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High mobility group protein B2 (HMGB2) is an abundant chromatin-associated protein with pivotal roles in transcription, cell proliferation, differentiation, inflammation, and tumorigenesis. However, its immune function in Nile tilapia (Oreochromis niloticus) remains unclear. In this study, we identified a homologue of HMGB2 from Nile tilapia (On-HMGB2) and investigated its functions in the immune response against streptococcus infection. The open reading frame (ORF) of On-HMGB2 spans 642 bp, encoding 213 amino acids, and contains two conserved HMG domains. On-HMGB2 shares over 80% homology with other fish species and 74%-76% homology with mammals. On-HMGB2 was widely distributed in various tissues, with its highest transcript levels in the liver and the lowest in the intestine. Knockdown of On-HMGB2 promoted the inflammatory response in Nile tilapia, increased the bacterial load in the tissues, and led to elevated mortality in Nile tilapia following Streptococcus agalactiae infection. Taken together, On-HMGB2 significantly influences the immune system of Nile tilapia in response to streptococcus infection.
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In mammals, siglec7, an integral component of the siglecs, is principally found on the surface of natural killer (NK) cells, macrophages, and monocytes, where it interacts with various pathogens to perform immunological regulatory activities. Nonetheless, the immune defense and mechanism of siglec7 in early vertebrates remain unknown. In this study, we identified siglec7 from Oreochromis niloticus (OnSiglec7) and revealed its immune functions. Specifically, OnSiglec7 was abundantly expressed in immune-related tissues of healthy tilapia and its transcription level was strongly activated after being challenged with A. hydrophila, S. agalactiae, and Poly: IC. Meanwhile, OnSiglec7 protein was purified and analyzed, which could recognize multiple pathogens through binding and agglutinating activity. Moreover, OnSiglec7-positive cells were mainly distributed in non-specific cytotoxic cells (NCC) of tilapia HKLs and showed cell membrane localization. Furthermore, OnSiglec7 blockage affected multiple innate immune responses (inflammation, apoptosis, and pyroptosis process) by regulating the activation of MAPK, NF-κB, TLR, and JAK-STAT pathways. Finally, OnSiglec7 blockage also greatly enhanced the cytotoxic effect of tilapia NCC. Summarily, this study uncovers immune functions and mechanisms of siglec7 in primitive vertebrates, thereby enhancing our understanding of the systemic evolution and ancient functions of other siglecs within the host's innate immune system (to our knowledge).
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BACKGROUND: It is common to see patients who need orthodontic treatment but with insufficient alveolar bone volume. However, safe and effective tooth movement requires sufficient alveolar bone width and height. The aim of this study is to compare the bone augmentation efficacy of Autologous Partially Demineralized Dentin Matrix (APDDM) and Deproteinized Bovine Bone Mineral (DBBM) in orthodontic patients with insufficient bone by using a randomized controlled clinical trial approach. MATERIALS AND METHODS: Twenty-seven orthodontic patients involving 40 posterior teeth alveolar sites (n = 40) with insufficient alveolar bone volume were randomly divided into a control group (n = 20) and an experimental group (n = 20). The patients in the experimental group were treated with APDDM, and those in the control group were treated with DBBM. After surgery, the adjacent teeth are moved toward the bone grafting sites according to the orthodontic treatment plan. Patients completed a postoperative response questionnaire by the Visual Analogue Scale (VAS) score to indicate pain and swelling in the bone grafted area at the time of suture removal; and CBCT scans were conducted before surgery, 6 months and 2 years after surgery to assess changes in buccal and central alveolar heights, as well as widths at the alveolar ridge apex and 3 mm, 5 mm below the apex, respectively. The CBCT image sequences were imported into Mimics 21.0 software in DICOM format. The data of the patients in both groups were collected and analyzed by SPSS 25.0. RESULTS: The VAS scores were significantly lower in the APDDM group than in the DBBM group (p < 0.05). Significant increases were observed in alveolar bone height and width at 6 months and 2 years postoperative (p < 0.05); At 2 years, the APDDM group exhibited a reduction in buccal crest height and in 3 mm, 5 mm width below alveolar ridge apex, relative to 6 months (p < 0.05), while the DBBM group showed a decrease only in the central height of the alveolar bone (p < 0.05). There was a significant bone augmentation increase found only 3 mm below the alveolar ridge apex in the APDDM group compared with the DBBM group among all 6 months group comparison (p < 0.05). At 2 years, the augmentation effects were similar across both groups (p > 0.05). CONCLUSION: Radiomics analysis indicates that APDDM serves as a viable bone augmentation material for orthodontic patients with insufficient alveolar bone volume, achieving comparable clinical efficacy to DBBM. Additionally, APDDM is associated with a milder postoperative response than DBBM. THE REGISTRATION NUMBER (TRN): ChiCTR2400084607.
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Dentina , Humanos , Femenino , Masculino , Bovinos , Animales , Dentina/trasplante , Dentina/diagnóstico por imagen , Resultado del Tratamiento , Adolescente , Tomografía Computarizada de Haz Cónico/métodos , Adulto Joven , Aumento de la Cresta Alveolar/métodos , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/cirugía , Técnicas de Movimiento Dental/métodos , Sustitutos de Huesos/uso terapéutico , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/patología , Minerales/uso terapéutico , Dimensión del Dolor , Adulto , Estudios de SeguimientoRESUMEN
Nucleic acid aptamers are oligonucleotide chains with molecular recognition properties. Compared with antibodies, aptamers show advantages given that they are readily produced via chemical synthesis and elicit minimal immunogenicity in biomedicine applications. Notably, aptamer-encoded nucleic acid assemblies further improve the binding affinity of aptamers with the targets due to their multivalent synergistic interactions. Specially, aptamers can be engineered with special topological arrangements in nucleic acid assemblies, which demonstrate spatial and valence matching towards antigens on viruses, thus showing potential in the detection and therapeutic applications of viruses. This review presents the recent progress on the aptamers explored for SARS-CoV-2 detection and infection treatment, wherein applications of aptamer-based assembly systems are introduced in detail. Screening methods and chemical modification strategies for aptamers are comprehensively summarized, and the types of aptamers employed against different target domains of SARS-CoV-2 are illustrated. The evolution of aptamer-based assembly systems for the detection and neutralization of SARS-CoV-2, as well as the construction principle and characteristics of aptamer-based DNA assemblies are demonstrated. The typically representative works are presented to demonstrate how to assemble aptamers rationally and elaborately for specific applications in SARS-CoV-2 diagnosis and neutralization. Finally, we provide deep insights into the current challenges and future perspectives towards aptamer-based nucleic acid assemblies for virus detection and neutralization in nanomedicine.
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Aptámeros de Nucleótidos , COVID-19 , SARS-CoV-2 , Aptámeros de Nucleótidos/química , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética , Humanos , COVID-19/diagnóstico , COVID-19/virología , COVID-19/terapia , Tratamiento Farmacológico de COVID-19 , Antivirales/química , Antivirales/farmacología , Antivirales/uso terapéuticoRESUMEN
The N2O emissions resulting from sludge incineration are estimated using the default values published by the Intergovernmental Panel on Climate Change (IPCC), which may differ significantly from the actual emissions. In this investigation, N2O emissions from four sludge incineration lines in two plants were monitored for varying durations. The variation in N2O emission factors (EFs) between incineration lines of the same plant was much smaller than the difference between different plants. Data on N2O EFs obtained from brief monitoring may contain variabilities of up to 30%. N2O EFs were more sensitive to temperature changes at low temperatures, necessitating extended monitoring periods to improve the reliability of N2O monitoring outcomes in cases of low furnace temperatures. Excessive use of the SNCR system to reduce NOx emissions resulted in concentrations of N2O and NH3 in the exhaust gases exceeding NOx levels. In the case of furnace temperature control and advanced reburning technology, it is advisable to utilize actual monitoring data or the smaller default values provided by the IPCC in China. Otherwise, the estimated N2O emissions may exceed the actual emissions.
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Contaminantes Atmosféricos , Incineración , Óxido Nitroso , Aguas del Alcantarillado , China , Incineración/métodos , Aguas del Alcantarillado/análisis , Contaminantes Atmosféricos/análisis , Óxido Nitroso/análisis , Monitoreo del Ambiente/métodos , TemperaturaRESUMEN
Long noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1-AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para-cancerous tissues were collected. CTBP1-AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1-AS did not affect TP63 expression; however it blocked the TP63-mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1-AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1-AS plays an oncogenic role in PCa by blocking TP63-mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.
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Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata , ARN Largo no Codificante , Factores de Transcripción , Proteínas Supresoras de Tumor , Animales , Humanos , Masculino , Ratones , Oxidorreductasas de Alcohol/genética , Oxidorreductasas de Alcohol/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , ARN sin Sentido/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Activación Transcripcional , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Broad-spectrum antiviral platforms are always desired but still lack the ability to cope with the threats to global public health. Herein, we develop a poly aptamer encoded DNA nanocatcher platform that can trap entire virus particles to inhibit infection with a broad antiviral spectrum. Ultralong single-stranded DNA (ssDNA) containing repeated aptamers was synthesized as the scaffold of a nanocatcher via a biocatalytic process, wherein mineralization of magnesium pyrophosphate on the ssDNA could occur and consequently lead to the formation of nanocatcher with interfacial nanocaves decorated with virus-binding aptamers. Once the viruses were recognized by the apatmers, they would be captured and trapped in the nanocaves via multisite synergistic interactions. Meanwhile, the size of nanocatchers was optimized to prevent their cellular uptake, which further guaranteed inhibition of virus infection. By taking SARS-CoV-2 variants as a model target, we demonstrated the broad virus-trapping capability of a DNA nanocatcher in engulfing the variants and blocking the infection to host cells.
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Aptámeros de Nucleótidos , Virus , Aptámeros de Nucleótidos/farmacología , ADN de Cadena Simple , Antivirales/farmacologíaRESUMEN
BACKGROUND: Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking. OBJECTIVE: This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo. METHODS: In vivo AKI mouse models were established by inducing them with cisplatin and renal ischemia-reperfusion. In vitro injury models of mouse renal tubular epithelial cells were established by inducing them with cisplatin and hypoxia and reoxygenation, respectively. The mechanism of MA effects was further explored using molecular docking and RNA-sequencing. RESULTS: MA could significantly reduce kidney injury in the cisplatin-and renal ischemia-reperfusion (IRI)-induced AKI. Further validation in the two cellular models also showed that MA had protect effects. MA can alleviate AKI in vitro and in vivo by inhibiting inflammation, cell apoptosis, and oxidative stress. MA exhibited high permeability across the Caco-2 cell, can enter cells directly. Through RNA-seq and molecular docking analysis, this study further demonstrated that MA inhibits its activity by directly binding to JNK kinase, thereby inhibiting c-JUN mediated cell apoptosis and improving AKI. In addition, MA has better renal protective effects compared to curcumin and JNK inhibitor SP600125. CONCLUSION: The results demonstrate that MA might be a potential drug for the treatment of AKI and act through the JNK/c-JUN signaling pathway.
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Lesión Renal Aguda , Daño por Reperfusión , Triterpenos , Humanos , Ratones , Animales , Cisplatino/efectos adversos , Células CACO-2 , Simulación del Acoplamiento Molecular , Lesión Renal Aguda/inducido químicamente , Apoptosis , Riñón , Estrés Oxidativo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Isquemia , Inflamación/metabolismo , Hipoxia , Ratones Endogámicos C57BLRESUMEN
Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.
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Enfermedades Renales , Humanos , Acetilación , Enfermedades Renales/tratamiento farmacológico , Riñón , Epigénesis Genética , EpigenómicaRESUMEN
CRISPR-Cas9 has been explored as a therapeutic agent for down-regulating target genes; the controlled delivery of Cas9 ribonucleoprotein (RNP) is essential for therapeutic efficacy and remains a challenge. Here, we report cascade dynamic assembly/disassembly of DNA nanoframework (NF) that enables the controlled delivery of Cas9 RNP. NF was prepared with acrylamide-modified DNA that initiated cascade hybridization chain reaction (HCR). Through an HCR, single-guide RNA was incorporated to NF; simultaneously, the internal space of NF was expanded, facilitating the loading of Cas9 protein. NF was designed with hydrophilic acylamino and hydrophobic isopropyl, allowing dynamic swelling and aggregation. The responsive release of Cas9 RNP was realized by introducing disulfide bond-containing N,N-bis(acryloyl)cystamine that was specifically in response to glutathione of cancer cells, triggering the complete disassembly of NF. In vitro and in vivo investigations demonstrated the high gene editing efficiency in cancer cells, the hypotoxicity in normal cells, and notable antitumor efficacy in a breast cancer mouse model.
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Sistemas CRISPR-Cas , ADN , Animales , Ratones , ADN/genética , Acrilamida , Proteína 9 Asociada a CRISPR/genética , Cistamina , RibonucleoproteínasRESUMEN
Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders. Several pathological conditions which may involve STAT3 include diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and renal cell carcinoma. STAT3 is expressed in various renal tissues under these pathological conditions. To better understand the role of STAT3 in the kidney and provide a theoretical foundation for STAT3-targeted therapy for renal disorders, this review covers the current work on the activities of STAT3 and its mechanisms in the pathophysiological processes of various types of renal diseases.
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Carcinoma de Células Renales , Neoplasias Renales , Nefritis Lúpica , Humanos , Factor de Transcripción STAT3/metabolismo , Riñón/patología , Nefritis Lúpica/metabolismo , Carcinoma de Células Renales/patología , Neoplasias Renales/patologíaRESUMEN
The tanning sludge (TS) and other tanning solid wastes are produced in significant quantities by the leather industry. To evaluate the combustion properties, acid gaseous pollutant conversion, and ash management, co-firing of TS with various wastes was investigated in a bubbling fluidized bed. TG-FTIR test indicated that tanning solid wastes had superior combustion properties and include more gaseous pollutants than TS. The leather mixed solid waste (LMSW) formed by mixing had better fuel characteristics than TS. The conversion rates of SO2 and HCl of LMSW incineration were 67% and 40%, respectively. The co-combustion of TS and solid wastes reduces the conversion rate of acid gas. Increasing the proportion of high-inorganic chlorine raw material could further reduce the conversion rate and increase the ash fusion temperature appropriately. Because ash and slag were primarily composed of Ca and Fe elements, the addition of calcium carbonate (CaCO3) can increase ash melting point while reducing acid gas emissions. When CaCO3 was added at a calcium to sulfur (Ca/S) ratio of 2, the acid gas emission was reduced by more than 80% and the softening temperature was raised by 90 °C. When Ca/S is greater than 2, the economics of adding CaCO3 decreased.
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Contaminantes Ambientales , Residuos Sólidos , Residuos Sólidos/análisis , Incineración , Gases , Cloro , Aguas del Alcantarillado , Ceniza del Carbón/análisisRESUMEN
BACKGROUND AND PURPOSE: Necroptosis plays an essential role in acute kidney injury and is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like pseudokinase (MLKL). A novel RIPK3 inhibitor, compound 42 (Cpd-42) alleviates the systemic inflammatory response. The current study was designed to investigate whether Cpd-42 exhibits protective effects on acute kidney injury and reveal the underlying mechanisms. EXPERIMENTAL APPROACH: The effects of Cpd-42 were determined in vivo through cisplatin- and ischaemia/reperfusion (I/R)-induced acute kidney injury and in vitro through cisplatin- and hypoxia/re-oxygenation (H/R)-induced cell damage. Transmission electron microscopy and periodic acid-Schiff staining were used to identify renal pathology. Cellular thermal shift assay and RIPK3-knockout mouse renal tubule epithelial cells were used to explore the relationship between Cpd-42 and RIPK3. Molecular docking and site-directed mutagenesis were used to determine the binding site of RIPK3 with Cpd-42. KEY RESULTS: Cpd-42 reduced human proximal tubule epithelial cell line (HK-2) cell damage, necroptosis and inflammatory responses in vitro. Furthermore, in vivo, cisplatin- and I/R-induced acute kidney injury was alleviated by Cpd-42 treatment. Cpd-42 inhibited necroptosis by interacting with two key hydrogen bonds of RIPK3 at Thr94 and Ser146, which further blocked the phosphorylation of RIPK3 and mitigated acute kidney injury. CONCLUSION AND IMPLICATIONS: Acting as a novel RIPK3 inhibitor, Cpd-42 reduced kidney damage, inflammatory response and necroptosis in acute kidney injury by binding to sites Thr94 and Ser146 on RIPK3. Cpd-42 could be a promising treatment for acute kidney injury.
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Lesión Renal Aguda , Cisplatino , Ratones , Animales , Humanos , Cisplatino/farmacología , Necroptosis , Simulación del Acoplamiento Molecular , Lesión Renal Aguda/metabolismo , Proteínas Quinasas/metabolismo , Ratones Noqueados , Apoptosis , Proteína Serina-Treonina Quinasas de Interacción con ReceptoresRESUMEN
Urinary tract infections caused by catheter insertion are prevalent in hospital clinics, which can induce serious complications such as bacteriuria and sepsis, and even lead to patient death. The disposable catheters currently used in clinical practice suffer from poor biocompatibility and high infection rate. In this paper, we developed a polydopamine (PDA)-carboxymethylcellulose (CMC)-Ag nanoparticles (AgNPs) coating with both good antibacterial and anti-adhesion properties to bacteria on the surfaces of a disposable medical latex catheter by a simple dipping method. The antibacterial efficiency of the coated catheters against Gram-negative E. coli and Gram-positive S. aureus bacteria was evaluated with both inhibition zone tests and fluorescence microscopy. Compared with the untreated catheter, the PDA-CMC-AgNPs coated catheters showed both good antibacterial and anti-adhesion properties to bacteria, which inhibited the adhesion of live bacteria and dead bacteria by 99.0% and 86.6%, respectively. This novel PDA-CMC-AgNPs composite hydrogel coating has great potential in applications in catheters and other biomedical devices to reduce infections.
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Carboximetilcelulosa de Sodio , Nanopartículas del Metal , Humanos , Catéteres Urinarios , Escherichia coli , Staphylococcus aureus , Hidrogeles , Plata/farmacología , Antibacterianos/farmacologíaRESUMEN
With the increase in global environmental pollution, it is important to understand the concentration characteristics and correlations with other pollutants of atmospheric particulate matter as affected by relevant policies. The data presented in this paper were obtained at monitoring stations in Xi'an, China, in the years from 2016 to 2020, and the spatial distribution characteristics of the mass and quantity concentrations of particulate matter in the atmosphere, as well as its correlation with other pollutants, were analyzed in depth. The results showed that the annual average concentrations of PM10 and PM2.5 decreased year by year from 2016 to 2020. The annual concentrations of PM2.5 decreased by 20.3 µg/m3, and the annual concentrations of PM10 decreased by 47.3 µg/m3. The days with concentrations of PM10 exceeding the standards decreased by 82 days, with a decrease of 66.7%. The days with concentrations of PM2.5 exceeding the standards decreased by 40 days, with a decrease of 35.4%. The concentration values of PM10 and PM2.5 were roughly consistent with the monthly and daily trends. The change in monthly concentrations was U-shaped, and the change in daily concentrations showed a double-peak behavior. The highest concentrations of particulate matter appeared at about 8:00~9:00 am and 11:00 pm, and they were greatly affected by human activity. The proportion of particles of 0~1.0 µm decreased by 1.94%, and the proportion of particles of 0~2.5 µm decreased by 2.00% from 2016 to 2020. A multivariate linear regression model to calculate the concentrations of the pollutants was established. This study provides a reference for the comprehensive analysis and control of air pollutants in Xi'an and even worldwide.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Ambientales , Humanos , Material Particulado/análisis , Contaminantes Ambientales/análisis , Monitoreo del Ambiente/métodos , Estaciones del Año , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China , PolíticasRESUMEN
Slippery silicone-oil-infused (SOI) surfaces have recently emerged as a promising alternative to conventional anti-infection coatings for urinary catheters to combat biofilm and encrustation formation. Benefiting from the ultralow low hysteresis and slippery behavior, the liquid-like SOI coatings have been found to effectively reduce bacterial adhesion under both static and flow conditions. However, in real clinical settings, the use of catheters may also trigger local inflammation, leading to release of host-secreted proteins, such as fibrinogen (Fgn) that deposits on the catheter surfaces, creating a niche that can be exploited by uropathogens to cause infections. In this work, we report on the fabrication of a silicone oil-infused silver-releasing catheter which exhibited superior durability and robust antibacterial activity in aqueous conditions, reducing biofilm formation of two key uropathogens Escherichia coli and Proteus mirabilis by â¼99%, when compared with commercial all-silicone catheters after 7 days while remaining noncytotoxic toward L929 mouse fibroblasts. After exposure to Fgn, the oil-infused surfaces induced conformational changes in the protein which accelerated adsorption onto the surfaces. The deposited Fgn blocked the interaction of silver with the bacteria and served as a scaffold, which promoted bacterial colonization, resulting in a compromised antibiofilm activity. Fgn binding also facilitated the migration of Proteus mirabilis over the catheter surfaces and accelerated the deposition and spread of crystalline biofilm. Our findings suggest that the use of silicone oil-infused silver-releasing urinary catheters may not be a feasible strategy to combat infections and associated complications arising from severe inflammation.
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Cateterismo Urinario , Catéteres Urinarios , Animales , Ratones , Catéteres Urinarios/microbiología , Aceites de Silicona , Plata/farmacología , Biopelículas , SiliconasRESUMEN
Background: The purpose of this study was to determine whether oxybuprocaine hydrochloride gel could alleviate pain during male catheterization. Methods: Between September 2021 and March 2022, a randomized controlled trial was conducted at the Urology Department of Harbin Medical University Cancer Hospital (China). A total of 192 adult male patients requiring catheterization were enrolled and randomly assigned to one of two groups: 96 in the test group and 96 in the control group. The test group included patients who received oxybuprocaine hydrochloride gel as urethral lubricant, while patients in the control group received liquid paraffin. The preoperative and postoperative pain scores were compared using nonparametric tests. Results: At the baseline, there was no significant difference between the two groups. There was no significant difference in preoperative pain scores between the test group (mean ± SD = 20.04 ± 2.68 mm) and the control group (mean ± SD = 20.21 ± 3.23 mm) (p=0.694). Postoperative pain scores increased significantly in the test (mean ± SD = 31.98 ± 2.57 mm, p < 0.001) and control groups (mean ± SD = 38.96 ± 2.02 mm, p < 0.001) groups. Postoperative pain scores were significantly lower in the test group (mean ± SD = 31.98 ± 2.57 mm) than those in the control group (mean ± SD = 38.96 ± 2.02 mm (p < 0.001). Conclusions: The use of oxybuprocaine hydrochloride gel significantly reduced pain during male urethral catheterization. The study provides evidence for clinicians to use oxybuprocaine hydrochloride gel during male catheterization.
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Anestésicos Locales , Cateterismo Urinario , Adulto , Anestésicos Locales/efectos adversos , Humanos , Lubricantes , Masculino , Aceite Mineral , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Procaína/análogos & derivados , Cateterismo Urinario/efectos adversosRESUMEN
The control of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from the flue gas in hazardous waste incinerators (HWIs) is an intractable problem. To figure out the formation mechanism of PCDD/Fs and reduce the emission, a field study was carried out in a full-scale HWI. Ca(OH)2 & (NH4)H2PO4 or CH4N2S & (NH4)H2PO4 were injected into the quench tower, and the detailed inhibition effect on PCDD/Fs formation by the inhibitors coupled with quench tower was studied. Gas and ash samples were collected to analyze PCDD/Fs. XPS, EDS characterization and Principal component analysis were adopted to further analyze the de novo and precursors synthesis. The PCDD/Fs emissions reduced from 0.135 ng I-TEQ/Nm3 to 0.062 or 0.025 ng I-TEQ/Nm3 after the injection of Ca(OH)2 & (NH4)H2PO4 or CH4N2S & (NH4)H2PO4, respectively. The quench tower was found mainly hindering de novo synthesis by reducing reaction time. CP-route was the dominant formation pathway of PCDD/Fs in quench tower ash. Ca(OH)2 & (NH4)H2PO4 effectively inhibit precursors synthesis and reduce proportions of organic chlorine from 4.11% to 2.86%. CH4N2S & (NH4)H2PO4 show good control effects on both de novo and precursors synthesis by reducing chlorine content and inhibiting metal-catalysts. Sulfur-containing inhibitors can cooperate well with the quench tower to inhibit PCDD/Fs formation and will be effective to reduce dioxins formation in high chlorine flue gas. The results pave the way for further industrial application of inhibition to reduce PCDD/Fs emissions in the HWIs flue gas.
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Contaminantes Atmosféricos , Benzofuranos , Dioxinas , Dibenzodioxinas Policloradas , Residuos Peligrosos/análisis , Dibenzofuranos/análisis , Dibenzodioxinas Policloradas/análisis , Dioxinas/análisis , Cloro/análisis , Contaminantes Atmosféricos/análisis , Benzofuranos/análisis , Monitoreo del Ambiente , Incineración/métodos , Azufre/análisis , Dibenzofuranos Policlorados/análisisRESUMEN
Hantaan virus (HTNV) is the main cause of hemorrhagic fever with renal syndrome (HFRS) around the world, which results in profound morbidity and mortality. However, there are currently no FDA-approved therapeutics or vaccines against HFRS. To find new anti-HTNV drugs, the inhibitory activity of 901 small molecule kinase inhibitors against HTNV is analyzed. Among these compounds, compound 8G1 inhibits HTNV with a relatively high inhibition rate and lower toxicity. The viral titer and nucleocapsid protein of HTNV are reduced after compound 8G1 treatment in a dose-dependent manner at concentrations ranging from 1 to 20 µM. In addition, the administration of compound 8G1 at the early stage of HTNV infection can inhibit the replication of HTNV. The molecular docking result reveals that compound 8G1 forms interactions with the key amino acid residues of serine/threonine-protein kinase B (Akt), which is responsible for the observed affinity. Then, the mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) signaling pathways are inhibited. Our results may help to design novel targets for therapeutic intervention against HTNV infection and to understand the anti-HTNV mechanism of protein kinase inhibitors.
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The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction. Global knockout of IGFBP7 ameliorated kidney dysfunction, inflammatory responses, and programmed cell death in murine models of cisplatin-, kidney ischemia/reperfusion-, and lipopolysaccharide-induced AKI. IGFBP7 mainly originated from kidney tubular epithelial cells. Conditional knockout of IGFBP7 from the kidney protected against AKI. By contrast, rescue of IGFBP7 expression in IGFBP7-knockout mice restored kidney damage and inflammation. IGFBP7 function was determined in vitro using recombinant IGFBP7 protein, IGFBP7 knockdown, or overexpression. Additionally, IGFBP7 was found to bind to poly [ADP-ribose] polymerase 1 (PARP1) and inhibit its degradation by antagonizing the E3 ubiquitin ligase ring finger protein 4 (RNF4). Thus, IGFBP7 in circulation acts as a biomarker and key mediator of AKI by inhibiting RNF4/PARP1-mediated tubular injury and inflammation. Hence, over-activation of the IGFBP7/PARP1 axis represents a promising target for AKI treatment.