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PURPOSE OF REVIEW: New-onset atrial fibrillation (NOAF) is the most prevalent arrhythmia among critically ill patients, correlating with heightened morbidity and mortality rates. Current evidence for managing NOAF in this patient population is limited. RECENT FINDINGS: Numerous meta-analyses have been conducted to assess the efficacy of atrial fibrillation treatments in acute settings, including rate or rhythm control strategies, anticoagulation, and intensive care interventions. The employment of ß-blockers for rate control appears to confer greater benefits in critically ill patients. However, the advantage of anticoagulation remains ambiguous because of bleeding risks, which is partly attributed to the scarcity of evidence in the complex context of critical illness. Approximately one-third of patients with transient atrial fibrillation face recurrence within a year. Therefore, vigilant posthospitalization follow-up and monitoring should be considered for high-risk patients to detect atrial fibrillation recurrence. Long-term anticoagulation strategies should be tailored to individual patient profiles, weighing the risks of thromboembolism. SUMMARY: Factors predicting atrial fibrillation recurrence include age, the burden of atrial fibrillation, and atrial size. There are significant knowledge gaps concerning NOAF in critically ill patients, highlighting the need for further research, particularly randomized clinical trials.
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BACKGROUND: The aim of this study is to explore surgical treatment techniques and clinical attributes associated with calvarial metastases, while providing a comprehensive review of the treatment experiences relevant to this particular type of tumor. METHODS: This study involves a retrospective analysis of clinical data from 12 patients diagnosed with calvarial metastatic tumors who underwent surgical intervention. Among these patients, 5 had a history of previous malignant tumor resections, while 7 presented with calvarial metastatic tumors as their initial symptom. In all cases, the surgical approach consisted of calvarial tumor resection followed by titanium mesh repair. Following the surgical intervention, all patients underwent a comprehensive course of treatment, encompassing both local radiotherapy and systemic chemotherapy. RESULTS: In 1 instance, a patient presented with multiple tumors located in the central area of the frontal bone and the right temporal bone. The larger tumor situated in the middle of the frontal bone was surgically excised, while the tumor in the right temporal bone was treated using radiotherapy. In 2 cases characterized by multiple metastases within the skull, a comprehensive excision of all tumors was accomplished in a single surgical procedure. In the remaining cases featuring a solitary metastatic growth, the respective tumors were surgically removed. There were 10 instances of dura mater invasion and 3 cases involving the invasion of brain tissue. Pathologic examinations revealed 1 case of metastatic lung adenocarcinoma, 1 case of metastatic paraganglioma, 1 case of metastatic hepatocellular carcinoma, 2 cases of metastatic thyroid carcinoma, and 7 cases of metastatic clear cell renal cell carcinoma. Throughout the follow-up period, spanning from 14 to 90 months, various outcomes were noted. These included three occurrences of in situ recurrence. In addition, 1 patient required 3 distinct surgical interventions, while 2 other patients underwent 2 separate surgical procedures each. Notably, 1 of these cases involved the exposure of the titanium mesh on the scalp, necessitating the removal of the titanium mesh. Regrettably, there have been 9 recorded fatalities among the patients, while 3 individuals have survived. CONCLUSION: Solitary metastasis of calvarium region is rare, and surgical resection is effective. However, it is necessary to extend the resection range and combine with local radiotherapy to avoid local recurrence. Surgical intervention can significantly enhance the quality of life for affected patients. The prognosis of the patients mainly depends on the treatment of the primary disease and the situation of important organ dissemination and treatment.
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Primula medogensis W.B Ju, B. Xu & X.F. Gao 2023, a new species categorized under P. sect. Cordifoliae, was officially described in 2023. Given its recent classification, the genetic resources for this species are currently very limited. Here, we sequenced and assembled the first complete chloroplast genome of P. medogensis using Illumina sequencing technology. The complete chloroplast genome of P. medogensis is 151,486 bp in length, exhibiting a typical quadripartite structure. It consists of a large single-copy region (LSC; 83,407 bp) and a small single-copy region (SSC;17675 bp), separated by a pair of inverted repeat regions (IRs; 25202 bp). A total of 131 genes were annotated, including 86 protein-coding, 37 tRNA, and eight rRNA genes. The overall GC content was 37.1%. Phylogenetic analysis of 59 Primula species revealed a close relationship between P. medogensis and P. calliantha subsp. bryophila.
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Abnormal levels of zinc ions within endo-lysosomes have been implicated in the progression of Alzheimer's disease (AD), yet the detection of low-concentration zinc ions at the organelle level remains challenging. Here we report the design of an endo-lysosome-targeted fluorescent reporter, Znluorly, for imaging endogenous zinc ions. Znluorly is constructed from an amphiphilic DNA framework (DNF) with programmable size and shape, which can encapsulate zinc-responsive fluorophores within its hydrophobic nanocavity. We find that the tetrahedral DNFs of 20 bp in the edge length are effectively located within endo-lysosomes, which can detect zinc ions with a detection limit of â¼31.9 nM (a sensitivity that is â¼2.5 times that of the free fluorophore). Given the organelle-targeting ability and high zinc sensitivity of Znluorly, we employ it to detect endogenous endo-lysosomal zinc ions in neuron cells. We monitor the dynamics of zinc levels in AD model cells and zebrafish, corroborating the positive correlation between zinc levels and AD hallmarks including Aß aggregates and learning/memory impairments. Our study provides a generalizable strategy for organelle-specific theranostic applications.
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Angiogenesis, the process of formation of new capillaries from existing blood vessels, is required for multiple physiological and pathological processes. Complement factor H (CFH) is a plasma protein that inhibits the alternative pathway of the complement system. Loss of CFH enhances the alternative pathway and increases complement activation fragments with pro-angiogenic capacity, including complement 3a, complement 5a, and membrane attack complex. CFH protein contains binding sites for C-reactive protein, malondialdehyde, and endothelial heparan sulfates. Dysfunction of CFH prevents its interaction with these molecules and initiates pro-angiogenic events. Mutations in the CFH gene have been found in patients with age-related macular degeneration characterized by choroidal neovascularization. The Cfh-deficient mice show an increase in angiogenesis, which is decreased by administration of recombinant CFH protein. In this review, we summarize the molecular mechanisms of the anti-angiogenic effects of CFH and the regulatory mechanisms of CFH expression. The therapeutic potential of recombinant CFH protein in angiogenesis-related diseases has also been discussed.
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Type 2 diabetes (T2D) genome-wide association studies (GWASs) often overlook rare variants as a result of previous imputation panels' limitations and scarce whole-genome sequencing (WGS) data. We used TOPMed imputation and WGS to conduct the largest T2D GWAS meta-analysis involving 51,256 cases of T2D and 370,487 controls, targeting variants with a minor allele frequency as low as 5 × 10-5. We identified 12 new variants, including a rare African/African American-enriched enhancer variant near the LEP gene (rs147287548), associated with fourfold increased T2D risk. We also identified a rare missense variant in HNF4A (p.Arg114Trp), associated with eightfold increased T2D risk, previously reported in maturity-onset diabetes of the young with reduced penetrance, but observed here in a T2D GWAS. We further leveraged these data to analyze 1,634 ClinVar variants in 22 genes related to monogenic diabetes, identifying two additional rare variants in HNF1A and GCK associated with fivefold and eightfold increased T2D risk, respectively, the effects of which were modified by the individual's polygenic risk score. For 21% of the variants with conflicting interpretations or uncertain significance in ClinVar, we provided support of being benign based on their lack of association with T2D. Our work provides a framework for using rare variant GWASs to identify large-effect variants and assess variant pathogenicity in monogenic diabetes genes.
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Background: Primary hepatic neuroendocrine tumors (PHNETs) are an utterly rare entity. The diagnosis of PHNETs could legitimize when an extrahepatic primary NET must always be excluded. PHNETs can achieve a high survival rate after complete surgical resection, however, most patients still have an 18% risk of recurrence within 5 years after surgery. In our case, the recurrence occurred 8 years after the first hepatectomy, which is relatively rare in the current literature. Therefore, rigorous postoperative follow-up is necessary for early detection and timely treatment of recurrent PHNETs. Case information: We report a case of PHNET in a 24-year-old previously healthy female patient who relapsed 8 years after hepatectomy. This case focuses on the importance of diagnosis of primary and recurrent PHNETS in young patients, rare pathological types, and post-operative follow-up. Conclusion: This case report detailed the rare pathological morphology and characteristic immunohistochemical markers in our case for PHNETS, which enhanced the new understanding of the diagnosis of this entity. In addition, we also highlighted the variable duration of recurrence after treatment of PHNETs. The 8-year recurrent period in our case suggests the importance of regular examination in patients with PHNETs by following the doctor's instructions.
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OBJECTIVE: Malignant transformation of craniofacial fibrous dysplasia (FD) is not common and its clinicopathological as well as molecular characteristics remain largely unknown with limited literature reports. STUDY DESIGN: Patients diagnosed with FD including McCune-Albright syndrome (MAS), polyostotic fibrous dysplasia (PFD), and monostotic fibrous dysplasia (MFD), accompanied by malignant transformation at our institution over the past 18 years (2005-2023) were retrospectively screened and analyzed to investigate the epidemiology and clinicopathological features of these tumors. RESULTS: Three hundred and five patients were diagnosed as FD in our hospital from 2005 to 2023, with 176 females (57.7 %) and 129 males (42.3 %). The average age at diagnosis was 28.35 years, ranging from 7 to 70 years. A total number of 15 (4. 9 %) cases of FD with malignant transformation were selected. Among these 15 patients, the age of the initial diagnosis of FD ranged from 6 to 54 years (mean age 28.87 ± 16.77), and the ages when malignant transformation occurred ranged from 18 to 57 years (mean age 38.53 ± 13.05). Among 15 patients, 12 patients were female (80 %) and 3 were male (20 %). Fifteen cases included MSA in 2 patients, PFD in 4 patients, and MFD in 9 patients. Of the anatomical sites in craniofacial bones, the most common site of the lesion was the maxilla, followed by the mandible. Malignant neoplasm arising in FD were osteosarcoma (12/15), chondrosarcoma (1/15) and high-grade sarcoma of uncertain differentiation (2/15). The 3- and 5-year overall survival rate was 33.3 % (5/15) and 20 % (3/15) respectively. In secondary osteosarcoma from FD, MDM2 and CDK4 positivity were 33.3 % and 41.7 % respectively, and only one case was MDM2-amplified and CDK4-amplified. CONCLUSION: Malignant transformation in fibrous dysplasia was an exceedingly rare event and with a female predominance. The overall survival rate was poor. Osteosarcoma was the most common malignant neoplasm arising in FD. MDM2 and CDK4 expression may aid in the diagnosis of secondary osteosarcoma in FD.
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OBJECTIVE: This study aimed to develop and internally validate a prognostic nomogram for predicting nodal recurrence-free survival (NRFS) in patients with early-stage oral squamous cell carcinoma (OSCC) with clinically negative neck lymph nodes. MATERIALS AND METHODS: The management of early-stage oral cancer patients with clinically negative neck lymph nodes (cN0) remains controversial, especially concerning the need for elective neck dissection. Data from a single institution spanning 2010 to 2020 were utilized to develop and evaluate the nomogram. The nomogram was constructed using multivariable Cox regression and LASSO regression analyses to identify independent risk factors for lymph node metastasis. Internal validation was performed using bootstrap resampling to assess the nomogram's predictive accuracy. RESULTS: A total of 930 cN0 patients with T1 and T2 stage OSCC were randomly divided into training and validation cohorts (8:2 ratio). Independent risk factors for lymph node metastasis included tumor pathological grade (well: reference, moderate/poor: OR 1.69), cT (cT1: reference, cT2: OR 2.01), history of drinking (never: reference, current/former: OR 1.72), and depth of invasion (0 mm < DOI ≤ 5 mm: reference, 5 mm < DOI ≤ 10 mm: OR 1.31). The nomogram, incorporating these variables, demonstrated good predictive accuracy with a C-index of 0.67 (95% CI: 0.58-0.76) in the validation set. In both training and validation groups, the nomogram effectively stratified patients into low-risk and high-risk groups for occult cervical nodal metastases (p < 0.05). CONCLUSIONS: The nomogram enables risk stratification and improved identification of occult cervical nodal metastases in clinically node-negative OSCC patients by incorporating tumor-specific and patient-specific risk factors.
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Background: This retrospective cohort study and meta-analysis aims to explore the association between microvascular invasion (MVI) and clinicopathologiccal features, as well as survival outcomes of patients with renal cell carcinoma (RCC). Material and methods: The retrospective cohort study included 30 RCC patients with positive MVI and another 75 patients with negative MVI as controls. Clinicopathological features and follow-up data were compiled. The meta-analysis conducted searches on PubMed, Cochrane Library, Web of Science, Embase, and WanFang Data from the beginning to 30 September 2023, for comparative studies relevant to MVI patients. The Newcastle-Ottawa Scale and Egger Test were used to assess the risk of biases and certainty of evidence in the included studies. Results: The cohort study showed that MVI was associated with advanced primary tumor stage, high pathological grades, high tumor size, high clinical symptoms and lymph node invasion (P <0.05). Kaplan-Meier analyses demonstrated MVI was associated with worse CSS rates when compared to MVI negative group (P <0.05). However, in the multivariate analysis it was not presented as an independent predictor of cancer survival mortality (P >0.05). The meta-analysis part included 11 cohort studies. The results confirmed that patients with MVI positive had worse 12 and 60 mo CSS rates (HR12mo = 0.86, 95%CI 0.80-0.92; HR60mo = 0.63, 95% CI 0.55-0.72; P < 0.00001). Moreover, the meta-analysis also confirmed that MVI group was associated with higher rate of advanced tumor stage, pathological grades, tumor size diameter, higher rate of clinical symptoms and lymph node invasion (P <0.05). Conclusions: The presence of MVI in renal cell carcinoma patients is linked to poorer survival outcomes and worse clinicopathological features. In spite of this, it does not seem to be an independent predictor for cancer survival mortality in renal cell carcinoma. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023470640, identifier CRD42023470640.
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The nitrogen cycle is of great importance for material circulation and energy flow in lake ecosystems. It is driven by microorganisms in lake sediments and can contribute to balancing lake ecosystems. In this study, physical and chemical properties of the sediments sampled from Hongfeng Lake in Guizhou Province were assayed and analyzed using metagenomics to reveal relevant microorganisms, functional genes, metabolic pathways, and their relationships throughout nitrogen metabolism. The results showed that bacteria were dominant, and the top three relative abundant genera were Thiobacillus ï¼16.64%ï¼, Rubrivivaxï¼9.43%ï¼, and Nitrospira ï¼7.09%ï¼. Only six pathways, including nitrogen fixation, nitrification, denitrification, assimilatory nitrate reduction, dissimilatory nitrate reduction, and complete nitrification, were detected in total, of which denitrification and dissimilatory nitrate reduction were the primary processes, but anaerobic ammonia oxidation was not detected. Bacteria and archaea participated in these six pathways, while eukaryotes only functioned in dissimilatory nitrate reduction, denitrification, and complete nitrification. Ammonia nitrogen, nitrate nitrogen, and total phosphorus, as main environmental factors affecting the distribution of functional genes for nitrogen metabolism, differentiated with each other in their respective real-world conditions. A positive correlation ï¼95.04%ï¼ was observed between the functional genes and microorganisms, and narG, narZ, and nxrA possessed the highest abundance and the highest host genes. On this basis, these findings are expected to further elucidate the nitrogen cycle of typical karst lakes in Guizhou Province.
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Archaea , Bactérias , Sedimentos Geológicos , Lagos , Nitrogênio , Lagos/microbiologia , Sedimentos Geológicos/microbiologia , China , Nitrogênio/metabolismo , Bactérias/metabolismo , Bactérias/classificação , Bactérias/genética , Archaea/genética , Archaea/metabolismo , Archaea/classificação , Redes e Vias Metabólicas , Desnitrificação , Nitrificação , Thiobacillus/metabolismo , Thiobacillus/genética , Ciclo do Nitrogênio , Fixação de NitrogênioRESUMO
To investigate the mechanical properties and microstructure evolution of P92 steel during long-term service, the operated P92 main steam pipes from the first ultra-supercritical units in China were sectioned into samples representing various service durations and stresses (0# (as-received state, 1# (82,000 h, 67.3 MPa), 2# (85,000 h, 78.0 MPa), and 3# (100,000 h, 80.3 MPa)). Thereafter, a comprehensive assessment of their mechanical properties, including tensile strength, impact, hardness, and creep resistance, as well as a detailed microstructure analysis, was carried out. The effect of stress on the aging of material properties during operation is discussed. The results show that the circumferential stress caused by the increase in the internal steam pressure can significantly promote the creep life consumption of P92 steel, resulting in the degradation of mechanical properties and the expedited aging of the microstructure. The Rp0.2 and Rm of the P92 main steam pipe at room temperature and 605 °C decreased with the service time increase, reflecting the influence of stress in operation, which is expected to be used for the residual life evaluation of P92 steel. The relationship between the impact absorption energy (FATT50), Brinell hardness, and the operating time of P92 operating pipes is non-monotonic, indicating that these parameters are not sensitive indicators of material aging due to stress. The evaluation of performance degradation in P92 operating pipes due to stress-induced aging is not reliably discernible through optical metallography alone. To achieve a thorough assessment, the use of transmission electron microscopy (TEM) is essential.
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Synthesizing viral genomes plays an important role in fundamental virology research and in the development of vaccines and antiviral drugs. Herpes simplex virus type 1 (HSV-1) is a large DNA virus widely used in oncolytic virotherapy. Although de novo synthesis of the HSV-1 genome has been previously reported, the synthetic procedure is still far from efficient, and the synthesized genome contains a vector sequence that may affect its replication and application. In the present study, we developed an efficient vector-free strategy for synthesis and rescue of synthetic HSV-1. In contrast to the conventional method of transfecting mammalian cells with a completely synthesized genome containing a vector, overlapping HSV-1 fragments synthesized by transformation-associated recombination (TAR) in yeast were linearized and cotransfected into mammalian cells to rescue the synthetic virus. Using this strategy, a synthetic virus, F-Syn, comprising the complete genome of the HSV-1 F strain, was generated. The growth curve and electron microscopy of F-Syn confirmed that its replication dynamics and morphogenesis are similar to those of the parental virus. In addition, by combining TAR with in vitro CRISPR/Cas9 editing, an oncolytic virus, F-Syn-O, with deleted viral genes ICP6, ICP34.5, and ICP47 was generated. The antitumor effect of F-Syn-O was tested in vitro. F-Syn-O established a successful infection and induced dose-dependent cytotoxic effects in various human tumor cell lines. These strategies will facilitate convenient and systemic manipulation of HSV-1 genomes and could be further applied to the design and construction of oncolytic herpesviruses.
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Genoma Viral , Herpesvirus Humano 1 , Terapia Viral Oncolítica , Vírus Oncolíticos , Herpesvirus Humano 1/genética , Vírus Oncolíticos/genética , Humanos , Terapia Viral Oncolítica/métodos , Replicação Viral/genética , Sistemas CRISPR-Cas , Animais , Chlorocebus aethiops , Células Vero , Vetores Genéticos/genéticaRESUMO
Apoptosis associated speck like protein containing a card (ASC), the key adaptor protein of the assembly and activation of canonical inflammasomes, has been found to play a significant role in neuroinflammation after spinal cord injury (SCI). The previous studies indicated that widely block or knockout ASC can ameliorate SCI. However, ASC is ubiquitously expressed in infiltrated macrophages and local microglia, so further exploration is needed on which type of cell playing the key role. In this study, using the LysMcre;Ascflox/flox mice with macrophage-specifc ASC conditional knockout (CKO) and contusive SCI model, we focus on evaluating the specific role of ASC in lysozyme 2 (LysM)+ myeloid cells (mainly infiltrated macrophages) in this pathology. The results revealed that macrophage-specifc Asc CKO exhibited the follow effects: (1) A significant reduction in the numbers of infiltrated macrophages in the all phases of SCI, and activated microglia in the acute and subacute phases. (2) A significant reduction in ASC, caspase-1, interleukin (IL)-1ß, and IL-18 compared to control mice. (3) In the acute and subacute phases of SCI, M1 subset differentiation was inhibited, and M2 differentiation was increased. (4) Histology and hindlimb motor recoveries were improved. In conclusion, this study elucidates that macrophage-specific ASC CKO can improve nerve function recovery after SCI by regulating M1/M2 polarization through inhibiting ASC-dependent inflammasome signaling axis. This indicates that ASC in peripheral infiltrated macrophages may play an important role in SCI pathology, at least in mice, could be a potential target for treatment.
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Proteínas Adaptadoras de Sinalização CARD , Inflamassomos , Macrófagos , Transdução de Sinais , Traumatismos da Medula Espinal , Animais , Camundongos , Proteínas Adaptadoras de Sinalização CARD/genética , Deleção de Genes , Inflamassomos/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Muramidase/metabolismo , Transdução de Sinais/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/genéticaRESUMO
BACKGROUND: In Sjögren's syndrome (SS)-an autoimmune disease characterized by dry mouth and eyes-salivary gland epithelial cells (SGECs) undergo ferroptosis, which disrupts their integrity and impairs saliva secretion. Apigenin, a phytoestrogen, is known to activate estrogen signalling and alleviate xerostomia in ovariectomized mice; however, its effect on SGEC survival and function in SS remains unclear. We hypothesized that apigenin alleviates SS symptoms and progression by inhibiting ferroptosis in SGECs and aimed to elucidate the underlying mechanism. METHODS: Apigenin (50 mg/kg) was orally gavaged to non-obese diabetic (NOD)/LtJ female mice (SS model); changes in SS functional indicators were analyzed using mRNA sequencing and bioinformatic analyses of submandibular glands. Interferon-gamma (IFN-γ)-stimulated SGECs were used to model SS in vitro; SGEC activity and aquaporin 5 (AQP5) expression were analyzed. Immunohistochemical staining, transmission electron microscopy, RT-qPCR, western blotting and other methods were used to verify the mechanisms. RESULTS: Apigenin significantly increased salivary secretion and AQP5 expression while inhibiting ferroptosis and immune infiltration in NOD mouse submandibular glands. The oxidative stress gene ATF3 was upregulated and GPX4 was downregulated in NOD mice compared to that in control group (ICR mice); however, apigenin reversed this effect. IFN-γ treatment downregulated AQP5, SLC7A11, and GPX4 expression while promoting ATF3 expression and ferroptosis, which was mitigated by apigenin. ATF3 knockdown increased SLC7A11 and GPX4 expression, inhibiting SS and ferroptosis. Furthermore, apigenin inhibited ferroptosis in SGECs through ESR1 binding to ATF3. CONCLUSION: Apigenin alleviates SS by regulating SGEC ferroptosis via the ERα-regulated ATF3/SLC7A11 axis, highlighting its therapeutic potential in SS.
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Objective: The aim of this study was to elucidate the effects of fermented hawthorn extract on high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats, and explore the possible underlying mechanisms. Methods: A total of 42 male adult Sprague-Dawley rats were randomly divided into five groups: normal control group (given a normal feed diet and distilled water by gavage), NAFLD model (given HFD and distilled water by gavage), low-, medium-, and high-dose fermented hawthorn extract treatment groups (given HFD and different doses of fermented hawthorn extract by gavage). After 12 weeks of gavage administration, changes in body weight, liver/body weight ratio, serum liver enzymes, as well as triglyceride (TG) content and oxidative stress levels in rat liver tissueswere detected. Histological evaluation was performed to observe the degree of fat accumulation (steatosis). qRT-PCR and western blotting were performed to detect the mRNA and protein expression of cytochrome P4502E1 (CYP2E1, a key enzyme associated with lipid peroxidation), and lipogenic factors (sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS)) in rat liver tissues. Results: Fermented hawthorn extract significantly reduced the body weight, decreased the levels of liver enzymes, improved hepatic steatosis, and exhibited obvious antioxidant effects. Fermented hawthorn extract also significantly down-regulated the mRNA and protein expression levels of CYP2E1, SREBP-1c and FAS. Conclusion: Our findings suggested that fermented hawthorn extract can markedly reduce body weight, ameliorate HFD-induced NAFLD in rats, and exhibits significant antioxidant effects. Its underlying mechanism may depend on the inhibition of CYP2E1, SREBP-1c, and FAS expression.
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Enantioselective transition metal-catalyzed C-H alkylation emerges as one of the most atom- and step-economical routes to chiral quaternary carbons, while big challenges still remain with acyl C-H alkylations. Herein, we use a Ni-Al bimetallic catalyst to facilitate a highly regioselective and highly enantioselective C-H alkylation of formamides with alkenes, constructing various oxindoles bearing a chiral quaternary carbon in up to 94% yield and up to 95% ee.