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INTRODUCTION: The aim of this study was to explore the safety and feasibility of single-port nephroscopy combined with a needle electrode technique to unroof single dorsal simple renal cysts (SRCs). METHODS: This was a retrospective analysis of the clinical data for 18 patients with single dorsal SRCs treated with single-port nephroscopy and a needle electrode technique at Zhongshan City People's Hospital from August 2021 to August 2022. The basic information included the cyst condition, surgical methods and recurrence rate, and follow-up was conducted with CT imaging. RESULTS: The surgery was successful in all 18 patients. The duration of surgery ranged from 24 to 46 min, with an average of 35.83 ± 1.62 min; the intraoperative bleeding volume ranged from 2 to 20 mL, with an average of 9.0 ± 1.3 mL; and the visual analog scale (VAS) score within 24 h after surgery ranged from 1 to 6 points, with an average of 2.72 ± 0.36 points. There were no significant postoperative complications, such as bleeding, urinary fistula, or infection. All drainage tubes were removed on the first day after surgery. After 1 year of postoperative follow-up, 1 patient experienced recurrence, for a recurrence rate of 5.6%. CONCLUSION: Single-port nephroscopy combined with a needle electrode technique is a safe, feasible, and effective minimally invasive surgical approach for treating single dorsal SRCs.
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Estudos de Viabilidade , Doenças Renais Císticas , Agulhas , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Doenças Renais Císticas/cirurgia , Doenças Renais Císticas/diagnóstico por imagem , Eletrodos , Resultado do Tratamento , Laparoscopia , IdosoRESUMO
OBJECTIVE: Despite adequate dialysis, the prevalence of hyperkalemia in Chinese hemodialysis (HD) patients remains elevated. This study aims to evaluate the effectiveness of a dietary recommendation system driven by generative pretrained transformers (GPTs) in managing potassium levels in HD patients. METHODS: We implemented a bespoke dietary guidance tool utilizing GPT technology. Patients undergoing HD at our center were enrolled in the study from October 2023 to November 2023. The intervention comprised of two distinct phases. Initially, patients were provided with conventional dietary education focused on potassium management in HD. Subsequently, in the second phase, they were introduced to a novel GPT-based dietary guidance tool. This artificial intelligence (AI)-powered tool offered real-time insights into the potassium content of various foods and personalized dietary suggestions. The effectiveness of the AI tool was evaluated by assessing the precision of its dietary recommendations. Additionally, we compared predialysis serum potassium levels and the proportion of patients with hyperkalemia among patients before and after the implementation of the GPT-based dietary guidance system. RESULTS: In our analysis of 324 food photographs uploaded by 88 HD patients, the GPTs system evaluated potassium content with an overall accuracy of 65%. Notably, the accuracy was higher for high-potassium foods at 85%, while it stood at 48% for low-potassium foods. Furthermore, the study examined the effect of GPT-based dietary advice on patients' serum potassium levels, revealing a significant reduction in those adhering to GPTs recommendations compared to recipients of traditional dietary guidance (4.57 ± 0.76 mmol/L vs. 4.84 ± 0.94 mmol/L, P = .004). Importantly, compared to traditional dietary education, dietary education based on the GPTs tool reduced the proportion of hyperkalemia in HD patients from 39.8% to 25% (P = .036). CONCLUSION: These results underscore the promising role of AI in improving dietary management for HD patients. Nonetheless, the study also points out the need for enhanced accuracy in identifying low potassium foods. It paves the way for future research, suggesting the incorporation of extensive nutritional databases and the assessment of long-term outcomes. This could potentially lead to more refined and effective dietary management strategies in HD care.
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African swine fever (ASF), caused by the African swine fever virus (ASFV), is one of the most important infectious diseases that cause high morbidity and mortality in pigs and substantial economic losses to the pork industry of affected countries due to the lack of effective vaccines. The need to develop alternative robust antiviral countermeasures, especially anti-ASFV agents, is of the utmost urgency. This study shows that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid found in the roots of Stephania tetrandra of the family Menispermaceae, significantly inhibits ASFV replication in porcine alveolar macrophages (PAMs) at micromolar concentrations (IC50 = 1.66 µM). Mechanistically, the infection of ASFV triggers the AKT/mTOR/NF-κB signaling pathway. FAN significantly inhibits ASFV-induced activation of such pathways, thereby suppressing viral replication. Such a mechanism was confirmed using an AKT inhibitor MK2206 as it inhibited AKT phosphorylation and ASFV replication in PAMs. Altogether, the results suggest that the AKT/mTOR pathway could potentially serve as a treatment strategy for combating ASFV infection and that FAN could potentially emerge as an effective novel antiviral agent against ASFV infections and deserves further in vivo antiviral evaluations.
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Vírus da Febre Suína Africana , Antivirais , Benzilisoquinolinas , Macrófagos Alveolares , NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Replicação Viral , Animais , Macrófagos Alveolares/virologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Replicação Viral/efeitos dos fármacos , Vírus da Febre Suína Africana/efeitos dos fármacos , Vírus da Febre Suína Africana/fisiologia , Suínos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Benzilisoquinolinas/farmacologia , Antivirais/farmacologia , Febre Suína Africana/virologia , Febre Suína Africana/tratamento farmacológico , Febre Suína Africana/metabolismoRESUMO
Background: Scarless endoscopic thyroidectomy (ET) is increasingly accepted by the growing amount of surgeons. The target of this study is to assess the efficacy and summarise the experiences of total areola approach for ET (TAAET). Subjects and Methods: TAAET was performed on 529 patients between January 2016 and October 2021. All operated patients were divided into two groups according to the chronological order. Demographic data, perioperative data and post-operative complications were collected to assess the effectiveness of TAAET. Results: Five hundred and twenty-eight patients were successfully treated with TAAET, while 1 case was converted to open surgery due to bleeding. The surgical approach consists of lobectomy or total thyroidectomy with or without central lymph node dissection. The post-operative pathology of 433 (81.9%) patients was diagnosed with T1 ~2N0M0. The average number of unilateral lymph node dissection was 7.72 ± 2.44 while the bilateral lymph node was 10.70 ± 3.72. In terms of complications, 38 cases had transient hoarseness, 28 cases had tetany and numbness, 3 cases had post-operative bleeding, 1 case had infection and 33 cases had subcutaneous fluid. There were statistically significant differences between the two groups with respect to transient hoarseness (P < 0.001), tetany and numbness (P = 0.005), intraoperative blood loss (P = 0.003) and operation time for malignant tumour (P < 0.001) because of the accumulation of surgical experience and the maturation of technology. Conclusions: TAAET which conforms to the anatomical pathway of open thyroidectomy is a safe, effective and feasible technique and is highly suitable for novices.
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Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to the whole slide images from 789 transplant biopsies (478 baseline [pre-implantation] and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.
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Aprendizado Profundo , Transplante de Rim , Biópsia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Rim/patologia , Transplante de Rim/efeitos adversosRESUMO
OBJECTIVES: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share many clinical manifestations and serological features. The aim of this study was to identify the common transcriptional profiling and composition of immune cells in peripheral blood in these autoimmune diseases (ADs). METHODS: We analysed bulk RNA-seq data for enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types from peripheral blood mononuclear cells (PBMCs) in 119 treatment-naive patients (41 RA, 38 pSS, 28 SLE and 12 polyautoimmunity) and 20 healthy controls. The single-cell RNA-seq (scRNA-seq) and flow cytometry had been performed to further define the immune cell subsets on PBMCs. RESULTS: Similar transcriptional profiles and common gene expression signatures associated with nucleosome assembly and haemostasis were identified across RA, SLE, pSS and polyautoimmunity. Distinct TF ensembles and gene regulatory network were mainly enriched in haematopoiesis. The upregulated cell-lineage-specific TFs PBX1, GATA1, TAL1 and GFI1B demonstrated a strong gene expression signature of megakaryocyte (MK) expansion. Gene expression-based cell type enrichment revealed elevated MK composition, specifically, CD41b+CD42b+ and CD41b+CD61+ MKs were expanded, further confirmed by flow cytometry in these ADs. In scRNA-seq data, MKs were defined by TFs PBX1/GATA1/TAL1 and pre-T-cell antigen receptor gene, PTCRA. Cellular heterogeneity and a distinct immune subpopulation with functional enrichment of antigen presentation were observed in MKs. CONCLUSIONS: The identification of MK expansion provided new insights into the peripheral immune cell atlas across RA, SLE, pSS and polyautoimmunity. Aberrant regulation of the MK expansion might contribute to the pathogenesis of these ADs.
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Artrite Reumatoide/sangue , Autoimunidade/genética , Lúpus Eritematoso Sistêmico/sangue , Megacariócitos/imunologia , Síndrome de Sjogren/sangue , Adulto , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Leucócitos Mononucleares , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , RNA-Seq , Síndrome de Sjogren/imunologia , Transcriptoma/imunologiaRESUMO
INTRODUCTION: To describe the clinical and laboratory features of systemic lupus erythematosus (SLE) enteritis and to establish a predictive model of risk and severity of lupus enteritis (LE). METHODS: Records of patients with SLE complaining about acute digestive symptoms were reviewed. The predictive nomogram for the diagnosis of LE was constructed by using R. The accuracy of the model was tested with correction curves. The receiver operating characteristic curve (ROC curve) program and a Decision curve analysis (DCA) were used for the verification of LE model. Receiver operating characteristic curve was also employed for evaluation of factors in the prediction of severity of LE. RESULTS: During the eight year period, 46 patients were in the LE group, while 32 were in the non-LE group. Abdominal pain, emesis, D-dimer >5 µg/mL, hypo-C3, and anti-SSA positive remained statistically significant and were included into the prediction model. Area under the curve (AUC) of ROC curve in this model was 0.909. Correction curve indicated consistency between the predicted rate and actual diagnostic rates. The DCA showed that the LE model was of benefit. Forty-four patients were included in developing the prediction model of LE severity. Infection, SLE disease activity index (SLEDAI), CT score, and new CT score were validated as risk factors for LE severity. The AUC of the combined SLEDAI, infection and new CT score were 0.870. CONCLUSION: The LE model exhibits good predictive ability to assess LE risk in SLE patients with acute digestive symptoms. The combination of SLEDAI, infection, and new CT score could improve the assessment of LE severity.
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Enterite , Lúpus Eritematoso Sistêmico , Dor Abdominal/etiologia , Enterite/diagnóstico , Enterite/etiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Curva ROC , Índice de Gravidade de DoençaRESUMO
Contrast-induced acute kidney injury (CI-AKI) is a main cause of hospital-acquired renal failure. Nevertheless, limited measures have been shown to be effective for the treatment of CI-AKI. Here, we demonstrated that αKlotho, which is highly expressed in kidney, has therapeutic activity in CI-AKI. Our data showed that αKlotho expression levels were decreased both in the kidney and serum of CI-AKI mice. Administration of αKlotho protein protected the kidney and HK-2 cells against contrast-induced injury. Mechanistically, αKlotho reduced contrast-induced renal tubular cells pyroptosis by limiting NLRP3 inflammasome activation. Meanwhile, αKlotho up-regulated autophagy via inhibiting the AKT/mTOR pathway and decreased mitochondrial ROS level. Inhibition of autophagy blunted the suppression effect of αKlotho on NLRP3 inflammasome activation and cell pyroptosis in contrast-treated HK-2 cells. Taken together, our data suggest that αKlotho protein protects against CI-AKI through inhibiting NLRP3 inflammasome-mediated pyroptosis, which is likely by promoting autophagy. αKlotho may be a promising therapeutic strategy for CI-AKI.
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Injúria Renal Aguda/tratamento farmacológico , Inflamassomos/metabolismo , Proteínas Klotho/uso terapêutico , Substâncias Protetoras/uso terapêutico , Piroptose/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Animais , Autofagia/efeitos dos fármacos , Meios de Contraste/efeitos adversos , Proteínas Klotho/administração & dosagem , Masculino , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Substâncias Protetoras/administração & dosagemRESUMO
Quasi-one-dimensional materials exhibit not only unique crystal structure but also abundant physical properties such as charge density wave, Luttinger liquid, and superconductivity. Here we report the discovery, structure, and physical properties of a new manganese-based quasi-one-dimensional material RbMn6Bi5, which crystallizes in a monoclinic space group C2/m (No. 12) with lattice parameters a = 23.286(5) Å, b = 4.6215(9) Å, c = 13.631(3) Å, and ß = 125.00(3)°. The structure features [Mn6Bi5]-1 double-walled column extending along the [010] direction, together with Bi-Bi homoatomic bonds linking the columns and the countercation Rb+. The temperature-dependent resistivity clearly indicates a significant resistivity anisotropy for RbMn6Bi5, whereas the magnetic susceptibility and specific heat measurements show that RbMn6Bi5 is antiferromagnetic below 82 K. The density functional theory calculations indicate that RbMn6Bi5 is a quasi-one-dimensional metal with possible helical antiferromagnetic configuration. The discovery of RbMn6Bi5 confirms the viability of discovering new quasi-one-dimensional materials in manganese-based compounds.
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Progressive focal segmental glomerulosclerosis, characterized by podocyte loss, is often refractory to treatment and leads to progressive proteinuric chronic kidney disease. Interleukin-9 (IL-9) is reported to play important roles in innate and adaptive immunity in extrarenal inflammatory diseases. By using an IL-9 knockout mouse model, Xiong et al. demonstrate IL-9 as a novel pro-podocyte survival cytokine in the adriamycin nephropathy model of focal segmental glomerulosclerosis. Sequential in vitro and in vivo data corroborate a direct protective role, rather than an immunologic role, for IL-9 on podocyte survival. This commentary highlights these novel data and discusses the necessary steps for developing IL-9 as a potential novel therapeutic for focal segmental glomerulosclerosis.
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Glomerulosclerose Segmentar e Focal , Podócitos , Animais , Citocinas , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Interleucina-9 , Camundongos , Camundongos KnockoutRESUMO
Donor-recipient (D-R) differences at human leukocyte antigen (HLA) loci are currently incorporated into organ sharing, allocation and immunosuppression decisions. However, while acute rejection episodes have substantially diminished, progressive histologic damage occurs in allografts and improved long-term survival remains an unrealized goal among kidney recipients. Here we tested the hypothesis that non-HLA dependent, genome-wide D-R genetic differences could contribute to unchecked alloimmunity with histologic and functional consequences, culminating in long-term allograft failure. Genome-wide single nucleotide polymorphism (SNP) array data, excluding the HLA region, was utilized from 385 transplants to study the role of D-R differences upon serial histology and allograft survival. ADMIXTURE analysis was performed to quantitatively estimate ancestry in each D-R pair and PLINK was used to estimate the proportion of genome-shared identity-by-descent (pIBD) between D-R pairs. Subsequently, quantitative measures of recipient ancestry based on non-HLA SNPs was associated with death-censored allograft survival in adjusted Cox models. In D-R pairs of similar ancestry, pIBD was significantly associated with allograft survival independent of HLA mismatches in 224 transplants. Surprisingly, pIBD and recipient ancestry were not associated with clinical or subclinical rejection at any time post-transplant. Significantly, in multivariable analysis, pIBD inversely correlated with vascular intimal fibrosis in 160 biopsies obtained less than one year which in turn was significantly associated with allograft survival. Thus, our novel data show that non-HLA D-R differences associate with early vascular intimal fibrosis and allograft survival.
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Transplante de Rim , Aloenxertos , Fibrose , Rejeição de Enxerto/genética , Sobrevivência de Enxerto/genética , Antígenos HLA/genética , Humanos , Rim , Transplante de Rim/efeitos adversosRESUMO
OBJECTIVES: Familial aggregation of primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and co-aggregation of these autoimmune diseases (ADs) (also called familial autoimmunity) is well recognised. However, the genetic predisposition variants that explain this clustering remains poorly defined. METHODS: We used whole-exome sequencing on 31 families (9 pSS, 11 SLE, 6 RA and 5 mixed autoimmunity), followed by heterozygous filtering and cosegregation analysis of a family-focused approach to document rare variants predicted to be pathogenic by in silico analysis. Potential importance in immune-related processes, gene ontology, pathway enrichment and overlap analyses were performed to prioritise gene sets. RESULTS: A range from 1 to 50 rare possible pathogenic variants, including 39 variants in immune-related genes across SLE, RA and pSS families, were identified. Among this gene set, regulation of T cell activation (p=4.06×10-7) and T cell receptor (TCR) signalling pathway (p=1.73×10-6) were particularly concentrated, including PTPRC (CD45), LCK, LAT-SLP76 complex genes (THEMIS, LAT, ITK, TEC, TESPA1, PLCL1), DGKD, PRKD1, PAK2 and NFAT5, shared across 14 SLE, RA and pSS families. TCR-interactive genes P2RX7, LAG3, PTPN3 and LAX1 were also detected. Overlap analysis demonstrated that the antiviral immunity gene DUS2 variant cosegregated with SLE, RA and pSS phenotypes in an extended family, that variants in the TCR-pathway genes CD45, LCK and PRKD1 occurred independently in three mixed autoimmunity families, and that variants in CD36 and VWA8 occurred in both RA-pSS and SLE-pSS families. CONCLUSIONS: Our preliminary results define common genetic characteristics linked to familial pSS, SLE and RA and highlight rare genetic variations in TCR signalling pathway genes which might provide innovative molecular targets for therapeutic interventions for those three ADs.
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Artrite Reumatoide/genética , Autoimunidade/genética , Mutação em Linhagem Germinativa/imunologia , Lúpus Eritematoso Sistêmico/genética , Síndrome de Sjogren/genética , Linfócitos T/imunologia , Artrite Reumatoide/imunologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Síndrome de Sjogren/imunologiaRESUMO
OBJECTIVE: Idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) significantly increases morbidity and mortality. Lung ultrasound B-lines and Krebs von den Lungen-6 (KL-6) are identified as new sonographic and serum markers of ILD, respectively. The aim of our work was to assess the role of B-lines and KL-6 as markers of the severity of IIM-ILD. For this purpose, the correlation among B-lines score, serum KL-6 levels, high-resolution CT (HRCT) score, and pulmonary function tests were investigated in IIM-ILD patients. METHODS: Thirty-eight patients with IIM-ILD underwent chest HRCT scans, lung ultrasound and pulmonary function tests (independently performed within 1 week) examination. To assess severity and extent of ILD at HRCT, the Warrick score was used. The B-lines score denoting the extension of ILD was calculated by summing the number of B-lines on a total of 50 scanning sites. Serum KL-6 levels (U/ml) was measured by chemiluminescent enzyme immunoassay. RESULTS: A significant correlation was found between the B-lines score and serum KL-6 levels (r = 0.43, P < 0.01), and between the Warrick score and serum KL-6 levels (r = 0.45, P < 0.01). A positive correlation between B-lines score and the Warrick score (r = 0.87, P < 0.0001) was also confirmed. Both B-lines score and KL-6 levels inversely correlated to diffusion capacity for carbon monoxide (r = -0.77, P < 0.0001 and r = -0.42, P < 0.05, respectively) and total lung capacity (r = -0.73, P < 0.0001 and r = -0.36, P < 0.05, respectively). Moreover, B-lines correlated inversely with forced vital capacity (r = -0.73, P < 0.0001), forced expiratory volume in 1 s (r = -0.69, P < 0.0001). CONCLUSION: B-lines score and serum KL-6 levels correlate with HRCT findings and pulmonary function tests, supporting their use as measures of IIM-ILD severity.
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Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Mucina-1/sangue , Miosite/diagnóstico por imagem , Adulto , Biomarcadores/sangue , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/complicações , Testes de Função Respiratória , Índice de Gravidade de Doença , UltrassonografiaRESUMO
BACKGROUND/AIMS: The NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome is involved in the progression of chronic kidney disease in several rodent models. Here, we investigated whether a specific inhibitor of NLRP3 inflammasome, MCC950, can attenuate cisplatin-induced renal fibrosis. MATERIALS: Renal fibrosis was induced via a series of three injections of cisplatin to male C57BL/6 mice (7.5â¯mg/kg body weight). Activation of NLRP3 inflammasome was detected by immunoblotting, real-time PCR, and immunofluorescence. To validate the protective effect of NLRP3 inflammasome inhibition, MCC950(20â¯mg/kg body weight) was daily injected into multiple-cisplatin-treated mice intraperitoneally for 14 days, starting from 4 weeks after the first dose of cisplatin. NLRP3-/- mice were used to confirm the role of NLRP3 inflammasome in cisplatin-induced renal fibrosis. RESULTS: Mice were euthanized at 6 weeks after the first dose of cisplatin treatment. In multiple-cisplatin-induced murine model, renal fibrosis was accompanied by the activation of NLRP3 inflammasome. MCC950, the specific inhibitor of NLRP3 inflammasome, reduced cisplatin-induced renal dysfunction, tubular damage, interstitial collagen deposit, and the expression of profibrotic parameters. NLRP3 inhibition might protect against cisplatin-induced renal fibrosis through the alleviation of oxidative stress and inflammation. Furthermore, inhibition of NLRP3 inflammasome activation by deleting NLRP3 gene halted the progression of cisplatin-induced renal fibrosis. CONCLUSION: Inhibition of NLRP3 inflammasome attenuates renal fibrosis due to repeated cisplatin injections, and might be identified as a potential target for attenuating cisplatin-induced chronic kidney disease.
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Cisplatino/toxicidade , Fibrose/tratamento farmacológico , Furanos/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamação/tratamento farmacológico , Nefropatias/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Antineoplásicos/toxicidade , Fibrose/induzido quimicamente , Fibrose/metabolismo , Fibrose/patologia , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Indenos , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estudos Retrospectivos , SulfonasRESUMO
Intermetallic compounds represent an extensive pool of candidates for energy related applications stemming from magnetic, electric, optic, caloric, and catalytic properties. The discovery of novel intermetallic compounds can enhance understanding of the chemical principles that govern structural stability and chemical bonding as well as finding new applications. Valence electron-poor polar intermetallics with valence electron concentrations (VECs) between 2.0 and 3.0 e-/atom show a plethora of unprecedented and fascinating structural motifs and bonding features. Therefore, establishing simple structure-bonding-property relationships is especially challenging for this compound class because commonly accepted valence electron counting rules are inappropriate. During our efforts to find quasicrystals and crystalline approximants by valence electron tuning near 2.0 e-/atom, we observed that compositions close to those of quasicrystals are exceptional sources for unprecedented valence electron-poor polar intermetallics, e.g., Ca4Au10In3 containing (Au10In3) wavy layers, Li14.7Mg36.8Cu21.5Ga66 adopting a type IV clathrate framework, and Sc4MgxCu15-xGa7.5 that is incommensurately modulated. In particular, exploratory syntheses of AAu3T (A = Ca, Sr, Ba and T = Ge, Sn) phases led to interesting bonding features for Au, such as columns, layers, and lonsdaleite-type tetrahedral frameworks. Overall, the breadth of Au-rich polar intermetallics originates, in part, from significant relativistics effect on the valence electrons of Au, effects which result in greater 6s/5d orbital mixing, a small effective metallic radius, and an enhanced Mulliken electronegativity, all leading to ultimate enhanced binding with nearly all metals including itself. Two other successful strategies to mine electron-poor polar intermetallics include lithiation and "cation-rich" phases. Along these lines, we have studied lithiated Zn-rich compounds in which structural complexity can be realized by small amounts of Li replacing Zn atoms in the parent binary compounds CaZn2, CaZn3, and CaZn5; their phase formation and bonding schemes can be rationalized by Fermi surface-Brillouin zone interactions between nearly free-electron states. "Cation-rich", electron-poor polar intermetallics have emerged using rare earth metals as the electropositive ("cationic") component together metal/metalloid clusters that mimic the backbones of aromatic hydrocarbon molecules, which give evidence of extensive electronic delocalization and multicenter bonding. Thus, we can identify three distinct, valence electron-poor, polar intermetallic systems that have yielded unprecedented phases adopting novel structures containing complex clusters and intriguing bonding characteristics. In this Account, we summarize our recent specific progress in the developments of novel Au-rich BaAl4-type related structures, shown in the "gold-rich grid", lithiation-modulated Ca-Li-Zn phases stabilized by different bonding characteristics, and rare earth-rich polar intermetallics containing unprecedented hydrocarbon-like planar Co-Ge metal clusters and pronounced delocalized multicenter bonding. We will focus mainly on novel structural motifs, bonding analyses, and the role of valence electrons for phase stability.
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Planar hydrocarbon-like metal clusters may foster new insights linking organic molecules with conjugated π-π bonding interactions and inorganic structures in terms of their bonding characteristics. However, such clusters are uncommon in polar intermetallics. Herein, we report two polar intermetallic phases, Pr5 Co2 Ge3 and Pr7 Co2 Ge4 , both of which feature such planar metal clusters, namely, ethylene-like [Co2 Ge4 ] clusters plus the concatenated forms and polyacene-like [Co2 Ge2 ]n ribbons in Pr5 Co2 Ge3 , and 1,2,4,5-tetramethylbenzene-like [Co4 Ge6 ] cluster in Pr7 Co2 Ge4 . Just as in the related planar organic structures, these metal-metalloid species are dominated by covalent bonding interactions. Both compounds magnetically order at low temperature with net ferromagnetic components: Pr5 Co2 Ge3 through a series of transitions below 150â K and Pr7 Co2 Ge4 through a single ferromagnetic transition at 19â K. Spin-polarized electronic structure calculations for Pr7 Co2 Ge4 reveal strong spin-orbit coupling within Pr and considerable magnetic contributions from Co atoms. This work suggests that similar structural chemistry can emerge for other rare-earth/late-transition-metal/main-group systems.
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We use high resolution angle resolved photoemission spectroscopy and density functional theory with measured crystal structure parameters to study the electronic properties of CaKFe_{4}As_{4}. In contrast to the related CaFe_{2}As_{2} compounds, CaKFe_{4}As_{4} has a high T_{c} of 35 K at stochiometric composition. This presents a unique opportunity to study the properties of high temperature superconductivity in the iron arsenides in the absence of doping or substitution. The Fermi surface consists of several hole and electron pockets that have a range of diameters. We find that the values of the superconducting gap are nearly isotropic (within the explored portions of the Brillouin zone), but are significantly different for each of the Fermi surface (FS) sheets. Most importantly, we find that the momentum dependence of the gap magnitude plotted across the entire Brillouin zone displays a strong deviation from the simple cos(k_{x})cos(k_{y}) functional form of the gap function, proposed by the scenario of Cooper pairing driven by a short range antiferromagnetic exchange interaction. Instead, the maximum value of the gap is observed on FS sheets that are closest to the ideal nesting condition, in contrast to previous observations in other ferropnictides. These results provide strong support for the multiband character of superconductivity in CaKFe_{4}As_{4}, in which Cooper pairing forms on the electron and the hole bands interacting via a dominant interband repulsive interaction, enhanced by band nesting.
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Cluster chemistry of intermetallics with valence electron counts (VECs) in the range of 2.0-3.0 is intriguing. Lithiation of polar intermetallics in this VEC region is found to be an effective chemical route to produce new complex structures with different stability mechanisms. In this work, two new complex intermetallic structures have been discovered in the Ca-Li-Zn system: Ca12LixZn59-x and Ca15LixZn75-x. Ca12LixZn59-x, x ≈ 5.65(3)-14.95(3), forms in the trigonal space group R3Ì m, with a = 9.074(1)-9.1699(2) Å, c = 53.353(1)-53.602(1) Å, and Z = 3. In comparison, Ca15LixZn75-x, x ≈ 19.07(2), crystallizes in the space group P63/mmc, with a ≈ 9.183(1) Å, c ≈ 45.191(5) Å), and Z = 2. Both structures are members of a large intergrowth family featuring slabs of dimers (D) and trimers (T) stacking along [001], with the sequences DTDDTDDTD for Ca12LixZn59-x and TDDDTDDD for Ca15LixZn75-x. Each dimer consists of two face-sharing Zn-centered hypho-icosahedra, and each trimer comprises a Li-centered icosahedron sandwiched by two hypho-icosahedra. This intergrowth family includes several known intermetallic structure types involving very electropositive metals, e.g., SrMg5.2, Ba2Li4.21Al4.79, and Sr9Li17.5Al25.5. Because of cluster defects and condensation, both Ca12LixZn59-x and Ca15LixZn75-x are electronically akin to close-packed metals, and their structural stabilities can be interpreted by a Hume-Rothery mechanism rather than the Zintl-Klemm concept.
RESUMO
Zinc clusters are not common for binary intermetallics with relatively low zinc content, but this work shows that zinc clustering can be triggered by lithiation, as exemplified by Ca(â¼30)Li(3+x)Zn(60-x), P6/mmm, Z = 1, which can be directly converted from CaZn(2). Two end members of the solid solution (x = 0.44 and 1.38) were established and structurally characterized by single-crystal X-ray diffraction analyses: Ca(30)Li(3.44(6))Zn(59.56(6)), a = 15.4651(9) Å, c = 9.3898(3) Å; Ca(30.45(2))Li(4.38(6))Zn(58.62(6)), a = 15.524(3) Å, c = 9.413(2) Å. The structures of Ca(â¼30)Li(3+x)Zn(60-x) feature a condensed anionic network of Zn(3) triangles, lithium-centered Zn(12) icosahedra, and arachno-(Zn,Li)18 tubular clusters that are surrounded respectively by Ca(14), Ca(20), and Ca(30) polyhedra. These polyhedra share faces and form a clathrate-like cationic framework. The specific occupation of lithium in the structure is consistent with theoretical "coloring" analyses. Analysis by the linear muffin-tin orbital (LMTO) method within the atomic sphere approximation reveals that Ca(â¼30)Li(3+x)Zn(60-x) is a metallic, Zintl-like phase with an open-shell electronic structure. The contribution of Ca-Zn polar covalent interactions is about 41%.