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An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs.

Late embryogenesis abundant (LEA) proteins are extremely hydrophilic proteins imperatively associated with plant growth and development, as well as cell protection from abiotic stress. However, the genome-wide characterization of LEA gene family remains limited, especially in aquatic species such as lotus (Nelumbo spp.). Here, 57 putative LEA genes, including 28 NnLEAs and 29 NlLEAs were identified in the N.nucifera and N.lutea genomes, respectively. A total of 27 homologous LEA gene pairs were identified, indicating high degree of sequence homologies between the two Nelumbo species. Secondary structure prediction indicated high prevalence of alpha (α) helix structure among LEA proteins in the LEA_1, LEA_4, and SMP groups. Screening of putative promoter cis-elements revealed that NnLEA genes were involved in diverse biological processes. Most NnLEA genes were predominantly expressed in the late cotyledons and plumules development stages, suggesting their potential vital roles in lotus seed maturation. In addition, genes co-expressed with NnLEAs were involved in ABA signaling, seed maturation, and development processes. Overall, this study provides new insights for the in-depth understanding of the functions of NnLEA proteins in lotus seed development, and could act as a useful reference for the molecular breeding of seeds with prolonged lifespan.

Automatic whole heart segmentation plays an important role in the treatment and research of cardiovascular diseases. In this paper, we propose an improved Deep Forest framework, named Multi-Resolution Deep Forest Framework (MRDFF), which accomplishes whole heart segmentation in two stages. We extract the heart region by binary classification in the first stage, thus avoiding the class imbalance problem caused by too much background. The results of the first stage are then subdivided in the second stage to obtain accurate cardiac substructures. In addition, we also propose hybrid feature fusion, multi-resolution fusion and multi-scale fusion to further improve the segmentation accuracy. Experiments on the public dataset MM-WHS show that our model can achieve comparable accuracy in about half the training time of neural network models.

Pseudosperma species are widely distributed worldwide. Many of them cause poisoning incidents every year, and the toxin responsible for poisoning is muscarine, which could stimulate the parasympathetic nervous system. This study established a method using multiwalled carbon nanotube purification and liquid chromatography-tandem mass spectrometry for the targeted screening of mushroom toxins (muscarine, isoxazole derivatives, tryptamine alkaloids, three amatoxins and three phallotoxins) from Pseudosperma umbrinellum, a common poisonous mushroom distributed in north and northwestern China. Surprisingly, in addition to muscarine, phalloidin was also detected in P. umbrinellum, and the contents were 3022.2 ± 604.4 to 4002.3 ± 804.6 mg/kg (k = 2; p = 95%) muscarine and 5.9 ± 1.2 to 9.3 ± 1.8 mg/kg (k = 2; p = 95%) phalloidin.

Trigeminal neuropathic pain (TNP) arises due to peripheral nerve injury, the mechanisms underlying which are little known. The altered gene expression profile in sensory ganglia is critical for neuropathic pain generation and maintenance. We, therefore, assessed the transcriptome of the trigeminal ganglion (TG) from mice at different periods of pain progression. Trigeminal neuropathic pain was established by partial infraorbital nerve transection (pIONT). High-throughput RNA sequencing was applied to detect the mRNA profiles of TG collected at 3 and 10 days after modeling. Injured TG displayed dramatically altered mRNA expression profiles compared to Sham. Different gene expression profiles were obtained at 3 and 10 days after pIONT. Moreover, 314 genes were significantly upregulated, and 81 were significantly downregulated at both 3 and 10 days post-pIONT. Meanwhile, enrichment analysis of these persistent differentially expressed genes (DEGs) showed that the MAPK pathway was the most significantly enriched pathway for upregulated DEGs, validated by immunostaining. In addition, TG cell populations defined by single-nuclei RNA sequencing displayed cellular localization of DEGs at a single-cell resolution. Protein-protein interaction (PPI) and sub-PPI network analyses constructed networks and identified the top 10 hub genes for DEGs at different time points. The present data provide novel information on the gene expression signatures of TG during the development and maintenance phases of TNP, and the identified hub genes and pathways may serve as potential targets for treatment.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Mushroom poisoning is a deeply concerning food safety problem that affects the public in China every year. Although there are statistics on the number of poisonings and incidents, there is a lack of data on the types of toxic mushrooms, clinical manifestations and toxins. A case of wild mushroom poisoning occurred in Xiamen. Descriptive epidemiological investigation, toxins detection, and morphological and phylogenetic identification were immediately performed. The patients exhibited typical neurotoxic symptoms after consuming wild mushrooms, including chills, vertigo, drowsiness, salivation and coma. The average incubation period was 30 min. Treatments that were adopted included fluid infusion, gastric lavage, catharsis, and liver protection treatment. All patients recovered within 10 days. The species was identified as Amanita pseudosychnopyramis, and its contents of muscarine, muscimol and ibotenic acid were 170.3 ± 5.9 mg/kg, 835.4 ± 43.1 mg/kg and 637.9 ± 54.8 mg/kg in dry weight, respectively, as detected by ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). To our knowledge, this is the first report of Amanita pseudosychnopyramis poisoning worldwide.

Purpose Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). Patients and methods From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). Results Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9%vs.36.5%, P=0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4%vs.21.7%, P=0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P Conclusion Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.

This research proposes the one-pot preparation of polydopamine (PDA) decorated mesoporoussilica nanoparticle (PMSN) for the thermal and tumor micro-environment (TME) responsive colorectal tumor therapy. The pores of PMSN were used for the Fe

In this study, a multilevel correction-type goal-oriented adaptive finite element method is designed for semilinear elliptic equations. Concurrently, the corresponding convergence property is theoretically proved. In the novel goal-oriented adaptive finite element method, only a linearized primal equation and a linearized dual equation are required to be solved in each adaptive finite element space. To ensure convergence, the approximate solution of the primal equation was corrected by solving a small-scale semilinear elliptic equation after the central solving process in each adaptive finite element space. Since solving of the large-scale semilinear elliptic equations is avoided and the goal-oriented technique is absorbed, there has been a significant improvement in the solving efficiency for the goal functional of semilinear elliptic equations.

Lanthipeptides are one of the largest groups of ribosomally synthesized and post-translationally modified peptides (RiPPs) and are characterized by the presence of lanthionine (Lan) or methyllanthionine residues (MeLan). Only very few lanthipeptides contain a C-terminal 2-aminovinyl-cysteine (AviCys) motif, but all of them show potent antibacterial activities. Recent advances of genome sequencing led to the rapid accumulation of new biosynthetic gene clusters (BGCs) for lanthipeptides. In this study, through our genome mining strategy, we found the AviCys containing lanthipeptides are widespread in the bacterial kingdom. A lanthipeptide-type biosynthetic gene cluster was identified from public bacterial genome database. Two new lanthipeptides, daspyromycins A and B (1 and 2) containing AviCys motif, along with two degraded products, daspyromycins C and D (3 and 4), were obtained after heterologous expression of the gene cluster in Streptomyces albus J1074. Daspyromycins A and B showed potent antimicrobial activity against a spectrum of Gram-positive and -negative bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE).

Total Lagrangian - Smoothed Particle Hydrodynamics (TL-SPH) is a classical algorithm to improve the tensile instability encountered in the conventional Eulerian kernel-based SPH method for solid mechanics. Meanwhile, the gradient correction usually is employed in TL-SPH to enhance the consistency of approximation, which would generate unavoidable time costs. Therefore, a simplified gradient correction under the initial configuration is derived. Aiming at different particle configurations, the corresponding selection modes are provided and verified. Then the simplified gradient correction is introduced into TL-SPH, which is the Improved TL-SPH (ITL-SPH) method. Firstly, a classical example – elastic rubber collision is simulated to verify ITL-SPH has the same ability as TL-SPH to improve tensile instability. Then, the convergence and high efficiency of ITL-SPH is demonstrated via the uniaxial tension of a plate. Moreover, the plate with square and triangle holes also is simulated to show the adaptation and stability of ITL-SPH for the extreme boundary. Under the Total Lagrangian frame, the treatment to model the crack is necessary. So, this paper proposes a damage model and combines it with the ITL-SPH method for crack initiation and propagation, which is verified by the plate with holes and the notched beam examples.

Spiking neural P systems with rules on synapses (RSSNP systems) are a class of computation models which are inspired by the information processing and communication manner of neurons. In this work, we consider labeled RSSNP systems (lRSSNP systems), where each rule is assigned either with a label chosen from an alphabet Σ or with the empty label λ. A string over an alphabet is accepted by an lRSSNP system if the string is processed from left to right by the system in the sense that in a step only rules labeled with the processed symbol or with λ are used (not both), and the system reaches a final configuration in the moment when the whole string is processed. The set of all accepted strings is categorized as the restricted (computations are done with the application of the rules labeled with symbols from the given alphabet) control language and the unrestricted (rules labeled with λ are allowed in the computations) control language of the system. We study the language accepting power of lRSSNP systems using only standard spiking rules by comparing the family of control languages of lRSSNP systems with the families of languages in the Chomsky hierarchy. It is proved that restricted lRSSNP systems can accept no more than context-sensitive languages, and unrestricted lRSSNP systems can accept recursively enumerable languages.