RESUMEN

Frequent occurrence of wound infection caused by multiple-resistant bacteria (MRB) has posed a serious challenge to the current healthcare system relying on antibiotics. The development of novel antimicrobial materials with high safety and efficacy to heal wound infection is of great importance in combating this crisis. Herein, we prepared a promising antibacterial hydrogel by cross-linking ferrous ions (Fe2+) with the deprotonated carboxyl anion in sodium alginate (Na-ALG) to cure wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, ferrous-modified Na-ALG (Fe-ALG) hydrogel demonstrated better properties compared to the traditional Na-ALG-based hydrogels, including injectability, self-healing, appropriate fluidity, high-water retention, potent MRSA-killing efficacy, and excellent biocompatibility. Importantly, the addition of Fe2+ enhances the antibacterial efficacy of the Na-ALG hydrogel, enabling it to effectively eliminate MRSA and accelerate the healing of antibiotic-resistant bacterial-infected wounds in a remarkably short period (10 days). This modification not only facilitates wound closure and fur generation, but also mitigates systemic inflammation, thereby effectively impeding the spread of MRSA to the lungs. Taken together, Fe-ALG hydrogel is a promising therapeutic material for treating wound infections by Staphylococcus aureus, especially by antibiotic-resistant strains like MRSA.

Asunto(s)

Alginatos , Antibacterianos , Compuestos Ferrosos , Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Cicatrización de Heridas , Infección de Heridas , Alginatos/química , Alginatos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Infecciones Estafilocócicas/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones , Pruebas de Sensibilidad Microbiana , Masculino

RESUMEN

In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.

Asunto(s)

Bronquitis , Coinfección , Gripe Humana , Infecciones Estafilocócicas , Staphylococcus aureus , Traqueítis , Humanos , Coinfección/diagnóstico , Masculino , Femenino , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/complicaciones , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Preescolar , Traqueítis/diagnóstico , Traqueítis/microbiología , Traqueítis/complicaciones , Bronquitis/diagnóstico , Bronquitis/microbiología , Bronquitis/complicaciones , Estudios Retrospectivos , Staphylococcus aureus/aislamiento & purificación , Lactante , Niño , Broncoscopía/métodos , Unidades de Cuidado Intensivo Pediátrico , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Necrosis , Virus de la Influenza A/aislamiento & purificación

RESUMEN

Sulfur-containing compounds have diverse biological functions and are crucial in crop protection chemistry. In this study, a series of novel 1-methyl-1H-pyrazol-5-amine derivatives incorporating disulfide moieties were synthesized and evaluated for their antimicrobial properties. In vitro bioassays demonstrated that compound 7f displayed potent antifungal activity against Valsa mali, with an EC50 value of 0.64 mg/L, outperforming allicin (EC50 = 26.0 mg/L) but lower than tebuconazole (EC50 = 0.33 mg/L). In vivo experiments confirmed that compound 7f could effectively inhibit V. mali infection on apples at a concentration of 100 mg/L, similar to the positive control tebuconazole. Mechanistic studies revealed that compound 7f could induce hyphal shrinkage and collapse, trigger intracellular reactive oxygen species accumulation, modulate antioxidant enzyme activities, initiate lipid peroxidation, and ultimately cause irreversible oxidative damage to the cells of V. mali. Additionally, compound 7b exhibited notable antibacterial activity, particularly against Pseudomonas syringae pv. actinidiae, with a MIC90 value of 1.56 mg/L, surpassing the positive controls allicin, bismerthiazol, and streptomycin sulfate. These findings suggest that 1-methyl-1H-pyrazol-5-amine derivatives containing disulfide moieties hold promise as potent candidates for the development of novel antimicrobial agents.

RESUMEN

BACKGROUND: Currently, prostate cancer (PCa) prebiopsy medical image diagnosis mainly relies on mpMRI and PI-RADS scores. However, PI-RADS has its limitations, such as inter- and intra-radiologist variability and the potential for imperceptible features. The primary objective of this study is to evaluate the effectiveness of a machine learning model based on radiomics analysis of MRI T2-weighted (T2w) images for predicting PCa in prebiopsy cases. METHOD: A retrospective analysis was conducted using 820 lesions (363 cases, 457 controls) from The Cancer Imaging Archive (TCIA) Database for model development and validation. An additional 83 lesions (30 cases, 53 controls) from Hong Kong Queen Mary Hospital were used for independent external validation. The MRI T2w images were preprocessed, and radiomic features were extracted. Feature selection was performed using Cross Validation Least Angle Regression (CV-LARS). Using three different machine learning algorithms, a total of 18 prediction models and 3 shape control models were developed. The performance of the models, including the area under the curve (AUC) and diagnostic values such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were compared to the PI-RADS scoring system for both internal and external validation. RESULTS: All the models showed significant differences compared to the shape control model (all p < 0.001, except SVM model PI-RADS+2 Features p = 0.004, SVM model PI-RADS+3 Features p = 0.002). In internal validation, the best model, based on the LR algorithm, incorporated 3 radiomic features (AUC = 0.838, sensitivity = 76.85%, specificity = 77.36%). In external validation, the LR (3 features) model outperformed PI-RADS in predictive value with AUC 0.870 vs. 0.658, sensitivity 56.67% vs. 46.67%, specificity 92.45% vs. 84.91%, PPV 80.95% vs. 63.64%, and NPV 79.03% vs. 73.77%. CONCLUSIONS: The machine learning model based on radiomics analysis of MRI T2w images, along with simulated biopsy, provides additional diagnostic value to the PI-RADS scoring system in predicting PCa.

RESUMEN

An efficient pyridine-catalyzed chemoselective four-component cascade reaction of aromatic aldehydes, malononitrile/cyanoacetates, Morita-Baylis-Hillman (MBH) carbonates, and alcohols has been established. This one-pot reaction progressed in an unusual reaction with solvent participation via a Knoevenagel condensation/oxa-Michael addition/SN2' substitution sequence. This method allowed for facile access to an array of functionalized chain alkylbenzenes and dihydroquinolinones bearing one all-carbon quaternary center in moderate to excellent yields. It is worth noting that the configuration of the all-carbon quaternary center could be modulated by changing only the electron-withdrawing groups via a tandem reduction/cyclization reaction.

RESUMEN

BACKGROUND: Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, the relationship between these depression-like behaviors and demyelination remains unclear. Arketamine, the (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects in CRS-exposed mice. METHODS: We examined whether arketamine can improve both depression-like behaviors and demyelination in the brains of CRS-exposed mice. Additionally, we investigated the role of transforming growth factor ß1 (TGF-ß1) in the beneficial effects of arketamine. RESULTS: A single dose of arketamine (10 mg/kg) improved both depression-like behavior and demyelination in the corpus callosum of CRS-exposed mice. Correlations were found between depression-like behaviors and demyelination in this region. Furthermore, pretreatment with RepSox, an inhibitor of TGF-ß1 receptor, significantly blocked the beneficial effects of arketamine on depression-like behaviors and demyelination in CRS-exposed mice. Finally, a single intranasal administration of TGF-ß1 ameliorated both depression-like behaviors and demyelination in CRS-exposed mice. LIMITATIONS: The precise mechanisms by which TGF-ß1 contributes to the effects of arketamine remain unclear. CONCLUSIONS: These data suggest that CRS-induced demyelination in the corpus callosum may contribute to depression-like behaviors, and that arketamine can mitigate these changes through a TGF-ß1-dependent mechanism.

RESUMEN

PURPOSE: The objective of this systematic review and metaanalysis is to compare the efficacy and safety of decompression alone versus decompression plus fusion in single-level lumbar spinal stenosis with spondylolisthesis. METHODS: A comprehensive search of the PubMed, Embase, Cochrane Library, and Ovid Medline databases was conducted to find randomized control trials (RCTs) or cohort studies that compared decompression alone and decompression plus fusion in single-level lumbar spinal stenosis with spondylolisthesis. Operation time; reoperation; postoperative complications; postoperative Oswestry disability index(ODI) scores and scores related to back and leg pain were collected from eligible studies for meta-analysis. RESULTS: We included 3 randomized controlled trials and 9 cohort studies with 6182 patients. The decompression alone group showed less operative time(P < 0.001) and intraoperative blood loss(p = 0.000), and no significant difference in postoperative complications was observed in randomized controlled trials(p = 0.428) or cohort studies(p = 0.731). There was no significant difference between the other two groups in reoperation(P = 0.071), postoperative ODI scores and scores related to back and leg pain. CONCLUSIONS: In this study, we found that the decompression alone group performed better in terms of operation time and intraoperative blood loss, and there was no significant difference between the two surgical methods in rate of reoperation and postoperative complications, ODI, low back pain and leg pain. Therefore, we come to the conclusion that decompression alone is not inferior to decompression and fusion in patients with single-level lumbar spinal stenosis with spondylolisthesis.

Asunto(s)

Descompresión Quirúrgica , Vértebras Lumbares , Fusión Vertebral , Estenosis Espinal , Espondilolistesis , Humanos , Estenosis Espinal/cirugía , Descompresión Quirúrgica/métodos , Descompresión Quirúrgica/efectos adversos , Fusión Vertebral/métodos , Fusión Vertebral/efectos adversos , Espondilolistesis/cirugía , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tempo Operativo , Reoperación

RESUMEN

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening condition with high mortality, categorized into 5 Groups based on distinct etiologies. Fasudil, a potent vasodilator targeting the RhoA/Rho kinase pathway, holds promise for diverse PH pathologies. However, a comprehensive systematic evaluation of its clinical benefits remains elusive. METHODS: We conducted a systematic search across several databases. Meta-analysis using odds ratio and mean difference was performed, with an assessment of studies' quality and pooled evidence. RESULTS: Studies on Group-2 and -3 PH reports eligible data for meta-analysis. Inclusion of 3269 patients with Group-3 PH demonstrated that fasudil significantly increased effective events, FEV1, 6-minute walking distance (6MWD) and arterial PaO2, and decreased mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP); Inclusion of 197 patients with Group-2 PH suggested that fasudil significantly increased 6MWD and PaO2, and decreased PASP. Subgroup analysis revealed no significant difference between dosages of 30 and 60 mg/day, while durations and methods of fasudil administration might affect therapeutic effectiveness in patients with Group-3 PH. CONCLUSIONS: By providing comprehensive and robust evidence, our study favor the beneficial effects of fasudil by enhancing FEV1, 6MWD and PaO2, and reducing mPAP and PASP on patients with Group-3 PH, suggesting fasudil as a viable treatment recommendation for these patients and highlighting the need for further studies to inform healthcare policies. PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42022308947.

RESUMEN

Melanocytes derived from neural crest cells harbor the BRAF V600E mutation, which is the predominant driver of nevus formation in humans. This mutation leads to malignant cell proliferation and subsequent cell cycle arrest, culminating in oncogene-induced senescence and nevus development. Nevertheless, emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAF V600E-induced senescent melanocytes. Moreover, the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAF V600E, via the mitogen-activated protein kinase signaling pathway, triggers nevus formation. This study provides an overview and discussion of the molecular mechanisms underpinning BRAF V600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation. It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAF V600E animal models created through gene editing technologies.

Asunto(s)

Nevo , Proteínas Proto-Oncogénicas B-raf , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Humanos , Animales , Nevo/genética , Nevo/metabolismo , Melanocitos/metabolismo , Mutación , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo

RESUMEN

Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine's protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis.

Asunto(s)

Alcaloides , Proteína Axina , Factores de Crecimiento de Fibroblastos , Análisis de la Aleatorización Mendeliana , Alcamidas Poliinsaturadas , Sepsis , Humanos , Sepsis/metabolismo , Sepsis/genética , Alcamidas Poliinsaturadas/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Proteína Axina/metabolismo , Proteína Axina/genética , Piperidinas/uso terapéutico , Benzodioxoles , Inflamación/metabolismo , Interleucina-2/metabolismo , Interleucina-2/genética , Mediadores de Inflamación/metabolismo , Factor-23 de Crecimiento de Fibroblastos

RESUMEN

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical, and food importance, such as mycotoxins, antibiotics, and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expressions that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition of the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulate production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

RESUMEN

Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin's structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound 3g demonstrating the most potent in vivo anti-TMV activity. At 500 µg/mL, compound 3g achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides ningnanmycin and ribavirin. Notably, the syn-diastereomer (syn-3g) exhibited superior antiviral activity compared to the anti-diastereomer (anti-3g). Mechanistic studies revealed that syn-3g could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound 3g, with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.

Asunto(s)

4-Butirolactona , Antivirales , Podofilotoxina , Virus del Mosaico del Tabaco , Podofilotoxina/química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , Antivirales/síntesis química , Antivirales/farmacología , Virus del Mosaico del Tabaco/efectos de los fármacos , Ensamble de Virus/efectos de los fármacos , Proteínas de la Cápside/metabolismo , Protección de Cultivos , Cristalografía por Rayos X , Relación Estructura-Actividad , Nicotiana/efectos de los fármacos , Nicotiana/metabolismo , Nicotiana/virología , Simulación del Acoplamiento Molecular

RESUMEN

In response to corneal injury, an activation of corneal epithelial stem cells and their direct progeny the early transit amplifying (eTA) cells to rapidly proliferate is critical for proper re-epithelialization. Thus, it is important to understand how such stem/eTA cell activation is regulated. Angiotensin-converting enzyme 2 (ACE2) is predominantly expressed in the stem/eTA-enriched limbal epithelium but its role in the limbal epithelium was unclear. Single cell RNA sequencing (scRNA-seq) suggested that Ace2 involved the proliferation of the stem/eTA cells. Ace2 was reduced following corneal injury. Such reduction enhanced limbal epithelial proliferation and downregulated LCN2, a negative regulator of proliferation in a variety of tissues, via upregulating TGFA and consequently activating epidermal growth factor receptor (EGFR). Inhibition of EGFR or overexpression of LCN2 reversed the increased proliferation in limbal epithelial cells lacking ACE2. Our findings demonstrate that after corneal injury, ACE2 is downregulated, which activates limbal epithelial cell proliferation via a TGFA/EGFR/LCN2 pathway.

RESUMEN

Reprogramming tumor-associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF-κB p65, MAPK p38 and JNK by glycolysis-mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti-PD-L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.

RESUMEN

Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C- IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/ß-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.

Asunto(s)

Lesión Pulmonar Aguda , Movimiento Celular , Interleucina-17 , Pulmón , Ratones Endogámicos C57BL , Sepsis , Animales , Sepsis/inmunología , Sepsis/complicaciones , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Ratones , Interleucina-17/metabolismo , Interleucina-17/inmunología , Pulmón/inmunología , Pulmón/patología , Masculino , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Vía de Señalización Wnt/inmunología , Macrófagos Alveolares/inmunología , Intestino Delgado/inmunología , Intestino Delgado/patología , Linfocitos Intraepiteliales/inmunología , Modelos Animales de Enfermedad , Antígenos Ly/metabolismo , Memoria Inmunológica

RESUMEN

Fusarium crown and root rot (FCRR) has emerged as a highly destructive soil-borne disease, posing a significant threat to the safe cultivation of tomatoes in recent years. The pathogen of tomato FCRR is Fusarium oxysporum f. sp. radicis-lycopersici (Forl). To explore potential phytotoxins from Forl, eight undescribed diterpenoids namely fusariumic acids A-H (1-8) were isolated. Their structures were elucidated by using spectroscopic data analyses, quantum chemical calculations, and X-ray crystallography. Fusariumic acids A (1) and C-H (3-8) were typical isocassadiene-type diterpenoids, while fusariumic acid B (2) contained a cage-like structure with an unusual 7,8-seco-isocassadiene skeleton. A biosynthetic pathway of 2 was proposed. Fusariumic acids A (1) and C-H (3-8) were further assessed for their phytotoxic effects on tomato seedlings at 200 µg/mL. Among them, fusariumic acid F (6) exhibited the strongest inhibition against the hypocotyl and root elongation of tomato seedlings, with inhibitory rates of 61.3 and 45.3%, respectively.

Asunto(s)

Diterpenos , Fusarium , Enfermedades de las Plantas , Raíces de Plantas , Solanum lycopersicum , Fusarium/efectos de los fármacos , Solanum lycopersicum/microbiología , Diterpenos/química , Diterpenos/farmacología , Enfermedades de las Plantas/microbiología , Raíces de Plantas/microbiología , Raíces de Plantas/química , Estructura Molecular

RESUMEN

The origin of life on Earth is believed to be from the ocean, which offers abundant resources in its depths. However, deep-sea operations are limited due to the lack of underwater robots and rigid grippers with sensitive force sensors. Therefore, it is crucial for deep-sea pressure sensors to be integrated with mechanical hands for manipulation. Here, a flexible stress sensor is presented that can function effectively under high water pressure in the deep ocean. Inspired by biological structures found in the abyssal zone, our sensor is designed with an internal and external pressure balance structure (hollow interlocking spherical structure). The digital light processing (DLP) three-dimensional (3D) printing technology is utilized to construct this complex structure after obtaining optimized structural parameters using finite element simulation. The sensor exhibits linear sensitivity of 0.114 kPa-1 within the range of 0-15 kPa and has an extremely short response time of 32 ms, good dynamic-static load response capability, and excellent resistance cycling stability. It shows high sensitivity of 1.74 kPa-1 even under 30 MPa static water pressures and the theoretical working pressure can exceed 110 MPa, which provides a new solution for deep-sea robots.

RESUMEN

Subways are widely used in major cities around the world, and subway fine particulate matter (PM2.5) is the main source of daily PM2.5 exposure for urban residents. Exposure to subway PM2.5 leads to acute inflammatory damage in humans, which has been confirmed in mouse in vivo studies. However, the concrete mechanism by which subway PM2.5 causes airway damage remains obscure. In this study, we found that subway PM2.5 triggered release of pro-inflammatory cytokines such as interleukin 17E, tumor necrosis factor α, transforming growth factor ß, and thymic stromal lymphopoietin from human bronchial epithelial cells (BEAS-2B) in a dose-effect relationship. Subsequently, supernatant recovered from the subway PM2.5 group significantly increased expression of the aforementioned cytokines in BEAS-2B cells compared with the subway PM2.5 group. Additionally, tight junctions (TJs) of BEAS-2B cells including zonula occludens-1, E-cadherin, and occludin were decreased by subway PM2.5 in a dose-dependent manner. Moreover, supernatant recovered from the subway PM2.5 group markedly decreased the expression of these TJs compared with the control group. Furthermore, inhibitors of toll-like receptors (TLRs) and nuclear factor-kappa B (NF-κB), as well as chelate resins (e.g., chelex) and deferoxamine, remarkably ameliorated the observed changes of cytokines and TJs caused by subway PM2.5 in BEAS-2B cells. Therefore, these results suggest that subway PM2.5 induced a decline of TJs after an initial ascent of cytokine expression, and subway PM2.5 altered expression of both cytokines and TJs by activating TLRs/NF-κB-dependent pathway in BEAS-2B cells. The metal components of subway PM2.5 may contribute to the airway epithelial injury.

RESUMEN

Erianin, crepidatin, and chrysotobibenzyl are typical medicinal polymethoxylated bibenzyls (PMBs) that are commercially produced in Dendrobium species. PMBs' chemo-diversity is mediated by the manifold combinations of O-methylation and hydroxylation in a definite order, which remains unsolved. To unequivocally elucidate the methylation mechanism of PMBs, 15 possible intermediates in the biosynthetic pathway of PMBs were chemically synthesized. DcOMT1-5 were highly expressed in tissues where PMBs were biosynthesized, and their expression patterns were well-correlated with the accumulation profiles of PMBs. Moreover, cell-free orthogonal tests based on the synthesized intermediates further confirmed that DcOMT1-5 exhibited distinct substrate preferences and displayed hydroxyl-group regiospecificity during the sequential methylation process. The stepwise methylation of PMBs was discovered from SAM to dihydro-piceatannol (P) in the following order: P → 3-MeP → 4-OH-3-MeP → 4-OH-3,5-diMeP → 3,3'(4'),5-triMeP → 3,4,4',5-tetraMeP (erianin) or 3,3',4,5-tetraMeP (crepidatin) → 3,3',4,4',5-pentaMeP (chrysotobibenzyl). Furthermore, the regioselectivities of DcOMTs were investigated by ligand docking analyses which corresponded precisely with the catalytic activities. In summary, the findings shed light on the sequential catalytic mechanisms of PMB biosynthesis and provide a comprehensive PMB biosynthetic network in D. catenatum. The knowledge gained from this study may also contribute to the development of plant-based medicinal applications and the production of high-value PMBs.