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Decarbonylative and dehydrogenative cascade annulation of aldehydes with N‐(o‐cyanobiaryl)acrylamides was developed for the synthesis of a broad spectrum of alkyl‐ and carbonyl‐substituted pyrido[4,3,2‐gh]phenanthridines. Secondary and tertiary aldehydes can undergo the decarbonylative cascade under DTBP/malonic acid conditions, while aryl, primary, and secondary aldehydes can undergo dehydrogenative reaction under TBHP system. Such transformations were triggered by alkyl and acyl radicals, and the annulations were accomplished through intramolecular additions of carbon‐centered radical to nitrile group and iminyl radical to aromatic ring. [ABSTRACT FROM AUTHOR]

Precise regulation of mitochondrial fusion and fission is essential for cellular activity and animal development. Imbalances between these processes can lead to fragmentation and loss of normal membrane potential in individual mitochondria. In this study, we show that MIRO‐1 is stochastically elevated in individual fragmented mitochondria and is required for maintaining mitochondrial membrane potential. We further observe a higher level of membrane potential in fragmented mitochondria in fzo‐1 mutants and wounded animals. Moreover, MIRO‐1 interacts with VDAC‐1, a crucial mitochondrial ion channel located in the outer mitochondrial membrane, and this interaction depends on the residues E473 of MIRO‐1 and K163 of VDAC‐1. The E473G point mutation disrupts their interaction, resulting in a reduction of the mitochondrial membrane potential. Our findings suggest that MIRO‐1 regulates membrane potential and maintains mitochondrial activity and animal health by interacting with VDAC‐1. This study provides insight into the mechanisms underlying the stochastic maintenance of membrane potential in fragmented mitochondria. Synopsis: MIRO‐1 interacts with VDAC‐1 to modulate its activity and regulate mitochondrial membrane potential in C. elegans, which provides mechanistic insight into the stochastic maintenance of activity in fragmented mitochondria. MIRO‐1 levels are elevated in individual fragmented mitochondria.MIRO‐1 is required for the maintenance of mitochondrial membrane potential.MIRO‐1 interacts with VDAC‐1 to regulate mitochondrial membrane potential.MIRO‐1 regulates VDAC‐1 activity via their direct interaction. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) are responsible for drug resistance, cancer relapse, and metastasis. Here, we report the first analysis of Palladin expression and its impacts on stem cell‐like properties in lung cancer. Methods: Tissue microarrays were used to investigate Palladin expression and its association with prognosis. Immunofluorescence (IF), flow fluorescence assay, and Western blot were performed to detect Palladin expression in 6 NSCLC cell lines. Cell phenotypes and drug resistance were evaluated. Xenograft models were constructed to confirm the role of Palladin in vivo. Results: By using the tissue microarrays, Palladin was identified to be highly expressed in the cytoplasm, specifically in the cytomembrane of NSCLC, and its high expression is associated with poor prognosis. Palladin is widely expressed and enriched in the sphere cells. The in vitro and in vivo studies showed that Palladin promoted stem cell‐like properties, including cell viability, invasion, migration, self‐renewal abilities, taxol resistance, and tumorigenicity. Western blot revealed that Palladin promoted the accumulation of β‐catenin and activated Wnt/β‐catenin signaling. Tissue microarrays analysis further confirmed the positive correlation between Palladin and β‐catenin. Wnt/β‐catenin pathway inhibitor blocked the Palladin‐induced enhancement of sphere‐forming. Conclusions: Palladin might act as an oncogene by promoting CSCs‐like properties and tumorigenicity of NSCLC cells via the Wnt/β‐catenin signaling pathway. Besides, Palladin was identified to have the potential as a cell surface marker for LCSCs identification. These findings provide a possible target for developing putative agents targeted to LCSCs. [ABSTRACT FROM AUTHOR]

The cage-ladder-structure phosphorus-containing amino-functionalized polyhedral oligomeric silsesquinoxanes (CLNH2-POSS) have been synthesized through a facile catalyst-free hydrolytic condensation of 9,10-dihydro-9-oxa10-phosphaphenanthrene-10-oxide-vinyltrimethoxysilane (DOPO-VTMS) with 3-aminopropyl trimethoxysilane (KH540). The successful preparation of CLNH2-POSS has been proven by the characterization of Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy (1 H-NMR, 29Si-NMR), matrix-assisted laser desorption ionization time of flight (MALDITOF), and X-ray diffraction (XRD). Then flame retardant (FR) epoxy resins (EPs) were prepared by the addition of different content of CLNH2-POSS into EPs with thermal curing technology. The CLNH2-POSS showed good solubility in EP matrix. The well-dispersed CLNH2-POSS contributed to thermal, mechanical, and FR properties of EP. Dynamic scanning calorimetry nonisothermal curing scans showed that CLNH2-POSS had accelerating effect on the curing of EP. With the addition of only 3 wt% CLNH2-POSS (0.30% phosphorus loading), the limiting oxygen index value of the EP composite increased from 25.5 of pure EP to 31.8, and vertical burning (UL-94) V-0 ratings was achieved. In addition, the EP composites showed improved thermal and mechanical properties. The investigations on char residue and pyrolysis volatiles of cured EP further revealed that CLNH2-POSS exerted FR effects in condensed and gas phase simultaneously. [ABSTRACT FROM AUTHOR]

Summary: Background: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large‐scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. Objectives: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. Methods: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. Results: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. Conclusion: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. [ABSTRACT FROM AUTHOR]

Background and Purpose: Our previous studies revealed that hypidone hydrochloride (YL-0919), which acts as a selective 5-HT (serotonin) reuptake inhibitor (SSRI) and displays partial 5-HT1A receptor agonist properties, exerts a significant antidepressant effect in various animal models. The aim of present research was to further investigate the pharmacology of YL-0919.Experimental Approach: We first investigated the target profile of YL-0919 using [35 S]-GTPγS binding and microdialysis. To determine whether the 5-HT or noradrenergic systems are involved in the antidepressant-like effect of YL-0919, the 5-hydroxytryptophan (5-HTP)-induced head-twitch test and antagonism with a high dose of apomorphine were performed. Using the learned helplessness paradigm, the novelty suppressed feeding test, the Vogel-type conflict and elevated plus-maze test, we further verified the antidepressant-like and anxiolytic-like effects of YL-0919. The effects of YL-0919 on hippocampal long-term potentiation (LTP) and sexual behaviour were also evaluated.Key Results: Data from the present study demonstrated that YL-0919 displays partial 5-HT1A receptor agonist properties, producing a greater impact on extracellular 5-HT levels than a conventional SSRI (fluoxetine), as well as significant antidepressant and anxiolytic effects. Furthermore, YL-0919 treatment rapidly influenced the synaptic plasticity (enhancing LTP) of rats. Finally, at doses close to those producing antidepressant-like effects, YL-0919 did not result in a marked inhibition of sexual function.Conclusions and Implications: These data suggest that YL-0919 is probably a fast-onset potent antidepressant with few side effects. [ABSTRACT FROM AUTHOR]

Objective: The incidence and mortality rate of lung cancer ranks first among all malignant tumors. Lymph node metastasis is the most common mode of metastasis in lung cancer, and it is also an important indicator for treatment strategies and prognosis. Several studies have shown that the carboxypeptidase family plays important roles in cancer metastasis. In the present study, we investigated the effect of carboxypeptidase A4 (CPA4) on human lung cancer cells, and the clinical significance of its levels in lung cancer tissues and corresponding lymph node metastasis tissues. Methods: Real‐time quantitative polymerase chain reaction and western blotting were used to detect the expression levels of CPA4 in cancer cells after transfecting them with CPA4 interference sequence (siRNA‐CPA4) and the negative control sequence. Transwell assay with/without Matrigel was used to assess the effect of CPA4 on cell invasion and migration. CPA4 expression was detected in eight normal lung tissues, 46 lung cancer tissues, and the corresponding lymph node metastasis tissues using immunohistochemistry. Results: Reverse transcription polymerase chain reaction and western blot showed that siRNA‐CPA4 significantly decreased CPA4 mRNA levels in H226 and SKMES‐1 cells compared with the control cells. Knockdown of CPA4 in lung cancer cells significantly inhibited cell invasion by 62.3% and 77.3% in H226 and SKMES‐1 cell, respectively. Furthermore, siRNA‐CPA4 significantly suppressed cell migration in H226 and SKMES‐1 cells by 48.1% and 42.4%, respectively. Immunohistochemistry results showed that the positive expression rate of CPA4 in lung normal tissues, cancer tissues, and lymph node metastatic tissues was 12.5% (1/8), 50.0% (23/46), and 76.1% (35/46), respectively. Importantly, the levels of CPA4 in the lymph node metastatic tissues were significantly higher than those in corresponding primary lung cancer tissues (t = 5.176, P < 0.001). The clinical correlation analysis showed that high levels of CPA4 were closely associated with the tumor pathology type, differentiation, and stage; however, there was no significant correlation with the age, sex, and depth of invasion. Conclusions: CPA4 promoted the invasion and migration of human lung cancer cells, H226, and SKMES‐1, in vitro. The levels of CPA4 were gradually elevated in primary lung cancer and corresponding lymph node metastasis tissues, and CPA4 could be a potential candidate therapeutic target for lung cancer. [ABSTRACT FROM AUTHOR]

We describe a 28-year-old man with linear atrophoderma of Moulin ( LAM), whose serum immunological markers were abnormal (including antinuclear antibody, ribonucleoprotein, immunoglobulin M and anti- SM antibody). In addition, however, a histological analysis identified unexpected connective tissue disease changes in this patient. We speculate that the pathogenesis of LAM is associated with immunity or that LAM itself is a kind of connective tissue disease. [ABSTRACT FROM AUTHOR]

The ethanolic extract (E) of propolis was further fractionated with supercritical CO2 into four fractions (R, F1, F2 and F3). The extracts and the four fractions were characterised in terms of antioxidant and hepatoprotective activity against tert-butyl hydroperoxide (t-BHP)-induced damage in vitro and in a rat model. The in vitro study revealed that pre-treatment with propolis extract or its fractions significantly protected the primary hepatocytes against damage by t-BHP ( P < 0.05). The hepatoprotective capacity increased with the dose of propolis. The R and F1 fractions had the highest flavinoid contents and most effectively protected the liver from damage by t-BHP. This study also demonstrated that the oral pre-treatment with propolis (50 and 100 mg kg−1) 5 days before a single dose of t-BHP (1.5 mm kg−1, s.c. injection) was administered significantly kept the serum levels of hepatic enzyme markers (aspirate aminotransferase and alanine aminotransferase) low, even after treatment with t-BHP ( P < 0.05). A pathological examination showed that lesions of liver were partially protected by treatment with propolis extract and fractions. Oxidative stress induced by t-BHP led to lipid peroxidation (malondialdehyde) and changes in the levels of the antioxidant enzymes. However, all the fractions, except F3 at low concentration (50 mg kg−1), markedly suppressed lipid peroxidation and any increase in the activity of antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Sampling techniques with centimeter-scale spatial resolution were applied to investigate biogeochemical processes controlling groundwater arsenic fate across the groundwater--surface water interface at a site characterized by fine sediments (40% sand, 46% silt, 14% clay). Freeze-core sediment collection gave more detailed and depth-accurate arsenic and iron contaminant and microbial distributions than could be obtained with the use of a hand auger. Selective chemical extractions indicated that greater than 90% of the arsenic was strongly sorbed to very amorphous iron oxyhydroxides. These solids accounted for more than 80% of the total iron in the sediments. Microbial enrichments indicated that iron-oxidizing bacteria (IOB) were up to 1% of the total bacterial abundance, whereas iron-reducing bacteria (IRB) were about two orders of magnitude less abundant than IOB. The abundance of IRB mirrored the IOB depth profile. Push-point pore-water sampling captured large amounts of sediment fines, even with controlled (20 ml/min) water withdrawal, thereby necessitating filtration before water quality analysis. Bead columns containing glass media enabled short-term (29 d) characterization of pore water-to-sediment transfer of arsenic and iron. Bead columns indicated quantitative capture of groundwater arsenic and iron during 2003, suggesting that freeze-core inventories corresponded to 2 to 20 years of accumulation, depending on location. [ABSTRACT FROM AUTHOR]

Summary: When the implicit, conservative difference scheme with the fractional centered difference formula is employed to discretize the space fractional coupled nonlinear Schrödinger equations, in each time step, we need to solve a complex symmetric linear system. The real part of the coefficient matrix is a symmetric Toeplitz‐plus‐diagonal matrix, whereas the imaginary part is the identity matrix. In this paper, a structure preserving preconditioner and a circulant preconditioner are proposed for such Toeplitz‐like matrix. Theoretically, tight bounds for eigenvalues of the preconditioned matrices are derived. Numerical implementations show that Krylov subspace iteration methods such as BiCGSTAB, when accelerated by the proposed preconditioners, are efficient solvers for solving the discretized linear system. [ABSTRACT FROM AUTHOR]

The article describes a case of a 16-month-old boy who was diagnosed with infantile onychomycosis and treated with amorolfine nail lacquer.