Thermal properties of glycinin in crowded environments.

Crowded environments, commonly found in the food system, are utilized to enhance the properties of soybean proteins. Despite their widespread application, little information exists regarding the impact of crowded environments on the denaturation behaviors of soybean proteins. In this study, we investigated how crowding agents with varying molecular weights, functional groups, and topology affect the denaturation behavior of glycinin under crowded conditions. The results reveal that thermal stability in PEG crowded environments is mainly influenced by both preferential hydration and binding. The stabilization is primarily enthalpy-driven, with aggregation contributing additional entropic stabilization. Specifically, ethylene glycol and diethylene glycol exhibit temperature-dependent, bilateral effects on glycinin stability. At the denaturation temperature, hydrophobic interactions play a predominant role, decreasing glycinin's thermal stability. However, at a molecular weight of 200 g/mol, there is a delicate balance between destabilizing and stabilizing effects, leading to no significant change in thermal stability. With the addition of PEG 400, 1000, and 2000, besides preferential hydration, additional hard-core repulsions between glycinin molecules enhance thermal stability. Methylation modification experiments demonstrated that 2-methoxyethyl ether exerted a more pronounced denaturing effect. Additionally, the cyclization of PEG 1000 decreased its stabilizing effect.

A new pepper allergen Zan b 1.01 of 2S albumins: Identification, cloning, characterization, and cross-reactivity.

BACKGROUND: Zanthoxylum bungeanum (Sichuan pepper; in Chinese) is used as a spice worldwide and is a potentially life-threatening allergenic food source, as first reported by our team in 2005. However, its allergen components are unknown. OBJECTIVE: We aim to identify and characterize its major allergen and determine its cross-reactivities with citrus seeds, pistachios, and cashew seeds. METHODS: Ionic exchange and molecular exclusion chromatography were used to isolate the protein components from Sichuan pepper seed. A protein fraction was characterized by SDS-PAGE, analytical ultracentrifugation, mass spectrometry, and circular dichroism spectroscopy. The coding region of it was amplified from the genome. ELISA and competitive ELISA assays were used to investigate the allergenicity and cross-reactivity of allergens. RESULTS: This protein allergen was around 14 kDa. It was a 2S albumin similar to an α-Amylase inhibitor (AAI) domain-containing protein of Citrus sinensis. Circular dichroism spectroscopy showed its thermal stability was high. A 303 bps DNA sequence of the AAI domain was cloned from the genome of the Sichuan pepper. Competitive ELISA assays showed positive cross-reactivities between this allergen and citrus seeds, pistachios, and cashew seeds. CONCLUSION: A major allergen of around 14 kDa from Sichuan pepper seed was confirmed, which belongs to the 2S albumin of plant seed storage proteins. Based on the nomenclature of the IUIS Subcommittee for Allergen Nomenclature, this allergen is designated as Zan b 1.01. The cross-reactivities were demonstrated between Zan b 1.01 and citrus seeds, pistachios, and cashew seeds.

An engineered bispecific nanobody in tetrameric secretory IgA format confers broad neutralization against SARS-CoV-1&2 and most variants.

SARS-CoV-2, a type of respiratory virus, has exerted a great impact on global health and economy over the past three years. Antibody-based therapy was initially successful but later failed due to the accumulation of mutations in the spike protein of the virus. Strategies that enable antibodies to resist virus escape are therefore of great significance. Here, we engineer a bispecific SARS-CoV-2 neutralizing nanobody in secretory Immunoglobulin A (SIgA) format, named S2-3-IgA2m2, which shows broad and potent neutralization against SARS-CoV-1, SARS-CoV-2 and its variants of concern (VOCs) including XBB and BQ.1.1. S2-3-IgA2m2 is ∼1800-fold more potent than its parental IgG counterpart in neutralizing XBB. S2-3-IgA2m2 is stable in mouse lungs at least for three days when administrated by nasal delivery. In hamsters infected with BA.5, three intranasal doses of S2-3-IgA2m2 at 1 mg/kg significantly reduce viral RNA loads and completely eliminate infectious particles in the trachea and lungs. Notably, even at single dose of 1 mg/kg, S2-3-IgA2m2 prophylactically administered through the intranasal route drastically reduces airway viral RNA loads and infectious particles. This study provides an effective weapon combating SARS-CoV-2, proposes a new strategy overcoming the virus escape, and lays strategic reserves for rapid response to potential future outbreaks of "SARS-CoV-3".

Direct bilirubin: A predictor of hematoma expansion after intracerebral hemorrhage.

BACKGROUND: Previous evidence demonstrated that several biomarkers involved in the pathological process of coagulation/hemostasis dysfunction, impairment of brain vascular integrity and inflammation are associated with hematoma expansion (HE) after intracerebral hemorrhage (ICH). We aimed to explore whether there were unreported laboratory biomarkers associated with HE that were readily and commonly available in clinical practice. METHODS: We retrospectively analyzed consecutive acute ICH patients from 2012 to 2020 with admission laboratory tests and baseline and follow-up computed tomography (CT) scans. Univariate and multivariate regression analyses were used to evaluate associations between conventional laboratory indicators and HE. The results were verified in a prospective validation cohort. The relationship of candidate biomarker and 3-month outcomes was also investigated and mediation analysis was undertaken to determine causal associations among candidate biomarker, HE and outcome. RESULTS: Of 734 ICH patients, 163 (22.2%) presented HE. Among the included laboratory indicators, higher direct bilirubin (DBil) was associated with HE (adjusted odds ratio [OR] of per 1.0 µmol/L change 1.082; 95% confidence interval [CI] 1.011-1.158). DBil >5.65 µmol/L was a predictor of HE in validation cohort. Higher DBil was also associated with poor 3-month outcomes. The mediation analysis indicated that the association of higher DBil and poor outcomes was partially mediated by HE. CONCLUSIONS: DBil is a predictor of HE and poor 3-month outcomes after ICH. DBil's metabolic process and involvement in the pathological mechanism of HE are likely to contribute to the association between DBil and HE. Interventions targeting DBil to improve post-ICH prognosis may be meaningful and worthy of further exploration.

A 6-month prognostic nomogram incorporating hemoglobin level for intracerebral hemorrhage in younger adults.

OBJECTIVE: Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH. METHODS: Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves. RESULTS: In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490-9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014-1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002-1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969-0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037-1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069-1.141; P < 0.001) were independent risk factors. Based on these 6 factors, the nomogram can be employed to predict early functional prognosis with high accuracy (AUC 0.791). Decision curve analysis and clinical impact curves showed an increased net benefit for utilizing the nomogram. CONCLUSION: The haemoglobin level at admission may be an easily overlooked factor in clinical work. This new nomogram model could be a promising and convenient tool to predict the early functional prognosis of adults with ICH. More prospective multicentre studies are needed to validate these findings.

Apolipoprotein E ɛ2 Is Associated with the White Matter Hyperintensity Multispot Pattern in Spontaneous Intracerebral Hemorrhage.

The white matter hyperintensity (WMH) multispot pattern, as multiple punctate subcortical foci, could differentiate cerebral amyloid angiopathy (CAA) from hypertensive arteriolopathy. Nevertheless, the pathophysiology underlying the multispot sign is still inexplicit. We aimed to explore risk factors for multispot patterns in cerebral small vessel disease (CSVD)-related intracerebral hemorrhage (ICH). Between June 2018 and January 2020, we retrospectively rated the WMH multispot pattern while blinded to our prospective spontaneous ICH cohort's clinical data. Demographic, genetic, and neuroimaging characteristics were applied in establishing the multispot pattern models via multiple logistic regression. In total, 268 participants were selected from our cohort. The possession of apolipoprotein E (APOE) ε2 (P = 0.051) was associated with multispot WMH in univariate analysis. Multispot WMHs were accompanied by multiple CAA features, such as centrum semiovale (CSO)-perivascular space (PVS) predominance (P = 0.032) and severe CSO-PVS (P < 0.001). After adjusting for confounding factors, APOE ε2 possession (OR 2.99, 95% CI [1.07, 8.40]; P = 0.037), severe CSO-PVS (OR 2.39, 95% CI [1.09, 5.26]; P = 0.031), and large posterior subcortical patches (P = 0.001) were independently correlated with the multispot pattern in multivariate analysis. Moreover, APOE ε2 possession (OR 4.34, 95% CI [1.20, 15.62]; P = 0.025) and severe CSO-PVS (OR 3.39, 95% CI [1.23, 9.34]; P = 0.018) remained statistically significant among the participants older than 55 years of age and with categorizable CSVD. APOE ε2 and severe CSO-PVS contribute to the presence of WMH multispot patterns. Because the multispot pattern is a potential diagnostic biomarker in CAA, genetics-driven effects shed light on its underlying vasculopathy. Clinical Trial Registration: URL- http://www.chictr.org.cn . Unique identifier: ChiCTR-ROC-2000039365. Registration date 2020/10/24 (retrospectively registered).

Trifluoromethyl Selenoxides: Electrophilic Reagents for C-H Trifluoromethylselenolation of (Hetero)Arene.

The trifluoromethylselenyl group (CF3Se) has become an emerging fluorinated moiety in synthetic chemistry due to its high Hansch lipophilicity parameter and strong electron-withdrawing effect. The trifluoromethylselenolation is hampered by limited synthetic methods and related reagents. Herein, we designed and synthesized the new electrophilic trifluoromethylselenolation reagents, trifluoromethyl selenoxides, which are easy to prepare and easy-to-handle and are not moisture or air sensitive. The selenoxides are successfully applied to metal-free C-H trifluoromethylselenolation of a series of (hetero)arenes.

Caspase-1: A Promising Target for Preserving Blood-Brain Barrier Integrity in Acute Stroke.

The blood-brain barrier (BBB) acts as a physical and biochemical barrier that plays a fundamental role in regulating the blood-to-brain influx of endogenous and exogenous components and maintaining the homeostatic microenvironment of the central nervous system (CNS). Acute stroke leads to BBB disruption, blood substances extravasation into the brain parenchyma, and the consequence of brain edema formation with neurological impairment afterward. Caspase-1, one of the evolutionary conserved families of cysteine proteases, which is upregulated in acute stroke, mainly mediates pyroptosis and compromises BBB integrity via lytic cellular death and inflammatory cytokines release. Nowadays, targeting caspase-1 has been proven to be effective in decreasing the occurrence of hemorrhagic transformation (HT) and in attenuating brain edema and secondary damages during acute stroke. However, the underlying interactions among caspase-1, BBB, and stroke still remain ill-defined. Hence, in this review, we are concerned about the roles of caspase-1 activation and its associated mechanisms in stroke-induced BBB damage, aiming at providing insights into the significance of caspase-1 inhibition on stroke treatment in the near future.

SMASH-U aetiological classification: A predictor of long-term functional outcome after intracerebral haemorrhage.

BACKGROUND: SMASH-U is a systematic aetiological classification system for intracerebral haemorrhage (ICH) proven to be a predictor of post-ICH haematoma expansion and mortality. However, its role in predicting functional outcome remains elusive. Therefore, we aimed to investigate whether SMASH-U is associated with long-term functional outcome after ICH and improves the accuracy of prediction when added to max-ICH score. METHODS: Consecutive acute ICH patients from 2012 to 2018 from the neurology department of Tongji Hospital were enrolled. ICH aetiology was classified according to the SMASH-U system. The association of SMASH-U with 12-month functional outcome after ICH and the predictive value were evaluated. RESULTS: Of 1938 ICH patients, the aetiology of 1295 (66.8%) patients were classified as hypertension, followed by amyloid angiopathy (n = 250, 12.9%), undetermined (n = 159, 8.2%), structural lesions (n = 149, 7.7%), systemic disease (n = 74, 3.8%) and medication (n = 11, 0.6%). The baseline characteristics were different among the six aetiologies. In multivariate analysis, SMASH-U was proven to be a predictor of 12-month unfavourable functional outcome. When adding the SMASH-U system, the predictive performance of max-ICH score was improved (area under the receiver operating characteristic curve from 0.802 to 0.812, p = 0.010) and the predictive accuracy was enhanced (integrated discrimination improvement [IDI]: 1.60%, p < 0.001; continuous net reclassification improvement [NRI]: 28.16%, p < 0.001; categorical NRI: 3.34%, p = 0.004). CONCLUSIONS: SMASH-U predicted long-term unfavourable functional outcomes after acute ICH and improved the accuracy of prediction when added to max-ICH score. Integrating the aetiology to a score model to predict the post-ICH outcome may be meaningful and worthy of further exploration.

Decatungstate Catalyzed Synthesis of Trifluoromethylthioesters from Aldehydes via a Radical Process.

Here we report a mild and general method for the trifluoromethylthiolation of aldehydes using N-trifluoromethylthiosaccharin as the CF3S radical source and sodium decatungstate (NaDT) as the photocatalyst. This reaction proceeds via hydrogen atom abstraction by photoactivated DT and features good functional groups and substrate tolerance. Generally, electron-rich aldehydes demonstrate better reactivity than electron-deficient ones and good selectivity is observed for the trifluoromethylthiolation of aldehydic C-H bonds over tertiary and benzylic C-H bonds. Preliminary mechanistic studies have shown that a free radical process is involved.

Assembly status transition offers an avenue for activity modulation of a supramolecular enzyme.

Nature has evolved many supramolecular proteins assembled in certain, sometimes even seemingly oversophisticated, morphological manners. The rationale behind such evolutionary efforts is often poorly understood. Here, we provide atomic-resolution insights into how the dynamic building of a structurally complex enzyme with higher order symmetry offers amenability to intricate regulation. We have established the functional coupling between enzymatic activity and protein morphological states of glutamine synthetase (GS), an old multi-subunit enzyme essential for cellular nitrogen metabolism. Cryo-EM structure determination of GS in both the catalytically active and inactive assembly states allows us to reveal an unanticipated self-assembly-induced disorder-order transition paradigm, in which the remote interactions between two subcomplex entities significantly rigidify the otherwise structurally fluctuating active sites, thereby regulating activity. We further show in vivo evidences that how the enzyme morphology transitions could be modulated by cellular factors on demand. Collectively, our data present an example of how assembly status transition offers an avenue for activity modulation, and sharpens our mechanistic understanding of the complex functional and regulatory properties of supramolecular enzymes.

Predicting the occurrence of early seizures after cerebral venous thrombosis using a comprehensive nomogram.

BACKGROUND: Seizure is a common clinical manifestation of cerebral venous thrombosis (CVT). The mortality rate of patients with CVT with seizure is three times higher than that of patients without seizure. The aim of this study was to develop a nomogram to predict the individual probability of acute seizure events in patients with CVT. METHOD: This was a single-center, retrospective cohort study. We analyzed and compared demographic variables, epidemiological risk factors, clinical presentation, laboratory results and imaging data in a cohort of 142 patients who were diagnosed with CVT in our hospital from January 2013 to December 2018. A nomogram was constructed to predict the risk of early seizure (ES) in these patients according to the multivariable logistic regression analysis results. The concordance index, GiViTi calibration belt and decision curve analysis (DCA) were used to assess nomogram performance. RESULTS: Forty-three (30.28%) patients experienced seizure within 2 weeks after a CVT diagnosis. Multivariate analysis identified focal neurologic deficit, Glasgow Coma Scale (GCS) scores ≤ 8 on admission, hemorrhagic lesions, superior sagittal sinus thrombosis (SSST) and frontal lobe lesions as independent predictive factors for ES occurrence after CVT. A nomogram was generated based on these predictive factors with the concordance index reaching 0.82, indicating that the clinical tool was well calibrated. DCA showed that the model was useful with a threshold probability in the range of 0-77%. CONCLUSIONS: We developed the first nomogram that could predict the risk of ES in CVT patients. This effective and convenient tool has shown promising clinical benefit and will assist clinicians in making treatment decisions.

Apolipoprotein E genotype predicts subarachnoid extension in spontaneous intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Spontaneous intracerebral haemorrhage (ICH) with subarachnoid extension (SAHE) predicts poor outcomes and haematoma expansion in spontaneous ICH and is also a potential predictor of the severity of vascular amyloid deposition. The biological underpinnings of SAHE remain elusive. A study was conducted to identify risk factors associated with SAHE. METHODS: A retrospective analysis was performed of an ongoing prospective cohort of primary spontaneous supratentorial ICH patients admitted to Tongji Hospital. SAHE was rated on baseline noncontrast computed tomography images by investigators blinded to the clinical data. RESULTS: A total of 189 patients were enrolled. Apolipoprotein E (APOE) ε2 copies (p = 0.020), but not APOE ε4 copies (p > 0.2), were more common in patients with SAHE in univariate analysis. After controlling for confounding factors in multiple logistic regression, lobar haematoma (odds ratio [OR] 14.21, 95% confidence interval [CI] 5.89-34.33; p < 0.001), large haematoma volume (OR 1.04, 95% CI 1.02-1.06; p < 0.001) and APOE ε2 copies (OR 3.07, 95% CI 1.05-8.97; p = 0.041) were three independent predictors of SAHE. For subgroup analysis stratified by location, APOE ε2 showed a possible association with SAHE in lobar ICH (p = 0.026) but not in deep ICH (p > 0.2). No significant association was found between APOE ε4 copies and either lobar (p > 0.2) or deep ICH (p > 0.2). CONCLUSIONS: The APOE ε2 allele predicts SAHE in spontaneous supratentorial ICH. The association may predominantly apply to lobar ICH. Given the established relationship between the APOE ε2 allele and pathological cerebrovascular changes, our findings suggest that SAHE involves genetically driven vessel pathology.

Improved hydrogen production from pharmaceutical intermediate wastewater in an anaerobic maifanite-immobilized sludge reactor.

A novel anaerobic maifanite-immobilized sludge reactor (AMSR) was employed to investigate the feasibility and performance of continuous hydrogen production for the treatment of pharmaceutical intermediate wastewater (PIW) at different organic loading rates (OLR) (from 12 to 96 g COD L-1 d-1) according to changes in the hydraulic retention time (HRT). A reactor without maifanite was also employed as a control. The results indicate that maifanite accelerates granular sludge formation and the AMSR presents more efficient and stable performance than the control in terms of the hydrogen production rate. In the AMSR, the highest hydrogen production rate of 11.2 ± 0.4 mmol L-1 h-1 was achieved at an optimum OLR of 72 g COD L-1 d-1. The main metabolic route for hydrogen production was ethanol-type fermentation, which was reflected in the relative abundance of E. harbinense, which was dominant for all of the OLRs. The maximum energy conversion efficiency in the dual production of hydrogen and ethanol was determined to be 24.5 kJ L-1 h-1 at an OLR of 72 g COD L-1 d-1.

Crystal structure of caspase-11 CARD provides insights into caspase-11 activation.

Murine caspase-11 is the centerpiece of the non-canonical inflammasome pathway that can respond to intracellular LPS and induce pyroptosis. Caspase-11 contains two components, an N-terminal caspase recruitment domain (CARD) and a C-terminal catalytic domain. The aggregation of caspase-11 is thought to promote the auto-processing and activation of caspase-11. However, the activation mechanism of caspase-11 remains unclear. In this study, we purified the caspase-11 CARD fused to an MBP tag and found it tetramerizes in solution. Crystallographic analysis reveals an extensive hydrophobic interface formed by the H1-2 helix mediating homotypic CARD interactions. Importantly, mutations of the helix H1-2 hydrophobic residues abolished the tetramerization of MBP-tagged CARD in solution and failed to induce pyroptosis in cells. Our study provides the first evidence of the homotypic interaction mode for an inflammatory caspase by crystal model. This finding demonstrates that the tetramerization of the N-terminal CARD can promote releasing of the catalytic domain auto-inhibition, leading to the caspase-11 activation.

MiR-181c-5p Promotes Inflammatory Response during Hypoxia/Reoxygenation Injury by Downregulating Protein Tyrosine Phosphatase Nonreceptor Type 4 in H9C2 Cardiomyocytes.

BACKGROUND: Constitutive nuclear factor kappa B (NFκB) activation has been shown to exacerbate during myocardial ischemia/reperfusion (I/R) injury. We recently showed that miR-181c-5p exacerbated cardiomyocytes injury and apoptosis by directly targeting the 3'-untranslated region of protein tyrosine phosphatase nonreceptor type 4 (PTPN4). However, whether miR-181c-5p mediates cardiac I/R injury through NFκB-mediated inflammation is unknown. Thus, the present study aimed to investigate the role of miR-181c-5p during myocardial I/R injury and explore its mechanism in relation to inflammation in H9C2 cardiomyocytes. METHODS AND RESULTS: In hypoxia/reoxygenation (H/R, 6 h hypoxia followed by 6 h reoxygenation)-stimulated H9C2 cardiomyocytes or postischemic myocardium of rat, the expression of miR-181c-5p was significantly upregulated, which was concomitant increased NFκB activity when compared to the nonhypoxic or nonischemic control groups. This is indicative that miR-181c-5p may be involved in NFκB-mediated inflammation during myocardial I/R injury. To investigate the potential role of miR-181c-5p in H/R-induced cell inflammation and injury, H9C2 cardiomyocytes were transfected with the miR-181c-5p agomir. Overexpression of miR-181c-5p significantly aggravated H/R-induced cell injury (increased lactate dehydrogenase (LDH) level) and exacerbated NFκB-mediated inflammation (greater phosphorylation and degradation of IκBα, phosphorylation of p65, and increased levels of proinflammatory cytokines tumor necrosis factor α (TNFα), interleukin (IL)-6, and IL-1ß). In contrast, inhibition of miR-181c-5p by its antagomir transfection in vitro had the opposite effect. Furthermore, overexpression of miR-181c-5p significantly enhanced lipopolysaccharide-induced NFκB signalling. Additionally, knockdown of PTPN4, the direct target of miR-181c-5p, significantly aggravated H/R-induced phosphorylation and degradation of IκBα, phosphorylation of p65, and the levels of proinflammatory cytokines. PTPN4 knockdown also cancelled miR-181c-5p antagomir mediated anti-inflammatory effects in H9C2 cardiomyocytes during H/R injury. CONCLUSIONS: It is concluded that miR-181c-5p may exacerbate myocardial I/R injury and NFκB-mediated inflammation via PTPN4, and that targeting miR-181c-5p/PTPN4/NFκB signalling may represent a novel strategy to combat myocardial I/R injury.

Activation of autophagy inhibits nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome activation and attenuates myocardial ischemia-reperfusion injury in diabetic rats.

AIMS/INTRODUCTION: Diabetic hearts are more vulnerable to ischemia-reperfusion injury (I/RI). The activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome can mediate the inflammatory process, and hence might contribute to myocardial I/RI. Activation of autophagy can eliminate excess reactive oxygen species and alleviate myocardial I/RI in diabetes. The present study aimed to investigate whether the activation of autophagy can alleviate diabetic myocardial I/RI through inhibition of NLRP3 inflammasome activation. MATERIALS AND METHODS: A dose of 65 mg/kg streptozotocin was given by tail vein injection to establish a type 1 diabetes model in the rats. The left anterior descending coronary artery was ligated for 30 min followed by reperfusion for 2 h to establish a myocardial I/RI model. H9C2 cardiomyocytes were exposed to high glucose (33 mmol/L) and subjected to hypoxia-reoxygenation (6 h hypoxia followed by 4 h reoxygenation). RESULTS: The diabetic rats showed significant inhibition of cardiac autophagy (decreased LC3-II/I and increased p62) that was concomitant with increased activation of NLRP3 inflammasome (increased NLRP3, apoptosis-related spots protein cleaved caspase-1, interleukin-18, interleukin-1ß) and more severe myocardial I/RI (elevated creatine kinase myocardial band, lactate dehydrogenase and larger infarct size). However, administration of rapamycin, an inhibitor of the autophagy, to activate autophagy resulted in the inhibition of NLRP3 inflammasome, and finally alleviated myocardial I/RI. In vitro, high glucose inhibited autophagy, while activating NLRP3 inflammasome in H9C2 cardiomyocytes and aggravating hypoxia-reoxygenation injury, but rapamycin reversed these adverse effects of high glucose. CONCLUSION: Activation of autophagy can suppress the formation of NLRP3 inflammasome, which in turn attenuates myocardial ischemia-reperfusion injury in diabetic rats.

Biased Lewis Pairs: A General Catalytic Approach to Ether-Ester Block Copolymers with Unlimited Ordering of Sequences.

Polymerizing epoxides after cyclic esters remains a major challenge, though their block copolymers have been extensively studied and used for decades. Reported here is a simple catalytic approach based on a metal-free Lewis pair that addresses the challenge. When the Lewis acid is used in excess of a base, selective (transesterification-free) polymerization of epoxides occurs in the presence of esters, while selectivity toward cyclic esters is achieved by an oppositely biased catalyst. Hence, one-pot block copolymerization can be performed in both ester-first and ether-first orders with selectivity being switchable at any stage, yielding ether-ester-type block copolymers with unlimited ordering of sequences as well as widely variable compositions and architectures. The selectivity can also be switched back and forth several times to generate a multiblock copolymer. Experimental and calculational results indicate that the selectivity originates mainly from the state of catalyst-activated hydroxy species.

Nickel/NHC-Catalyzed Asymmetric C-H Alkylation of Fluoroarenes with Alkenes: Synthesis of Enantioenriched Fluorotetralins.

Chiral polyfluoroarene derivatives are an important scaffold in chemistry. An unprecedented enantioselective C-H alkylation of polyfluoroarenes with alkenes is described. The reaction employs bulky chiral N-heterocyclic carbene (NHC) ligands for nickel catalysts to enable exclusive activation of C-H bonds over C-F bonds and complete endo-selective C-H annulation and excellent enantioselectivity. A wide variety of chiral fluorotetralins, compounds otherwise difficultly accessed but serve as important bioisosteric analogs of both tetralin and heterocycle units for drug design, are expediently synthesized from easily available substrates. To our knowledge, this is the first example of catalytic enantioselective C-H functionalization of polyfluoroarenes.

Universal Synthetic Strategy for the Construction of Topological Polystyrenesulfonates: The Importance of Linkage Stability during Sulfonation.

Polystyrenesulfonate (PSS), as one of the most important categories of polyelectrolytes, has received increasing attention due to its great potential in the applications of energy- and biomedical-related fields. However, most of the previous studies only focused on linear PSS and its derivatives, but little attention was paid to nonlinear topological PSSs. So far, the synthesis of nonlinear PSSs with well-defined structures is still a challenging task, and the main obstacle lies in the stability issue of functional chemical linkages during the sulfonation process of polystyrene (PS) precursors, such as the carbon-oxygen-containing linkages. Herein, by rationally designing the chemical structure of the functional linkage, we introduce a versatile and efficient strategy for the preparation of topological PSSs. Specifically, by embedding firm triazole linkages (without carbon-oxygen linkages) into the backbone structure of cyclic and hyperbranched PS precursors, the backbone and functional linkages are found to present excellent chemical stability under certain sulfonation conditions, which eventually lead to the successful preparation of cyclic and hyperbranched PSSs. By using two sets of PSS samples with varied molar masses, the scaling relations between the number of repeating units and the sedimentation coefficient are established for both linear and cyclic PSSs. We believe that our proposed synthetic strategy is universal and could be extended to the synthesis of other types of topological PSSs.