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1.
Artículo en Inglés | MEDLINE | ID: mdl-39255010

RESUMEN

Two novel strains, YIM 133132T and YIM 133296, were isolated from lichen samples collected from Yunnan Province, Southwest PR China. YIM 133132T and YIM 133296 are aerobic, Gram-staining-positive, non-motile actinomycetes. They are also catalase-positive and oxidase-negative, and YIM 133132T formed flat yellowish colonies that were relatively dry on YIM38 agar medium. Flat yellowish colonies of YIM 133296 were also observed on YIM38 agar medium. YIM 133132T grew at 25-35 °C (optimum 25-30 °C), pH 6.0-9.0 (optimum pH 7.0) and in the presence of 0-8% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains YIM 133132T and YIM 133296 represented members of the genus Luteipulveratus and exhibited high sequence similarity (96.93%) with Luteipulveratus halotolerans C296001T. The genomic DNA G+C content of both strains was 71.8%. The DNA-DNA hybridisation (dDDH) values between YIM 133132T and YIM 133296 were 85.1%, and the DNA-DNA hybridisation value between YIM 133132T and YIM 133296 and L. halotolerans C296001T was 23.4%. On the basis of the draft genome sequences, the average nucleotide identity (ANI) between strains YIM 133132T and YIM 133296 and L. halotolerans C296001T was 80.8%. The major menaquinones that were identified were MK-8(H4), MK-9 and MK-8(H2). The polar lipids were diphosphatidylglycerol and phosphatidylinositol. On the basis of the morphological, physiological, biochemical, genomic, phylogenetic and chemotaxonomic characteristics, strains YIM 133132T and YIM 133296 can be clearly distinguished from L. halotolerans C296001T, and the two strains represent a novel species for which the name L. flavus sp. nov. is proposed. The type strain is YIM 133132T (CGMCC= 1.61357T and KCTC= 49824T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Líquenes , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , ARN Ribosómico 16S/genética , China , ADN Bacteriano/genética , Líquenes/microbiología , Ácidos Grasos/química , Ácidos Grasos/análisis , Fosfolípidos
2.
ISME J ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255373

RESUMEN

Heterotrophic nitrification remains a mystery for decades. It has been commonly hypothesized that heterotrophic nitrifiers oxidize ammonia to hydroxylamine and then to nitrite in a way similar to autotrophic AOA and AOB. Recently, heterotrophic nitrifiers from Alcaligenes were found to oxidize ammonia to hydroxylamine and then to N2 ("dirammox", direct ammonia oxidation) by the gene cluster dnfABC with a yet-to-be-reported mechanism. The role of a potential glutamine amidotransferase DnfC clues the heterotrophic ammonia oxidation might involving in glutamine. Here, we found Alcaligenes faecalis JQ135 could oxidize amino acids besides ammonia. We discovered that glutamine is an intermediate of the dirammox pathway and the glutamine synthetase gene is essential for both A. faecalis JQ135 and the E. coli cells harboring dnfABC gene cluster to oxidize amino acids and ammonia. Our study expands understanding of heterotrophic nitrifiers and challenges the classical paradigm of heterotrophic nitrification.

3.
J Colloid Interface Sci ; 678(Pt B): 795-807, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39270382

RESUMEN

The membrane process is an effective way to realize resource reutilization. Most membrane devices are made of cold-roll steel (CRS), which is easy to corrode when operating in acid conditions. Herein, the biodegradable surfactant dodecyl dimethyl betaine (BS-12) was used as the inhibitor to protect the CRS in the trichloroacetic acid (TCA) solution. The long-term stability membrane tests showed that adding BS-12 will not harm the membrane performance. The weight loss experiments proved that adding BS-12 with trace amount (10 mg·L-1) endowed the CRS with good inhibition efficiency (95.3 %). The electrochemical tests indicated that the mixed inhibitor- BS-12 works by inhibiting the anode and cathode simultaneously, and the polarization resistance increased to 21 times. The SEM, AFM, and CLSM tests proved that adding BS-12 enabled the CRS surface to remain stable. The FTIR and XPS tests proved that BS-12 adsorbed on the CRS surface via physical and chemical adsorption. The theoretical calculations proved the horizontal adsorption of BS-12 on the CRS surface and the existence of the electron transfer within the BS-12 and CRS. The BS-12 showed great potential in the CRS inhibition of the membrane separation and purification processing.

4.
Water Environ Res ; 96(9): e11132, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39285708

RESUMEN

In this study, the siphon-type composite vertical flow constructed wetland (Sc-VSsFCW) was constructed with anthracite and shale ceramsite chosen as the substrate bed materials. During the 90-day experiment, typical pollutant removal effects of wastewater and extracellular polymeric substance (EPS) accumulation were investigated. Meanwhile, X-ray diffraction and scanning electron microscopy were used to examine the phase composition and surface morphology to analyze adsorptive property. Additionally, we evaluated the impact of siphon effluent on clogging and depolymerization by measuring the EPS components' evolution within the system. The findings reveal that both the anthracite and shale ceramsite systems exhibit impressive removal efficiencies for total phosphorus (TP), total dissolved phosphorus (TDP), soluble reactive phosphorus (SRP), chemical oxygen demand (COD), ammonium nitrogen (NH4 +-N), and nitrate nitrogen (NO3 --N). However, as the experiment progressed, TP removal rates in both systems gradually declined because of the saturation of adsorption sites on the substrate surfaces. Although the dissolved oxygen (DO) levels remained relatively stable throughout the experiment, pH exhibited distinct patterns, suggesting that the anthracite system relies primarily on chemical adsorption, whereas the shale ceramsite system predominantly utilizes physical adsorption. After an initial period of fluctuation, the permeability coefficient and porosity of the system gradually stabilized, and the protein and polysaccharide contents in both systems exhibited a downward trend. The study underscores that anthracite and shale ceramsite have good effectiveness in pollutant removal as substrate materials. Overall, the hydraulic conditions of the double repeated oxygen coupling siphon in the Sc-VSsFCW system contribute to enhanced re-oxygenation capacity and permeability coefficient during operation. The changes in EPS content indicate that the siphon effluent exerts a certain depolymerization effect on the EPS within the system, thereby mitigating the risk of biological clogging to a certain extent. PRACTITIONER POINTS: The system can still maintain good pollutant treatment effect in long-term operation. The re-oxygenation method of the system can achieve efficient and long-term re-oxygenation effect. The siphon effluent has a certain improvement effect on the permeability coefficient and porosity, but it cannot effectively inhibit the occurrence of clogging. The EPS content did not change significantly during the operation of the system, and there was a risk of biological clogging.


Asunto(s)
Matriz Extracelular de Sustancias Poliméricas , Eliminación de Residuos Líquidos , Aguas Residuales , Humedales , Aguas Residuales/química , Eliminación de Residuos Líquidos/métodos , Matriz Extracelular de Sustancias Poliméricas/química , Fósforo/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos
5.
Environ Res ; 263(Pt 1): 120029, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39299446

RESUMEN

The understanding of activated sludge microbial status and roles is imperative for improving and enhancing the performance of wastewater treatment plants (WWTPs). In this study, we conducted a deep analysis of activated sludge microbial communities across five compartments (inflow, effluent, and aerobic, anoxic, anaerobic tanks) over temporal scales, employing high-throughput sequencing of 16S rRNA amplicons and metagenome data. Clearly discernible seasonal patterns, exhibiting cyclic variations, were observed in microbial diversity, assembly, co-occurrence network, and metabolic functions. Notably, summer samples exhibited higher α-diversity and were distinctly separated from winter samples. Our analysis revealed that microbial community assembly is influenced by both stochastic processes (66%) and deterministic processes (34%), with winter samples demonstrating more random assembly compared to summer. Co-occurrence patterns were predominantly mutualistic, with over 96% positive correlations, and summer networks were more organized than those in winter. These variations were significantly correlated with temperature, total phosphorus and sludge volume index. However, no significant differences were found among microbial community across five compartments in terms of ß diversity. A core community of keystone taxa was identified, playing key roles in eight nitrogen and eleven phosphorus cycling pathways. Understanding the assembly mechanisms, co-occurrence patterns, and functional roles of microbial communities is essential for the design and optimization of biotechnological treatment processes in WWTPs.

6.
Heliyon ; 10(18): e37661, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39315196

RESUMEN

Background: The extensive community of gut microbiota significantly influences various biological functions throughout the body, making its characterization a focal point in biomedicine research. Over the past few decades, studies have revealed a potential link between specific gut bacteria, their associated metabolic pathways, and influenza. Bacterial metabolites can communicate directly or indirectly with organs beyond the gut via the intestinal barrier, thereby impacting the physiological functions of the host. As the microbiota increasingly emerges as a 'gut signature' in influenza, gaining a deeper understanding of its role may offer new insights into its pathophysiological relevance and open avenues for novel therapeutic targets. In this Review, we explore the differences in gut microbiota between healthy individuals and those with influenza, the relationship between gut microbiota metabolites and influenza, and potential strategies for preventing and treating influenza through the regulation of gut microbiota and its metabolites, including fecal microbiota transplantation and microecological preparations. Methods: We utilized PubMed and Web of Science as our search databases, employing keywords such as "influenza," "gut microbiota," "traditional Chinese medicine," "metabolites," "prebiotics," "probiotics," and "machine learning" to retrieve studies examining the potential therapeutic connections between the modulation of gut microbiota and its metabolites in the treatment of influenza. The search encompassed literature from the inception of the databases up to December 2023. Results: Fecal microbiota transplantation (FMT), microbial preparations (probiotics and prebiotics), and traditional Chinese medicine have unique advantages in regulating intestinal microbiota and its metabolites to improve influenza outcomes. The primary mechanism involves increasing beneficial intestinal bacteria such as Bacteroidetes and Bifidobacterium while reducing harmful bacteria such as Proteobacteria. These interventions act directly or indirectly on metabolites such as short-chain fatty acids (SCFAs), amino acids (AAs), bile acids, and monoamines to alleviate lung inflammation, reduce viral load, and exert anti-influenza virus effects. Conclusion: The gut microbiota and its metabolites have direct or indirect therapeutic effects on influenza, presenting broad research potential for providing new directions in influenza research and offering references for clinical prevention and treatment. Future research should focus on identifying key strains, specific metabolites, and immune regulation mechanisms within the gut microbiota to accurately target microbiota interventions and prevent respiratory viral infections such as influenza.

7.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4329-4337, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39307770

RESUMEN

This study aims to investigate the mechanism of Xuanbai Chengqi Decoction in treating acute lung injury(ALI) based on network pharmacology and animal experiments. The potential targets and signaling pathways of Xuanbai Chengqi Decoction in regulating ALI were predicted by network pharmacology. The rat model of ALI was constructed and administrated with different doses of Xuanbai Chengqi Decoction. The pathological changes in the lung tissue of rats were observed by hematoxylin-eosin(HE) staining. The levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein levels of factors in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway were determined by quantitative real-time PCR(qPCR) and Western blot, respectively. A total of 52 compounds from Xuanbai Chengqi Decoction were predicted to be involved in the treatment of ALI, including ß-sitosterol, emodin, stigmasterol, glabridin, and aloe-emodin, which corresponded to 112 targets,and 4 723 targets of ALI were predicted. The compounds and ALI shared 94 common targets. The key targets included TNF, IL-1ß,prostaglandin-endoperoxide synthase 2(PTGS2), and tumor protein 53(TP53). Lipids and atherosclerosis, p53 signaling pathway,IL-17 signaling pathway, and PI3K/Akt signaling pathway were mainly involved in the treatment. Animal experiments showed that compared with the model group, Xuanbai Chengqi Decoction alleviated the pathological changes in the lung tissue, lowered the serum levels of IL-6, IL-1ß, and TNF-α, down-regulated the mRNA and protein levels of PI3K, Akt, and mTOR, and reduced the p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratios in ALI rats. The results showed that Xuanbai Chengqi Decoction exerted its therapeutic effects on ALI via multiple components, targets, and pathways. Meanwhile, Xuanbai Chengqi Decoction may reduce the inflammation and attenuate the lung injuries of ALI rats by inhibiting the PI3K/Akt/mTOR signaling pathway.


Asunto(s)
Lesión Pulmonar Aguda , Medicamentos Herbarios Chinos , Interleucina-1beta , Farmacología en Red , Ratas Sprague-Dawley , Transducción de Señal , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Ratas , Transducción de Señal/efectos de los fármacos , Masculino , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo
8.
Plant Cell Environ ; 2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39308044

RESUMEN

Plant organs achieve their specific size and shape through the coordination of cell division and cell expansion, processes that are profoundly influenced by environmental cues. Cytokinesis during cell division depends on the position of the cytokinetic wall, but how this process responses to environment fluctuations remains underexplored. Here, we investigated a regulatory module involving C2H2-type zinc finger protein (C2H2-ZFP) in leaf morphology during drought stress. A total of 123 C2H2-ZFP members were identified through a comparative genome survey in Populus alba × P. glandulosa '84K'. Among them, PagSUPa, an orthologous gene of Arabidopsis SUPERMAN, was selected due to its responsiveness to drought stress and was further confirmed to play a role in leaf development. Phenotypic characterization and cellular analysis revealed that PagSUPa fine-tunes the duration of cell proliferation in the adaxial epidermis, thereby influencing leaf morphology by modulating leaf adaxial-abaxial polarity. Additionally, we found that PagSUPa directly suppresses the expression of PHRAGMOPLAST ORIENTING KINESIN1 (PagPOK1) and PagPOK2, genes encoding proteins involved in phragmoplast orientation and position, which results in impaired cytokinesis and cell wall organization. This study provides novel insights into the regulatory network governed by the SUP gene during leaf development, specifically in relation to cell division.

9.
Adv Mater ; : e2411968, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313989

RESUMEN

Despite high theoretical efficiencies and rapid improvements in performance, high-efficiency ≈1.2 eV mixed Sn-Pb perovskite solar cells (PSCs) generally rely on poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT: PSS) as the hole transport layer (HTL); a material that is considered to be a bottleneck for long-term stability due to its acidity and hygroscopic nature. Seeking to replace PEDOT: PSS with an alternative HTL with improved atmospheric and thermal stability, herein, a silole derivative (Silole-COOH) tuned with optimal electronic properties and efficient carrier transport by incorporating a carboxyl functional group is designed, which results in an optimal band alignment for hole extraction from Sn-Pb perovskites and robust air and thermal stability. Thin films composed of the Silole-COOH exhibit superior conductivity and carrier mobility compared to PEDOT: PSS, in addition to reduced nonradiative quasi-Fermi-level splitting losses at the HTL/perovskite interface and improved quality of Sn-Pb perovskite. Replacement of PEDOT: PSS with Silole-COOH leads to 23.2%-efficient single-junction Sn-Pb PSCs, 25.8%-efficient all-perovskite tandems, and long operating stability in ambient air.

10.
medRxiv ; 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39252932

RESUMEN

Accurate intraoperative diagnosis is crucial for differentiating between primary CNS lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge. We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&E-like images within less than three minutes. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and two additional independent test cohorts. We trained on 54,000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS tumor/non-tumor lesions. Training and test data were collected from four tertiary international medical centers. The final histopathological diagnosis served as ground-truth. In the prospective test cohort of PCNSL and non-PCNSL entities (n=160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ±0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 78.94%). The additional test cohorts (n=420, n=59) reached balanced accuracy rates of 95.44% ±0.74 and 95.57% ±2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma's capabilities to detect class-specific histomorphological key features. RapidLymphoma is valid and reliable in detecting PCNSL and differentiating from other CNS entities within three minutes, as well as visual feedback in an intraoperative setting. This leads to fast clinical decision-making and further treatment strategy planning.

11.
Zhonghua Nan Ke Xue ; 30(3): 217-223, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-39177387

RESUMEN

OBJECTIVE: To investigate the causal correlation between depression and stress urinary incontinence (SUI) using Mendelian randomization (MR) analysis. METHODS: We searched the FinnGen Consortium database for genome-wide association studies (GWAS) on depression and obtained 23 424 case samples and 192 220 control samples, with the GWAS data on SUI provided by the UK Biobank, including 4 340 case samples and 458 670 control samples. We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium (PGC). We employed inverse-variance weighting as the main method for the MR study, and performed sensitivity analysis to verify the accuracy and stability of the findings. RESULTS: Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI (P=0.005), but not SUI with the risk of depression (P=0.927). And analysis of the PGC data verified the correlation of depression with the increased risk of SUI (P=0.043). CONCLUSION: Depression is associated with an increased risk of SUI, while SUI does not increase the risk of depression.


Asunto(s)
Depresión , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Incontinencia Urinaria de Esfuerzo , Humanos , Depresión/genética , Incontinencia Urinaria de Esfuerzo/genética , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Femenino
12.
Cardiovasc Diabetol ; 23(1): 302, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152431

RESUMEN

BACKGROUND: The binary diagnosis of Metabolic Syndrome(MetS) fails to accurately evaluate its severity, and the association between MetS severity and frailty progression remains inadequately elucidated. This study aims to clarify the relationship between the severity of MetS and the progression of frailty among the middle-aged and elderly population in China. METHOD: Participants from the 2011-2018 China Health and Retirement Longitudinal Study(CHARLS) were included for a longitudinal analysis. The study employs a frailty index(FI) based on 32 health deficits to diagnose frailty and to assess FI trajectories. An age-sex-ethnicity-specific MetS scoring model (MetS score) was used to assess metabolic syndrome severity in Chinese adults. The Cumulative MetS score from 2012 to 2015 was calculated using the formula: (MetS score in wave 1 + MetS score in wave 3) / 2 × time(2015 - 2012). The association between MetS score, Cumulative MetS score, and the risk and trajectory of frailty were evaluated using Cox regression/logistic regression, and linear mixed models. Restricted Cubic Splines(RCS) models were utilized to detect potential non-linear associations. RESULTS: A higher MetS score was significantly associated with an increased risk of frailty(HR per 1 SD increase = 1.205; 95%CI: 1.14 to 1.273) and an accelerated FI trajectory(ß per 1 SD increase = 0.113 per year; 95%CI: 0.075 to 0.15 per year). Evaluating changes in MetS score using a Cumulative MetS score indicated that each 1 SD increase in the Cumulative MetS score increased the risk of frailty by 22.2%(OR = 1.222; 95%CI: 1.133 to 1.319) and accelerated the rate of increase in FI(ß = 0.098 per year; 95%CI: 0.058 to 0.138 per year). RCS model results demonstrated a dose-response curve relationship between MetS score and Cumulative MetS score with frailty risk. Stratified analysis showed consistency across subgroups. The interaction results indicate that in males and individuals under aged 60, MetS score may accelerate the increase in FI, a finding consistent across both models. CONCLUSIONS: Our findings underscore the positive correlation between the severity of MetS and frailty progression in the middle-aged and elderly, highlighting the urgent need for early identification of MetS and targeted interventions to reduce the risk of frailty.


Asunto(s)
Progresión de la Enfermedad , Anciano Frágil , Fragilidad , Evaluación Geriátrica , Síndrome Metabólico , Índice de Severidad de la Enfermedad , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/fisiopatología , Fragilidad/diagnóstico , Fragilidad/epidemiología , Fragilidad/fisiopatología , Masculino , Femenino , Estudios Longitudinales , China/epidemiología , Anciano , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Factores de Edad , Factores de Tiempo , Anciano de 80 o más Años , Pronóstico , Pueblos del Este de Asia
13.
ACS Appl Mater Interfaces ; 16(32): 41828-41842, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39088848

RESUMEN

The bacterium Pseudomonas aeruginosa is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHPplus, which can circumvent the drug resistance mechanism of Pseudomonas aeruginosa and effectively combat Pseudomonas aeruginosa infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate Pseudomonas aeruginosa. Furthermore, dHTSN1@pHPplus was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHPplus exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of P. aeruginosa lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of Pseudomonas aeruginosa compared to untreated mice with Pseudomonas aeruginosa-infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHPplus in treating drug-resistant P. aeruginosa infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant P. aeruginosa.


Asunto(s)
Antibacterianos , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Factores de Virulencia , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/patogenicidad , Animales , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/microbiología , Inmunidad Adaptativa/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Humanos , Farmacorresistencia Bacteriana/efectos de los fármacos , Ratones Endogámicos BALB C , Femenino
14.
J Med Chem ; 67(17): 15080-15097, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39145509

RESUMEN

The activation of PP5 is essential for a variety of cellular processes, as it participates in a variety of biological pathways by dephosphorylating substrates. However, activation of PP5 by small molecules has been a challenge due to its native "self-inhibition" mechanism, which is controlled by the N-terminal TPR domain and the C-terminal αJ helix. Here, we reported the discovery of DDO-3733, a well-identified TPR-independent PP5 allosteric activator, which facilitates the dephosphorylation process of downstream substrates. Considering the negative regulatory effect of PP5 on heat shock transcription factor HSF1, pharmacologic activation of PP5 by DDO-3733 was found to reduce the HSP90 inhibitor-induced heat shock response. These results provide a chemical tool to advance the exploration of PP5 as a potential therapeutic target and highlight the value of pharmacological activation of PP5 to reduce heat shock toxicity of HSP90 inhibitors.


Asunto(s)
Proteínas HSP90 de Choque Térmico , Fosfoproteínas Fosfatasas , Regulación Alostérica/efectos de los fármacos , Humanos , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/química , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas Fosfatasas/química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico/química , Fosforilación/efectos de los fármacos , Respuesta al Choque Térmico/efectos de los fármacos , Relación Estructura-Actividad , Proteínas Nucleares
15.
ACS Appl Mater Interfaces ; 16(35): 46495-46505, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39167418

RESUMEN

Investigating organic carriers' utilization efficiency and bioactivity within organic-inorganic hybrid nanoflowers is critical to constructing sensitive immunosensors. Nevertheless, the sensitivity of immunosensors is interactively regulated by different classes of biomolecules such as antibodies and enzymes. In this work, we introduced a new alkaline phosphatase-antibody-CaHPO4 hybrid nanoflowers (AAHNFs) microreactor based colorimetric immunoprobe. This system integrates a biometric unit (antibody) with a signal amplification element (enzyme) through the biomineralization process. Specifically, the critical factors affecting antibody recognition activity in the formation mechanism of AAHNFs are investigated. The designed AAHNFs retain antibody recognition ability with enhanced protection for encapsulated proteins against high temperature, organic solvents, and long-term storage, facilitating the selective construction of lock structures against antigens. Additionally, a colorimetric immunosensor based on AAHNFs was developed. After ascorbic acid 2-phosphate hydrolysis by alkaline phosphatase (ALP), the generated ascorbic acid decomposes I2 to I-, inducing the localized surface plasmon resonance in the silver nanoplate, which is effectively tuned through shape conversion to develop the sensor. Further, a 3D-printed portable device is fabricated, integrated with a smartphone sensing platform, and applied to the data of collection and analysis. Notably, the immunosensor exhibits improved analytical performance with a 0.1-6.25 ng·mL-1 detection range and a 0.06 ng·mL-1 detection limit for quantitative saxitoxin (STX) analysis. The average recoveries of STX in real samples ranged from 85.9% to 105.9%. This study presents a more in-depth investigation of the recognition element performance, providing insights for improved antibody performance in practical applications.


Asunto(s)
Fosfatasa Alcalina , Colorimetría , Saxitoxina , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/química , Saxitoxina/análisis , Saxitoxina/química , Colorimetría/métodos , Técnicas Biosensibles/métodos , Biocatálisis , Límite de Detección , Nanoestructuras/química , Inmunoensayo/métodos , Ácido Ascórbico/química , Ácido Ascórbico/análisis , Ácido Ascórbico/análogos & derivados , Plata/química
16.
Front Cardiovasc Med ; 11: 1388024, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108669

RESUMEN

Background: Percutaneous left atrial appendage closure (LAAC) serves as an alternative prophylactic strategy for patients with non-valvular atrial fibrillation (AF) who cannot undergo anti-coagulation therapy. Proper management of associated complications is crucial to enhancing the procedure's success rate and mitigating perioperative risks and adverse events during follow-up. Aims: This study aims to summarize our center's experience and strategies in managing procedural-related complications encountered in 512 cases of LAAC with or without ablation for AF conducted from January 2020 to December 2023. Results: We identified 11 significant intervention-requiring complications associated with LAAC with or without Ablation procedure. These included three cases of intraoperative thrombosis, three instances of pericardial effusion or tamponade, one case of device-related thrombosis, one peri-device leak, one systemic embolism, one bleeding episode, and one additional device-related complication. The categorization of intraoperative thrombosis was as follows: one patient exhibited heparin resistance; one experienced thrombosis due to prolonged device implantation during the LAAC with ablation procedure; and one had unexplained intraoperative thrombosis. The pericardial effusion or tamponade likely resulted from damage to the atrial appendage during LAAC device insertion. Two patients encountered device-related thrombosis and systemic embolism events possibly caused by non-standard postoperative antithrombotic medication use; one patient's peri-device leak may have resulted from incomplete endothelialization of the occluder post-surgery; one patient experienced postoperative bladder bleeding; and one patient's device-related complications occurred due to a dislodged strut frame that damaged the left atrial appendage, leading to pericardial effusion. Our proactive interventions enabled all patients with these surgical-related complications to be safely discharged, with subsequent follow-ups showing no adverse events. Conclusion: Implementing targeted interventions for immediate procedural-related complications during the LAAC with or without ablation procedures enhances procedural success rates, diminishes postoperative mortality and patient disability, and bolsters stroke prevention efforts. This approach underscores the importance of a strategic response to complications, affirming the procedure's viability and safety in managing non-valvular AF in patients contraindicated for anticoagulation.

17.
J Cardiovasc Pharmacol ; 84(2): 199-209, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39115719

RESUMEN

ABSTRACT: Sepsis is characterized as a systemic inflammatory response syndrome resulting from infection, leading to the development of multiple organ dysfunction syndrome. Sepsis-induced cardiomyopathy (SICM) is a frequently encountered condition in clinical settings. Mesenchymal stem cells (MSCs) possess inherent immunomodulatory and anti-inflammatory attributes, rendering them a promising therapeutic approach to reestablish the equilibrium between anti-inflammatory and proinflammatory systems in septic patients. Consequently, MSCs are frequently employed in clinical investigations. In this study, the author established a mouse SICM model through cecal ligation and puncture and administered MSCs through the tail vein. Following successful modeling, the myocardial function and histopathological changes were detected by echocardiography, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, enzyme-linked immunosorbent assay,, and other experiments. As a result, MSCs demonstrated the ability to enhance myocardial function, promote cardiac tissue repair, suppress inflammatory response, reduce levels of myocardial injury markers, and mitigate oxidative stress. In addition, transcriptome and proteome analyses were conducted. Through differential expression analysis, functional enrichment analysis, and multiomics association analysis, it was revealed that the transcriptional factors nuclear receptor subfamily 1 (NR1D2) and target gene lipocalin 2 (LCN2) played key roles in mediating the effects of MSCs on SICM. JASPAR website and ChIP-qPCR experiment were used to predict and confirm the targeting relationship between them. Subsequent cell coculture experiments and a series of experiments confirmed that MSCs attenuated cardiomyocyte injury by downregulating the expression of NR1D2 and its downstream target gene LCN2. In conclusion, MSCs alleviate mice SICM through inhibiting NR1D2/LCN2 pathway.


Asunto(s)
Cardiomiopatías , Modelos Animales de Enfermedad , Lipocalina 2 , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Sepsis , Transducción de Señal , Animales , Sepsis/complicaciones , Sepsis/metabolismo , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Cardiomiopatías/etiología , Cardiomiopatías/fisiopatología , Cardiomiopatías/terapia , Células Madre Mesenquimatosas/metabolismo , Masculino , Lipocalina 2/metabolismo , Lipocalina 2/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Células Cultivadas , Estrés Oxidativo , Función Ventricular Izquierda , Ratones , Apoptosis
18.
Biomed Chromatogr ; : e5987, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39126351

RESUMEN

The traditional formulation Hanchuan zupa granules (HCZPs) have been widely used for controlling coronavirus disease 2019 (COVID-19). However, its active components remain unknown. Here, HCZP components targeting the spike receptor-binding domain (S-RBD) of SARS-CoV-2 were investigated using a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). Recombinant S-RBD proteins were immobilized on the SPR chip by amine coupling for the prescreening of nine HCZP medicinal herbs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified gallic acid (GA) and methyl gallate (MG) from Rosa rugosa as S-RBD ligands, with KD values of 2.69 and 0.95 µM, respectively, as shown by SPR. Molecular dynamics indicated that GA formed hydrogen bonds with G496, N501, and Y505 of S-RBD, and MG with G496 and Y505, inhibiting S-RBD binding to angiotensin-converting enzyme 2 (ACE2). SPR-based competition analysis verified that both compounds blocked S-RBD and ACE2 binding, and SPR demonstrated that GA and MG bound to ACE2 (KD = 5.10 and 4.05 µM, respectively), suggesting that they blocked the receptor and neutralized SARS-CoV-2. Infection with SARS-CoV-2 pseudovirus showed that GA and MG suppressed viral entry into 293T-ACE2 cells. These S-RBD inhibitors have potential for drug design, while the findings provide a reference on HCZP composition and its use for treating COVID-19.

19.
Plants (Basel) ; 13(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39204626

RESUMEN

Flowering is critical to the success of plant propagation. The MYB family transcription factor CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) is an essential component of the core loop of the circadian clock and plays a crucial role in regulating plant flowering time. In this study, we found that photoperiod affects the expression pattern and expression level of BcCCA1, which is delayed flowering time under short-day conditions in Pak-choi [Brassica campestris (syn. Brassica rapa) ssp. chinensis]. We detected overexpression and silencing of BcCCA1 in Pak-choi, resulting in delayed and promoted flowering time, respectively. Furthermore, we also discovered that FLOWERING LOCUS C (BcFLC) and SUPPRESSOR OF CONSTANS1 (BcSOC1) were expressed significantly differently in BcCCA1 overexpression and silencing plants compared with control plants. Therefore, we further investigated the interaction relationship between BcCCA1, BcFLC, and BcSOC1, and the results showed that BcCCA1 and BcFLC as a complex interacted with each other. Moreover, both BcCCA1 and BcFLC can directly bind to the promoter of BcSOC1 and repress its transcription, and BcCCA1 can form a complex with BcFLC to enhance the transcriptional inhibition of BcSOC1 by BcFLC. This study reveals a new mechanism by which the circadian clock regulates flowering time.

20.
Plants (Basel) ; 13(16)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39204650

RESUMEN

In the relay intercropping system of maize/sweet potato, the growth of the sweet potatoes is seriously limited by weak light stress in the early stage due to shade from maize plants. However, it is not clear how the weak light affects sweet potatoes and causes tuberous root loss. By setting two light intensity levels (weak light = 30% transmittance of normal light), this study evaluated the responses of two sweet potato cultivars with different tolerances to weak light in a field-based experiment and examined the divergence of gene expression related to light and photosynthesis in a pot-based experiment. The results showed that under weak light, the anatomic structure of functional leaves changed, and the leaf thickness decreased by 39.98% and 17.32% for Yuhongxinshu-4 and Wanshu-7, respectively. The ratio of S/R increased, and root length, root superficial area, and root volume all decreased. The photosynthetic enzyme rubisco was weakened, and the net photosynthetic rate (Pn) declined as well. The level of gene expression in Wanshu-7 was higher than that of Yuhongxinshu-4. The KEGG analysis showed that differentially expressed genes from the two cultivars under weak-light stress used the same enrichment pathway, mainly via glutathione metabolism and flavonoid biosynthesis. After full light levels were restored, the differentially expressed genes were all enriched in pathways such as photosynthesis, photosynthetic pigment synthesis, and carbon metabolism. These findings indicated that weak light changed the plant morphology, photosynthetic physiology and gene expression levels of sweet potatoes, which eventually caused losses in the tuberous root yield. The more light-sensitive cultivar (Wanshu-7) had stronger reactions to weak light. This study provides a theoretical basis and strategy for breeding low-light-tolerant varieties and improving relay intercropping production in sweet potatoes.

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