Ag-Catalyzed Selective C-C Bond Activation of Cyclopropenones to Access α-Alkylidene Lactones.

A novel Ag-catalyzed ring opening of unsymmetric cyclopropenones for the stereoselective synthesis of a diverse range of α-alkylidene lactones has been developed. In this protocol, two different C-C(O) bonds were distinguished, demonstrating selective C-C bond activation. This reaction features a wide substrate scope, good functional group compatibility, and high atom economy, providing a versatile and general approach to the construction of α-alkylidene lactones.

Accurate diagnosis of severe coronary stenosis based on resting magnetocardiography: a prospective, single-center, cross-sectional analysis.

OBJECTIVE: To evaluate the role of resting magnetocardiography in identifying severe coronary artery stenosis in patients with suspected coronary artery disease. METHODS: A total of 513 patients with angina symptoms were included and divided into two groups based on the extent of coronary artery disease determined by angiography: the non-severe coronary stenosis group (< 70% stenosis) and the severe coronary stenosis group (≥ 70% stenosis). The diagnostic model was constructed using magnetic field map (MFM) parameters, either individually or in combination with clinical indicators. The performance of the models was evaluated using receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Calibration plots and decision curve analysis were performed to investigate the clinical utility and performance of the models, respectively. RESULTS: In the severe coronary stenosis group, QR_MCTDd, S_MDp, and TT_MAC50 were significantly higher than those in the non-severe coronary stenosis group (10.46 ± 10.66 vs. 5.11 ± 6.07, P < 0.001; 7.2 ± 8.64 vs. 4.68 ± 6.95, P = 0.003; 0.32 ± 57.29 vs. 0.26 ± 57.29, P < 0.001). While, QR_MVamp, R_MA, and T_MA in the severe coronary stenosis group were lower (0.23 ± 0.16 vs. 0.28 ± 0.16, P < 0.001; 55.06 ± 48.68 vs. 59.24 ± 53.01, P < 0.001; 51.67 ± 39.32 vs. 60.45 ± 51.33, P < 0.001). Seven MFM parameters were integrated into the model, resulting in an area under the curve of 0.810 (95% CI: 0.765-0.855). The sensitivity, specificity, PPV, NPV, and accuracy were 71.7%, 80.4%, 93.3%, 42.8%, and 73.5%; respectively. The combined model exhibited an area under the curve of 0.845 (95% CI: 0.798-0.892). The sensitivity, specificity, PPV, NPV, and accuracy were 84.3%, 73.8%, 92.6%, 54.6%, and 82.1%; respectively. Calibration curves demonstrated excellent agreement between the nomogram prediction and actual observation. The decision curve analysis showed that the combined model provided greater net benefit compared to the magnetocardiography model. CONCLUSIONS: The novel quantitative MFM parameters, whether used individually or in combination with clinical indicators, have been shown to effectively predict the risk of severe coronary stenosis in patients presenting with angina-like symptoms. Magnetocardiography, an emerging non-invasive diagnostic tool, warrants further exploration for its potential in diagnosing coronary heart disease.

Pd-Catalyzed Three-Component Coupling of Cyclopropenones via Sequential C-C Bond Activation and Allylation.

A novel Pd-catalyzed three-component domino reaction for the stereoselective synthesis of highly functionalized allyl cinnamates has been developed. In this protocol, a sequential process of C-C bond activation and intermolecular allylic substitution was well-organized. The key for this transformation is the in situ generated hydrolysis product of cyclopropenone, which triggered a new reaction with vinylethylene carbonates. The reaction mechanism was investigated, demonstrating the high stereoselectivity and excellent atomic economy in this process.

Effects of microcystin on protein profile in hepatopancreas of Litopenaeus vannamei.

For intensive aquaculture in freshwater ponds, microcystin (MC-LR) generated from cyanobacterial blooms is one of the bottlenecks for the healthy and sustainable development of shrimp aquaculture industry. In this study, we measured the MC-LR content in the hepatopancreas and muscles of Litopenaeus vannamei stressed by MC-LR, and analyzed protein expression in the hepatopancreas using DIA high-throughput proteomics technology. The results showed that MC-LR content in the hepatopancreas and muscles reached the highest at 1 h after MC-LR injection, which was (6.12±0.45) µg·kg-1 and (5.00±0.19) µg·kg-1, respectively. Then, it decreased gra-dually, with that in the hepatopancreas being significantly higher than in muscles. We identified 820 differential expressed proteins, including 586 up-regulated and 234 down-regulated ones. Results of bioinformatics analysis showed that MC-LR stress significantly affected immune-related pathways such as lysosome, RIG-Ⅰ receptor signals and interleukin-2. It also altered energy metabolisms including citrate cycle, metabolism of starch and sucrose, and interconversion of pentose and glucoronate, which in turn led to the disorder of carbohydrate metabolism. In addition, MC-LR significantly upregulated 19 cytoskeleton-related blood shadow proteins and damaged the hepatopancreas cytoskeleton. It was concluded that MC-LR mainly affected the physiological processes associated with immunity, energy metabolism, and cytoskeleton in the hepatopancreas of L. vannamei.

Identification of plasma SAA2 as a candidate biomarker for the detection and surveillance of non-small cell lung cancer.

This study aimed to measure the expression of SAA2 in plasma and to assess its diagnostic efficacy as a biomarker for non-small cell lung cancer (NSCLC). The gene expression of SAA2 in NSCLC was analyzed based on a database. Then, SAA2 expression was detected by immunohistochemistry in lung tissue and by enzyme-linked immunosorbent assay in 90 patients with NSCLC and 61 normal controls. Finally, the diagnostic performance was assessed in terms of accuracy, sensitivity, and specificity. At the gene and protein levels, the SAA2 expression was significantly higher in the NSCLC group than in the control group (p<0.01). It was higher in lung squamous carcinoma than in lung adenocarcinoma and in males than in females, and this trend was also observed in the lung squamous carcinoma group. Of note, the expression of SAA2 increased with increasing disease stage. Receiver operating characteristic (ROC) curve analysis revealed that the sensitivity of SAA2 was 83.61%, the specificity was 91.11%, and the area under the curve (AUC) was 0.9252. Its accuracy was 68.89%, which was higher than that of other conventional diagnostic biomarkers, and the combined application can effectively improve the diagnostic efficiency. Based on the results, SAA2 expression was positively correlated with the disease stage of NSCLC. Notably, SAA2 is more concerning in male patients with lung squamous carcinoma, and it can help in the screening and diagnosis of NSCLC. SAA2 may represent a novel diagnostic biomarker in NSCLC.

A Rapid and Accurate Detection Approach for Multidrug-Resistant Tuberculosis Based on PCR-ELISA Microplate Hybridization Assay.

Rapid and accurate diagnosis of multidrug-resistant tuberculosis (MDR-TB) is important for timely and appropriate therapy. In this study, a rapid and easy-to-perform molecular test that integrated polymerase chain reaction (PCR) amplification and a specific 96-well microplate hybridization assay, called PCR-ELISA (enzyme-linked immunosorbent assay), were developed for detection of mutations in rpoB, katG, and inhA genes responsible for rifampin (RIF) and isoniazid (INH) resistance and prediction of drug susceptibility in Mycobacterium tuberculosis clinical isolates. We evaluated the utility of this method by using 32 multidrug-resistent (MDR) isolates and 22 susceptible isolates; subsequently, we compared the results with data obtained by conventional drug susceptibility testing and DNA sequencing. The sensitivity and specificity of the PCR-ELISA test were 93.7% and 100% for detecting RIF resistance, and 87.5% and 100% for detecting INH resistance, respectively. These results were comparable to those yielded by commercially available molecular tests such as the GenoType MTBDRplus assay. Based on the aforementioned results, we conclude that the PCR-ELISA microplate hybridization assay is a rapid, inexpensive, convenient, and reliable test that will be useful for rapid diagnosis of MDR-TB, for improved clinical care.

Solution and rheological properties of cationic cellulose/gemini surfactant: Effect of the alkyl chain and spacer length.

In this paper, three sulfonate-containing gemini surfactants, sodium 1,1'-(4,4'-methylenebis(4,1-phenylene))bis(1-oxooctane-2-sulfonate) (C8-M1-C8), sodium 1,1'-(4,4'-(ethane-1,2-diyl)bis(4,1-phenylene))bis(1-oxooctane-2-sulfonate) (C8-M2-C8), sodium 1,1'-(4,4'-methylenebis(4,1-phenylene))-bis(1-oxododecane-2-sulfonate) (C12-M2-C12), were synthesized and characterized with FT-IR, 1H NMR and MS. Furthermore, interaction between a cationic cellulose-based polyelectrolyte, PQ-10, and gemini surfactants were investigated by surface tension, turbidity, flow and low-amplitude oscillation rheology analysis. For comparing, the interaction of their corresponding monomeric counterpart sodium dodecyl sulfate (SDS), sodium 1-octanesulfate (SOS) was also studied. Results showed that the concentration value at T1, defined as critical surface complex concentration, for the PQ-10/surfactant was in order of PQ-10/C8-M2-C8> PQ-10/C8-M1-C8 > PQ-10/C12-M2-C12. Precipitation appeared at low concentration for Gemini surfactants than their monomeric counterparts, and for the gemini surfactants with shorter spacer or longer hydrocarbon chain. The increase/decrease of the crossover frequency (ωc) (the relaxation time, τc) for PQ-10/C12-M2-C12 indicated the formation/collapse of network structures, while PQ-10/SDS showed no obvious change.

Pharmacologic ascorbate as a pro-drug for hydrogen peroxide release to kill mycobacteria.

BACKGROUND AND PURPOSE: Tuberculosis is one of the most highly fatal diseases worldwide, and one-third of the world's population has been infected with Mycobacterium tuberculosis (M. tuberculosis). A previous study showed that M. tuberculosis was highly susceptible to being killed by ascorbate (i.e. vitamin C, VC), but the molecular mechanisms of the bactericidal activity of VC against M. tuberculosis are still not well understood. EXPERIMENTAL APPROACH: We assayed the effects of VC as an anti-tuberculosis drug against mycobacteria (i.e. M. bovis BCG or M. tuberculosis H37Rv) in macrophages (i.e. RAW 264.7 cells). Relative global protein expression changes in 5 mM VC-treated and control samples of H37Rv were investigated by Tandem mass tag (TMT)-based quantitative proteomic analysis. qRT-PCR was also used to measure the differential expression of six intracellular stress response mycobacteria genes. KEY RESULTS: Quantitative proteomic analysis showed that 11 peptide components including rip3, fdxA, Rv2028c, mtp, LH57_00670, hspX, pfkB, Rv1824, Rv1813c, LH57_08410 and Rv2030c were up-regulated and 17 peptide components were down-regulated in 5 mM VC-treated H37Rv compared with the control samples. qRT-PCR also verified that VC could induce the expression of six genes (hsp, fdxD, furA, devR, hspX, and dnaB) in BCG and H37Rv. We also found that exosomes from RAW 264.7 cells treated with pharmacologic VC could kill M. bovis BCG in vitro. CONCLUSION AND IMPLICATIONS: Our results demonstrated that the bactericidal activity of VC against mycobacteria, as a pro-drug for hydrogen peroxide formation (H2O2), was dependent on reactive oxygen species production and the activated oxidative stress pathway, which suggested that pharmaceutical VC and exosomes from macrophages treated with VC could be used as potential anti-tuberculosis drugs.

Direct generation of vortex beams from a double-end polarized pumped Yb:KYW laser.

Double-end polarized pumping scheme combined with off-axis pumping technique has been first introduced to generate vortex beams in a z-type cavity. By employing double-end pumping, two different transverse modes can be excited simultaneously. The phase delay between these two modes can be finely tuned by manipulating the cavity structure. Direct emission of a chirality controllable Laguerre Gaussian LG01 vortex beam with slope efficiency of more than 40% has been realized by a double-end polarized pumped Yb:KYW laser. Other modes, such as dual-LG01 mode, cross-shaped mode, and LG10 mode, have also been demonstrated from our laser setup.

Generation of wavelength- and OAM-tunable vortex beam at low threshold.

Wavelength- and OAM- tunable laser with large tunable range is the key source for the application in large capacity optical communications. In this paper, we demonstrate a wavelength- and OAM-tunable vortex laser in a 1.2 W single mode fiber coupled LD pumped Yb:phosphate laser. A z-type cavity has been used to precisely control the laser mode diameter. A thin film polarizer (TFP) is inserted to finely control the intra-cavity loss and tune the wavelength. Corresponding laser fundamental mode to pump beam ratio has been optimized to decrease the pump threshold for high order HG mode running. A pair of cylindrical lenses has been used to convert the HG mode to vortex output. The vortex beam with OAM-tunable range from 1h to 14 h with wavelength tuning range of ~36.2 nm for LG0,1 vortex beam, and ~14.5 nm for LG0,14 vortex beam at pump power of only 1.2 W have been realized, which is the largest tuning range of both OAM and wavelength at ~1 W pump power range to the best of our knowledge.

[Chemical constitutes from Clerodendrum japonicum].

The chemical constituents from the ethanol extract of Clerodendrum japonicum were isolated by a combination of various chromatographic techniques including column chromatography over silica gel, sephadex LH-20, ODS and reversed phase HPLC. Sixteen compounds with a pair of epimers were elucidated through the application of physicochemical properties with modern spectral analysis technology as 7α-hydroxy syringaresinol (1), (-)-syringaresinol (2), (-)-medioresinol (3), 2″,3″-O-acetylmartyonside (4), 2″-O-acetyl-martyonside (5), martinoside (6), monoacetyl martinoside (7)，cytochalasin O (8), 9-epi-blumenol B (9), (6R, 9S) and (6R,9R)-9-hydroxy-4-megastigmen-3-one (10a，10b), (6R,9S)-3-oxo-α-ionol (11), (-)-dehydrovomifoliol (12)，megastigm-5-en-3,9-diol (13), (3R,6E,10S)-2,6,10-trimethyl-3-hydroxydodeca-6,11-diene-2,10-diol (14), (2R)-butylitaconic acid (15), 3-(3&-hydroxybutyl)-2,4,4-trimethylcyclohexa-2,5-dienone (16), (-)-loliolide (17), of which compound 1 and 15 are new natural product, the other compounds were isolated for the first time from Clerodendrum japonicum except for compounds 4, 6 and 7.

Oleanane-type triterpenoid saponins from Lysimachia fortunei Maxim.

Six previously undescribed oleanane-type triterpenoid saponins, fortunosides A-F, together with six known ones, were isolated from the aerial parts of Lysimachia fortunei Maxim. Their structures were established by spectroscopic data analyses (1D, 2D-NMR and HRESIMS) and chemical methods. All isolated triterpenoid saponins were evaluated for their cytotoxicity against four human liver cancer cell lines (SMMC-7721, Hep3B, HuH7, and SK-Hep-1). Three saponins with the aglycone protoprimulagenin A exhibited moderate cytotoxicity against all of the tested human cancer cell lines, with IC50 values ranging from 4.76 to 15.12 µM.

Displacement and acoustic vibration sensor based on gold nanobipyramids doped PDMS micro-fiber.

We propose and demonstrate a novel flexible and elastic vibration-displacement fiber sensor with a doped polydimethylsiloxane (PDMS) micro-fiber based on model interference. High resolution three-dimensional displacement measurement is achieved through monitoring the output pattern and variation of power. The sensor with a length of about 200 µm reveals frequency range from 50 Hz to 14 kHz, covering all the human voice frequency, with greatly enhanced high signal to noise ratio (SNR) reaching up to 66 dB. This work suggests a simple structure, small size and low cost fiber-based convenient way to achieve a multifunctional sensing applications including human motion detection.

[Effect of SRT on Stability of Yeast-SBR in Treating Oil-containing Wastewater].

Sludge retention time(SRT) is a crucial parameter to influence the stability of biological wastewater treatment systems. Especially, the effects of SRT on yeast-wastewater treatment remain unclear. In this study, mixtures of yeast strains were applied to treat oil-containing wastewater in sequencing batch reactors(SBR) and the effects of sludge retention time(SRT as 5, 10, 20, 40 d) on the removal efficiency of pollutants, contents and composition of extracellular polymeric substances(EPS), yeast cells settleability and yeast communities were investigated. The results showed that the recommended SRT was 5-10 d for the yeast-SBR system; Higher SRT led to decrease of COD removal rate and content of EPS; the tightly-bounded EPS was the major one which consisted of polysaccharides. SRT of 5-40 d had no significant effects on the SVI of yeast cells, however, longer SRT (>20 d) resulted in the increase of mycelial cells and a tendency to produce the filamentous bulking. In the continuous operation of SBR, three extraneous yeast strains capable of utilizing or degrading oil were identified in the systems under the short and long SRT. To conclude, shorter SRT was favorable for the system stability in treating oil-containing wastewater by yeasts.

[Dioxin Pollution and Occupational Inhalation Exposure of PCDD/Fs in Municipal Solid Waste Incinerator].

To assess the pollution levels, characteristics, and the pollution sources and occupational inhalation exposure of polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs)in the workshops,ambient air samples in different types of incinerators of two municipal solid waste incinerators(MSWI) were collected and analyzed. The results showed that ① The I-TEQ concentration ranged from 0.034-2.152 pg·m-3in the two waste incineration plants, and the most sites' I-TEQ exceeded the ambient air quality standard. Besides, the I-TEQ concentration behind the incineration plant was higher than others. ② The dioxins in incineration plant were dominated by OCDD and 1,2,3,4,6,7,8-HpCDD. For MSWI A, the flue gas and the fly ash had major effect on PCDD/Fs, while the dioxins pollution in MSWI B was only affected by the fly ash. ③ Occupational inhalation exposure of PCDD/Fs was 0.01-1.10 pg·(kg·d)-1 in incineration plant, some occupational inhalation exposure values exceeded the evaluation standard, and the areas behind the incinerators were evaluated to have a high exposure risk.

In silico identification of cytotoxic T lymphocyte epitopes encoded by RD5 region of Mycobacterium tuberculosis.

INTRODUCTION: While CD8+ T cells (cytotoxic T lymphocytes, CTLs) play important roles in immunity against Mycobacterium tuberculosis, only a small number of human leukocyte differentiation antigen (HLA) class I-restricted CTL epitopes for TB have been identified. The current study evaluates CTL epitopes of Rv3117 and Rv3120 proteins, two newly found M. tuberculosis region-diffference-5 (RD5)-encoded antigens, and their population coverage. METHODOLOGY: The amino acid sequences of the two proteins were subjected to epitope analysis under HLA-A2, A3 and B7 supertype restriction using NetCTL, SYFPEITHI, BIMAS, NetCTLPan, IEDB, NetMHC and NetMHCPan prediction online servers. RESULTS: Eight RD5-encoded CTL epitopes were identified in the two proteins and the average population coverage of these epitopes was 87.2% among populations worldwide. CONCLUSION: These CTL epitopes that were identified in silico and may have potential use for CD8+ T cell-mediated TB vaccine design.

Identification and characterization of non-tuberculous mycobacteria isolated from tuberculosis suspects in Southern-central China.

The incidence of non-tuberculous mycobacteria (NTM)-related death has increased globally recently. To obtain information of the species and characterization of pathogens involved in NTM pulmonary infection in Southern-central China, we identified 160 non-tuberculous infection cases from 3995 acid-fast bacilli (AFB)-positive tuberculous suspects. We then randomly selected 101 non-tuberculous patients, isolated bacteria from their sputa and genotyped the pathogens using the 16S rRNA gene and 16S-23S rRNA internal transcribed spacer sequences. M. intracellulare (32.67%, 33/101), M. abscessus (32.67%, 33/101) and M. fortuitum (7.92%, 8/101) are identified in these isolates. Surprisingly, non-mycobacteria including Gordonia (8.91%, 9/101), Nocardia (5.94%, 6/101) and Tsukamurella (0.99%, 1/101) are also discovered, and the case of Tsukamurella pulmonis infection is first discovered in Southern-central China. Moreover, species of M. mucogenicum group, M. chubuense, M. kansasii, M. gastri, M. avium, M. porcinum and M. smegmatis are identified. In addition, nine immune compromised cases (8.91%, 9/101), including type two diabetes mellitus and HIV/AIDS are found to be infected with non-tuberculous bacteria. This study revealed the distribution and characteristics of non-tuberculous AFB pathogen infection occurred in Southern-central China, and suggested that physicians should be alert of the emerging of NTM and non-mycobacteria infection in AFB positive cases and take caution when choosing chemotherapy for tuberculosis-like pulmonary infections. Generally, this study may help with the development of new strategy for the diagnosis and treatment of mycobacterial infection.

Mycobacterial 3-hydroxyacyl-l-thioester dehydratase Y derived from Mycobacterium tuberculosis induces COX-2 expression in mouse macrophages through MAPK-NF-κB pathway.

Tuberculosis (TB) is a leading cause of global mortality due to infectious diseases. Expression of cyclooxygenase-2 (COX-2) acts as an important influencing factor favoring bacillary survival during TB infection. In this study, we investigated the Mycobacterium tuberculosis proteins recognized by sera from TB patient collected before and after anti-TB therapy by dynamic immunoproteomics and identified a novel immune-regulating protein 3-hydroxyacyl-l-thioester dehydratase Y (HtdY), which could induce COX-2 expression in mouse macrophages. Signaling perturbation data showed that the activation of p38, ERK 1/2 and JNK 1/2 MAPK as well as NF-κB played critical role in this immune response. Taken together, our findings indicated that mycobacterial HtdY might contribute to the persistence of the TB infection by inducing COX-2 expression through MAPK-NF-κB signaling pathway.

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolated from south-central in China.

Rifampicin (RIF) and isoniazid (INH) Mycobacterium tuberculosis isolates were characterized from south-central China and transmission patterns within the Beijing genotype were detected in multidrug-resistant isolates. Six genetic regions, including rpoB for RIF, and katG, inhA, ahpC, mabA-inhA promoter and oxyR-ahpC intergenic region for INH were analyzed by DNA sequencing in 60 multidrug-resistant isolates, including 7 extensively drug-resistant isolates. The genomic deletion RD105 was characterized by genotyping. The results showed that 91.7% of MDR isolates carried mutations in the rpoB gene and 85.0% of the MDR isolates had at least one mutation in the INH resistance-associated loci detected. In total, these six genetic regions are responsible for 95.0% of MDR isolates. Mutations in the XDR isolates were focused on rpoB 531 or rpoB 526, and katG 315, correlating to a higher frequency level of resistance to RIF MIC ⩾8 µg ml⁻¹ and INH MIC ⩾4 µg m⁻¹. Three novel katG mutants (G273S, I266T and P232S) and three new alleles (E458A, S509R and P535S) in the rpoB gene were identified. Among the 85 clinical isolates, 78 are Beijing genotypes and the other 7 are non-Beijing genotypes. The results present the identification of genetic markers in M. tuberculosis isolates, some of which may be unique to this particular geographic niche. An understanding of the mutations in these drug-resistant strains may aid in choosing the appropriate chemotherapy regimens on the pharmacogenetic properties of the mutations for the prevention and control of tuberculosis.

Mutation abundance affects the efficacy of EGFR tyrosine kinase inhibitor readministration in non-small-cell lung cancer with acquired resistance.

There is no consensus in the salvage treatment for non-small-cell lung cancer (NSCLC) with acquired resistance to primary epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Fifty-one consecutive EGFR-mutated NSCLC patients with TKI retreatment after acquired resistance were enrolled in this study. The quantitation of mutation abundance was performed by real-time fluorescent quantitative PCR. The correlation between mutation abundance and outcomes of readministrated TKI was analyzed by survival analysis. Patients with high (H) mutation abundance (24/51) had a significantly (log-rank, P < 0.05) longer (5.27-2.53 months) median progression-free survival (PFS), compared with the low (L) abundance group (27/51), whereas the median overall survival showed no difference (21.00-18.20 months, log-rank P = .403) between the two groups. Objective response and disease control rates in group H and group L regarding the second round TKI treatment were 8.3, 70.8 and 0, 48.1 %, respectively. Groupings with different mutation abundances were significantly associated with PFS under multivariate Cox proportional hazards regression model [hazard ratio (HR) for group H vs. L, 0.527; P = .036]. Mutation abundance affects the efficacy of EGFR-TKIs readministration in NSCLC with acquired resistance. The quantitative mutation abundance of EGFR may be a potential predictor for selecting optimal patients to readministrate EGFR-TKIs after acquired resistance to primary TKI.