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The fermentation of the high-viscosity polysaccharide WL gum has always been associated with poor mass transfer. Appropriate impeller configurations are key factors in maintaining homogeneity and sufficient mass transfer conditions. Therefore, a flat-folded disc turbine impeller (FFDT) taking into account both the reduced cavitation effect and the increased contact area was designed. Besides, a curved cross impeller (CC) and a fishbone-shaped impeller (FS) generating axial flow were also designed. The energy consumption and efficiency of the designed impellers and eight reported impellers were evaluated through fermentation and principal component analysis (PCA). Compared to the commonly-used six-blade flat-blade disc turbine (FBDT), the ungassed power number of FFDT was reduced by 50 %. Combinations of six-blade Brumajin impeller (BM) + FFDT and CC + FFDT produced high WL gum production and viscosity (34.0 g/L, 35.50 g/L, and 62.64 Pa·s, 61.68 Pa·s, respectively) and were suitable impellers for WL biosynthesis. WL gum from BM + FFDT showed higher viscosity, viscoelasticity, and molecular weight than that from FBDT + FBDT. In addition, fewer amino acids and pyruvic acid intermediates were formed using BM + FFDT, indicating a greater metabolic flux towards WL gum synthesis. This work provided an important reference for the design of impellers in high-viscosity fermentation systems.
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Fermentação , Viscosidade , Polissacarídeos Bacterianos/química , Peso Molecular , Análise de Componente PrincipalRESUMO
Ulcerative colitis is a chronic disease with colonic mucosa injury. Nitazoxanide is an antiprotozoal drug in clinic. Nitazoxanide and its metabolite tizoxanide have been demonstrated to activate AMPK and inhibit inflammation, therefore, the aim of the present study is to investigate the effect of nitazoxanide on dextran sulfate sodium (DSS)-induced colitis and the underlying mechanism. Oral administration of nitazoxanide ameliorated the symptoms of mice with DSS-induced colitis, as evidenced by improving the increased disease activity index (DAI), the decreased body weight, and the shortened colon length. Oral administration of nitazoxanide ameliorated DSS-induced intestinal barrier dysfunction and reduced IL-6 and IL-17 expression in colon tissues. Mechanistically, nitazoxanide and its metabolite tizoxanide treatment activated AMPK and inhibited JAK2/STAT3 signals. Nitazoxanide and tizoxanide treatment increased caudal type homeobox 2 (CDX2) expression, increased alkaline phosphatase (ALP) activity and promoted tight junctions in Caco-2 cells. Nitazoxanide and tizoxanide treatment restored the decreased zonula occludens-1(ZO-1) and occludin protein levels induced by LPS or IL-6 in Caco-2 cells. On the other hand, nitazoxanide and tizoxanide regulated macrophage bias toward M2 polarization, as evidenced by the increased arginase-1expression in bone marrow-derived macrophages (BMDM). Nitazoxanide and tizoxanide reduced the increased IL-6, iNOS and CCL2 pro-inflammatory gene expressions and inhibited JAK2/STAT3 activation in BMDM induced by LPS. In conclusion, nitazoxanide protects against DSS-induced ulcerative colitis in mice through improving intestinal barrier and inhibiting inflammation and the underlying mechanism involves AMPK activation and JAK2/STAT3 inhibition.
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Colite Ulcerativa , Sulfato de Dextrana , Mucosa Intestinal , Nitrocompostos , Fator de Transcrição STAT3 , Tiazóis , Animais , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Nitrocompostos/farmacologia , Camundongos , Humanos , Células CACO-2 , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Sulfato de Dextrana/toxicidade , Fator de Transcrição STAT3/metabolismo , Masculino , Janus Quinase 2/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Inflamação/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Interleucina-6/metabolismo , Modelos Animais de DoençasRESUMO
A novel polycyclic quinazoline alkaloid (1) along with one new natural quinoline alkaloid (2) and two known quinoline alkaloids (3,4) were isolated from the marine-derived fungus Trichoderma longibrachiatum QD01. Structural determinations of those isolates were established by comprehensive spectroscopic analyses and literature comparison. Single-crystal X-ray diffraction analysis of novel compound verified its structure and stereochemistry, representing the first characterised crystal structure of a trimeric-type of tetrahydroquinazoline. Compound 4 exhibited potential antibacterial and anti-quorum sensing activity against C. violaceum and C. violaceum CV026. The sub-MIC of 4 observably decreased the violacein production in C. violaceum CV026 by 55% on 15 µg/mL. Furthermore, molecular docking results revealed that 4 has stronger binding interactions with CviR receptor than ligand C6-HSL with lower binding energy of -8.68 kcal/mol. Hydrogen bond and π-π interactions formed by Trp84, Tyr88, Trp111, and Phe126 were predicted to play an important role in the inhibition against C. violaceum CV026.
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We introduce a biotinylated D-amino acid probe capable of metabolically incorporating into bacterial PG. Leveraging the robust affinity between biotin and streptavidin, the probe has demonstrated efficacy in imaging, capture, and targeted inactivation of Gram-positive bacteria through synergistic pairings with commercially available streptavidin-modified fluorescent dyes and nanomaterials. The versatility of the probe is underscored by its compatibility with a variety of commercially available streptavidin-modified reagents. This adaptability allows the probe to be applied across diverse scenarios by integrating with these commercial reagents.
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Bactérias , Biotina , Estreptavidina/química , Biotina/química , Bactérias/metabolismo , Corantes Fluorescentes/química , Bactérias Gram-Positivas/metabolismoRESUMO
Silver nanoparticles (AgNPs) are extensively used as an antibacterial agent, and monitoring the dissolution behavior of AgNPs in native biological environments is critical in both optimizing their performance and regulating their safety. However, current assessment methods rely on sophisticated analytical tools that are off-site and time-consuming with potential underestimations, due to complicated sample preparation. Although localized surface plasmon resonance (LSPR) sensing offers a facile method for the detection of AgNP dissolution, it is limited by low sensitivity and poor nanoparticle stability in native biological environments. Herein, we constructed a highly sensitive and stable LSPR sensor using gold-silver core-shell nanoparticles (Au@AgNPs), in combination with polymeric stabilizing agents, for the direct measurement of the Ag shell dissolution in native biological media. The high sensitivity was attributed to the acute and large LSPR shift generated by bimetallic nanoparticles. The sensor was used for the real-time monitoring of the Ag dissolution of Au@AgNPs during their co-culture with both bacteria and fibroblast cells. The media pH was found to dominate the Ag dissolution process, where Au@AgNPs exhibited bactericidal effects in the bacteria environment with relatively low pH, but they showed little toxicity towards fibroblast cells at pH 7.4. The minimum inhibition concentration of Au@AgNPs for bacterial growth was found similar to that of AgNO3 in terms of released Ag amount. Thus, stabilized Au@AgNPs not only allow the in-situ monitoring of Ag dissolution via LSPR sensing but also constitute an effective antibacterial agent with controlled toxicity, holding great potential for future biomedical and healthcare applications.
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Nanopartículas Metálicas , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Prata , Antibacterianos/farmacologia , OuroRESUMO
Stimuli-responsive polymers can respond to internal stimuli, such as reactive oxygen species (ROS), glutathione (GSH), and pH, biological stimuli, such as enzymes, and external stimuli, such as lasers and ultrasound, etc., by changing their hydrophobicity/hydrophilicity, degradability, ionizability, etc., and thus have been widely used in biomedical applications. Due to the characteristics of the tumor microenvironment (TME), stimuli-responsive polymers that cater specifically to the TME have been extensively used to prepare smart nanovehicles for the targeted delivery of therapeutic and diagnostic agents to tumor tissues. Compared to conventional drug delivery nanosystems, TME-responsive nanosystems have many advantages, such as high sensitivity, broad applicability among different tumors, functional versatility, and improved biosafety. In recent years, a great deal of research has been devoted to engineering efficient stimuli-responsive polymeric nanosystems, and significant improvement has been made to both cancer diagnosis and therapy. In this review, we summarize some recent research advances involving the use of stimuli-responsive polymer nanocarriers in drug delivery, tumor imaging, therapy, and theranostics. Various chemical stimuli will be described in the context of stimuli-responsive nanosystems. Accordingly, the functional chemical groups responsible for the responsiveness and the strategies to incorporate these groups into the polymer will be discussed in detail. With the research on this topic expending at a fast pace, some innovative concepts, such as sequential and cascade drug release, NIR-II imaging, and multifunctional formulations, have emerged as popular strategies for enhanced performance, which will also be included here with up-to-date illustrations. We hope that this review will offer valuable insights for the selection and optimization of stimuli-responsive polymers to help accelerate their future applications in cancer diagnosis and treatment.
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Neoplasias , Polímeros Responsivos a Estímulos , Humanos , Medicina de Precisão , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Microambiente TumoralRESUMO
BACKGROUND: Over the last few decades of treatment, the outcomes for at least some subsets of neuroendocrine neoplasms (NENs) have improved. However, the identification of new vulnerabilities for this heterogeneous group of cancers remains a priority. METHODS: Using two libraries of compounds selected for potential repurposing, we identified the inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylases (HDAC) as the agents with the highest activity. We validated the hits in an expanded set of neuroendocrine cell lines and examined the mechanisms of action. RESULTS: In Kelly, NH-6, and NCI-H82, which are two neuroblastoma and one small cell lung cancer cell lines, respectively, metabolic studies suggested that cell death following NAMPT inhibition is the result of a reduction in basal oxidative phosphorylation and energy production. NAMPT is the rate-limiting enzyme in the production of NAD+, and in the three cell lines, NAMPT inhibition led to a marked reduction in the ATP and NAD+ levels and the catalytic activity of the citric acid cycle. Moreover, comparative analysis of the mRNA expression in drug-sensitive and -insensitive cell lines found less dependency of the latter on oxidative phosphorylation for their energy requirement. Further, the analysis of HDAC and NAMPT inhibitors administered in combination found marked activity using low sub-lethal concentrations of both agents, suggesting a synergistic effect. CONCLUSION: These data suggest NAMPT inhibitors alone or in combination with HDAC inhibitors could be particularly effective in the treatment of neuroendocrine neoplasms.
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The broad-spectrum antimicrobial ability of de novo designed amphiphilic antimicrobial peptides (AMPs) G(IIKK)3I-NH2 (G3) and C8-G(IIKK)2I-NH2 (C8G2) have been demonstrated. Nonetheless, their potential as anti-quorum-sensing (anti-QS) agents, particularly against the opportunistic pathogen Pseudomonas aeruginosa at subinhibitory concentrations, has received limited attention. In this study, we proved that treating P. aeruginosa PAO1 with both AMPs at subinhibitory concentrations led to significant inhibition of QS-regulated virulence factors, including pyocyanin, elastase, proteases, and bacterial motility. Additionally, the AMPs exhibited remarkable capabilities in suppressing biofilm formation and their elimination rate of mature biofilm exceeded 95%. Moreover, both AMPs substantially downregulated the expression of QS-related genes. CD analysis revealed that both AMPs induced structural alterations in the important QS-related protein LasR in vitro. Molecular docking results indicated that both peptides bind to the hydrophobic groove of the LasR dimer. Notably, upon mutating key binding sites (D5, E11, and F87) to Ala, the binding efficiency of LasR to both peptides significantly decreased. We revealed the potential of antibacterial peptides G3 and C8G2 at their sub-MIC concentrations as QS inhibitors against P. aeruginosa and elucidated their action mechanism. These findings contribute to our understanding of the therapeutic potential of these peptides in combating P. aeruginosa infections by targeting the QS system.
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Peptídeos Antimicrobianos , Pseudomonas aeruginosa , Pseudomonas aeruginosa/fisiologia , Simulação de Acoplamento Molecular , Percepção de Quorum , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/química , Proteínas de Bactérias/metabolismoRESUMO
Bacterial infections and excessive inflammation can impede the healing of wounds. Hydrogels have emerged as a promising approach for dressing bacterial-infected injuries. However, some antibacterial hydrogels are complex, costly, and even require assistance with other instruments such as light, making them unsuitable for routine outdoor injuries. Here, we developed an in-situ generating hydrogel via hybridizing oxidized ß-D-glucan with antimicrobial peptide C8G2 through the Schiff base reaction. This hydrogel is easily accessible and actively contributes to the whole healing process of bacterial-infected wounds, demonstrating remarkable antibacterial activity and biological compatibility. The pH-sensitive reversible imine bond enables the hydrogel to self-heal and sustainably release the antibacterial peptide, thereby improving its bioavailability and reducing toxicity. Meanwhile, the immunoregulating ß-D-glucan inhibits the release of inflammatory factors while promoting the release of anti-inflammatory factors. In methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin wound models, the hybrid hydrogel showed superior antibacterial and anti-inflammatory activity, enhanced the M2 macrophage polarization, expedited wound closure, and regenerated epidermis tissue. These features make this hydrogel an appealing wound dressing for treating multi-drug-resistant bacteria-infected wounds.
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Surdez , Staphylococcus aureus Resistente à Meticilina , beta-Glucanas , Humanos , beta-Glucanas/uso terapêutico , Hidrogéis , Cicatrização , Glucanos , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêuticoRESUMO
The development of autoclavable hydrogels has been driven by the need for materials that can withstand the rigors of sterilization without compromising their properties or functionality. Many conventional hydrogels cannot withstand autoclave treatment owing to the breakdown of their composition or structure under the high-temperature and high-pressure environment of autoclaving. Here, the effect of autoclaving on the physical, mechanical, and biological properties of bovine serum albumin methacryloyl (BSAMA) cryogels at three protein concentrations (3, 5, and 10%) was extensively studied. We found that BSAMA cryogels at three concentrations remained little changed after autoclaving in terms of gross shape, pore structure, and protein secondary structure. Young's modulus of autoclaved BSAMA cryogels (BSAMAA) at low concentrations (3 and 5%) was similar to that of BSAMA cryogels, whereas 10% BSAMAA exhibited a higher Young's modulus value, compared with 10% BSAMA. Interestingly, BSAMAA cryogels prolonged degradation. Importantly, cell viability, drug release, and hemolytic behaviors were found to be similar among the pre- and post-autoclaved cryogels. Above all, autoclaving proved to be more effective in sterilizing BSAMA cryogels from bacteria contamination than UV and ethanol treatments. Thus, autoclavable BSAMA cryogels with uncompromising properties would be useful for biomedical applications.
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INTRODUCTION: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria. METHODS: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable tumor, necrosis, and stroma. For each slide, tumor bed area was measured microscopically, and pre-embedded formulas calculated unweighted and weighted major pathologic response (MPR) averages to reflect variable tumor bed proportion. RESULTS: Unanimous agreement among pathologists for MPR was observed in 68 patients (81%), and inter-rater agreement (IRA) was 0.84 (95% confidence interval [CI]: 0.76-0.92) and 0.86 (95% CI: 0.79-0.93) for unweighted and weighted averages, respectively. Overall, unweighted and weighted methods did not reveal significant differences in the classification of MPR. The highest concordance by both methods was observed for cases with more than 95% viable tumor (IRA = 0.98, 95% CI: 0.96-1) and 0% viable tumor (IRA = 0.94, 95% CI: 0.89-0.98). The most common reasons for discrepancies included interpretations of tumor bed, presence of prominent stromal inflammation, distinction between reactive and neoplastic pneumocytes, and assessment of invasive mucinous adenocarcinoma. CONCLUSIONS: Our study revealed excellent reliability in cases with no residual viable tumor and good reliability for MPR with the IASLC recommended less than or equal to 10% cutoff for viable tumor after neoadjuvant therapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante/métodos , Reprodutibilidade dos Testes , Carcinoma Pulmonar de Células não Pequenas/patologia , Pulmão/patologiaRESUMO
Cobalt-ceria binary oxide nanojunctions were prepared by a sol-gel method with various chelating agents. The formed interfaces among CeO2 and Co3O4 can promote the generation of nucleophilic â¢O2- from O2 and then tune the catalytic oxidizability of the as-prepared CoCe nanojunctions. Given the results of HMF oxidations, malic acid as a complexing agent during the preparation process of the cobalt-ceria binary oxide nanojunctions can lead to a good catalytic performance on HMF oxidations to FDCA, and a remarkable FDCA selectivity of 92.3% and almost 100% HMF conversion were obtained at 110 °C under O2 and alkali conditions. By comparing the catalytic performance of the nanojunctions and physical mixing of cobalt-ceria binary oxide on oxidations of HMF, 5-hydroxymethyl-2-furancarboxylic acid (HFCA), and 5-formyl-2-furancarboxylic acid (FFCA), the interfaces intrinsically enhanced the FDCA yield dominantly via boosting the HMF oxidation to HFCA with â¢O2- during the stepwise oxidation of HMF to FDCA. It can be enlightening that the introduction of the active sites for transforming O2 to â¢O2- to promote the transformation of HMF into HFCA is the key to boosting the selective aerobic oxidation of HMF to FDCA.
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Recent Alzheimer's research has shown increasing interest in the caspase-2 (Casp2) enzyme. However, the available Casp2 inhibitors, which have been pentapeptides or peptidomimetics, face challenges for use as CNS drugs. In this study, we successfully screened a 1920-compound chloroacetamide-based, electrophilic fragment library from Enamine. Our two-point dose screen identified 64 Casp2 hits, which were further evaluated in a ten-point dose-response study to assess selectivity over Casp3. We discovered compounds with inhibition values in the single-digit micromolar and sub-micromolar range, as well as up to 32-fold selectivity for Casp2 over Casp3. Target engagement analysis confirmed the covalent-irreversible binding of the selected fragments to Cys320 at the active site of Casp2. Overall, our findings lay a strong foundation for the future development of small-molecule Casp2 inhibitors.
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Caspase 2 , Inibidores de Caspase , Caspase 2/metabolismo , Caspase 3/metabolismo , Domínio Catalítico , Inibidores de Caspase/químicaRESUMO
In this paper, a unified optimization model for medical image fusion based on tensor decomposition and the non-subsampled shearlet transform (NSST) is proposed. The model is based on the NSST method and the tensor decomposition method to fuse the high-frequency (HF) and low-frequency (LF) parts of two source images to obtain a mixed-frequency fused image. In general, we integrate low-frequency and high-frequency information from the perspective of tensor decomposition (TD) fusion. Due to the structural differences between the high-frequency and low-frequency representations, potential information loss may occur in the fused images. To address this issue, we introduce a joint static and dynamic guidance (JSDG) technique to complement the HF/LF information. To improve the result of the fused images, we combine the alternating direction method of multipliers (ADMM) algorithm with the gradient descent method for parameter optimization. Finally, the fused images are reconstructed by applying the inverse NSST to the fused high-frequency and low-frequency bands. Extensive experiments confirm the superiority of our proposed TDFusion over other comparison methods.
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We investigated the influence of hydroxyl groups on the anti-quorum-sensing (anti-QS) and anti-biofilm activity of structurally similar cyclic dipeptides, namely cyclo(L-Pro-L-Tyr), cyclo(L-Hyp-L-Tyr), and cyclo(L-Pro-L-Phe), against Pseudomonas aeruginosa PAO1. Cyclo(L-Pro-L-Phe), lacking hydroxyl groups, displayed higher virulence factor inhibition and cytotoxicity, but showed less inhibitory ability in biofilm formation. Cyclo(L-Pro-L-Tyr) and cyclo(L-Hyp-L-Tyr) suppressed genes in both the las and rhl systems, whereas cyclo(L-Pro-L-Phe) mainly downregulated rhlI and pqsR expression. These cyclic dipeptides interacted with the QS-related protein LasR, with similar binding efficiency to the autoinducer 3OC12-HSL, except for cyclo(L-Pro-L-Phe) which had lower affinity. In addition, the introduction of hydroxyl groups significantly improved the self-assembly ability of these peptides. Both cyclo(L-Pro-L-Tyr) and cyclo(L-Hyp-L-Tyr) formed assembly particles at the highest tested concentration. The findings revealed the structure-function relationship of this kind of cyclic dipeptides and provided basis for our follow-up research in the design and modification of anti-QS compounds.
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Bacterial infections are one of the major contributing factors to human mortality, which can cause secondary damage to the injured area, such as leading to inflammation, tissue death, and even personal death. Herein, we developed a novel cyclodextrin (CD)-modified amphiphilic microgel with a 3D network nanostructure that encapsulates hydrophilic indocyanine green (ICG) as a trigger for photothermal therapy (PTT) and hydrophobic N,N'-disubstituted-butyl-N,N'-dinitro-1,4-benzenediamine (BNN6) as a heat-sensitive nitric oxide (NO) donor (CD@I-B) to cope with bacteria-infected wound therapy. This biocompatible microgel showed excellent broad-spectrum antibacterial capability under near-infrared (NIR) laser irradiation, while the photothermal conversion process promotes the deswelling of the microgel and release of NO, which synergistically accelerates wound healing. The therapy strategy by synergizing NO delivery with PTT promoted the formation of neovascularization and collagen fiber as well as the elimination of inflammation cells, thus facilitating wound healing. Our study further demonstrates the fantastic opportunities of applying high-performance microgels to provide all-in-one sites for treating wound sterilization and healing.
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Microgéis , Óxido Nítrico , Humanos , Terapia Fototérmica , Doadores de Óxido Nítrico , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , InflamaçãoRESUMO
The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild-type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII-VENUS and DR5-GFP lines) in B-deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis-related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport-related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN-Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis-related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Boro/metabolismo , Raízes de Plantas/metabolismoRESUMO
Bacterial resistance has led to increased interest in the use of antibacterial peptides (AMPs), but their clinical application is limited by poor stability and solubility, as well as complex cytotoxicity. Chemical modification is a common strategy to modulate AMPs. In this study, a de novo designed AMP (G3) was modified by adding an alkyl acid at the N-terminal and a monosaccharide at the C-terminal. Bio-activity assays demonstrated that conjugation with n-caprylic acid increased the peptide's antibacterial activity and permeabilized the membrane. Attachment of glucose or galactose at the C-terminal improved its biofilm inhibitory capacity and marginally reduced cytotoxicity. The hybrid peptide, containing both n-caprylic acid and galactose, exhibited excellent antibacterial and antibiofilm activity, as well as permeabilized the outer membrane.
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Peptídeos Catiônicos Antimicrobianos , Galactose , Peptídeos Catiônicos Antimicrobianos/química , Glicosilação , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade MicrobianaRESUMO
Heterogeneous image fusion (HIF) is an enhancement technique for highlighting the discriminative information and textural detail from heterogeneous source images. Although various deep neural network-based HIF methods have been proposed, the most widely used single data-driven manner of the convolutional neural network always fails to give a guaranteed theoretical architecture and optimal convergence for the HIF problem. In this article, a deep model-driven neural network is designed for this HIF problem, which adaptively integrates the merits of model-based techniques for interpretability and deep learning-based methods for generalizability. Unlike the general network architecture as a black box, the proposed objective function is tailored to several domain knowledge network modules to model the compact and explainable deep model-driven HIF network termed DM-fusion. The proposed deep model-driven neural network shows the feasibility and effectiveness of three parts, the specific HIF model, an iterative parameter learning scheme, and data-driven network architecture. Furthermore, the task-driven loss function strategy is proposed to achieve feature enhancement and preservation. Numerous experiments on four fusion tasks and downstream applications illustrate the advancement of DM-fusion compared with the state-of-the-art (SOTA) methods both in fusion quality and efficiency. The source code will be available soon.
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Recently, unpaired medical image enhancement is one of the important topics in medical research. Although deep learning-based methods have achieved remarkable success in medical image enhancement, such methods face the challenge of low-quality training sets and the lack of a large amount of data for paired training data. In this paper, a dual input mechanism image enhancement method based on Siamese structure (SSP-Net) is proposed, which takes into account the structure of target highlight (texture enhancement) and background balance (consistent background contrast) from unpaired low-quality and high-quality medical images. Furthermore, the proposed method introduces the mechanism of the generative adversarial network to achieve structure-preserving enhancement by jointly iterating adversarial learning. Experiments comprehensively illustrate the performance in unpaired image enhancement of the proposed SSP-Net compared with other state-of-the-art techniques.