Microglia induce auditory dysfunction after status epilepticus in mice.

Auditory dysfunction and increased neuronal activity in the auditory pathways have been reported in patients with temporal lobe epilepsy, but the cellular mechanisms involved are unknown. Here, we report that microglia play a role in the disinhibition of auditory pathways after status epilepticus in mice. We found that neuronal activity in the auditory pathways, including the primary auditory cortex and the medial geniculate body (MGB), was increased and auditory discrimination was impaired after status epilepticus. We further demonstrated that microglia reduced inhibitory synapses on MGB relay neurons over an 8-week period after status epilepticus, resulting in auditory pathway hyperactivity. In addition, we found that local removal of microglia from the MGB attenuated the increase in c-Fos+ relay neurons and improved auditory discrimination. These findings reveal that thalamic microglia are involved in auditory dysfunction in epilepsy.

ProBDNF contributed to patrolling monocyte infiltration and renal damage in systemic lupus erythematosus.

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1+ patrolling monocytes (PMo) numbers were decreased in SLE. ProBDNF was specifically expressed in CX3CR1+ PMo and was closely correlated with disease activity and the degree of renal injury in SLE patients. In MRL/lpr mice, elevated proBDNF was found in circulating PMo and the kidney, and blockade of proBDNF restored the balance of circulating and kidney-infiltrating PMo. This blockade also led to the reversal of pro-inflammatory responses in monocytes and a noticeable improvement in renal damage in lupus mice. Overall, the results indicate that the upregulation of proBDNF in PMo plays a crucial role in their infiltration into the kidney, thereby contributing to nephritis in SLE. Targeting of proBDNF offers a potential therapeutic role in modulating monocyte-driven renal damage in SLE.

P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

Apatinib Plus Toripalimab (Anti-PD1 Therapy) as Second-Line Therapy in Patients With Advanced Gastric or Esophagogastric Junction Cancer: Results From a Randomized, Open-Label Phase II Study.

BACKGROUND: This study aimed to assess the activity of apatinib plus toripalimab in the second line for patients with advanced gastric or esophagogastric junction cancer (GC/EGJC). METHODS: In this open-label, phase II, randomized trial, patients with advanced GC/EGJC who progressed after first-line chemotherapy were enrolled and received 250 mg apatinib per day plus 240 mg toripalimab on day 1 per 3 weeks (arm A) or physician's choice of chemotherapy (PC, arm B). The primary endpoint of this study was the 1-year survival rate. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed as secondary endpoints. RESULTS: Twenty-five patients received apatinib plus toripalimab while 26 were enrolled in arm B. The 1-year survival rates of the 2 groups were 43.3% and 42.3%, respectively (P = .903). The PFS was 2.77 versus 2.33 months (P = .660). The OS was 8.30 versus 9.88 months (P = .539). An objective response was reported in 20.0% of patients in arm A compared to 26.9% in arm B (P = .368), respectively. A total of 6 (24.0%) patients experienced adverse events of grade ≥ 3 in arm A, while 9 (34.6%) patients suffered from adverse events of grade ≥ 3 in arm B. No drug-related deaths occurred in either group. CONCLUSION: Toripalimab plus apatinib treatment in second-line therapy of advanced GC/EGJC showed manageable toxicity but did not improve clinical outcomes relative to PC treatment (ClinicalTrials.gov Identifier: NCT04190745).

The role of the methyltransferase METTL3 in prostate cancer: a potential therapeutic target.

The incidence of prostate cancer (PCa), the most prevalent malignancy, is currently at the forefront. RNA modification is a subfield of the booming field of epigenetics. To date, more than 170 types of RNA modifications have been described, and N6-methyladenosine (m6A) is the most abundant and well-characterized internal modification of mRNAs involved in various aspects of cancer progression. METTL3, the first identified key methyltransferase, regulates human mRNA and non-coding RNA expression in an m6A-dependent manner. This review elucidates the biological function and role of METTL3 in PCa and discusses the implications of METTL3 as a potential therapeutic target for future research directions and clinical applications.

Bortezomib elevates intracellular free Fe2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 to inhibit multiple myeloma cells.

Iron contributes to tumor initiation and progression; however, excessive intracellular free Fe2+ can be toxic to cancer cells. Our findings confirmed that multiple myeloma (MM) cells exhibited elevated intracellular iron levels and increased ferritin, a key protein for iron storage, compared with normal cells. Interestingly, Bortezomib (BTZ) was found to trigger ferritin degradation, increase free intracellular Fe2+, and promote ferroptosis in MM cells. Subsequent mechanistic investigation revealed that BTZ effectively increased NCOA4 levels by preventing proteasomal degradation in MM cells. When we knocked down NCOA4 or blocked autophagy using chloroquine, BTZ-induced ferritin degradation and the increase in intracellular free Fe2+ were significantly reduced in MM cells, confirming the role of BTZ in enhancing ferritinophagy. Furthermore, the combination of BTZ with RSL-3, a specific inhibitor of GPX4 and inducer of ferroptosis, synergistically promoted ferroptosis in MM cell lines and increased cell death in both MM cell lines and primary MM cells. The induction of ferroptosis inhibitor liproxstatin-1 successfully counteracted the synergistic effect of BTZ and RSL-3 in MM cells. Altogether, our findings reveal that BTZ elevates intracellular free Fe2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 by increasing ferroptosisin MM cells.

Protein quality of commercially important edible bivalves.

Bivalves are a high-quality source of animal protein for human consumption. In recent years, the demand for bivalve proteins has increased dramatically, leading to a sharp increase in global production of marine bivalves. To date, although the amino acid profiles of many bivalves have been reported, such information has not been well organized. Therefore, there is an urgent need for a comprehensive scientific review of the protein quality of bivalves, especially commercially important edible bivalves. In this context, this study was conducted to evaluate the protein quality of commercially important edible bivalves. In general, most bivalves are rich in protein (> 50% of their dry weight) and amino acids (> 30 g/100g protein). Although most species of bivalves are rich in essential amino acids (EAA) (up to 50 g/100g protein), some species of edible bivalves have very low levels of EAA (< 5 g/100g protein). Based on the AA score, almost all bivalves have at least two limiting AAs. Most bivalve proteins provides delicious flavors with unami, sweetness and a hint of bitterness. The findings of this study not only serve as a a guide for selecting appropriate bivalves based on consumer preferences for specific AAs or AA scores, but also provide information on potential bivalve species for aquaculture to produce higher protein quality to meet the growing demand for high quality animal protein.

Thrombectomy improves functional independence in severe basilar artery occlusion with favorable collateral circulation.

BACKGROUND AND PURPOSE: This study aimed to investigate the effect of collateral circulation on the outcomes of thrombectomy versus medical management alone in basilar artery occlusion (BAO) patients with varying stroke severities. METHODS: Data from the ATTENTION cohort were used to perform a post-hoc analysis comparing the outcomes of thrombectomy with medical management in BAO patients with varying degrees of collateral circulation and stroke severity. Basilar Artery on Computed Tomography Angiography (BATMAN) scores were used to quantify the collateral circulation, and the effect was estimated through a primary outcome of 90-day functional independence (modified Rankin Scale score, mRS ≤2). Favorable versus unfavorable BATMAN scores were analyzed as both continuous and categorical variables, and an adjusted multivariate regression model was applied. RESULTS: Among 221 BAO patients, thrombectomy significantly improved functional independence compared to medical management in patients with favorable BATMAN scores (aOR 7.75, 95% CI 2.78-26.1), but not in those with unfavorable BATMAN scores (aOR 1.33, 95% CI 0.28-6.92; pinteraction = 0.028). When treated as a continuous variable, increased BATMAN score was found to be associated with a higher likelihood of functional independence in the thrombectomy group (aOR 1.97, 95% CI 1.44-2.81; pinteraction = 0.053). In severe stroke patients with higher BATMAN scores (National Institutes of Health Stroke Scale (NIHSS) ≥21), we identified a significant interaction for treatment effect with thrombectomy compared to medical management (pinteraction = 0.042). CONCLUSION: An increased BATMAN score was significantly associated with a higher probability of functional independence after thrombectomy than after medical management, particularly in patients with severe BAO.

MiCOL6, MiCOL7A and MiCOL7B isolated from mango regulate flowering and stress response in transgenic Arabidopsis.

The CONSTANS/CONSTANS-Like (CO/COL) family has been shown to play important roles in flowering, stress tolerance, fruit development and ripening in higher plants. In this study, three COL genes, MiCOL6, MiCOL7A and MiCOL7B, which each contain only one CCT domain, were isolated from mango (Mangifera indica), and their functions were investigated. MiCOL7A and MiCOL7B were expressed mainly at 20 days after flowering (DAF), and all three genes were highly expressed during the flowering induction period. The expression levels of the three genes were affected by light conditions, but only MiCOL6 exhibited a clear circadian rhythm. Overexpression of MiCOL6 promoted earlier flowering, while overexpression of MiCOL7A or MiCOL7B delayed flowering compared to that in the control lines of Arabidopsis thaliana under long-day (LD) and short-day (SD) conditions. Overexpressing MiCOL6, MiCOL7A or MiCOL7B in transgenic plants increased superoxide dismutase (SOD) and proline levels, decreased malondialdehyde (MAD) levels, and improved survival under drought and salt stress. In addition, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses showed that the MiCOL6, MiCOL7A and MiCOL7B proteins interact with several stress- and flower-related proteins. This work demonstrates the functions of MiCOL6, MiCOL7A and MiCOL7B and provides a foundation for further research on the role of mango COL genes in flowering regulation and the abiotic stress response.

F-box proteins and gastric cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.

Gastric cancer (GC) is a prevalent malignancy characterized by significant morbidity and mortality, yet its underlying pathogenesis remains elusive. The etiology of GC is multifaceted, involving the activation of oncogenes and the inactivation of antioncogenes. The ubiquitin-proteasome system (UPS), responsible for protein degradation and the regulation of physiological and pathological processes, emerges as a pivotal player in GC development. Specifically, the F-box protein (FBP), an integral component of the SKP1-Cullin1-F-box protein (SCF) E3 ligase complex within the UPS, has garnered attention for its prominent role in carcinogenesis, tumor progression, and drug resistance. Dysregulation of several FBPs has recently been observed in GC, underscoring their significance in disease progression. This comprehensive review aims to elucidate the distinctive characteristics of FBPs involved in GC, encompassing their impact on cell proliferation, apoptosis, invasive metastasis, and chemoresistance. Furthermore, we delve into the emerging role of FBPs as downstream target proteins of non-coding RNAs(ncRNAs) in the regulation of gastric carcinogenesis, outlining the potential utility of FBPs as direct therapeutic targets or advanced therapies for GC.

Biomechanical evaluation of different medial column fixation patterns for valgus pilon fractures.

BACKGROUND: The purpose of this study was to perform a biomechanical analysis to compare different medial column fixation patterns for valgus pilon fractures in a case-based model. METHODS: Based on the fracture mapping, 48 valgus pilon fracture models were produced and assigned into four groups with different medial column fixation patterns: no fixation (NF), K-wires (KW), intramedullary screws (IS), and locking compression plate (LCP). Each group contained wedge-in and wedge-out subgroups. After fixing each specimen on the machine, gradually increased axial compressive loads were applied with a load speed of one millimeter per minute. The maximum peak force was set at 1500 N. Load-displacement curves were generated and the axial stiffness was calculated. Five different loads of 200 N, 400 N, 600 N, 800 N, 1000 N were selected for analysis. The specimen failure was defined as resultant loading displacement over 3 mm. RESULTS: For the wedge-out models, Group-IS showed less displacement (p < 0.001), higher axial stiffness (p < 0.01), and higher load to failure (p < 0.001) than Group-NF. Group-KW showed comparable displacement under loads of 200 N, 400 N and 600 N with both Group-IS and Group-LCP. For the wedge-in models, no statistical differences in displacement, axial stiffness, or load to failure were observed among the four groups. Overall, wedge-out models exhibited less axial stiffness than wedge-in models (all p < 0.01). CONCLUSIONS: Functional reduction with stable fixation of the medial column is essential for the biomechanical stability of valgus pilon fractures and medial column fixation provides the enough biomechanical stability for this kind of fracture in the combination of anterolateral fixation. In detail, the K-wires can provide a provisional stability at an early stage. Intramedullary screws are strong enough to provide the medial column stability as a definitive fixation. In future, this technique can be recommended for medial column fixation as a complement for holistic stability in high-energy valgus pilon fractures.

Locking Patterned Carbon Nanotube Cages by Nanofibrous Mats to Construct Cucurbituril[n]-Based Ultrapermselective Dye/Salt Separation Membranes.

Surface patterning is a promising strategy to overcome the trade-off effect of separation membranes. Herein, a bottom-up patterning strategy of locking micron-sized carbon nanotube cages (CNCs) onto a nanofibrous substrate is developed. The strongly enhanced capillary force triggered by the abundant narrow channels in CNCs endows the precisely patterned substrate with excellent wettability and antigravity water transport. Both are crucial for the preloading of cucurbit[n]uril (CB6)-embeded amine solution to form an ultrathin (∼20 nm) polyamide selective layer clinging to CNCs-patterned substrate. The CNCs-patterning and CB6 modification result in a 40.2% increased transmission area, a reduced thickness, and a lowered cross-linking degree of selective layer, leading to a high water permeability of 124.9 L·m-2 h-1 bar-1 and a rejection of 99.9% for Janus Green B (511.07 Da), an order of magnitude higher than that of commercial membranes. The new patterning strategy provides technical and theoretical guidance for designing next-generation dye/salt separation membranes.

Isolation of three MiDi19-4 genes from mango, the ectopic expression of which confers early flowering and enhances stress tolerance in transgenic Arabidopsis.

MAIN CONCLUSION: Three Di19-4 genes were identified in mango. Overexpression of MiDi19-4B in A. thaliana promoted earlier flowering and enhanced drought, salt, and ABA resistance. Drought-induced protein 19 (Di19) is a drought-induced protein that is mainly involved in multiple stress responses. Here, three Di19-4 genes (MiDi19-4A/B/C) in mango (Mangifera indica L.) were identified, and the coding sequences (CDS) had lengths of 684, 666, and 672 bp and encoded proteins with 228, 222, and 224 amino acids, respectively. The promoters of the MiDi19-4 genes contained phytohormone-, light-, and abiotic stress-responsive elements. The MiDi19-4 genes were expressed in every tissue and highly expressed in leaves. Moreover, MiDi19-4 genes were highly correlated with the vegetative growth period and induced by polyethylene glycol (PEG) or salt stress. MiDi19-4B displayed the highest expression during the vegetative growth period and then showed decreased expression, and MiDi19-4B was highly expressed at both the late stage of the vegetative growth period and the initial stage of the flowering induction period. The 35S::GFP-MiDi19-4B fusion protein was located in the cell nucleus. The transgenic plants ectopically expressing MiDi19-4B exhibited earlier flowering and increased expression patterns of FRUITFULL (AtFUL), APETALA1 (AtAP1), and FLOWERING LOCUS T (AtFT). The drought and salt tolerance of MiDi19-4B transgenic plants was significantly increased, and these plants showed decreased sensitivity to abscisic acid (ABA) and considerably increased expression levels of drought- and salt-related genes and ABA signalling pathway genes. Additionally, bimolecular fluorescence complementation (BiFC) experiments revealed that the MiDi19-4B protein interacted with CAULIFLOWER (MiCAL1), MiCAL2, MiAP1-1, and MiAP1-2. Taken together, these results highlighted the important regulatory roles of MiDi19-4B in tolerance to multiple abiotic stresses and in flowering.

Clinical outcomes and affecting factors of ipsilateral femoral neck and shaft fractures - Multination, multicenter analysis.

BACKGROUND: This study aimed to evaluate the clinical outcomes of ipsilateral femoral neck and shaft fractures and identify the risk factors associated with missed diagnosis of femoral neck fractures and clinical outcomes of this fracture. METHODS: The ipsilateral femoral neck and shaft fractures from seven centers were retrospectively reviewed. Data on injury mechanism, fracture pattern, and fracture classification; surgical factors including fixation method; and timing of detection of femoral neck fracture were analyzed. The clinical outcomes, complications, and the incidence of avascular necrosis of the femoral head (AVNFH) were reviewed. Risk factors for missed femoral neck fracture and complications were analyzed. RESULTS: In total, 74 patients with an average age of 43.6 years were included. Of the femoral shaft fractures, 56.8% were type A, 21.6% were type B, and 21.6% were type C. Sixteen patients had an open fracture of the femoral shaft. Femoral neck fracture was initially missed in 27% patients and the timing of delayed diagnosis was at an average of 11.1 days after injury. For detecting femoral neck fractures, minimal displacement of the femoral neck fracture was a risk factor, whereas computed tomography (CT) was a protective factor. The incidence of AVNFH was 6.8% at an average of 36.8 months after injury. The AVNFH group had more displaced femoral neck fractures at the time of surgery, but there was no difference in the timing of diagnosis compared to non-AVNFH group. The femoral shaft showed considerable healing problems, with an average union time of 29.7 weeks and a 20.2% nonunion rate. CONCLUSION: Ipsilateral femoral neck and shaft fractures had a high rate of missed diagnosis, especially in minimally displaced fractures; however, CT was a protective factor. AVNFH occurred in 6.8% and was related to femoral neck fracture displacement, but not delayed diagnosis. The femur nonunion rate was high, which warrants attention.

Technology development and cost analysis of multiple pollutant abatement for ultra-low emission coal-fired power plants in China.

The implementation of ultra-low emission (ULE) limits (SO2: 35 mg/m3, NOx: 50 mg/m3, PM: 10 mg/m3) promoted the development of flue gas treatment technologies in China. Pollutant control technology development for Chinese coal-fired power plants was summarized and an analysis of the applicability and cost of pollutant control technologies was conducted. Detailed data were collected from 30 ultra-low emission coal-fired units across China. Based on a cost analysis model, the average unit power generation incremental costs were 0.0144 and 0.0095 CNY/(kW·hr) for SO2 and NOx control technologies, respectively. The unit power generation incremental cost of twin spray tower technology was 7.2% higher than that of dual-loop spray tower technology. The effect of key parameters on operating cost was analyzed. The unit power generation incremental cost increased because of increments in the electricity price for SO2 control technology and the price of the reductant in NOx control technology. With high sulfur content or NOx concentration, the unit power generation incremental cost caused by pollutant control increased, whereas the unit pollutant abatement cost decreased. However, the annual operating hours or load increased, thereby leading to a decline in unit power generation incremental cost and unit pollutant abatement cost.

SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer.

BACKGROUND: Homologous recombination deficiency (HRD) is closely associated with patient prognosis and treatment options in prostate cancer (PCa). However, there is a lack of quantitative indicators related to HRD to predict the prognosis of PCa accurately. METHODS: We screened HRD-related genes based on the HRD scores and constructed an HRD cluster system to explore different clinicopathological, genomic, and immunogenomic patterns among the clusters. A risk signature, HRDscore, was established and evaluated by multivariate Cox regression analysis. We noticed that SLC26A4, a model gene, demonstrated unique potential to predict prognosis and HRD in PCa. Multi-omics analysis was conducted to explore its role in PCa, and the results were validated by qRT-PCR and immunohistochemistry. RESULTS: Three HRD clusters were identified with significant differences in patient prognosis, clinicopathological characteristics, biological pathways, immune infiltration characteristics, and regulation of immunomodulators. Further analyses revealed that the constructed HRDscore system was an independent prognostic factor of PCa patients with good stability. Finally, we identified a single gene, SLC26A4, which significantly correlated with prognosis in three independent cohorts. Importantly, SLC26A4 was confirmed to distinguish PCa (AUC for mRNA 0.845; AUC for immunohistochemistry score 0.769) and HRD (AUC for mRNA 0.911; AUC for immunohistochemistry score 0.689) at both RNA and protein levels in our cohort. CONCLUSION: This study introduces HRDscore to quantify the HRD pattern of individual PCa patients. Meanwhile, SLC26A4 is a novel biomarker and can reasonably predict the prognosis and HRD in PCa.

A chemical probe inhibitor targeting STAT1 restricts cancer stem cell traits and angiogenesis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a worldwide cancer with rising annual incidence. New medications for patients with CRC are still needed. Recently, fluorescent chemical probes have been developed for cancer imaging and therapy. Signal transducer and activator of transcription 1 (STAT1) has complex functions in tumorigenesis and its role in CRC still needs further investigation. METHODS: RNA sequencing datasets in the NCBI GEO repository were analyzed to investigate the expression of STAT1 in patients with CRC. Xenograft mouse models, tail vein injection mouse models, and azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were generated to study the roles of STAT1 in CRC. A ligand-based high-throughput virtual screening approach combined with SWEETLEAD chemical database analysis was used to discover new STAT1 inhibitors. A newly designed and synthesized fluorescently labeled 4',5,7-trihydroxyisoflavone (THIF) probe (BODIPY-THIF) elucidated the mechanistic actions of STAT1 and THIF in vitro and in vivo. Colonosphere formation assay and chick chorioallantoic membrane assay were used to evaluate stemness and angiogenesis, respectively. RESULTS: Upregulation of STAT1 was observed in patients with CRC and in mouse models of AOM/DSS-induced CRC and metastatic CRC. Knockout of STAT1 in CRC cells reduced tumor growth in vivo. We then combined a high-throughput virtual screening approach and analysis of the SWEETLEAD chemical database and found that THIF, a flavonoid abundant in soybeans, was a novel STAT1 inhibitor. THIF inhibited STAT1 phosphorylation and might bind to the STAT1 SH2 domain, leading to blockade of STAT1-STAT1 dimerization. The results of in vitro and in vivo binding studies of THIF and STAT1 were validated. The pharmacological treatment with BODIPY-THIF or ablation of STAT1 via a CRISPR/Cas9-based strategy abolished stemness and angiogenesis in CRC. Oral administration of BODIPY-THIF attenuated colitis symptoms and tumor growth in the mouse model of AOM/DSS-induced CRC. CONCLUSIONS: This study demonstrates that STAT1 plays an oncogenic role in CRC. BODIPY-THIF is a new chemical probe inhibitor of STAT1 that reduces stemness and angiogenesis in CRC. BODIPY-THIF can be a potential tool for CRC therapy as well as cancer cell imaging.

Photocatalytic Synthesis of Diarylmethyl Silanes via 1,6-Conjugate Addition of Silyl Radicals to p-Quinone Methides.

A novel photocatalytic method for the preparation of diarylmethyl silanes was reported through silyl radicals addition strategy to p-QMs (p-quinone methides). This protocol could tolerate a variety of functional groups affording the corresponding silylation products with moderate to excellent yields. The resulting silylation products could be easily converted into a series of bioactive GPR40 agonists and useful p-QMs precursors for the synthesis of compounds possessing both quaternary carbon centers and silicon substituents through simple operation. A plausible mechanism of silyl radicals to p-QMs was proposed on the basis of experimental results and previous literature.

Oxidant free synthesis of α-pyrones via an NHC-catalyzed [3 + 3] annulation of bromoenals with 2-chloro-1,3-diketones.

An NHC-catalyzed [3 + 3] annulation reaction between α-bromo enals and 2-chlorocyclohexane-1,3-diones was developed for the rapid and efficient synthesis of various 4,5,6-trisubstituted α-pyrones, which are core structures in numerous natural products and synthetic bioactive molecules, in generally good to excellent yields.

Influence of ionic liquids on the chain dynamics and enthalpy relaxation of poly(methyl methacrylate).

Imidazolium ionic liquids (ILs) with various alkyl chain lengths on the cations ([Cnmim]+, n = 2, 4 and 8) and different combined anions ([TFSI]- and [PF6]-) were blended with poly(methyl methacrylate) (PMMA), and the effects of the IL structure on the chain dynamics of PMMA were experimentally investigated by rheology and DSC measurements combined with a simulation method. The results indicate that the interaction between PMMA and ILs becomes stronger as the alkyl chain length on the imidazolium ring increases or the anion changes from [PF6]- to [TFSI]-. As a result, a higher critical entanglement concentration and a larger entanglement molecular weight of PMMA were found in [C8mim][TFSI] due to the stiffer conformation. Molecular dynamics (MD) simulations further demonstrated stronger interactions between PMMA and ILs with longer cationic alkyl chain lengths or [TFSI]- anions, which showed smaller Flory-Huggins interaction parameters and larger radii of gyration, Rg. However, the larger size of alkyl chains or [TFSI]- anions produced a larger free volume in the system as evidenced by positron annihilation lifetime spectroscopy (PALS), which competed with the molecular interaction and dominated the segmental motion. Therefore, a lower Tg and accelerated segmental relaxation were observed. Compared to alkyl chain length, the effect of anions on the interactions between ILs and PMMA is more prominent.