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The dysregulation of long non-coding RNAs (lncRNAs) are involved in regulating tumor progression in multiple manner. However, little is known about whether lncRNA is involved in the translation regulation of proteins. Here, we identified that the suppressor of inflammatory macrophage apoptosis lncRNA (SIMALR) was highly expressed in nasopharyngeal carcinoma (NPC) tissues by analyzing the lncRNA microarray. Clinically, the high expression of SIMALR served as an independent predictor for inferior prognosis in NPC patients. SIMALR functioned as an oncogenic lncRNA that promoted the proliferation and metastasis of NPC cells in vitro and in vivo. Mechanistically, SIMALR served as a critical accelerator of protein synthesis by binding to eEF1A2 (eukaryotic translation elongation factor 1 alpha 2), one of the most crucial regulators in the translation machinery of the eukaryotic cells, and enhancing its endogenous GTPase activity. Furthermore, SIMALR mediated the activation of eEF1A2 phosphorylation to accelerate the translation of ITGB4/ITGA6, ultimately promoting the malignant phenotype of NPC cells. In addition, N-acetyltransferase 10 (NAT10) enhanced the stability of SIMALR and caused its overexpression in NPC through the N4-acetylcytidine (ac4C) modification. In sum, our results illustrate SIMALR functions as an accelerator for protein translation and highlight the oncogenic role of NAT10-SIMALR-eEF1A2-ITGB4/6 axis in NPC.
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Calcination of MgCO3 is an important industrial reaction, but it causes significant and unfavorable CO2 production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO2 release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO3 interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO3 coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO2*â COOH*transâ COOH*cisâ CO*â CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO3. For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO3 laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O-CO â sur-O-HCO â sur-O-HCOH â sur-O-HC â sur-O-CH2 â sur-O-CH3 â sur-O + CH4*).
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Nitrogen loss from rice systems is an important source of agricultural non-point source pollution. Many studies revolve around reducing the rate of nitrogen fertilizer application. However, studies examining the characteristics of nitrogen loss in multiple loss paths ï¼runoff, leaching, and lateral seepageï¼ under different straw and fertilizer managements are lacking. Therefore, a study was carried out based on a rice field planted for more than 20 years with straw continuously returned to the field for more than 5 years in Taihu lake basin. The effects of straw and fertilizer managements on nitrogen loss in different paths during the whole growth period of rice were studied. Moreover, straw and fertilizer managements were evaluated by their production suitability and environmental friendliness based on crop yield, nitrogen use efficiency, and nitrogen loss. The results showed that straw removal from the field increased the response sensitivity of nitrogen accumulation in plant tissue to nitrogen application. The nitrogen loss in the rice season was 9-17 kg·hm-2, accounting for 5%-7% of the nitrogen application rate. Straw removal increased the risk of nitrogen loss when soaking water discharged. Straw returning could decrease the nitrogen loss by more than 15%, though the effect of straw on nitrogen loss via lateral seepage was not clear. Furthermore, the suitable substitution of organic fertilizer ï¼30% in this studyï¼ could respectively reduce the amount of nitrogen loss via runoff, leaching, and lateral seepage by 16%, 26%, and 37% compared with the fertilizer application under the same nitrogen gradient. In conclusion, the implementation of straw returning and fertilizer type optimization measures effectively reduced the nitrogen loss for unit weight of rice production and realized the balance between agricultural production and environmental protection.
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Fertilizantes , Lagos , Nitrógeno , Oryza , Tallos de la Planta , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Nitrógeno/metabolismo , China , Tallos de la Planta/metabolismo , Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/química , Agricultura/métodos , Fragaria/crecimiento & desarrollo , Fragaria/metabolismoRESUMEN
Carbon electrodes are ideal for electrochemistry with molecular catalysts, exhibiting facile charge transfer and good stability. Yet for solar-driven catalysis with semiconductor light absorbers, stable semiconductor/carbon interfaces can be difficult to achieve, and carbon's high optical extinction means it can only be used in ultrathin layers. Here, we demonstrate a plasma-enhanced chemical vapor deposition process that achieves well-controlled deposition of out-of-plane "fuzzy" graphene (FG) on thermally oxidized Si substrates. The resulting Si|FG interfaces possess a silicon oxycarbide (SiOC) interfacial layer, implying covalent bonding between Si and the FG film that is consistent with the mechanical robustness observed from the films. The FG layer is uniform and tunable in thickness and optical transparency by deposition time. Using p-type Si|FG substrates, noncovalent immobilization of cobalt phthalocyanine (CoPc) molecular catalysts was employed for the photoelectrochemical reduction of CO2 in aqueous solution. The Si|FG|CoPc photocathodes exhibited good catalytic activity, yielding a current density of â¼1 mA/cm2, Faradaic efficiency for CO of â¼70% (balance H2), and stable photocurrent for at least 30 h at -1.5 V vs Ag/AgCl under 1-sun illumination. The results suggest that plasma-deposited FG is a robust carbon electrode for molecular catalysts and suitable for further development of aqueous-stable Si photocathodes for CO2 reduction.
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OBJECTIVE: To establish the diagnostic accuracy of RASSF1A (Ras association domain family 1 isoform) methylation using bronchial aspirates as an auxiliary method for diagnosing lung cancer through a systematic review and meta-analysis. METHODS: Studies published prior to October 30, 2022, were retrieved from the Embase, PubMed, Web of Science, and Wan Fang databases using the keywords "lung cancer", "RASSF1A", "methylation", and "bronchial aspirates". A fixed or random effect model was used to calculate the combined sensitivity, specificity, positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), along with the respective 95% confidence intervals (CIs) and the area under the curve (AUC) with Q index. The threshold effect was defined by using the Spearman correlation coefficient, and the Deeks funnel plot was generated to evaluate publication bias. RESULTS: Among the 12 trials that met the inclusion criteria, a total of 2388 participants were involved. The pooled results for the diagnosis of lung cancer were as follows, when compared to the pathological diagnosis: sensitivity of 0.47 (95% CI: 0.45-0.50), specificity of 0.96 (95% CI: 0.95-0.97), positive LR of 12.18 (95% CI: 8.96-16.55), negative LR of 0.56 (95% CI: 0.52-0.61), DOR of 24.05 (95% CI: 17.29-33.47), and AUC of 0.78 (Q index = 0.72), respectively. The sensitivity of the RASSF1A methylation assay was relatively low in a detailed subgroup analysis, fluctuating between 0.39 and 0.90, indicating a limitation in its diagnostic value for lung cancer. The RASSF1A methylation assay, on the other hand, demonstrated excellent specificity, suggesting a high exclusion value. Of note, the diagnostic sensitivity, specificity, DOR, and AUC for small cell lung cancer were 0.90 (0.84-0.94), 0.95 (0.94-0.97), 249.5 (103.94-598.8), and 0.98, respectively, showing that RASSF1A methylation was a promising biomarker for diagnosing small cell lung cancer with both high diagnostic and exclusion value. Furthermore, RASSF1A methylation using bronchial washings and bronchial aspirates showed a high AUC of 0.998 and 0.93, respectively, indicating excellent diagnostic performance. CONCLUSIONS: The methylation of RASSF1A in bronchial aspirates demonstrated a high level of diagnostic accuracy and has the potential to be a valuable supplementary diagnostic method, especially for identifying small cell lung cancer.
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Metilación de ADN , Neoplasias Pulmonares , Proteínas Supresoras de Tumor , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Sensibilidad y Especificidad , Bronquios/metabolismo , Bronquios/patologíaRESUMEN
Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.
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Anthracenylidene is an intriguing structural unit with potential in various fields. The study presents a novel approach to introducing axial chirality into this all-carbon core skeleton through a remotely controlled desymmetrization strategy. A palladium-catalyzed enantioselective Heck arylation of exocyclic double bond of anthracene with two distinct substituents at the C10 position is harnessed to realize such a transformation. The judicious identification of the P-centrally chiral ligand is pivotal to ensure the competitive competence in reactivity and stereocontrol when the heteroatom handle is absent from the anthracenylidene skeleton. Both C10 mono- and disubstituted substrates were compatible for the established catalytic system, and structurally diverse anthracenylidene-based frameworks were forged with good-to-high enantiocontrol. The subsequent derivatization of the obtained products yielded a valuable array of centrally and axially chiral molecules, thus emphasizing the practicality of this chemistry. DFT calculations shed light on the catalytic mechanism and provided insights into the origin of the experimentally observed enantioselectivity for this reaction.
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The key to enhancing water electrolysis efficiency lies in selecting highly efficient catalysts. Currently, high-entropy alloys (HEAs) are utilized in electrocatalysis applications owing to their diverse elemental composition, disordered elemental distribution, and the high solubility of each element, endowing them with excellent catalytic performance. The experiments were conducted using isoatomic FeNiCrMo HEA as a precursor, with a high-activity three-dimensional nanoporous structure rapidly synthesized via electrochemical one-step dealloying in a choline chloride-thiourea (ChCl-TU) deep eutectic solvent (DES). The results indicate that the dealloyed Fe20Co20Ni20Cr20Mo20 HEA mainly consists of two phases: face-centered cubic and σ phases. The imbalance in the distribution of elements in these two phases leads to quite different corrosion speeds with the FCC phase being preferentially corroded. Furthermore, synergistic electron coupling between surface atoms in the three-dimensional nanoporous structure strengthens the behavior of the oxygen evolution reaction (OER). At a current density of 40 mA cm-2, the overpotential after dealloying decreased to 370 mV, demonstrating excellent stability. The technique demonstrated in this work provides a novel approach to improve the catalytic activity of OER.
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Background: The incidence and risk factors for recurrent primary spontaneous pneumothorax (PSP) after video-assisted thoracoscopic surgery (VATS) remain controversial. A systematic review and meta-analysis were conducted to determine the incidence and risk factors for recurrence of PSP after VATS. Methods: A systematic search of PubMed, Web of Science, Embase, and Cochrane Library databases was conducted to identify studies that reported the rate and risk factors for recurrence of PSP after VATS published up to December 2023. The pooled recurrence rate and odds ratio (OR) with 95% confidence interval (CI) were calculated using a random-effects model. In addition, risk factors were similarly included in the meta-analysis, and sources of heterogeneity were explored using meta-regression analysis. Results: A total of 72 studies involving 23,531 patients were included in the meta-analysis of recurrence. The pooled recurrence rate of PSP after VATS was 10% (95% CI: 8-12%). Male sex (OR: 0.61; 95% CI: 0.41-0.92; P=0.02), younger age [mean difference (MD): -2.01; 95% CI: -2.57 to -1.45; P<0.001), lower weight (MD: -1.57; 95% CI: -3.03 to -0.11; P=0.04), lower body mass index (BMI) (MD: -0.73; 95% CI: -1.08 to 0.37; P<0.001), and history of contralateral pneumothorax (OR: 2.46; 95% CI: 1.56-3.87; P<0.001) were associated with recurrent PSP, whereas height, smoking history, affected side, stapling line reinforcement, and pleurodesis were not associated with recurrent PSP after VATS. Conclusions: The recurrence rate of PSP after VATS remains high. Healthcare professionals should focus on factors, including sex, age, weight, BMI, and history of contralateral pneumothorax, that may influence recurrence.
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Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitinâproteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.
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BACKGROUND: Accurately identifying the risk level of drug combinations is of great significance in investigating the mechanisms of combination medication and adverse reactions. Most existing methods can only predict whether there is an interaction between two drugs, but cannot directly determine their accurate risk level. METHODS: In this study, we propose a multi-class drug combination risk prediction model named AERGCN-DDI, utilizing a relational graph convolutional network with a multi-head attention mechanism. Drug-drug interaction events with varying risk levels are modeled as a heterogeneous information graph. Attribute features of drug nodes and links are learned based on compound chemical structure information. Finally, the AERGCN-DDI model is proposed to predict drug combination risk level based on heterogenous graph neural network and multi-head attention modules. RESULTS: To evaluate the effectiveness of the proposed method, five-fold cross-validation and ablation study were conducted. Furthermore, we compared its predictive performance with baseline models and other state-of-the-art methods on two benchmark datasets. Empirical studies demonstrated the superior performances of AERGCN-DDI. CONCLUSIONS: AERGCN-DDI emerges as a valuable tool for predicting the risk levels of drug combinations, thereby aiding in clinical medication decision-making, mitigating severe drug side effects, and enhancing patient clinical prognosis.
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Redes Neurales de la Computación , Humanos , Interacciones Farmacológicas , Combinación de Medicamentos , Medición de Riesgo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Reproducibilidad de los Resultados , Gráficos por ComputadorRESUMEN
Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.
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Docetaxel , Resistencia a Antineoplásicos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Piroptosis , Ubiquitina-Proteína Ligasas , Ubiquitinación , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Docetaxel/farmacología , Docetaxel/uso terapéutico , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Dinaminas/metabolismo , Dinaminas/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Gasderminas , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas Fosfatasas/genética , Fosforilación/efectos de los fármacos , Piroptosis/efectos de los fármacos , Piroptosis/genética , Especies Reactivas de Oxígeno/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
An ammonium ylide-based relay annulation was disclosed, which uses DABCO as the catalyst and oxindole-derived α,ß-unsaturated ketimines and γ-bromo-crotonates as the starting materials. This method enables the rapid assembly of a series of structurally novel spiro-polycyclic oxindoles containing a bicyclo[4.1.0]heptane moiety through simultaneous generation of three new bonds and two rings in one step under mild reaction conditions.
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Twelve compounds, comprising of four new ones, 6ß,7α-limondiol (1) and ethyl 19-hydroxyisoobacunoate diosphenol (2), N-benzoyl 3-prenyltyramine (9) and 9-O-methyl integrifoliodiol (12), were isolated from the twigs with leaves of Tetradium trichotomum. The structures were elucidated by analysis of MS, NMR, and single-crystal X-ray diffraction. Compounds 1, 6, 8, 9 and 12 exhibited immunosuppressive activities in vitro against the proliferation of ConA-induced T lymphocytes and LPS-induced B cells.
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Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15â¯% of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.
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ARN Helicasas DEAD-box , Desoxicitidina , Gemcitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , ARN Largo no Codificante , Animales , Humanos , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , ARN Helicasas DEAD-box/metabolismo , ARN Helicasas DEAD-box/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/metabolismo , Proteínas de Neoplasias , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ubiquitinación/efectos de los fármacosRESUMEN
Immunosuppression tumor microenvironment (TME) seriously impedes anti-tumor immune response, resulting in poor immunotherapy effect of cancer. This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells, resulting in high CKb11 secretion from tumor cells, successfully activating immune cells and increasing cytokine secretion to reshape the TME, and ultimately delaying tumor progression. The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME. It can cause high expression of IFN-γ, which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells. Therefore, combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense, leading to a collaborative anti-tumor outcome. Thus, utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites, thereby reshaping immunosuppressive TME for cancer treatment, has great potential as an immunogene therapy in clinical applications.
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The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,ß-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (ß-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.
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In the original publication [...].
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Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease characterized by dryness of the eyes and mouth. The histological feature is mononuclear cell infiltration in exocrine glands, primarily salivary and lachrymal glands. As the disease progresses, some other tissues and organs may be involved and extraglandular manifestations ensue. The major current treatments are palliative and empirical, and in most cases the outcomes are not satisfactory. Emerging data indicate a critical role of lymphocytes in its development and progression. While pioneering work targeting B cells has demonstrated some encouraging results, more trials are warranted to validate the safety and efficacy. In addition, modulation of T cell function with abatacept ameliorates the severity of pSS. Furthermore, clinical trials to inhibit important cytokines involved in its formation have been carried out. In this article, we summarize and compare current biological therapies in order to find new and effective treatments for pSS.