Tracking the deprotonation site of dehydroandrographolide with electrospray ionization mass spectrometry by deuteration.

RATIONALE: Dehydroandrographolide (DA) is a diterpene compound of biological interest that contains one α,ß-unsaturated lactone group and two hydroxy groups. In the ESI (electrospray ionization) negative ion mode mass spectral analysis of 15-dideuterodehydroandrographolide (15-D2 -DA), the deuterium nucleus at the γ position of the α,ß-unsaturated lactone was more easily dedeuterated than deprotonation of the protons from the hydroxy groups. Exploring the rationality of deuteration as a tool for deprotonation position tracking is significant for gas-phase acidity. METHODS: The mass spectra of DA and 15-D2 -DA in positive and negative ion mode were acquired by liquid chromatography/ion trap time-of-flight mass spectrometry (LC/IT-TOF) systems. The deprotonation and dedeuteration energies at specific sites were calculated by the B3LYP and M06-2X density functional theory (DFT) methods with the program Gaussian 16. RESULTS: The [M + H]+ ion of 15-D2 -DA was 2 amu larger than that of DA due to the substitution of two hydrogens with two deuteriums; however, the anion base peak of 15-D2 -DA was only 1 amu larger than that of the [M - H]- ion of DA. Dedeuteration at the C15 site was proposed according to the mass spectral data. The deprotonation (dedeuteration) energies calculated by the B3LYP/6-311++G(3df,3pd)//B3LYP/6-31 + G(d) and M06-2X-D3/ma-TZVP methods showed that the C-H and C-D bonds at the C15 site have lower deprotonation (dedeuteration) energies than the energies of the hydroxy groups of DA, making their deprotonation (dedeuteration) more thermodynamically favourable. CONCLUSIONS: Deuteration of DA provided direct evidence of the deprotonation site of DA in the ESI source of the mass spectrometer, and the DFT method well predicted the gas-phase deprotonation site of DA.

Preliminary assessment of genotoxic effects induced by radiation from EAST usingVicia fabamicronucleus assay.

During long-pulse deuterium plasma operations in the Experimental Advanced Superconducting Tokamak (EAST), a mixed radiation field is generated, which is mainly composed of fusion neutrons, gamma rays, and x-rays. More accurate and effective dose monitoring methods have been developed and established to determine the ionizing radiation intensity both for the stable operation of the device and for the radiation safety of personnel. As far as we know, there are few reports about the biological effects of radiation induced by fusion neutrons andγradiation, which are of vital importance for the assessment of radiation hazards presented by fusion devices, such as EAST, to human beings and the environment. In this study, three positions in the EAST hall were selected to detect genotoxic effects induced by nuclear fusion radiation using aVicia fabamicronucleus (MN) test for the first time. The doses of neutrons and gamma rays at these places were measured by thermoluminescence dosimeters four times between June 2019 and May 2020. The radiation doses decreased as the distances from the EAST device shell gradually increased from S1 to S3. The radiation in the EAST hall resulted in a significant induction of MN in theVicia fabaroot tip cells compared to a negative control, which was different from the MN frequency induced by fission neutrons,γ-rays and other kinds of radiation in previous studies. These results indicate the existence of potential genotoxic effects induced by radiation from EAST which is different from other radiation and suggest that personnel should not be permitted to enter the experimental hall during the discharge process, and that radiation protection measures should be taken during necessary maintenance to avoid radiation damage. These newly acquired results will certainly increase our knowledge about the biological effects induced by radiation from nuclear fusion and provide good data support for developing more effective environmental and personnel fusion radiation protection.

A Concise Approach to N-Substituted Rhodanines through a Base-Assisted One-Pot Coupling and Cyclization Process.

An efficient approach to obtain functionalized rhodanines was developed through a base-assisted one-pot coupling and continuous cyclization of a primary amine, carbon disulfide, and methyl (2-chloroacetyl)carbamate. This conversion tolerates a broad range of functional groups and can be used to scale the preparation of N-substituted rhodanines in excellent yields.

Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the chemical space of a less explored "hydrophobic channel".

A new series of diarylpyrimidines (DAPYs) were designed, synthesized and evaluated as novel HIV-1 NNRTIs to further explore the chemical space surrounding the "hydrophobic channel" of the NNRTI binding pocket (NNIBP), guided by the comprehensive analysis of X-ray structural biology data of HIV-1 RT/NNRTI complexes and molecular modeling. Encouragingly, most of the synthesized DAPYs were found to be active against the HIV-1 wild-type (WT) strain with EC50 values ranging from 3 nM to 63 nM, and displayed significantly reduced cytotoxicity compared with etravirine (ETV) and rilpivirine (RPV). Among them, two most promising compounds Z10 (EC50 = 3 nM) and Z13 (EC50 = 3 nM) showed equivalent potency against the HIV-1 WT strain to the reference drugs efavirenz (EFV, EC50 = 3 nM) and ETV (EC50 = 3 nM). Notably, Z13 also showed the most potent activity against HIV-1 mutant strains including K103N (EC50 = 10 nM), E138K (EC50 = 22 nM) and RES056 (EC50 = 0.935 µM). Against mutant strains Y181C, Y188L and F227L + V106A, Z17 showed double-digit nanomolar inhibitory activity with EC50 values 27 nM, 98 nM and 30 nM, respectively. The structure-activity relationships (SARs) and molecular docking studies provided important clues for further molecular elaboration. Collectively, this study provides useful information to guide lead optimization and drug discovery via the exploration of this seldom investigated region.

Core and variable antimicrobial resistance genes in the gut microbiomes of Chinese and European pigs.

Monitoring the prevalence of antimicrobial resistance genes (ARGs) is vital for addressing the global crisis of antibiotic-resistant bacterial infections. Despite its importance, the characterization of ARGs and microbiome structures, as well as the identification of indicators for routine ARG monitoring in pig farms, are still lacking, particularly concerning variations in antimicrobial exposure in different countries or regions. Here, metagenomics and random forest machine learning were used to elucidate the ARG profiles, microbiome structures, and ARG contamination indicators in pig manure under different antimicrobial pressures between China and Europe. Results showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs ( P<0.05). ANT(6)-Ib, APH(3')-IIIa, and tet(40) were identified as shared core ARGs between the two pig populations. Furthermore, the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical regions. Lactobacillus and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs, respectively. Forty ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100% and 98.7%, respectively. Indicators for assessing ARG contamination in Chinese and European pigs also achieved high accuracy ( r=0.72-0.88). Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 ARGs. The results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.

Discovery of novel tubulin CBSI (R)-9k from the indanone scaffold for the treatment of colorectal cancer.

In view of the serious adverse reactions and clinical toxicity of first line therapy 5-fluorouracil and lack of small molecule therapeutics in colorectal cancer chemotherapy, a series of natural scaffold-based 3-arylindanone derivatives (9a-q) were designed, synthesized and evaluated as tubulin polymerization inhibitors targeting the colchicine site. The most potent colchicine binding site inhibitor (CBSI), (R)-9k, exhibited 14-38 times more dominant anti-proliferative activity against three colon cancer cell lines than 5-fluorouracil. Particularly, (R)-9k showed higher selectivity against human normal cells compared with 5-fluorouracil and colchicine, and displayed negligible cardiotoxicity through hERG assessment. Furthermore, the binding of (R)-9k to the colchicine site was strongly supported by EBI competition assay and (R)-9k inhibited more tubulin polymerization than colchicine. Besides, the mechanism of action and binding modes of (R)-9k were verified by molecular dynamics simulations and docking. Therefore, (R)-9k could be regarded as a promising CBSI for colorectal cancer therapy.

Naked-eye on-site detection platform for Pasteurella multocida based on the CRISPR-Cas12a system coupled with recombinase polymerase amplification.

Pasteurella multocida (P. multocida) is an important pathogenic bacterium that poses a serious threat to the development of the livestock economy and human health. Currently, the existing methods for P. multocida detection are time-consuming and require complex professional operations, limiting the application of field detection. In the study, we presented a single-pot naked-eye CRISPR-Cas12a platform (Cas12a-NEye) for the detection of P. multocida. The round tube cover allowed more Cas12a detection solution to be temporarily stored than the flat cap, enabling single-pot assays and avoiding aerosol contamination. The positive samples generated obvious red using naked eye using no excitation light and the negative samples generated blue. The limit of detection (LOD) was a single copy, without cross-reactivity with other closely related bacteria. Furthermore, we validated this platform using 16 P. multocida clinical lung samples and obtained consistent results with the real-time quantitative polymerase chain reaction (qPCR) method. The entire experimental process included rapid DNA extraction (<1 h) and Cas12a-NEye assay (25 min), which was accomplished within 1.5 h. Thus, this "sample-to-answer" platform has significant potential for P. multocida detection.

Effects of zinc oxide nanoparticles transformation in sulfur-containing water on its toxicity to microalgae: Physicochemical analysis, photosynthetic efficiency and potential mechanisms.

The environmental transformation of nanomaterials will have a significant impact on their ecotoxicity. Sulfidation process is one of the most important transformation processes in the aquatic environment. Although the sulfidation of ZnO nanoparticles (ZnO NPs) has been previously reported, the transformation characteristics and the relationship between the transformation process and toxicity mechanism to aquatic organisms, especially microalgae, require further study. Therefore, we systematically investigated the transformation properties of ZnO NPs in sulfur-containing water and its impact on the toxicity to microalgae. The results showed that the transformation products of ZnO NPs mainly contained ZnS nanoparticles, and their contents increased with the increase of sulfur-zinc molar ratio in the aqueous solution. After the first week of treatment, the sulfidized ZnO NPs showed less toxicity to microalgae than the pristine ZnO NPs, and interestingly, they exhibited higher toxicity over time. The zinc ions and transformation products played a major role in different treatment periods, resulting in different toxicity. The results of photosynthetic pigments, photosynthetic efficiency, and the relative electron transport rates indicated that the sulfidation process of ZnO NPs had a remarkable influence on algal photosynthesis. These newly acquired results will help us explore the transformation characteristics of ZnO NPs and reasonably assess their potential risks in the aquatic environment.

Application of 2H stable isotope labelling methodology and ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the metabolite identification of dehydroandrographolide in rats.

Dehydroandrographolide (DA), one of the crucial diterpenoids of Andrographis paniculata (Burm.F.) Nees, which has been widely used clinically due to its excellent biological activities and pharmacological safety. Until now, various investigations about the biological activities, pharmacokinetic profiles, and in vitro metabolism of DA have been conducted. However, information about the in vivo biotransformation of DA was still not available. In this study, a rapid and reliable approach based on stable isotope labeling and UPLC-Q/TOF-MS was developed and applied for the first systematic research about the in vivo metabolism of DA. As a result, a total of 35 metabolites were identified in rat urine, bile, plasma, and feces samples after DA was orally administered at the dose of 95 mg/kg, and 33 of them were further verified based on stable isotope labeling. The major metabolic pathways for DA were hydroxylation, hydration, sulfonation, sulfate conjugation, and glucuronidation. Meanwhile, sulfonation, sulfate conjugation, and amino acids conjugation of DA were reported for the first time. This is the first systematic investigation of the in vivo metabolism of DA in rats, and the identification of these metabolites might provide scientific and reliable support for a full understanding of the metabolism of DA.

Discovery of pyrimidine-bridged CA-4 CBSIs for the treatment of cervical cancer in combination with cisplatin with significantly reduced nephrotoxicity.

A series of pyrimidine-bridged CA-4 derivatives (9a-u) targeting colchicine site were designed, synthesized and evaluated. Among them, the most potent compound 9j showed favorable anti-proliferative activities against a panel of cervical cancer cells (IC50 = 0.09-0.15 µM) and tubulin polymerization inhibitory activity (IC50 = 4.6 µM). Meanwhile, compound 9j exhibited superior anti-proliferative activity against cisplatin-resistant HeLa/DDP and SiHa/DDP cells than CA-4 and cisplatin. Particularly, the combination of 30 mg/kg 9j with 3 mg/kg cisplatin resulted in a 73% tumor suppression rate in HeLa xenograft model and reduced the renal dysfunction and injuries caused by high doses of cisplatin. Moreover, 9j was highly selective over the normal human proximal tubular cells (HK-2 cells, IC50 = 188 µM). Mechanism studies revealed that 9j could disrupt tubulin polymerization and vasculature, arrest the cell cycle at the G2/M phase, induce apoptosis, and suppress clonogenesis and migration in HeLa cells. Further druggability characterization in terms of pharmacokinetic profile, acute toxicity, and hERG inhibition confirmed 9j could serve as a promising and safe combination agent for cervical cancer therapy.

Systematic review and Meta-analysis of 26 randomized controlled clinical trials of Compound Danshen Dripping Pill for non-proliferating diabetic retinopathy.

Objective: Diabetic retinopathy (DR) is the retinal consequence of chronic progressive diabetic microvascular leakage and occlusion. Non-proliferating diabetic retinopathy (NPDR) is the early stage of DR. It eventually occurs to some degree in all patients with diabetes mellitus. In recent years, many clinical trials have shown that Compound Danshen Dripping Pill (CDDP) may be associated with the improvement of NPDR symptoms. The aim of this study was to quantitatively summarize the association between CDDP and the therapeutic effects of NPDR. Methods: It was conducted that a systematic literature search of PubMed, Web of Science, CNKI, VIP and Wanfang Data updated in June 2020 with the following search terms: "diabetic retinopathy" or "retinopathy" or "DR" or "NPDR", in combination with "Compound Danshen Dripping Pill" or "Salvia miltiorrhiza" or "Danshen". Risk ratio (RR) and weighted mean difference (WMD) with their 95% confidence interval (CI) was calculated between treatment and control groups. The sensitivity analyses were undertaken by removing each individual study when high heterogeneity appeared. Subgroup analysis, Meta-regression, and publication bias analysis were also conducted. The strength of evidence was evaluated with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Results: Twenty-six RCTs involving 2047 subjects were included to conduct a Meta-analysis after screening the studies, extracting the data, and assessing the study quality. The Stata15.0 software was utilized for processing. Meta-analysis indicated that curative effects of treatment group with CDDP was significantly better than control [RR = 0.54, 95% CI (0.40, 0.73); moderate-quality evidence]. In addition, the results showed that CDDP was significantly associated with improving retinal hemorrhages [WMD = -0.62, 95% CI (-0.78, -0.46); low-quality evidence], the vision [WMD = 0.14, and 95% CI (0.09, 0.19), low-quality evidence], fundus fluorescence angiography [RR = 0.37 and 95% CI (0.23, 0.60); low-quality evidence], reduction of retinal microaneurysm [WMD = -3.74 and 95% CI (-4.38, -3.11); moderate-quality evidence], hemangioma volume [WMD = -3.15, 95%CI (-3.45, -2.85); moderate-quality evidence], macular thickness [WMD = -5.52, 95%CI = (-64.27, -48.78); low-quality evidence], mean defect [WMD = -1.65 and 95% CI (-1.95, -1.34); very low-quality evidence], fasting blooding glucose [WMD = -0.95, 95% CI (-1.19, -0.70); low-quality evidence), hemoglobin A1c [WMD = -0.62, 95% CI (-0.93, -0.30); low-quality evidence], high sensitive C reaction protein [WMD = -5.66, 95% CI (-8.01, -3.31); low-quality evidence]. Sensitivity, subgroup, and Meta-regression analyses were also assessed. Conclusion: The study demonstrated that CDDP has beneficial clinical effects for treating NPDR and improve the vision. Moreover, it indicated that oral CDDP in NPDR patients led to significant regulation of serum level of fasting blooding glucose, hemoglobin A1c and high sensitive C reaction protein, which was associated with the pathogenesis of NPDR. However, high-quality and large randomized clinical trials will be needed to prove the consequence in future.

Metagenomic Insights into Chicken Gut Antibiotic Resistomes and Microbiomes.

The chicken gut microbiota, as a reservoir of antibiotic resistance genes (ARGs), poses a high risk to humans and animals worldwide. Yet a comprehensive exploration of the chicken gut antibiotic resistomes remains incomplete. In this study, we established the largest chicken gut resistance gene catalogue to date through metagenomic analysis of 629 chicken gut samples. We found significantly higher abundance of ARGs in the Chinese chicken gut than that in the Europe. tetX, mcr, and blaNDM, the genes resistant to antibiotics of last resort for human and animal health, were detected in the Chinese chicken gut. The abundance of ARGs was linearly correlated with that of mobile genetic elements (MGEs). The host-tracking analysis identified Escherichia, Enterococcus, Staphylococcus, Klebsiella, and Lactobacillus as the major ARG hosts. Especially, Lactobacillus, an intestinal probiotic, carried multiple drug resistance genes, and was proportional to ISLhe63, highlighting its potential risk in agricultural production processes. We first established a reference gene catalogue of chicken gut antibiotic resistomes. Our study helps to improve the knowledge and understanding of chicken antibiotic resistomes for knowledge-based sustainable chicken meat production. IMPORTANCE The prevalence of antibiotic resistance genes in the chicken gut environment poses a serious threat to human health; however, we lack a comprehensive exploration of antibiotic resistomes and microbiomes in the chicken gut environment. The results of this study demonstrate the diversity and abundance of antibiotic resistance genes and flora in the chicken gut environment and identify a variety of potential hosts carrying antibiotic resistance genes. Further analysis showed that mobile genetic elements were linearly correlated with antibiotic resistance genes abundance, implying that we should pay attention to the role played by mobile genetic elements in antibiotic resistance genes transmission. We established a reference genome of gut antibiotic resistance genes in chickens, which will help to rationalize the use of drugs in poultry farming.

Swine manure facilitates the spread of antibiotic resistome including tigecycline-resistant tet(X) variants to farm workers and receiving environment.

The prevalence of antibiotic resistance genes (ARGs) in livestock and poultry manure is a severe threat to human health. However, the comprehensive characterization of antibiotic resistance in swine, workers, and the receiving environment is still lacking in the actual breeding environment. Hence, the ARG profile and the potential bacterial hosts producing among swine manure (including sows, piglets, finishing pigs, and nursery pigs), worker feces, and the receiving environment (including sediment and vegetable soil) were comprehensively analyzed based on the metagenomic method. The results showed that swine manure exhibited the high levels of richness and diversity of ARGs. Inactivating tetracycline resistance genes such as tet(X), tet(X1), and tet(X10) were prevalent on swine farms. Workers and the environment were the primary recipients of ARGs, and shared ARGs accounted for at least 90% of their ARG abundances. Network analysis revealed that Escherichia, Acinetobacter, and Erysipelothrix were the most dominant genera co-occurring with specific shared ARGs. The abundance of coexisting ARGs in swine at different developmental stages accounted for 76.4% to 90.8% of the shared ARGs in swine, workers, and environmental samples. The Mantel test revealed that Firmicutes and Proteobacteria had a significant correlation with the ARG profiles. In addition, variation partitioning analysis (VPA) showed that the joint effects of mobile genetic elements (MGEs) and bacterial communities accounted for 24.7% of the resistome variation and played a significant role in the ARG profiles. These results improve our understanding of the transmission and persistence of ARGs in the actual breeding environment.

Sulfite as the substrate of C-sulfonate metabolism of α, ß-unsaturated carbonyl containing andrographolide: analysis of sulfite in rats' intestinal tract and the reaction kinetics of andrographolide with sulfite.

One-sixth of the currently known natural products contain α, ß-unsaturated carbonyl groups. Our previous studies reported a rare C-sulfonate metabolic pathway. Sulfonate groups were linked to the ß-carbon of α, ß-unsaturated carbonyl-based natural compounds through this pathway. However, the mechanism of this type of metabolism is still not fully understood, especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition. In this work, the enzyme-mediated and non-enzymatic pathways were studied. First, the sulfite content in rat intestine was determined by LC-MS/MS. The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383 µg·g-1, whereas the amount of sulfite in rat feed was lower than the lower limit of quantitation (20 µg·g-1). Second, the reaction kinetics of sulfite-andrographolide reactions in phosphate buffer solutions (pH 6-8) was studied. The half-lives of andrographolide ranged from minutes to hours. This was suggested that the C-sulfonate reaction of andrographolide was very fast. Third, the C-sulfonate metabolites of andrographolide were both detected when andrographolide and L-cysteine-S-conjugate andrographolide were incubated with the rat small intestine contents or sulfite, indicating that the sulfite amount in rat intestine contents was high enough to react with andrographolide, which assisted a significant portion of andrographolide metabolism. Finally, the comparison of andrographolide metabolite profiles among liver homogenate (with NADPH), liver S9 (with NADPH), small intestine contents homogenate (with no NADPH), and sulfite solution incubations showed that the C-sulfonate metabolites were predominantly generated in the intestinal tract by non-enzymatic pathway. In summary, sulfite can serve as a substrate for C-sulfonate metabolism, and these results identified non-enzymatically nucleophilic addition as the potential mechanism for C-sulfonate metabolism of compounds containing α, ß-unsaturated carbonyl moiety.

Transcriptomic study of the mechanism by which the Kai Yu Zhong Yu recipe improves oocyte quality in a stressed mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The Kai Yu Zhong Yu recipe (KYZY) is a classic herbal formula in traditional Chinese medicine (TCM) that has been used to treat infertility associated with psychological stress for more than three hundred years. AIM OF THE STUDY: Psychological stress has major impacts on fertility, with variable outcomes depending on the nature, strength, and duration of the stress. Stress can directly disturb ovulation, oocyte quality, maturation, and embryo development. The aim of this study is to investigate the molecular mechanism by which KYZY improves oocyte developmental potential under psychological stress. MATERIALS AND METHODS: ICR female mice aged 4-5 weeks were randomly divided into five groups: control, stressed in the chronic unpredictable stress model (CUSM), and stressed plus KYZY treatment at 38.2 g/kg (KYZYH), 19.1 g/kg (KYZYM), or 9.6 g/kg (KYZYL). Ovary function was assessed by measuring serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH). Oocyte quality was evaluated in terms of reactive oxygen species (ROS) levels, apoptotic DNA fragmentation, and mitochondria distribution. We used RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) between groups and then further analyzed the DEGs for gene ontology (GO) term enrichment and protein-protein interactions. RESULTS: Mice in the stressed group had reduced serum E2, LH, and FSH as well as increased ROS levels, increased apoptosis, and disturbed mitochondria distribution in oocytes. Treatment with KYZY at all three doses reversed or ameliorated these negative effects of stress. DEG analysis identified 187 common genes between the two comparisons (stressed vs. control and KYZYM vs. stressed), 33 of which were annotated with six gene ontology (GO)'s biological process (BP) terms: cell differentiation, apoptosis, ATP synthesis, protein homo-oligomerization, neuron migration, and negative regulation of peptidase activity. Protein-protein interaction network analysis of DEGs identified key hub genes. Notably, the genes Atp5o and Cyc1 were both involved in the ATP synthesis and among the top three hub genes, suggesting that regulation of oocyte mitochondrial electron transport and ATP synthesis is important in the response to stress and also is a possible mechanism of action for KYZY. CONCLUSIONS: KYZY was effective in ameliorating the adverse effects of stress on oocyte competence, possibly by targeting the mitochondrial respiratory chain and ATP synthase.

Effects of the polysaccharides extracted from Chinese yam (Dioscorea opposita Thunb.) on cancer-related fatigue in mice.

The aim of this study was to investigate the anti-fatigue activity of Chinese Yam polysaccharides (CYPs). The structural characterization of CYPs was conducted using Fourier transform-infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography-light scattering-refractive index, and ion chromatography. The weight-loaded swimming capability, behavior performance, tumor growth, content of adenosine triphosphate (ATP), and biochemical markers of CYP in a cancer-related fatigue mouse model were tested. The results showed that CYP is a mixture with an average Mw of 75.57 kDa and is mainly composed of rhamnose, glucuronic acid, glucose, galactose, and arabinose with a molar ratio of 0.01 : 0.06 : 1.00 : 0.17 : 0.01. CYP increased the exhausting swimming time, which was decreased in the cisplatin (DDP) control group and the model group. CYP also increased the content of ATP in musculus gastrocnemius, which was down-regulated by DDP; the DDP had significantly enhanced the contents of interleukin-1ß (IL-lß), malondialdehyde (MDA), blood urea nitrogen (BUN) and lactic dehydrogenase (LDH) and inhibited the activity of superoxide dismutase (SOD) in the muscle. Administration of CYP decreased the levels of IL-lß, MDA, BUN and LDH, and up-regulated the SOD activity. The DDP + CYP group presented a decreased tumor volume and a lower tumor weight as compared with the model group. Moreover, the mice in the CYP or DDP + CYP groups had heavier body weights than the mice in the model group and DDP group. These results suggest that CYP should improve cancer-related fatigue via the regulation of inflammatory responses, oxidative stress and increase in energy supplementation.

Controlling Factors and Formation Models of Organic Matter Accumulation for the Upper Permian Dalong Formation Black Shale in the Lower Yangtze Region, South China: Constraints from Geochemical Evidence.

The black shale in the upper Permian Dalong Formation is considered as an excellent source rock in the Lower Yangtze region. However, mechanisms of organic matter (OM) accumulation in such a setting are scarcely understood. Here, the characteristics of total organic carbon (TOC) and elemental geochemistry of 33 rock samples from GD1 well are systematically investigated to characterize the paleoenvironmental conditions and OM accumulation mechanisms. Results show that the lower and middle parts of Dalong Formation (section A) display high TOC contents ranging from 1.19 to 6.45% (average 3.19%), whereas the upper part (section B) exhibits medium TOC contents varying from 1.18 to 4.90% (average 2.09%). These data also elucidate that the target shales were deposited in a complex paleoenvironment with moderate to strong water-mass restriction that was characterized by warm and semiarid-semihumid paleoclimate, high biotic productivity, fluctuating plaeoredox conditions, and a relatively high sedimentary rate. Compared to the organic-rich shales from section A mainly developed under an anoxic condition, shales from section B formed in an oxic-to-dysoxic water environment exhibited a comparatively higher sedimentary rate. Moreover, among all these factors that might affect OM accumulation, the paleoredox conditions appear to be the dominant controlling factors for section A, whereas the biotic productivity, paleoredox conditions, and sedimentary rate are the main controlling factors for section B. Finally, two formation models for OM accumulation in Dalong Formation shale in the Lower Yangtze region are proposed. The "preservation model" for OM accumulation in section A emphasizes that the reducing deep-water environment, which was mainly caused by the regional sea level rise, is favorable for OM preservation. The "integrated model" for OM accumulation in section B stresses that greater biotic productivity intensifies respiratory oxygen consumption in a water column and a higher sedimentary rate can greatly shorten OM exposure time for respiration by oxygen, both of which cause OM accumulation under an oxidizing water environment. These findings also add to our knowledge that despite the oxygenated water environment during shale deposition, TOC contents are not necessarily lower.

Low molecular mass organogelator based gel electrolyte with effective charge transport property for long-term stable quasi-solid-state dye-sensitized solar cells.

Stable quasi-solid-state dye-sensitized solar cells (DSC) were fabricated using 12-hydroxystearic acid as a low molecular mass organogelator (LMOG) to form gel electrolyte. TEM image of the gel exhibited the self-assembled network constructed by the LMOG, which hindered flow and volatilization of the liquid. The formation of less-mobile polyiodide ions such as I 3 (-) and I 5 (-) confirmed by Raman spectroscopy increased the conductivity of the gel electrolytes by electronic conduction process, which should be rationalized by the Grotthuss-type electron exchange mechanism caused by rather packed polyiodide species in the electrolytes. The results of the accelerated aging tests showed that the gel electrolyte based dye-sensitized solar cell could retain over 97% of its initial photoelectric conversion efficiency value after successive heating at 60 degrees C for 1000 h and device degradation was also negligible after one sun light soaking with UV cutoff filter for 1000 h.

Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors.

We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3-triazole derivatives via a Cu(i)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. The newly synthesized compounds were evaluated for their inhibition activity against Electrophorus electricus acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited potent inhibition against AChE and BChE with IC50 values of 4.89 µM and 3.61 µM, respectively. Further structure-activity relationship (SAR) and molecular modeling studies may provide valuable insights into the design of better tacrine-triazole analogues with potential therapeutic applications for AD.