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Abstract Achieving the United Nations’ Sustainable Development Goals (SDGs) requires an overall and well-balanced achievement of all SDGs rather than cherry-picking a few. While it is vital to assess the evenness of SDGs achievement, such analysis, particularly on a global scale, is still evidently absent from the existing literature. To remedy such a scholarly gap, this paper measures the evenness of SDGs achievement for 193 countries from 2010 to 2019 by adapting the evenness assessment method originating from ecology and biodiversity literature. Our analyses regarding the country-level SDG evenness index scores (EIS) indicate a significant heterogeneity across countries. Global South countries usually underperform in the evenness of 17 goals, while a significant portion of Global North countries also suffer from the unbalanced developments in SDGs. By integrating the evenness measures into the conventional global SDG monitoring framework, this study identifies six development paths in pursuing the SDGs and shows that maintaining the overall SDGs improvements while balancing the development of each goal is practical but has not taken place in at least 35% of countries. We estimate that the SDG evenness and average performance could further increase by 3.5 p.p. and 2.1 p.p., or 74 percent and 50 percent of the growth in the baseline continue past paths scenario, respectively, if each country could follow the effective development path of frontier counterparts with similar income levels. Our SDG evenness measures, complemented by inter-temporal cross-country analyses, could inform policies and cooperation strategies to identify the weaknesses in sustainable development, boost effective growth, and protect unevenly developed countries. Future research could further develop these measures to provide deeper insights into achieving rapid and well-balanced development of SDGs at various levels.

Abstract Oncolytic viruses (OVs) have emerged as a powerful tool in cancer therapy. Characterized with the unique abilities to selectively target and lyse tumor cells, OVs can expedite the induction of cell death, thereby facilitating effective tumor eradication. Nanoengineering‐derived OVs overcome traditional OV therapy limitations by enhancing the stability of viral circulation, and tumor targeting, promising improved clinical safety and efficacy and so on. This review provides a comprehensive analysis of the multifaceted mechanisms through which engineered OVs can suppress tumor progression. It initiates with a concise delineation on the fundamental attributes of existing OVs, followed by the exploration of their mechanisms of the antitumor response. Amid rapid advancements in nanomedicine, this review presents an extensive overview of the latest developments in the synergy between nanomaterials, nanotechnologies, and OVs, highlighting the unique characteristics and properties of the nanomaterials employed and their potential to spur innovation in novel virus design. Additionally, it delves into the current challenges in this emerging field and proposes strategies to overcome these obstacles, aiming to spur innovation in the design and application of next‐generation OVs.

Abstract Turbo product codes (TPCs) have been widely used for bit error correction in high‐speed applications such as data storage. This letter introduces an efficient hard‐input hard‐output iterating TPC decoder module. A transpose memory utilizing static random access memory (SRAM) is integrated into the decoder to achieve a low hardware overhead. The transpose memory, based on an 8T SRAM bit‐cell, supports both horizontal (row‐wise), and vertical (column‐wise) read/write operations. It is prototyped under a 28nm high‐k/metal gate stack process with bit‐cell size of 0.582 µm2. This specialized SRAM significantly reduces the hardware overhead when compared with a register‐array‐based transpose memory without significant throughput loss. A field programmable gate array (FPGA) evaluation platform is utilized to emulate the TPC decoder module, and the maximum decoder throughput is up to 6.49 Gbps at 250 MHz.

As an essential crop that provides vegetable oil and protein, soybean (Glycine max (L.) Merr.) is widely planted all over the world. However, the scarcity of water resources worldwide has seriously impacted on the quality and yield of soybean. To address this, exploring excellent genes for improving drought resistance in soybean is crucial. In this study, we identified natural variations of GmFNSII-2 (flavone synthase II) significantly affect the drought resistance of soybeans. Through sequence analysis of GmFNSII-2 in 632 cultivated and 44 wild soybeans nine haplotypes were identified. The full-length allele GmFNSII-2C, but not the truncated allele GmFNSII-2A possessing a nonsense nucleotide variation, increased enzyme activity. Further research found that GmDREB3, known to increase soybean drought resistance, bound to the promoter region of GmFNSII-2C. GmDREB3 positively regulated the expression of GmFNSII-2C, increased flavone synthase abundance and improved the drought resistance. Furthermore, a single-base mutation in the GmFNSII-2C promoter generated an additional drought response element (CCCCT), which had stronger interaction strength with GmDREB3 and increased its transcriptional activity under drought conditions. The frequency of drought-resistant soybean varieties with Hap 1 (Pro:GmFNSII-2C) has increased, suggesting that this haplotype may be selected during soybean breeding. In summary, GmFNSII-2C could be used for molecular breeding of drought-tolerant soybean.

Abstract Peripheral nerve deficits give rise to motor and sensory impairments within the limb. The clinical restoration of extensive segmental nerve defects through autologous nerve transplantation often encounters challenges such as axonal mismatch and suboptimal functional recovery. These issues may stem from the limited regenerative capacity of proximal axons and the subsequent Wallerian degeneration of distal axons. To achieve the integration of sensory and motor functions, a spatially differential plasmid DNA (pDNA) dual‐delivery nanohydrogel conduit scaffold is devised. This innovative scaffold facilitates the localized administration of the transforming growth factor β (TGF‐β) gene in the proximal region to accelerate nerve regeneration, while simultaneously delivering nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) to the distal region to mitigate Wallerian degeneration. By promoting autonomous and selective alignment of nerve fiber gap sutures via structure design, the approach aims to achieve a harmonious unification of nerve regeneration, neuromotor function, and sensory recovery. It is anticipated that this groundbreaking technology will establish a robust platform for gene delivery in tissue engineering.

Abstract Cities are at the heart of climate change mitigation as they account for over 70% of global carbon emissions. However, cities vary in their energy systems and socioeconomic capacities to transition to renewable energy. To address this heterogeneity, this study proposes an Energy Transition Index (ETI) specifically designed for cities, and applies it to track the progress of energy transition in Chinese cities. The city-level ETI framework is based on the national ETI developed by the World Economic Forum (WEF) and comprises two sub-indexes: the Energy System Performance sub-index, which evaluates the current status of cities’ energy systems in terms of energy transition, and the Transition Readiness sub-index, which assesses their socioeconomic capacity for future energy transition. The initial version of the dataset includes ETI and its sub-indexes for 282 Chinese cities from 2003 to 2019, with annual updates planned. The spatiotemporal data provided by the dataset facilitates research into the energy transition roadmap for different cities, which can help China achieve its energy transition goals.

Approximately 71% of the Earth’s surface is covered by vast oceans. With the exacerbation of global climate change, high-precision monitoring of sea surface height variations is of vital importance for constructing global ocean gravity fields and preventing natural disasters in the marine system. Global Navigation Satellite System Interferometry Reflectometry (GNSS-IR) sea surface altimetry is a method of inferring sea surface height based on the signal-to-noise ratio of satellite signals. It enables the retrieval of sea surface height variations with high precision. However, navigation satellite signals are influenced by the ionosphere during propagation, leading to deviations in the measured values of satellite elevation angles from their true values, which significantly affects the accuracy of GNSS-IR sea surface altimetry. Based on this, the contents of this paper are as follows: Firstly, a new ionospheric stratified elevation angle correction model (ISEACM) was developed by integrating the International Reference Ionosphere Model (IRI) and ray tracing methods. This model aims to improve the accuracy of GNSS-IR sea surface altimetry by correcting the ionospheric refraction effects on satellite elevation angles. Secondly, four GNSS stations (TAR0, PTLD, GOM1, and TPW2) were selected globally, and the corrected sea surface height values obtained using ISEACM were compared with observed values from tide gauge stations. The calculated average Root Mean Square Error (RMSE) and Pearson Correlation Coefficient (PCC) were 0.20 m and 0.83, respectively, indicating the effectiveness of ISEACM in sea surface height retrieval. Thirdly, a comparative analysis was conducted between sea surface height retrieval before and after correction using ISEACM. The optimal RMSE and PCC values with tide gauge station observations were 0.15 m and 0.90, respectively, representing a 20.00% improvement in RMSE and a 4.00% improvement in correlation coefficient compared to traditional GNSS-IR retrieval heights. These experimental results demonstrate that correction with ISEACM can effectively enhance the precision of GNSS-IR sea surface altimetry, which is crucial for accurate sea surface height measurements.

Purple-fleshed sweetpotato (PFSP) (Ipomoea batatas (L.) Lam), whose flesh is purple to dark purple, is a special variety type of sweetpotato, which has the characteristics of food crop, industrial crop and medicinal crop. The storage root (SR) of PFSP is rich in anthocyanins, starch, protein, soluble sugar, mineral elements, polyphenol, dietary fiber and so on, which has balanced and comprehensive nutritional value. And in recent years, its unique nutritional elements are increasingly known for their health functions. At present, there is no article on the characteristics and quality analysis of industrial xz8 variety. To explore the influence of different environments on the processing quality of xz8, we selected nine regions (Xuzhou, Jiawang, Pizhou, Xinyi, Peixian, Sihong, Yanchen, Xiangyang and Tianshui) to measure its yield and quality changes. The data demonstrated that xz8 has a very consistent high yield performance. In Tianshui, the anthocyanins, protein and minerals contents were significantly higher and yield also above average. Moreover, the variety with the lowest starch content exhibited the best taste. On the basis of the above results, it suggested that quite practicable to promote xz8 cultivation and suitable for processing in these areas. Thus, our present findings improve our understanding of xz8 variety and provide the basis for the industrial production of PFSP with strong prospects for success.

Summary: Food plays a vital role in human sustenance and well-being, and the fluctuations in its price exert a significant impact on the attainment of the Sustainable Development Goals (SDGs) from social, economic, and environmental perspectives. This paper conducts an analysis utilizing data from 163 countries, revealing that an upsurge in global food commodity prices entails trade-offs with 13 SDGs, while exhibiting synergies with a few others. By considering specific food products, various types of countries, and the supply and demand shocks, further analysis confirms predominantly negative associations between spikes in food prices and the SDGs. Our findings highlight the urgent imperative to mitigate abrupt increases in food prices, such as those witnessed during the 2022 food crisis, to ensure the comprehensive fulfillment of the 2030 agenda for SDGs.

Rice (Oryza sativa L.) is a vital crop that feeds more than half of the world’s population. Gibberellins (GAs), a crucial phytohormone, play a significant role in the growth and development of rice. Since 1985, there has been a notable increase in the number of studies investigating the effects of GA on various biological processes in rice. Nevertheless, conducting scientific and quantitative research on the extensive literature available poses significant challenges, particularly in understanding the development trajectory of the field, examining major contributors, and identifying emerging research trends. The objective of this study is to address these challenges by analyzing global research patterns and trends using bibliometric methods from 1985 to 2024. Through the application of advanced analytical tools, progress in this field is studied in depth and the global research landscape is characterized from multiple dimensions including countries, institutions, authors, and journals. The analysis of 2118 articles extracted and screened from the Web of Science Core dataset shows a steady growth in the number of publications. The research published in China and the USA has significantly advanced the development of the field. In particular, institutions such as the Chinese Academy of Sciences and Nagoya University have shown impressive productivity. Lee In-Jung stands out as the most influential author. The journal Plant Physiology publishes the highest number of articles. The study also provides a thorough examination of current research hotspots, indicating a predominant focus on understanding the role of GAs in the biological processes that regulate diverse rice phenotypes, including plant height, seed dormancy, germination, and stress resistance. By tracing the development characteristics and key points in this area, this study contributes to a quantitative and comprehensive understanding of the impact of GAs on rice.

While mesenchymal stem cell (MSC) shows great potentials in treating intervertebral disc degeneration, most MSC die soon after intradiscal transplantation, resulting in inferior therapeutic efficacy. Currently, bulk hydrogels are the common solution to improve MSC survival in tissues, although hydrogel encapsulation impairs MSC migration and disrupts extracellular microenvironment. Cell hydrogel encapsulation has been proposed to overcome the limitation of traditional bulk hydrogels, yet this technique has not been used in treating disc degeneration. Using a layer-by-layer self-assembly technique, we fabricated alginate and gelatin microgel to encapsulate individual MSC for treating disc degeneration. The small size of microgel allowed intradiscal injection of coated MSC. We demonstrated that pyroptosis was involved in MSC death under oxidative stress stimulation, and microgel coating suppressed pyroptosis activation by maintaining mitochondria homeostasis. Microgel coating protected MSC in the harsh disc microenvironment, while retaining vital cellular functions such as migration, proliferation, and differentiation. In a rat model of disc degeneration, coated MSC exhibits prolonged retention in the disc and better efficacy of attenuating disc degeneration, as compared with bare MSC treatment alone. Further, microgel-coated MSC exhibited improved therapeutic effects in treating disc degeneration via suppressing the activation of pyroptosis in the disc. For the first time, microgel-encapsulated MSC was used to treat disc degeneration and obtain encouraging outcomes. The developed biocompatible single-cell hydrogel is an effective strategy to protect MSC and maintain cellular functions and may be an efficacious approach to improving the efficacy of MSC therapy in treating disc degeneration. The objective of this study is to improve the efficacy of cell therapy for treating disc degeneration using single-cell hydrogel encapsulation and further to understand related cytoprotective mechanisms.

Hyperspectral image classification using deep learning techniques has received great attention in recent years, considering the powerful spatial feature mining ability of deep learning. Fully convolutional network is an effective deep learning architecture that exploits spatial contextual information through a hierarchical convolutional structure. However, it often ignores the relationships between samples of the same category and different categories within the global context. Therefore, a fully convolutional spectral–spatial fusion network based on supervised contrastive learning (FCSCL) is proposed for hyperspectral image classification to enhance the separability between different categories and class aggregation among the same category. In the FCSCL framework, the spectral–spatial fusion classification network is developed to capture subtle spectral variations and spatial patterns by adaptively fusing the features extracted by the spectral branch and spatial branch. To improve intraclass compactness and interclass separability, the SCL module is integrated into the FCSCL framework. The positive and negative sample pairs are constructed by the designed hard example pairs sampling strategy. These constructed sample pairs are used to guide the network to learn more discriminative feature representations that pixels of the same category are closer to each other and pixels of different categories are pushed further apart in the feature space. The experiments using three public hyperspectral datasets verify the effectiveness of the FCSCL algorithm, and the FCSCL method achieves better classification performance.

Abstract Background This study aimed to use single-cell RNA-seq (scRNA-seq) to discover marker genes in endothelial cells (ECs) and construct a prognostic model for glioblastoma multiforme (GBM) patients in combination with traditional high-throughput RNA sequencing (bulk RNA-seq). Methods Bulk RNA-seq data was downloaded from The Cancer Genome Atlas (TCGA) and The China Glioma Genome Atlas (CGGA) databases. 10x scRNA-seq data for GBM were obtained from the Gene Expression Omnibus (GEO) database. The uniform manifold approximation and projection (UMAP) were used for downscaling and cluster identification. Key modules and differentially expressed genes (DEGs) were identified by weighted gene correlation network analysis (WGCNA). A non-negative matrix decomposition (NMF) algorithm was used to identify the different subtypes based on DEGs, and multivariate cox regression analysis to model the prognosis. Finally, differences in mutational landscape, immune cell abundance, immune checkpoint inhibitors (ICIs)-associated genes, immunotherapy effects, and enriched pathways were investigated between different risk groups. Results The analysis of scRNA-seq data from eight samples revealed 13 clusters and four cell types. After applying Fisher’s exact test, ECs were identified as the most important cell type. The NMF algorithm identified two clusters with different prognostic and immunological features based on DEGs. We finally built a prognostic model based on the expression levels of four key genes. Higher risk scores were significantly associated with poorer survival outcomes, low mutation rates in IDH genes, and upregulation of immune checkpoints such as PD-L1 and CD276. Conclusion We built and validated a 4-gene signature for GBM using 10 scRNA-seq and bulk RNA-seq data in this work.

Diabetic nephropathy (DN) is a major healthcare challenge worldwide. MiRNAs exert a regulatory effect on the progress of DN. Our study proposed to investigate the miR-320c expression and its function on the pathogenesis of DN in vitro. The level of miR-320c in HK-2 cells was quantified by RT-qPCR. Cell morphology, invasion, and migration were observed by optical microscope, Transwell invasion assay, and scratch wound assay. Then, the levels of PTEN, α-SMA, vimentin, E-cadherin, p-PI3K, PI3K, AKT, and p-AKT were analyzed through western blotting. A Dual-luciferase reporter assay was conducted to explore the target relationship between miR-320c and PTEN. It was discovered that miR-320c was over-expressed in high glucose (HG)-treated HK-2 cells. Furthermore, inhibition of miR-320c could alleviate the epithelial-mesenchymal transition (EMT) of HG-induced HK-2 cells and retain the normal morphology of HK-2 cells. Additionally, the miR-320c inhibitor decreased the invasiveness and migration of HG-treated HK-2 cells. Next, the target gene of miR-320c, PTEN, was identified, and the function of miR-320c was reversed by down-regulation of PTEN. Finally, we found inhibition of miR-320c restrained the PI3K/AKT pathway. Therefore, inhibition of miR-320c could alleviate toxicity of HK-2 cells induced by HG via targeting PTEN and restraining the PI3K/AKT pathway, illustrating that miR-320c may act as a new biomarker in the diagnosis of DN.

Flavonol synthase (FLS) is a key enzyme of the flavonoid biosynthetic pathway, which catalyzes the conversion of dihydroflavonols into flavonols. In this study, the FLS gene IbFLS1 was cloned and characterized from sweet potato. The resulting IbFLS1 protein showed a high similarity with other plant FLSs. The conserved amino acids (HxDxnH motifs) binding ferrous iron and residues (RxS motifs) binding 2-oxoglutarate were found in IbFLS1 at conserved positions, as in other FLSs, suggesting that IbFLS1 belongs to the 2-oxoglutarate-dependent dioxygenases (2-ODD) superfamily. qRT-PCR analysis showed an organ-specific pattern of expression of the IbFLS1 gene, which was predominantly expressed in young leaves. The recombinant IbFLS1 protein could catalyze the conversion of dihydrokaempferol and dihydroquercetin to kaempferol and quercetin, respectively. The results of subcellular localization studies indicated that IbFLS1 was found mainly in the nucleus and cytomembrane. Furthermore, silencing the IbFLS gene in sweet potato changed the color of the leaves to purple, substantially inhibiting the expression of IbFLS1 and upregulating the expression of genes involved in the downstream pathway of anthocyanin biosynthesis (i.e., DFR, ANS, and UFGT). The total anthocyanin content in the leaves of the transgenic plants was dramatically increased, whereas the total flavonol content was significantly reduced. Thus, we conclude that IbFLS1 is involved in the flavonol biosynthetic pathway and is a potential candidate gene of color modification in sweet potato.

Porosity is considered to be one of the key factors affecting the structural properties of porous lattices, but in fact, pore size also plays an important role, and it has great potential to adjust pore size and porosity independently to improve structural properties. In this work, by adjusting the sheet thickness of the triply periodic minimal surface (TPMS) lattice structures and adjusting the height of the single row structure according to linear and constant laws, the TPMS lattice structures with given porosity and adjustable pore size are designed, and the mechanical response is investigated. Based on preparing samples by Ti6Al4V laser powder bed fusion, the results of the tests show that the elastic modulus ranges of linear change TPMS (LC-TPMS) and constant TPMS (C-TPMS) lattice structures are 3625.6 MPa–4575.1 MPa and 3820.0 MPa–4509.1 MPa, respectively. In the plateau stage, the LC-TPMS lattice structures have a longer and more stable plateau stage, higher yield stress and better energy absorption capacity than the C-TPMS lattice structures. The maximum energy absorption difference is 62.7 MJ/mm3 and the maximum energy absorption efficiency difference is 0.12. The LC-TPMS lattice structures can also obtain a larger damping ratio under larger compressive strain.

Abstract Mitochondrial homeostasis is of great importance for cartilage integrity and associated with the progression of osteoarthritis (OA); however, the underlying mechanisms are unknown. This study aims to investigate the role of mitochondrial deacetylation reaction and investigate the mechanistic relationship OA development. Silent mating type information regulation 2 homolog 3 (SIRT3) expression has a negative correlation with the severity of OA in both human arthritic cartilage and mice inflammatory chondrocytes. Global SIRT3 deletion accelerates pathological phenotype in post‐traumatic OA mice, as evidenced by cartilage extracellular matrix collapse, osteophyte formation, and synovial macrophage M1 polarization. Mechanistically, SIRT3 prevents OA progression by targeting and deacetylating cytochrome c oxidase subunit 4 isoform 2 (COX4I2) to maintain mitochondrial homeostasis at the post‐translational level. The activation of SIRT3 by honokiol restores cartilage metabolic equilibrium and protects mice from the development of post‐traumatic OA. Collectively, the loss of mitochondrial SIRT3 is essential for the development of OA, whereas SIRT3‐mediated proteins deacetylation of COX4I2 rescues OA‐impaired mitochondrial respiratory chain functions to improve the OA phenotype. Herein, the induction of SIRT3 provides a novel therapeutic candidate for OA treatment.

Radioresistance is the major reason for the failure of radiotherapy in esophageal squamous cell carcinoma (ESCC). Previous evidence indicated that stanniocalcin 2 (STC2) participates in various biological processes of malignant tumors. However, researches on its effect on radioresistance in cancers are limited. In this study, STC2 was screened out by RNA-sequencing and bioinformatics analyses as a potential prognosis predictor of ESCC radiosensitivity and then was determined to facilitate radioresistance. We found that STC2 expression is increased in ESCC tissues compared to adjacent normal tissues, and a higher level of STC2 is associated with poor prognosis. Also, STC2 mRNA and protein expression levels were higher in radioresistant cells than in their parental cells. Further investigation revealed that STC2 could interact with protein methyltransferase 5 (PRMT5) and activate PRMT5, thus leading to the increased expression of symmetric dimethylation of histone H4 on Arg 3 (H4R3me2s). Mechanistically, STC2 can promote DDR through the homologous recombination and non-homologous end joining pathways by activating PRMT5. Meanwhile, STC2 can participate in SLC7A11-mediated ferroptosis in a PRMT5-dependent manner. Finally, these results were validated through in vivo experiments. These findings uncovered that STC2 might be an attractive therapeutic target to overcome ESCC radioresistance.

Livestock intensification improves production efficiency and enhances the demand for quality forage to feed ruminants. Novel combinations of forage plants, especially including Gramineae and Leguminous plants, benefit both ruminant animals and contribute to a sustainable environment. This study explored an oat-pea mixed seeding strategy as an approach to improving silage quality. Before ensialing, lactic acid bacteria (Lactobacillus plantarum and Lactobacillus brucelli) were added to forage from five different mixed seeding proportions of oats (O) and peas (P) (10:0, 8:2, 7:3, 5:5, and 0:10 oat to pea ratio) at two harvesting periods (the early flowering stage and the milk ripening stage for the oats). The results showed that mixed seeding changed the soil quality parameters. Moreover, the silage from the O5P5 (5:5 oat to pea ratio) group showed the lowest pH values (4.16) and highest LA contents (7.74% DM) after ensiling for 7d (p < 0.05) in early flowering stage. Also, the O5P5 group increased the number of tillers/branches and produced silage with the highest CP content (13.14–14.06) after ensiling for 7d in early flowering stage and both 7d and 30d in early flowering stage and milk ripening stage (p < 0.05). In conclusion, this study found that the selection of oat-pea mixed seeding as O5P5 and harvesting at the milk ripening stage of oat is recommended as a desirable oat-pea mixed seeding strategy for producing high quality silage.

Summary: Cities’ transition from fossil-based systems of energy production and consumption to renewable energy sources—the energy transition—is critical to mitigating climate change impact as cities’ energy consumption and CO2 emissions account for two-thirds and over 70% of the world’s total, respectively. Given cities’ heterogeneity, they need specific low-carbon roadmaps instead of one-size-fits-all approaches. Here, we used an Energy Transition Index (ETI) to characterize the city-level energy transitions from energy system performance and transition readiness dimensions. The ETI scores for 282 cities in China revealed a significant heterogeneity across cities and over time, and the gap between the cities in the top and bottom quartiles was persistent. We estimated that China’s energy and carbon intensity could decrease by 34% and 32%, respectively, and that carbon per capita could fall by 17% if each city modestly follows the sustainable development path forged by the best performing cities with similar economic structures.

Osteoarthritis (OA) is a common degenerative joint disease worldwide and currently there is no effective strategy to stop its progression. It is known that oxidative stress and inflammation can promote the development of OA, and therapeutic strategies against these conditions may alleviate OA. Arbutin (ARB), a major ingredient of the Chinese medicinal herb cowberry leaf, exerts good antioxidant and anti-inflammatory activities yet has not been studied in OA. Here we developed ARB-loaded gelatine methacryloyl-Liposome (GM-Lipo@ARB) microspheres which showed long-term release of ARB and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1β-treated arthritic chondrocytes. Moreover, the synthesized GM-Lipo@ARB microspheres regulated cartilage extracellular matrix (ECM) homeostasis through anti-inflammation effect via inhibiting NF-κB signaling and anti-oxidative stress effect via activating Nrf2 pathway. Intra-articular use of GM-Lipo@ARB can effectively reduce inflammation and oxidative stress in the articular cartilage and thus, attenuating OA progression in a mouse model. The study proposed a novel ARB-laden functional microsphere, GM-Lipo@ARB, and demonstrated that this compound may be used as an alternative therapeutics for treating OA.

Citalopram (CIT) is a commonly prescribed medication for depression. However, the photodegradation mechanism of CIT has not yet been fully analyzed. Therefore, the photodegradation process of CIT in water is studied by density functional theory and time-dependent density functional theory. The calculated results show that during the indirect photodegradation process, the indirect photodegradation of CIT with ·OH occurs via OH-addition and F-substitution. The minimum activation energy of C10 site was 0.4 kcal/mol. All OH-addition and F-substitution reactions are exothermic. The reaction of 1O2 with CIT includes the substitution of 1O2 for F and an addition reaction at the C14 site. The Ea value of this process is 1.7 kcal/mol, which is the lowest activation energy required for the reaction of 1O2 with CIT. C–C/C–N/C–F cleavage is involved in the direct photodegradation process. In the direct photodegradation of CIT, the activation energy of the C7-C16 cleavage reaction was the lowest, which was 12.5 kcal/mol. Analysis of the Ea values found that OH-addition and F-substitution, the substitution of 1O2 for F and addition at the C14 site, as well as the cleavage reactions of C6–F/C7–C16/C17–C18/C18–N/C19–N/C20–N are the main pathways of photodegradation of CIT.

Developing natural product-based anti-cancer drugs/agents is a promising way to overcome the serious side effects and toxicity of traditional chemotherapeutics for cancer treatment. However, rapid assessment of the in vivo anti-cancer activities of natural products is a challenge. Alternatively, zebrafish are useful model organisms and perform well in addressing this challenging issue. Nowadays, a growing number of studies have utilized zebrafish models to evaluate the in vivo activities of natural compounds. Herein, we reviewed the application of zebrafish models for evaluating the anti-cancer activity and toxicity of natural products over the past years, summarized its process and benefits, and provided future outlooks for the development of natural product-based anti-cancer drugs.

The inter-story drift ratio (IDR) is a crucial parameter in structural health monitoring to judge the safety, stability, and serviceability of buildings. Real-time, continuous, and widely applicable detection on IDRs is essential. However, the current methods present some challenges in conducting such detection, including adverse effects from weather, the requirement for large amounts of space, and fragile instruments. This study proposes an alternative method to overcome these defects to measure IDRs and evaluate the structural conditions using ambient noise recordings. Ambient noise is a random and continuous wave signal with various sources and is modified by its propagating medium. Taking the Zhonghe Building on the campus of Tongji University, Shanghai, China, as an example, 24 three-component seismometers were deployed to capture and record the ambient noise continuously from 20 November 2021 to 9 December 2021. Using analysis of the polarization parameters of ambient noise during the building’s most dangerous time and ordinary time, a deflection curve, IDRs, and harmful IDRs of the Zhonghe Building during the most dangerous time were calculated. The computed maximum drift was 0.06 m, the maximum IDR was 1.140×10−3, and the maximum harmful IDR was −2.573×10−4. These results were compared with the relevant specifications in China, and it was found that the structure was in good condition. The study proposes an alternative method to measure IDRs with high applicability and continuity in real time and underscores the need for further research to achieve a localized and real-time structural health monitoring system.

PurposeTo assess the value of automatic disc-fovea angle (DFA) measurement using the DeepLabv3+ segmentation model.MethodsA total of 682 normal fundus image datasets were collected from the Eye Hospital of Nanjing Medical University. The following parts of the images were labeled and subsequently reviewed by ophthalmologists: optic disc center, macular center, optic disc area, and virtual macular area. A total of 477 normal fundus images were used to train DeepLabv3+, U-Net, and PSPNet model, which were used to obtain the optic disc area and virtual macular area. Then, the coordinates of the optic disc center and macular center were obstained by using the minimum outer circle technique. Finally the DFA was calculated.ResultsIn this study, 205 normal fundus images were used to test the model. The experimental results showed that the errors in automatic DFA measurement using DeepLabv3+, U-Net, and PSPNet segmentation models were 0.76°, 1.4°, and 2.12°, respectively. The mean intersection over union (MIoU), mean pixel accuracy (MPA), average error in the center of the optic disc, and average error in the center of the virtual macula obstained by using DeepLabv3+ model was 94.77%, 97.32%, 10.94 pixels, and 13.44 pixels, respectively. The automatic DFA measurement using DeepLabv3+ got the less error than the errors that using the other segmentation models. Therefore, the DeepLabv3+ segmentation model was finally chosen to measure DFA automatically.ConclusionsThe DeepLabv3+ segmentation model -based automatic segmentation techniques can produce accurate and rapid DFA measurements.

The Arctic stratospheric response to El Niño–Southern Oscillation (ENSO) is assessed using the historical simulations provided by the Coupled Model Intercomparison Project Phases 5 and 6 (CMIP5 and CMIP6, respectively). CMIP6 models can well reproduce the ENSO signals in the Arctic stratosphere and have an ameliorated performance compared to CMIP5 models. Specifically, El Niño is associated with an intensified Pacific–North American pattern that leads to a considerable enhancement of planetary wavenumber 1 but a small reduction of planetary wavenumber 2, and thus, a warm and weakened stratospheric polar vortex. The case for La Niña is nearly the opposite, with a cool and strengthened stratospheric polar vortex. In CMIP6, the ENSO-related stratospheric signal matures in the February–March–April season and increases with ENSO magnitude, regardless of the ENSO phase. However, the stratospheric response to strong El Niño (La Niña) is weaker (stronger) than that which should be achieved if the response changes linearly with the amplitude of El Niño (La Niña). An asymmetric time evolution of stratospheric signals exists between strong El Niño and La Niña events. The stratospheric response caused by strong El Niño is weaker from late winter to early spring but stronger in middle and late spring compared to that caused by strong La Niña. By contrast, the Arctic stratospheric signal in moderate El Niño events is larger than that in moderate La Niña. Compared to ENSO-neutral winters, stratospheric sudden warming occurs more (less) frequently in El Niño (La Niña), as simulated by CMIP6 high-top models.

Underwater gravity gradient detection techniques are conducive to ensuring the safety of submersible sailing. In order to improve the accuracy of underwater obstacle detection based on gravity gradient detection technology, this paper studies the gravity gradient underwater obstacle detection method based on the combined support vector regression (SVR) algorithm. First, the gravity gradient difference ratio (GGDR) equation, which is only related to the obstacle’s position, is obtained based on the gravity gradient equation by using the difference and ratio methods. Aiming at solving the shortcomings of the GGDR equation based on Newton–Raphson method (NRM), combined with SVR algorithm, a novel SVR–gravity gradient joint method (SGJM) is proposed. Second, the differential ratio dataset is constructed by simulating the gravity gradient data generated by obstacles, and the obstacle location model is trained using SVR. Four measuring lines were selected to verify the SVR-based positioning model. The verification results show that the mean absolute error of the new method in the x, y, and z directions is less than 5.39 m, the root-mean-square error is less than 7.58 m, and the relative error is less than 4% at a distance of less than 500 m. These evaluation metrics validate the reliability of the novel SGJM-based detection of underwater obstacles. Third, comparative experiments based on the novel SGJM and traditional NRM were carried out. The experimental results show that the positioning accuracy of x and z directions in the obstacle’s position calculation based on the novel SGJM is improved by 88% and 85%, respectively.

Traditional spaceborne Global Navigation Satellite Systems Reflectometry (GNSS-R) sea surface height (SSH) retrieval methods have the disadvantages of complicated error models, low retrieval accuracy, and difficulty using full DDM information. To compensate for these deficiencies while considering the heterogeneity of the input data, this paper proposes an end-to-end Modified Residual Multimodal Deep Learning (MRMDL) method that can utilize the entire range of DDM information. First, the MRMDL method is constructed based on the modified Residual Net (MResNet) and Multi-Hidden layer neural network (MHL-NN). The MResNet applicable to DDM structures is used to adaptively capture productive features of the full DDM and to convert the two-dimensional DDM data into one-dimensional numerical form. Then, the extracted features and auxiliary parameters are fused as the input data for MHL-NN to retrieve the SSH. Second, the reliability of the model is verified using SSH with tide-corrected DTU Sea Surface Height 18 (DTU18) and spaceborne radar altimeters (Jason3, HY-2C, HY-2B). Compared to the SSH provided by the DTU18 validation model and the spaceborne radar altimeter, the Pearson correlation coefficients (PCC) are 0.98 and 0.97, respectively. However, the CYGNSS satellite is not primarily employed for ocean altimetry, and the mean absolute differences (MAD) are 3.92 m and 4.32 m, respectively. Finally, the retrieval accuracy of the MRMDL method and the HALF retracking approach are compared and analyzed. Finally, this study also implements the HALF retracking algorithm to derive the SSH, and the results are compared with those computed by the MRMDL method. The MRMDL method is more accurate than the HALF retracking approach according to MAD, Root-Mean-Square Error (RMSE), and PCC, with an improvement of 35.21%, 17.25%, and 2.08%, respectively. The MRMDL method will contribute a new theoretical and methodological reference for future GNSS-R altimetry satellites with high spatiotemporal SSH retrieval.

Flood events have caused huge disasters with regard to human life and economic development, especially short-term flood events that have occurred in recent years. Gravity Recovery and Climate Experiment (GRACE) satellites can directly detect the spatiotemporal characteristics of terrestrial water storage anomalies (TWSA), which play an important role in capturing flood signals. However, the monthly resolution of GRACE-derived TWSA limits its application in monitoring sub-monthly flood events. Therefore, this paper first reconstructs the daily TWSA based on a statistical model with near real-time precipitation and temperature as input variables, and then three daily flood monitoring indexes are developed based on the reconstructed TWSA. Furthermore, these indexes are employed to evaluate the temporal and spatial characteristics of the 2016 short-term flood event in the Haihe River basin (HRB), including the flood potential index (FPI), water storage deficit index (WSDI), and combined climate deviation index (CCDI). In contrast to previous studies, the temporal resolution of TWSA-based indexes is improved from the monthly scale to the daily scale, which largely improves the temporal characterization of flood monitoring. Results demonstrate that (1) among ten kinds of “Temperature-Precipitation” combinations, the reconstructed TWSA based on CN05.1-CN05.1 match well with the GRACE TWSA, as well as publicly available daily TWSA datasets with a Nash-Sutcliffe efficiency coefficient (NSE) of 0.96 and 0.52 ~ 0.81 respectively. (2) The short-term flood characteristics can be better characterized by the reconstructed daily TWSA based on CN05.1-CN05.1, reaching the peak of 216.19 mm on July 20 in the flood center. Additionally, the spatial characteristics of the equivalent water height (EWH) are detected to evolve from southwest to northeast during the short-term flood. (3) FPI, WSDI, and CCDI are proven to be effective in monitoring flood events in the HRB, which validates the reliability of the reconstructed daily TWSA. Moreover, compared to the 56% and 66% coverage of damage quantified by FPI and CCDI, the 45% damage coverage of the flood mapped by WSDI is more consistent with the governmental reports within the HRB. This paper is expected to provide a valuable reference for the assessment of short-term events caused by extreme climate change.

GRACE observations and land subsidence data derived from InSAR both assess groundwater storage changes. However, GRACE data at local scales are restricted by the coarser spatial resolution of satellite systems, and inversion of Groundwater Storage Anomalies (GWSA) by InSAR requires extensive and unavailable lithological data. Here, we propose a New Subsidence Feature Weighted Combination (NSFWC) scheme to enhance the spatial resolution of GRACE-derived GWSA from 0.5° to 0.05°. This method can not only retain the spatial distribution of groundwater changes but also reflect local details related to surface subsidence. A case study was executed to evaluate the performance of the NSFWC scheme in the Beijing Plain, which has seriously overexploited groundwater. Results showed that the simulated GWSA were consistent with in situ measurements in most regions, with a correlation coefficient of 0.85 and an RMSE of 4.41 mm/year. Additionally, there were 22 overexploited wells in the Beijing Plain, although groundwater levels generally recovered after the South to North Water Diversion Project. Simultaneously, four cones of depression were detected by the InSAR technology, where the maximum cumulative subsidence and subsidence rate achieved −198.52 mm and −53.09 mm/year, respectively. This paper provides data support and technical guarantees for small-scale groundwater resources management.

To improve the reliability of the Global Positioning System (GPS) and Gravity Recovery and Climate Experiment (GRACE) feature extraction, this paper uses a correlation coefficient combined with the traditional variational mode decomposition (VMD), proposing a new correlation variational mode decomposition (CVMD). In contrast to previous studies, the CVMD denoises the sequences before feature extraction and it is the first time that be used in the GPS and GRACE. First, the correlation between the intrinsic mode function (IMF) and the original sequence is obtained to denoise the original sequence. Moreover, the algorithm reuses the VMD to obtain the IMF components with different frequencies. Then the Lomb Scargle (L-S) spectral analysis and energy density are used to obtain the trend-, seasonal, and residual items. Second, the features of the GPS and GRACE time series are extracted based on the CVMD and multidimensional ensemble empirical mode decomposition (MEEMD) to verify the availability of the CVMD. The results indicate that the CVMD is more superior to the MEEMD in feature extraction. Third, the CVMD is used to extract the trend- and seasonal terms of GPS and GRACE in the North China Plain (NCP). The conclusions are as follows: (1) the seasonal items of GRACE are used to correct the GPS sequences, and the average reduction of the weighted root mean square (WRMS) of each GPS station is 0.69, which demonstrates a strong consistency between the seasonal terms of the GPS sequence and GRACE sequence; (2) during 2003-2015, the mean slope of vertical displacements is 0.20 ± 0.07 mm / yr, and the uplift rate increases substantially (1.66 ± 0.62 mm / yr) after 2013. Then, the temporal and spatial relationship between rainfall and crustal load-deformation in the NCP is analyzed, and it is found that the crustal load-deformation is primarily related to rainfall, while human activities play a leading role in the southwestern regions where agricultural irrigation is relatively strong.

Combined with wireless power transfer (WPT) technology, mobile edge computing can provide continuous energy supply and computing resources for mobile devices, and improve their battery life and business application scenarios. This article first designs the mobile edge computing (MEC) model of mobile devices with random mobility and hybrid access point (HAP) with data transmission and energy transmission. On this basis, the selection of target server and the amount of data offloading are taken as the learning objectives, and the task offloading strategy based on multi-agent deep reinforcement learning is constructed. Then combined with MADDPG algorithm and SAC algorithm, the problems of multi-agent environment instability and the difficulty of convergence are solved. The final experimental results show that the improved algorithm based on MADDPG and SAC has good stability and convergence. Compared with other algorithms, it has achieved good results in energy consumption, delay and task failure rate.

Abstract Diabetic ulcers, a difficult problem faced by clinicians, are strongly associated with an increase in cellular senescence. Few empirical studies have focused on exploring a targeted strategy to cure diabetic wounds by eliminating senescent fibroblasts (SFs) and reducing side effects. In this study, poly‐l‐lysine/sodium alginate (PLS) is modified with talabostat (PT100) and encapsulates a PARP1 plasmid (PARP1@PLS‐PT100) for delivery to target the dipeptidyl peptidase 4 (DPP4) receptor and eliminate SFs. PARP1@PLS‐PT100 releases encapsulated plasmids, displaying high selectivity for SFs over normal fibroblasts by targeting the DPP4 receptor, decreasing senescence‐associated secretory phenotypes (SASPs), and stimulating the secretion of anti‐inflammatory factors. Furthermore, the increased apoptosis of SFs and the disappearance of cellular senescence alleviates SASPs, accelerates re‐epithelialization and collagen deposition, and significantly induces macrophage M2 polarization, which mediates tissue repair and the inflammatory response. This innovative strategy has revealed the previously undefined role of PARP1@PLS‐PT100 in promoting diabetic wound healing, suggesting its therapeutic potential in refractory wound repair.

As the largest groundwater drainage region in China, the per capita water resources in the North China Plain (NCP) account for only one-seventh of the country’s available water resources. Currently, the NCP is experiencing a serious water shortage due to the overexploitation of groundwater resources and a subsequent series of natural disasters. Thus, accurate regional assessments and effective water resource management policies are of critical importance. To accomplish this phenomenon, the daily terrestrial water storage anomaly (TWSA) over the NCP is calculated from the combination of the GNSS vertical deformation sequences (seasonal items) and GRACE (trend items). The groundwater storage anomaly (GWSA) in the NCP is obtained by subtracting the canopy water, soil water, and snow water equivalent components from the TWSA. The inversion results of this study are verified by comparisons with the Global Land Data Assimilation System (GLDAS) data products. The elevated annual amplitude areas are located in Beijing and Tianjin, and the Pearson correlation coefficient (PCC), root mean square error (RMSE), and Nash–Sutcliffe efficiency (NSE) between the two GWSA results are 0.67, 4.01 cm, and 0.61, respectively. This indicates that the methods proposed in this study are reliable. Finally, the groundwater drought index was calculated for the period from 2011 to 2021, and the results showed that 2019 was the driest year, with a drought severity index value of −0.12, indicative of slightly moderate drought conditions. By calculating and analyzing the annual GWSA, this work shows that the South–North Water Transfer Project does provide some regional drought mitigation.

Tongluo Yishen (TLYS) decoction is an herb that is extensively applied for the treatment of chronic kidney disease (CKD) in traditional Chinese medicine. In this study, 37 different dominant chemical constituents of TLYS were identified. Rats with unilateral ureteral obstruction (UUO) were used as animal models, and TLYS decoction was administered orally for 14 days. TLYS decoction reduced the levels of renal function indicators, serum creatinine levels and blood urea nitrogen levels and alleviated renal pathological changes. Gene Ontology (GO) and KEGG pathway analyses of RNA sequencing data showed that TLYS decoction had significant effects on biological processes, cellular components and molecular functions in UUO rats and that the phagosome (a membrane source in the early stages of autophagy), lysosome (an important component of autolysosome), and oxidation pathways (which contribute to mitochondrial function) might be related to the antifibrotic effects of TLYS decoction. Moreover, we found significant mitochondrial function impairment, including a decreased mitochondrial membrane potential (MMP) and an imbalance in mitochondrial dynamics, excessive oxidative stress, and activation of Pink1/Parkin-mediated mitophagy in UUO rats. Treatment with TLYS decoction significantly increased the MMP, normalized mitochondrial dynamics and ameliorated renal injury. Moreover, TLYS alleviated the mitophagy clearance deficiency. In conclusion, our study showed that TLYS decoction can ameliorate mitochondrial dynamics by reducing oxidative stress and regulating mitophagy, thereby relieving renal injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research on TLYS decoction.

The altimetry precision of conventional spaceborne Global Navigation Satellite Systems Reflectometry (GNSS-R) is limited, and the error models are complicated. To compensate for the shortcomings of conventional methods, we present a new grid search multihidden layer neural network feature optimization method (GSMHLFO) for sea surface height (SSH) retrieval. Firstly, the GSMHLFO is constructed by combining the multihidden layer neural network, feature engineering, and a grid search algorithm. Moreover, the retrieval performance of the GSMHLFO and its sensitivity to various features are analyzed. By analyzing 14 feature sets with different information details, we concluded that the elevation, signal-to-noise ratio (SNR), atmospheric delay, and ocean wind speed can provide essential contributions to the SSH retrieval based on GSMHLFO. Secondly, the Technical University of Denmark 18 mean sea surface (DTU18 MSS), which is corrected by the TPXO8 global tide model, was used to verify the GSMHLFO. The number of hidden layers and neurons was optimized using the grid search algorithm. The experimental results show that the proposed GSMHLFO with four hidden layers and 200 neurons per layer has a better retrieval performance. Compared with DTU18, the mean absolute difference (MAD), the root mean square error (RMSE), and the Pearson correlation coefficient (PCC) equal 4.23 m, 5.94 m, and 0.98, respectively. The retrieval precision obtained is significantly improved compared to that reported in the literature for the TDS-1 SSH retrieval. Finally, the retrieval performance of the GSMHLFO and the traditional HALF single-point retracking method were compared. The precision of GSMHLFO is higher than that of traditional retracking method according to MAD, RMSE, and PCC, which are increased by 32.86, 25.00, and 8.99%. The GSMHLFO will provide innovative theoretical and methodological support for the high-precision SSH retrieval of GNSS-R altimetry satellites in the future.

The objective of this study was to investigate the effect of a diet supplemented with fresh amla fruit as a natural feed additive on blood metabolic parameters, milk antioxidant capacity, and milk fatty acid (FA) proportions in lactating dairy cows. Eight ruminally cannulated mid-lactation dairy cows were used in a repeated crossover design. The first group of four cows received total mixed ration (TMR) feed without fresh amla fruit (control group). The remaining four cows sequentially supplemented fresh amla fruit (FAF) at three levels (200, 400, then 600 g/d) (treatment group) at 14-day intervals. In second period, control and treatment groups were exchanged. The first ten days were adjusted to diet adaptation for each sub-period, and the last four days for sampling milk and blood. A total of 514 metabolites were detected from FAF using UPLC-ESI-MS/MS. The five main metabolites in FAF were phenolic acids (22%), flavonoids (20%), lipids (20%), amino acids and derivatives (9%), and tannins (7%). Amla fruit supplementation reduced total saturated fatty acid and the omega-6/omega-3 ratio at 200 or 400 g/d FAF dose compared to controls. In addition, amla fruit increased unsaturated FA, such as C20:5 (Eicosapentaenoic acid, EPA) and C22:6 (docosahexaenoic acid, DHA), and branched-chain FA in a dose-dependent manner at 200 or 400 g/d compared to controls. In addition, amla fruit increased the antioxidant capacity biomarkers in the blood, such as superoxide dismutase (SOD) and albumin; this confirms that amla fruit is an excellent antioxidant, inhibiting reactive oxygen species’ (ROS) metabolism, and can thereby protect cells from oxidative stress. Moreover, the most remarkable improvement of ferric reducing-antioxidant power (FRAP) and total antioxidant capacity (TAC) in milk was recorded at 400 g/d FAF doses compared to controls. Therefore, fresh amla fruit doses for lactating cows at 400 g/d on an as-fed basis can be used as an alternative additive feed in dairy cow diets to improve antioxidant capacity, protein efficiency, butter quality, and to produce more desirable milk fatty acid profiles for human consumption.

Articular cartilage has limited self-regenerative capacity and the therapeutic methods for cartilage defects are still dissatisfactory in clinic. Recent studies showed that exosomes derived from mesenchymal stem cells promoted chondrogenesis by delivering bioactive substances to the recipient cells, indicating exosomes might be a novel method for repairing cartilage defect. Herein, we investigated the role and mechanism of human umbilical cord mesenchymal stem cells derived small extracellular vesicles (hUC-MSCs-sEVs) on cartilage regeneration. In vitro results showed that hUC-MSCs-sEVs promoted the migration, proliferation and differentiation of chondrocytes and human bone marrow mesenchymal stem cells (hBMSCs). MiRNA microarray showed that miR-23a-3p was the most highly expressed among the various miRNAs contained in hUC-MSCs-sEVs. Our data revealed that hUC-MSCs-sEVs promoted cartilage regeneration by transferring miR-23a-3p to suppress the level of PTEN and elevate expression of AKT. Moreover, we fabricated Gelatin methacrylate (Gelma)/nanoclay hydrogel (Gel-nano) for sustained release of sEVs, which was biocompatible and exhibited excellent mechanical property. In vivo results showed that hUC-MSCs-sEVs containing Gelma/nanoclay hydrogel (Gel-nano-sEVs) effectively promoted cartilage regeneration. These results indicated that Gel-nano-sEVs have a promising capacity to stimulate chondrogenesis and heal cartilage defects, and also provided valuable data for understanding the role and mechanism of hUC-MSCs-sEVs in cartilage regeneration.

It is an effective measure to estimate groundwater storage anomalies (GWSA) by combining Gravity Recovery and Climate Experiment (GRACE) data and hydrological models. However, GWSA results based on a single hydrological model and GRACE data may have greater uncertainties, and it is difficult to verify in some regions where in situ groundwater-level measurements are limited. First, to solve this problem, a groundwater weighted fusion model (GWFM) is presented, based on the extended triple collocation (ETC) method. Second, the Shiyang River Basin (SYRB) is taken as an example, and in situ groundwater-level measurements are used to evaluate the performance of the GWFM. The comparison indicates that the correlation coefficient (CC) and Nash-Sutcliffe efficiency coefficient (NSE) are increased by 9–40% and 23–657%, respectively, relative to the original results. Moreover, the root mean squared error (RMSE) is reduced by 9–28%, which verifies the superiority of the GWFM. Third, the spatiotemporal distribution and influencing factors of GWSA in the Hexi Corridor (HC) are comprehensively analyzed during the period between 2003 and 2016. The results show that GWSA decline, with a trend of −2.37 ± 0.38 mm/yr from 2003 to 2010, and the downward trend after 2011 (−0.46 ± 1.35 mm/yr) slow down significantly compared to 2003–2010. The spatial distribution obtained by the GWFM is more reliable compared to the arithmetic average results, and GWFM-based GWSA fully retain the advantages of different models, especially in the southeastern part of the SYRB. Additionally, a simple index is used to evaluate the contributions of climatic factors and human factors to groundwater storage (GWS) in the HC and its different subregions. The index indicates that climate factors occupy a dominant position in the SLRB and SYRB, while human factors have a significant impact on GWS in the Heihe River Basin (HRB). This study can provide suggestions for the management and assessments of groundwater resources in some arid regions.

Densely distributed Global Navigation Satellite System (GNSS) stations can invert the terrestrial water storage anomaly (TWSA) with high precision. However, the uneven distribution of GNSS stations greatly limits the application of TWSA inversion. The purpose of this study was to compensate for the spatial coverage of GNSS stations by simulating the vertical deformation in unobserved grids. First, a new deep learning weight loading inversion model (DWLIM) was constructed by combining the long short-term memory (LSTM) algorithm, inverse distance weight, and the crustal load model. DWLIM is beneficial for improving the inversion accuracy of TWSA based on the GNSS vertical displacement. Second, the DWLIM-based and traditional GNSS-derived TWSA methods were utilized to derive TWSA over mainland China. Furthermore, the TWSA results were compared with the TWSA solutions of the Gravity Recovery and Climate Experiment (GRACE) and Global Land Data Assimilation System (GLDAS) model. The results indicate that the maximum Pearson’s correlation coefficient (PCC), Nash–Sutcliffe efficiency (NSE) coefficient, and root mean square error (RMSE) equal 0.81, 0.61, and 2.18 cm, respectively. The accuracy of DWLIM was higher than that of the traditional GNSS inversion method according to PCC, NSE, and RMSE, which were increased by 67.11, 128.15, and 22.75%. The inversion strategy of DWLIM can effectively improve the accuracy of TWSA inversion in regions with unevenly distributed GNSS stations. Third, this study investigated the variation characteristics of TWSA based on DWLIM in 10 river basins over mainland China. The analysis shows that the TWSA amplitudes of Songhua and Liaohe River basins are significantly higher than those of the other basins. Moreover, TWSA sequences in each river basin contain annual seasonal signals, and the wave peaks of TWSA estimates emerge between June and July. Overall, DWLIM provides a useful measure to derive TWSA in regions where GNSS stations are uneven or sparse.

Abstract Background Previous researches pointed out that the measurement of urine fibronectin (Fn) could be a potential diagnostic test for bladder cancer (BCa). We conducted this meta-analysis to fully assess the diagnostic value of urine Fn for BCa detection. Methods A systematic literature search in PubMed, ISI Web of Science, EMBASE, Cochrane library, and CBM was carried out to identify eligible studies evaluating the urine Fn in diagnosing BCa. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with their 95% confidence intervals (CIs) were calculated, and summary receiver operating characteristic (SROC) curves were established. We applied the STATA 13.0, Meta-Disc 1.4, and RevMan 5.3 software to the meta-analysis. Results Eight separate studies with 744 bladder cancer patients were enrolled in this meta-analysis. The pooled sensitivity, specificity, and DOR were 0.80 (95%CI = 0.77–0.83), 0.79 (95%CI = 0.73–0.84), and 15.18 (95%CI = 10.07–22.87), respectively, and the area under the curve (AUC) of SROC was 0.83 (95%CI = 0.79–0.86). The diagnostic power of a combined method (urine Fn combined with urine cytology) was also evaluated, and its sensitivity and AUC were significantly higher (0.86 (95%CI = 0.82–0.90) and 0.89 (95%CI = 0.86–0.92), respectively). Meta-regression along with subgroup analysis based on various covariates revealed the potential sources of the heterogeneity and the detailed diagnostic value of each subgroup. Sensitivity analysis supported that the result was robust. No threshold effect and publication bias were found in this meta-analysis. Conclusions Urine Fn may become a promising non-invasive biomarker for bladder cancer with a relatively satisfactory diagnostic power. And the combination of urine Fn with cytology could be an alternative option for detecting BCa in clinical practice. The potential value of urine Fn still needs to be validated in large, multi-center, and prospective studies.

Dense Global Position System (GPS) arrays can be used to invert the terrestrial water-storage anomaly (TWSA) with higher accuracy. However, the uneven distribution of GPS stations greatly limits the application of GPS to derive the TWSA. Aiming to solve this problem, we grid the GPS array using regression to raise the reliability of TWSA inversion. First, the study uses the random forest (RF) model to simulate crustal deformation in unobserved grids. Meanwhile, the new Machine-Learning Loading-Inverted Method (MLLIM) is constructed based on the traditional GPS derived method to raise the truthfulness of TWSA inversion. Second, this research selects southwest China as the study region, the MLLIM and traditional GPS inversion methods are used to derive the TWSA, and the inverted results are contrasted with datasets of the Gravity Recovery and Climate Experiment (GRACE) Mascon and the Global Land Data Assimilation System (GLDAS) model. The comparison shows that values of Pearson Correlation Coefficient (PCC) between the MLLIM and GRACE and GRACE Follow-On (GRACE-FO) are equal to 0.91 and 0.88, respectively; and the values of R-squared (R2) are equal to 0.76 and 0.65, respectively; the values of PCC and R2 between MLLIM and GLDAS solutions are equal to 0.79 and 0.65. Compared with the traditional GPS inversion, the MLLIM improves PCC and R2 by 8.85% and 7.99% on average, which indicates that the MLLIM can improve the accuracy of TWSA inversion more than the traditional GPS method. Third, this study applies the MLLIM to invert the TWSA in each province of southwest China and combines the precipitation to analyze the change of TWSA in each province. The results are as follows: (1) The spatial distribution of TWSA and precipitation is coincident, which is highlighted in southwest Yunnan and southeast Guangxi; (2) this study compares TWSA of MLLIM with GRACE and GLDAS solutions in each province, which indicates that the maximum value of PCC is as high as 0.86 and 0.94, respectively, which indicates the MLLIM can be used to invert the TWSA in the regions with sparse GPS stations. The TWSA based on the MLLIM can be used to fill the vacancy between GRACE and GRACE-FO.

Abstract Background Fibronectin (FN) is associated with tumorigenesis and progression in bladder cancer, however, the underlying mechanisms causing this remain largely unknown. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to play important regulatory roles in cancer proliferation. Here, we investigated whether FN regulates CIP2A expression to promote bladder cancer cell proliferation. Methods The correlations of stromal FN with CIP2A and proliferating cell nuclear antigen (PCNA) expression were analyzed in a cohort bladder cancer patients. The roles of FN and CIP2A in regulating bladder cancer cell proliferation were evaluated in cell and animal models. Cycloheximide treatment was used to determine the effects of CIP2A on β-catenin stabilization. The CIP2A-β-catenin interaction was confirmed by immunofluorescence staining and co-immunoprcipitation. Results In this study, we found that stromal FN expression correlated positively with the levels of CIP2A and PCNA in bladder cancer tissues. Meanwhile, in human bladder cancer cell lines (T24 and J82), exogenous FN significantly promoted cell proliferation, however, CIP2A depletion inhibited this process. Furthermore, the interaction between CIP2A and β-catenin enhanced the stabilization of β-catenin, which was involved in FN-induced cell proliferation. In vivo, CIP2A depletion repressed FN-accelerated subcutaneous xenograft growth rates. Conclusions These data reveal that CIP2A is a crucial mediator of FN-induced bladder cancer cell proliferation via enhancing the stabilization of β-catenin. Promisingly, FN and CIP2A could serve as potential therapeutic targets for bladder cancer treatment.

Stowage planning is the core of ship planning. It directly influences the seaworthiness of container ship and the handling efficiency of container terminal. As the latter step of container ship stowage plan, terminal stowage planning optimizes terminal cost according to pre-plan. Group-Bay stowage planning is the smallest sub problem of terminal stowage planning problem. A group-bay stowage planning model is formulated to minimize relocation, crane movement and target weight gap satisfying both ship owner and container terminal. A GA-A* hybrid algorithm is designed to solve this problem. Numerical experiment shown the validity and the efficiency.