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The nacre-inspired multi-nanolayer structure offers a unique combination of advanced mechanical properties, such as strength and crack tolerance, making them highly versatile for various applications. Nevertheless, a significant challenge lies in the current fabrication methods, which is difficult to create a scalable manufacturing process with precise control of hierarchical structure. In this work, a novel strategy is presented to regulate nacre-like multi-nanolayer films with the balance mechanical properties of stiffness and toughness. By utilizing a co-continuous phase structure and an extensional stress field, the hierarchical nanolayers is successfully constructed with tunable sizes using a scalable processing technique. This strategic modification allows the robust phase to function as nacre-like platelets, while the soft phase acts as a ductile connection layer, resulting in exceptional comprehensive properties. The nanolayer-structured films demonstrate excellent isotropic properties, including a tensile strength of 113.5 MPa in the machine direction and 106.3 MPa in a transverse direction. More interestingly, these films unprecedentedly exhibit a remarkable puncture resistance at the same time, up to 324.8 N mm-1, surpassing the performance of other biodegradable films. The scalable fabrication strategy holds significant promise in designing advanced bioinspired materials for diverse applications.
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Biodegradable flocculants are rarely used in waste activated sludge (WAS) fermentation. This study introduces an alginate-based biodegradable flocculant (ABF) to enhance both the dewatering and degradation of WAS during its fermentation. Alginate was identified in structural extracellular polymeric substances (St-EPS) of WAS, with alginate-producing bacteria comprising â¼4.2% of the total bacterial population in WAS. Owing to its larger floc size, higher contact angle, and lower free energy resulting from the Lewis acid-base interaction, the addition of the prepared ABF with a network structure significantly improved the dewaterability of WAS and reduced capillary suction time (CST) by 72%. The utilization of ABF by an enriched alginate-degrading consortium (ADC) resulted in a 35.5% increase in the WAS methane yield owing to its higher hydrolytic activity on both ABF and St-EPS. Additionally, after a 30 day fermentation, CST decreased by 62% owing to the enhanced degradation of St-EPS (74.4%) and lower viscosity in the WAS + ABF + ADC group. The genus Bacteroides, comprising 12% of ADC, used alginate lyase (EC 4.2.2.3) and pectate lyase (EC 4.2.2.2 and EC 4.2.2.9) to degrade alginate and polygalacturonate in St-EPS, respectively. Therefore, this study introduces a new flocculant and elucidates its dual roles in enhancing both the dewaterability and degradability of WAS. These advancements improve WAS fermentation, resulting in higher methane production and lower CSTs.
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Alginatos , Fermentação , Floculação , Esgotos , Anaerobiose , Eliminação de Resíduos Líquidos , Biodegradação AmbientalRESUMO
Polysaccharides in extracellular polymeric substances (EPS) can form a hybrid matrix network with proteins, impeding waste-activated sludge (WAS) fermentation. Amino sugars, such as N-acetyl-d-glucosamine (GlcNAc) polymers and sialic acid, are the non-negligible components in the EPS of aerobic granules or biofilm. However, the occurrence of amino sugars in WAS and their degradation remains unclear. Thus, amino sugars (â¼6.0%) in WAS were revealed, and the genera of Lactococcus and Zoogloea were identified for the first time. Chitin was used as the substrate to enrich a chitin-degrading consortium (CDC). The COD balances for methane production ranged from 83.3 and 95.1%. Chitin was gradually converted to oligosaccharides and GlcNAc after dosing with the extracellular enzyme. After doing enriched CDC in WAS, the final methane production markedly increased to 60.4 ± 0.6 mL, reflecting an increase of â¼62%. Four model substrates of amino sugars (GlcNAc and sialic acid) and polysaccharides (cellulose and dextran) could be used by CDC. Treponema (34.3%) was identified as the core bacterium via excreting chitinases (EC 3.2.1.14) and N-acetyl-glucosaminidases (EC 3.2.1.52), especially the genetic abundance of chitinases in CDC was 2.5 times higher than that of WAS. Thus, this study provides an elegant method for the utilization of amino sugar-enriched organics.
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Quitinases , Esgotos , Amino Açúcares , Fermentação , Ácido N-Acetilneuramínico , Quitina/química , Quitina/metabolismo , Polissacarídeos , Quitinases/química , Quitinases/metabolismo , MetanoRESUMO
BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .
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Analgésicos Opioides , Dor Irruptiva , Fentanila , Humanos , Fentanila/uso terapêutico , Fentanila/administração & dosagem , Feminino , Masculino , Dor Irruptiva/tratamento farmacológico , Dor Irruptiva/etiologia , Pessoa de Meia-Idade , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Idoso , Administração Bucal , Adulto , Medição da Dor/métodos , Dor do Câncer/tratamento farmacológico , Manejo da Dor/métodos , Manejo da Dor/normas , Manejo da Dor/estatística & dados numéricos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Idoso de 80 Anos ou maisRESUMO
Despite great progress in the construction of non-equilibrium systems, most approaches do not consider the structure of the fuel as a critical element to control the processes. Herein, we show that the amino acid side chains (A, F, Nal) in the structure of abiotic phosphates can direct assembly and reactivity during transient structure formation. The fuels bind covalently to substrates and subsequently influence the structures in the assembly process. We focus on the ways in which the phosphate esters guide structure formation and how structures and reactivity cross regulate when constructing assemblies. Through the chemical functionalization of energy-rich aminoacyl phosphate esters, we are able to control the yield of esters and thioesters upon adding dipeptides containing tyrosine or cysteine residues. The structural elements around the phosphate esters guide the lifetime of the structures formed and their supramolecular assemblies. These properties can be further influenced by the peptide sequence of substrates, incorporating anionic, aliphatic and aromatic residues. Furthermore, we illustrate that oligomerization of esters can be initiated from a single aminoacyl phosphate ester incorporating a tyrosine residue (Y). These findings suggest that activated amino acids with varying reactivity and energy contents can pave the way for designing and fabricating structured fuels.
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Peptídeos , Fosfatos , Fosfatos/química , Peptídeos/química , Ésteres/química , Estrutura MolecularRESUMO
RIPK1, a receptor-interacting serine/threonine protein kinase, plays a crucial role in maintaining cellular and tissue homeostasis by integrating inflammatory responses and cell death signaling pathways including apoptosis and necroptosis, which have been implicated in diverse physiological and pathological processes. Suppression of RIPK1 activation is a promising strategy for restraining the pathological progression of many human diseases. Neuroinflammation and neuronal apoptosis are two pivotal factors in the pathogenesis of brain injury following subarachnoid hemorrhage (SAH). In this study, we established in vivo and in vitro models of SAH to investigate the activation of RIPK1 kinase in both microglia and neurons. We observed the correlation between RIPK1 kinase activity and microglia-mediated inflammation as well as neuronal apoptosis. We then investigated whether inhibition of RIPK1 could alleviate neuroinflammation and neuronal apoptosis following SAH, thereby reducing brain edema and ameliorating neurobehavioral deficits. Additionally, the underlying mechanisms were also explored. Our research findings revealed the activation of RIPK1 kinase in both microglia and neurons following SAH, as marked by the phosphorylation of RIPK1 at serine 166. The upregulation of p-RIPK1(S166) resulted in a significant augmentation of inflammatory cytokines and chemokines, including TNF-α, IL-6, IL-1α, CCL2, and CCL5, as well as neuronal apoptosis. The activation of RIPK1 in microglia and neurons following SAH could be effectively suppressed by administration of Nec-1 s, a specific inhibitor of RIPK1. Consequently, inhibition of RIPK1 resulted in a downregulation of inflammatory cytokines and chemokines and attenuation of neuronal apoptosis after SAH in vitro. Furthermore, the administration of Nec-1 s effectively mitigated neuroinflammation, neuronal apoptosis, brain edema, and neurobehavioral deficits in mice following SAH. Our findings suggest that inhibiting RIPK1 kinase represents a promising therapeutic strategy for mitigating brain injury after SAH by attenuating RIPK1-driven neuroinflammation and neuronal apoptosis.
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Edema Encefálico , Lesões Encefálicas , Hemorragia Subaracnóidea , Animais , Camundongos , Apoptose , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Lesões Encefálicas/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Doenças Neuroinflamatórias , Ratos Sprague-Dawley , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Serina , Hemorragia Subaracnóidea/metabolismoRESUMO
Passive radiative cooling (PRC) that realizes thermal management without consuming any energy has attracted increasing attention. Unfortunately, polymer fibers with radiative cooling function fabricated via a facile, continuous, large-scale and eco-friendly method have been scarcely reported. Herein, polyethylene fibers containing directional microchannels (PFCDM) are facilely fabricated via melt extrusion and water leaching. Interestingly, fabric based on such hydrophobic PFCDM shows high sunlight reflectivity (93.6%), and mid-infrared emissivity (93.9%), endowing it with remarkable PRC performance. Compared with other reported examples, the as-prepared PFDCM fabric has the highest cooling power (i.e., 104.285 W m-2) and temperature drop (i.e., 27.71 °C). Furthermore, decent self-cleaning performance can keep the PFCDM fabric away from contamination and enable it to retain an excellent radiative cooling effect. The method proposed to fabricate PFCDM in this paper will widen the potential application of thermoplastic polyolefins in the field of radiative cooling.
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As a highly invasive malignancy, esophageal cancer (EC) is a global health issue, and was the eighth most prevalent cancer and the sixth leading cause of cancer-related death worldwide in 2020. Due to its highly immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy in treating EC; however, certain limitations and challenges still exist. In addition, tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment (TIME); thus, understanding the TIME is urgent and crucial, especially given the im-portance of an immunosuppressive microenvironment in tumor progression. The aim of this review was to better elucidate the mechanisms of the suppressive TIME, including cell infiltration, immune cell subsets, cytokines and signaling pathways in the tumor microenvironment of EC patients, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells, to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies. Therefore, personalized treatments could be developed to maximize the advantages of immunotherapy.
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Neoplasias Esofágicas , Imunoterapia , Microambiente Tumoral , Microambiente Tumoral/imunologia , Humanos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Imunoterapia/métodos , Transdução de Sinais/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Citocinas/metabolismo , Citocinas/imunologia , Evasão Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismoRESUMO
Dyes pollution is well known for their hazardous impacts on human health and the environment. The removal of dyes from wastewater has become an important issue. In this study, magnetic micrometer-sized particles AL-CTS@MNPs were synthesized from alkaline lignin (AL) and chitosan (CTS) by "one-pot method". The adsorbent presented higher selectivity adsorption effect on anionic dyes than amphoteric and cationic dyes, and even no adsorption effect on cationic methylene blue (MB), which showed that the anionic dyes could be better separated from the other two types of dyes. The adsorption isotherms of the dyes were highly consistent with the Langmuir model, and the maximum adsorption capacity was 329.50 mg/g for methyl orange (MO) and 20.00 mg/g for rhodamine B (RhB). AL-CTS@MNPs showed good adsorption of anionic dyes (MO) in the pH range of 3-9. Meanwhile, the adsorbent AL-CTS@MNPs were also characterized, showing rough surface with specific surface areas of 37.38 m2/g, pore diameter of 95.8 nm and porosity of 17.62 %. The particle sizes were ranged from 800 µm to 1300 µm. The electrostatic attraction and π-π* electron donor-acceptor interactions were the main forces between the adsorbent and anionic dyes. While the electrostatic repulsive force between the adsorbent and the cationic dyes resulted in the non-absorption of MB by AL-CTS@MNPs. Subsequently, the adsorbent maintained a removal rate of >95 % after five adsorption-desorption cycles, demonstrating its excellent stability and recoverability. Ultimately, the prepared AL-CTS@MNPs illuminated good prospect on complex components dyes wastewater treatment.
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Quitosana , Corantes , Lignina , Poluentes Químicos da Água , Quitosana/química , Adsorção , Lignina/química , Corantes/química , Corantes/isolamento & purificação , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Ânions/química , Porosidade , Purificação da Água/métodos , Concentração de Íons de Hidrogênio , Azul de Metileno/química , Azul de Metileno/isolamento & purificação , Cinética , Águas Residuárias/química , Nanopartículas de Magnetita/química , Compostos AzoRESUMO
BACKGROUND: Gliomas are the most common primary malignant tumours of the central nervous system, and neddylation may be a potential target for the treatment of gliomas. Our study analysed neddylation's potential role in gliomas of different pathological types and its correlation with immunotherapy. METHODS: Genes required for model construction were sourced from existing literature, and their expression data were extracted from the TCGA and CGGA databases. LASSO regression was employed to identify genes associated with the prognosis of glioma patients in TCGA and to establish a clinical prognostic model. Biological changes in glioma cell lines following intervention with hub genes were evaluated using the CCK-8 assay and transwell assay. The genes implicated in the model construction were validated across various cell lines using Western blot. We conducted analyses to examine correlations between model scores and clinical data, tumor microenvironments, and immune checkpoints. Furthermore, we investigated potential differences in molecular functions and mechanisms among different groups. RESULTS: We identified 249 genes from the Reactome database and analysed their expression profiles in the TCGA and CGGA databases. After using LASSO-Cox, four genes (BRCA1, BIRC5, FBXL16 and KLHL25, p < 0.05) with significant correlations were identified. We selected FBXL16 for validation in in vitro experiments. Following FBXL16 overexpression, the proliferation, migration, and invasion abilities of glioma cell lines all showed a decrease. Then, we constructed the NEDD Index for gliomas. The nomogram indicated that this model could serve as an independent prognostic marker. Analysis of the tumour microenvironment and immune checkpoints revealed that the NEDD index was also correlated with immune cell infiltration and the expression levels of various immune checkpoints. CONCLUSION: The NEDD index can serve as a practical tool for predicting the prognosis of glioma patients, and it is correlated with immune cell infiltration and the expression levels of immune checkpoints.
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BACKGROUND: The mitochondrial unfolded protein response (UPRmt) is a vital biological process that regulates mitochondrial protein homeostasis and enables glioblastoma cells to cope with mitochondrial oxidative stress in the tumor microenvironment. We previously reported that the binding of mitochondrial stress-70 protein (mtHSP70) to GrpE protein homolog 1 (GrpEL1) is involved in the regulation of the UPRmt. However, the mechanisms regulating their binding remain unclear. Herein, we examined the UPRmt in glioblastoma and explored whether modulating the interaction between mtHSP70 and GrpEL1 affects the UPRmt. METHODS: Western blot analysis, aggresome staining, and transmission electron microscopy were used to detect the activation of the UPRmt and protein aggregates within mitochondria. Molecular dynamics simulations were performed to investigate the impact of different mutations in mtHSP70 on its binding to GrpEL1. Endogenous site-specific mutations were introduced into mtHSP70 in glioblastoma cells using CRISPR/Cas9. In vitro and in vivo experiments were conducted to assess mitochondrial function and glioblastoma progression. RESULTS: The UPRmt was activated in glioblastoma cells in response to oxidative stress. mtHSP70 regulated mitochondrial protein homeostasis by facilitating UPRmt-progress protein import into the mitochondria. Acetylation of mtHSP70 at Lys595/653 enhanced its binding to GrpEL1. Missense mutations at Lys595/653 increased mitochondrial protein aggregates and inhibited glioblastoma progression in vitro and in vivo. CONCLUSIONS: We identified an innovative mechanism in glioblastoma progression by which acetylation of mtHSP70 at Lys595/653 influences its interaction with GrpEL1 to regulate the UPRmt. Mutations at Lys595/653 in mtHSP70 could potentially serve as therapeutic targets and prognostic indicators of glioblastoma.
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Glioblastoma , Proteínas de Choque Térmico HSP70 , Humanos , Proteínas de Choque Térmico HSP70/metabolismo , Acetilação , Glioblastoma/genética , Glioblastoma/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Microambiente TumoralRESUMO
Bridged chiral biaryls are axially chiral compounds with a medium-sized ring connecting the two arenes. Compared with plentiful methods for the enantioselective synthesis of biaryl compounds, synthetic approaches for this subclass of bridged atropisomers are limited. Here we show an atroposelective synthesis of 1,3-diaxial bridged eight-membered terphenyl atropisomers through an Co/SPDO (spirocyclic pyrrolidine oxazoline)-catalyzed aerobic oxidative coupling/desymmetrization reaction of prochiral phenols. This catalytic desymmetric process is enabled by combination of an earth-abundant Co(OAc)2 and a unique SPDO ligand in the presence of DABCO (1,4-diaza[2.2.2]bicyclooctane). An array of diaxial bridged terphenyls embedded in an azocane can be accessed in high yields (up to 99%) with excellent enantio- (>99% ee) and diastereoselectivities (>20:1 dr).
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Background: Phosgene is a chemical material widely used worldwide. No effective method has been developed to reverse its pathological injuries. Some studies have shown that neuronal inflammation in lung tissue is involved, but the specific mechanism has not been reported. Objective: To analyze the expression alterations of whole transcriptome gene sequencing bioinformatics and protein expression profile in lung tissue after phosgene aspiration lung injury (P-ALI) and find the main factors and pathways affecting the prognosis of P-ALI. Methods: Rat models of P-ALI were made by phosgene. Rats were divided into a P-ALI group and a blank group. Hematoxylin-eosin (HE) staining and lung wet/dry ratio measurement were used to evaluate the lung injury. The levels of inflammatory factors were measured by ELISA. High-throughput sequencing was used to measure the expression profile of each gene. Protein expression profiles were determined by label-free relative quantification of the differential proteome. Results: Lung injury such as the disordered structure of alveolar wall and inflammatory factors (IL-1ß, IL-18, and IL-33) were significantly increased in the P-ALI group (p < 0.05). There were 225 differentially expressed lncRNAs, including 85 upregulated and 140 downregulated genes. They were also the genomes with the most significant changes in transcriptome gene expression, mainly constituting cytoplasmic, synaptic structures and transporters, and involved in amino acid and carbon metabolism. There were 42 differentially expressed circRNAs, including 25 upregulated genes and 17 downregulated genes, mainly involved in cell composition, growth, differentiation, and division. There were only 10 differentially expressed miRNAs genes, all upregulated and mainly involved in the inflammatory response pathway. Proteome identification showed 79 differentially expressed proteins. KEGG enrichment analysis showed that it was mainly involved in the N-glycan biosynthesis pathway. Conclusion: We discovered that differentially regulated genes (lncRNAs, circRNAs, and miRNAs) were primarily associated with neuronal reflexes and synaptic signaling, including neurotransmitter transmission, ion signaling pathway conduction, neuronal projection, and synaptic vesicle circulation. They affected inflammatory factors and other metabolic pathways. This finding could be explored in future studies.
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Plasmonic photocatalysis demonstrates great potential for efficiently harnessing light energy. However, the underlying mechanisms remain enigmatic due to the transient nature of the reaction processes. Typically, plasmonic photocatalysis relies on the excitation of surface plasmon resonance (SPR) in plasmonic materials, such as metal nanoparticles, leading to the generation of high-energy or "hot electrons", albeit accompanied by photothermal heating or Joule effect. The ability of hot electrons to participate in chemical reactions is one of the key mechanisms, underlying the enhanced photocatalytic activity observed in plasmonic photocatalysis. Interestingly, surface-enhanced Raman scattering (SERS) spectroscopy allows the analysis of chemical reactions driven by hot electrons, as both SERS and hot electrons stem from the decay of SPR and occur at the hot spots. Herein, we propose a highly efficient SERS substrate based on cellulose paper loaded with either Ag nanoplates (Ag NPs) or AgPd hollow nanoplates (AgPd HNPs) for the in situ monitoring of C-C homocoupling reactions. The data analysis allowed us to disentangle the impact of hot electrons and the Joule effect on plasmon-enhanced photocatalysis. Computational simulations revealed an increase in the rate of excitation of hot carriers from single/isolated AgPd HNPs to an in-plane with a vertical stacking assembly, suggesting its promise as a photocatalyst under broadband light. In addition, the results suggest that the incorporation of Pd into an alloy with plasmonic properties may enhance its catalytic performance under light irradiation due to the collection of plasmon-excitation-induced hot electrons. This work has demonstrated the performance-oriented synthesis of hybrid nanostructures, providing a unique route to uncover the mechanism of plasmon-enhanced photocatalysis.
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Protein homeostasis is fundamental to the development of tumors. Ribosome-associated quality-control (RQC) is able to add alanine and threonine to the stagnant polypeptide chain C-terminal (CAT-tail) when protein translation is hindered, while Ankyrin repeat and zinc-finger domain-containing-protein 1 (ANKZF1) can counteract the formation of the CAT-tail, preventing the aggregation of polypeptide chains. In particular, ANKZF1 plays an important role in maintaining mitochondrial protein homeostasis by mitochondrial RQC (mitoRQC) after translation stagnation of precursor proteins targeting mitochondria. However, the role of ANKZF1 in glioblastoma is unclear. Therefore, the current study was aimed to investigate the effects of ANKZF1 in glioblastoma cells and a nude mouse glioblastoma xenograft model. Here, we reported that knockdown of ANKZF1 in glioblastoma cells resulted in the accumulation of CAT-tail in mitochondria, leading to the activated mitochondrial unfolded protein response (UPRmt) and inhibits glioblastoma malignant progression. Excessive CAT-tail sequestered mitochondrial chaperones HSP60, mtHSP70 and proteases LONP1 as well as mitochondrial respiratory chain subunits ND1, Cytb, mtCO2 and ATP6, leading to mitochondrial oxidative phosphorylation dysfunction, membrane potential impairment, and mitochondrial apoptotic pathway activation. Our study highlights ANKZF1 as a valuable target for glioblastoma intervention and provides an innovative insight for the treatment of glioblastoma through the regulating of mitochondrial protein homeostasis.
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Progressão da Doença , Glioblastoma , Camundongos Nus , Mitocôndrias , Proteínas Mitocondriais , Animais , Humanos , Camundongos , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Silenciamento de Genes , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Resposta a Proteínas não Dobradas , Ensaios Antitumorais Modelo de Xenoenxerto , Repetição de AnquirinaRESUMO
This study addresses the longstanding absence of a comprehensive phylogenetic backbone for the apple tribe Maleae, a deficiency attributed to limited taxon and marker sampling. We conducted an extensive taxon sampling, incorporating 563 plastomes from a diverse range of 370 species encompassing 26 presently recognized genera. Employing a range of phylogenetic inference methods, including RAxML and IQ-TREE2 for Maximum Likelihood (ML) analyses, we established a robust phylogenetic framework for the Maleae tribe. Our phylogenomic investigations provided compelling support for three major clades within Maleae. By integrating nuclear phylogenetic data with morphological and chromosomal evidence, we propose an updated infra-tribal taxonomic system, comprising subtribe Malinae Reveal, subtribe Lindleyinae Reveal, and subtribe Vauqueliniinae B.B.Liu (subtr. nov.). Plastid phylogenetic analysis also confirmed the monophyly of most genera, except for Amelanchier, Malus, Sorbus sensu lato, and Stranvaesia. In addition, we present a comprehensive taxonomic synopsis of Photinia and its morphological allies in the Old World, recognizing 27 species and ten varieties within Photinia, three species and two varieties within Stranvaesia, and two species and three varieties within Weniomeles. Furthermore, we also lectotypified 12 names and made two new combinations, Photiniamicrophylla (J.E.Vidal) B.B.Liu and Weniomelesatropurpurea (P.L.Chiu ex Z.H.Chen & X.F.Jin) B.B.Liu.
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In this work, we seek to learn multiple mainstream vision tasks concurrently using a unified network, which is storage-efficient as numerous networks with task-shared parameters can be implanted into a single consolidated network. Our framework, vision transformer (ViT)-MVT, built on a plain and nonhierarchical ViT, incorporates numerous visual tasks into a modest supernet and optimizes them jointly across various dataset domains. For the design of ViT-MVT, we augment the ViT with a multihead self-attention (MHSE) to offer complementary cues in the channel and spatial dimension, as well as a local perception unit (LPU) and locality feed-forward network (locality FFN) for information exchange in the local region, thus endowing ViT-MVT with the ability to effectively optimize multiple tasks. Besides, we construct a search space comprising potential architectures with a broad spectrum of model sizes to offer various optimum candidates for diverse tasks. After that, we design a layer-adaptive sharing technique that automatically determines whether each layer of the transformer block is shared or not for all tasks, enabling ViT-MVT to obtain task-shared parameters for a reduction of storage and task-specific parameters to learn task-related features such that boosting performance. Finally, we introduce a joint-task evolutionary search algorithm to discover an optimal backbone for all tasks under total model size constraint, which challenges the conventional wisdom that visual tasks are typically supplied with backbone networks developed for image classification. Extensive experiments reveal that ViT-MVT delivers exceptional performances for multiple visual tasks over state-of-the-art methods while necessitating considerably fewer total storage costs. We further demonstrate that once ViT-MVT has been trained, ViT-MVT is capable of incremental learning when generalized to new tasks while retaining identical performances for trained tasks. The code is available at https://github.com/XT-1997/vitmvt.