Iridium-catalyzed asymmetric cascade dearomative allylation/acyl transfer rearrangement: access to chiral N-substituted 2-pyridones.

Iridium-catalyzed dearomative allylation/acyl transfer rearrangement has been developed using easily available 2-pyridinyl benzoates and vinyl ethylene carbonate. This protocol enabled the expedient synthesis of a variety of chiral N-substituted 2-pyridones in good to high yields with excellent enantioselectivity. It has the advantages of high atom economy, wide substrate scope, gram-scale synthesis, and versatile synthetic transformations.

Incremental value of amyloid PET in a tertiary memory clinic setting in China.

INTRODUCTION: The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aß-PET) in a tertiary memory clinic setting in China. METHODS: A total of 1073 patients were offered Aß-PET using 18F-florbetapir. The neurologists determined a suspected etiology (Alzheimer's disease [AD] or non-AD) with a percentage estimate of their confidence and medication prescription both before and after receiving the Aß-PET results. RESULTS: After disclosure of the Aß-PET results, etiological diagnoses changed in 19.3% of patients, and diagnostic confidence increased from 69.3% to 85.6%. Amyloid PET results led to a change of treatment plan in 36.5% of patients. Compared to the late-onset group, the early-onset group had a more frequent change in diagnoses and a higher increase in diagnostic confidence. DISCUSSION: Aß-PET has significant impacts on the changes of diagnoses and management in Chinese population. Early-onset cases are more likely to benefit from Aß-PET than late-onset cases. HIGHLIGHTS: Amyloid PET contributes to diagnostic changes and its confidence in Chinese patients. Amyloid PET leads to a change of treatment plans in Chinese patients. Early-onset cases are more likely to benefit from amyloid PET than late-onset cases.

An Investigation of the Effects of B7-H4 Gene rs10754339 and miR-125a Gene rs12976445 on Cancer Susceptibility.

Objective: To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis. Methods: A total of 1,490 cancer patients (lung/gastric/liver/: 550/460/480) and 800 controls were recruited in this case-control study. The meta-analysis was performed by pooling the data from previous related studies and the present study. Results: The results of this study showed that in the Hubei Han Chinese population, the rs10754339 gene was significantly associated with the risk of lung and gastric cancer but not liver cancer, and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer. The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339 and breast cancer risk, as well as between rs12976445 and lung cancer risk. Conclusion: The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population, which should be validated in future studies with larger sample sizes in other ethnic populations.

Effects of osthole on osteoporotic rats: a systematic review and meta-analysis.

CONTEXT: Cnidium monnieri Cusson (Apiaceae) has been used in traditional Asian medicine for thousands of years. Recent studies showed its active compound, osthole, had a good effect on osteoporosis. But there was no comprehensive analysis. OBJECTIVE: This meta-analysis evaluates the effects of osthole on osteoporotic rats and provides a basis for future clinical studies. METHODS: Chinese and English language databases (e.g., PubMed, Web of Science, Cochrane Library, Google Scholar, Embase, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, Weipu Chinese Sci-tech periodical full-text database, and Chinese BioMedical Literature Database) were searched from their establishment to February 2021. The effects of osthole on bone mineral density, osteoclast proliferation, and bone metabolism markers were compared with the effects of control treatments. RESULTS: To our knowledge, this is the first meta-analysis to evaluate osthole for the treatment of osteoporosis in rats. We included 13 randomized controlled studies conducted on osteoporotic rats. Osthole increased bone mineral density (standardized mean difference [SMD] = 3.08, 95% confidence interval [CI] = 2.08-4.09), the subgroup analysis showed that BMD significantly increased among rats in osthole <10 mg/kg/day and duration of osthole treatment >2 months. Osthole improved histomorphometric parameters and biomechanical parameters, also inhibited osteoclast proliferation and bone metabolism. CONCLUSIONS: Osthole is an effective treatment for osteoporosis. It can promote bone formation and inhibit bone absorption.

Photothermal Thin Films with Highly Efficient NIR Conversion for Miniaturized Liquid-Crystal Elastomer Actuators.

This work presents the development of highly efficient photothermal thin films (PTFs) and the demonstration of their application on miniaturized polymer-based soft actuators. The proposed PTF, which comprises acrylic-based black paint and EGaIn liquid metal (LM) microdroplets, serves as an excellent absorber for efficiently converting near-infrared (NIR) irradiation into heat for actuating liquid-crystal elastomer (LCE) actuators. The introduction of LM microdroplets into the PTFs effectively increases the overall thermal efficiency of PTFs. Miniaturized soft crawlers monolithically integrated with the NIR-driven LCE actuators are also implemented for demonstrating the application of the proposed PTF. The crawler's locomotion, which is inspired by the rectilinear movement of snakes, is generated with the proposed PTF for inducing the LC-to-isotropic phase transition of the LCEs. The experimental results show that introducing LM microdroplets into the PTF can effectively reduce the thermal time constants of LCE actuators by 70%. Under periodic on/off NIR illumination cycles, the locomotion of crawlers with different dimensions is also demonstrated. The measurement results indicate that the proposed PTF is not only essential for enabling photothermal LCE actuation but also quite efficient and durable for repeated operation.

Cryptococcal antigen testing of lung tissue homogenate improves pulmonary cryptococcosis diagnosis: Two case reports.

BACKGROUND: Pulmonary cryptococcosis (PC) is an opportunistic infectious disease of the respiratory system. Lung tissue biopsies, culture of respiratory samples (e.g., sputum, lung tissue, pleural fluid, and bronchoalveolar lavage fluid), and cryptococcal antigen (CrAg) testing are helpful for a definitive diagnosis. However, these tests are sometimes falsely negative. PC is often misdiagnosed or underdiagnosed owing to the absence of obvert symptoms, poor imaging specificity, and false-negative laboratory tests. CASE SUMMARY: We report two female patients who underwent computed tomography-guided percutaneous needle pulmonary biopsy of a lung nodule for a confirmed diagnosis. In both patients, the CrAg test on the lung biopsy tissue homogenate was positive, while the serum CrAg test was negative. Combined with the lung tissue pathology, we made the diagnosis of PC. Antifungal therapy was effective in both patients. CONCLUSION: Given the findings of our cases and the literature review, lung tissue homogenate CrAg testing can be helpful in improving the diagnosis of PC.

Stereodivergent Construction of 1,4-Nonadjacent Stereocenters via Hydroalkylation of Racemic Allylic Alcohols Enabled by Copper/Ruthenium Relay Catalysis.

An unprecedented hydroalkylation of racemic allylic alcohols and racemic ketimine esters enabled by Cu/Ru relay catalysis has been developed via merging the ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with a copper-catalyzed asymmetric Michael addition in a one-pot procedure. The current method enables the efficient preparation of highly functionalized δ-hydroxyesters bearing 1,4-nonadjacent stereocenters in good yields with high levels of diastereoselectivity and excellent enantioselectivity under mild reaction conditions. The full complement of the four stereoisomers of hydroalkylation products could be readily accessed by orthogonal permutations of two chiral metal catalysts. The current work highlights the power of relay catalysis for the stereodivergent construction of 1,4-nonadjacent stereocenters that were otherwise inaccessible.

Pulmonary Cladosporium infection coexisting with subcutaneous Corynespora cassiicola infection in a patient: A case report.

BACKGROUND: Cladosporium and Corynespora cassiicola (C. cassiicola) infections rarely occur in humans. Mutations in human caspase recruitment domain protein 9 (CARD9) are reported to be associated with fungal diseases. Pulmonary Cladosporium infection coexisting with subcutaneous C. cassiicola infection in a patient with a CARD9 mutation has not been reported in the literature. CASE SUMMARY: A 68-year-old male patient was hospitalized for hypertrophic erythema and deep ulcers on the left upper extremity. He was diagnosed with pneumonia caused by Cladosporium, as identified through bronchoalveolar lavage fluid analysis, and deep dermatophytosis caused by C. cassiicola, as identified through morphological characteristics of the wound secretion culture. He underwent antifungal therapy (voriconazole) and recovered successfully. He carried two mutations in CARD9 (chr9:139266425 and chr9:139262240) and was therefore susceptible to fungal infections. CONCLUSION: This case study is the first to report the coexistence of pulmonary Cladosporium infection and subcutaneous C. cassiicola infection in a patient with CARD9 mutation. Our findings will be helpful in enriching the phenotypic spectrum of fungal infections underlying CARD9 deficiency.

Unprecedented diterpenoid dimers with soluble epoxide hydrolase inhibitory effect from Euphorbia fischeriana.

Biseuphoids A (1) and B (2), two unprecedented ent-abietane-type diterpenoid dimers linked by monomeric blocks through C-17-C-12' and C-17-C-11', respectively, were isolated from Euphorbia fischeriana, along with their biogenesis related diterpenoid monomers, 17-hydroxyjolkinolide B (3), caudicifolin (4), and fischeriabietane C (5). Their structures were elucidated by extensive spectroscopy assisted by quantum chemical NMR and ECD calculations. The unusual dimeric skeletons are possibly derived from the adduct of diterpenoid monomers through Michael-like reactions. The novel dimers 1 and 2 exhibited inhibitory activities on soluble epoxide hydrolase (sEH) with IC50 values of 8.17 and 5.61 µM, respectively. Molecular dynamics studies illustrated that both 1 and 2 can occupy the catalytic pocket of sEH by forming stable hydrogen bonds with the key amino acid residues including Gln384, Asn378, Pro361, Ala365, Asn366, and Asn472.

Cytotoxic diterpenoid dimer containing an intricately caged core from Euphorbia fischeriana.

Bislangduoids A and B, a novel class of dimeric diterpenoids based on ent-abietanes tethered by C-17-C-15' bridge, were identified as trace components from a traditional Chinese medicine Euphorbia fischeriana (Langdu). Bislangduoid A features a highly oxidized scaffold incorporating a cage-like pentacyclic core. Their structures were elucidated by extensive spectroscopic techniques, electronic circular dichroism, and NMR calculations. The biosynthetic pathway for the dimeric skeleton and the unique caged moiety via Michael and acetal-formation reactions was proposed. Bislangduoid A showed pronounced cytotoxicity against HepG2 cells through the mitochondria-dependent apoptosis pathway.

Value of eosinophil count in bronchoalveolar lavage fluid for diagnosis of allergic bronchopulmonary aspergillosis: A case report.

BACKGROUND: An immediate hypersensitive immune response to Aspergillus fumigatus antigens is one of the main characteristic features of allergic bronchopulmonary aspergillosis (ABPA). As ABPA is an allergic respiratory disease, immunoglobulin E and peripheral-blood eosinophilia have been used as diagnostic indicators. However, eosinophilia in bronchoalveolar lavage fluid (BALF) has not been considered in the diagnostic criteria for ABPA. CASE SUMMARY: We present a case of ABPA in which the eosinophil count in peripheral blood was not increased, whereas the eosinophil percentage in BALF reached 60%. After antifungal and hormone therapy, imaging revealed very good resolution of lung infiltration. CONCLUSION: The value of the eosinophil count in BALF for the diagnosis of ABPA is worthy of the clinician's attention, especially when the patient's clinical features lack specificity and the diagnostic parameters are negative.

Serum Metabolomic Indicates Potential Biomarkers and Metabolic Pathways of Pediatric Kashin-Beck Disease.

OBJECTIVE: To explore potential serum biomarkers of children with Kashin-Beck Disease (KBD) and the metabolic pathways to which the biomarkers belong. METHODS: A two-stage metabolomic study was employed. The discovery cohort included 56 patients, 51 internal controls, and 50 external controls. The metabolites were determined by HPLC-(Q-TOF)-MS and confirmed by Human Metabolome Databases (HMDB) and Metlin databases. MetaboAnalyst 3.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to analyze the metabolic pathways of the candidate metabolites. The use of HPLC-(Q-TRAP)-MS enabled quantitative detection of the target metabolites which were chosen using the discovery study and verified in another independent verification cohort of 31 patients, 41 internal controls, and 50 external controls. RESULTS: Eight candidate metabolites were identified out in the discovery study, namely kynurenic acid, N-α-acetylarginine, 6-hydroxymelatonin, sphinganine, ceramide, sphingosine-1P, spermidine, and glycine. These metabolites exist in sphingolipid, glutathione, and tryptophan metabolic pathways. In the second-stage study, five candidate metabolites were validated, including kynurenic acid, N-α-acetylarginine, sphinganine, spermidine, and sphingosine-1P. Except for spermidine, all substances exhibited low expression in the case group compared with the external control group, and the difference in levels of sphinganine, spermidine, and sphingosine-1P was statistically significant. CONCLUSION: The direction of change of levels of sphinganine, spermidine, and sphingosine-1P in the two-stage study cohorts was completely consistent, and the differences were statistically significant. Therefore, these substances can be used as potential biomarkers of KBD. Furthermore, these results raise the possibility that sphingolipid metabolic pathways may be closely related to KBD.

Asymmetric Synthesis of Nabscessin A from Inositol and d-Camphor.

An enantiomer of nabscessin A (1), an aminocyclitol amide with antimicrobial activity, was synthesized from myo-inositol and dimethyl d-camphor acetal in 14 steps. Formal synthesis of natural nabscessin A was also achieved through the new approach to access both enantiomers of 4,5-di-O-benzyl-myo-inositol, derived from the same set of starting materials. This synthesis features utilizations of the existing framework of myo-inositol and a regioselective esterification.

[The Integration and Regulation of Hormone-Sensitive Lipase in Reproductive System].

Hormone-sensitive lipase (HSL) has long been considered as a classical rate-limiting enzyme during lipolysis since it was first described in 1960s. HSL is regulated mainly by catecholamine, including adrenalin. Studies in recent years indicated that the substrates for HSL are not only triglycerides, but also diacylglycerol with the catalytic activity is ten times that of triglycerides, glycerol esters and cholesterol esters, which overthrow the opinion that HSL is specific to triglyceride. The scientists have generated HSL gene knockout mice and confirmed HSL is widely located in the reproductive system, which indicates that HSL may play an important role in the regulation of physiological and pathophysiological process in the reproductive system. Here, we will focus on the features of the HSL gene, mRNA and its protein, and summarize the HSL functions in the reproductive system.

Antioxidant activities of extracts and metabolites isolated from the fungus Antrodia cinnamomea.

Three different solvent partitions (n-hexane, ethyl acetate [EtOAc] and n-BuOH) of the culture broth from Antrodia cinnamomea were assayed with two different radical scavenging methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and superoxide radical scavenging (SOD) assay. The EtOAc layer exhibited the best antioxidant activity. Two major antioxidant metabolites were isolated from the active EtOAc layer. The antioxidant activities of compounds 1-6 were further evaluated by DPPH, SOD and trolox equivalent antioxidant capacity (TEAC) assays. Compounds 3 and 5 showed stronger free radical scavenging than the reference BHA, ED50 = 1.36 and 34.24 µM. Compound 5 displayed moderate SOD activity (ED50 = 310.0 µM), and its antioxidant capacity of TEAC value was 2.2 mM trolox equivalency.

Identification of the mokH gene encoding transcription factor for the upregulation of monacolin K biosynthesis in Monascus pilosus.

Monacolin K is a secondary metabolite synthesized by polyketide synthases (PKS) from Monascus. The monacolin K biosynthetic gene cluster, mokA-mokI, has been characterized in Monascus pilosus. The mokH gene encoding Zn(II)2Cys6 binuclear DNA binding protein is assumed to be an activator for monacolin K production. In this study, the mokH gene was cloned and driven by the glyceraldehyde-3-phosphate dehydrogenase (gpd) promoter for overexpression in M. pilosus. The transformants containing an extra copy of the mokH gene were obtained and verified by PCR and Southern hybridization. The transcripts of mokH in the transformants were expressed significantly higher than those of the wild-type strain. The transformants were stably inherited through the next generation, as determined by observation of the enhanced green fluorescent protein (EGFP). The transformant T-mokH1 also showed a 1.7-fold higher production of monacolin K than the wild-type strain in a time course analysis. Analysis of the RT-PCR products demonstrated that the monacolin K biosynthetic genes in the transformant were expressed to a greater extent than those in the wild-type strain. These results indicated that mokH upregulated the transcription of monacolin K biosynthetic genes and increased monacolin K production.