to fuse the DR grading results from the fine-grained network and the knowledge-based collaborative network to make the final grading. Extensive experiments are carried out on four widely-used datasets, the DDR, Messidor, APTOS, and EyePACS to evaluate the efficacy of our method and compare with other state-of-the-art (SOTA) DL models. Simulation results show that proposed FA+KC-Net is accurate and stable, achieves the best performances on the DDR, Messidor, and APTOS datasets.

Background: Inflammation has a significant role in the onset and progression of inflammatory bowel disease (IBD). Increasing attention has been paid to the use of acupuncture in IBD patients; however, its regulatory effects on inflammatory factors in IBD still require validation. Here, we systematically evaluated the effects of acupuncture on inflammatory factors in IBD patients. Methods: Eight electronic databases were searched for studies that met the inclusion criteria. After evaluating the quality of the studies selected by two reviewers, the meta-analysis was performed to assess the efficacy of acupuncture in IBD patients and the impact on inflammatory factors (TNF-α, IL-1, IL-8 and IL-10). Results: Four randomized controlled trials with a total of 228 patients satisfied the inclusion criteria. Acupuncture has a positive therapeutic impact on IBD (MD = 1.22, 95% CI [1.07, 1.39], P = 0.003). Moreover, it regulates the levels of TNF-α (MD =−60.58, 95% CI [−100.30, −20.89], P = 0.003), IL-8 (MD =−56.40, 95% CI [−60.02, −52.14], P

Ecosystem water use efficiency (WUEe) is a key metric of the coupled carbon and water cycles. Understanding WUEe variations along the climate gradient (arid to humid) and across different vegetation ecosystems is crucial for assessing the impacts of climate variability on these ecosystems. Based on the Penman-Monteith-Leuning version 2 (PML-V2) dataset from a coupled diagnostic biophysical model, this study investigated the spatiotemporal variations and driving factors of WUEe under different aridity conditions and across vegetation types in China from 2001 to 2020. The results showed that the annual mean WUEe was 1.36 ± 0.07 g C kg−1 H2O in China, and humid regions had higher WUEe than other arid regions except for the extremely arid regions (the top level of aridity classification). Annual WUEe showed an increasing trend of 0.084 g C kg−1 H2O/10a in China, which mainly occurred in humid areas. The forest ecosystem had the highest WUEe (2.48 g C kg−1 H2O), followed by shrubland (2.11 g C kg−1 H2O) and cropland (1.99 g C kg−1 H2O) ecosystems. Leaf Area Index (LAI) and vapor pressure deficit (VPD) contributed the most to increases in WUEe, which accounted for areal proportions of 63.82% and 77.36% of China, and average relative contributions of 31.80% and 14.73%, respectively. In contrast, air temperature (TEM) contributed the most to WUEe decreases, with an areal proportion of 61.73% and an average relative contribution of 12.42%. Normalized Difference Vegetation Index (NDVI), precipitation (PRE) and downward short-wave radiation (SSRD) showed little differences in the proportions of land area where they either promoted and suppressed WUEe and their respective relative contributions were 16.99%, 14.32% and 8.61%.

Flowering time is strongly related to the environment, while the genotype-by-environment interaction study for flowering time is lacking in Brassica napus. Here, a total of 11,700,689 single nucleotide polymorphisms in 490 B. napus accessions were used to associate with the flowering time and related climatic index in eight environments using a compressed variance-component mixed model, 3VmrMLM. As a result, 19 stable main-effect quantitative trait nucleotides (QTNs) and 32 QTN-by-environment interactions (QEIs) for flowering time were detected. Four windows of daily average temperature and precipitation were found to be climatic factors highly correlated with flowering time. Ten main-effect QTNs were found to be associated with these flowering-time-related climatic indexes. Using differentially expressed gene (DEG) analysis in semi-winter and spring oilseed rapes, 5,850 and 5,511 DEGs were found to be significantly expressed before and after vernalization. Twelve and 14 DEGs, including 7 and 9 known homologs in Arabidopsis, were found to be candidate genes for stable QTNs and QEIs for flowering time, respectively. Five DEGs were found to be candidate genes for main-effect QTNs for flowering-time-related climatic index. These candidate genes, such as BnaFLCs, BnaFTs, BnaA02.VIN3, and BnaC09.PRR7, were further validated by the haplotype, selective sweep, and co-expression networks analysis. The candidate genes identified in this study will be helpful to breed B. napus varieties adapted to particular environments with optimized flowering time.

Although the clinical application of nanoparticles is still limited by biological barriers and distribution, with the deepening of our understanding of nanoparticles over the past decades, people are gradually breaking through the previous limitations in the diagnosis and treatment of tumors, providing novel strategies for clinical decision makers. The transition of nanoparticles from passive targeting to active tumor-targeting by abundant surface-modified nanoparticles is also a development process of precision cancer treatment. Different particles can be used as targeted delivery tools of antitumor drugs. The mechanism of gold nanoparticles inducing apoptosis and cycle arrest of tumor cells has been discovered. Moreover, the unique photothermal effect of gold nanoparticles may be widely used in tumor therapy in the future, with less side effects on surrounding tissues. Lipid-based nanoparticles are expected to overcome the blood–brain barrier due to their special characteristics, while polymer-based nanoparticles show better biocompatibility and lower toxicity. In this paper, we discuss the development of nanoparticles in tumor therapy and the challenges that need to be addressed.

The evaporation of intercepted precipitation (Ei) is an important component of evapotranspiration. Investigating the spatial and temporal variations of Ei and its driving factors can improve our understanding of water and energy balance in the context of China’s greening. This study investigated the spatial and temporal variation of Ei across China during 2001−2020 using PML ET product with a temporal resolution of 8 days and a spatial resolution of 500 m. The results showed that Ei generally decreased from southeast to northwest, which was contributed by the coupled effect of precipitation and vegetation coverage variation across China. Generally, Ei showed an increasing trend over the last two decades with an average changing rate of 0.45 mm/year. The changing rate varied greatly among different regions, with the most obvious change occurring in tropical and humid regions. Precipitation was the most important climatic factor driving the interannual change of Ei over the past two decades, with an average contribution rate of 30.18~37.59%. Relative humidity was the second most important climatic factor following precipitation. Temperature showed contracting contribution in different thermal regions. The contribution rates of NDVI and LAI followed a similar spatial pattern. Both the contribution rates of NDVI and LAI generally increased along the moisture gradient from east to west and generally increased from south to north.

OBJECTIVES:To better guide clinicians to choose the appropriate chairside system, we compared and evaluated the morphology of crowns generated by three different biogeneric design modes (biogeneric copy (BC), biogeneric individual (BI), and biogeneric reference (BR)) of the CEREC software. METHODS:Maxillary and mandibular casts were obtained from twelve volunteers and digital impressions were acquired. All ceramic crown preparations of all right maxillary central incisors were prepared and digital impressions were taken. Then, crowns were automatically designed under BC, BI and BR modes separately and their morphologies were evaluated by six doctors. The "optimal fitting alignment" and "3D analysis" functions of the Geomagic Qualify software were carried out between original teeth and auto-generated full crowns. The auto-generated crowns were modified by a technician according to clinical criteria and the adjustment time was recorded. The discrepancies between technician modified crowns and the auto-generated full crowns were evaluated with the same functions in the Geomagic Qualify software. RESULTS:The subjective evaluation results of BC group were significantly better than those of BI and BR group (p < 0.05). Compared with the original teeth and modified crowns, auto-generated crowns in BC group all had the smallest differences, followed by BR and BI group (p < 0.05). BC group needed the shortest adjustment time than BI and BR group (p < 0.05). CONCLUSIONS:Using crowns generated by BC mode is more aesthetic and suitable in clinics use than those generated by BI and BR modes and can reduce clinic adjustment time.

A novel exponential varying-parameter neural network (EVPNN) is presented and investigated to solve the inverse redundancy scheme of the mobile manipulators via quadratic programming (QP). To suspend the phenomenon of drifting free joints and guarantee high convergent precision of the end effector, the EVPNN model is applied to trajectory planning of mobile manipulators. Firstly, the repetitive motion scheme for mobile manipulators is formulated into a QP index. Secondly, the QP index is transformed into a time-varying matrix equation. Finally, the proposed EVPNN method is used to solve the QP index via the matrix equation. Theoretical analysis and simulations illustrate that the EVPNN solver has an exponential convergent speed and strong robustness in mobile manipulator applications. Comparative simulation results demonstrate that the EVPNN possesses a superior convergent rate and accuracy than the traditional ZNN solver in repetitive trajectory planning with a mobile manipulator.

Existing spectrum auction algorithms rarely consider the collusion-resistant, which decreases the spectrum allocation efficiency. In this paper, we propose a collusion-resistant spectrum auction algorithm based on K-Nearest Neighbor (KNN) learning in small cell networks. The algorithm can satisfy the increasing requirements of broadband services, improve the utilization of spectrum and also enhance the power-transmitting efficiency in small cells. Considering the interference among small cells, the KNN algorithm is used to classify all the small cells according to the small cells' geographic locations and interference radius, which can improve the collusion-resistance ability of spectrum auction and improve the spectrum allocation efficiency. Simulation results are presented to verify the effectiveness of the proposed algorithm.

The dynamics of the mid-channel bars (MCBs) in the Three Gorges Reservoir (TGR) were substantially impacted by the large water-level changes due to the impoundments of the TGR. However, it is still not clear how the morphology of the MCBs changed under the influence of water level and hydrological regime changes induced by the impoundments and operation of the TGR. In this work, the MCBs in the TGR were retrieved using Landsat remote sensing images from 1989 to 2019, and the spatio-temporal variations in the number, area, morphology and location of the MCBs during different impoundment periods were investigated. The results showed that the number and area of MCBs changed dramatically with water-level changes, and the changes were dominated by MCBs with an area less than 0.03 km2 and larger than 1 km2. The area of MCBs decreased progressively with the rising water level, and the number generally showed a decreasing trend, with the minimum number occurring at the third stage when the water level reached 139 m, resulting in the maximum average area at this period. The ratio of length to width of the MCBs generally decreased with the changes in hydrological and sediment regimes, leading to a shape adjustment from narrow–long to relatively short–round with the rising of the water level. The water impoundments of the TGR led to the migration of the dominant area from the upper section to the middle section of the TGR and resulted in a more even distribution of MCBs in the TGR. The results improve our understanding of the mechanisms of the development of MCBs in the TGR under the influence of water impoundment coupled with the annually cyclic hydrological regime and longer periods of inundation and exposure.

Highland barley is the unique germplasm resource and dominant crop in Tibet with low-level precipitation and a severe shortage of available water resources. Understanding the characteristics and dynamics of evapotranspiration (ET) components (vegetation transpiration (Ec), soil evaporation (Es), and canopy interception evaporation (Ei)) of highland barley can help better optimize water management practices. The seasonal and interannual variations in ET components of highland barley were investigated using the PML-V2 ET product during 2001–2020. The results suggested that Es was the most important ET component and accounted for 77% of total ET for highland barley in Tibet. ET components varied obviously over the altitude, Es, and Es/ET ratio; a decreasing trend was observed with the increase in altitude from 3500 m to 3800 m and then this changed to an increasing trend until reaching the altitude of 4100 m, while Ec, Ei, and their ratios presented an opposite changing pattern to that of Es. Seasonal variation in daily ET components of highland barley displayed a parabolic pattern, peaked in August, while the temporal distributions differed considerably among different ET component ratios. The seasonal variations in ET components were correlated significantly with air temperature, relative humidity, and precipitation, while ET components ratios were more influenced by the environment, irrigation practice, and management rather than meteorological variables. Es and its ratio in highland barley decreased significantly during 2001–2020, while the Ec/ET ratio generally showed an opposite trend to the Es/ET ratio, and Ei and its ratio presented an insignificantly decreasing trend. The interannual variations in ET components were not correlated significantly with meteorological variables, while Ei was more influenced by meteorological variables, especially the precipitation characteristics.

Identifying the spatiotemporal variations and influencing climate factors of evapotranspiration (ET) and its components (vegetation transpiration (Ec), soil evaporation (Es), and canopy interception evaporation (Ei)) can greatly improve our understanding of water cycle, carbon cycle, and biogeochemical processes in a warming climate. As the world′s largest hydropower project, the construction of the Three Gorges Project (TGP) coupled with the significant land use/land cover change affected the regional water and energy exchange in the Three Gorges Reservoir Area (TGRA). This study aimed to reveal the spatiotemporal variations and influencing climate factors in ET and its components using PML-V2 products in TGRA during 2000–2020. Results showed that the mean annual ET, Ec, Es, and Ei in TGRA were 585.12, 328.49, 173.07, and 83.56 mm, respectively. The temporal variation of ET was dominated by Ec, with no significant change in the time trend. Es decreased (2.92 mm/y) and Ei increased (1.66 mm/y) significantly mainly in the cultivated land. ET, Ec, and Ei showed a similar seasonal variation pattern with a single peak, while Es presented a bimodal pattern. From the pre-impoundment to the first impoundment period, ET and Ec mainly increased in the head of TGRA, meanwhile, Es in urban area increased significantly by 27.8%. In the subsequent impoundment periods, ET and Ec changed slightly while Es sharply decreased. The Ei increased persistently during different impoundment period. The dominant climate factors affecting changes in Ec and Es were air temperature, vapor pressure deficit, and sunshine hours, while the variation of Ei was mainly affected by air temperature, vapor pressure deficit, and precipitation.

This study was conducted in order to investigate when low-calcium fly ash plays a physical or chemical effect and what is the chemical effect proportion of low-calcium fly ash. Two types of low-calcium fly ash and quartz powder, with similar fineness as active and inert admixtures, were used as materials in this study. Under different water/binder ratios and hydration ages, the effects of the different types of admixtures and their dosages on the flexural and compressive strength of the composites were studied. X-ray diffraction (XRD), scanning electron microscopy (SEM) and nitrogen adsorption methods, in addition to an assessment of the degree of hydration of the fly ash, were employed to observe the hydration products at different ages, the microstructures of the hydration products, as well as their surface areas and pore size distributions. The results show that during the hydration period of 28 days, the low-calcium fly ash has a micro-aggregate filling physical effect. However, after 56 days, the hydration degree of fly ash begins to exceed 1%. This illustrates that the low-calcium fly ash has both the pozzolanic activity effect and micro-aggregate filling effect. In contrast, the low-calcium fly ash hydrated for 90 days is still dominated by the physical filling effect.

The study aims to explore whether internationalization by state-owned enterprises is a curse or blessing in the context of aspirant industrial economies, such as China. What do state-owned enterprises' global production aspirations, such as outward foreign direct investment, bring into their home country? To answer this question, this study proposes a unique, co-evolutionary perspective of the state-driven industrialized economy by leveraging insights from economic discoveries such as Adam Smith's wealth of nations, David Ricardo's comparative advantage, and Michael Porter's competitive advantage. This view suggests that an outward foreign investment strategy may likely provide state-owned enterprises with access to resources and advanced production technologies, enhance innovation capabilities, gain more competitive advantage, and achieve superior performance, thus leading to spillover effects on their home country's wealth, comparative advantage, and competitiveness. This study discusses China's grand policies, economic performance, and successful cross-border industrial acquisitions. [ABSTRACT FROM AUTHOR]