Buchwald-Hartwig Amination of Coordinating Heterocycles Enabled by Large-but-Flexible Pd-BIAN-NHC Catalysts.

A new class of large-but-flexible Pd-BIAN-NHC catalysts (BIAN=acenaphthoimidazolylidene, NHC=N-heterocyclic carbene) has been rationally designed to enable the challenging Buchwald-Hartwig amination of coordinating heterocycles. This robust class of BIAN-NHC catalysts permits cross-coupling under practical aerobic conditions of a variety of heterocycles with aryl, alkyl, and heteroarylamines, including historically challenging oxazoles and thiazoles as well as electron-deficient heterocycles containing multiple heteroatoms with BIAN-INon (N,N'-bis(2,6-di(4-heptyl)phenyl)-7H-acenaphtho[1,2-d]imidazol-8-ylidene) as the most effective ligand. Studies on the ligand structure and electronic properties of the carbene center are reported. The study should facilitate the discovery of even more active catalyst systems based on the unique BIAN-NHC scaffold.

[Prediction of Q-markers of Astragali Radix based on network pharmacology and fingerprint].

Astragali Radix is one of the most commonly used medicinal materials. In recent years, its cultivated varieties and a variety of adulterants have flooded the market, which makes its quality uneven, and the development of quality control methods has become a research hotspot. Therefore, figuring out the quality markers of Astragali Radix is of great significance for its comprehensive evaluation. In this study, the fingerprints of 15 batches of Astragali Radix were established by HPLC, and the main components causing intergroup differences were screened out by PLS-DA. On the basis of literature review and network pharmacology analysis, the targets and pathways of active ingredients were obtained from SwissTargetPrediction, PubChem Compound and other databases, and then the "component-target-pathway" network was constructed with Cytoscape 3.7.1 for the prediction of potential quality markers. Twenty-eight common peaks were identified in the established fingerprint, and three differential components were selected as potential quality markers for Astragali Radix, which were astragaloside Ⅳ, calycosin-7-O-ß-D-glucoside and ononin. The proposed method based on HPLC fingerprint of Astragali Radix is convenient and feasible, facilitating the improvement in its quality control.

[Comparative study of Astragali Radix Praeparata cum Melle and Hedysari Radix Praeparata cum Melle on spleen Qi deficiency rats].

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"Bulky-Yet-Flexible" α-Diimine Palladium-Catalyzed Reductive Heck Cross-Coupling: Highly Anti-Markovnikov-Selective Hydroarylation of Alkene in Air.

To pursue a highly regioselective and efficient reductive Heck reaction, a series of moisture- and air-stable α-diimine palladium precatalysts were rationally designed, readily synthesized, and fully characterized. The relationship between the structures of the palladium complexes and the catalytic properties was investigated. It was revealed that the"bulky-yet-flexible"palladium complexes allowed highly anti-Markovnikov-selective hydroarylation of alkenes with (hetero)aryl bromides under aerobic conditions. Further synthetic application of the present protocol could provide rapid and straightforward access to functional and biologically active molecules.

Development of Functional Phthalocyanine-Based Associate towards an Effective Fluorimetric Detection of Hg(II).

In acidic media, cationic phthalocyanine Alcian blue 8GX, has an efficient fluorescence quenching effect on anionic phthalocyanine tetrasulphoaluminium phthalocyanines (AlS4Pc), forming an almost non-fluorescent associate. Based on this discovery, a red-emitting fluorescent probe consisted of AlS4PC and Alcian blue 8GX has been developed through molecular assembly. Further studies indicated that the presence of Hg(II) ion has a significant fluorescence recovery effect of the probe. Notably, only Hg(II) can significantly restore the fluorescence of AlS4Pc-Alcian blue 8GX system which was revealed from the screening experiments of common metal ions, which confirmed that the fluorescence recovery by other metal ions is very weak or even unrestored, showing high specificity and sensitivity AlS4Pc-Alcian blue 8GX to Hg(II). Thus, a new fluorimetry for Hg(II) with high specificity and high sensitivity in a wide concentration range has been established using AlS4Pc-Alcian blue 8GX associate as a red-emitting fluorescent probe. It is more noteworthy that this study opens a new way for development and application of functional phthalocyanine based red-emitting fluorescent probes.

Longitudinal Measurement of Hemodynamic Changes within the Posterior Optic Nerve Head in Rodent Nonarteritic Anterior Ischemic Optic Neuropathy.

Objective To assess the in vivo dynamic blood flow features of posterior optic nerve head (ONH) in rat model of nonarteritic anterior ischemic optic neuropathy (rNAION). Methods rNAION was established with Rose Bengal and argon green laser in Sprague-Dawley rats. Fundus photography and fundus fluorescein angiography (FFA) were performed to assess the dynamic changes of optic disc in morphology in 90 days and in blood perfusion in 3 hours after the induction of disease. Histological examinations were performed to evaluate the success of modeling. The dynamic blood flow kinetics of posterior ONH in rNAION were measured by Laser Doppler Flowmetry (LDF) on the day 3, 7, 14, 21, and 40 after the disease induction. One-way ANOVA, Student's t-test and Bonferroni adjustment were used for multiple comparisons of kinetic measurements of blood flow. Results Optic disc edema and subsequent resolution associated with the development of optic disc pallor were observed in rNAION. FFA showed that the optic disc was hypofluorescence in the early phase and hyperfluorescence in the late phase. Histological studies suggested edema and loosened tissues of ONH, loss of retinal ganglion cells (RGCs), optic nerve substance and gliosis. Compared to the naive rats, the blood flow kinetics of posterior ONH in rNAION significant reduced at each time point after modeling (F=175.06, P<0.0001). The reductions were specifically remarkable in 14 days after the disease induction (All P<0.01). Conclusions Continuous blood perfusion reduction was found in rNAION, with significant alteration in 14 days after disease induction. Our results provided important information for understanding the hemodynamic changes in rNAION.

[Research and application of quality standard for standard decoction of Chrysanthemi Flos].

Standard decoction of traditional Chinese medicine (TCM) is prepared by standardized process, and can be used as references to evaluate the quality of dosage forms such as decoction and dispensing granules. In order to determine the quality evaluation method for standard decoction of Chrysanthemi Flos and investigate its application, 10 batches of white chrysanthemum of Hangzhou were collected to prepare the standard decoction of white chrysanthemum of Hangzhou with standardized process parameters. Parameters such as traits, relative density, pH value, extraction ratio, transfer rate and fingerprint were selected as the indexes for quality evaluation. The established quality evaluation method for standard decoction of Chrysanthemi Flos was applied in the detection of two types of commercial Chrysanthemum dispensing granules. The results showed that the standard decoction of Chrysanthemi Flos was a clear yellow-brown aqueous solution; the relative density was 1.007-1.011; the pH value was between 5.37-5.56; the average extraction ratio was 23.6%, ranging from 19.93% to 29.69%; the average transfer ratewas 56.2% in terms of chlorogenic acid, 57.4% in terms of luteoloside and 30.6% in terms of 3,5-O-dicaffeoylquinic acid. Fingerprint similarity was between 0.864-0.989.The method showed good precision, stability and repeatability in fingerprint analysis, indicating reliable and representative results for standard decoction of Chrysanthemi Flos, and it can be used to evaluate and standardize other dosage forms.

Formaldehyde exposure inhibits the expression of mammalian target of rapamycin in rat testis.

Formaldehyde (FA), a ubiquitous environmental pollutant, has long been suspected of causing adverse male reproductive effects. However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The overall aim of this study is to clarify the role of mammalian target of rapamycin (mTOR) in male reproductive injuries induced by FA exposure, by which we can further understand the molecular mechanism of FA male reproductive toxicity. In this study, immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction analysis were used to detect the expression of mTOR molecule in testicular tissues. We found that FA exposure inhibits the expression of mTOR in a dose-dependent manner. Combined with our earlier finding, we found the decreasing expression of mTOR in testicular tissue were consistent with the changes of testicular structure and autophagy levels. In summary, our data suggested that mTOR molecule might be involved in male reproductive injuries induced by FA exposure.

[Application of Cationic Aluminum Phthalocyanine, a Red-Emitting Fluorescent Probe, for Sensitive Quantitative Analysis of RNA at Nanogram Level].

Tetrasubstituted trimethyl ammonium iodide aluminum phthalocyanine (TTMAAlPc), a positively charged phthalocyanine compound, is an emerging and potentially useful red-emitting fluorescence probe. The study showed that the fluorescence of TTMAAlPc could be quenched by RNA with high efficiency in weak alkaline media, and the degree of quenching has a linear relationship with RNA in a wide concentration range. The mechanism of quenching behavior of RNA on TTMAAlPc was discussed. It was attributed by the static interaction between RNA and TTMAAlPc, and the assembly of TTMAAlPc induced by RNA. Based on this new discovery, a novel method for quantitative determination of RNA at nanogram level has been established. The factors, including the pH of medium, buffer system, reaction time, reaction temperature, the usage of TTMAAlPc as well as the interferences, which affected the determination, were investigated and discussed. Under optimum conditions, the linear range of the calibration curve was 7.71-1 705.57 ng x mL(-1). The detection limit for RNA was 1.55 ng x mL(-1). This method has been applied to the analysis of practical samples with satisfied results. The constructed method is of high sensitivity and has a wide linear range, it also showed strong ability in the tolerance of foreign substances from anions, cations, surfactants and vitamins, all of which are common interferences encountered in the determination of RNA. Besides, it is the first report that the fluorescence quantum yield of TTMAAlPc has been measured at different pH by reference method in this work. The achieved data indicated that the fluorescence quantum yield of TTMAAlPc is larger than 20% and it keeps constant in a wide range of acidity, implying that TTMAAlPc is a high-quality red-emitting fluorescence probe, it has great potential for practical applications, thus is worthy of further study. This work expands the application of phthalocyanine compound in analytical sciences.

[Sensitive Determination of Chondroitin Sulfate by Fluorescence Recovery of an Anionic Aluminum Phthalocyanine-Cationic Surfactant Ion-Association Complex Used as a Fluorescent Probe Emitting at Red Region].

Determination of chondroitin sulfate in the biomedical field has an important value. The conventional methods for the assay of chondroitin sulfate are still unsatisfactory in sensitivity, selectivity or simplicity. This work aimed at developing a novel method for sensitive and selective determination of chondroitin sulfate by fluorimetry. We found that some kinds of cationic surfactants have the ability to quench the fluorescence of tetrasulfonated aluminum phthalocyanine (AlS4Pc), a strongly fluorescent compound which emits at red region, with high efficiency. But, the fluorescence of the above-mentioned fluorescence quenching system recovered significantly when chondroitin sulfate (CS) exits. Tetradecyl dimethyl benzyl ammonium chloride(TDBAC) which was screened from all of the candidates of cationic surfactants was chosen as the quencher because it shows the most efficient quenching effect. It was found that the fluorescence of AlS4Pc was extremely quenched by TDBAC because of the formation of association complex between AlS4Pc and TDBAC. Fluorescence of the association complex recovered dramatically after the addition of chondroitin sulfate (CS) due to the ability of chondroitin sulfate to shift the association equilibrium of the association, leading to the release of AlS4Pc, thus resulting in an increase in the fluorescence of the reaction system. Based on this phenomenon, a novel method with simplicity, accuracy and sensitivity was developed for quantitative determination of CS. Factors including the reaction time, influencing factors and the effect of coexisting substances were investigated and discussed. Under optimum conditions the linear range of the calibration curve was 0.20~10.0 µg · mL(-1). The detection limit for CS was 0.070 µg · mL(-1). The method has been applied to the analysis of practical samples with satisfied results. This work expands the applications of AlS4Pc in biomedical area.

[Rationality of the processing methods of aconiti lateralis radix (Fuzi) based on chemical analysis].

In this study, we explored the rationality of processing methods and mechanism of Aconiti Lateralis Radix (Fuzi) through comparing the chemical contents of diester alkaloids (DAs) and monoester alkaloids (MAs) in the raw material of Fuzi and its processed products. The results showed that the toxicity potency of MAs is at least lower than 1/64 to 1/180 of the toxicity potency of DAs. The contents of DAs in processed Fuzi decreased to 1/76.5 to 1/38.3 of the value of raw Fuzi. The contents of MAs in processed Fuzi significantly increased by 4.6 to 5.2 fold or basically the same as that of the raw Fuzi. The values of MAs/DAs of processed Fuzi were enhanced by 30 to 390 fold of the raw Fuzi. It was found that the contents of DAs were insignificantly different between "Wu dan fu pian" (steaming or stir-frying without Danba) and "Dan fu pian" (steaming or stir-frying with Danba). The result suggested that the abilities of "eliminating toxicity" of different processing methods were equivalent at all. In contrast, the contents of MAs contained in "Wu dan fu pian" were of 5.3 to 8.7 fold higher than the values in "Dan fu pian". This result suggested the processing method by steaming or stir-frying without Danba might have better effect for "conserving property" than the method processed with Danba stipulated by China Pharmacopoeia. We believe that the new processing method without Danba can be recommended in further application due to it offers a simple procedure and it will not introduce inorganic impurities in the products.

[Improving accumulation-mode fraction based on spectral aerosol optical depth in Beijing].

In the present study, the authors put forward a parameterization method of correcting fine-mode Angstrom index with aerosol optical depth and volume distribution of aerosol derived from AERONET in Beijing over 2011. The parameterization method is coupled with aerosol optical depth spectral deconvolution algorithm to improve the accuracy of accumulation-mode fraction. The errors of estimated AMF are derived from underestimate of fine-mode Angstrom index errors. We calculate and simulate the extreme values of fine-mode Angstrom index, getting constraint conditions, and then establish the extreme values correction method. Results from sensitivity test suggest that extreme values of fine-mode Angstrom index are constrained in the reasonable range. Finemode Angstrom index and AMF are sensitive to normalized volume distribution of aerosol, ranging from 0.662 to 2.849 and from 0.08 to 0.84 due to different distribution. Mean deviation of accumulation-mode fraction is reduced from 0.072 to 0.044, and the difference is 38.89%, especially in winter and summer. Improving computational accuracy of accumulation-mode fraction can enhance that of anthropogenic aerosol optical thickness, and it has important significance of anthropogenic aerosol direct radiation force estimation and environmental quality assessment.

Discovery and verification of gelsolin as a potential biomarker of colorectal adenocarcinoma in the Chinese population: Examining differential protein expression using an iTRAQ labelling-based proteomics approach.

OBJECTIVE: To identify and validate potential biomarkers of colorectal adenocarcinoma using a proteomic approach. METHODS: Multidimensional liquid chromatography/mass spectrometry was used to analyze biological samples labelled with isobaric mass tags for relative and absolute quantitation to identify differentially expressed proteins in human colorectal adenocarcinoma and paired normal mucosa for the discovery of cancerous biomarkers. Cancerous and noncancerous samples were compared using online and offline separation. Protein identification was performed using mass spectrometry. The downregulation of gelsolin protein in colorectal adenocarcinoma samples was confirmed by Western blot analysis and validated using immunohistochemistry. RESULTS: A total of 802 nonredundant proteins were identified in colorectal adenocarcinoma samples, 82 of which fell outside the expression range of 0.8 to 1.2, and were considered to be potential cancer-specific proteins. Immunohistochemistry revealed a complete absence of gelsolin expression in 86.89% of samples and a reduction of expression in 13.11% of samples, yielding a sensitivity of 86.89% and a specificity of 100% for distinguishing colorectal adenocarcinoma from normal tissue. CONCLUSIONS: These findings suggest that decreased expression of gelsolin is a potential biomarker of colorectal adenocarcinoma.

[Retrieval of dust fraction of atmospheric aerosols based on spectra characteristics of refractive indices obtained from remote sensing measurements].

Mineral dust is an important chemical component of aerosol, which has a significant impact on the climate and environmental changes. The spectral behavior of aerosol refractive indices at four wavelengths from 440 to 1 020 nm was analyzed based on one year observation obtained from Beijing AERONET site. The real parts of refractive index (n) in each band did not differ greatly, however the imaginary parts (k) showed a significant difference due to the absorption of mineral dust in aerosol. From 440 to 670 nm k decreased rapidly, while from 670 to 1 020 nm featured a lower, constant value. Accordingly, k(440 nm) could be considered separately with other three bands. Hence, we added mineral dust into the currently used three-component aerosol chemical model to form a new four-component model (i. e. BC, AS, dust and water) which is more suitable to represent the aerosol chemical composition. Then we presented a method to retrieve dust content in aerosols using this four-component model and refractive indices obtained from the sunphotometer measurements. Finally the dust content in aerosol was investigated under different weather conditions, i. e. clear, haze and dust in Beijing. The results showed that volume fractions of the dust component were 88%, 37% and 48% for clear, hazy and dusty day respectively, which was consistent with the coarse mode proportion in aerosols calculated from aerosol size distributions.

[Analysis of fundus fluorescein angiography, indocyanine green angiography and choroidal thickness in central serous chorioretinopathy].

OBJECTIVE: To evaluate the characteristics of choroidal thickness changes and abnormalities in choroidal circulation in cases of central serous chorioretinopathy (CSC). METHODS: This was a case control study, we measured the bilateral choroidal thickness in 21 patients with unilateral CSC and 24 eyes of 24 age- and sex-matched normal subjects using enhanced depth imaging optical coherence tomography (EDI-OCT). The choroid was measured from the posterior edge of the retinal pigment epithelium (RPE) to the choroid-scleral junction at 500 µm intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Paired-samples t-test was conducted to compare mean choroidal thicknesses between symptomatic eyes and fellow eyes of patients. The datum between patients and normal subjects were analyzed by independent-samples t-test. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed and the digital images were analyzed in CSC patients. RESULTS: The 21 CSC patients had a mean age of 45.6 years, and 12 patients (57.1%) were male. The choroid in symptomatic eyes was thickest beneath the fovea (519.0 ± 102.5) µm. It was significantly thicker than that in the fellow eyes (439.3 ± 94.1) µm (t = 4.171, P < 0.05). Choroidal thickness in both groups was significantly greater than that in the eyes of age- and sex-matched normal subjects (332.0 ± 67.3) µm (t = 7.125, 4.441; P < 0.05). Choroidal thickness at each of the other 12 points showed a similar tendency (t = 2.544 to 3.819, 4.799 to 7.816, 2.487 to 5.236; P < 0.05). ICGA showed a choroidal filling delay (100%), vessels dilation (90.5%), and focal choroidal hyperfluorescence (100%) surrounding leakage from the RPE in symptomatic eyes. Pigment epithelium detachment with abnormal choroidal circulation was observed in 6 fellow eyes. In 4 symptomatic eyes and 11 fellow eyes, ICGA revealed choroidal hyperfluorescence but FFA showed normal appearance. CONCLUSIONS: CSC seems to be a bilateral eye disease with choroidal focal ischemia followed by vessels congestion and hyperpermeability. EDI OCT is a useful tool for monitoring choroidal thickness changes caused by choroidal vascular hyperpermeability.

Dual-Stage Blue-Light-Guided Membrane and DNA-Targeted Photodynamic Inactivation Using Octyl Gallate for Ultraefficient Eradication of Planktonic Bacteria and Sessile Biofilms.

This study aimed to investigate the synergistic bactericidal activity and mechanism of dual-stage light-guided membrane and DNA-targeted photodynamic inactivation (PDI) by the combination of blue light (BL, 420 nm) and the food additive octyl gallate (OG) against Vibrio parahaemolyticus in planktonic and biofilm growth modes. While OG serves as an outstanding exogenous photosensitizer, the planktonic cells were not visibly detectable after the OG-mediated PDI treatment with 0.2 mM OG within 15 min (191.7 J/cm2), and its biofilm was nearly eradicated within 60 min (383.4 J/cm2). Gram-positive Staphylococcus aureus was more susceptible to the PDI than Gram-negative V. parahaemolyticus. The cellular wall and proteins, as well as DNA, were the vulnerable targets for PDI. The membrane integrity could be initially disrupted by OG bearing a hydrophilic head and a hydrophobic tail via transmembrane insertion. The enhancement of OG uptake due to the first-stage light-assisted photochemical internalization (PCI) promoted the accumulation of OG in cells. It further boosted the second-stage light irradiation of the photosensitizer-inducing massive cell death. Upon the second-stage BL irradiation, reactive oxygen species (ROS) generated through the OG-mediated PDI in situ could extensively deconstruct membranes, proteins, and DNA, as well as biofilms, while OG could be activated by BL to carry out photochemical reactions involving the formation of OG-bacterial membrane protein (BMP) covalent conjugates and the interactions with DNA. This dual-stage light-guided subcellular dual-targeted PDI strategy exhibits encouraging effects on the eradication of planktonic bacteria and sessile biofilms, which provides a new insight into the development of an ultraeffective antimicrobial and biofilm removing/reducing technique to improve microbiological safety in the food industry.

[Pyrolysis and gas emissions characteristics of six tree species in Heilongjiang Province, China]. / 黑龙江省6种乔木叶片热解特性及气体释放特征.

Forest fuels are the basis of fire occurrences, while ground dead fuels are an important part of forest fuels. Undestanding the pyrolysis characteristics and gas emissions of forest fuels is of great significance to explore the effects of forest fire on atmospheric environment and carbon balance, as well as to prevent and combat forest fire. In this study, the thermogravimetric analysis and gas emission analysis were conducted on leaf litter of six tree species (Pinus sylvestris var. mongolica, Picea koraiensis, Fraxinus mandshurica, Juglans mandshurica, Quercus mongolica, Betula platyphylla) in Heilongjiang Province to explore the pyrolysis process and combustibility of forest fuels, to analyze their pyrolysis characteristics, pyrolysis kinetics characteristics, gas emission characteristics. A four-dimensional evaluation of their combustibility was conducted based on pyrolysis parameters. The results showed that the pyrolysis temperature of holocellulose in the leaves of those six tree species ranged in 143.31-180.48 ℃ at the beginning and 345.04-394.38 ℃ at the end, lignin pyrolysis temperature ranged in 345.04-394.38 ℃ at the beginning and 582.85-609.31 ℃ at the end. The pyrolysis of the six kinds of arbor blades during the pyrolysis process affected fuel ash content, quality and temperature of the total pyrolysis. The activation energies of two main pyrolysis stages of leaves of six tree species were 18.88-27.08 kJ·mol-1 and 13.25-27.54 kJ·mol-1, respectively, and the pre-exponential factors were 3.13-26.28 min-1 and 1.30-22.55 min-1. The holocellulose activation energy and pre-exponential factor of the pyrolysis stage for P. koraiensis, F. mandshurica, Q. mongolica, and B. platyphylla were greater than that of the lignin pyrolysis stage, while the opposite was true for P. sylvestris var. mongolica and J. mandshurica. The release amounts of CO and CO2 at the pyrolysis stage of the holocellulose was 535.16-880.11 mg·m-3 and 7004.97-10302.05 mg·m-3, and that at the pyrolysis stage of lignin was 240.31-1104.67 mg·m-3 and 20425.60-33946.68 mg·m-3, respectively. The release of CO and CO2 at the pyrolysis stage of healdellulose was less, but mass loss was greater than that at the pyrolysis stage of lignin. In the four-dimensional combustibility ranking of the six tree species leaves, B. platyphylla was the best ignitable, P. koraiensis was the most combustible, and P. sylvestris var. mongolica was the most sustainable and consumable. The ignitability was significantly positively correlated with pyrolysis kinetics parameters of the holocellulose, while the sustainability was negatively correlated with that of lignin.

Enhanced antibacterial efficacy and mechanism of octyl gallate/beta-cyclodextrins against Pseudomonas fluorescens and Vibrio parahaemolyticus and incorporated electrospun nanofibers for Chinese giant salamander fillets preservation.

A series of alkyl gallates were evaluated for the antibacterial activity against two common Gram-negative foodborne bacteria (Pseudomonas fluorescens and Vibrio parahaemolyticus) associated with seafood. The length of the alkyl chain plays a pivotal role in eliciting their antibacterial activities and octyl gallate (OG) exerted an excellent inhibitory efficacy. To extend the aqueous solubility, stability, and bactericidal properties of octyl gallate (OG), an inclusion complex between OG and ß-cyclodextrin (ßCD), OG/ßCD, was prepared and identified with various methods including X-ray diffraction (XRD), differential scanning calorimeter (DSC) and Fourier transform infrared spectroscopy (FTIR). Furthermore, the enhanced inhibitory effect and potential antibacterial mechanism of OG/ßCD against two Gram-negative and Gram-positive foodborne bacteria were comprehensively investigated. The results show that OG/ßCD could function against bacteria through effectively damaging the membrane, permeating into cells, and then disturbing the activity of the respiratory electron transport chain to cause the production of high-level intracellular hydroxyl radicals. Moreover, the reinforced OG/ßCD-incorporated polylactic acid (PLA) nanofibers were fabricated using the electrospinning technique as food packaging to extend the Chinese giant salamander fillet's shelf life at 4 °C. This research highlights the antibacterial effectiveness of OG/ßCD in aqueous media, which can be used as a safe multi-functionalized food additive combined with the benefits of electrospun nanofibers to extend the Chinese giant salamander fillets shelf life by 15 d at 4 °C.

Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands.

Drug resistance caused by epidermal growth factor receptor (EGFR) mutation has largely limited the clinical use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for the treatment of non-small-cell lung cancer (NSCLC). Herein, to overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated. As a consequence, covalent PROTAC CP17, with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFRL858R/T790M and EGFRdel19, reaching the lowest DC50 values among all reported EGFR-targeting PROTACs. Furthermore, CP17 exhibited excellent cellular activity against the H1975 and HCC827 cell lines with high selectivity. Mechanism investigation indicated that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be an effective approach for the design of PROTACs targeting EGFRL858R/T790M, which laid the practical foundation for further development of potent EGFR-targeting PROTACs.

[Association of PARK 16 polymorphisms with Parkinson's disease in Han population of Suzhou area].

OBJECTIVE: To investigate whether there is an association of PARK 16 locus with Parkinson's disease (PD) in Han population of Suzhou area. METHODS: Polymerase chain reaction (PCR), sequencing analysis, allele-specific PCR mediated by pfu DNA polymerases and real-time PCR were employed to determine the genotype of each subject. The PARK16 representative SNP rs947211 was analyzed in 160 PD patients and 200 age-matched healthy controls. RESULTS: The results of pfu-mediated allele-specific PCR were 100% concordant with the direct-sequencing analysis. All genotypes were found in this study. A significant distinction occurred in the allelic frequency of rs947211. There was a higher expression of G allele in PD patients versus the controls (60.63% vs 51.00%; χ(2) = 6.662, P = 0.010, OR = 0.676, 95%CI 0.502 - 0.911). There were remarkable differences between G/G genotype and A/G + A/A genotype of two groups (χ(2) = 8.401, P = 0.004, OR = 1.951, 95%CI 1.238 - 3.076). In addition, a significant distinction also existed in different genotypes through H&Y stage (P < 0.05). For example, the stage of G/G was higher than A/A genotype (P = 0.025, 95%CI 0.059 - 0.851) or A/G genotype (P = 0.020, 95%CI 0.058 - 0.654). CONCLUSION: We have established a simple and reliable rs947211 genotyping method mediated by pfu DNA polymerases. The results confirmed the existence of PARK16 in Han population of Suzhou area, rs947211 G/G genotype maybe a risk factor for PD and G/G genotype carriers perhaps obtain higher illness severity.