Investigating the efficacy and mechanisms of Jinfu'an decoction in treating non-small cell lung cancer using network pharmacology and in vitro and in vivo experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinfu'an Decoction (JFAD) is a traditional Chinese decoction used in lung cancer treatment to improve patient quality of life and survival. Previous research has established that JFAD has a significant therapeutic effect on non-small cell lung cancer (NSCLC), although the underlying molecular mechanisms have not been largely underexplored. AIM OF THE STUDY: We used network pharmacology to identify the putative active ingredients of JFAD and conducted experimental studies to determine the potential molecular mechanism of JFAD in NSCLC treatment. MATERIALS AND METHODS: The herbal components in JFAD-containing serum were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), and targets associated with the anti-lung cancer metastasis effects of JFAD were retrieved from various databases. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Next, the protein-protein interactions network and the "JFAD-Chemical Component-Target-KEGG Pathway" network were constructed. The network pharmacology findings were confirmed by in vitro and in vivo experiments. In vitro experiments were conducted to assess cell viability by CCK8 assay, cell cycle analysis by propidium iodide (PI) assay, and migration and invasion ability of cells by the transwell assay. In vivo experiments were performed to assess the efficacy of JFAD on the tumor by observing the growth of transplanted tumor models in nude mice and evaluated by in vivo bioluminescence imaging. Moreover, we assessed the effect of JFAD on the PI3K/Akt signaling pathway and proteins of Lumican, p120ctn, and specific RhoGTP enzyme family members (RhoA, Rac1, and RhoC) by Western Blot and immunohistochemistry. RESULTS: 32 herbal components were identified in the JFAD-containing serum, which potentially acted on 229 targets related to lung cancer metastasis. Network pharmacology results suggested that JFAD may treat lung cancer metastasis by targeting the PI3K/Akt pathway via regulating multiple core targets. Our experiments showed that JFAD suppressed the proliferation of A549 cells in vitro, induced cell cycle arrest, and reduced the migration and invasion ability of A549 cells. Our in vivo study revealed that JFAD inhibited tumor growth in a nude mouse model. Additionally, we found that JFAD could downregulate the expression of the PI3K/Akt pathway and affect the expression of Lumican, p120ctn, and specific RhoGTPase family members. CONCLUSIONS: In conclusion, through network pharmacology, we have unveiled the underlying mechanisms that link the various components, targets, and pathways influenced by JFAD in the context of lung cancer metastasis. Our experimental results suggest that the oncostatic effects of JFAD may be achieved by upregulating the expression of Lumican/p120ctn and downregulating the levels of specific RhoGTPase family members, which in turn block the PI3K/Akt signaling pathway.

Quality evaluation of Pterocephali Herba through simultaneously quantifying 18 bioactive components by UPLC-TQ-MS/MS analysis.

Pterocephali Herba (PH), the dried whole plant of Pterocephalus hookeri, is a Tibetan medicine commonly used to treat rheumatoid arthritis (RA). Iridoids, triterpenoids, flavonoids and phenylpropanoids are the major groups of bioactive constituents from PH. However, only ursolic acid and oleanolic acid, two unspecific triterpenoid components, are used as markers for the quality control of PH in Chinese Pharmacopoeia. Herein, an UPLC-TQ-MS/MS integrating SIR and MRM mode method for simultaneously quantifying 18 components, i.e., 9 iridoids, 3 triterpenoids, 3 phenylpropanoids, 2 flavonoids and quinic acid, in PH was developed and validated, and was used to evaluate 10 batches of PH samples from different origins. Hierarchical cluster analysis (HCA) was used to show the clustering of PH samples, while spearman correlation analysis was adopted to evaluate the correlation between ursolic acid/oleanolic acid and other quantified components. It was found that the established method was sensitive, precise, and accurate enough for the simultaneous quantification of 18 analytes in PH samples. Significant differences were found among the contents of 18 components in PH samples, no apparent clustering of the quality of PH samples was found to be related to its origins, and the contents of ursolic acid/oleanolic acid were only significantly correlated to the content of sylvestroside I, dipsanoside B, dipsanoside A in PH. Our results suggested that the newly established multi-components quantitative method is an improved approach for quality evaluation of PH samples. Furthermore, the holistic quality was inconsistent among PH samples, and ursolic acid/oleanolic acid alone could not indicate the holistic quality variation trend of PH.

Assembly and analysis of the complete mitochondrial genome of Forsythia suspensa (Thunb.) Vahl.

BACKGROUND: Forsythia suspensa (Thunb.) Vahl is a valuable ornamental and medicinal plant. Although the nuclear and chloroplast genomes of F. suspensa have been published, its complete mitochondrial genome sequence has yet to be reported. In this study, the genomic DNA of F. suspensa yellowish leaf material was extracted, sequenced by using a mixture of Illumina Novaseq6000 short reads and Oxford Nanopore PromethION long reads, and the sequencing data were assembled and annotated. RESULT: The F. suspensa mitochondrial genome was obtained in the length of 535,692 bp with a circular structure, and the GC content was 44.90%. The genome contains 60 genes, including 36 protein-coding genes, 21 tRNA genes, and three rRNA genes. We further analyzed RNA editing of the protein-coding genes, relative synonymous codon usage, and sequence repeats based on the genomic data. There were 25 homologous sequences between F. suspensa mitochondria and chloroplast genome, which involved the transfer of 8 mitochondrial genes, and 9473 homologous sequences between mitochondrial and nuclear genomes. Analysis of the nucleic acid substitution rate, nucleic acid diversity, and collinearity of protein-coding genes of the F. suspensa mitochondrial genome revealed that the majority of genes may have undergone purifying selection, exhibiting a slower rate of evolution and a relatively conserved structure. Analysis of the phylogenetic relationships among different species revealed that F. suspensa was most closely related to Olea europaea subsp. Europaea. CONCLUSION: In this study, we sequenced, assembled, and annotated a high-quality F. suspensa mitochondrial genome. The results of this study will enrich the mitochondrial genome data of Forsythia, lay a foundation for the phylogenetic development of Forsythia, and promote the evolutionary analysis of Oleaceae species.

Publications on ultrasound-guided thermal ablation for thyroid nodules from 2000 to 2022: a bibliometric analysis.

BACKGROUND: Thyroid nodules are increasingly treated with minimally invasive surgery. Thermal ablation could efficiently treat patients with benign thyroid nodules, recurrent thyroid cancer, and low-risk papillary thyroid carcinoma. This research aims to explore the research field of thermal ablation for thyroid nodules using bibliometric analysis. METHODS: The web of science core collection (WoSCC) database was utilized from its inception to 1 October 2022, to collect research articles and reviews on ultrasound-guided thermal ablation for thyroid nodules. We applied the R package 'bibliometrix' to summarize the main findings, calculate the occurrences of the top keywords and visualize the international collaboration networks. The co-authorship and co-occurrence analyses were conducted with VOSviewer software. CiteSpace was used to identify the top references and keywords with the highest citation bursts. RESULTS: A total of 820 publications from 32 countries were retrieved. The annual number of related publications showed an increasing trend. China, Italy, and Korea were the most contributing countries. The University of Ulsan College of Medicine in Korea was the most productive institution, and Jung Hwan Baek published the maximum number of articles. The International Journal of Hyperthermia was the most productive journal. 'Papillary thyroid micro-carcinoma (PTMC)' and 'association guideline' were the most frequently used keywords in the field of thermal ablation for thyroid nodules, which indicated the potential hot research topics and frontiers in the future. CONCLUSION: This bibliometric study conducts a comprehensive analysis of publications on thermal ablation for thyroid nodules, which aids investigators in discovering potential research directions.

Acceptor engineering-facilitated versatile AIEgen for mitochondria-targeted multimodal imaging-guided cancer photoimmunotherapy.

Photoimmunotherapy has been acknowledged to be an unprecedented strategy to obtain significantly improved cancer treatment efficacy. In this regard, the exploitation of high-performance multimodal phototheranostic agents is highly desired. Apart from tailoring electron donors, acceptor engineering is gradually rising as a deliberate approach in this field. Herein, we rationally designed a family of aggregation-induced emission (AIE)-active compounds with the same donors but different acceptors based on the acceptor engineering. Through finely adjusting the functional groups on electron acceptors, the electron affinity of electron acceptors and the conformation of the compounds were simultaneously modulated. It was found that one of the molecules (named DCTIC), bearing a moderately electrophilic electron acceptor and the best planarity, exhibited optimal phototheranostic properties in terms of light-harvesting ability, fluorescence emission, reactive oxygen species (ROS) production, and photothermal performance. For the purpose of amplified therapeutic outcomes, DCTIC was fabricated into tumor and mitochondria dual-targeted DCTIC nanoparticles (NPs), which afforded good performance in the fluorescence/photoacoustic/photothermal trimodal imaging-guided photodynamic/photothermal-synergized cancer immunotherapy with the combination of programmed cell death protein-1 (PD-1) antibody. Not only the primary tumors were totally eradicated, but efficient growth inhibition of distant tumors was also realized.

The effectiveness of blood-activating and stasis-transforming traditional Chinese medicines (BAST) in lung cancer progression-a comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Blood-activating and stasis-transforming traditional Chinese medicines (BAST) are a class of herbs that have the effect of dilating blood vessels and dispersing stagnation. Modern pharmaceutical research has demonstrated that they are capable of improving hemodynamics and micro-flow, resist thrombosis and promote blood flow. BAST contain numerous active ingredients, which can theoretically regulate multiple targets at the same time and have a wide range of pharmacological effects in the treatment of diseases including human cancers. Clinically, BAST have minimal side effects and can be used in combination with Western medicine to improve patients' quality of life, lessen adverse effects and minimize the risk of recurrence and metastasis of cancers. AIM OF THE REVIEW: We aimed to summarize the research progression of BAST on lung cancer in the past five years and present a prospect for the future. Particularly, this review further analyzes the effects and molecular mechanisms that BAST inhibit the invasion and metastasis of lung cancer. MATERIALS AND METHODS: Relevant studies about BSAT were collected from PubMed and Web of science. RESULTS: Lung cancer is one of the malignant tumors with the highest mortality rate. Most patients with lung cancer are diagnosed at an advanced stage and are highly susceptible to metastasis. Recent studies have shown that BAST, a class of traditional Chinese medicine (TCM) with the function of opening veins and dispersing blood stasis, significantly improve hemodynamics and microcirculation, prevent thrombosis and promote blood flow, and thereby inhibiting the invasion and metastasis of lung cancer. In the current review, we analyzed 51 active ingredients extracted from BAST. It was found that BAST and their active ingredients contribute to the prevention of invasion and metastasis of lung cancer through multiple mechanisms, such as regulation of EMT process, specific signaling pathway and metastasis-related genes, tumor blood vessel formation, immune microenvironment and inflammatory response of tumors. CONCLUSIONS: BSAT and its active ingredients have showed promising anticancer activity and significantly inhibit the invasion and metastasis of lung cancer. A growing number of studies have realized their potential clinical significance in the therapy of lung cancer, which will provide substantial evidences for the development of new TCM for lung cancer therapy.

Hybrid mental tasks based human computer interface via integration of pronunciation and motor imagery.

Objective.Among the existing active brain-computer interfaces (BCI), the motor imagination (MI) is widely used. To operate the MI BCI effectively, subjects need to carry out trainings on corresponding imagining tasks. Here, we studied how to reduce the discomfort and fatigue of active BCI imaginary tasks and the inability to concentrate on them while improving the accuracy.Approach.This paper proposes a hybrid BCI composed of MI and pronunciation imagination (PI). The electroencephalogram signals of ten subjects are recognized by the adaptive Riemannian distance classification and the improved frequency selective filter-bank Common Spatial Pattern recognition.Main results.The results show that under the new paradigm with the combination of MI and PI, the recognition accuracy is higher than the MI alone. The highest recognition rate of the proposed hybrid system can reach more than 90%. Furthermore, through the subjects' scoring results of the operation difficulty, it is concluded that the designed hybrid paradigm is more operable than the traditional BCI paradigm.Significance.The separable tasks in the active BCI are limited and the accuracy needs to be improved. The new hybrid paradigm proposed by us improves the accuracy and operability of the active BCI system, providing a new possibility for the research direction of the active BCI.

Assembly and comparative analysis of the complete mitochondrial genome of Bupleurum chinense DC.

BACKGROUND: Bupleurum chinense(B. chinense) is a plant that is widely distributed globally and has strong pharmacological effects. Though the chloroplast(cp) genome of B. chinense has been studied, no reports regarding the mitochondrial(mt) genome of B. chinense have been published yet. RESULTS: The mt genome of B.chinense was assembled and functionally annotated. The circular mt genome of B. chinense was 435,023 bp in length, and 78 genes, including 39 protein-coding genes, 35 tRNA genes, and 4 rRNA genes, were annotated. Repeat sequences were analyzed and sites at which RNA editing would occur were predicted. Gene migration was observed to occur between the mt and cp genomes of B. chinense via the detection of homologous gene fragments. In addition, the sizes of plant mt genomes and their GC content were analyzed and compared. The sizes of mt genomes of plants varied greatly, but their GC content was conserved to a greater extent during evolution. Ka/Ks analysis was based on code substitutions, and the results showed that most of the coding genes were negatively selected. This indicates that mt genes were conserved during evolution. CONCLUSION: In this study, we assembled and annotated the mt genome of the medicinal plant B. chinense. Our findings provide extensive information regarding the mt genome of B. chinense, and help lay the foundation for future studies on the genetic variations, phylogeny, and breeding of B. chinense via an analysis of the mt genome.

Oxidation and Reduction Dual-Responsive Polymeric Prodrug Micelles Co-delivery Precisely Prescribed Paclitaxel and Honokiol for Laryngeal Carcinoma Combination Therapy.

Laryngeal carcinoma is the most common head and neck malignancy globally, and chemotherapy is still the most common treatment for this type of carcinoma. Monotherapy has become powerless because of the lack of drugs in the anticancer agent library, the difficult process of new drug discovery, and the widespread drug resistance. Combination therapy with two agents, in particular Chinese herbal medicines with chemotherapy drugs, is a potential alternative to chemotherapy alone. However, combination therapy faces difficulties in delivering multiple drugs to tumor tissue in a precise ratio. Here, a cocktail polymeric prodrug micelle (PHPPM) was developed using an oxidation and reduction dual-responsive polymeric paclitaxel (PTX) and polymeric honokiol (HK) prodrugs. Both of them were obtained by covalently conjugating the drug to dextran via diselenium bonds. Following optimization and characterization, the PHPPM with the precise mass ratio of PTX and HK was obtained, enabling ratiometric drug loading, synchronized drug release in response to tumor high-level reactive oxygen species and glutathione environment, long blood circulation, and high tumor accumulation. This co-delivery system can effectively inhibit laryngeal carcinoma growth in vitro and in vivo. Codelivery of chemotherapy agents and Chinese herbal medicine with a precise ratio and controlled release of the two drugs at the tumor site provides an effective approach to clinical therapy for other laryngeal carcinomas.

Effect of Fu Yan Qing prescription on pelvic effusion, mass absorption and microenvironment of pelvic blood stasis in patients with sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type.

Objective: To investigate the effect of Fu Yan Qing prescription on sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type. Methods: Total 80 patients with sequelae of sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type were admitted to Baoding No.1 Central Hospital from December, 2018 to April, 2020 and divided into two groups according to the random number table, with 40 cases in each group. Patients in the control group were treated with conventional western medicine, while patients in the observation group were treated with Fu Yan Qing prescription orally. The clinical efficacy, the changes of traditional Chinese medicine (TCM) syndromes, local sign scores, visual analog scale (VAS) of pain, pelvic mass size, pelvic fluid volume and uterine blood flow parameters of the two groups before and after treatment were observed and compared, and the safety of the two groups was evaluated. Results: The total efficacy after treatment in the observation group was 87.5%, which was significantly higher than that of 67.5% in the control group (p<0.05). The TCM syndrome scores, local signs scores, pain scores, size of pelvic mass and pelvic effusion in both groups decreased significantly after treatment (p<0.05), PSV indexes of the two groups were significantly increased after treatment (p<0.05), and these changes were even more pronounced in the observation group (p<0.05). Compared with before treatment, PI and RI indexes of the observation group were significantly decreased after treatment (p<0.05). The observation group experienced an adverse reaction in 7.5% cases considerably lower than the 27.5% of the control group (p<0.05). Conclusion: Fu Yan Qing prescription is a safe and reliable treatment for patients with sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type. It is worth promotion in clinical practice.

Selenium nanoparticles are effective in penetrating pine and causing high oxidative damage to Bursaphelenchus xylophilus in pine wilt disease control.

BACKGROUND: Research on selenium nanoparticles (SeNPs) in chemical defense and chemotherapy of plants has developed rapidly owing to their high microbial toxicity, environmental safety, and degradability. Pine wilt disease (PWD) threatens pine forests worldwide; however, it is difficult to kill the nematodes (Bursaphelenchus xylophilus) inside the tree that cause PWD using traditional pesticide formulations. SeNPs could be the key to controlling PWD. RESULTS: In this study, approximately 50 nm SeNPs were prepared using a simple and green method, and chitosan was used to increase their biocompatibility and stability. The preparation and characterization results showed that the prepared SeNPs coated with chitosan (SeNPs@CS) were spherical and evenly dispersed. The bioassay results showed that SeNPs@CS had an LC50 of 15.627 mg L-1 against B. xylophilus. In addition, the killing mechanism of SeNPs@CS against B. xylophilus was studied. Confocal microscopy and transmission electron microscopy demonstrated that B. xylophilus were killed by reactive oxygen species, and the penetration of nano-form materials to B. xylophilus was higher than that of non-nano-form materials. To verify the effective penetration of SeNPs in pine tissues, Cy5-labeled SeNPs@CS was observed inside pine needles and branches using frozen sections and confocal microscopy. In addition, the cytotoxicity of SeO2 and SeNPs@CS was tested, and the results showed that the cytotoxicity of SeNPs@CS to MC3T3-E1 cells was reduced. CONCLUSION: These results show that SeNPs are expected to be used as a new strategy for the control of PWD with oxidative damage and high penetration to B. xylophilus and effective target penetration and biosafety. © 2022 Society of Chemical Industry.

Analysis of Molecular Mechanism of YiqiChutan Formula Regulating DLL4-Notch Signaling to Inhibit Angiogenesis in Lung Cancer.

In order to explore the specific mechanism of YiqiChutan formula (YQCTF) in inhibiting the angiogenesis of lung cancer and its relationship with delta-like ligand 4- (DLL4-) Notch signaling, 30 healthy BALB/c-nu/nu rats were selected and divided into three groups: A549 group (implanted with lung adenocarcinoma cell line A549), NCI-H460 group (implanted with human lung large-cell carcinoma cell line NCI-H460), and NCI-H446 group (implanted with human lung small cell carcinoma cell line NCI-H446) for constructing lung cancer transplanted tumor models. After modeling, the group treated with normal saline was taken as control group, 200 mg/kg of YQCTF was adopted for intervention, and the tumor volume and growth inhibition rate were compared with the vascular targeted inhibitor Sorafenib. HE staining, CD31 fluorescent antibody staining, and microelectron microscopy were adopted to observe the neovascular endothelial cells of the transplanted tumor. The expression of VEGF, HIF-1α, DLL4, and Notch-1 in the transplanted tumors in each group was detected by Western blot and RT-PCR at the protein level or mRNA level. Compared with the control group, the YQCTF-treated group had obvious inhibitory effect on lung cancer transplanted tumor and lung cancer angiogenesis. In the YQCTF-treated group, the density of angiogenesis decreased significantly and the vascular lumen structure also decreased, and the expression levels of VEGF, HIF-1α, DLL4, and Notch-1 in the YQCTF-treated group were all lower than those in the control group. YQCTF could inhibit the growth of lung cancer transplanted tumor through antiangiogenesis, and it could also reduce the amount of angiogenesis in lung cancer transplanted tumor. In addition, the generation of lumen structure was also hindered, which was realized through the VEGF signaling pathway and DLL4-Notch signaling pathway.

Chemical constituents of Ferula seravschanica.

Phytochemical investigation of Ferula seravschanica afforded seven new compounds, including three new bicyclic-type sesquiterpene coumarins (1-3), two new monocyclic-type sesquiterpene coumarins (16-17), two new phenylpropanoids (23-24) as well as twenty-two known compounds (4-15, 18-22, and 25-29). The structures of new compounds were determined by HRESIMS, NMR, ECD calculations, and X-ray single-crystal diffraction analysis. Furthermore, crude EtOAc extract and separated fractions (F1-F12) possessed cytotoxic activity against four human tumor cell lines (HT-29, DU145, HeLa, and Jurkat). Subsequently, we examined Jurkat inhibitory activity of isolated compounds. Compound 12 significantly inhibited the proliferation of the leukemia cells with IC50 value of 2.50 µM.

Cortical reorganization following auditory deprivation predicts cochlear implant performance in postlingually deaf adults.

Long-term hearing loss in postlingually deaf (PD) adults may lead to brain structural changes that affect the outcomes of cochlear implantation. We studied 94 PD patients who underwent cochlear implantation and 37 patients who were MRI-scanned within 2 weeks after the onset of sudden hearing loss and expected with minimal brain structural changes in relation to deafness. Compared with those with sudden hearing loss, we found lower gray matter (GM) probabilities in bilateral thalami, superior, middle, inferior temporal cortices as well as the central cortical regions corresponding to the movement and sensation of the lips, tongue, and larynx in the PD group. Among these brain areas, the GM in the middle temporal cortex showed negative correlation with disease duration, whereas the other areas displayed positive correlations. Left superior, middle temporal cortical, and bilateral thalamic GMs were the most accurate predictors of post-cochlear implantation word recognition scores (mean absolute error [MAE] = 10.1, r = .82), which was superior to clinical variables used (MAE: 12.1, p < .05). Using the combined brain morphological and clinical features, we achieved the best prediction of the outcome (MAE: 8.51, r = .90). Our findings suggest that the cross-modal plasticity allowing the superior temporal cortex and thalamus to process other modal sensory inputs reverses the initially lower volume when deafness becomes persistent. The middle temporal cortex processing higher-level language comprehension shows persistent negative correlations with disease duration, suggesting this area's association with degraded speech comprehensions due to long-term deafness. Morphological features combined with clinical variables might play a key role in predicting outcomes of cochlear implantation.

Immunogenic exosome-encapsulated black phosphorus nanoparticles as an effective anticancer photo-nanovaccine.

Tumor vaccines are a promising form of cancer immunotherapy, but difficulties such as neo-antigen identification, activation of immune cells, and tumor infiltration prevent their clinical breakthrough. Interestingly, nanotechnology-based photothermal therapy (PTT) has great potential to overcome these barriers. Previous studies have shown that serum exosomes (hEX) from hyperthermia-treated tumor-bearing mice displayed an array of patient-specific tumor-associated antigens (TAAs), and strong immunoregulatory abilities in promoting dendritic cell (DC) differentiation and maturation. Here, we developed a tumor vaccine (hEX@BP) by encapsulating black phosphorus quantum dots (BPQDs) with exosomes (hEX) against a murine subcutaneous lung cancer model. In comparison with BPQDs alone (BP), hEX@BP demonstrated better long-term PTT performance, greater elevation of tumor temperature and tumor targeting efficacy in vivo. Vaccination with hEX@BP in combination with PTT further demonstrated an outstanding therapeutic efficacy against established lung cancer, and promoted the infiltration of T lymphocytes into the tumor tissue. Our findings demonstrated that hEX@BP might be an innovative cancer photo-nanovaccine that offers effective immuno-PTT against cancers.

Preparation of Strong Antioxidative, Therapeutic Nanoparticles Based on Amino Acid-Induced Ultrafast Assembly of Tea Polyphenols.

Nanoformulations offer the opportunity to overcome the shortcomings of drug molecules, such as low solubility, side effects, insufficient stability, etc., but in most of the current nanomedicines, nanocarriers as excipients do not directly participate in the therapy procedure. Accordingly, it is promising to develop the nanotherapeutics composed entirely of pharmaceutically active molecules. Tea polyphenols, especially epigallocatechin gallate (EGCG), are a kind of natural antioxidants with various biological and health beneficial effects and are extensively investigated as nutrients and anticancer drugs. Here, the size-tunable and highly active polyphenol nanoparticles were conveniently synthesized in water and could be massively produced with a simple facility. Compared to the previous strategies, either molecular assembly via oxidative coupling or combination with other biomacromolecules, the present preparation was conducted by the amino acid-triggered Mannish condensation reactions, thus permitting the flexible molecular design of various polyphenol nanoparticles by selecting different amino acids. This straightforward and ultrafast method actually opens up a novel means to make use of naturally reproducible polyphenols. Moreover, inheriting the salient properties of EGCG, these nanoparticles show strong antioxidation capacity, 10-fold higher than the extensively investigated polydopamine nanoparticles, and they are biosafe but have therapeutic effects, according to the in vitro and in vivo assessments of anticancer activity, which is promising for various biomedical purposes.

Discovery of diverse diterpenoid scaffolds from Euphorbia antiquorum and their activity against RANKL-induced osteoclastogenesis.

Seven new diterpenoids, euphorantones A-D (1, 3, 6, and 10), 8,12,13-epi-3,7,12-O-triacetyl-8-O-(2-methylbutanoyl)-ingol (9), 8,12,13-epi-3,12-O-diacetyl-7-O-benzoyl-8-methoxyingol (11), 2,3-epi-7,12-diacetate-8-benzoate-ingol (12), together with eighteen known compounds (2, 4-5, 7-8, and 13-25), were isolated from the aerial parts of Euphorbia antiquorum L.. The structures of new compounds 1, 3, 6, and 9-12 were elucidated by extensive spectroscopic analyses. The absolute configurations of new compounds were assigned using X-ray diffraction, Rh2(OCOCF3)4-induced CD spectrum, and confirmed through comparison of the calculated and experimental 13C NMR and electronic circular dichroism (ECD) data. Compounds 1-25 were evaluated for their inhibition of RANKL-induced osteoclastogenesis. Compound 1 showed the most potent inhibition of RANKL-induced osteoclastogenesis with IC50 value of 0.3 µM. It inhibited NFAT transcript activity and osteoclast related genes TRAcP, CTSK, and NFATc1 expression.

Effects of yeast culture supplementation and the ratio of non-structural carbohydrate to fat on growth performance, carcass traits and the fatty acid profile of the longissimus dorsi muscle in lambs.

The effects of yeast culture (YC) supplementation and the dietary ratio of non-structural carbohydrate to fat (NSCFR) on growth performance, carcass traits and fatty acid profile of the longissimus dorsi (LD) muscle in lambs were determined in a 2 × 3 full factorial experiment. Thirty-six Small-tailed Han lambs were randomly divided into six groups with six replicates per group. The lambs were fed one of the six pelleted total mixed rations (TMRs) for 60 days after 15 adaption days. The six rations were formed by two NSCFRs (11.37 and 4.57) and three YC supplementation levels (0, 0.8 and 2.3 g/kg dietary dry matter). The average daily gain (ADG), dry matter intake (DMI) and feed conversion ratio (FCR) data of each lamb were recorded and calculated. All the lambs were slaughtered for determining carcass traits and fatty acid profile of the LD muscle. DMI was significantly increased (p < 0.05) in a quadratic fashion with 0.8 g/kg of YC supplementation. Carcass weight (CW) and dressing percentage (DP) were significantly increased (p < 0.05) in a linear fashion with 2.3 g/kg of YC supplementation. Animals fed with high-NSCFR diet had higher (p < 0.05) contents of myristoleic acid (C14:1), pentadecanoic acid (C15:0) and cis-10-heptadecenoic acid (C17:1), and lower (p < 0.05) stearic acid (C18:0) content in LD muscle than those fed with low-NSCFR diet. Moreover, ADG, growth rate (GR), backfat thickness (BFT), percentages of crude fat (CF) and crude protein (CP), SFAs, MUFAs and PUFAs in LD muscle, were significantly affected (p < 0.05) by interaction of dietary NSCFR and supplemental YC level. Overall, YC not only improved the growth performance and carcass traits of the animals but also modified the fatty acid profile of the LD muscle. Furthermore, the effects of YC supplementation may depend on dietary compositions.

Effect of Yeast Culture (Saccharomyces cerevisiae) on Broilers: A Preliminary Study on the Effective Components of Yeast Culture.

This study was aimed at determining the effective ingredients of yeast culture (YC) for animal breeding. First, the contents of YCs obtained from various fermentation times were detected using gas-chromatography. A total of 85 compounds were identified. Next, 336 Arbor Acres (AA) broilers were randomly divided into seven experimental groups and fed a basal diet, diets supplemented with YCs obtained at various fermentation times, or SZ1 (a commercial YC product). A significant increase in body weight gain (BWG) and a significant decrease in feed conversion ratio (FCR) of AA broiler chicks were observed with YC supplementation. Additionally, most of blood and immunological indices were improved with YC supplementation. According to the production performance and the results of multivariate analysis, glycine, fructose, inositol, galactose, and sucrose were found as the potential effective compounds of YC and were involved in metabolic pathways including glycine, serine, and threonine metabolism. Supplementation with diets based on combinations of effective compounds improved weight gain, feed efficiency, serum immunoglobulin A, and immunoglobulin G, but decreased blood urea concentration. These findings suggest YCs as effective and harmless feed additives with improved nutritional properties for broiler chicks.

Differences in safety and efficacy of oral anticoagulants in patients with non-valvular atrial fibrillation: A Bayesian analysis.

BACKGROUND: Novel oral anticoagulants are the cornerstone of therapy for non-valvular atrial fibrillation patients to lower the risk of ischaemic stroke. Given the lack of head-to-head comparisons among oral anticoagulants, a Bayesian analysis was used to evaluate their safety and efficacy based on studies from real-world practice. METHODS: The PubMed, Embase, Cochrane and Web of Science databases were searched for relevant studies. Bayesian analyses were conducted to estimate hazard ratios (HR) and 95% credible intervals (CrI) for the safety and efficacy of oral anticoagulants. RESULTS: In the 22 studies included in our analysis, novel oral anticoagulants exhibited a clear advantage over warfarin in preventing ischaemic stroke, haemorrhagic stroke and, especially, intracranial haemorrhage. Incidence of major bleeding was lowest for apixaban, followed by dabigatran, warfarin and rivaroxaban. Gastrointestinal bleeding risk was lowest for apixaban, followed by warfarin, and was slightly lower for dabigatran than for rivaroxaban with no statistical difference (HR 1.05, 95% CrI 0.99-1.11). Ischaemic stroke risk was lowest for rivaroxaban, followed by apixaban, dabigatran and warfarin (HR 1.13, 95% CrI 1.07-1.20). CONCLUSION: In real-world practice, apixaban may represent the optimal treatment in terms of safety and efficacy for patients with non-valvular atrial fibrillation. For patients with high risk of ischaemic events but low bleeding risk, rivaroxaban may be preferable.