U-shaped association between low-density lipoprotein cholesterol levels and risk of futile reperfusion mediated by stroke-associated pneumonia in acute ischemic stroke after endovascular thrombectomy.

OBJECTIVE: Futile reperfusion (FR) is becoming a major challenge in the treatment of patients with acute ischaemic stroke (AIS) undergoing endovascular thrombectomy. This study aims to determine the dose-response relationship between low-density lipoprotein cholesterol (LDL-C) levels and the risk of FR in patients with AIS undergoing endovascular thrombectomy and to investigate potential mediators. METHODS: A total of 614 patients with AIS undergoing endovascular thrombectomy were enrolled and divided into five groups according to quintiles of LDL-C levels: Q1(≤2.27 mmol/l), Q2 (2.27-2.5 mmol/l), Q3 (2.5-2.59 mmol/l), Q4 (2.59-2.97 mmol/l) and Q5 (≥2.97 mmol/l). Associations between LDL-C levels and the risk of FR and stroke-associated pneumonia (SAP) were estimated using multivariate logistic regression models. Restricted cubic spline curves were used to describe the dose-response relationship between LDL-C levels and the risk of FR and SAP. Mediation effect analysis was performed in R software with 100 bootstrap samples. RESULTS: After adjustment for confounders, both low and high LDL-C levels were significantly associated with a higher risk of FR compared with the reference group (Q3). We observed a U-shaped association between LDL-C levels and the risk of FR (P for nonlinear =0.012). Mediation analysis showed that the association between LDL-C levels and the risk of FR was 29.7 % (95 % CI: 2.96 %-75.0 %, P=0.02) mediated by SAP. CONCLUSIONS: We found a U-shaped association between LDL-C levels and the risk of FR that was mediated by SAP. Clinicians should note that in AIS patients undergoing endovascular thrombectomy, lower LDL-C levels are not always better.

Alterations in the gut mycobiome with coronary artery disease severity.

BACKGROUND: Coronary artery disease (CAD) is a prevalent cardiovascular condition, and numerous studies have linked gut bacterial imbalance to CAD. However, the relationship of gut fungi, another essential component of the intestinal microbiota, with CAD remains poorly understood. METHODS: In this cross-sectional study, we analyzed fecal samples from 132 participants, split into 31 healthy controls and 101 CAD patients, further categorized into stable CAD (38), unstable angina (41), and acute myocardial infarction (22) groups. We conducted internal transcribed spacer 1 (ITS1) and 16S sequencing to examine gut fungal and bacterial communities. FINDINGS: Based on ITS1 analyses, Ascomycota and Basidiomycota were the dominant fungal phyla in all the groups. The α diversity of gut mycobiome remained unaltered among the control group and CAD subgroups; however, the structure and composition of the mycobiota differed significantly with the progression of CAD. The abundances of 15 taxa gradually changed with the occurrence and progression of the disease and were significantly correlated with major CAD risk factor indicators. The mycobiome changes were closely linked to gut microbiome dysbiosis in patients with CAD. Furthermore, disease classifiers based on gut fungi effectively identified subgroups with different degrees of CAD. Finally, the FUNGuild analysis further categorized these fungi into distinct ecological guilds. INTERPRETATION: In conclusion, the structure and composition of the gut fungal community differed from healthy controls to various subtypes of CAD, revealing key fungi taxa alterations linked to the onset and progression of CAD. Our study highlights the potential role of gut fungi in CAD and may facilitate the development of novel biomarkers and therapeutic targets for CAD. FUNDING: This work was supported by the grants from the National Natural Science Foundation of China (No. 82170302, 92168117, 82370432), National clinical key specialty construction project- Cardiovascular Surgery, the Reform and Development Program of Beijing Institute of Respiratory Medicine (No. Ggyfz202417, Ggyfz202308), the Beijing Natural Science Foundation (No. 7222068); and the Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (No. CYFH202209).

A CT texture-based nomogram for predicting futile reperfusion in patients with intraparenchymal hyperdensity after endovascular thrombectomy for acute anterior circulation large vessel occlusion.

Background: Post-thrombectomy intraparenchymal hyperdensity (PTIH) in patients with acute anterior circulation large vessel occlusion is a common CT sign associated with a higher incidence of futile reperfusion (FR). We aimed to develop a nomogram to predict FR specifically in patients with PTIH. Methods: We retrospectively collected information on patients with acute ischemic stroke who underwent endovascular thrombectomy (EVT) at two stroke centers. A total of 398 patients with PTIH were included to develop and validate the nomogram, including 214 patients in the development cohort, 92 patients in the internal validation cohort and 92 patients in the external validation cohort. The nomogram was developed according to the independent predictors obtained from multivariate logistic regression analysis, including clinical factors and CT texture features extracted from hyperdense areas on CT images within half an hour after EVT. The performance of the nomogram was evaluated with integrated discrimination improvement (IDI), category-free net reclassification improvement (NRI), the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analyses for discrimination, calibration ability, and clinical net benefits, respectively. Results: Our nomogram was constructed based on three clinical factors (age, NIHSS score and ASPECT score) and two CT texture features (entropy and kurtosis), with AUC-ROC of 0.900, 0.897, and 0.870 in the development, internal validation, and external validation cohorts, respectively. NRI and IDI further validated the superior predictive ability of the nomogram compared to the clinical model. The calibration plot revealed good consistency between the predicted and the actual outcome. The decision curve indicated good positive net benefit and clinical validity of the nomogram. Conclusion: The nomogram enables clinicians to accurately predict FR specifically in patients with PTIH within half an hour after EVT and helps to formulate more appropriate treatment plans in the early post-EVT period.

Regio- and Diastereoselective Annulation of α,ß-Unsaturated Aldimines with Alkenes via Allylic C(sp3)-H Activation by Rare-Earth Catalysts.

The [3 + 2] or [4 + 2] annulation of α,ß-unsaturated aldimines with alkenes via ß'- or γ-allylic C(sp3)-H activation is, in principle, an atom-efficient route for the synthesis of five- or six-membered-ring cycloalkylamines, which are important structural motifs in numerous natural products, bioactive molecules, and pharmaceuticals. However, such a transformation has remained undeveloped to date probably due to the lack of suitable catalysts. We report herein for the first time the regio- and diastereoselective [3 + 2] and [4 + 2] annulations of α,ß-unsaturated imines with alkenes via allylic C(sp3)-H activation by half-sandwich rare-earth catalysts having different metal ion sizes. The reaction of α-methyl-substituted α,ß-unsaturated aldimines with alkenes by a C5Me4SiMe3-ligated scandium catalyst took place in a trans-diastereoselective [3 + 2] annulation fashion via C(sp3)-H activation at the α-methyl group (ß'-position), exclusively affording alkylidene-functionalized cyclopentylamines with excellent trans-diastereoselectivity. In contrast, the reaction of ß-methyl-substituted α,ß-unsaturated aldimines with alkenes by a C5Me5-ligated cerium catalyst proceeded in a cis-diastereoselective [4 + 2] annulation fashion via γ-allylic C(sp3)-H activation, selectively yielding multisubstituted 2-cyclohexenylamines with excellent cis-diastereoselectivity. The mechanistic details of these transformations have been elucidated by deuterium-labeling experiments, kinetic isotope effect studies, and the isolation and transformations of key reaction intermediates. This work offers an efficient and selective protocol for the synthesis of a new family of cycloalkylamine derivatives, featuring 100% atom efficiency, high regio- and diastereoselectivity, broad substrate scope, and an unprecedented reaction mechanism.

CT texture-based nomogram in ischaemic stroke to differentiate intracerebral hemorrhage from contrast extravasation after thrombectomy.

INTRODUCTION: Post-thrombectomy intraparenchymal hyperdense (PTIH) in patients with acute ischaemic stroke (AIS) is a common CT sign, making it difficult for physicians to distinguish intracerebral hemorrhage in the early post-thrombectomy period. The aim of this study is to develop an effective model to differentiate intracerebral hemorrhage from contrast extravasation in patients with PTIH. METHODS: We retrospectively collected information on patients who underwent endovascular thrombectomy (EVT) at two stroke centers between August 2017 and January 2023. A total of 222 patients were included in the study, including 118 patients in the development cohort, 52 patients in the internal validation cohort and 52 patients in the external validation cohort. The nomogram was constructed using R software based on independent predictors derived from the multivariate logistic regression analysis, including clinical factors and CT texture features extracted from hyperdense areas on CT images. The performance and accuracy of the derived nomogram was assessed by the area under the receiver operating characteristic curve (AUC-ROC) and calibration curves. Additionally, decision curve analysis was conducted to appraise the clinical utility of the nomogram. RESULTS: Our nomogram was derived from two clinical factors (ASPECT score and onset to reperfusion time) and two CT texture features ( variance and uniformity), with AUC-ROC of 0.943, 0.930 and 0.937 in the development, internal validation and external validation cohorts, respectively. Furthermore, the calibration plot exhibited a strong agreement between the predicted outcome and the actual outcome. In addition, the decision curve analysis revealed the clinical utility of the nomogram in accurately predicting hemorrhage in patients with PTIH. CONCLUSION: The developed nomogram, based on clinical factors and CT texture features, proves to be effective in distinguishing intracerebral hemorrhage from contrast extravasation in patients with PTIH.

Association between uric acid levels and the risk of futile reperfusion in stroke after thrombectomy: A propensity score matching study.

INTRODUCTION: Currently, futile reperfusion (FR) is becoming a major challenge in the endovascular treatment of patients with acute ischemic stroke (AIS). The relationship between serum uric acid (SUA) and FR has not been investigated. This study aims to determine the relationship between SUA and FR using propensity score matching (PSM) analysis. METHODS: A total of 441 patients with AIS undergoing mechanical thrombectomy (MT) between August 2017 and January 2023 were included and divided into two groups based on the median SUA (297.4 µmol/L). Two groups were balanced using PSM analysis at a 1:1 ratio. The standardized mean difference (SMD) were used to assess the efficacy of the matching. Finally, 158 patients with low SUA (≤ 297.4 µmol/L) were matched with 158 patients with high SUA (>297.4 µmol/L). Predictors of FR were analyzed by multivariate logistic regression analysis in the PSM cohort. RESULTS: After PSM, patients with low SUA (≤ 297.4 µmol/L) had a significant higher incidence of FR (72.8 %, 115/158) than patients with high SUA (>297.4 µmol/L) (48.1 %, 76/158) (P<0.001). Multivariate logistic regression analysis in the PSM cohort showed that low SUA (≤ 297.4 µmol/L) was an independent risk factor for the efficacy of reperfusion (OR: 6.403, 95 % CI: 3.123-13.129, P<0.001), suggesting that patients with SUA ≤ 297.4 µmol/L have a 6.403 times higher risk of FR than patients with SUA>297.4 µmol/L. CONCLUSION: The results of this study suggest that low SUA (≤ 297.4 µmol/L) at admission increases the risk of FR in AIS patients undergoing MT by PSM analysis.

High levels of uric acid inhibit BAT thermogenic capacity through regulation of AMPK.

Hyperuricemia (HUA) is strongly associated with the increasing prevalence of obesity, but the underlying mechanism remains elusive. Dysfunction of brown adipose tissue (BAT) could lead to obesity. However, studies on the role of HUA on BAT are lacking. Our retrospective clinical analysis showed that serum uric acid (UA) is significantly associated with BAT in humans. To investigate the role of UA in regulating BAT function, we used UA to treat primary brown adipocytes (BACs) in vitro and established HUA mice. In vitro results showed that HUA suppressed thermogenic gene expression and oxygen consumption rate. Accordingly, HUA mice exhibited lower energy expenditure and body temperature, with larger lipid droplets and lower thermogenic gene expression. These results demonstrate that HUA inhibits BAT thermogenic capacity in vitro and in vivo. To further elucidate the mechanism of UA on adipocytes, mRNA-sequencing analysis was performed and screened for "AMP-activated protein kinase (AMPK) signaling pathway" and "mitochondrial biogenesis." Further tests in vivo and in vitro showed that the phosphorylation of AMPK was suppressed by HUA. Activation of AMPK alleviated the inhibition of AMPK phosphorylation by HUA and increased mitochondrial biogenesis, subsequently restoring the impaired BAT thermogenic capacity in vitro and vivo. Thus, we confirmed that HUA suppresses mitochondrial biogenesis by regulating AMPK, thereby inhibiting BAT thermogenic capacity. Taken together, our study identifies UA as a novel regulator of BAT thermogenic capacity, providing a new strategy to combat obesity.NEW & NOTEWORTHY To investigate the effect and mechanism of UA on BAT thermogenic capacity, we established HUA models in vitro and in vivo, and performed RNA sequencing analysis. Our results revealed that HUA suppresses mitochondrial biogenesis by regulating AMPK, thereby inhibiting BAT thermogenic capacity. Taken together, our study identifies UA as a novel regulator of BAT thermogenic capacity, providing a new strategy to combat obesity.

Diastereo- and Enantioselective Hydrophosphination of Cyclopropenes under Lanthanocene Catalysis.

The asymmetric hydrophosphination of cyclopropenes with phosphines is of much interest and importance, but has remained hardly explored to date probably because of the lack of suitable catalysts. We report here the diastereo- and enantioselective hydrophosphination of 3,3-disubstituted cyclopropenes with phosphines by a chiral lanthanocene catalyst bearing the C2 -symmetric 5,6-dioxy-4,7-trans-dialkyl-substituted tetrahydroindenyl ligands. This protocol offers a selective and efficient route for the synthesis of a new family of chiral phosphinocyclopropane derivatives, featuring 100 % atom efficiency, good diastereo- and enantioselectivity, broad substrate scope, and no need for a directing group.

TET3 as a non-invasive screening tool for the detection of fibrosis in patients with chronic liver disease.

Ten-eleven translocation protein 3 (TET3) is one of the key enzymes in DNA demethylation which can be expressed in liver tissues. However, the clinical value of TET3 for diagnosis and treatment of chronic liver disease have not been reported previously. We investigated the diagnostic accuracy of serum TET3 as a non-invasive screening tool for liver fibrosis. 212 patients with chronic liver disease from were enrolled in this study. Enzyme-linked immunosorbent assay was used to measure the serum levels of TET3. Receiver operating characteristics (ROC) were determined to examine the diagnostic accuracy of TET3 and combination model for diagnosis fibrosis. Serum TET3 level in fibrosis cases was significantly higher than that in non-fibrosis and controls, respectively. The areas under the ROC curve of the TET3 and fibrosis-4 index for liver fibrosis were 0.863 and 0.813, and 0.916 and 0.957 for liver cirrhosis. The combination of TET3 and fibrosis-4 index had a highly promising positive predictive value for detecting liver fibrosis and cirrhosis different stages of (93.5% and 100%) as compared with each diagnostic tool alone. TET3 is related to the development of liver fibrosis and cirrhosis. The TET3-fibrosis-4 model enhances discriminatory power and represents a promising non-invasive tool for the diagnosis and screening of liver fibrosis.

Regio- and Diastereoselective Formal [2+2] Cycloaddition of Allenes with Amino-Functionalized Alkenes by Rare-Earth-Catalyzed C(sp2 )-H Activation.

The [2+2] cycloaddition of allenes with alkenes is of much interest and importance as a straightforward route for the construction of four-membered carbocycles but has remained much underexplored to date. Herein we report for the first time the intermolecular regio- and diastereoselective formal [2+2] cycloaddition of a wide range of allenes with amino-functionalized alkenes by half-sandwich rare-earth catalysts. The reaction proceeded through an allene C(sp2 )-H activation mechanism initiated by the site-selective deprotonation of the allene unit by a rare-earth metal alkyl species followed by alkene insertion into the resulting metal-allenyl bond and the subsequent intramolecular cycloaddition to an allene C=C bond. This protocol offers a unique route for the synthesis of a new family of cyclobutane and cyclobutene derivatives which were difficult to access previously.

Rhodium hydride enabled enantioselective intermolecular C-H silylation to access acyclic stereogenic Si-H.

The tremendous success of stereogenic carbon compounds has never ceased to inspire researchers to explore the potentials of stereogenic silicon compounds. Intermolecular C-H silylation thus represents the most versatile and straightforward strategy to construct C-Si bonds, however, its enantioselective variant has been scarcely reported to date. Herein we report a protocol that allows for the enantioselective intermolecular C-H bond silylation, leading to the construction of a wide array of acyclic stereogenic Si-H compounds under simple and mild reaction conditions. Key to the success is (1) a substrate design that prevents the self-reaction of prochiral silane and (2) the employment of a more reactive rhodium hydride ([Rh]-H) catalyst as opposed to the commonly used rhodium chloride ([Rh]-Cl) catalyst. This work unveils opportunities in converting simple arenes into value-added stereogenic silicon compounds.

Modular Access to Spiro-dihydroquinolines via Scandium-Catalyzed Dearomative Annulation of Quinolines with Alkynes.

The catalytic enantioselective construction of three-dimensional molecular architectures from planar aromatics such as quinolines is of great interest and importance from the viewpoint of both organic synthesis and drug discovery, but there still exist many challenges. Here, we report the scandium-catalyzed asymmetric dearomative spiro-annulation of quinolines with alkynes. This protocol offers an efficient and selective route for the synthesis of spiro-dihydroquinoline derivatives containing a quaternary carbon stereocenter with an unprotected N-H group from readily accessible quinolines and diverse alkynes, featuring high yields, high enantioselectivity, 100% atom-efficiency, and broad substrate scope. Experimental and density functional theory studies revealed that the reaction proceeded through the C-H activation of the 2-aryl substituent in a quinoline substrate by a scandium alkyl (or amido) species followed by alkyne insertion into the Sc-aryl bond and the subsequent dearomative 1,2-addition of the resulting scandium alkenyl species to the C═N unit in the quinoline moiety. This work opens a new avenue for the dearomatization of quinolines, leading to efficient and selective construction of spiro molecular architectures that were previously difficult to access by other means.

A Combined Computational and Experimental Study of Rh-Catalyzed C-H Silylation with Silacyclobutanes: Insights Leading to a More Efficient Catalyst System.

The study of new C-H silylation reagents and reactions remains an important topic. We reported that under Rh catalysis, silacyclobutanes (SCBs) for the first time were able to react with C(sp2)-H and C(sp3)-H bonds, however the underlying reasons for such a new reactivity were not understood. Through this combined computational and experimental study on C-H silylation with SCBs, we not only depict a reaction pathway that fully accounts for the reactivity and all the experimental findings but also streamline a more efficient catalyst that significantly improves the reaction rates and yields. Our key findings include: (1) the active catalytic species is a [Rh]-H as opposed to the previously proposed [Rh]-Cl; (2) the [Rh]-H is generated via a reductive elimination/ß-hydride (ß-H) elimination sequence, as opposed to previously proposed endocyclic ß-H elimination; (3) the regio- and enantio-determining steps are identified; (4) and of the same importance, the discretely synthesized [Rh]-H is shown to be a more efficient catalyst. This work suggests that the [Rh]-H/diphosphine system should find further applications in C-H silylations involving SCBs.

Rhodium-Catalyzed Synthesis of Chiral Monohydrosilanes by Intramolecular C-H Functionalization of Dihydrosilanes.

The preparation of chiral monohydrosilanes remains a rarely achieved goal. To this end a Rh-catalyzed desymmetrization of dihydrosilanes by way of intramolecular C(sp2 )-H functionalization under simple and mild conditions has now been developed. This method provides easy access to a broad range of chiral monohydrosilanes in good yields with excellent enantioselectivities (up to >99 % ee). The resulting monohydrosilanes constitute a good platform to access stereogenic silicon compounds, as well as useful compounds to probe silicon stereochemistry.

Self-Assembly of Linear Amphiphilic Pentablock Terpolymer PAAx-PS48-PEO46-PS48-PAAxin Dilute Aqueous Solution.

A series of linear amphiphilic pentablock terpolymer PAAx-b-PS48-b-PEO46-b-PS48-b-PAAx (AxS48O46S48Ax) with various lengths x of the PAA block (x = 15, 40, 60, and 90) were synthesized via a two-step atom transfer radical polymerization (ATRP) using Br-poly(ethylene oxide)-Br (Br-PEO46-Br) as the macroinitiator, styrene (St) as the first monomer, and tert-butyl acrylate (tBA) as the second monomer, followed with the hydrolysis of PtBA blocks. The AxS48O46S48Ax pentablock terpolymers formed micelles in dilute aqueous solution, of which the morphologies were dependent on the length x of the PAA block. Cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and zeta potential measurement were employed to investigate the morphologies, chain structures, size, and size distribution of the obtained micelles. The morphology of AxS48O46S48Ax micelles changed from spherical vesicles with ordered porous membranes to long double nanotubes, then to long nanotubes with inner modulated nanotubes or short nanotubes, and finally, to spherical micelles or large compound vesicles with spherical micelles inside when x increased from 15 to 90. The hydrophobic PS blocks formed the walls of vesicles and nanotubes as well as the core of spherical micelles. The hydrophilic PEO and PAA block chains were located on the surfaces of vesicle membranes, nanotubes, and spherical micelles. The PAA block chains were partially ionized, leading to the negative zeta potential of AxS48O46S48Ax micelles in dilute aqueous solutions.

Application of Deep Compression Technique in Spiking Neural Network Chip.

In this paper, a reconfigurable and scalable spiking neural network processor, containing 192 neurons and 6144 synapses, is developed. By using deep compression technique in spiking neural network chip, the amount of physical synapses can be reduced to 1/16 of that needed in the original network, while the accuracy is maintained. This compression technique can greatly reduce the number of SRAMs inside the chip as well as the power consumption of the chip. This design achieves throughput per unit area of 1.1 GSOP/([Formula: see text]) at 1.2 V, and energy consumed per SOP of 35 pJ. A 2-layer fully-connected spiking neural network is mapped to the chip, and thus the chip is able to realize handwritten digit recognition on MNIST with an accuracy of 91.2%.

Frequency Invariability of (Pb,La)(Zr,Ti)O3 Antiferroelectric Thick-Film Micro-Cantilevers.

Micro-electromechanical systems comprising antiferroelectric layers can offer both actuation and transduction to integrated technologies. Micro-cantilevers based on the (Pb0.97La0.02)(Zr0.95Ti0.05)O3 (PLZT) antiferroelectric thick film are fabricated by the micro-nano manufacturing process, to utilize the effect of phase transition induced strain and sharp phase switch of antiferroelectric materials. When micro-cantilevers made of antiferroelectric thick films were driven by sweep voltages, there were two resonant peaks corresponding to the natural frequency shift from 27.8 to 27.0 kHz, before and after phase transition. This is the compensation principle for the PLZT micro-cantilever to tune the natural frequency by the amplitude modulation of driving voltage, rather than of frequency modulation. Considering the natural frequency shift about 0.8 kHz and the frequency tuning ability about 156 Hz/V before the phase transition, this can compensate the frequency shift caused by increasing temperature by tuning only the amplitude of driving voltage, when the ultrasonic micro-transducer made of antiferroelectric thick films works for such a long period. Therefore, antiferroelectric thick films with hetero-structures incorporated into PLZT micro-cantilevers not only require a lower driving voltage (no more than 40 V) than rival bulk piezoelectric ceramics, but also exhibit better performance of frequency invariability, based on the amplitude modulation.

Congestion patterns of electric vehicles with limited battery capacity.

The path choice behavior of battery electric vehicle (BEV) drivers is influenced by the lack of public charging stations, limited battery capacity, range anxiety and long battery charging time. This paper investigates the congestion/flow pattern captured by stochastic user equilibrium (SUE) traffic assignment problem in transportation networks with BEVs, where the BEV paths are restricted by their battery capacities. The BEV energy consumption is assumed to be a linear function of path length and path travel time, which addresses both path distance limit problem and road congestion effect. A mathematical programming model is proposed for the path-based SUE traffic assignment where the path cost is the sum of the corresponding link costs and a path specific out-of-energy penalty. We then apply the convergent Lagrangian dual method to transform the original problem into a concave maximization problem and develop a customized gradient projection algorithm to solve it. A column generation procedure is incorporated to generate the path set. Finally, two numerical examples are presented to demonstrate the applicability of the proposed model and the solution algorithm.

Relationship of miRNA-146a to primary Sjögren's syndrome and to systemic lupus erythematosus: a meta-analysis.

Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE) are common systemic autoimmune diseases, which impact not only patient health but also their quality of life. miRNA-146a is a microRNA that participates in the pathophysiology of SjS and SLE. In this investigation, we conducted a meta-analysis to determine the relationship of miR-146a to primary SjS (PSS) and to SLE. The following databases were interrogated; Pubmed, Cochrane Central Register of Controlled Trials, WANFANG, Chinese National Knowledge Infrastructure, and WEIPU. Standard mean difference with 95% confidence intervals (CI) were used to study the relationship between miRNA-146a expression and thee diseases by random-effects model. A total of six studies, with 158 cases and 124 controls were included for the meta-analysis. The meta-analysis shows that miRNA-146a expression is associated with the risk of PSS (MD = 6.32, p = 0.005). No relationship between miR-146a expression and SLE was identified (MD = -0.86, p = 0.26). SLE subgroup analysis (peripheral blood mononuclear cells and serum) confirmed this result. The risk for PSS is related to miR-146a expression, while miRNA-146a expression is not related to SLE. As such, miRNA-146a may serve as a novel biomarker for the diagnosis of PSS, but not SLE.

Tautomeric-Dependent Lactam Cycloaddition with Nitrile Oxide: Facile Synthesis of 1,2,4-Oxadiazole[4,5-a]indolone Derivatives.

A concise, metal-free, and gram-scale strategy to convert indoline-2,3-diones to 1,2,4-oxadiazole[4,5-a]indolones through an improved [3 + 2] cycloaddition of α-ketone-lactam with nitrile oxides has been developed. The lactim form of the resonance structure of isatin in protic solvents is the key active dipolarophile that shows chemo- and regioselectivity under experimental and theoretical conditions. This strategy conveniently enabled the assembly of several 1,2,4-oxadiazole[4,5-a]indolines with a broad range of functional groups. Compounds 3a and 4b exhibit cytotoxicity in the NCI/ADR-RES, SKOV3, and OVCAR8 cell lines.