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BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disease that poses challenges in terms of treatment. The precise mechanism underlying the role of human umbilical cord mesenchymal stem cell-derived exosome (HucMSC-Ex) in the inflammatory repair process of IBD remains elusive. Mucosal mast cells accumulate within the intestinal tract and exert regulatory functions in IBD, thus presenting a novel target for addressing this intestinal disease. METHODS: A mouse model of Dextran Sulfate Sodium (DSS)-induced colitis was established and hucMSC-Ex were administered to investigate their impact on the regulation of intestinal mast cells. An in vitro co-culture model using the human clonal colorectal adenocarcinoma cell line (Caco-2) and human mast cell line (LAD2) was also established for further exploration of the effect of hucMSC-Ex. RESULTS: We observed the accumulation of mast cells in the intestines of patients with IBD as well as mice. In colitis mice, there was an upregulation of mast cell-related tryptase, interleukin-33 (IL-33), and suppression of tumorigenicity 2 receptor (ST2 or IL1RL1), and the function of the intestinal mucosal barrier related to intestinal tight junction protein was weakened. HucMSC-Ex treatment significantly reduced mast cell infiltration and intestinal damage. In the co-culture model, a substantial number of mast cells interact with the epithelial barrier, triggering activation of the IL-33/IL1RL1 (ST2) pathway and subsequent release of inflammatory factors and trypsin. This disruption leads to aberrant expression of tight junction proteins, which can be alleviated by supplementation with hucMSC-Ex. CONCLUSION: Our results suggest that hucMSC-Ex may reduce the release of mast cell mediators via the IL-33/IL1RL1 (ST2) axis, thereby mitigating its detrimental effects on intestinal barrier function.
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Mesenchymal stem cells (MSCs) have shown great potential in the treatment of several inflammatory diseases due to their immunomodulatory ability, which is mediated by exosomes secreted by MSCs (MSC-Exs). The incidence of inflammatory bowel disease (IBD) is increasing globally, but there is currently no long-term effective treatment. As an emerging therapy, MSC-Exs have proven to be effective in alleviating IBD experimentally, and the specific mechanism continues to be explored. The gut microbiota plays an important role in the occurrence and development of IBD, and MSCs and MSC-Exs can effectively regulate gut microbiota in animal models of IBD, but the mechanism involved and whether the outcome can relieve the characteristic dysbiosis necessary to alleviate IBD still needs to be studied. This review provides current evidence on the effective modulation of the gut microbiota by MSC-Exs, offering a basis for further research on the pathogenic mechanism of IBD and MSC-Ex treatments through the improvement of gut microbiota.
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Flexible perovskite solar cells (pero-SCs) have the potential to overturn the application scenario of silicon photovoltaic technology. However, their mechanical instability severely impedes their practical applicability, and the corresponding intrinsic degradation mechanism remains unclear. In this study, the degradation behavior of flexible pero-SCs is systematically analyzed under mechanical stress and it is observed that the structural failure first occurs in the polycrystal perovskite film, then extend to interfaces. To suppress the structural failure, pentaerythritol triacrylate, a crosslinked molecule with three stereoscopic crosslink sites, is employed to establish a 3D polymer network in both the interface and bulk perovskite. This network reduced the Young's modulus of the perovskite and simultaneously enhanced the interfacial toughness. As a result, the formation of cracks and delamination, which occur under a high mechanical stress, is significantly suppressed in the flexible pero-SC, which consequently retained 92% of its initial power conversion efficiency (PCE) after 20 000 bending cycles. Notably, the flexible device also shows a record PCE of 24.9% (certified 24.48%).
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Fetal structural anomalies and birth defects are primarily caused by genetic variants such as chromosomal number abnormalities, copy number variations (CNV), single nucleotide variants (SNV), and small insertions and deletions (indel). Whole-genome sequencing (WGS) based on next-generation sequencing (NGS) as an emerging technology for genetic disease diagnosis can detect the aforementioned types of variants. In recent years, high-depth WGS (> 30×) for prenatal diagnosis has also become available, and proved to be practical for unraveling the genetic etiology of fetal developmental abnormalities. To facilitate clinical practice, test development and preliminary implementation of WGS for diagnosing fetal structural anomalies, we have formulated a consensus over the application of WGS in prenatal diagnosis by compiling previously published consensuses, guidelines, and research findings to provide a guidance on data analysis, reporting recommendations, and consultation of prenatal WGS results.
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Diagnóstico Prenatal , Secuenciación Completa del Genoma , Humanos , Secuenciación Completa del Genoma/métodos , Diagnóstico Prenatal/métodos , Femenino , Embarazo , Variaciones en el Número de Copia de ADN , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Feto/anomalías , Aberraciones Cromosómicas , ConsensoRESUMEN
Perovskite solar cells (pero-SCs) are highly unstable even under trace water. Although the blanket encapsulation (BE) strategy applied in the industry can effectively block moisture invasion, the commercial UV-curable adhesives (UVCAs) for BE still trigger power conversion efficiency deterioration, and the degradation mechanism remains unknown. For the first time, the functions of commercial UVCAs are revealed in BE-processed pero-SCs, where the small-sized monomer easily permeates to the perovskite surface, forming an insulating barrier to block charge extraction, while the high-polarity moiety can destroy perovskite lattice. To solve these problems, a macromer, named PIBA is carefully designed, by grafting two acrylate terminal groups on the highly gastight polyisobutylene and realizes an increased molecular diameter as well as avoided high-polarity groups. The PIBA macromer can stabilize on pero-SCs and then sufficiently crosslink, forming a compact and stable network under UV light without sacrificing device performance during the BE process. The resultant BE devices show negligible efficiency loss after storage at 85% relative humidity for 2000 h. More importantly, these devices can even reach ISO 20653:2013 Degrees of protection IPX7 standard when immersed in one-meter-deep water. This BE strategy shows good universality in enhancing the moisture stability of pero-SCs, irrespective of the perovskite composition or device structure.
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This study presents a case of a female infertile patient suffering from embryonic arrest and recurrent implantation failure. The primary objective was to assess the copy number variations (CNVs) and DNA methylation of her embryos. Genetic diagnosis was conducted by whole-exome sequencing and validated through Sanger sequencing. CNV evaluation of two cleavage stage embryos was performed using whole-genome sequencing, while DNA methylation and CNV assessment of two blastocysts were carried out using whole-genome bisulfite sequencing. We identified two novel pathogenic frameshift variants in the MEI1 gene (NM_152513.3, c.3002delC, c.2264_2268 + 11delGTGAGGTATGGACCAC) in the proband. These two variants were inherited from her heterozygous parents, consistent with autosomal recessive genetic transmission. Notably, two Day 3 embryos and two Day 6 blastocysts were all aneuploid, with numerous monosomy and trisomy events. Moreover, global methylation levels greatly deviated from the optimized window of 0.25-0.27, measuring 0.344 and 0.168 for the respective blastocysts. This study expands the mutational spectrum of MEI1 and is the first to document both aneuploidy and abnormal methylation levels in embryos from a MEI1-affected female patient presenting with embryonic arrest. Given that females affected by MEI1 mutations might experience either embryonic arrest or monospermic androgenetic hydatidiform moles due to the extrusion of all maternal chromosomes, the genetic makeup of the arrested embryos of MEI1 patients provides important clues for understanding the different disease mechanisms of the two phenotypes.
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Variaciones en el Número de Copia de ADN , Metilación de ADN , Humanos , Femenino , Embarazo , Metilación de ADN/genética , Variaciones en el Número de Copia de ADN/genética , Mutación , Aneuploidia , Cromosomas , Proteínas de Ciclo CelularRESUMEN
Staphylococcus aureus (S. aureus) is one of the important human pathogens and causes both superficial and systemic infections. More importantly, the formation of S. aureus biofilms, a main cause of its pathogenicity and drug resistance, has been a critical challenge in clinical treatment. Carvacrol, a plant-based natural product, has gained great interest for therapeutic purposes due to its effective biological activity with low cytotoxicity. The present study aimed to investigate the effect of carvacrol on anti-biofilm activity. Growth curve analysis showed that applying a sub-inhibitory concentration of carvacrol (4 µg mL-1) was not lethal to S. aureus SYN; however, the inhibition rate of biofilm formation was as high as 63.6%, and the clearance rate of mature biofilms was as high as 30.7%. In addition, carvacrol effectively reduced the production of biofilm-associated extracellular polysaccharides and showed no effect on eDNA release. Furthermore, qPCR analysis revealed that carvacrol significantly down-regulated the expression of icaA, icaB, icaC, agrA, and sarA (P < 0.05). The in vivo efficacy of carvacrol against biofilm infection was further verified with a biological model of G. mellonella larvae. The results showed that carvacrol was non-toxic to the larvae and can effectively increase the survival rate of the larvae infected with S. aureus strain SYN.
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BACKGROUND: Biparametric MRI (bpMRI) is a faster, contrast-free, and less expensive MRI protocol that facilitates the detection of prostate cancer. The aim of this study is to determine whether a biparametric MRI PI-RADS v2.1 score-based model could reduce unnecessary biopsies in patients with suspected prostate cancer (PCa). METHODS: The patients who underwent MRI-guided biopsies and systematic biopsies between January 2020 and January 2022 were retrospectively analyzed. The development cohort used to derive the prediction model consisted of 275 patients. Two validation cohorts included 201 patients and 181 patients from 2 independent institutions. Predictive models based on the bpMRI PI-RADS v2.1 score (bpMRI score) and clinical parameters were used to detect clinically significant prostate cancer (csPCa) and compared by analyzing the area under the curve (AUC) and decision curves. Spearman correlation analysis was utilized to determine the relationship between International Society of Urological Pathology (ISUP) grade and clinical parameters/bpMRI score. RESULTS: Logistic regression models were constructed using data from the development cohort to generate nomograms. By applying the models to the all cohorts, the AUC for csPCa was significantly higher for the bpMRI PI-RADS v2.1 score-based model than for the clinical model in both cohorts (p < 0.001). Considering the test trade-offs, urologists would agree to perform 10 fewer bpMRIs to avoid one unnecessary biopsy, with a risk threshold of 10-20% in practice. Correlation analysis showed a strong correlation between the bpMRI score and ISUP grade. CONCLUSION: A predictive model based on the bpMRI score and clinical parameters significantly improved csPCa risk stratification, and the bpMRI score can be used to determine the aggressiveness of PCa prior to biopsy.
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Imagen por Resonancia Magnética , Neoplasias de la Próstata , Masculino , Humanos , Imagen por Resonancia Magnética/métodos , Próstata/diagnóstico por imagen , Próstata/patología , Nomogramas , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodosRESUMEN
Background: Staphylococcus haemolyticus is an opportunistic pathogen that belongs to coagulase-negative Staphylococci (CoNS). Increasing infection and multi-drug resistance cases caused by this strain have been reported and thus it poses a great health threat. Methods: The third-generation sequencing technology was performed on a S. haemolyticus SH-1 isolated from a clinical sample to analyze the drug resistance genes, which included vancomycin resistance related genes. In addition, antimicrobial susceptibility tests, transmission electron microscopy and Triton X-100 stimulated autolysis were conducted to understand its biological characteristics. Results: The study shows that this clinical isolate is a vancomycin intermediate-resistant strain. Genome comparison also revealed that WalK(N70K) and WalK(R280Q) mutations may contribute to the vancomycin resistant phenotype. Besides, S. haemolyticus SH-1 exhibit common features of thicker cell wall and decreased autolytic activity. Conclusion: S. haemolyticus SH-1 with WalKR mutations shows typical characteristics of vancomycin resistant strains. Combining the genome features and biological properties, our findings may provide important information for the understanding of the molecular mechanism of S. haemolyticus to vancomycin intermediate-resistance.
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Flexible perovskite solar cells (pero-SCs) are the best candidates to complement traditional silicon SCs in portable power applications. However, their mechanical, operational, and ambient stabilities are still unable to meet the practical demands because of the natural brittleness, residual tensile strain, and high defect density along the perovskite grain boundaries. To overcome these issues, a cross-linkable monomer TA-NI with dynamic covalent disulfide bonds, H-bonds, and ammonium is carefully developed. The cross-linking acts as "ligaments" attached on the perovskite grain boundaries. These "ligaments" consisting of elastomers and 1D perovskites can not only passivate the grain boundaries and enhance moisture resistance but also release the residual tensile strain and mechanical stress in 3D perovskite films. More importantly, the elastomer can repair bending-induced mechanical cracks in the perovskite film because of dynamic self-healing characteristics. The resultant flexible pero-SCs exhibit promising improvements in efficiency, and record values (23.84% and 21.66%) are obtained for 0.062 and 1.004 cm2 devices; the flexible devices also show overall improved stabilities with T90 >20 000 bending cycles, operational stability with T90 >1248 h, and ambient stability (relative humidity = 30%) with T90 >3000 h. This strategy paves a new way for the industrial-scale development of high-performance flexible pero-SCs.
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Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we found that patients with long viral RNA course (LC) exhibited prolonged high-level IgG antibodies and higher regulatory T (Treg) cell counts compared to those with short viral RNA course (SC) in terms of viral load. Longitudinal proteomics and metabolomics analyses of the patient sera uncovered that prolonged viral RNA shedding was associated with inhibition of the liver X receptor/retinoid X receptor (LXR/RXR) pathway, substantial suppression of diverse metabolites, activation of the complement system, suppressed cell migration, and enhanced viral replication. Furthermore, a ten-molecule learning model was established which could potentially predict viral RNA shedding period. In summary, this study uncovered enhanced inflammation and suppressed adaptive immunity in COVID-19 patients with prolonged viral RNA shedding, and proposed a multi-omic classifier for viral RNA shedding prediction.
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BACKGROUND: Inflammatory bowel disease (IBD) is a kind of chronic, idiopathic, and recurrent inflammation, associated with dysregulated intestinal mucosal immunity. Caspase (casp) 11/4-induced macrophage pyroptosis contributes to the development of inflammation, while human umbilical cord mesenchymal stem cell-secreted exosomes (hucMSC-Ex) play a reparative role in IBD. OBJECTIVE: The present study focused on the treatment of IBD with hucMSC-Ex and its regulatory mechanism via the casp11/4 pathway. METHODS: BALB/c mice were used to establish a dextran sulfate sodium (DSS)-induced colitis model, and hucMSC-Ex was administered intravenously to estimate its therapeutic effect. In vitro, RAW264.7 cells line, THP-1 cells line, and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) to activate an inflammatory environment of pyroptosis, followed by repairing with hucMSC-Ex. MicroRNA mimics and inhibitors were provided to verify the role of miR-203a-3p.2 from hucMSC-Ex in inflammation. The results were analyzed by Western blot, RT-qPCRãELISA, and LDH secretion. RESULTS: HucMSC-Ex inhibited the activation of casp11 and reduced the secretion of interleukin (IL)-1ß, IL-6, and casp11, which relieved macrophage pyroptosis to alleviate murine colitis. A consistent outcome was revealed in the cell experiments, where hucMSC-Ex contributed to a decreased casp11/4 expression, and lactate dehydrogenase (LDH) release, as a marker of cell damage. Moreover, miR-203a-3p.2 from hucMSC-Ex functioned as an effective mediator in the interaction with casp4 in THP-1 macrophage pyroptosis. CONCLUSION: HucMSC-Ex ameliorates colitis through the suppression of casp11/4-induced macrophage pyroptosis, and hucMSC-Ex carrying miR-203a-3p.2 inhibits casp4-induced macrophage pyroptosis in an inflammatory environment.
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Colitis , Enfermedades Inflamatorias del Intestino , Células Madre Mesenquimatosas , MicroARNs , Animales , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/terapia , Humanos , Inflamación/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Macrófagos , Células Madre Mesenquimatosas/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , PiroptosisRESUMEN
Right here, flower-like FeMoO4@1T-MoS2 composites were prepared by modifying FeMoO4 microspheres with two-dimensional lamellar 1T-MoS2 as co-catalyst, which was used for photo-Fenton catalysis degradation of binary dyes mixed with methylene blue (MB) and rhodamine B (RhB). Then various parameters affecting the generation of ·OH in the system were investigated. Systematic research shows that the degradation efficiency of MB and RhB can reach 99.8% in 18 min when the Mo/Fe molar ratio of the composite is 1:1. Furthermore, these experiments data were fitted by pseudo-first order kinetics model and pseudo-second order kinetics model. Subsequently the density functional theory (DFT) simulation results showed that FeMoO4 exhibited excellent adsorption for H2O2, and the introduction of 1T-MoS2 played a certain role in the adsorption and activation of H2O2. Finally, the degradation pathways of MB and RhB were proposed to determine intermediates during photo-Fenton process by LC-MS and the reaction mechanism was detailed investigated by quenching experiment of active free radicals. FeMoO4@1T-MoS2 has also excellent stability and highlights the potential and prospect of the composite for dye wastewater treatment.
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Colorantes , Peróxido de Hidrógeno , Catálisis , Hierro , Azul de Metileno , Molibdeno , Oxidación-ReducciónRESUMEN
Bacteria can form biofilms in natural and clinical environments on both biotic and abiotic surfaces. The bacterial aggregates embedded in biofilms are formed by their own produced extracellular matrix. Staphylococcus aureus (S. aureus) is one of the most common pathogens of biofilm infections. The formation of biofilm can protect bacteria from being attacked by the host immune system and antibiotics and thus bacteria can be persistent against external challenges. Therefore, clinical treatments for biofilm infections are currently encountering difficulty. To address this critical challenge, a new and effective treatment method needs to be developed. A comprehensive understanding of bacterial biofilm formation and regulation mechanisms may provide meaningful insights against antibiotic resistance due to bacterial biofilms. In this review, we discuss an overview of S. aureus biofilms including the formation process, structural and functional properties of biofilm matrix, and the mechanism regulating biofilm formation.
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Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted bacterial disease worldwide. However, unlike that in female infertility, the role of CT infection in male infertility remains controversial. The objective of this retrospective study was to explore the impacts of CT infection in the genital tract on sperm quality, sperm acrosin activity, antisperm antibody levels, and inflammation in a large cohort of infertile males in China. A total of 7154 semen samples were collected from infertile male subjects, 416 of whom were CT positive (CT+ group) and 6738 of whom were CT negative (CT- group), in our hospital between January 2016 and December 2018. Routine semen parameters (semen volume, pH, sperm concentration, viability, motility, morphology, etc.), granulocyte elastase levels, antisperm antibody levels, and sperm acrosin activity were compared between the CT+ and CT- groups. Our results showed that CT infection was significantly correlated with an abnormally low semen volume, as well as an increased white blood cell count and granulocyte elastase level (all P < 0.05) in the semen of infertile males; other routine semen parameters were not negatively impacted. The antisperm antibody level and sperm acrosin activity were not affected by CT infection. These findings suggested that CT infection might contribute to inflammation and hypospermia but does not impair sperm viability, motility morphology, and acrosin activity or generate antisperm antibodies in the infertile males of China.
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Chlamydia trachomatis , Infertilidad Masculina , Femenino , Genitales , Humanos , Infertilidad Masculina/epidemiología , Inflamación/epidemiología , Masculino , Estudios Retrospectivos , Semen , EspermatozoidesRESUMEN
Waste residue of Chinese prickly ash seeds were simply treated with aqueous ZnCl2 to prepared the high-performed activated carbon. It was characterized by the methods of XRD, SEM, EDX, FT-IR, BET and XPS. The synergetic adsorption performance of Chinese prickly ash seeds activated carbon for Pb2+, Ni2+ and Acid Orange IΙ (AO) was studied. In the single-component system, the adsorption capacity of Pb2+, Ni2+ and AO were 15.1, 10.7 and 188.4â mg/g, respectively. In the AO-Pb2+ system, the maximum adsorption capacity of Pb2+ and AO were 79.40 and 332.68â mg/g under temperature of 30°C and pH of 5.0, respectively. For AO-Ni2+ system, it was 375.6 and 38.3â mg/g, respectively. The adsorption kinetics was satisfactorily fitted by the pseudo-second-order model. The synergic adsorption process can be smoothly described by the non-modified Sips isotherm.
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Carbón Orgánico , Contaminantes Químicos del Agua , Adsorción , China , Espectroscopía Infrarroja por Transformada de Fourier , Termodinámica , Contaminantes Químicos del Agua/análisisRESUMEN
S-doped NiFe-based particles were prepared by a solvothermal method and used to degrade methylene blue (MB) aqueous solutions with visible light in a heterogeneous Fenton reaction. The obtained solid samples were characterized by XRD, SEM, TEM, and XPS. It was found that 0.2 g L-1 NiFe2S4 can degrade 99.8% MB solution within 6 min in the presence of 5 mM H2O2 and natural pH. The recycle experiments results indicate that the NiFe2S4 catalyst possessed better stability than NiFe2O4. Furthermore, NiFe2S4 particles can be easily separated from contaminant solution by using a magnet due to their excellent ferromagnetism. COD analysis experiments indicated that the COD removal rate of NiFe2S4 is 73.1% in 30 min. A possible mechanism was proposed, and the degradation products were measured by LC-MS.
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Peróxido de Hidrógeno , Azul de Metileno , Catálisis , Hierro , LuzRESUMEN
Objective To evaluate the quality of exosomes extracted from plasma samples by two different kits and the effects of different storage conditions on the stability of exosomes. Methods Plasma from healthy volunteers were stored at room temperature, 4DegreesCelsius, -20DegreesCelsius and -80DegreesCelsius for 0 hour, 24 hours, one week and one month. After storage, plasma exosomes were extracted using ExoQuickTM or Umibio kits. The morphology of exosomes was examined using transmission electron microscopy. Total protein concentrations were quantified by bicinchoninic acid (BCA) assay. The levels of CD9 and flotillin-1 were determined by Western blotting. The morphology and particle sizes of exosomes were studied by nanoparticle tracking analysis. Results A typical circular or elliptical exosomes were observed under an electron microscope with a diameter of 30-150 nm. The total protein concentration of exosomes extracted by ExoQuickTM kits was significantly higher than that by Umibio kits. Compared with ExoQuickTM, the expression of CD9 and flotillin-1 in the exosomes extracted by Umibio were higher, but the latter method took more time. The concentrations of exosomes extracted from plasma stored at room temperature were significantly lower than those stored at 4DegreesCelsius, -20DegreesCelsius and -80DegreesCelsius. The diameters of exosomes changed with temperature. Conclusion Compared with ExoQuickTM extraction method, Umibio extraction method takes longer time, but the purity of exosomes is higher. Low plasma storage temperature has little effect on the stability of plasma exosomes, but it affects the particle size of exosomes.