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Superlattices-a periodic stacking of two-dimensional layers of two or more materials-provide a versatile scheme for engineering materials with tailored properties1,2. Here we report an intrinsic heterodimensional superlattice consisting of alternating layers of two-dimensional vanadium disulfide (VS2) and a one-dimensional vanadium sulfide (VS) chain array, deposited directly by chemical vapour deposition. This unique superlattice features an unconventional 1T stacking with a monoclinic unit cell of VS2/VS layers identified by scanning transmission electron microscopy. An unexpected Hall effect, persisting up to 380 kelvin, is observed when the magnetic field is in-plane, a condition under which the Hall effect usually vanishes. The observation of this effect is supported by theoretical calculations, and can be attributed to an unconventional anomalous Hall effect owing to an out-of-plane Berry curvature induced by an in-plane magnetic field, which is related to the one-dimensional VS chain. Our work expands the conventional understanding of superlattices and will stimulate the synthesis of more extraordinary superstructures.
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The high level of lactate in tumor microenvironment not only promotes tumor development and metastasis, but also induces immune escape, which often leads to failures of various tumor therapy strategies. We here report a sono-triggered cascade lactate depletion strategy by using semiconducting polymer nanoreactors (SPNLCu) for cancer cuproptosis-immunotherapy. The SPNLCu mainly contain a semiconducting polymer as sonosensitizer, lactate oxidase (LOx) conjugated via a reactive oxygen species (ROS)-cleavable linker and chelated Cu2+. Upon ultrasound (US) irradiation, the semiconducting polymer generates singlet oxygen (1O2) to cut ROS-cleavable linker to allow the release of LOx that catalyzes lactate depletion to produce hydrogen peroxide (H2O2). The Cu2+ will be reduced to Cu+ in tumor microenvironment, which reacts with the produced H2O2 to obtain hydroxyl radical (â OH) that further improves LOx release via destroying ROS-cleavable linkers. As such, sono-triggered cascade release of LOx achieves effective lactate depletion, thus relieving immunosuppressive roles of lactate. Moreover, the toxic Cu+ induces cuproptosis to cause immunogenic cell death (ICD) for activating antitumor immunological effect. SPNLCu are used to treat both subcutaneous and deep-tissue orthotopic pancreatic cancer with observably enhanced efficacy in restricting the tumor growths. This study thus provides a precise and effective lactate depletion tactic for cancer therapy.
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Cobre , Imunoterapia , Ácido Láctico , Neoplasias Pancreáticas , Polímeros , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Ácido Láctico/química , Ácido Láctico/metabolismo , Polímeros/química , Polímeros/farmacologia , Cobre/química , Humanos , Animais , Camundongos , Semicondutores , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/química , Oxigenases de Função Mista/metabolismo , Oxigenases de Função Mista/química , Ondas Ultrassônicas , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Regulation of gene expression is conducive to understanding the physiological roles of specific genes and provides therapeutic potentials, which however still remains a great challenge. Nonviral carriers have some advantages for gene delivery compared to traditional physical delivery strategies, but they often fail to control the delivery of genes in targeting regions, and thus lead to off-target side effects. Although endogenous biochemical signal-responsive carriers have been used to improve the transfection efficiency, their selectivity and specificity are still poor because of the coexistence of biochemical signals in both normal tissues and disease sites. In contrast, light-responsive carriers can be adopted to precisely control gene transgenic behaviors at the specified locations and time, thus reducing the off-target gene editing at nontarget positions. Particularly, the near-infrared (NIR) light has better tissue penetration depth and lower phototoxicity than ultraviolet and visible light sources, showing great promise for intracellular gene expression regulation. In this review, we summarize the recent progress of NIR photoresponsive nanotransducers for precision regulation of gene expression. These nanotransducers can achieve controlled gene expression via three different mechanisms (photothermal activation, photodynamic regulation, and NIR photoconversion) to allow various applications, such as gene therapy of cancer, which will be discussed in detail. A conclusion and discussion of the challenges and outlook will be given at the end of this review.
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The anomalous Hall effect (AHE), a protocol of various low-power dissipation quantum phenomena and a fundamental precursor of intriguing topological phases of matter, is usually observed in ferromagnetic materials with an orthogonal configuration between the electric field, magnetization, and the Hall current. Here, based on the symmetry analysis, we find an unconventional AHE induced by the in-plane magnetic field (IPAHE) via the spin-canting effect in PT-symmetric antiferromagnetic (AFM) systems, featuring a linear dependence of magnetic field and 2π angle periodicity with a comparable magnitude to conventional AHE. We demonstrate the key findings in the known AFM Dirac semimetal CuMnAs and a new kind of AFM heterodimensional VS_{2}-VS superlattice with a nodal-line Fermi surface and, also, briefly discuss the experimental detection. Our Letter provides an efficient pathway for searching and/or designing realistic materials for a novel IPAHE that could greatly facilitate their application in AFM spintronic devices. National Science Foundation.
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BACKGROUND: Extensive research has shown abnormal cerebral blood flow (CBF) in patients with major depressive disorder (MDD) that is a heritable disease. The objective of this study was to investigate the genetic mechanisms of CBF abnormalities in MDD. METHODS: To achieve a more thorough characterization of CBF changes in MDD, we performed a comprehensive neuroimaging meta-analysis of previous literature as well as examined group CBF differences in an independent sample of 133 MDD patients and 133 controls. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial association analyses were conducted to identify genes whose expression correlated with CBF changes in MDD, followed by a set of gene functional feature analyses. RESULTS: We found increased CBF in the reward circuitry and default-mode network and decreased CBF in the visual system in MDD patients. Moreover, these CBF changes were spatially associated with expression of 1532 genes, which were enriched for important molecular functions, biological processes, and cellular components of the cerebral cortex as well as several common mental disorders. Concurrently, these genes were specifically expressed in the brain tissue, in immune cells and neurons, and during nearly all developmental stages. Regarding behavioral relevance, these genes were associated with domains involving emotion and sensation. In addition, these genes could construct a protein-protein interaction network supported by 60 putative hub genes with functional significance. CONCLUSIONS: Our findings suggest a cerebral perfusion redistribution in MDD, which may be a consequence of complex interactions of a wide range of genes with diverse functional features.
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BACKGROUND: The implementation of automated peritoneal dialysis (APD) has considerably increased in many countries. We conducted a bibliometric analysis to evaluate the accumulating studies on APD in the last two decades quantitatively and qualitatively. METHODS: Publications regarding APD research between 2000 and 2020 were retrieved from the Web of Science Core Collection database by using the index term "automated peritoneal dialysis." CiteSpace, VOSviewer, and an online platform were employed to analyze the number of publications and the collaboration relationships between countries, institutions, authors, and co-cited journals. Cluster analysis and burst keywords detection were performed on co-cited references and keywords, respectively. RESULTS: We obtained a record of 545 publications related to APD in total. The United States was the country that contributes most, and Baxter Healthcare Corporation was the leading institution. Peritoneal Dialysis International was the most active journals in this field. Claudio Ranco was the most productive author, and Simon J Davies ranked the first in the cited authors. Co-cited reference cluster analysis and high frequency keywords showed that survival, ultrafiltration and peritonitis are continuous hot topics. While remote monitoring (RM) and telemedicine may be APD research frontiers according to burst keywords detection. CONCLUSION: This bibliometric study provides comprehensive overview on the publications of APD over the past two decades. These findings help to identify the hotspots and explore new directions for future research. RM has become an emerging trend in APD field.
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Diálise Peritoneal , Peritonite , Humanos , Diálise Renal , Bibliometria , Bases de Dados FactuaisRESUMO
INTRODUCTION: Along with the peritoneal dialysis (PD)-favored policy in China and the implementation of more comprehensive PD management, PD has evolved in Chinese mainland over the last decade. Despite the existence of national registries and several provincial epidemiological descriptive studies, there was almost no national research on the changing trajectory in PD population. A comparison study, based on two national surveys that were 10 years apart, was conducted to reveal the evolvement of PD care in Chinese mainland. METHODS: Two national surveys have been done respectively in 2010 and 2020 to capture the epidemiological status, application of different modalities, management of perioperative infection, and long-term complications among PD patients. RESULTS: In the study with 730 participating hospitals (n = 14,912 PD patients) in 2010 and 746 hospitals (n = 101,537) in 2020, prevalent PD patients have increased in the past 10 years with increased numbers of PD patients in both secondary (average 5 ± 16 vs. 43 ± 41, p < 0.01) and tertiary hospitals (32 ± 53 vs. 153 ± 215, p < 0.01). Automated PD has been accessible in 0.4% of all hospitals, only in tertiary centers in 2010 and its application increased to 51% in 2020. PD centers have become more engaged in PD catheter placement, treated properly for the PD-related infection, and carried out the follow-up in compliance with the national protocols. CONCLUSIONS: Our study indicates that over the past decade, the prevalent PD population has quickly expanded with increased APD availability in Chinese mainland. The management of PD patients has become better conforming to the guidelines and long-term follow-up of patients have remained stable. Further studies are warranted to evaluate whether the rapidly changing paradigm of PD could translate into the socio-economic benefits in the society.
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Diálise Peritoneal , Peritonite , Humanos , População do Leste Asiático , Diálise Renal , Diálise Peritoneal/métodos , Inquéritos e Questionários , CateterismoRESUMO
INTRODUCTION: Peritoneal dialysis (PD)-related peritonitis is a serious complication of PD. Improving the diagnostic rate of peritonitis pathogens may substantially benefit peritonitis patients. METHODS: The study was conducted in the People's Liberation Army (PLA) General Hospital from 1 June 2021 to 31 May 2022. Information about peritonitis, culture and metagenomic next-generation sequencing (mNGS) results and so on were collected. Patients were divided into antibiotic-use and antibiotic-free groups. The culture and mNGS results were compared using the paired χ2 test. RESULTS: Data from 26 patients with peritonitis were collected. 50% of the patients had used antibiotics before samples were obtained (antibiotic-use group). The positivity rate using culture was 92.3% (12 cases) in the antibiotic-free group and 38.5% (5 cases) in the antibiotic-use group (p = 0.011). However, the positivity rate using mNGS was 92.3% (12 cases) regardless of whether antibiotics were used (p = 1.000). After revising the mNGS results, the positivity rate was 84.6% (11 cases) in both groups (p = 1.000). A significant difference between culture and mNGS results of all groups was observed (p = 0.039). The difference no matter between culture and mNGS (p = 0.016) or between culture and modified mNGS (p = 0.031) of the antibiotic-use group was observed. CONCLUSION: For patients with PD-related peritonitis who previously received antibiotics, mNGS is suggested. For other patients, mNGS testing can be performed, but the results should be interpreted with caution. Much more research should be done to identify a powerful and ideal tool to detect pathogens underlying PD-related peritonitis.
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Diálise Peritoneal , Peritonite , Humanos , Projetos Piloto , Sequenciamento de Nucleotídeos em Larga Escala , Antibacterianos/uso terapêutico , Diálise Peritoneal/efeitos adversos , Peritonite/diagnóstico , Peritonite/etiologia , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Lysosomes are degradative organelles that maintain cellular homeostasis and protein quality control. Transcription factor EB (TFEB)-mediated lysosome biogenesis enhances lysosome-dependent degradation and alleviates neurodegenerative diseases, but the mechanisms underlying TFEB regulation and modification are still poorly understood. METHODS: By screening novel small-molecule compounds, we identified a group of lysosome-enhancing compounds (LYECs) that promote TFEB activation and lysosome biogenesis. RESULTS: One of these compounds, LH2-051, significantly inhibited the function of the dopamine transporter (DAT) and subsequently promoted lysosome biogenesis. We uncovered cyclin-dependent kinase 9 (CDK9) as a novel regulator of DAT-mediated lysosome biogenesis and identified six novel CDK9-phosphorylated sites on TFEB. We observed that signal transduction by the DAT-CDK9-TFEB axis occurs on lysosomes. Finally, we found that LH2-051 enhanced the degradation of amyloid beta plaques and improved the memory of amyloid precursor protein (APP)/Presenilin 1 (PS1) mice. DISCUSSION: We identified the DAT-CDK9-TFEB signaling axis as a novel regulator of lysosome biogenesis. Our study sheds light on the mechanisms of protein quality control under pathophysiological conditions.
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Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Lisossomos/metabolismo , AutofagiaRESUMO
The Berry curvature and orbital magnetic moment (OMM) come from either inversion symmetry or time-reversal symmetry breaking in quantum materials. Here, we demonstrate the significance of OMMs and Berry curvature in planar Hall effect (PHE) in antiferromagnetic topological insulator MnBi2Te4 flakes. We observe a PHE with period of π and positive magnitude at low fields, resembling the PHE of the surface states in nonmagnetic topological insulators. Remarkably, a novel predominant PHE with period of π/2 and negative magnitude emerges below the Néel temperature with B > 10 T. Our theoretical calculations reveal that this unusual π/2-periodic PHE originates from the topological OMMs of bulk Dirac electrons. Moreover, the competition between the contributions from the bulk and the surface states leads to nontrivial evolutions of PHE and anisotropic magnetoresistance. Our results reveal intriguing electromagnetic response due to the OMMs and also provide insight into the potential applications of magnetic topological insulators in spintronics.
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Unlike conventional bulk measurements, single-cell protein analysis permits quantification of protein expression in individual cells. This has shed light on the cell-to-cell variation in heterogeneous biological systems, such as solid tumors, brain tissues, and developing embryos. Herein, a microfluidic method is developed to profile protein expression in individual cells by performing single-cell intracellular protein immunoassay in picoliter paired droplets. The high sensitivity of single-cell protein analysis on a chip is achieved by the confined reaction volume of picoliter droplets, efficient kinetic characteristics of the immunoassay through active mixing, and minimum single-cell protein loss by integrated operations. The abundance of an intracellular prostate specific antigen at the single-cell level is measured, and then the platform is applied to identify cell types and investigate heterogeneity within cell populations. Overall, a paired chip for single-cell immunoassay establishes a foundation for parallel, sensitive, and integrated protein quantification at the single-cell level and will find wide applications in the field of single-cell proteomics.
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Técnicas Analíticas Microfluídicas , Microfluídica , Imunoensaio/métodos , Cinética , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/métodos , Análise de Célula ÚnicaRESUMO
Surface stress and surface energy are two fundamental parameters that determine the surface properties of any material. While it is commonly believed that the surface stress and surface energy of liquids are identical, the relationship between the two parameters in soft polymeric gels remains debatable. In this work, we measured the surface stress and surface energy of soft silicone gels with varying weight ratios of crosslinkers in soft wetting experiments. Above a critical density, k0, the surface stress was found to increase significantly with crosslinking density while the surface energy remained unchanged. In this regime, we can estimate a non-zero surface elastic modulus that also increases with the ratio of crosslinkers. By comparing the surface mechanics of the soft gels with their bulk rheology, the surface properties near the critical density k0 were found to be closely related to the underlying percolation transition of the polymer networks.
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BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.
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Eritropoetina , Hematínicos , Eritropoese , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Humanos , Diálise Renal , Estudos RetrospectivosRESUMO
Growth mixture modeling is a common tool for longitudinal data analysis. One of the key assumptions of traditional growth mixture modeling is that repeated measures within each class are normally distributed. When this normality assumption is violated, traditional growth mixture modeling may provide misleading model estimation results and suffer from nonconvergence. In this article, we propose a robust approach to growth mixture modeling based on conditional medians and use Bayesian methods for model estimation and inferences. A simulation study is conducted to evaluate the performance of this approach. It is found that the new approach has a higher convergence rate and less biased parameter estimation than the traditional growth mixture modeling approach when data are skewed or have outliers. An empirical data analysis is also provided to illustrate how the proposed method can be applied in practice.
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Modelos Estatísticos , Projetos de Pesquisa , Teorema de Bayes , Simulação por Computador , HumanosRESUMO
Nodal-line semimetals (NLSMs), a large family of new topological phases of matter with continuous linear band crossing points in the momentum space, attract considerable attention. Here, we report the direct observation of plasmons originating from topological nodal-line states in a prototypical NLSM ZrSiS by high-resolution electron energy loss spectroscopy. There exist three temperature-independent plasmons with energies ranging from the near- to the mid-infrared frequencies. With first-principles calculations of a slab model, these plasmons can be ascribed to the correlations of electrons in the bulk nodal lines and their projected surface states, dubbed nodal-line plasmons. An anomalous surface plasmon has higher excitation energy than the bulk plasmon due to the larger contribution from the nodal-line projected surface states. This work reveals the novel plasmons related to the unique nodal-line states in a NLSM.
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An interesting Rh(III)-catalyzed dual C-H functionalization/cyclization cascade of azomethine imine with diazophosphonate by a removable directing group for the synthesis of highly fused pyrano[de]isochromene has been achieved. The transformation shows that the desired pyrano[de]isochromenes with two oxygen atoms on its core scaffold could be constructed with good to excellent yields (up to 86%) via a facile one-pot, multiple-step cascade reaction, along with broad generality and versatility.
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BACKGROUND: Event-related potentials (ERP) data are widely used in brain studies that measure brain responses to specific stimuli using electroencephalogram (EEG) with multiple electrodes. Previous ERP data analyses haven't accounted for the structured correlation among observations in ERP data from multiple electrodes, and therefore ignored the electrode-specific information and variation among the electrodes on the scalp. Our objective was to evaluate the impact of early adversity on brain connectivity by identifying risk factors and early-stage biomarkers associated with the ERP responses while properly accounting for structured correlation. METHODS: In this study, we extend a penalized generalized estimating equation (PGEE) method to accommodate structured correlation of ERPs that accounts for electrode-specific data and to enable group selection, such that grouped covariates can be evaluated together for their association with brain development in a birth cohort of urban-dwelling Bangladeshi children. The primary ERP responses of interest in our study are N290 amplitude and the difference in N290 amplitude. RESULTS: The selected early-stage biomarkers associated with the N290 responses are representatives of enteric inflammation (days of diarrhea, MIP1b, retinol binding protein (RBP), Zinc, myeloperoxidase (MPO), calprotectin, and neopterin), systemic inflammation (IL-5, IL-10, ferritin, C Reactive Protein (CRP)), socioeconomic status (household expenditure), maternal health (mother height) and sanitation (water treatment). CONCLUSIONS: Our proposed group penalized GEE estimator with structured correlation matrix can properly model the complex ERP data and simultaneously identify informative biomarkers associated with such brain connectivity. The selected early-stage biomarkers offer a potential explanation for the adversity of neurocognitive development in low-income countries and facilitate early identification of infants at risk, as well as potential pathways for intervention. TRIAL REGISTRATION: The related clinical study was retrospectively registered with https://doi.org/ClinicalTrials.gov , identifier NCT01375647, on June 3, 2011.
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Eletroencefalografia , Potenciais Evocados , Biomarcadores , Encéfalo , Criança , Humanos , Lactente , Projetos de PesquisaRESUMO
BACKGROUND: A large body mass index (BMI) has been considered as a relative contraindication for percutaneous catheter insertion, although this technique has many advantages. Up to now, there are few studies on peritoneal catheter placement and obesity. The aim of this study was to determine whether patients with large BMI can also choose the percutaneous technique for peritoneal dialysis catheter insertion. METHODS: One hundred eighty seven consecutive patients underwent peritoneal catheter insertions in the Chinese PLA General Hospital between January 1, 2015 and December 31, 2016, with 178 eligible cases being included in the analysis. Two groups were created based on the catheter insertion techniques, the percutaneous group (group P) and the surgical group (group S). Subgroups were created according to BMI > 28 or ≤ 28. The outcomes included catheter related complications and catheter survival. RESULTS: Total infectious complication rates were significantly lower in group P than in group S. There were no significant differences in peritonitis rate between group P and group S (1.20% vs. 3.16% with P = 0.71 in early stage, and 4.82% vs. 11.58% with P = 0.11 in late stage). All other measured complications were similar between the two groups. Though the one-year infection-free catheter survival in group P was 7.5% higher than group S, the difference was not significant. The one-year dysfunction-free catheter survival, one-year dysfunction-and-infection-free catheter survival, and overall catheter survival were similar between the two groups. Subgroup analyses showed a superior one-year infection-free catheter survival of percutaneous technique in patients with BMI > 28, which was confirmed by Kaplan-Meier analysis. CONCLUSIONS: Despite the challenges that may be encountered with patients who have a large BMI, the percutaneous technique seems to be a safe and effective approach to placing a peritoneal dialysis catheter.
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Índice de Massa Corporal , Cateterismo/efeitos adversos , Cateteres de Demora/efeitos adversos , Falha de Equipamento , Diálise Peritoneal , Peritonite/etiologia , Adulto , Idoso , Cateterismo/métodos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de TempoRESUMO
Rh(III) catalysts have played increasingly important roles in the activation of C-H bonds to build heterocyclic scaffolds. However, there are few reports on the more challenging synthesis of pharmaceutically important 2 H-isoindoles and fused 2 H-isoindoles. The process reported herein is an effective strategy to produce 2 H-isoindole or fused 2 H-isoindole derivatives via a Rh(III)-catalyzed transformation of α-iminonitriles or α-imino esters with acrylates.