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Adenosine receptor-mediated signaling, especially adenosine A2A receptor (A2AR) signaling, has been implicated in wound healing. However, the role of endothelial cells (ECs) in A2AR-mediated wound healing and the mechanism underlying this effect are still unclear. Here, we showed that the expression of A2AR substantially increased after wounding and was especially prominent in granulation tissue. The delaying effects of A2AR knockout (KO) on wound healing are due mainly to the effect of A2AR on endothelial cells, as shown with A2AR-KO and EC-A2AR-KO mice. Moreover, the expression of c-Ski, which is especially prominent in CD31-positive cells in granulation tissue, increased after wounding and was decreased by both EC-A2AR KO and A2AR KO. In human microvascular ECs (HMECs), A2AR activation induced EC proliferation, migration, tubule formation and c-Ski expression, whereas c-Ski depletion by RNAi abolished these effects. Mechanistically, A2AR activation promotes the expression of c-Ski through an ERK/CREB-dependent pathway. Thus, A2AR-mediated angiogenesis plays a critical role in wound healing, and c-Ski is involved mainly in the regulation of angiogenesis by A2AR via the ERK/CREB pathway. These findings identify A2AR as a therapeutic target in wound repair and other angiogenesis-dependent tissue repair processes.

Asunto(s)

Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Ratones Noqueados , Receptor de Adenosina A2A , Cicatrización de Heridas , Cicatrización de Heridas/fisiología , Cicatrización de Heridas/genética , Animales , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2A/genética , Ratones , Humanos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Células Endoteliales/metabolismo , Neovascularización Fisiológica , Transducción de Señal , Sistema de Señalización de MAP Quinasas/fisiología , Proliferación Celular/genética , Movimiento Celular/genética , Angiogénesis

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Impacts of co-cold extrusion (≤50 °C) of whey protein isolate (WPI) and cysteine (Cys, 0, 20, 40, 60, 80 and 100 mmol/L) on its physicochemical, in vitro digestion and rheological properties were investigated. As Cys concentration increased, the emulsifying properties and in vitro digestibility of co-extruded WPI-Cys products showed an increasing trend. Specifically, when Cys reached 100 mmol/L, surface hydrophobicity, emulsification activity index (EAI), emulsification stability index (ESI) and in vitro stomach digestibility of the co-extruded WPI-Cys products increased by 205.07%, 77.51%, 193.95% and 71.81% compared with WPI, respectively. Principal component analysis (PCA) results further indicated that co-extruded WPI-Cys at a concentration of 100 mmol/L had the best functional properties. In addition, co-extruded WPI-Cys exhibited the strongest Péclet number (Pe) value and apparent viscosity at a Cys concentration of 100 mmol/L among all samples. Therefore, co-extrusion would be an effective method for modifying WPI, providing whey protein-based ingredients with excellent functional properties for food processing.

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Vδ1T cells, a rare subset of γδT cells, hold promise for treating solid tumors. Unlike conventional T cells, they recognize tumor antigens independently of the MHC antigen-presentation pathway, making them a potential "off-the-shelf" cell therapy product. However, isolation and activation of Vδ1T cells is challenging, which has limited their clinical investigation. Here, we developed a large-scale clinical-grade manufacturing process for Vδ1T cells and validated the therapeutic potential of B7-H3-CAR-modified Vδ1T cells in treating solid tumors. Co-expression of interleukin-2 with the B7-H3-CAR led to durable anti-tumor activity of Vδ1T cells in vitro and in vivo. In multiple subcutaneous and orthotopic mouse xenograft tumor models, a single intravenous administration of the CAR-Vδ1T cells resulted in complete tumor regression. These modified cells demonstrated significant in vivo expansion and robust homing ability to tumors, akin to natural tissue-resident immune cells. Additionally, the B7-H3-CAR-Vδ1T cells exhibited a favorable safety profile. In conclusion, B7-H3-CAR-modified Vδ1T cells represent a promising strategy for treating solid tumors.

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Rationale: Food allergy is a prevalent disease in the U.S., affecting nearly 30 million people. The primary management strategy for this condition is food avoidance, as limited treatment options are available. The elevation of pathologic IgE and over-reactive mast cells/basophils is a central factor in food allergy anaphylaxis. This study aims to comprehensively evaluate the potential therapeutic mechanisms of a small molecule compound called formononetin in regulating IgE and mast cell activation. Methods: In this study, we determined the inhibitory effect of formononetin on the production of human IgE from peripheral blood mononuclear cells of food-allergic patients using ELISA. We also measured formononetin's effect on preventing mast cell degranulation in RBL-2H3 and KU812 cells using beta-hexosaminidase assay. To identify potential targets of formononetin in IgE-mediated diseases, mast cell disorders, and food allergies, we utilized computational modeling to analyze mechanistic targets of formononetin from various databases, including SEA, Swiss Target Prediction, PubChem, Gene Cards, and Mala Cards. We generated a KEGG pathway, Gene Ontology, and Compound Target Pathway Disease Network using these targets. Finally, we used qRT-PCR to measure the gene expression of selected targets in KU812 and U266 cell lines. Results: Formononetin significantly decreased IgE production in IgE-producing human myeloma cells and PBMCs from food-allergic patients in a dose-dependent manner without cytotoxicity. Formononetin decreased beta-hexosaminidase release in RBL-2H3 cells and KU812 cells. Formononetin regulates 25 targets in food allergy, 51 in IgE diseases, and 19 in mast cell diseases. KEGG pathway and gene ontology analysis of targets showed that formononetin regulated disease pathways, primary immunodeficiency, Epstein-Barr Virus, and pathways in cancer. The biological processes regulated by formononetin include B cell proliferation, differentiation, immune response, and activation processes. Compound target pathway disease network identified NFKB1, NFKBIA, STAT1, STAT3, CCND1, TP53, TYK2, and CASP8 as the top targets regulated at a high degree by formononetin. TP53, STAT3, PTPRC, IL2, and CD19 were identified as the proteins mostly targeted by formononetin. qPCR validated genes of Formononetin molecular targets of IgE regulation in U266 cells and KU812 cells. In U266 cells, formononetin was found to significantly increase the gene expression of NFKBIA, TP53, and BCL-2 while decreasing the gene expression of BTK TYK, CASP8, STAT3, CCND1, STAT1, NFKB1, IL7R. In basophils KU812 cells, formononetin significantly increased the gene expression of NFKBIA, TP53, and BCL-2 while decreasing the gene expression of BTK, TYK, CASP8, STAT3, CCND1, STAT1, NFKB1, IL7R. Conclusion: These findings comprehensively present formononetin's mechanisms in regulating IgE production in plasma cells and degranulation in mast cells.

Asunto(s)

Hipersensibilidad a los Alimentos , Inmunoglobulina E , Isoflavonas , Quinasas Janus , Leucocitos Mononucleares , Mastocitos , Factores de Transcripción STAT , Transducción de Señal , Isoflavonas/farmacología , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina E/metabolismo , Mastocitos/inmunología , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Transcripción STAT/metabolismo , Quinasas Janus/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Femenino , Adulto , Degranulación de la Célula/efectos de los fármacos , Animales , Persona de Mediana Edad

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In this study, the synergistic effect and weak gel mechanism of XG and Gleditsia sinensis polysaccharide (GSP) in different ratios were studied through the rheological properties, microstructure and molecular simulation based on density functional theory (DFT). The results of rheological properties showed that the mixtures formed a weak gel at the concentration of 0.5 % (w/v), with the synergistic impact peaking at a XG/GSP ratio of 3:7. Weak gels produced by XG and GSP had the intersection of G' and G" within the temperature sweep range, and the largest change in the G' slope at a XG/GSP ratio of 3:7. By calculating the interaction energy, it was found that the backbone of XG was more likely to interact with the backbone of GSP. Furthermore, the XG mainchain intersected with the backbone of GSP in a cross shape ("X" shape). As a result, this paper proposed a possible mechanism for the formation of the XG/GSP weak gel, with XG as the main chain and GSP as the grid point, and the main interaction type being hydrogen bonding, with the van der Waals force also involved. The results provide new insight for designing and producing physical gels with specific interactions in food industry.

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Pulmonary fibrosis (PF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults with poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. However, the molecular mechanisms regulating AEC senescence in PF are incompletely understood. Herein, we provided evidence to support the function of Krüppel-like factor 14 (KLF14), a novel Krüppel-like transcription factor, in the regulation of AEC senescence during PF. We confirmed that the expression of KLF14 was up-regulated in PF patients and mice treated with bleomycin (BLM). KLF14 knockdown resulted in more pronounced structural disruption of the lung tissue and swelling of the alveolar septum, which led to significantly increased mortality in BLM-induced PF mice. Mechanistically, RNA-seq analysis indicated that KLF14 decreased the senescence of AECs by inhibiting endoplasmic reticulum (ER) stress. Furthermore, the pharmacological activation of KLF14 conferred protection against PF in mice. In conclusion, our findings reveal a protective role for KLF14 in preventing AECs from senescence and shed light on the development of KLF14-targeted therapeutics for PF.

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Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.

Asunto(s)

Cannabinoides , Mieloma Múltiple , Telomerasa , Telómero , Proteína p53 Supresora de Tumor , Humanos , Mieloma Múltiple/tratamiento farmacológico , Línea Celular Tumoral , Telómero/efectos de los fármacos , Telómero/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Cannabinoides/farmacología , Telomerasa/metabolismo , Supervivencia Celular/efectos de los fármacos , FN-kappa B/metabolismo , Inmunoglobulina E , Inmunoglobulina G , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos

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Background: The biochemical and genetic characteristics of four very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) patients, clarifying their pathogenic genetic factors and evaluating the application value of genetic diagnosis in the early diagnosis of VLCADD, are reported and discussed in this article. Methods: Patients underwent blood tandem mass spectrometry (MS/MS), urine gas chromatography (GC/MS), and high-throughput sequencing technology. New variants were analyzed for pathogenicity using bioinformatics software. Swiss-PdbViewer software was used to predict the effect of variants on the structure of the very-long-chain acyl-CoA dehydrogenase (VLCAD) protein. Result: A total of four VLCADD patients were diagnosed. They revealed elevated levels of C14, C14:1, C14:2, C14:1/C2, C14:1/C10, and C14:1/C12:1. Two patients were early-onset neonatal cases and died during infancy and the neonatal period, respectively. Seven kinds of variants were detected, including four novel variants. Bioinformatics software revealed that the variants were harmful, and the Swiss-PdbViewer results suggest that variation affects protein conformation. Conclusion: This study identified four novel ACADVL gene variants. These findings contribute to the understanding of the genetic basis and pathogenesis of VLCADD. Meanwhile, the study enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of VLCADD, indicating that genetic diagnosis plays an essential role in the early diagnosis and treatment of VLCADD.

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The mitochondrial distribution and morphology family 33 gene (MDM33) regulates mitochondrial homeostasis by mediating the mitochondrial fission process in yeast. The wheat head blight Fusarium graminearum contains an FgMdm33 protein that is orthologous to Saccharomyces cerevisiae Mdm33, albeit its function remains unknown. We have reported here the roles of FgMdm33 in regulating fungal morphogenesis, mitochondrial morphology, autophagy, apoptosis, and fungal pathogenicity. The ΔFgmdm33 mutants generated through a homologous recombination strategy in this study exhibited defects in terms of mycelial growth, conidia production, and virulence. Hyphal cells lacking FgMDM33 displayed elongated mitochondria and a dispensable respiratory-deficient growth phenotype, indicating the possible involvement of FgMDM33 in mitochondrial fission. The ΔFgmdm33 mutants displayed a remarkable reduction in the proteolysis of GFP-FgAtg8, whereas the formation of autophagic bodies in the hyphal cells of mutants was recorded under the induction of mitophagy. In addition, the transcriptional expression of the apoptosis-inducing factor 1 gene (FgAIF1) was significantly upregulated in the ΔFgmdm33 mutants. Cumulatively, these results indicate that FgMDM33 is involved in mitochondrial fission, non-selective macroautophagy, and apoptosis and that it regulates fungal growth, conidiation, and pathogenicity of the head blight pathogen.

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Phthalic acid esters (PAEs) are emerging pollutants that need to be analyzed precisely. Chromatography-based determination of PAE content in soils are frequently affected by matrix effect, which may limit the quantification of different kinds of PAEs from different types of soil. Here we optimized a QuEChERS protocol combined with gas chromatography-mass spectrometry (GC-MS) for simultaneous determination of 16 PAEs in different soils. PAEs in different type of soils (fluvo-aquic soil, red soil, and black soil) were extracted with acetonitrile followed by GC-MS detection based on quantitative ion internal standard method. All 16 PAEs showed excellent linear relationships with mass peak areas (R2 > 0.99). The limits of detection (LOD) and limits of quantitation (LOQ) of all the samples were in the range of 0.91-66.97 µg/kg and 2.7-200.9 µg/kg, respectively. The accurate test at 0.5, 0.1, and 1.0 mg/kg spiking level recorded recovery rate between 80.11% and 100.99% with relative standard deviations (RSDs) ranging from 0.37 to 8.50% in tested matrices. No significant matrix effect was observed for most tested PAEs. This is a simple method with high sensitivity and strong stability, which is suitable and reproducible for quantifying large number of PAEs in different types of soil.

Asunto(s)

Ésteres , Cromatografía de Gases y Espectrometría de Masas , Ácidos Ftálicos , Contaminantes del Suelo , Suelo , Ácidos Ftálicos/análisis , Suelo/química , Ésteres/análisis , Contaminantes del Suelo/análisis , Límite de Detección

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Gas molecules, as a family of unique polyatomic building blocks, have long been considered hard to involve in molecular assembly or construct assembled materials due to their structural simplicity yet paucity of defined interacting sites. To solve this non-trivial challenge, a core idea is to break the limit of current ways of bonding gas molecules, endowing them with new modes of interactions that match the basic requirements of molecular assembly. In recent years, a new concept, named the dynamic gas-bridged bond (DGB), has emerged, which allows for gas molecules to constitute a dynamic bridging structure between other building blocks with the aid of frustrated Lewis pairs. This makes it possible to harness gas in a supramolecular or dynamic manner. Herein, this perspective discusses distinct dynamic natures of DGBs and manifests their particular functions in various fields, including the control of molecular/polymeric self-assembly nanostructures, creation of multidimensional assembled materials, and recyclable catalysts. The future research direction and challenges of dynamic gas-bridged chemistry toward gas-programmed self-assembly and gas-constructed adaptive materials are highlighted.

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BACKGROUND: OFA (Opioid-free anesthesia) has the potential to reduce the occurrence of opioid-related adverse events and enhance postoperative recovery. Our research aimed to investigate whether OFA, combining esketamine and dexmedetomidine, could serve as an alternative protocol to traditional OBA (opioid-based anesthesia) in shoulder arthroscopy, particularly in terms of reducing PONV (postoperative nausea and vomiting). METHODS: A total of 60 patients treated with shoulder arthroscopy from September 2021 to September 2022 were recruited. Patients were randomly assigned to the OBA group (n = 30) and OFA group (n = 30), receiving propofol-remifentanil TIVA (total intravenous anesthesia) and esketamine-dexmedetomidine intravenous anesthesia, respectively. Both groups received ultrasound-guided ISBPB(interscalene brachial plexus block)for postoperative analgesia. RESULTS: The incidence of PONV on the first postoperative day in the ward (13.3% vs. 40%, P < 0.05) was significantly lower in the OFA group than in the OBA group. Moreover, the severity of PONV was less severe in the OFA group than in the OBA group in PACU (post-anesthesia care unit) (0 [0, 0] vs. 0 [0, 3], P<0.05 ) and in the ward 24 h postoperatively ( 0 [0, 0] vs. 0 [0, 2.25], P<0.05). Additionally, the OFA group experienced a significantly shorter length of stay in the PACU compared to the OBA group (39.4 ± 6.76 min vs. 48.7 ± 7.90 min, P < 0.001). CONCLUSIONS: Compared to the OBA with propofol-remifentanil, the OFA with esketamine- dexmedetomidine proved to be feasible for shoulder arthroscopy, resulting in a reduced incidence of PONV and a shorter duration of stay in the PACU. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (No: ChiCTR2100047355), 12/06/2021.

Asunto(s)

Analgésicos Opioides , Anestésicos Intravenosos , Artroscopía , Dexmedetomidina , Ketamina , Náusea y Vómito Posoperatorios , Propofol , Remifentanilo , Humanos , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Dexmedetomidina/administración & dosificación , Masculino , Remifentanilo/administración & dosificación , Propofol/administración & dosificación , Femenino , Artroscopía/métodos , Persona de Mediana Edad , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Adulto , Náusea y Vómito Posoperatorios/prevención & control , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/etiología , Anestésicos Intravenosos/administración & dosificación , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnóstico , Anestesia Intravenosa/métodos , Bloqueo del Plexo Braquial/métodos

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Osimertinib is a third-generation tyrosine kinase inhibitor that targets mutant epidermal growth factor receptor (EGFR). The success of FLAURA and ADAURA trials prompted the license of Osimertinib for the treatment of EGFR mutant non-small cell lung cancer (NSCLC) at advanced stage and for patients with stages IB to IIIA disease in post-operative setting. In the present study, we described neoadjuvant use of Osimertinib in an EGFR mutant NSCLC patient with locally metastatic disease (T2aN2M0). Intriguingly, the cavitated NSCLC resembled an impressive"Halloween pumpkin" appearance that dramatically responded to Osimertinib treatment. Downstaging of N2 metastatic disease was reached and surgical resection was scheduled. The post-operative clinical stage was IA3. The patient was recommended to continue Osimertinib adjuvant treatment and our follow-ups showed no signs of disease recurrence. Our case study underscored the feasibility of Osimertinib as a neoadjuvant and adjuvant therapy for patients with locally advanced EGFR mutant NSCLC.

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INTRODUCTION: Skin blanching assay has been established as a surrogate method for assessing bioequivalence of topical corticosteroids. This study aimed to apply the skin blanching assay to evaluate the bioequivalence of a test desonide cream (T) compared with the reference Desonide® (R) using Chinese skins. Additionally, the pharmacokinetics and safety profiles were also assessed. METHODS: By detecting the degree of skin blanching under different dose duration in a pilot dose-duration-response study, the area under the observed effect-time curve (AUEC) and half of the maximum effect (ED50) was calculated. Based on this, the skin color of different time points after a dose duration of ED50, D1 (0.5×ED50) and D2 (2×ED50) were detected as a pharmacodynamic indicator to compare between test and reference creams. A single-center, single-dose, randomized, open-label, two-cycle crossover pharmacokinetic studies were designed to make sure the exposure of tested formulations was not higher than that of the reference formulations. Subjects experiencing adverse events (AEs) were monitored and utilized for safety analysis. RESULTS: These studies involved twelve subjects for the dose-duration-response study, 100 subjects for the bioequivalence study, and twelve subjects for pharmacokinetic study. The results showed that the population ED50 was 0.88±0.45 h, the mean ratio of area under effective curve (AUEC0-24h) of test and reference preparations was 0.95, with a 90% confidence interval as 88.09%-101.72%, indicating the bioequivalence of the test formulation and Desonide®. The maximum concentration (Cmax) and exposure (AUC0-t) of T and R were 20.8 ± 11.5 pg/mL versus 19.7 ± 10.1 pg/mL, respectively, and 451.04 ± 363.65 pg∙h/mL versus 541.47 ± 581.41 pg∙h/mL, respectively. The systemic exposure of a single dose of the test cream was not higher than that of the reference preparation. All of the volunteers experienced grade 1 adverse events (AEs), suggesting that single administration of the test desonide cream is well tolerated in the Chinese healthy population. CONCLUSIONS: This study demonstrated the applicability of skin blanching assay in Chinese skins and established the bioequivalence of test and reference desonide creams.

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Pinewood nematodes (PWN, Bursaphelenchus xylophilus) are destructive plant parasitic nematodes that cause pine wilt disease (PWD) by attacking the vascular systems of pine trees, resulting in widespread tree mortality. Research has shown that there are connections between nematode-associated microbes and PWD. Yet the variations in microbial communities across different geographic regions are not well-understood. In this study, we examined the bacterial and fungal communities associated with nematodes and infested wood collected from 34 sites across three vegetation zones in China, as well as samples from the United States, using 16S rRNA and internal transcribed spacer (ITS) gene amplicon sequencing. The predominant genera Pseudomonas and Rhodococcus were found in nematodes, and Acinetobacter was present in the wood of PWD-infected pine trees across China. Network analysis revealed that core bacterial taxa belonged to the Pseudomonadota and Actinomycetota phyla for the nematodes, whereas the Pseudomonadota and Bacteroidota phyla were dominant in the infested wood. Identification of enriched key microbial taxa in nematodes and infested wood across vegetation zones indicates distinct biogeographic microbial community structures and key bacterial species. Although the nematode-associated bacterial community showed consistency across geographic distances, the similarity of the PWD pine trees' bacterial community decreased with distance, suggesting a spatial correlation with environmental variables. Our findings enhance our understanding of the microbiota associated with pinewood nematode (PWN) and offer valuable insights into PWD management. IMPORTANCE: Our research uncovered specific bacteria and fungi linked to pinewood nematode (PWN) and infested wood in three different vegetation zones in China, as well as samples from the United States. This sheds light on the critical roles of certain microbial groups, such as Pseudomonas, Acinetobacter, and Stenotrophomonas, in influencing PWN fitness. Understanding these patterns provides valuable insights into the dynamics of PWN-associated microbiomes, offering potential strategies for managing pine wilt disease (PWD). We found significant correlations between geographic distance and similarity in bacterial communities in the infested wood, indicating a spatial influence on wood-associated microbial communities due to limited dispersal and localized environmental conditions. Further investigations of these spatial patterns and driving forces are crucial for understanding the ecological processes that shape microbial communities in complex ecosystems and, ultimately, for mitigating the transmission of PWN in forests.

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BACKGROUND: Sclerotinia sclerotiorum is a highly destructive phytopathogenic fungus that poses a significant threat to a wide array of crops. The current constraints in genetic manipulation techniques impede a thorough comprehension of its pathogenic mechanisms and the development of effective control strategies. RESULTS: Herein, we present a highly efficient genetic transformation system for S. sclerotiorum, leveraging the use of fusiform nanoparticles, which are synthesized with FeCl3 and 2,6-diaminopyrimidine (DAP). These nanoparticles, with an average longitude length of 59.00 nm and a positively charged surface, facilitate the direct delivery of exogenous DNA into the mycelial cells of S. sclerotiorum, as well as successful integration with stable expression. Notably, this system circumvents fungal protoplast preparation and tedious recovery processes, streamlining the transformation process considerably. Furthermore, we successfully employed this system to generate S. sclerotiorum strains with silenced oxaloacetate acetylhydrolase-encoding gene Ss-oah1. CONCLUSIONS: Our findings demonstrate the feasibility of using nanoparticle-mediated delivery as a rapid and reliable tool for genetic modification in S. sclerotiorum. Given its simplicity and high efficiency, it has the potential to significantly propel genetic research in filamentous fungi, offering new avenues for elucidating the intricacies of pathogenicity and developing innovative disease management strategies.

Asunto(s)

Ascomicetos , Nanopartículas , Transformación Genética , Ascomicetos/genética , Nanopartículas/química , Pirimidinas , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo

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To understand the land use development trends in Shaanxi Province under different scenarios and effectively assess the spatiotemporal evolution of terrestrial ecological carbon stocks in Shaanxi Province under land use changes, the study used Markov-FLUS and InVEST models to analyze the impact of land use changes in Shaanxi Province from 2000 to 2020. The impact of carbon storage changes and the spatiotemporal changes in land use structure, carbon storage, and carbon density under three different scenarios were simulated and assessed in Shaanxi Province in 2025 and 2030. The results showed： ① The ROC values of various categories in the coupled Markov-FLUS model were all above 0.7, showing high accuracy and excellent classification performance. The model had a good ability to explain the land use driving factors in the study area, with high accuracy and excellent classification performance. ② From 2000 to 2020, the cultivated land in Shaanxi Province increased significantly. Forest land increased significantly, and the increase in forest land area with high carbon sequestration efficiency caused the carbon storage in Shaanxi Province to increase from 1 546.95 Tg to 1 616.25 Tg. The changes in various regions in Shaanxi Province from 2000 to 2020 were different, among which the carbon storage in Yan'an was significantly increased by 18.89 Tg, whereas the carbon storage in Yulin significantly decreased by 3.29 Tg in 20 years. ③ Altitude, precipitation, and temperature became the main factors affecting the spatiotemporal changes in carbon storage in Shaanxi Province from 2020 to 2030. In three of the years between 2025 and 2030, under different scenarios, the carbon stocks under the ecological priority scenario were 1 632.27 Tg and 1 647.43 Tg, respectively. The carbon storage and its growth rate were significantly higher than in the natural development scenario and the cultivated land protection scenario. ④ The proportion of carbon storage increase areas under the ecological priority scenario was high. In the cultivated land protection scenario, the proportion of reduction areas was lower than that of the natural development scenario, and the distribution of carbon storage was the most balanced. At the same time, the southern and northern areas of the Loess Plateau in northern Shaanxi need to focus on the protection of the ecological environment in future development. The research results can, to a certain extent, provide reference for promoting the construction of ecological Shaanxi and formulating carbon neutral strategic planning.

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Designing a high-performance cathode is essential for the development of proton-conducting solid oxide fuel cells (H-SOFCs), and nanocomposite cathodes have proven to be an effective means of achieving this. However, the mechanism behind the nanocomposite cathodes' remarkable performance remains unknown. Doping the Co element into BaZrO3 can result in the development of BaCoO3 and BaZr0.7Co0.3O3 nanocomposites when the doping concentration exceeds 30%, according to the present study. The construction of the BaCoO3/BaZr0.7Co0.3O3 interface is essential for the enhancement of the cathode catalytic activity, as demonstrated by thin-film studies using pulsed laser deposition to simulate the interface of the BCO and BZCO individual particles and first-principles calculations to predict the oxygen reduction reaction steps. Eventually, the H-SOFC with a BaZr0.4Co0.6O3 cathode produces a record-breaking power density of 2253 mW cm-2 at 700°C.

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Radiotherapy (RT) is often administered, either alone or in combination with other therapies, for most malignancies. However, the degree of tumor oxygenation, damage to adjacent healthy tissues, and inaccurate guidance remain issues that result in discontinuation or failure of RT. Here, a multifunctional therapeutic platform based on Ir@WO3-x is developed which simultaneously addresses these critical issues above for precision radiosensitization. Ir@WO3-x nanoreactors exhibit strong absorption of X-ray, acting as radiosensitizers. Moreover, ultrasmall Ir enzyme-mimic nanocrystals (NCs) are decorated onto the surface of the nanoreactor, where NCs have catalyst-like activity and are sensitive to H2O2 in the tumor microenvironment (TME) under near infrared-II (NIR-II) light stimulation. They efficiently catalyze the conversion of H2O2 to O2, thereby ameliorating hypoxia, inhibiting the expression of HIF-1α, and enhancing RT-induced DNA damage in cancerous tissue, further improving the efficiency of RT. Additionally, in response to high H2O2 levels in TME, the Ir@WO3-x nanoreactor also exerts peroxidase-like activity, boosting exogenous ROS, which increases oxidative damage and enhances ROS-dependent death signaling. Furthermore, Ir@WO3-x can serve as a high-quality computed tomography contrast agent due to its high X-ray attenuation coefficient and generation of pronounced tumor-tissue contrast. This report highlights the potential of advanced health materials to enhance precision therapeutic modalities.

RESUMEN

Loop-mediated isothermal amplification (LAMP) is a novel method for nucleic acid detection known for its isothermal properties, high efficiency, sensitivity, and specificity. LAMP employs 4 to 6 primers targeting 6 to 8 regions of the desired sequence, allowing for amplification at temperatures between 60 and 65°C and the production of up to 109 copies within a single hour. The product can be monitored by various methods such as turbidimetry, fluorometry, and colorimetry. However, it faces limitations such as the risk of non-specific amplification, challenges in primer design, unsuitability for short gene sequences, and difficulty in multiplexing. Recent advancements in polymerase and primer design have enhanced the speed and convenience of the LAMP reaction. Additionally, integrating LAMP with technologies like rolling circle amplification (RCA), recombinase polymerase amplification (RPA), and CRISPR-Cas systems has enhanced its efficiency. The combination of LAMP with various biosensors has enabled real-time analysis, broadening its application in point-of-care testing (POCT). Microfluidic technology has further facilitated the automation and miniaturization of LAMP assays, allowing for the simultaneous detection of multiple targets and preventing contamination. This review highlights advancements in LAMP, focusing on primer design, polymerase engineering, and its integration with other technologies. Continuous improvements and integration of LAMP with complementary technologies have significantly enhanced its diagnostic capabilities, making it a robust tool for rapid, sensitive, and specific nucleic acid detection with promising implications for healthcare, agriculture, and environmental monitoring.