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An inclusion-free edge-coloring of a graph G with δ (G) ≥ 2 is a proper edge-coloring in which the color set of a vertex u is not contained in the color set of a neighbor of u. The least number of colors required in an inclusion-free edge-coloring is the inclusion chromatic index , denoted by χ ⊂ ′ (G). In the paper, we show that if G is a bipartite graph with bipartition (A , B) where Δ (A) ≤ 3 and δ (G) ≥ 2 , then χ ⊂ ′ (G) ≤ 2 Δ + 1. [ABSTRACT FROM AUTHOR]

With the introduction of concepts such as ubiquitous mapping, mapping-related technologies are gradually applied in autonomous driving and target recognition. There are many problems in vision measurement and remote sensing, such as difficulty in automatic vehicle discrimination, high missing rates under multiple vehicle targets, and sensitivity to the external environment. This paper proposes an improved RES-YOLO detection algorithm to solve these problems and applies it to the automatic detection of vehicle targets. Specifically, this paper improves the detection effect of the traditional YOLO algorithm by selecting optimized feature networks and constructing adaptive loss functions. The BDD100K data set was used for training and verification. Additionally, the optimized YOLO deep learning vehicle detection model is obtained and compared with recent advanced target recognition algorithms. Experimental results show that the proposed algorithm can automatically identify multiple vehicle targets effectively and can significantly reduce missing and false rates, with the local optimal accuracy of up to 95% and the average accuracy above 86% under large data volume detection. The average accuracy of our algorithm is higher than all five other algorithms including the latest SSD and Faster-RCNN. In average accuracy, the RES-YOLO algorithm for small data volume and large data volume is 1.0% and 1.7% higher than the original YOLO. In addition, the training time is shortened by 7.3% compared with the original algorithm. The network is then tested with five types of local measured vehicle data sets and shows satisfactory recognition accuracy under different interference backgrounds. In short, the method in this paper can complete the task of vehicle target detection under different environmental interferences. [ABSTRACT FROM AUTHOR]

It remains challenging to treat tumor metastasis currently in the light of multiple cascade processes of tumor metastasis. Additionally, multiple clinical drugs for metastasis have quite limited therapeutic potential and even facilitate metastasis in preclinical models. Thus, potential metastasis targets and novel metastasis-directed drugs are urgently needed to be further developed. Herein, transforming growth factor-β (TGF-β) is verified to contribute to lung metastasis in a context-dependent manner in the 4T1 orthotopic tumor-bearing mice model, which induces epithelial-mesenchymal-transition (EMT) to promote tumor dissemination from the primary site and dampens the anti-tumor response of neutrophils to support tumor colonization at the metastatic niche. In view of neutrophils' superior tropism towards both inflammatory primary tumor and metastatic niche, SB525334, a TGF-β receptor inhibitor, is loaded into cationic liposome (SBLP) which is subsequently incorporated into neutrophils to yield the cyto-pharmaceuticals (SBLP/NE). The systemically infused SBLP/NE can simultaneously migrate into both primary and metastatic sites, then release SB525334 in response to tumor stimuli, and contextually inhibit TGF-β-mediated-EMT and phenotype reversal of infiltrated neutrophils, showing substantial metastasis suppression efficacy without causing any detectable toxicities. This project shifts the paradigm for metastasis suppression therapy by simultaneous blockage of contextual TGF-β using metastatic-cascades-targeting neutrophil cyto-pharmaceuticals. [Display omitted] • TGF-β contributes to metastasis including steps of dissemination and colonization. • TGF-β dampens the anti-tumor immune response of neutrophils at metastatic niche. • Cyto-pharmaceuticals of TGF-β inhibitor simultaneously target multi-step metastasis. • Cyto-pharmaceuticals overcome the dose-dependent organ toxicity of TGF-β inhibitors. [ABSTRACT FROM AUTHOR]

Ginseng is commonly used as a nutritional supplement and daily wellness product due to its ability to invigorate qi. As a result, individuals with Qi-deficiency often use ginseng as a health supplement. Ginsenosides and polysaccharides are the primary components of ginseng. However, the therapeutic effects and mechanisms of action of these components in Qi-deficiency remain unclear. This study aimed to determine the modulatory effects and mechanisms of ginseng water extract, ginsenosides, and ginseng polysaccharides in a rat model of Qi-deficiency using metabolomics and network analysis. The rat model of Qi-deficiency was established via swimming fatigue and a restricted diet. Oral administration of different ginseng water extracts for 30 days primarily alleviated oxidative stress and disrupted energy metabolism and immune response dysfunction caused by Qi-deficiency in rats. Ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for untargeted serum metabolomic analysis. Based on the analysis results, the active constituents of ginseng significantly reversed the changes in serum biomarkers related to Qi-deficiency in rats, particularly energy, amino acid, and unsaturated fatty acid metabolism. Furthermore, analysis of the metabolite-gene network suggested that the anti-Qi-deficiency effects of the ginseng components were mainly associated with toll-like receptor (TLR) signaling and inflammatory response. Additional verification revealed that treatment with the ginseng components effectively reduced the inflammatory response and activation of the myocardial TLR4/NF-κB pathway induced by Qi-deficiency, especially the ginseng water extracts. Therefore, ginseng could be an effective preventive measure against the progression of Qi-deficiency by regulating metabolic and inflammatory responses. [Display omitted] • Ginseng extracts can effectively relieve oxidative stress and immune response dysfunction caused by Qi-deficiency. • The active ingredients of ginseng reversed the changes in serum biomarkers in rats with Qi-deficiency. • Ginseng reduces the activation of myocardial TLR4/NF-κB pathway caused by Qi-deficiency. • Ginseng water extract has a more obvious therapeutic effect on Qi-deficiency. [ABSTRACT FROM AUTHOR]

To overcome the difficulty of automating and intelligently classifying the ground features in remote-sensing hyperspectral images, machine learning methods are gradually introduced into the process of remote-sensing imaging. First, the PaviaU, Botswana, and Cuprite hyperspectral datasets are selected as research subjects in this study, and the objective is to process remote-sensing hyperspectral images via machine learning to realize the automatic and intelligent classification of features. Then, the basic principles of the support vector machine (SVM) and extreme learning machine (ELM) classification algorithms are introduced, and they are applied to the datasets. Next, by adjusting the parameter estimates using a restricted Boltzmann machine (RBM), a new terrain classification model of hyperspectral images that is based on a deep belief network (DBN) is constructed. Next, the SVM, ELM, and DBN classification algorithms for hyperspectral image terrain classification are analysed and compared in terms of accuracy and consistency. The results demonstrate that the average detection accuracies of ELM on the three datasets are 89.54%, 96.14%, and 96.28%, and the Kappa coefficient values are 0.832, 0.963, and 0.924; the average detection accuracies of SVM are 88.90%, 92.11%, and 91.68%, and the Kappa coefficient values are 0.768, 0.913, and 0.944; the average detection accuracies of the DBN classification model are 92.36%, 97.31%, and 98.84%, and the Kappa coefficient values are 0.883, 0.944, and 0.972. The results also demonstrate that the classification accuracy of the DBN algorithm exceeds those of the previous two methods because it fully utilizes the spatial and spectral information of hyperspectral remote-sensing images. In summary, the DBN algorithm that is proposed in this study has high application value in object classification for remote-sensing hyperspectral images. [ABSTRACT FROM AUTHOR]

Guided tissue regeneration is a standard surgical treatment for periodontal regeneration. For the purpose of producing a novel guided tissue regeneration membrane with antibacterial activity and osteogenesis, coaxial electrospinning was utilized to manufacture core/shell structure fiber mats. Polyvinylpyrrolidone loaded with naringin was worked as the core of the fiber to enrich osteogenesis and poly(lactic-co-glycolic acid)–Poly- l -lactic acid–Poly- dl -lactic acid loaded with metronidazole was designed as the shell of the fiber to prevent or treat infections caused by bacteria. The loaded metronidazole with an initial short-term release and the loaded naringin with a long-term sustainable release allowed the membranes with multifunction of antibacterial activity and boosting the proliferation of osteoblast with improved osteogenesis, respectively. The fibrous membrane also shielded osteoblast and fibroblasts from ingrowth. The study provided a simple coaxial electrospinning crafts for fabricating multifunctional guided tissue regeneration membranes. A graphical abstract is available online as a supplementary material. [ABSTRACT FROM AUTHOR]

In shield tunnel digital twin modeling, constructing high-precision tunnel digital 3D models is essential but poses a challenging engineering problem that affects efficiency and accuracy. To address this, this paper presents a method based on 3D tunnel information models using image and point cloud data. A 3D Tunnel Information Model Construction Method (3DTIM) is proposed, based on vision and laser point cloud data, encompassing six core processing layers, and employing the YOLO-T tunnel inner wall image target recognition method alongside various point cloud data processing methods. Through this method, critical parameters can be rapidly and accurately extracted from images and point cloud data, enabling the direct creation of high-precision 3D tunnel models on the 3D modeling software with an accuracy better than 0.7 cm. The 3DTIM approach not only solves the problem of constructing high-precision tunnel 3D models, but also provides a valuable methodological reference for digital shield tunnel twin modeling, reducing the need for manual measurement and enhancing the efficiency of tunnel digital model construction. This research provides a new practical framework for future studies on tunnel 3D model construction and digital shield tunnel twin modeling based on image and point cloud data, forming a more valuable methodological reference. • Combined vision and laser point cloud data for tunnel modeling. • Parameter extraction and processing for 3D model accuracy. • High precision 3D base model for tunnel digital twin project. • Introduced a framework for building high-precision, centimeter-scale digital twin base models for tunnels. • Furthered the progression of digital twin modeling in tunnel engineering. [ABSTRACT FROM AUTHOR]

Soybean are one of the main oil crops in the world. The study demonstrated that co-inoculation with Trichoderma asperellum (Sordariomycetes, Hypocreomycetidae) and Irpex laceratus (Basidiomycota, Polyporales) isolated from Kosteletzkya virginica can promote the growth of soybean seedlings. The two fungi were found to produce various enzymes, including cellulase, amylase, laccase, protease, and urease. Upon inoculation, T. asperellum mainly colonized within the phloem of the roots in soybean seedlings, while I. laceratus mainly in the xylem and phloem of the roots. Physiological parameters, such as plant height, root length, and fresh weight, were significantly increased in soybean seedlings co-inoculated with T. asperellum and I. laceratus. Moreover, the expression of key genes related to N and P absorption and metabolism was also increased, leading to improved N and P utilization efficiency in soybean seedlings. These results indicate that the two fungi may have complementary roles in promoting plant growth, co-inoculation with T. asperellum and I. laceratus can enhance the growth and nutrient uptake of soybean. These findings suggest that T. asperellum and I. laceratus have the potential to be used as bio-fertilizers to improve soybean growth and yield. [ABSTRACT FROM AUTHOR]

Objective: Emerging pathological evidence suggests that there is an association between glymphatic dysfunction and the progression of Parkinson's disease (PD). However, the clinical evidence of this association remains lacking. Methods: In this study, the index for diffusion tensor image analysis along the perivascular space (ALPS index) was calculated to evaluate glymphatic function. Results: Overall, 289 patients with PD were enrolled in the cross‐sectional study. The ALPS index was found to be negatively correlated with age, disease severity, and dyskinesia. In the longitudinal study, the information on a total of 95 PD patients with 5‐year follow‐up examinations was collected from the Parkinson's Progression Marker Initiative, 33 of which were classified into the low ALPS index group, and all others were classified into the mid‐high ALPS index group based on the first tertile of the baseline ALPS index. The results of longitudinal regression indicated that there was a significant main group effect on autonomic dysfunction, as well as on activities of daily living. In addition, the low ALPS index group had faster deterioration in MDS‐UPDRS part III and part II, Symbol Digit Modalities Test and Hopkins Verbal Learning Test. Path analysis showed that ALPS index acted as a significant mediator between tTau/ Aβ1‐42 and cognitive change in the Symbol Digit Modalities Test score at year 4 and year 5. Interpretation: The ALPS index, an neuroimaging marker of glymphatic function, is correlated with PD disease severity, motor symptoms, and autonomic function, and is predictive of faster deterioration in motor symptoms and cognitive function. Additionally, glymphatic function may mediate the pathological role of toxic protein in cognitive decline. ANN NEUROL 2023;94:672–683 [ABSTRACT FROM AUTHOR]

Let G be a graph with a minimum degree δ of at least two. The inclusion chromatic index of G, denoted by χ ⊂ ′ (G) , is the minimum number of colors needed to properly color the edges of G so that the set of colors incident with any vertex is not contained in the set of colors incident to any of its neighbors. We prove that every connected subcubic graph G with δ (G) ≥ 2 either has an inclusion chromatic index of at most six, or G is isomorphic to K ^ 2 , 3 , where its inclusion chromatic index is seven. [ABSTRACT FROM AUTHOR]

[Display omitted] • β-CD-MOF with double channels structure was prepared for drug delivery. • β-CD-MOF brought a high entrapment efficiency of naringin. • Naringin loaded β-CD-MOF release the drug over 30 days according to zero-order rule. • No cytotoxicity of the drug delivery system was detected in vitro. A zero-order drug delivery system (DDS) is one of the most critical strategies in pharmaceutical technology. Herein, β-cyclodextrins-based metal–organic framework (CD-MOF) with double channel structures was obtained, which was used as a zero-order DDS for loading naringin (NAR). The drug release with a zero-order kinetic rule was observed over 30 days; while a high entrapment efficiency of over 80% was obtained. No negative effect was detected when NAR/CD-MOF co-cultured with MC3T3-E1 cells. Hence, CD-MOF would be a potential carrier for zero-order DDSs. [ABSTRACT FROM AUTHOR]

Chronic low-grade inflammation defines obesity as a metabolic disorder. Alterations in the structure of gut flora are strongly associated with obesity. Lactoferrin (LF) has a biological function in regulating intestinal flora. The present study aimed to investigate the therapeutic and anti-inflammatory effects of LF in obese mice based on intestinal flora. A total of 30 C57BL/6 mice were divided into three groups consisting of 10 mice each. Subsequently, one group was fed a normal diet (Group K), another group was fed a high-fat diet (Group M) and the remaining group switched from regular drinking to drinking 2% LF water (Group Z2) after 2 weeks of high-fat diet; all mice were fed for 12 weeks. After the experiment, the mouse blood lipid and lipopolysaccharide levels, levels of inflammatory factors and intestinal tight junction proteins were assessed. Mouse stool samples were analyzed using 16S ribosomal RNA sequencing. The results showed that LF reduced serum total cholesterol, triglycerides and low-density lipoprotein levels, elevated high-density lipoprotein levels, suppressed metabolic endotoxemia and attenuated chronic low-grade inflammatory responses in obese mice. In addition, LF upregulated zonula occludens-1 and occludin protein expression levels in the intestine, thereby improving intestinal barrier integrity. LF altered the intestinal microbial structure of obese mice, reduced the ratio of Firmicutes and an elevated ratio of Bacteroidota, modifying the bacterial population to the increased relative abundance of Alistipes, Acidobacteriota, Psychrobacter and Bryobacter. [ABSTRACT FROM AUTHOR]

Aim: Stochastic and deterministic (biotic factors such as intraspecies competition or abiotic factors) processes affect the spatial patterns of ecological communities. These processes can be quantitatively assessed based on spatial autocorrelation (SAC) parameters. However, the global patterns of SAC and their differences across vegetation types remain unknown. We aimed to (1) quantitatively assess the SAC global pattern in plant communities and their variation from 1990 to 2020 and (2) identify the key drivers of SAC in plant communities in protected areas (PAs). Location: Global. Time Period: 1990–2020. Major Taxa Studied: Terrestrial plants. Methods: Using normalized difference vegetation index data extracted from remote sensing datasets, we calculated the SAC parameters, including the Nugget, Partial Sill (PSill), and Sill, in 147 samples from 49 PAs in 1990, 2000, 2010, and 2020. The random forest model was employed to identify the drivers among 10 annual and 120 monthly climatic variables. Results: The SAC patterns of plant communities in global PAs differed across vegetation types. It reached the highest in grasslands and evergreen needleleaved forests, mainly explained by annual energy metrics, and the lowest in tropical evergreen rain forests around equator and boreal coniferous forests near the Arctic Circle. From 1990 to 2020, the Nugget, PSill, and Sill decreased by 92.36%, 58.36%, and 60.61%, respectively, indicating biological homogeneity. Monthly climatic variables explain SAC variations better than annual ones. Main Conclusions: From 1990 to 2020, the SAC parameters decreased sharply across vegetation types, indicating an obvious biologically homogenous trend that was mainly driven by monthly climatic variation, vary across sites and vegetation types. Our results highlight the need to assess the SAC in different vegetation types separately to understand the shifts of global plant communities under climate change. [ABSTRACT FROM AUTHOR]

The pathological accumulation of α‐synuclein (α‐Syn) and the transmission of misfolded α‐Syn underlie α‐synucleinopathies. Increased plasma α‐Syn levels are associated with cognitive impairment in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies, but it is still unknown whether the cognitive deficits in α‐synucleinopathies have a common vascular pathological origin. Here, it is reported that combined injection of α‐Syn preformed fibrils (PFFs) in the unilateral substantia nigra pars compacta, hippocampus, and cerebral cortex results in impaired spatial learning and memory abilities at 6 months post‐injection and that this cognitive decline is related to cerebral microvascular injury. Moreover, insoluble α‐Syn inclusions are found to form in primary mouse brain microvascular endothelial cells (BMVECs) through lymphocyte‐activation gene 3 (Lag3)‐dependent α‐Syn PFFs endocytosis, causing poly(ADP‐ribose)‐driven cell death and reducing the expression of tight junction proteins in BMVECs. Knockout of Lag3 in vitro prevents α‐Syn PFFs from entering BMVECs, thereby reducing the abovementioned response induced by α‐Syn PFFs. Deletion of endothelial cell‐specific Lag3 in vivo reverses the negative effects of α‐Syn PFFs on cerebral microvessels and cognitive function. In short, this study reveals the effectiveness of targeting Lag3 to block the spread of α‐Syn fibrils to endothelial cells in order to improve cognition. [ABSTRACT FROM AUTHOR]

As a well‐known traditional Chinese medicine formula, the chemical constituents of Shengxian Decoction still remain unclear due to its complexity. In this study, a multidimensional strategy based on ultra‐performance liquid chromatography coupled with ion mobility spectrometry quadrupole time‐of‐flight mass spectrometry and informatics UNIFI platform was applied to achieve rapid and comprehensive identification of the complex composition of Shengxian Decoction. Data‐independent acquisition, fast data‐directed analysis, and high‐definition MSE were used to obtain more and cleaner mass spectrum information. As a result, a total of 120 compounds including 74 saponins, 17 flavonoids, 7 cinnamic acid derivatives, 8 triterpenoids, and 14 others were identified or tentatively characterized by high‐resolution molecular mass, fragment ions, and collision cross‐section values. Furthermore, high‐definition MSE was used to identify six pairs of co‐eluting isomers that could not be detected from conventional data‐independent acquisition and fast data‐directed analysis. This research strategy has a certain potential for the analysis of other compound formulae and lays the foundation for the study of traditional Chinese medicine efficacy. [ABSTRACT FROM AUTHOR]

Abstract: Progesterone is a steroid hormone and plays an important role during pregnancy. But the regulation mechanisms of progesterone-progesterone receptor (P4-PR) signaling during pregnancy remain largely unknown. In this study, we used medroxyprogesterone 17-acetate (MPA) which is a synthetic variant of progesterone and has 20–30 times the activity of progesterone to find that at the same physiological concentration as progesterone during early pregnancy MPA had no significant influence on ES cells self-renewal. But with the increasing of dosage, MPA can inhibit the self-renewal capacity of mouse embryonic stem cells (ES cells) and promote differentiation untimely. We further determined that MPA can influence the miR-200a/zeb2 pathway by down regulating the level of miR-200a. miR-200a significantly higher expressed in ES cells to down-regulate the expression of zeb2 to inhibit the self-renewal and promote differentiation of ES cells. Then we found that the function of MPA can be rescued by over-expression of miR-200a or down-regulation of zeb2. Our findings revealed the progesterone signaling/miR-200a/zeb2 axis regulating the progesterone signaling to insure the balance of self-renewal and differentiation of ES cells. Our study also provided new insight into the dosage of progesterone and it's derivant in the hormone replacement therapy for pregnant woman. [Copyright &y& Elsevier]

For the first time, wheat bran was fermented with Eurotium cristatum (E. cristatum), and alterations in the structural and functional characteristics were explored. The results showed that the soluble dietary fibre (SDF) content significantly increased in fermented bran, and the water and oil holding capacities improved. The total polyphenols, anthocyanin, and main flavour substance phenylethyl alcohol were significantly increased by E. cristatum fermentation. The ferulic acid content was approximately 12.06 times higher in fermented bran than in unfermented bran. These changes may be due to the release of hydrolytic enzymes during E. cristatum fermentation. E. cristatum fermentation enhanced the antioxidant and anti-obesity activities of bran. Furthermore, this study showing that E. cristatum fermentation produced β-hydroxy acid metabolites of monacolin K (MKA) in wheat bran. Thus, this research suggests that E. cristatum can be a starter culture to produce functional foods. [Display omitted] • First application of Eurotium cristatum in solid-state fermentation of wheat bran. • Phenylethyl alcohol content significantly increased and produced a particular flavor. • Fermentation produced β-hydroxy acid metabolite of monacolin K in bran. • Fermentation enhanced bioactive compounds and functional activities of bran. •Eurotium cristatum could be a starter culture to produce functional foods. [ABSTRACT FROM AUTHOR]

Tumor metastasis is directly correlated to poor prognosis and high mortality. Circulating tumor cells (CTCs) play a pivotal role in metastatic cascades, of which CTC clusters is highly metastatic compared to single CTCs. Although platelets and neutrophils within the bloodstream could further exacerbate the pro-metastatic effect of single CTCs, the influence of platelets and neutrophils on CTC clusters mediated metastasis remains unclear. In this study, a pro-metastatic complex composed of CTC clusters, platelets and neutrophils, namely circulating tumor microemboli (CTM), was identified in vivo among different metastatic tumor, which was demonstrated with highly upregulation of hypoxia-inducible factor-1α (HIF-1α). While knock-out of HIF-1α or therapeutically downregulating of HIF-1α via HIF-1α inhibitor (BAY87–2243)-loaded neutrophil cyto-pharmaceuticals (PNEs) could efficiently restrain CTM mediated lung metastasis. The underlying mechanism of metastasis inhibition was attributed to the downregulation of HIF-1α-associated PD-L1, which would enhance immune response for inhibiting metastatic cells. Thus, our work here illustrates that hypoxia was an essential factor in promoting CTM colonization in lung. More importantly, we provide a promising strategy by targeted downregulation of HIF-1α in CTM via neutrophil cyto-pharmaceuticals for treatment of CTM mediated metastasis. Targeted downregulation of hypoxia-inducible factor-1α via neutrophil cyto-pharmaceuticals for restraining circulating tumor microemboli mediated metastasis [Display omitted] • CTC clusters, platelets and neutrophils constitute the pro-metastatic complex. • Circulating tumor microemboli was verified with upregulation of HIF-1α and PD-L1. • Neutrophil cyto-pharmaceuticals efficiently restrain CTM mediated lung metastasis. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, a novel optical biosensor for amantadine (AD) determination has been constructed successfully based on the fluorescence resonance energy transfer (FRET) between water-soluble β-Cyclodextrin (β-CD)-functionalized CdTe quantum dots (QDs) and Rhodamine B (RB). RB could enter the cavity of β-CD by hydrophobic interaction, and the process of FRET between QDs and RB occurred. However, the process of FRET was switched off with the addition of AD, due to its larger hydrophobic association constant with β-CD than that of RB. The fluorescence intensity of CdTe QDs (donor) would increase gradually with the increasing concentration of AD, which shown a good linear relationship in the range of 1×10−5–1.6×10−4 mol/L with a correlation coefficient R 2=0.998. We also obtained a satisfactory result using this spectrophotometric method for the determination of AD in pharmaceutical formulation. Furthermore, β-CD-functionalized CdTe QDs with AD in the cavity were incubated with target HepG2 cells and could be observed in the cytoplasm of cells. The β-CD-functionalized CdTe QDs could act as a visible biomarker for AD in cancer cells fluorescence imaging, which presents a potential application in biomedical field. [Copyright &y& Elsevier]

Schematic illustration of the design principle of the Glu-PEG-Azo/Mito-Cel 808 complex and its action mechanism about inhibiting tumor growth and metastasis. The complex could be actively transported by GLUT1-overexpressing tumor cell. Subsequently, mitochondrial targeting was activated when PEG detached from PAMAM stimulated by the hypoxic tumor microenvironment. Finally, the tumor mitochondria were completely destroyed after Cel were rapidly released in the alkaline mitochondrial matrix and IR808 produced great heat with laser irradiation. Thus, the complex possessed superior specificity and efficiency in inhibiting tumor growth and metastasis. [Display omitted] Mitochondria are appealing targets in cancer therapy for providing a suitable microenvironment and energy supply. Herein, we constructed a glycosylated poly(amido amine)/celastrol (PAMAM/Cel) complex for hypoxia-activated mitochondria-specific drug delivery and chemothermal therapy to inhibit tumor growth and metastasis. The complex was characterized by high photothermal conversion efficiency, hypoxia-sensitive polyethylene glycol (PEG) outer layer detachment, and alkaline-sensitive drug release. The complex showed specific cellular uptake in glucose transporter 1 (GLUT1)-overexpressing tumor cells and mitochondrial accumulation in a hypoxic environment. Combined with near-infrared (NIR) laser irradiation, the complex exhibited higher cytotoxicity, apoptosis induction, and metastasis inhibition rates due to the synergistic chemothermal effect. Similarly, the complex also targeted tumors and accumulated in mitochondria in tumor-bearing nude mice, resulting in superior inhibitory effects on tumor growth and metastasis as well as low systematic toxicity. Further mechanistic studies discovered that the complex impaired the mitochondrial membrane, reduced adenosine triphosphate (ATP) content, and regulated metastasis-related protein expression. Thus, the present study provides a promising nanomedicine for tumor therapy. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of low-, medium-, and high-dose puerarin on cognitive impairment induced by 50% alcohol in mice and revealed the role of autophagy-related signaling pathways (mTOR and JNK pathways) in this process. The alcohol-induced brain injury model was treated with different concentrations of puerarin. The cognitive function of mice was evaluated by the behavioral test, and the changes of target proteins in hippocampus of each experimental group were detected. 40 female Kunming mice were randomly divided into 5 groups. The cognitive ability of mice was tested by Morris water maze, the morphological changes in the CA1 area of hippocampus were observed by HE staining, and the target proteins in hippocampus were measured by WB and IHC. Compared with the 50% alcohol group, the expression of p-mTOR/mTOR and p-4E-BP1/4E-BP1 in hippocampus was significantly decreased, while the expression of p-JNK/JNK, Beclin1, and LC3 was significantly increased in the medium- and high-dose puerarin groups. Puerarin could improve the cognitive impairment induced by 50% alcohol. The mTOR and JNK pathways related to autophagy might be involved in this process. [ABSTRACT FROM AUTHOR]

The existing filtering methods for airborne LiDAR point cloud have low accuracy. An adaptive filtering algorithm is proposed which is improved based on multilevel resolution algorithm. First double index structure of Octree and KDtree is established. Then the initial reference surface is constructed by ground seed points. According to the slope fluctuation situation, the grid resolution of the ground referential surface is adjusted in an adaptive way. Finally, the refined surface is formed gradually by multilevel renewing resolution to provide filtered point cloud with high accuracy. Experimental results show that the error of Type II can be effectively reduced, the average Kappa coefficient increases by 0.53% and the average total error decreases by 0.44% compared with multiresolution hierarchical classification algorithm. The result tested by practically measured data shows that Kappa coefficient can reach 90%. Especially, it maintains advantages of high accuracy under complex topographic environment. [ABSTRACT FROM AUTHOR]

• A 3D object detection network based on Deep Convolutional Neural Networks. • A geometric location constrained backbone module for sufficient feature representations. • A line geometric feature constraint module to enhance object detection capabilities. 3D object detection, as the core of the autonomous vehicle perception module, is essential for efficient transportation and comfortable experiences. However, the challenge of 3D object detection under adverse weather conditions hinders the advancement of autonomous vehicles to higher levels. Hence, achieving accurate 3D object detection under adverse weather conditions is increasingly crucial as it forms the foundation for trajectory planning and driving strategy making in autonomous vehicles, thereby revolutionizing transportation modes for both goods and passengers. Advances in Light Detection and Ranging (LiDAR) technology have facilitated the development of 3D object detection in the past few years. Adverse weather, which inevitably occurs in real-world driving scenarios, could degrade measurement accuracy and point density of LiDAR and lead to particle interference. Detecting accurate 3D bounding boxes from sparse, incomplete point clouds with particle interference is difficult. Therefore, this research presents a novel geometric information constraint network for 3D object detection tasks from LiDAR point clouds under adverse weather (GIC-Net). In this study, we focus on how to incorporate geometric location information and line geometric feature information into the network against adverse weather. Further, we propose a geometric location constrained backbone module (GLC) to reduce rain and snow particle interference and ensure sufficient receptive fields. Then, we design a line geometric feature constraint module (LGFC) to add line constraints of 3D bounding boxes into the training process. Finally, a line loss function is designed, and features from the GLC and LGFC modules are fed into the multi-task detection head for accurate 3D bounding box prediction. Experiments on the Canadian Adverse Driving Conditions (CADC) autonomous vehicle dataset demonstrate the superiority of our method over six other state-of-the-art methods under adverse weather, which is at least 13.32 %, 4.67 %, and 10.44 % mAP higher than the other compared methods in the car, truck, and pedestrian classes respectively. Also, we further verify the better generalization ability of our network compared to other methods. [ABSTRACT FROM AUTHOR]

This study aims to determine the link between choroid plexus (CP) volume and cognitive decline in patients with early-stage Parkinson's disease (PD) and to test whether pathological proteins in the cerebrospinal fluid (CSF) are involved in the modulation of any detrimental effects from CP volume. Data on 95 early-stage PD patients with 5 years of follow-up were collected from the Parkinson's Progression Marker Initiative cohort. The patients were separated into three groups based on tertiles of baseline CP volume. We then used a linear mixed model for longitudinal analysis and conducted path analysis to investigate mediating effects. At baseline, the patients in both the upper and middle tertile group were older and had lower concentrations of CSF Aβ 1-42 than those in the lowest tertile group. Longitudinal analysis showed that the upper tertile group suffered from a more rapid cognitive decline in the Symbol Digit Modalities test, Hopkins Verbal Learning Test (HVLT)-retention, and HVLT delayed recalled score. Furthermore, path analysis showed that the pathological effects of CP volume on the 5-year decline in memory might be partly mediated by the CSF Aβ 1-42 /αsyn ratio. CP enlargement could be an independent risk factor for decreased cognition in patients with early-stage PD, and this risk may be mediated by CSF pathological proteins. • This study aimed to investigate the relationship of CP volume and PD cognitive progression. • Larger CP volume may suggest a rapid deterioration of memory in early PD. • CSF biomarker ratio of Aβ 1-42 /αsyn may partly mediate pathological effect of CP volume. [ABSTRACT FROM AUTHOR]

• This study verified two motor progression patterns of Parkinson's disease (PD). • A user-friendly nomogram model for predicting different trajectories was built. • The ALPS-index was found to be an independent variable in prediction model. Substantial heterogeneity of motor symptoms in Parkinson's disease (PD) poses a challenge to disease prediction. The aim of this study was to construct a nomogram model that can distinguish different longitudinal trajectories of motor symptom changes in early-stage PD patients. Data on 90 patients with 5-years of follow-up were collected from the Parkinson's Progression Marker Initiative (PPMI) cohort. We used a latent class mixed modeling (LCMM) to identify distinct progression patterns of motor symptoms, and backward stepwise logistic regression with baseline information was conducted to identify the potential predictors for motor trajectory and to develop a nomogram. The performance of the nomogram model was then evaluated using the optimism-corrected C-index for internal validation, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for discrimination, the calibration curve for predictive accuracy, and decision curve analysis (DCA) for its clinical value. We identified two trajectories for motor progression patterns. The first, Class 1 (Motor deteriorated group), was characterized by sustained, continuously worsening motor symptoms, and the second, Class 2 (Motor stable group), had stable motor symptoms throughout the follow-up period. The best combination of 7 baseline variables was identified and assembled into the nomogram: Scopa-AUT [odds ratio (OR), 1.11; p = 0.091], Letter number sequencing (LNS) (OR, 0.76; p = 0.068), the asymmetry index of putamen (OR, 0.95; p = 0.034), mean caudate uptake (OR, 0.14; p = 0.086), CSF pTau/α-synuclein (OR, 0.00; p = 0.011), CSF tTau/Aβ (OR, 25434806; p = 0.025), and the index for diffusion tensor image analysis along the perivascular space (ALPS-index) (OR, 0.02; p = 0.030). The nomogram achieved good discrimination, with an original AUC of 0.901 (95% CI, 0.813–0.989), and the bias-corrected concordance index (C-index) with 1,000 bootstraps was 0.834. The calibration curve and DCA also suggested both the high accuracy and clinical usefulness of the nomogram, respectively. This study proposes an effective nomogram to predict different motor progression patterns in early-stage PD. Furthermore, the imaging biomarker indicating glymphatic function could be an independent predictive factor for PD motor progression. [ABSTRACT FROM AUTHOR]

Abstract Endometritis, an inflammatory response of the uterus tissue, is characterized by the production of inflammatory cytokines and migration of neutrophil (PMN) into the uterus tissue. Melatonin has been demonstrated to have anti-inflammatory and antioxidant effects. The purpose of this study was to investigate the protective effects of melatonin on lipopolysaccharide (LPS)-induced endometritis in mice. An endometritis model was induced by LPS and melatonin was given 1 h before LPS treatment. The results showed that melatonin inhibited LPS-induced pathologic changes, Myeloperoxidase (MPO) activity, and levels of interleukin-1 beta (IL-1β). Melatonin also inhibited LPS-induced thioredoxin-interacting protein (TXNIP)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) activation, reactive oxygen species (ROS) production, and endoplasmic reticulum (ER) stress. Furthermore, melatonin was found to increase AMPK activity. In conclusion, our results demonstrated that melatonin inhibited ER stress-associated TXNIP/NLRP3 inflammasome activation with a regulation of adenosine monophosphate activated protein kinase (AMPK) in LPS-induced endometritis. Melatonin may serve as a promising nutritional supplement for the treatment of endometritis. Graphical abstract Unlabelled Image Highlights • Melatonin protects LPS-induced endometritis through anti-inflammation and anti-oxidant pathways. • Melatonin inhibits TXNIP/NLRP3 inflammasome activation induced by LPS. • Melatonin increases AMPK activity induced by LPS. [ABSTRACT FROM AUTHOR]

Mastitis is one of most prevalent production disease in dairy herds worldwide, and is responsible for enormous economic losses. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, which is involved in the response to oxidative stress and inflammatory response. The purpose of this study was to detect the protective effect of HO-1 on LPS-induced mastitis in mice. BALB/c mice were pretreated with hemin (HO-1 inducer) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) at 2 h before LPS stimulation. The results showed that the mammary gland damage, production of inflammatory cytokines IL-1β, and MPO activity in mammary gland tissues were significantly reduced after pretreated with hemin compared with the group of LPS stimulation only. However, ZnPP reversed the effects of hemin. Furthermore, we found that the levels of ROS and NLRP3 inflammasome were increased after LPS stimulation. The increases were inhibited by hemin and the inhibition of hemin on ROS production and NLRP3 inflammasome activation were blocked by ZnPP. In addition, the results showed that hemin reduced the expression of thioredoxin-interacting protein (TXNIP) induced by LPS, and ZnPP attenuated these changes. In conclusion, the results suggested that overproduction of HO-1 may inhibit the activation of NLRP3 inflammasome and the expression of TXNIP. Induction of HO-1 may be served as a promising method against mastitis induced by LPS. [ABSTRACT FROM AUTHOR]

The integrity of point cloud is the basis for smoothly ensuring subsequent data processing and application. For "Smart City" and "Scan to Building Information Modeling (BIM)", complete point cloud data is essential. At present, the most commonly used methods for repairing point cloud holes are multi-source data fusion and interpolation. However, these methods either make it difficult to obtain data, or they are ineffective at repairs or labor-intensive. To solve these problems, we proposed a point cloud "fuzzy" repair algorithm based on the distribution regularity of buildings, aiming at the façade of a building in an urban scene, especially for the vehicle Lidar point cloud. First, the point cloud was rotated to be parallel to the plane XOZ, and the feature boundaries of buildings were extracted. These boundaries were further classified as horizontal or vertical. Then, the distance between boundaries was calculated according to the Euclidean distance, and the points were divided into grids based on this distance. Finally, the holes in the grid that needed to be repaired were filled from four adjacent grids by the "copy–paste" method, and the final hole repairs were realized by point cloud smoothing. The quantitative results showed that data integrity improved after the repair and conformed to the state of the building. The angle and position deviation of the repaired grid were less than 0.54° and 3.25 cm, respectively. Compared with human–computer interaction and other methods, our method required less human intervention, and it had high efficiency. This is of promotional significance for the repair and modeling of point cloud in urban buildings. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the leading causes of cancer-associated mortality in gynecological diseases and ranks third among female cancers worldwide. Although early detection and vaccination have reduced incidence rates, cancer recurrence and metastasis lead to high mortality due to the lack of effective medicines. The present study aimed to identify novel drug candidates to treat cervical cancer. In the present study, lanatoside C, an FDA-approved cardiac glycoside used for the treatment of heart failure, was demonstrated to have anti-proliferative and cytotoxic effects on cervical cancer cells, with abrogation of cell migration in a dose-dependent manner. Lanatoside C also triggered cell apoptosis by enhancing reactive oxygen species production and reducing the mitochondrial membrane potential, which induced cell cycle arrest at the S and G2/M phases. Furthermore, lanatoside C inhibited the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 6 (STAT6), while inducing the expression of suppressor of cytokine signaling 2, a negative regulator of JAK2-STAT6 signaling. Taken together, the results of the present study suggest that lanatoside C suppresses cell proliferation and induces cell apoptosis by inhibiting JAK2-STAT6 signaling, indicating that lanatoside C is a promising agent for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Triptolide (TP), a diterpenoid triepoxide that is extracted from the plant Tripterygium wilfordii, has been found to be quite effective for treating many malignant tumors. Although TP was initially considered to be a promising chemotherapeutic agent, its poor solubility and high toxicity limited its potential clinical application. Consequently, we synthesized nanoformulated TP coated with hyaluronic acid (HA) for application in treating breast cancer. Our results showed that TP can prevent tumor progression, but at the cost of significant toxicity. By contrast, using the nanoformulated TP, uptake of drugs into the tumor can be facilitated, which leads to a further increase in efficacy while decreasing systemic toxicity. [ABSTRACT FROM AUTHOR]

Mastitis, as the main disease to affect the dry dairy cow with the characterized by increasing number of somatic cells in milk and reducing milk production, has been known as one of the most serious expensive disease for the dairy industry. Escherichia coli (E.coli), a gram negative bacterial, have normally been considered to be an opportunistic pathogen that can invade the mammary gland sometimes to cause inflammatory diseases. Lippolysacchride (LPS), as the co-cell wall component of the Escherichia coli (E.coli), is the main virulence factors to induce acute inflammation. Itaconate is an endogenous metabolite which has recently been reported to regulate the macrophage function and has the ability to reduce the secretion of pro-inflammatory cytokines, such as IL-6 and IL-12. Here, the aim of this study is to investigate the protective role of dimethyl itaconate (DI)-the membranepermeable derivative of itaconate, on LPS-induced mastitis in mice. To establish the model of mastitis, mice 5–7 day after delivery were utilized by nipple duct injection of LPS, while DI was treated 24h intraperitoneally before LPS injection. Further, the hematoxylin-eosin (H&E) staining was used to evaluate the pathological changes of the mammary gland, the inflammatory cytokines of TNF-α and IL-1β and the myeloperoxidase (MPO) activity were also measured respectively by enzyme-linked immunosorbent assay (ELISA) and MPO assay kit. To clarify the underling mechanisms of the protective role of DI on mastitis, the MAPKs, NF-κB and Nrf2 signaling pathways were detected via western blotting. The results demonstrated that DI markedly decreased the pathological injury of mammary, and considerably reduced the production of TNF-α and IL-1β, as well as up-regulated the Nrf2, HO-1, phosphorylation of p38 and ERK, but down-regulated TLR4 and phosphorylation of p65 NF-κB. Our research recommended that DI ameliorated LPS-induced mastitis which highlights itaconate may as a potential candidate to protect against mastitis. Image 1 • DI has protective effects against LPS-induced mastitis in mice. • DI significantly decreases the secretion of TNF-α and IL-1β. • DI inhibits LPS-induced TLR4 expression and NF-κB activation. • DI up-regulated the MAPKs and Nrf2 actiation. [ABSTRACT FROM AUTHOR]