Idiopathic membranous nephropathy (IMN) is a leading pathological type of the adult primary nephrotic syndrome. Some patients develop end-stage renal disease due to poor response to treatment with ...steroid and immunosuppressive agents. In order to explore the molecular mechanism of IMN, we collected renal tissue samples from IMN patients and healthy controls and performed analysis by single-cell RNA sequencing (scRNA-seq). A total of 11 kidney cell clusters were identified, including multiple myeloid cell clusters, NK/T cell clusters, and B cell clusters. Most kidney parenchymal and immune cells were enriched in the regulation of immune response, inflammation, fibrosis and endoplasmic reticulum stress. The macrophage population in the IMN group showed a highly activated profile with up-regulated genes related to chemotaxis, inflammation, phagocytosis and fibrosis. CD8+ T cells continued to be cytotoxic in IMN; however, a transition to “inflammageing” GZMK+ CD8+ T cells was observed. The proportion of activated B cells in renal tissues of IMN patients was much higher than that of normal controls, indicating that B cells in IMN might be activated by constant antigenic stimulation. Moreover, the cell-cell interaction analysis revealed the potential communication between renal glomerular cells and immune cells in IMN. Overall, scRNA-seq was applied to IMN to unravel the characteristics of immune cells and elucidate possible underlying mechanisms involved in the pathogenesis of IMN.
In this study, the phenomenon of column separation that occurs in the downstream pipeline of a rapid closure valve is experimentally investigated. Special attention is paid to the dynamic behavior of ...the formation, growth, and collapse processes of cavities, which are observed using a high-speed camera. Synchronized images of cavity patterns and measured pressure histories are analyzed to elucidate the process of water column separation, the mechanism of column separation events, and the influence of parameters on the transient flow. Experimental results indicate that during the collapse process of vapor cavities, a superposition phenomenon involving a positive pressure wave and collapse wave occurs, resulting in a nearly three times rise of Joukowsky pressure. In all test cases, the maximum pressure of the pipeline exceeded 150 times the reservoir static pressure. A new classification for a water hammer combined with cavitation (four types of pressure oscillation patterns) is proposed based on whether the duration of column separation decreases sequentially and the maximum pipeline pressure follows the first collapse of cavities at the valve. As the initial flow velocity increases, there is generally an increase in maximum pressure; however, this trend may be scattered under certain operation conditions.
In rice, an E-class gene,
OsMADS1
, acts to specify the identities of the lemma and palea. In this study, the
OsMADS1
gene with a CaMV35S promoter was transformed into a japonica cultivar, Zhonghua ...11. All transgenic plants successfully showed similar phenotypes, including dwarfism, distorted panicles, decreased numbers of branches and spikelets, and elongated sterile lemma. Histological analysis showed that the elongated sterile lemma developed with silicified epidermal and sclerenchymal cells, which were lacking in the wild-type sterile lemma, suggesting that the elongated sterile lemma had assumed the identity of the lemma or palea. Some marker genes were subjected to a detailed analysis of the distribution of their expression among the lemma, palea and sterile lemma.
DROOPING LEAF
(
DL)
and
OsMADS6
genes were only expressed in the normal lemma or palea, respectively. In the elongated sterile lemma, a high level of
DL
gene expression was detected, while no expression of
OsMADS6
was found, implying that the sterile lemma transformed into the lemma but not the palea. These results provide clues to elucidate the mechanism of evolution from lemma to sterile lemma in rice. qPCR analysis also suggested that the ectopic expression of
OsMADS1
induced abnormal brassinosteroid and gibberellin acid activation, and then resulted in developmental defects in the stem and panicle.
The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues ...of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages.
We found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth hormone (GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca
pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components (P < 0.05) in vitro. Transduction of ATDC5 cells with a GHR-RNAi lentiviral vector decreased the expression of the GHR pathway components (P < 0.05). Additionally, the expression of the IGF-1 gene in the liver was lower in Debao ponies than in Mongolian horses at the juvenile and adult stages. Detection of plasma hormone concentrations showed that Debao ponies expressed higher levels of IGF-1 as juveniles and higher levels of GH as adults than Mongolian horses, indicating that the hormone regulation in Debao ponies differs from that in Mongolian horses.
Our work provides insights into the genetic regulation of short stature growth in mammals and can provide useful information for the development of therapeutic strategies for small size.
Energy metabolism plays a crucial role in the immune system. In addition to providing vital energy for cell growth, reproduction and other cell activities, the metabolism of nutrients such as glucose ...and lipids also have significant effects on cell function through metabolites, metabolic enzymes, and changing metabolic status. Interleukin-10 (IL-10), as a pleiotropic regulator, can be secreted by a diverse set of cells and can also participate in regulating the functions of various cells, thereby playing an essential role in the formation and maintenance of immune tolerance in pregnancy. Studies on the regulatory effects and mechanisms of IL-10 on immune cells are extensive; however, research from a metabolic perspective is relatively negligible. Here, we have discussed old and new data on the relationship between IL-10 and metabolism. The data show that alterations in cellular metabolism and specific metabolites regulate IL-10 production of immune cells. Moreover, IL-10 regulates immune cell phenotypes and functions by modulating oxidative phosphorylation and glycolysis. This review summarizes some earlier observations regarding IL-10 and its relationship with immune cells in pregnancy, and also presents recent research on the link between IL-10 and metabolism, highlighting the potential relationship between IL-10, immune cells, and energy metabolism during pregnancy.
•IL-10 can be secreted by a diverse set of cells and can also participate in regulating the functions of various cells, playing an essential role in pregnancy.•Specific metabolites and the alteration in cellular metabolism may regulate the IL-10 production of immune cells during pregnancy•IL-10 may regulate decidual immune cell phenotype and function via modulating oxidative phosphorylation and glycolysis
We developed a QuEChERS (quick, easy, cheap, effective, rugged and safe) method for the high through-put determination of 28 common veterinary antibiotics in swine wastewater using one-step ...dispersive solid-phase extraction (d-SPE) for sample cleanup and ultra-performance liquid chromatography-tandem mass spectrometry for detection. The orthogonal test method was used to systematically investigate the parameters that might influence d-SPE efficiency. The optimal d-SPE procedure utilized 40 mg primary secondary amine sorbent and 3 g L-1 Na2EDTA. The recoveries ranged from 50 to 100% with relative standard deviations <20% for all target analytes except for enrofloxacin and chlortetracycline. The limits of detection and limits of quantification for all the analytes ranged from 0.002 to 0.200 ng mL-1 and 0.005–0.500 ng mL-1, respectively. The developed method was successfully applied to the analysis of 28 antibiotic residues in swine wastewater from 10 pig farms located in central China. Fourteen antibiotics including 4 sulfonamides (sulfadiazine, sulfamerazine, sulfamonomethoxine and trimethoprim), 5 fluoroquinolones (norfloxacin, ciprofloxacin, pefloxacin, enrofloxacin, and ofloxacin), 1 lincosamide (lincomycin) and 4 tetracyclines (doxycycline, tetracycline, oxytetracycline, and chlortetracycline) were detected at levels ranging from 0.0560 to 1793 ng mL-1. Our results demonstrated that the optimized method is a simple but reliable analytical technique for the routine monitoring of veterinary antibiotics in swine wastewater. Swine wastewater samples that we analyzed from 10 pig farms in Jiangxi Province, China were highly contaminated and pose a serious threat to ecosystems and to public health.
•Sample clean-up was achieved by only one-step d-SPE.•The method is economical and eco-friendly especially for environmental analyses.•The method is suited for high-throughput analysis in official control programs.•Swine wastewater from 10 pig farms in central China was highly contaminated.
IntroductionOrthopaedic trauma patients are at high risk of venous thromboembolism (VTE). As VTE prophylaxis has gradually raised public concerns, guidelines related to this topic have increased over ...time. However, the existing recommendations of thromboprophylaxis guidelines in orthopaedic trauma patients are still inconsistent, and the quality of the guidelines and recommendations for the topic still lacks comprehensive assessments. This review aims to critically appraise clinical practice guidelines for thromboprophylaxis in orthopaedic trauma patients.Methods and analysisWe will conduct a comprehensive literature search up to 31 October 2022 in databases (PubMed, EMBASE, CINAHL, Web of Science, the Cochrane Library, etc), academic websites and guideline repositories. The quality of the guidelines and recommendations will be assessed by five reviewers independently using the Appraisal of Guidelines Research and Evaluation II instrument (AGREE-II) and the AGREE - Recommendation EXcellence (AGREE-REX). We will summarise the characteristics of the guidelines and compare the differences between these recommendations.Ethics and disseminationThis study will follow the Declaration of Helsinki and has received approval from the Ethics Committee on Biomedical Research, West China Hospital, Sichuan University (ethics approval no. 2021-989). The results will be summarised as a paper, disseminated through peer-reviewed journals, and will help guide further research in the future.Protocol registration numberCRD42021273405.
The value of increased arterial wave reflection, usually assessed by the transit time-dependent augmentation index and augmented pressure (Pa), in the prediction of cardiovascular events may have ...been underestimated. We investigated whether the transit time-independent measures of reflected wave magnitude predict cardiovascular outcomes independent of arterial stiffness indexed by carotid-femoral pulse wave velocity. A total of 1272 participants (47% women; mean age: 52+/-13 years; range: 30 to 79 years) from a community-based survey were studied. Carotid pressure waveforms derived by tonometry were decomposed into their forward wave amplitudes, backward wave amplitudes (Pb), and a reflection index (=Pb/(forward wave amplitude+Pb)), in addition to augmentation index, Pa, and reflected wave transit time. During a median follow-up of 15 years, 225 deaths occurred (17.6%), including 64 cardiovascular origins (5%). In univariate Cox proportional hazard regression analysis, pulse wave velocity, Pa, and Pb predicted all-cause and cardiovascular mortality in both men and women, whereas augmentation index, reflected wave transit time, and reflection index were predictive only in men. In multivariate analysis accounting for age, height, and heart rate, Pb predicted cardiovascular mortality in both men and women, whereas Pa was predictive only in men. Per 1-SD increment (6 mm Hg), Pb predicted 15-year cardiovascular mortality independent of brachial but not central pressure, pulse wave velocity, augmentation index, Pa, and conventional cardiovascular risk factors with hazard ratios of approximately 1.60 (all P<0.05). In conclusion, Pb, a transit time-independent measure of reflected wave magnitude, predicted long-term cardiovascular mortality in men and women independent of arterial stiffness.
Fully covered self-expandable metallic stents (FCSEMSs) are inserted in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) to resolve malignant distal bile duct obstructions. Some ...patients receive FCSEMSs during primary endoscopic retrograde cholangiopancreatography (ERCP), and others receive FCSEMSs during a later session, after the placement of a plastic stent. We aimed to evaluate the efficacy of FCSEMSs for primary use or following plastic stent placement. A total of 159 patients with pancreatic adenocarcinoma (m:f, 102:57) who had achieved clinical success underwent ERCP with the placement of FCSEMSs for palliation of obstructive jaundice. One-hundred and three patients had received FCSEMSs in a first ERCP, and 56 had received FCSEMSs after prior plastic stenting. Twenty-two patients in the primary metal stent group and 18 in the prior plastic stent group had recurrent biliary obstruction (RBO). The RBO rates and self-expandable metal stent patency duration did not differ between the two groups. An FCSEMS longer than 6 cm was identified as a risk factor for RBO in patients with PDAC. Thus, choosing an appropriate FCSEMS length is an important factor in preventing FCSEMS dysfunction in patients with PDAC with malignant distal bile-duct obstruction.
Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% ...despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and
form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC
= 3.5 μM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 μM, better than fluconazole (17.2% at 1 μM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.
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