Design and simulation of light field patterns for angular color variation reduction in micro-LED and mini-LED RGB arrays.

We propose a methodology to mitigate angular color variation in full-color micron-scale LED arrays. By simulating light field distribution for red (AlGaAs) and green/blue (GaN) light across various RGB micro-LED sizes, we can select matching light field patterns for RGB chips, reducing angular color variation from 0.0201 to 0.0030. Applying this method to full-color mini-LED assemblies achieves a reduction from 0.0128 to 0.0032 by matching light field patterns with varying substrate thicknesses. This straightforward approach aligns with current mass transfer processes, offering practical implementation.

Utility of Ultrasound Elastography to Evaluate Poststroke Spasticity and Therapeutic Efficacy: A Narrative Review.

Poststroke spasticity (PSS) is a common complication that affects function and daily self-care. Conservative PSS treatments include traditional rehabilitation, botulinum toxin injection, and extracorporeal shock wave therapy. Currently, the Modified Ashworth Scale and Modified Tardieu Scale are widely used tools to clinically evaluate spasticity, but the best tool for PSS assessment remained controversial. Ultrasound elastography (UE), including shear wave and strain image as the emerging method to evaluate soft tissue elasticity, became popular in clinical applications. Spastic biceps and gastrocnemius muscles were reported to be significantly stiffer compared to nonparetic muscles or healthy control using shear wave or strain elastography. More studies investigated the utility, reliability, and validity of UE in patients with PSS, but the contemporary consensus for the utility of UE in the measurement and therapeutic follow-up of PSS remained lacking. Therefore, this narrative review aimed to appraise the literature on the shear wave and strain elastography on PSS and summarize the roles of UE in assessing the therapeutic efficacy of different PSS interventions.

Temporalis and masseter muscle thickness as predictors of post-stroke dysphagia after endovascular thrombectomy.

PURPOSE: Post-stroke dysphagia (PSD) is a common sequela of stroke. Given the association between dysphagia and sarcopenia, we aimed to investigate the association between PSD and temporal muscle thickness (TMT) and masseter muscle thickness (MMT) following endovascular thrombectomy (EVT) in patients with large-vessel occlusion (LVO). METHODS: This retrospective cohort study included hospitalized patients with LVO stroke who underwent EVT between January 1, 2018, and October 31, 2022. TMT and MMT were measured using brain computed tomography (CT) angiography. The correlation between relevant clinicodemographic factors and both TMT and MMT was examined. The relationship between each of two parameters (TMT and MMT) and PSD, which was defined as the retention of the nasogastric (NG) tube at 4 and 12 weeks, was evaluated in adjusted logistic regression models. RESULTS: Among the 148 participants, the mean TMT and MMT was 5.9 ± 1.6 and 11.2 ± 2.3 mm, respectively. Lower age, male sex, higher body mass index (BMI), higher albumin levels, and a lower initial National Institute of Health Stroke Scale (NIHSS) score were associated with higher TMT and MMT (p < 0.05). In the logistic regression analysis adjusted for age, sex, BMI, serum albumin, and NIHSS score, lower TMT and MMT significantly correlated with PSD at weeks 4 and 12 (p < 0.001). CONCLUSION: TMT and MMT are associated with age, sex, BMI, albumin, and the initial NIHSS score. Both TMT and MMT are independent indicators of post-EVT PSD in stroke patients and serve as reliable predictors of NG removal.

Nicotine-induced miR-21-3p promotes chemoresistance in lung cancer by negatively regulating FOXO3a.

Lung cancer is the leading cause of cancer-related mortality worldwide and cigarette smoking is reported to contribute to the lung cancer-related mortality. The present study aimed to investigate the molecular mechanism underlying nicotine-induced chemoresistance in lung cancer. The expression of microRNA (miR)-21-3p and its predicted target FOXO3a in lung cancer cells was detected via reverse transcription-quantitative PCR, in the presence or absence of nicotine. The regulatory effect of miR-21-3p and FOXO3a on lung cancer cell proliferation and apoptosis induced by docetaxel or cisplatin treatment was evaluated by performing Cell Counting Kit-8 and Annexin V/PI staining assays, respectively. The interaction between miR-21-3p and FOXO3a was analyzed by performing luciferase reporter assays and western blotting. FOXO3a overexpression rescue experiments were conducted in vitro and in vivo using a xenograft mouse model to assess the function of miR-21-3p/FOXO3a in lung cancer. Nicotine induced miR-21-3p expression in lung cancer cells in a dose-dependent manner. miR-21-3p downregulated FOXO3a expression by directly binding to the 3'-untranslated region of FOXO3a. Moreover, miR-21-3p knockdown sensitized lung cancer cells to docetaxel or cisplatin treatment. Mechanistically, FOXO3a was predicted as a direct target of miR-21-3p. FOXO3a overexpression promoted the chemosensitivity of lung cancer cells to docetaxel or cisplatin treatment. Furthermore, FOXO3a overexpression antagonized the regulatory function of miR-21-3p on docetaxel- or cisplatin-treated lung cancer cells. In the docetaxel- or cisplatin-treated lung cancer xenograft mouse model, miR-21-3p promoted chemoresistance via negatively regulating FOXO3a. Therefore, the present study demonstrated that nicotine-induced miR-21-3p promoted chemoresistance to docetaxel or cisplatin treatment via negatively regulating FOXO3a, which may serve as a novel therapeutic strategy for the treatment of patients with chemoresistant lung cancer.

Network meta-analysis and trial sequential analysis for atrial fibrillation patients receiving PCI or with ACS.

BACKGROUND: In patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), choosing the most appropriate antithrombotic treatment remains a dilemma. We aimed to compare the relative efficacy and safety outcomes of antithrombotic drugs in patients with AF after undergoing PCI or ACS. METHODS: Randomized controlled trials were systematically searched on PubMed, EMBASE, and the Cochrane Library. Five studies (11,532 patients) were included in the network meta-analysis. Trial sequential analysis (TSA) was performed to assess the reliability and conclusiveness of the meta-analysis comparing the dual antithrombotic therapy strategies with the triple antithrombotic therapy strategy. RESULTS: Compared with vitamin K antagonist + dual antiplatelet therapy, novel oral anticoagulant (NOAC) + P2Y12 inhibitor was associated with a significantly better trial-defined primary safety outcome (odds ratio: 0.53; 95% CI, 0.31-0.90) and the lowest probability of thrombolysis in myocardial infarction major bleeding and intracranial hemorrhage using the cumulative ranking technique. In patients omitting aspirin, TSA demonstrated conclusive evidence with significant decreases in all safety outcomes and inconclusive evidence with a nonsignificant increase in in-stent thrombosis (risk ratio: 1.32; TSA-adjusted 95% CI, 0.54-3.24) and myocardial infarction (risk ratio: 1.19; TSA-adjusted 95% CI, 0.84-1.68). CONCLUSIONS: In patients with AF receiving PCI or with ACS, NOAC + P2Y12 inhibitor was associated with the lowest bleeding risk but resulted in a statistically nonsignificant, numerically greater risk for stent thrombosis and myocardial infarction, suggesting that triple antithrombotic therapy should still be an option for certain patients at a high risk of stent thrombosis or myocardial infarction.

D-bifunctional protein deficiency caused by HSD17B4 gene mutation in a neonate. / HSD17B4åŸºå› çªå˜è‡´D-双功能蛋白缺乏症.

A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the HSD17B4 gene. This article reports a case of D-bifunctional protein deficiency caused by HSD17B4 gene mutation and summarizes the epidemiological and clinical features, diagnosis, and treatment of this disease, with a focus on the differential diagnosis of this disease from Ohtahara syndrome.

Increased risk of sensorineural hearing loss in patients with spinal cord injury: a nationwide longitudinal follow-up study.

STUDY DESIGN: Retrospective cohort study with 10 years follow-up. OBJECTIVE: To compare the risks of sensorineural hearing loss in patients with and without spinal cord injury, based on a nationally representative sample. SETTING: Taiwan's Longitudinal Health Insurance Database 2005. METHOD: A total of 2006 participants who had been aged between 20 and 69 and who had spinal cord injury as of 2002-06 were enrolled in the spinal cord injury group. The non-spinal cord injury group consisted of 8024 sex- and age-matched, randomly sampled participants without spinal cord injury. Then, their sensorineural hearing loss -cumulative incidence curves were generated using the Kaplan-Meier method. Stratified Cox proportional-hazard regression was employed to estimate the effect of having spinal cord injury on patients' subsequent risk of sensorineural hearing loss. RESULTS: During the follow-up, 30 patients in the spinal cord injury group and 87 in the non-spinal cord injury group developed sensorineural hearing loss. As such, the cumulative incidence of sensorineural hearing loss was significantly higher in the spinal cord injury group than the non-spinal cord injury group (2.16 vs. 1.21 per 1000 person-years, p = 0.008). The adjusted hazard ratio of sensorineural hearing loss for the spinal cord injury group was 1.75 times that of the non-spinal cord injury group (95% CI, 1.14-2.68, p = 0.01). The patients with non-cervical SCI appeared to have a higher magnitude of SNHL risk than their cervical SCI counterparts. CONCLUSION: Our study showed that patients with spinal cord injury have an increased risk of developing sensorineural hearing loss.

A single low-energy shockwave pulse opens blood-cerebrospinal fluid barriers and facilitates gastrodin delivery to alleviate epilepsy.

The blood-cerebrospinal fluid barrier (BCSFB) is another gatekeeper between systemic circulation and the central nervous system (CNS), mainly present at the boundary between choroid plexuses and the ventricular system. This study demonstrates BCSFB opening in rats by single pulse of low-energy focused shockwave (FSW, energy flux density 0.03 mJ/mm2, 2 × 106 microbubbles/kg) treatment at lateral ventricle, resulting in significantly elevated cerebrospinal fluid (CSF) concentrations of systemically-administered gastrodin (GTD) (4 times vs. control within 3 hrs) that remained detectable for 24 hrs. The FSW-GTD group had significantly lower Racine's scale (<4) and zero mortality (n = 30) after lithium-pilocarpine-induced epilepsy. Electrophysiological recordings showed decreased epileptiform discharges, and brain section histology revealed reduced inflammation, oxidative stress and apoptosis, when compared with groups without FSW (Racine's scale: 4 ∼ 5; mortality: 26.67 ∼ 36.67%). FSW-mediated BCSFB opening provides a promising alternative for controlled-delivery of therapeutics into the CNS, offering rapid and widespread medication distribution. The technique could by applied in the development of novel therapies for various CNS diseases.

STIM1 mediates IAV-induced inflammation of lung epithelial cells by regulating NLRP3 and inflammasome activation via targeting miR-223.

AIMS: Influenza A virus (IAV) infection accelerates the inflammatory injury of lung epithelial cells that contributes to pulmonary lesion. Recently, stromal interaction molecule 1 (STIM1) was found to mediate cellular immune response and participated in lung tumorigenesis. Our study aimed to illustrate the function and mechanism of STIM1 in IAV-induced inflammation injury and oxidative stress of lung epithelial cells. MAIN METHODS: We evaluated the levels of STIM1 in IAV-infected patients' serum and BEAS-2B cells using RT-qPCR, Elisa and western blotting methods. MTT and Elisa were performed to measure cell viability and cytokine contents. Besides, ROS intensity, SOD contents and cell apoptosis were detected based on DCFH-DA probe, colorimetry and cell death kits. A luciferase assay and Pearson's correlation analysis evaluated the associations between target genes. KEY FINDINGS: STIM1 was dramatically up-regulated in IAV-infected patients' serum and BEAS-2B cells. Silencing STIM1 in vitro inhibited oxidative stress and inflammatory responses induced by IAV, and reversed cell viability and suppressed apoptosis. Moreover, miR-223 and NLRP3 were negatively and positively correlated with STIM1. STIM1 was found to regulate NLRP3 expression by binding the AACUGAC motif in miR-223. STIM1/miR-223/NLRP3 axis modulated IAV-induced inflammation injury of lung epithelial cells. SIGNIFICANCE: Our evidence indicated that silencing STIM1 alleviated IAV-induced inflammation injury of lung epithelial cells by inactivating NLRP3 and inflammasome via promoting miR-223 expression. These findings may contribute to understand the mechanism of IAV-induced lung injury and help for therapy of IAV infection.

Exploration of multi-target effects of 3-benzoyl-5-hydroxychromen-2-one in Alzheimer's disease cell and mouse models.

Microtubule-associated protein Tau, abundant in the central nervous system (CNS), plays crucial roles in microtubule assembly and stabilization. Abnormal Tau phosphorylation and aggregation are a common pathogenic hallmark in Alzheimer's disease (AD). Hyperphosphorylation of Tau could change its conformation and result in self-aggregation, increased oxidative stress, and neuronal death. In this study, we examined the potential of licochalcone A (a natural chalcone) and five synthetic derivatives (LM compounds) for inhibiting Tau misfolding, scavenging reactive oxygen species (ROS) and providing neuroprotection in human cells expressing proaggregant ΔK280 TauRD -DsRed. All test compounds were soluble up to 100 µM in cell culture media and predicted to be orally bioavailable and CNS-active. Among them, licochalcone A and LM-031 markedly reduced Tau misfolding and associated ROS, promoted neurite outgrowth, and inhibited caspase 3 activity in ΔK280 TauRD -DsRed 293 and SH-SY5Y cells. Mechanistic studies showed that LM-031 upregulates HSPB1 chaperone, NRF2/NQO1/GCLC pathway, and CREB-dependent BDNF/AKT/ERK/BCL2 pathway in ΔK280 TauRD -DsRed SH-SY5Y cells. Decreased neurite outgrowth upon induction of ΔK280 TauRD -DsRed was rescued by LM-031, which was counteracted by knockdown of NRF2 or CREB. LM-031 further rescued the downregulated NRF2 and pCREB, reduced Aß and Tau levels in hippocampus and cortex, and ameliorated cognitive deficits in streptozocin-induced hyperglycemic 3 × Tg-AD mice. Our findings strongly indicate the potential of LM-031 for modifying AD progression by targeting HSPB1 to reduce Tau misfolding and activating NRF2 and CREB pathways to suppress apoptosis and promote neuron survival, thereby offering a new drug development avenue for AD treatment.

A Predictive Model Towards Site-Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl⋠LiCl.

The development of a predictive model towards site-selective deprotometalation reactions using TMPZnCl⋅LiCl is reported (TMP=2,2,6,6-tetramethylpiperidinyl). The pKa values of functionalized N-, S-, and O-heterocycles, arenes, alkenes, or alkanes were calculated and compared to the experimental deprotonation sites. Large overlap (>80 %) between the calculated and empirical deprotonation sites was observed, showing that thermodynamic factors strongly govern the metalation regioselectivity. In the case of olefins, calculated frozen state energies of the deprotonated substrates allowed a more accurate prediction. Additionally, various new N-heterocycles were analyzed and the metalation regioselectivities rationalized using the predictive model.

New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models.

Spinocerebellar ataxia type 17 (SCA17) is caused by a CAG/CAA expansion mutation encoding an expanded polyglutamine (polyQ) tract in TATA-box binding protein (TBP), a general transcription initiation factor. Suppression of cAMP-responsive element binding protein- (CREB-) dependent transcription, impaired nuclear factor erythroid 2-related factor 2 (NRF2) signaling, and interaction of AMP-activated protein kinase (AMPK) with increased oxidative stress have been implicated to be involved in pathogenic mechanisms of polyQ-mediated diseases. In this study, we demonstrated decreased pCREB and NRF2 and activated AMPK contributing to neurotoxicity in SCA17 SH-SY5Y cells. We also showed that licochalcone A and the related in-house derivative compound 3-benzoyl-5-hydroxy-2H-chromen-2-one (LM-031) exhibited antiaggregation, antioxidative, antiapoptosis, and neuroprotective effects in TBP/Q79-GFP-expressing cell models. LM-031 and licochalcone A exerted neuroprotective effects by upregulating pCREB and its downstream genes, BCL2 and GADD45B, and enhancing NRF2. Furthermore, LM-031, but not licochalcone A, reduced activated AMPKα. Knockdown of CREB and NRF2 and treatment of AICAR (5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside), an AMPK activator, attenuated the aggregation-inhibiting and neurite outgrowth promoting effects of LM-031 on TBP/Q79 SH-SY5Y cells. The study results suggest the LM-031 as potential therapeutics for SCA17 and probable other polyQ diseases.

Conservative Treatment of Tendon Injuries.

Tendon injuries or tendinopathy is a common painful and disabling conditions resulting from overuse and aging. Tendinopathy remains a challenging clinical problem because response to different treatment modalities is usually unsatisfactory and recovery is slow. We performed an extensive literature review focusing on nonsurgical treatment options for tendinopathies, including nonsteroidal anti-inflammatory drugs, corticosteroid, eccentric exercise, extracorporeal shock wave therapy, therapeutic ultrasound, hyaluronic acid, platelet-rich plasma, prolotherapy, polydeoxyribonucleotide, and stem cells, aimed at providing the most updated evidence as a guideline for caregivers.

Angular color variation in micron-scale light-emitting diode arrays.

A simulation scheme was developed to explore the light distribution of full-color micron-scale light-emitting diode (LED) arrays. The influences of substrate thickness, patterning, and cutting angle of the substrate on several important features, such as light field pattern, light extraction efficiency, and color variation, were evaluated numerically. An experiment was conducted; the results were consistent with simulation results for a 225 × 125 µm2 miniLED and those for an 80 × 80 µm2 microLED. Based on the simulation results, the light extraction efficiency of LED devices with a substrate increases by 67.75% over the extraction efficiency of those without a substrate. The light extraction efficiency of LED devices with a substrate increases by 113.55% when an additional patterned design is used on green and blue chips. The calculated large angle Δu'v' can be as low as 0.015 for miniLED devices.

Guiding Hypertension Management Using Different Blood Pressure Monitoring Strategies (GYMNs study): comparison of three different blood pressure measurement methods: study protocol for a randomized controlled trial.

BACKGROUND: Home blood pressure (BP) and unattended automated BP (uAOBP) monitoring have been recommended by guidelines for the care of hypertensive subjects. However, BP measurements in the peripheral arteries cannot serve as direct substitutes for their central counterparts. Moreover, the comparative effectiveness and safety of BP-guided strategies using these BP measuring devices have never been evaluated. METHODS/DESIGN: Patients with uncontrolled or newly diagnosed hypertension aged 20-90 years will be recruited via outpatient clinics and allocated into three arms by stratified randomization (baseline systolic BP 130-155 mmHg and 155-180 mmHg): home BP, uAOBP, and central BP-guided treatment. At each scheduled visit to the clinic, a patient's BP will be measured by each of the three methods of measuring BP. The blood pressure from three different methods will be confirmed available at each visit. Patients and physicians will be blinded to the allocated interventions because they will use measured BP values in the clinic through a standardized report format. A common BP target for systolic blood pressure (SBP) of 130 mmHg is adopted for these BP-guided strategies. The primary outcome is the change of 24-h mean ambulatory SBP at 3 months. A key secondary outcome is to determine the percentage achieving their target BPs at 3 months and the decrease of left ventricular mass at 12 months. DISCUSSION: To our knowledge, this is the first prospective double-blind randomized controlled trial to assess the optimal guiding strategy for hypertension. It will help to define which BP monitoring method is the most effective for guiding the clinical management of hypertension. It will provide good evidence to support future guideline recommendations for BP monitoring devices. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03578848 . Registered on 4 June 2018.

A vinylogous Michael addition-triggered quadruple cascade reaction for the enantioselective generation of multiple quaternary stereocenters.

An efficient organocatalytic quadruple cascade reaction resulting in spiroxindole scaffolds bearing five quaternary stereocenters is reported. The complex cascade reaction is triggered by the scarcely explored vinylogous Michael addition of 3-alkylidene oxindoles to fully substituted enones and demonstrates the usefulness of the latter as efficient Michael acceptors in generating complex caged products in 26-92% yields, 14-98% ee and up to >25 : 1 d.r. values.

Diagnostic value of medical thoracoscopy for undiagnosed pleural effusions.

To investigate the diagnostic value of medical thoracoscopy for the diagnosis of undiagnosed pleural effusions, a retrospective study was performed on the clinical data of 86 patients with undiagnosed pleural effusions who had medical thoracoscopy at Shaanxi Provincial People's Hospital (Xi'an, China) between May 2012 and November 2013. Of the 86 patients, 79 cases of pleural effusions were confirmed by medical thoracoscopic biopsy with a diagnosis rate of 91.9%. In these 79 confirmed patients, 37 had pleura cancer metastasis (43.0%) and 20 had tuberculous pleuritis (23.3%). The most common type of malignant tumor was lung cancer, accounting for 86.5% of the patients with pleural metastasis. Tuberculosis was often observed in the 16-35 years of age patient group, while malignant tumors were typically detected in the 36-65 year and 65 years and above patient groups. Notably, the overall diagnosis distribution had little connection with sex or smoking-history. Neither mortality nor major complications were observed in patients who received medical thoracoscopy examination. In conclusion, medical thoracoscopy is a safe and effective examination method and has an important diagnostic value for unidentified pleural effusion in patients.

Adiponectin gene polymorphisms and obesity increase the susceptibility to arsenic-related renal cell carcinoma.

Our recent study found that high urinary total arsenic levels were associated with renal cell carcinoma (RCC). Recent studies demonstrated that low circulating adiponectin was related to RCC. The aim of the present study was to explore the relationship between adiponectin gene (ADIPOQ) polymorphisms and RCC and investigate whether individuals with an ADIPOQ risk genotype, obesity, and high urinary total arsenic levels have a modified odds ratio (OR) of RCC. A total of 389 RCC patients and 389 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Image-guided biopsy or surgical resection of renal tumors was performed to pathologically verify RCC. Genomic DNA was used to examine the genotypes of the ADIPOQ rs182052, ADIPOQ rs2241766, ADIPOQ rs1501299, and ADIPOQ rs1063539 SNPs by PCR-RFLP. HPLC-HG-AAS was used to measure the concentrations of urinary arsenic species. Participants with the ADIPOQ rs182052 G/A+A/A genotype had a significantly higher OR of RCC compared with those with the ADIPOQ rs182052 G/G genotype. The OR (95% confidence interval [CI]) was 1.70 (1.23-2.36). The OR of RCC for the combined effect of high urinary total arsenic levels and obesity, which was dose-dependent, in individuals with the ADIPOQ rs182052 G/A+A/A genotype was 9.33 (3.85-22.62). The present study found significant combined effects of obesity and the ADIPOQ rs182052 G/A+A/A genotype on the arsenic-related risk of RCC in a population with low arsenic exposure. Arsenic exposure, obesity, and the ADIPOQ rs182052 polymorphism could be predictors of a higher OR of RCC.

Novel synthetic chalcone-coumarin hybrid for Aß aggregation reduction, antioxidation, and neuroprotection.

BACKGROUND: Aggregation of misfolded amyloid ß (Aß) in senile plaques causes oxidative stress and neuronal death in Alzheimer's disease (AD). Compounds possessing antiaggregation and antioxidant properties are promising candidate compounds for AD treatment. METHODS: We examined the potential of synthetic derivatives of licochalcone A and coumarin for inhibiting Aß aggregation, scavenging reactive oxygen species (ROS), and providing neuroprotection by using biochemical assays and Tet-On Aß-GFP 293/SH-SY5Y cell models for AD. RESULTS: Among test compounds, LM-031, a novel chalcone-coumarin hybrid, inhibited Aß aggregation and scavenged free oxygen radicals. LM-031 markedly reduced Aß misfolding and ROS as well as promoted neurite outgrowth and inhibited acetylcholinesterase in Tet-On Aß-GFP 293/SH-SY5Y cells. Mechanistic studies showed upregulation of the HSPB1 chaperone, NRF2/NQO1/GCLC pathway, and CREB/BDNF/BCL2 pathway. Decreased neurite outgrowth upon the induction of Aß-GFP was rescued by LM-031, which was counteracted by knockdown of HSPB1, NRF2, or CREB. CONCLUSION: Taken together, these findings demonstrate that LM-031 exhibited antiaggregation, antioxidant, and neuroprotective effects against Aß toxicity by enhancing HSPB1 and the NRF2-related antioxidant pathway as well as by activating the CREB-dependent survival and antiapoptosis pathway. These results imply that LM-031 may be a new therapeutic compound for AD.

Diversity-Oriented Synthesis of Furo[3,2-c]coumarins and Benzofuranyl Chromenones through Chemoselective Acylation/Wittig Reaction.

A highly efficient and chemoselective one-pot protocol for the diversity-oriented synthesis of two types of coumarin-based formal cross-coupling adducts, furo[3,2-c]coumarins and 3-benzofuranyl chromenones, is described. Key attributes of the methodology are an initial chemoselective acylation of functionalized phosphorus zwitterions and a subsequent chemoselective intramolecular Wittig reaction that preferentially resulted in one of the two coumarin derivatives in high yield, depending on relative reactivities and the addition sequence of the acylating agents.