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Abstract Background Organisms have evolved a range of phenotypic and genetic adaptations to live in different environments along an altitudinal gradient. Herein, we studied the widely distributed Chinese toad, Bufo gargarizans, as a model and used an integrated phenotype-genotype approach to assess adaptations to different altitudinal environments. Results Comparison of populations from four altitudes (50 m, 1200 m, 2300 m, and 3400 m) showed more effective defenses among high-altitude toads. These included thickened epidermis, more epidermal capillaries and granular glands, greater gland size in skin, and higher antioxidant enzyme activities in plasma. High-altitude toads also showed increased erythrocytes and hematocrit and elevated hemoglobin concentration, potentially improving oxygen delivery. Elevated altitude led to a metabolic shift from aerobic to anaerobic metabolism, and high-altitude populations favored carbohydrates over fatty acids to fuel for energy metabolism. Differentially expressed genes were associated with adaptive phenotypic changes. For instance, expression of genes associated with fatty acid metabolism showed greater suppression at high altitude (3400 m), consistent with decreased flux of β-hydroxybutyric acid and lower free fatty acids levels. Moreover, down-regulation of genes involved in carbon metabolism processes at high altitude (3400 m) were coincident with reduced TCA cycle flux. These results suggest that high-altitude toads adopt a metabolic suppression strategy for survival under harsh environmental conditions. Moreover, the hypoxia-inducible factor signaling cascade was activated at high altitude. Conclusions Collectively, these results advance our comprehension of adaptation to high-altitude environments by revealing physiological and genetic mechanisms at work in Chinese toads living along altitudinal gradients.

Compared to the traditional rote learning approach, open innovation experimentation in basic pathology experimental class is a student-centered educational model that offers a platform for active learning and bold exploration. It enhances students′ practical skills, innovative thinking, and teamwork, addressing the limitations of conventional pathology instruction and laying the groundwork for nurturing creative talents. This thesis uses the "Establishment of a Lung Metastasis Model of Mouse Liver Cancer" project as an example to illustrate the implementation of this experimental approach and the insights gained from it.

Abstract Smart highways endorse green and low-carbon handling construction infrastructures for promoting pollution-free environments and driving spaces. With the incorporation of artificial intelligence and smart computing features, sophisticated decision systems improve the aim of such smart highway constructions. For promoting green and low-carbon highway construction infrastructure, this research article introduces a pollution control-facilitated recommendation system (PCFRS). The system aims to satisfy eco-friendly driving demands and low-carbon emission requirements. In this system, eco-friendly driving demands and low-carbon emissions are the prime requirements for designing such highways. The research employs fuzzy control algorithms to analyze the relationship between green demands and demand satisfaction factors across different infrastructures based on policies from environmental departments and governing agencies. The green demands as formulated by the environmental department/ governing agencies are used for verifying the demand and relationship factors across various infrastructures. The fuzzy algorithm provides recommendations for optimal highway infrastructure design by identifying the maximum possible combinations of satisfaction factors, enabling cost-effective construction while meeting green environment and low-carbon emission goals. This process is aided by a fuzzy control algorithm with the relationship and demand factor as crisp inputs. The decisions on the maximum possible combinations of the satisfaction factor are used for infrastructure recommendations. The need for optimal design and promoting green environments are optimal across various highway lanes.

Abstract Background Mesenchymal stem cells (MSCs) are one of the most widely studied adult stem cells, while MSC replicative senescence occurs with serial expansion in vitro. We determined whether miR-34a can regulate MSC senescence by directly targeting glycolytic key enzymes to influence glycolysis. Methods Detected the effects of miR-34a on MSC senescence and glycolytic metabolism through gene manipulation. Bioinformatics prediction and luciferase reporter assay were applied to confirm that HK1 is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting HK1 in MSC senescence was further explored by a cellular function recovery experiment. Results In the current study, we revealed that miR-34a over-expression exacerbated senescence-associated characteristics and impaired glycolytic metabolism. Then we identified hexokinase1 (HK1) as a direct target gene of miR-34a. And HK1 replenishment reversed MSC senescence and reinforced glycolysis. In addition, miR-34a-mediated MSC senescence and lower glycolytic levels were evidently rescued following the co-treatment with HK1 over-expression. Conclusion The miR-34a-HK1 signal axis can alleviate MSC senescence via enhancing glycolytic metabolism, which possibly provides a novel mechanism for MSC senescence and opens up new possibilities for delaying and suppressing the occurrence and development of aging and age-related diseases.

Aim: Parkinson's disease (PD) tremor is associated with dysfunction in the basal ganglia (BG), cerebellum (CB), and sensorimotor networks (SMN). We investigated tremor-related static functional network connectivity (SFNC) and dynamic functional network connectivity (DFNC) in PD patients. Methods: We analyzed the resting-state functional MRI data of 21 tremor-dominant Parkinson's disease (TDPD) patients and 29 healthy controls. We compared DFNC and SFNC between the three networks and assessed their associations with tremor severity. Results: TDPD patients exhibited increased SFNC between the SMN and BG networks. In addition, they spent more mean dwell time (MDT) in state 2, characterized by sparse connections, and less MDT in state 4, indicating stronger connections. Furthermore, enhanced DFNC between the CB and SMN was observed in state 2. Notably, the MDT of state 2 was positively associated with tremor scores. Conclusion: The enhanced dynamic connectivity between the CB and SMN in TDPD patients suggests a potential compensatory mechanism. However, the tendency to remain in a state of sparse connectivity may contribute to the severity of tremor symptoms.

Abstract Background In response to seasonal cold and food shortage, the Xizang plateau frogs, Nanorana parkeri (Anura: Dicroglossidae), enter a reversible hypometabolic state where heart rate and oxygen consumption in skeletal muscle are strongly suppressed. However, the effect of winter hibernation on gene expression and metabolic profiling in these two tissues remains unknown. In the present study, we conducted transcriptomic and metabolomic analyses of heart and skeletal muscle from summer- and winter-collected N. parkeri to explore mechanisms involved in seasonal hibernation. Results We identified 2407 differentially expressed genes (DEGs) in heart and 2938 DEGs in skeletal muscle. Enrichment analysis showed that shared DEGs in both tissues were enriched mainly in translation and metabolic processes. Of these, the expression of genes functionally categorized as “response to stress”, “defense mechanisms”, or “muscle contraction” were particularly associated with hibernation. Metabolomic analysis identified 24 and 22 differentially expressed metabolites (DEMs) in myocardium and skeletal muscle, respectively. In particular, pathway analysis showed that DEMs in myocardium were involved in the pentose phosphate pathway, glycerolipid metabolism, pyruvate metabolism, citrate cycle (TCA cycle), and glycolysis/gluconeogenesis. By contrast, DEMs in skeletal muscle were mainly involved in amino acid metabolism. Conclusions In summary, natural adaptations of myocardium and skeletal muscle in hibernating N. parkeri involved transcriptional alterations in translation, stress response, protective mechanisms, and muscle contraction processes as well as metabolic remodeling. This study provides new insights into the transcriptional and metabolic adjustments that aid winter survival of high-altitude frogs N. parkeri.

ABSTRACTAccurate extraction of built-up areas is helpful to urban development and map updating. Nighttime light (NTL) data can capture the lighting signal of ground objects. However, most built-up area extraction is conducted on public limited coarse spatial resolution NTL images. The Sustainable Development Science Satellite-1 (SDGSAT-1) provides 10 m spatial resolution panchromatic NTL images, making it possible to map detailed urban lighting structures. In urban extraction, the boundaries of urban areas are easily confused with background objects due to the similar spectral and textual features. To address this problem, we proposed a multi-task deep learning model, CG-CFPANet, to extract illuminated built-up areas by synthesizing SDGSAT-1 NTL data and optical remote sensing images. In CG-CFPANet, a convolutional feature pyramid attention (CFPA) module for better contextual recognition and a concatenation group (CG) module to merge the two remote sensing images are developed. Our proposed CG-CFPANet achieved 1.3% higher precision in built-up area extraction than ten other recently proposed network structures: UNet, UNet++, PSPNet, DeeplabV3, FCN, ExtremeC3Net, SegNet, BiseNet, Res2-UNet, and CBRNet. It shows higher applicability for large-scale built-up area extraction.

Mesenchymal stem/stromal cells (MSCs) have the capacity to migrate to tumor sites in vivo and transmit paracrine signals by secreting extracellular vesicles (EVs) to regulate tumor biological behaviors. MSC-derived EVs (MSC-EVs) have similar tumor tropism and pro- or anti-tumorigenesis as their parental cells and exhibit superior properties in drug delivery. MSC-EVs can transfer microRNAs (miRNAs) to tumor cells, thereby manipulating multiple key cancer-related pathways, and further playing a vital role in the tumor growth, metastasis, drug resistance and other aspects. In addition, tumor cells can also influence the behaviors of MSCs in the tumor microenvironment (TME), orchestrating this regulatory process via miRNAs in EVs (EV-miRNAs). Clarifying the specific mechanism by which MSC-derived EV-miRNAs regulate tumor progression, as well as investigating the roles of EV-miRNAs in the TME will contribute to their applications in tumor pharmacotherapy. This article mainly reviews the multifaceted roles and mechanism of miRNAs in MSC-EVs affecting tumor progression, the crosstalk between MSCs and tumor cells caused by EV-miRNAs in the TME. Eventually, the clinical applications of miRNAs in MSC-EVs in tumor therapeutics are illustrated.

Abstract Circulating extracellular vesicles and particles (EVPs) are being investigated as potential biomarkers for early cancer detection, prognosis, and disease monitoring. However, the suboptimal purity of EVPs isolated from peripheral blood plasma has posed a challenge of in‐depth analysis of the EVP proteome. Here, we compared the effectiveness of different methods for isolating EVPs from healthy donor plasma, including ultracentrifugation (UC)‐based protocols, phosphatidylserine‐Tim4 interaction‐based affinity capture (referred to as “PS”), and several commercial kits. Modified UC methods with an additional UC washing or size exclusion chromatography step substantially improved EVP purity and enabled the detection of additional proteins via proteomic mass spectrometry, including many plasma membrane and cytoplasmic proteins involved in vesicular regulation pathways. This improved performance was reproduced in cancer patient plasma specimens, resulting in the identification of a greater number of differentially expressed EVP proteins, thus expanding the range of potential biomarker candidates. However, PS and other commercial kits did not outperform UC‐based methods in improving plasma EVP purity. PS yielded abundant contaminating proteins and a biased enrichment for specific EVP subsets, thus unsuitable for proteomic profiling of plasma EVPs. Therefore, we have optimized UC‐based protocols for circulating EVP isolation, which enable further in‐depth proteomic analysis for biomarker discovery.

Phosphorus (P) is a crucial macronutrient for plant growth and development, and low-Pi stress poses a significant limitation to maize production. While the role of the SPX domain in encoding proteins involved in phosphate (Pi) homeostasis and signaling transduction has been extensively studied in other model plants, the molecular and functional characteristics of the SPX gene family members in maize remain largely unexplored. In this study, we identified six SPX members, and the phylogenetic analysis of ZmSPXs revealed a close relationship with SPX genes in rice. The promoter regions of ZmSPXs were abundant in biotic and abiotic stress-related elements, particularly associated with various hormone signaling pathways, indicating potential intersections between Pi signaling and hormone signaling pathways. Additionally, ZmSPXs displayed tissue-specific expression patterns, with significant and differential induction in anthers and roots, and were localized to the nucleus and cytoplasm. The interaction between ZmSPXs and ZmPHRs was established via yeast two-hybrid assays. Furthermore, overexpression of ZmSPX1 enhanced root sensitivity to Pi deficiency and high-Pi conditions in Arabidopsis thaliana. Phenotypic identification of the maize transgenic lines demonstrated the negative regulatory effect on the P concentration of stems and leaves as well as yield. Notably, polymorphic sites including 34 single-nucleotide polymorphisms (SNPs) and seven insertions/deletions (InDels) in ZmSPX1 were significantly associated with 16 traits of low-Pi tolerance index. Furthermore, significant sites were classified into five haplotypes, and haplotype5 can enhance biomass production by promoting root development. Taken together, our results suggested that ZmSPX family members possibly play a pivotal role in Pi stress signaling in plants by interacting with ZmPHRs. Significantly, ZmSPX1 was involved in the Pi-deficiency response verified in transgenic Arabidopsis and can affect the Pi concentration of maize tissues and yield. This work lays the groundwork for deeper exploration of the maize SPX family and could inform the development of maize varieties with improved Pi efficiency.

Abstract Background Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. B cells are crucial factors in tumor suppression, and tertiary lymphoid structures (TLSs) facilitate immune cell recruitment to the tumor microenvironment (TME). However, the function and mechanisms of tumor-infiltrating B cells and TLSs in MIBC need to be explored further. Methods We performed single-cell RNA sequencing analysis of 11,612 B cells and 55,392 T cells from 12 bladder cancer patients and found naïve B cells, proliferating B cells, plasma cells, interferon-stimulated B cells and germinal center-associated B cells, and described the phenotype, gene enrichment, cell–cell communication, biological processes. We utilized immunohistochemistry (IHC) and immunofluorescence (IF) to describe TLSs morphology in MIBC. Results The interferon-stimulated B-cell subtype (B-ISG15) and germinal center-associated B-cell subtypes (B-LMO2, B-STMN1) were significantly enriched in MIBC. TLSs in MIBC exhibited a distinct follicular structure characterized by a central region of B cells resembling a germinal center surrounded by T cells. CellChat analysis showed that CXCL13 + T cells play a pivotal role in recruiting CXCR5 + B cells. Cell migration experiments demonstrated the chemoattraction of CXCL13 toward CXCR5 + B cells. Importantly, the infiltration of the interferon-stimulated B-cell subtype and the presence of TLSs correlated with a more favorable prognosis in MIBC. Conclusions The study revealed the heterogeneity of B-cell subtypes in MIBC and suggests a pivotal role of TLSs in MIBC outcomes. Our study provides novel insights that contribute to the precision treatment of MIBC.

Pesticides can induce target plants to release odors that are attractive or repellent to their herbivore insects. But, to date, the activity of volatile organic compounds (VOCs), singly or as mixtures, which play a crucial role in the olfactory behavior of herbivore insects, remains unclear. The objective of our research was to investigate the impact of thiamethoxam (TMX), a pesticide, on the emission of odors by wheat plants, and how these odors influence the behavior of grain aphids (Sitobion miscanthi). S. miscanthi showed a greater repellent response to the volatiles emitted by Thx-induced plants compared to those emitted by uncoated plants. Using gas chromatography–mass spectrometry (GCMS), we discovered that TMX greatly induced the release of VOCs in wheat plants. For instance, the levels of Bornyl acetate, 2-Oxepanone, Methyl acrylate, Cyclohexene, α-Pinene, and 1-Nonanol in coated wheat plants were significantly higher as compared to uncoated wheat plants. Moreover, varying concentrations also had an impact on the olfactory behavior of S. miscanthi. For instance, Cyclohexene exhibited clear attractiveness to aphids at concentrations of 100 μL/mL, whereas it displayed evident repellent properties at concentrations of 1 μL/mL and 10 μL/mL. These new findings demonstrate how TMX-induced VOCs affect the behavior of S. miscanthi and could help in developing innovative approaches to manage aphids by manipulating the emission of plant volatiles. Furthermore, these findings can also be utilized to evaluate substances that either attract or repel aphids, with the aim of implementing early monitoring and environmentally friendly methods to manage aphids, while simultaneously impeding the spread of viruses.

Summary: Characterization of isolated extracellular vesicles and particles (EVPs) is crucial for determining functions and biomarker potential. Here, we present a protocol to analyze size, number, morphology, and EVP protein cargo and to validate EVP proteins in both humans and mice. We describe steps for nanoparticle tracking analysis, transmission electron microscopy, single-EVP immunodetection, EVP proteomic mass spectrometry and bioinformatic analysis, and EVP protein validation by ExoELISA and western blot analysis. This allows for EVP cross-validation across different platforms.For complete details on the use and execution of this protocol, please refer to Hoshino et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Reservoir inventories are essential for investigating the impact of climate change and anthropogenic activities on water scape changes. They provide fundamental data sources to explore the sustainability and management efficiency of water resources. However, publicly released reservoir inventories are currently limited to a single temporal domain. As a result, the effectiveness of governmental policy implementation on water resources remains to be explored due to the lack of multi-time datasets. In this study, we generated a reservoir inventory for China for the years 2016 and 2021 with an overall accuracy of 99.71%. The reservoirs were visually interpreted from annually composited Landsat images, and each reservoir is represented by a polygon with attributes of reservoir name, area and storage capacity. About 10.32% of the reservoirs have increased storage capacity from 2016 to 2021, while 22.73% have decreased. Most provinces and river basins in China have expanded their accumulated storage capacity from 2016 to 2021.

The senescence of bone marrow mesenchymal stromal cells (MSCs) leads to the impairment of stemness and osteogenic differentiation capacity. In a previous study, we screened out stearoyl-CoA desaturase 2 (SCD2), the most evidently changed differential gene in lipid metabolism, using combined transcriptomic and metabolomic analyses, and verified that SCD2 could mitigate MSC senescence. However, the underlying molecular mechanism by which the rate-limiting enzyme of lipogenesis SCD2 manipulates MSC senescence has not been completely understood. In this study, we demonstrate that SCD2 over-expression alleviates MSC replicative senescence and ameliorates their osteogenic differentiation through the regulation of lipogenesis. Furthermore, SCD2 expression is reduced, whereas miR-200c-3p expression is elevated in replicative senescent MSCs. SCD2 is the direct target gene of miR-200c-3p, which can bind to the 3′-UTR of SCD2. MiR-200c-3p replenishment in young MSCs is able to diminish SCD2 expression levels due to epigenetic modulation. In addition, SCD2-rescued MSC senescence and enhanced osteogenic differentiation can be attenuated by miR-200c-3p repletion via suppressing lipogenesis. Taken together, we reveal the potential mechanism of SCD2 influencing MSC senescence from the perspective of lipid metabolism and epigenetics, which provides both an experimental basis for elucidating the mechanism of stem cell senescence and a novel target for delaying stem cell senescence.

The muscarinic acetylcholine receptor M3 (M3-mAChR) is involved in various physiological and pathological processes. Owing to specific cardioprotective effects, M3-mAChR is an ideal diagnostic and therapeutic biomarker for cardiovascular diseases (CVDs). Growing evidence has linked M3-mAChR to the development of multiple CVDs, in which it plays a role in cardiac protection such as anti-arrhythmia, anti-hypertrophy, and anti-fibrosis. This review summarizes M3-mAChR’s expression patterns, functions, and underlying mechanisms of action in CVDs, especially in ischemia/reperfusion injury, cardiac hypertrophy, and heart failure, opening up a new research direction for the treatment of CVDs.

Intermittent rivers and ephemeral streams are crucial for the water cycle and ecosystem services, yet they are often neglected by managers and researchers, especially in headwater areas. This oversight has caused a lack of comprehensive basemaps for these vital river systems. In headwater regions, water bodies are typically sparse and disconnected, with narrow and less distinct channels. Therefore, we propose a novel hybrid method that integrates topographic data and remote sensing imagery to delineate river networks. Our method reestablishes connectivity among sparsely distributed water bodies through topographic pairs, enhances less distinct channel features using the gamma function, and converts topographic and water indices data into a weighted graph to determine optimal channels with the A* algorithm. The topographic and water indices data are derived from the Multi-Error-Removed Improved-Terrain DEM (MERIT DEM) and an average composite of the Modified Normalized Difference Water Index (MNDWI), respectively. In the upper Lancang-Mekong River basin, our method outperformed five publicly available DEM datasets, achieving over 91% positional accuracy within a 30 m buffer. This hybrid method enhances positional accuracy and effectively connects sparse water bodies in headwater areas, offering promising applications for delineating intermittent rivers and ephemeral streams and providing baseline information for these river systems.

Muscles play an indispensable role in human life. Surface electromyography (sEMG), as a non-invasive method, is crucial for monitoring muscle status. It is characterized by its real-time, portable nature and is extensively utilized in sports and rehabilitation sciences. This study proposed a wireless acquisition system based on multi-channel sEMG for objective monitoring of grip force. The system consists of an sEMG acquisition module containing four-channel discrete terminals and a host computer receiver module, using Bluetooth wireless transmission. The system is portable, wearable, low-cost, and easy to operate. Leveraging the system, an experiment for grip force prediction was designed, employing the bald eagle search (BES) algorithm to enhance the Random Forest (RF) algorithm. This approach established a grip force prediction model based on dual-channel sEMG signals. As tested, the performance of acquisition terminal proceeded as follows: the gain was up to 1125 times, and the common mode rejection ratio (CMRR) remained high in the sEMG signal band range (96.94 dB (100 Hz), 84.12 dB (500 Hz)), while the performance of the grip force prediction algorithm had an R2 of 0.9215, an MAE of 1.0637, and an MSE of 1.7479. The proposed system demonstrates excellent performance in real-time signal acquisition and grip force prediction, proving to be an effective muscle status monitoring tool for rehabilitation, training, disease condition surveillance and scientific fitness applications.

Abstract Background Acute lung injury (ALI) is a life-threatening condition that fundamentally results from inflammation and edema in the lung. There are no effective treatments available for clinical use. Previously, we found that as a leakage blocker CU06-1004 prevents endothelial barrier disruption and enhances endothelial cell survival under inflammatory conditions. In this study, we aimed to elucidate the effect of CU06-1004 in terms of prevention of inflammation and endothelial dysfunction in an ALI mouse model. Methods An ALI model was established that included intraperitoneal administration of LPS. Following LPS administration, survival rates and lung wet/dry ratios were assessed. Histological analysis was performed using hematoxylin and eosin staining. Scanning electron microscopy was used to examine alveolar and capillary morphology. Cytokines such as IL-1β, IL-6, and TNF-α were analyzed using an ELISA assay of bronchoalveolar lavage fluid (BALF) and serum. Neutrophil infiltration was observed in BALF using Wright-Giemsa staining, and myeloperoxidase (MPO) activity was assessed. Pulmonary vascular leakage was confirmed using Evans-blue dye, and the expression of junctional proteins was evaluated using immunofluorescent staining. Expression of adhesion molecules was observed using immunofluorescence staining. NF-κB activation was determined using immunohistochemistry and western blot analysis. Results Survival rates and pulmonary edema were ameliorated with CU06-1004 treatment. Administration of CU06-1004 normalized histopathological changes induced by LPS, and alveolar-capillary wall thickening was reduced. Compared with the LPS-challenged group, after CU06-1004 treatment, the infiltration of immune cells was decreased in the BALF, and MPO activity in lung tissue was reduced. Similarly, in the CU06-1004 treatment group, pro-inflammatory cytokines were significantly inhibited in both BALF and serum. Evans-blue leakage was reduced, and the expression of junctional proteins was recovered in the CU06-1004 group. Adhesion molecules were downregulated and NF-κB activation was inhibited after CU06-1004 treatment. Conclusions These results suggested that CU06-1004 had a therapeutic effect against LPS-induced ALI via alleviation of the inflammatory response and protection of vascular integrity.

The gut microbiota plays a crucial role in the host’s metabolic processes. Many studies have shown significant changes in the gut microbiota of mammals during hibernation to adapt to the changes in the external environment, but there is limited research on the colonic epithelial tissue and gut microbiota of the wild chipmunks during hibernation. This study analyzed the diversity, composition, and function of the gut microbiota of the wild chipmunk during hibernation using 16S rRNA gene high-throughput sequencing technology, and further conducted histological analysis of the colon. Histological analysis of the colon showed an increase in goblet cells in the hibernation group, which was an adaptive change to long-term fasting during hibernation. The dominant gut microbial phyla were Bacteroidetes, Firmicutes, and Proteobacteria, and the relative abundance of them changed significantly. The analysis of gut microbiota structural differences indicated that the relative abundance of Helicobacter typhlonius and Mucispirillum schaedleri increased significantly, while unclassified Prevotella-9, unclassified Prevotellaceae-UCG-001, unclassified Prevotellaceae-UCG-003 and other species of Prevotella decreased significantly at the species level. Alpha diversity analysis showed that hibernation increased the diversity and richness of the gut microbiota. Beta diversity analysis revealed significant differences in gut microbiota diversity between the hibernation group and the control group. PICRUSt2 functional prediction analysis of the gut microbiota showed that 15 pathways, such as lipid metabolism, xenobiotics biodegradation and metabolism, amino acid metabolism, environmental adaptation, and neurodegenerative diseases, were significantly enriched in the hibernation group, while 12 pathways, including carbohydrate metabolism, replication and repair, translation, and transcription, were significantly enriched in the control group. It can be seen that during hibernation, the gut microbiota of the wild chipmunk changes towards taxa that are beneficial for reducing carbohydrate consumption, increasing fat consumption, and adapting more strongly to environmental changes in order to better provide energy for the body and ensure normal life activities during hibernation.

(1) Background: Alzheimer’s disease (AD) is characterized by β-amyloid (Aβ) peptide accumulation and mitochondrial dysfunction during the early stage of disease. PINK1 regulates the balance between mitochondrial homeostasis and bioenergy supply and demand via the PINK1/Parkin pathway, Na+/Ca2+ exchange, and other pathways. (2) Methods: In this study, we synthesized positively charged carbon dots (CA-PEI CDs) using citric acid (CA) and polyethyleneimine (PEI) and used them as vectors to express PINK1 genes in the APP/PS1-N2a cell line to determine mitochondrial function, electron transport chain (ETC) activity, and ATP-related metabolomics. (3) Results: Our findings showed that the CA-PEI CDs exhibit the characteristics of photoluminescence, low toxicity, and concentrated DNA. They are ideal biological carriers for gene delivery. PINK1 overexpression significantly increased the mitochondrial membrane potential in APP/PS1-N2a cells and reduced reactive-oxygen-species generation and Aβ1-40 and Aβ1-42 levels. An increase in the activity of NADH ubiquinone oxidoreductase (complex I, CI) and cytochrome C oxidase (complex IV, CIV) induces the oxidative phosphorylation of mitochondria, increasing ATP generation. (4) Conclusions: These findings indicate that the PINK gene can alleviate AD by increasing bioenergetic metabolism, reducing Aβ1-40 and Aβ1-42, and increasing ATP production.

In order to improve the seismic performance of reinforced concrete (RC) columns, a reinforcement technology using prestressed steel wire ropes embedded in polyurethane cement composite material is proposed. Four concrete columns reinforced with different materials were subjected to a combination of axial compression and horizontally repeated loading tests (one of which was not reinforced, while the remaining three were reinforced with prestressed steel wire rope, polyurethane cement composite material, and prestressed steel wire ropes embedded in polyurethane cement composite material). The experimental results show that the ductility and energy dissipation capacity of reinforced concrete columns after reinforcement are significantly improved. After strengthening with prestressed steel wire ropes embedded in polyurethane cement composite material, the ultimate horizontal displacement and energy dissipation capacity of reinforced concrete columns were significantly improved, which were 69% and 3.2 times higher than those of unreinforced columns, respectively.

Cardiovascular diseases pose a long-term risk to human health. This study focuses on the rich-spectrum mechanical vibrations generated during cardiac activity. By combining Fourier series theory, we propose a multi-frequency vibration model for the heart, decomposing cardiac vibration into frequency bands and establishing a systematic interpretation for detecting multi-frequency cardiac vibrations. Based on this, we develop a small multi-frequency vibration sensor module based on flexible polyvinylidene fluoride (PVDF) films, which is capable of synchronously collecting ultra-low-frequency seismocardiography (ULF-SCG), seismocardiography (SCG), and phonocardiography (PCG) signals with high sensitivity. Comparative experiments validate the sensor’s performance and we further develop an algorithm framework for feature extraction based on 1D-CNN models, achieving continuous recognition of multiple vibration features. Testing shows that the recognition coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) of the 8 features are 0.95, 2.18 ms, and 4.89 ms, respectively, with an average prediction speed of 60.18 us/point, meeting the re-quirements for online monitoring while ensuring accuracy in extracting multiple feature points. Finally, integrating the vibration model, sensor, and feature extraction algorithm, we propose a dynamic monitoring system for multi-frequency cardiac vibration, which can be applied to portable monitoring devices for daily dynamic cardiac monitoring, providing a new approach for the early diagnosis and prevention of cardiovascular diseases.

A previous metabolomic and genome-wide association analysis of maize screened a glucose-6-phosphate 1-epimerase (ZmG6PE) gene, which responds to low-phosphorus (LP) stress and regulates yield in maize’s recombinant inbred lines (RILs). However, the relationship of ZmG6PE with phosphorus and yield remained elusive. This study aimed to elucidate the underlying response mechanism of the ZmG6PE gene to LP stress and its consequential impact on maize yield. The analysis indicated that ZmG6PE required the Aldose_epim conserved domain to maintain enzyme activity and localized in the nucleus and cell membrane. The zmg6pe mutants showed decreased biomass and sugar contents but had increased starch content in leaves under LP stress conditions. Combined transcriptome and metabolome analysis showed that LP stress activated plant immune regulation in response to the LP stress through carbon metabolism, amino acid metabolism, and fatty acid metabolism. Notably, LP stress significantly reduced the synthesis of glucose-1-phosphate, mannose-6-phosphate, and β-alanine-related metabolites and changed the expression of related genes. ZmG6PE regulates LP stress by mediating the expression of ZmSPX6 and ZmPHT1.13. Overall, this study revealed that ZmG6PE affected the number of grains per ear, ear thickness, and ear weight under LP stress, indicating that ZmG6PE participates in the phosphate signaling pathway and affects maize yield-related traits through balancing carbohydrates homeostasis.

Inhibition of angiogenesis is considered a promising therapeutic approach for cancer treatment. Our previous genetic research showed that the use of a cell-penetrating peptide to inhibit the pleckstrin homology (PH) domain of 3-phosphoinositide-dependent kinase 1 (PDK1) was a viable approach to suppress pathological angiogenesis. Herein, we synthesized and characterized a novel small molecule, CU05-1189, based on our prior study and present evidence for the first time that this compound possesses antiangiogenic properties both in vitro and in vivo. The computational analysis showed that CU05-1189 can interact with the PH domain of PDK1, and it significantly inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration, invasion, and tube formation in human umbilical vein endothelial cells without apparent toxicity. Western blot analysis revealed that the Akt signaling pathway was specifically inhibited by CU05-1189 upon VEGF stimulation, without affecting other VEGF receptor 2 downstream molecules or cytosolic substrates of PDK1, by preventing translocation of PDK1 to the plasma membrane. We also found that CU05-1189 suppressed VEGF-mediated vascular network formation in a Matrigel plug assay. More importantly, CU05-1189 had a good pharmacokinetic profile with a bioavailability of 68%. These results led to the oral administration of CU05-1189, which resulted in reduced tumor microvessel density and growth in a xenograft mouse model. Taken together, our data suggest that CU05-1189 may have great potential and be a promising lead as a novel antiangiogenic agent for cancer treatment.

Vasculogenic mimicry (VM) differs from the classical tumor angiogenesis model. VM does not depend on endothelial cells; instead, highly aggressive tumor cells mimic endothelial cells to form a vascular-like channel structure. VM mediated by tumor cells is significantly and positively associated with a poor prognosis and low survival rates in patients with highly aggressive cancer. In the treatment of highly aggressive malignancies, the presence of VM is considered an important reason for the unsatisfactory clinical efficacy of anti-tumor–angiogenesis therapy (e.g., therapy targeting vascular endothelial growth factor A). Many targeted therapeutic drugs based on traditional tumor blood vessels have been used clinically. Although some progress has been made in certain tumors, problems such as drug resistance have restricted the expected therapeutic effects. Thrombospondin 2 (THBS2) is one of the most important genes associated with angiogenesis, and this gene exerts angiogenesis-related functions through the PI3K/AKT signaling pathway. Although the PI3K/AKT/mTOR signaling pathway is closely related to the progression of VM, the mechanism by which the promising biomarker THBS2 participates in and regulates tumor VM by activating the PI3K/AKT/mTOR signaling pathway is unclear. In this review, we analyze the monomer structure and biological activity of THBS2, the structure and potential synthesis mechanisms of VM, and the complex mechanisms between THBS2, the PI3K/AKT/mTOR signaling pathway, and VM.

Abstract Background Age-related changes in the cerebrovasculature, including blood–brain barrier (BBB) disruption and vascular dementia, are emerging as potential risks for many neurodegenerative diseases. Therefore, the endothelial cells that constitute the cerebrovasculature may play key roles in preventing brain injury. Our previous study showed that CU06-1004, an endothelial cell dysfunction blocker, prevented vascular leakage, enhanced vascular integrity in ischemic reperfusion injury, and promoted the normalization of tumor vasculature. Here, we evaluated the effects of CU06-1004 on age-related cerebrovascular functional decline in the aged mouse brain. Results In this study, we investigated the protective effects of CU06-1004 against oxidative stress–induced damage in human brain microvascular endothelial cells (HBMECs). HBMECs were treated with hydrogen peroxide (H2O2) to establish an oxidative stress–induced model of cellular injury. Compared with H2O2 treatment alone, pretreatment of HBMECs with CU06-1004 considerably reduced oxidative stress–induced cytotoxicity, reactive oxygen species generation, senescence-associated β-galactosidase activity, senescence marker expression, and the expression levels of inflammatory proteins. Based on the observed cytoprotective effects of CU06-1004 in HBMECs, we examined whether CU06-1004 displayed protective effects against cerebrovascular aging in mice. Long-term administration of CU06-1004 alleviated age-associated cerebral microvascular rarefaction and cerebrovascular senescence in the aged mouse brain. CU06-1004 supplementation also reduced the extravasation of plasma IgG by improving BBB integrity in the aged mouse brain, associated with reductions in neuronal injury. A series of behavioral tests also revealed improved motor and cognitive functions in aged mice that received long-term CU06-1004 administration. Conclusions These findings suggest that CU06-1004 may represent a promising therapeutic approach for delaying age-related cerebrovascular impairment and improving cognitive function in old age.

Abstract Aim To explore the coping strategies and corresponding influence factors in patients undergone surgeries for pituitary tumours. Design A cross‐sectional study. Methods Patients diagnosed with pituitary tumours were included. The Medical Coping Questionnaire (MCMQ) and a demographic questionnaire were used for data collection. Results A total of 150 patients with pituitary tumour undergoing surgery treatment were included. Compared with the a‐select sample, patients with pituitary tumours reported more avoidant coping (p

Abstract Background Brain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen–glucose deprivation (OGD). Methods We examined astrocytic NDRG2 expression after middle cerebral artery occlusion (MCAO) using western blot and immunofluorescence staining. Under hypoxia conditions, we added exogenous L-lactate sodium (lactate) to cultured primary astrocytes to explore the effects of lactate on the ubiquitination modification of NDRG2. We profiled the transcriptomic features of NDRG2 silencing in astrocytes after 8 h of OGD conditions as well as exogenous lactate treatment by performing RNA-seq. Finally, we evaluated the molecular mechanisms of NDRG2 in regulating TNFα under OGD conditions using western blot and immunohistochemistry. Results Reactive astrocytes strongly expressed NDRG2 in a rat model of MCAO. We also showed that lactate stabilizes astrocytic NDRG2 by inhibiting its ubiquitination. NDRG2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways. NDRG2 knockdown induced TNFα expression and secretion via c-Jun phosphorylation. Conclusions We revealed that under OGD conditions, lactate plays an important anti-inflammatory role and inhibits TNFα expression by stabilizing NDRG2, which is beneficial for neurological functional recovery. NDRG2 may be a new therapeutic target for cerebral ischemia.

In this study, laminar mixed convection of water/Ag nanofluid with volume fraction of nanoparticles φ = 0, 2, 4, and 6% and Grashof numbers Gr = 50,000, 150,000, 250,000 and 400,000 and Richardson numbers Ri = 0.1, 1, and 10 are simulated using finite volume method. Obtained results indicate that adding a higher volume fraction of nanoparticles at lower Richardson numbers leads to the enhancement of heat transfer and Nusselt number. Streamlines behavior in the cavity is under the influence of two main factors including lid-driven motion (which is the basic factor) and the viscosity of fluid (which transfers the fluid motion to bottom layers and affects the flow domain). Every factor stimulating the flow domain causes uniform temperature distribution in the cavity. The increase of Richardson number leads to the enhancement of lid-driven velocity, temperature penetration and a better mixture of fluid layers, and by increasing Grashof number; this issue can have a great effect on uniform temperature distribution.

Climate warming has resulted in significant changes in permafrost in Northeast China, leading to notable alterations in soil organic carbon (SOC) stocks. These changes are crucial for both the global carbon cycle and climate change, as well as directly impacting the sustainable development of ecosystems. In order to examine the SOC dynamics and the impact of permafrost changes on SOC, we investigate the changes of permafrost extent based on a regression model and TTOP (top temperature of permafrost) model and the relationship between land use and land cover (LULC), SOC stocks, and permafrost changes in Northeast China. The results showing a shrinking permafrost area from 37.43 × 104 km2 to 16.48 × 104 km2 during the period from the 1980s to the 2010s in Northeast China, and the SOC stock decreased by 24.18 Tg C from the 1980s to the 1990s and then rapidly increased by 102.84 Tg C in the 2000s. Permafrost degradation speeds up the succession of LULC, impacting about 90% of the SOC in permafrost regions. The relationship between permafrost changes and SOC in Northeast China shows that permafrost degradation significantly reduces SOC stocks in the short term but increases SOC stocks in the long term, and that LULC play a crucial role in regulating this relationship. The goals of this study are to acquire an understanding of permafrost status and deepening insights into the dynamics of SOC. Simultaneously, the study aims to furnish valuable scientific references for shaping policies on sustainable land use and management in the future, all the while advancing the cause of ecological equilibrium and sustainable development in Northeast China and other areas.

Abstract. Background:. To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. Methods:. This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. Results:. A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%–48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151–3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350–67.410, P 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions:. SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. Trial registration:. Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1

Watermelon (Citrullus lanatus) is one of the world's most important fruit crops, and China produces the most watermelons in the world. Recently, a watermelon variome consisting of 414 key resequenced accessions was reported. However, the genetic relationships and pedigree of Chinese watermelon varieties in the seed market remain unclear. In this study, 241 evenly distributed perfect single nucleotide polymorphisms (SNPs) derived from the watermelon variome were selected for variety identification. The diversity of 247 Chinese watermelon varieties was identified based on their SNP genotypes. The 247 watermelon varieties were clustered into five subpopulations: the East Asian ecotype, intermediate ecotype, small fruit with red flesh ecotype, small fruit with yellow flesh ecotype, and American ecotype. We further established the pedigree of four subpopulations, of which JingXinNo.1, ZaoChunHongYu, HuangXiaoYu and XiaoLan, and Sugarlee were the main doner of the East Asian ecotype, small fruit with red flesh ecotype, small fruit with yellow flesh ecotype, and American ecotype, respectively. Thirty-two core SNPs were selected and applied in watermelon variety identification. They were also validated by the Kompetitive allele-specific PCR (KASPar) platform. The present study furthered our understanding of the genetic relationships and pedigree of watermelon varieties in China, and will help to manage the plant variety protection in watermelon.

Abstract Background Multiple studies have demonstrated the involvement of low-density lipoprotein receptor-related protein 5 (LRP5) in metabolism-related diseases. This study explored the relationship between the LRP5 rs556442 gene polymorphism and the risks of non-alcoholic fatty liver disease (NAFLD) and coronary heart disease (CHD) in a Chinese Han population. Methods This retrospective case–control study included 247 patients with NAFLD, 200 patients with CHD, 118 patients with both NAFLD and CHD, and 339 healthy controls from June 2018 to June 2019 at Qingdao Municipal Hospital. Basic information and clinical characteristics were collected for all subjects. The genotype and allele frequency of LRP5 rs556442 were determined. Results The genotype distributions of LRP5 rs556442 differed significantly between the CHD and NAFLD + CHD groups (P

Background: Stomach adenocarcinoma (STAD) is the fourth highest cause of cancer mortality worldwide. Alterations in copper metabolism are closely linked to cancer genesis and progression. We aim to identify the prognostic value of copper metabolism-related genes (CMRGs) in STAD and the characteristic of the tumor immune microenvironment (TIME) of the CMRG risk model.Methods: CMRGs were investigated in the STAD cohort from The Cancer Genome Atlas (TCGA) database. Then, the hub CMRGs were screened out with LASSO Cox regression, followed by the establishment of a risk model and validated by GSE84437 from the Expression Omnibus (GEO) database. The hub CMRGs were then utilized to create a nomogram. TMB (tumor mutation burden) and immune cell infiltration were investigated. To validate CMRGs in immunotherapy response prediction, immunophenoscore (IPS) and IMvigor210 cohort were employed. Finally, data from single-cell RNA sequencing (scRNA-seq) was utilized to depict the properties of the hub CMRGs.Results: There were 75 differentially expressed CMRGs identified, 6 of which were linked with OS. 5 hub CMRGs were selected by LASSO regression, followed by construction of the CMRG risk model. High-risk patients had a shorter life expectancy than those low-risk. The risk score independently predicted STAD survival through univariate and multivariate Cox regression analyses, with ROC calculation generating the highest results. This risk model was linked to immunocyte infiltration and showed a good prediction performance for STAD patients’ survival. Furthermore, the high-risk group had lower TMB and somatic mutation counters and higher TIDE scores, but the low-risk group had greater IPS-PD-1 and IPS-CTLA4 immunotherapy prediction, indicating a higher immune checkpoint inhibitors (ICIs) response, which was corroborated by the IMvigor210 cohort. Furthermore, those with low and high risk showed differential susceptibility to anticancer drugs. Based on CMRGs, two subclusters were identified. Cluster 2 patients had superior clinical results. Finally, the copper metabolism-related TIME of STAD was concentrated in endothelium, fibroblasts, and macrophages.Conclusion: CMRG is a promising biomarker of prognosis for patients with STAD and can be used as a guide for immunotherapy.

Renal cell carcinoma (RCC) is the most frequent renal malignancy in the world, and its incidence is increasing year by year. RCC is a well-known drug resistant tumor, and the treatment methods are limited. Most patients with RCC are discovered at the advanced stage, and thus have poor prognosis even after treatment. Therefore, it is very urgent to find new markers for the diagnosis and treatment of RCC. Accumulating evidence shows that lncRNAs participate in the occurrence and progression of RCC, which is achieved by the lncRNA-miRNA-mRNA axis. It is widely known that metabolic defect is an essential pathogenesis in RCC. As is the case with other tumors, RCC can satisfy the demands of cancerous cells for uncontrolled proliferation through aerobic glycolysis. However, whether lncRNAs can modulate RCC progression through metabolic pathway is still not clarified. Taken together, this review mainly summarized the metabolic regulatory mechanisms of lncRNAs in RCC progression, especially their roles in glucose metabolism, lipid metabolism, amino acid metabolism and mitochondrial dynamics, as well as the clinical applications of lncRNAs via targeting metabolism in RCC therapy. It will provide the new targets and approaches for early clinical diagnosis, treatment and prognosis of RCC.

IntroductionArbuscular mycorrhizal fungi (AMF) perform a vital role in terrestrial ecosystems.MethodsTo investigate the diversity of AMF communities on the western slope of Helan Mountain at different altitudes and their influence factors, high-throughput sequencing was used to study the structure and diversity of soil AMF communities under different environments and their interrelationships between AMF and environmental factors.ResultsThe results revealed that there were significant differences (p < 0.05) in the physical and chemical properties of the soil along the different altitudes. A total of 1,145 OTUs were obtained by high-throughput sequencing, belonging to 1 phylum, 4 class, 6 orders, 13 families, 18 genera and 135 species, with the dominant genus being Glomus, which accounted for 75.27% of the relative abundance of the community. Soil AMF community structure was shown to be variable at the generic level according to NMDS analysis. Correlation analysis showed that soil pH, water content (WC), organic matter (OM), available K, available P and N were significantly correlated with AMF community diversity and species abundance (p < 0.05, p < 0.01). Based on redundancy analysis (RDA) and Monte Carlo test results, soil pH, WC and OM had highly significant effects (p < 0.01) on AMF community diversity and species abundance.DiscussionThis study investigates the relationship between AMF community structure and diversity and soil physicochemical properties at different elevations on the western slope of Helan Mountain, which is of great significance to the study of the Helan Mountain ecosystem.

Abstract Background Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined. Results In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence. Conclusions Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.

The study of yield traits can reveal the genetic architecture of grain yield for improving maize production. In this study, an association panel comprising 362 inbred lines and a recombinant inbred line population derived from X178 × 9782 were used to identify candidate genes for nine yield traits. High-priority overlap (HPO) genes, which are genes prioritized in a genome-wide association study (GWAS), were investigated using coexpression networks. The GWAS identified 51 environmentally stable SNPs in two environments and 36 pleiotropic SNPs, including three SNPs with both attributes. Seven hotspots containing 41 trait-associated SNPs were identified on six chromosomes by permutation. Pyramiding of superior alleles showed a highly positive effect on all traits, and the phenotypic values of ear diameter and ear weight consistently corresponded with the number of superior alleles in tropical and temperate germplasm. A total of 61 HPO genes were detected after trait-associated SNPs were combined with the coexpression networks. Linkage mapping identified 16 environmentally stable and 16 pleiotropic QTL. Seven SNPs that were located in QTL intervals were assigned as consensus SNPs for the yield traits. Among the candidate genes predicted by our study, some genes were confirmed to function in seed development. The gene Zm00001d016656 encoding a serine/threonine protein kinase was associated with five different traits across multiple environments. Some genes were uniquely expressed in specific tissues and at certain stages of seed development. These findings will provide genetic information and resources for molecular breeding of maize grain yield.

In this paper, the non-scaling backstepping approach is used to examine the controller design process and stability analysis of a class of leader-type stochastic nonlinear systems. By utilizing the non-scaling backstepping design method and Lyapunov method, the controller of the leader-type stochastic nonlinear system is derived. Different from the previous literature on controller design, we develop a more computationally efficient way for designing controllers because the scaling function in the coordinate transformation is not included. Meanwhile, the prescribed-time mean-square stabilization on the equilibrium and two important estimates are derived by combining the Lyapunov method with the matrix norm. Compared to the finite-time stabilization in other studies, the prescribed-time stabilization can determine the convergence time without relying on the initial value and has more real-world applicability. To illustrate the effectiveness of the controller derived in this paper, numerical examples are provided finally.

Fruit ripening is a highly complicated process that is accompanied by the formation of fruit quality. In recent years, a series of studies have demonstrated post-transcriptional control play important roles in fruit ripening and fruit quality formation. Till now, the post-transcriptional mechanisms for watermelon fruit ripening have not been comprehensively studied. In this study, we conducted PacBio single-molecule long-read sequencing to identify genome-wide alternative splicing (AS), alternative polyadenylation (APA) and long non-coding RNAs (lncRNAs) in watermelon fruit. In total, 6,921,295 error-corrected and mapped full-length non-chimeric (FLNC) reads were obtained. Notably, more than 42,285 distinct splicing isoforms were derived from 5,891,183 intron-containing full-length FLNC reads, including a large number of AS events associated with fruit ripening. In addition, we characterized 21,506 polyadenylation sites from 11,611 genes, 8703 of which have APA sites. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that fructose and mannose metabolism, starch and sucrose metabolism and carotenoid biosynthesis were both enriched in genes undergoing AS and APA. These results suggest that post-transcriptional regulation might potentially have a key role in regulation of fruit ripening in watermelon. Taken together, our comprehensive PacBio long-read sequencing results offer a valuable resource for watermelon research, and provide new insights into the molecular mechanisms underlying the complex regulatory networks of watermelon fruit ripening.

Abstract Background In sprouting angiogenesis, VEGFR2 level is regulated via a fine-tuned process involving various signaling pathways. Other than VEGF/VEGFR2 signaling pathway, Wnt/ β-catenin signaling is also important in vascular development. However, the crosstalk between these two signaling pathways is still unknown to date. In this study, we aimed to investigate the role of DIX domain containing 1 (DIXDC1) in vasculature, facilitating the crosstalk between VEGF/VEGFR2 and Wnt/ β-catenin signaling pathways. Results In mice, DIXDC1 deficiency delayed angiogenesis at the embryonic stage and suppressed neovascularization at the neonatal stage. DIXDC1 knockdown inhibited VEGF-induced angiogenesis in endothelial cells in vitro by downregulating VEGFR2 expression. DIXDC1 bound Dishevelled Segment Polarity Protein 2 (Dvl2) and polymerized Dvl2 stabilizing VEGFR2 protein via its direct interaction. The complex formation and stability of VEGFR2 was potentiated by Wnt signaling. Moreover, hypoxia elevated DIXDC1 expression and likely modulated both canonical Wnt/β-catenin signaling and VEGFR2 stability in vasculatures. Pathological angiogenesis in DIXDC1 knockout mice was decreased significantly in oxygen-induced retinopathy (OIR) and in wound healing models. These results suggest that DIXDC1 is an important factor in developmental and pathological angiogenesis. Conclusion We have identified DIXDC1 as an important factor in early vascular development. These results suggest that DIXDC1 represents a novel regulator of sprouting angiogenesis that links Wnt signaling and VEGFR2 stability and may have a potential role in pathological neovascularization.

Head pose estimation (HPE) is a key step in computation and quantification of 3D facial features and has a significant impact on the precision and accuracy of measurements. High-precision HPE is the basis for standardized facial data collection and analysis. The Camper’s plane is the standard (baseline) plane commonly used by anthropologists for head and face research, but there is no research on automatic positioning of the Camper’s plane using color and depth cameras. This paper presents a high-accuracy method for Camper’s plane localization and HPE based on multi-view RGBD depth sensors. The 3D facial point clouds acquired by the multi-view RGBD depth sensors are aligned to obtain a complete 3D face. Keypoint RCNN is used for facial keypoint detection to obtain facial landmarks. A method is proposed to build a general face datum model based on a self-built dataset. The head pose is estimated by applying rigid body transformation to an individual 3D face and the general 3D face model. In order to verify the accuracy of Camper’s plane localization and HPE, 102 cases of 3D facial data and experiments were collected and conducted. The tragus and nasal alar points are localized to within 7 pixels (about 0.83 cm) and the average accuracy of the three dimensions of Camper’s plane identified is 0.87°, 0.64° and 0.47° respectively. The average accuracies of the three dimensions of HPE were 1.17°, 0.90° and 0.97. The experiment results demonstrate the effectiveness of the method for Camper’s plane localization and HPE.

One of the most widely recognized tactics for ensuring long-term development at the national level, green economic growth approaches require the development of a nation to be implemented. The present study examines the effects of infrastructure development, oil consumption, and institution on carbon emission in the presence of economic complexity index, urbanization, infrastructure development, oil consumption, and institution quality in 30 provinces of China region from 2000 to 2020. This study employed second-generation panel cointegration methodologies. Similarly, the results of the CUP-FM and CUP-BC tests confirm the relationship between carbon emission and other variables used in this study. The estimation shows that the economic complexity index, urbanization, and oil consumption increase carbon emissions, whereas infrastructure development and institution have a significantly negative impact on carbon emissions. The robustness check findings obtained CUP-BC test validates the results. The study shows the moderate effect of institutions on the economic complexity index, urbanization, and infrastructure development has a negative impact on carbon emissions. In light of outcomes, the current study suggests decent policy implications to attain a green economic recovery.

Because of the open property of information sharing in integrated sensing and communication, it is inevitable to face security problems such as user information being tampered, eavesdropped, and copied. Radio frequency (RF) individual identification technology is an important means to solve its security problems at present. Whether using machine learning methods or current deep learning-based target fingerprint identification, its performance is based on how well the radio frequency features (RFF) are extracted. Since the received signal is affected by various factors, we believe that we should first find the intrinsic features that can describe the properties of the target, which is the key to enhance the RF fingerprint recognition. In this paper, we try to analyze the intrinsic characteristics of the components that influenced the signal by the transmitting source and derive a mathematical formula to describe the RF characteristics. We propose a method using dynamic wavelet transform and wavelet spectrum (DWTWS) to enhance RFF features. The performance of the proposed method was evaluated by experimental data. Using a support vector machine classifier, the recognition accuracy is 99.6% for 10 individuals at a signal-to-noise ratio (SNR) of 10 dB. In comparison with the dual-tree complex wavelet transform (DT-CWT) feature extraction method and the wavelet scattering transform method, the DWTWS method has increased the interclass distance of different individuals and enhanced the recognition accuracy. The DWTWS method is superior at low SNR, with performance improvements of 53.1% and 10.7% at 0 dB.

IntroductionMitochondria dysfunction is one of the primary causes of tubular injury in acute kidney injury (AKI). Notoginsenoside Fc (Fc), a new saponin isolated from Panax notoginseng, exhibited numerous pharmacological actions. However, the beneficial effects of Fc on renal tubular impairment and mitochondrial dysfunction in AKI have not been fully studied.MethodsIn this study, we established acetaminophen (APAP)-induced AKI model in mice to examine the therapeutic impacts of Fc on AKI.ResultsOur results showed that Fc could decrease the levels of the serum creatinine (Scr), blood urea nitrogen (BUN) and Cystatin C in mice with AKI. Fc also ameliorated renal histopathology, renal tubular cells apoptosis and restored expression of apoptosis-related proteins such as Bax, Bcl-2 and caspase3 (C-caspase3). Additionally, Fc increased the protein expression of SIRT3 and SOD2 in kidneys from mice with AKI. In vitro studies further showed Fc reduced the apoptosis of HK-2 cells exposure to APAP, attenuated the loss of mitochondrial membrane potential and decreased the formation of mitochondrial superoxide. Fc also partly restored the protein expression of Bax, Bcl-2, C-Caspase3, SIRT3, and SOD2 in HK-2 cells exposure to APAP.ConclusionIn summary, Fc might reduce renal tubular injury and mitochondrial dysfunction in AKI partly through the regulation of SIRT3/SOD2 pathway.

The identification of prognostic and therapeutic biomarkers is essential to reduce morbidity and mortality from lung adenocarcinoma (LUAD). This study aimed to identify a reliable prognostic and therapeutic biomarker for LUAD using integrated bioinformatics. Based on the cancer genome atlas (TCGA) and genome-tissue expression (GTEx) analyses, KIF20A has been identified as the hub gene. Following validation using a series of cohorts, survival analysis, meta-analysis, and univariate Cox analysis was conducted. ESTIMATE and CIBERSORT algorithms were then used to study the association of KIF20A with the tumor microenvironment (TME) and the percentage of tumor-infiltrating immune cells (TICs). In vitro experiments were conducted to determine the function of KIF20A. Finally, there was a negative association between the expression of the KIF20A and overall survival, progression-free survival, and disease-free survival, which was confirmed by meta-analysis and COX analysis. Furthermore, KIF20A also had a potential role of altering the TME and TICs proportions in LUAD. Validations in vitro were performed on A549 and PC-9 cell lines, and we found that the knockdown of KIF20A exhibited inhibitory effects on cell proliferation, resulted in cell cycle arrest during the G2/M phase, and induced cellular apoptosis. Our study demonstrated that KIF20A could be utilized as a reliable prognostic marker and treatment target for LUAD. However, further studies are required to validate these findings.

BackgroundA high body mass index (BMI) is a major risk factor for hypertension. The purpose of this study was to investigate the association between the BMI and hypertension in children and adolescents.MethodsWe analyzed physical examination data from 29,810 students aged 6–14 years old. A restricted cubic spline (RCS) function was used to investigate the dose-response relationship between the BMI and hypertension.ResultsThe prevalence of hypertension was 9.91%, followed by 11.71% in males and 7.9% in females, respectively. Compared to the normal weight group, the odds risk (OR) for hypertension in the overweight group was 1.729, and the OR for hypertension in the obesity group was 3.089. After adjusting for potential confounders, the adjusted ORs were 1.620 [95% confidence interval (CI): 1.457–1.800] in the overweight group and 3.092 (95% CI: 2.824–3.385) in the obesity group. According to the multivariate RCS regression analysis, there was a significant non-linear dose-response association between the BMI and the risk of hypertension (all P-values for non-linear < 0.001).ConclusionThe dose-response relationship analysis showed that the association strength of hypertension increased non-linearly along with the continuous change of BMI in children and adolescents.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) has been entitled as metabolic-dysfunction associated fatty liver disease (MAFLD). Therefore anthropometric indicators of adiposity may provide a non-invasive predictive and diagnostic tool for this disease. This study intended to validate and compare the MAFLD predictive and diagnostic capability of eight anthropometric indicators. Methods The study involved a population-based retrospective cross-sectional design. The Fangchenggang area male health and examination survey (FAMHES) was used to collect data of eight anthropometric indicators, involving body mass index (BMI), waist-to-height ratio (WHtR), waist-hip ratio (WHR), body adiposity index (BAI), cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and abdominal volume index (AVI). Receiver operating characteristics (ROC) curves and the respective areas under the curves (AUCs) were utilized to compare the diagnostic capacity of each indicator for MAFLD and to determine the optimal cutoff points. Binary logistic regression analysis was applied to identify the odds ratios (OR) with 95% confidence intervals (95% CI) for all anthropometric indicators and MAFLD. The Spearman rank correlation coefficients of anthropometric indicators, sex hormones, and MAFLD were also calculated. Results All selected anthropometric indicators were significantly associated with MAFLD (P

Abstract Clausena lansium (Lour.) Skeels seeds have been shown to have diverse beneficial medical value due to their unique active components. This study analysed the composition of essential oils (EOs) of C. lansium seeds and investigated their potential antifungal effects against Candida strains. A total of forty-six components were identified in all samples by gas chromatography-mass spectrometry (GC–MS). The main components were sabinene, β-phellandrene and 4-terpineol. Thirteen EOs of C. lansium seeds were classified into three clusters based on their components. Cluster analysis showed that the difference between the tropics and subtropics was the greatest. These EOs and the three main chemicals showed different antifungal activities against five Candida species (C. albicans, C. tropicalis, C. glabrata, C. krusei and C. parapsilosis). The antifungal activity against C. glabrata and C. krusei was higher than that against other Candida strains. EOs of C. lansium seeds displayed noteworthy antifungal activity against both sensitive and fluconazole-resistant strains, with inhibition zone diameters in the range of 9.4–23.4 mm. Comprehensive analysis illustrated the importance of sabinene, β-phellandrene and 4-terpineol to antifungal activity, and there may be some synergistic effects with other components. These results represent the first report about the correlation between the chemical composition of EOs of C. lansium seeds and antifungal activity. Taken together, the results obtained provide scientific evidence for the traditional use of C. lansium seeds waste.