Design, synthesis and biological evaluation of piperine derivatives as potent antitumor agents.

A series of piperine derivatives were designed and successfully synthesized. The antitumor activities of these compounds against 293 T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines, were assessed through the MTT assay. Notably, compound H7 exhibited moderate activity, displaying reduced toxicity towards non-tumor 293 T cells while potently enhancing the antiproliferative effects in Hela and MDA-MB-231 cells. The IC50 values were determined to be 147.45 ± 6.05 µM, 11.86 ± 0.32 µM, and 10.50 ± 3.74 µM for the respective cell lines. In subsequent mechanistic investigations, compound H7 demonstrated a dose-dependent inhibition of clone formation, migration, and adhesion in Hela cells. At a concentration of 15 µM, its inhibitory effect on Hela cell function surpassed that of both piperine and 5-Fu. Furthermore, compound H7 exhibited promising antitumor activity in vivo, as evidenced by significant inhibition of tumor angiogenesis and reduction in tumor weight in a chicken embryo model. These findings provide a valuable scientific foundation for the development of novel and efficacious antitumor agents, particularly highlighting the potential of compound H7 as a therapeutic candidate for cervical cancer and breast cancer.

Correction: Construction of durable superhydrophobic and anti-icing coatings via incorporating boroxine cross-linked silicone elastomers with good self-healability.

Correction for 'Construction of durable superhydrophobic and anti-icing coatings via incorporating boroxine cross-linked silicone elastomers with good self-healability' by Hengfei Liang et al., Soft Matter, 2022, https://doi.org/10.1039/d2sm01106a.

Construction of durable superhydrophobic and anti-icing coatings via incorporating boroxine cross-linked silicone elastomers with good self-healability.

The fragility of the micro-nano structure makes superhydrophobic coatings highly susceptible to stress, resulting in a decrease in their superhydrophobic and anti-icing performance. In this work, we proposed a new insight to improve durability by incorporating a thin layer of self-healable elastomer with a dynamic network on the micro-nano structure. We constructed superhydrophobic coatings (EP/SiO2/BFVSE) with a three-layered structure of the epoxy resin/silica nanoparticle/silicon elastomer. The silicon elastomer (BFVES) with a B-O dynamic cross-linked network and fluorinated moieties was synthesized by graft polymerization on vinyl silicon oil. The preparation route is facile and convenient for mass production. BFVES has rapid self-healing properties for scratches at room-temperature, underwater and at -18 °C. EP/SiO2/BFVSE preserved apparently higher CAs after being immersed in pH = 1, pH = 13, and NaCl solutions for 96 h as compared with the EP/SiO2 coating. In a water striking environment, the CA of EP/SiO2/BFVSE was slightly decreased to 153°. SEM images further reveal that the recovery of superhydrophobicity and icephobicity is attributed to the self-healing behavior of the boroxine-containing silicon elastomer. The EP/SiO2/BFVSE coating also possesses additional self-healing ability under chemical oxidation. The high durability of the self-healable superhydrophobic coating enables great application potential in aircraft, marine vessels, and outdoor facilities in harsh environments.

Clinical sequencing uncovers the genomic characteristics and mutation spectrum of the 2018 African swine fever virus in Guangdong, China.

African swine fever (ASF) outbreak have caused tremendous economic loss to the pig industry in China since its emergence in August 2018. Previous studies revealed that many published sequences are not suitable for detailed analyses due to the lack of data regarding quality parameters and methodology, and outdated annotations. Thus, high-quality genomes of highly pathogenic strains that can be used as references for early Chinese ASF outbreaks are still lacking, and little is known about the features of intra-host variants of ASF virus (ASFV). In this study, a full genome sequencing of clinical samples from the first ASF outbreak in Guangdong in 2018 was performed using MGI (MGI Tech Co., Ltd., Shenzhen, China) and Nanopore sequencing platforms, followed by Sanger sequencing to verify the variations. With 22 sequencing corrections, we obtained a high-quality genome of one of the earliest virulent isolates, GZ201801_2. After proofreading, we improved (add or modify) the annotations of this isolate using the whole genome alignment with Georgia 2007/1. Based on the complete genome sequence, we constructed the methylation profiles of early ASFV strains in China and predicted the potential 5mC and 6mA methylation sites, which are likely involved in metabolism, transcription, and replication. Additionally, the intra-host single nucleotide variant distribution and mutant allele frequency in the clinical samples of early strain were determined for the first time and found a strong preference for A and T substitution mutation, non-synonymous mutations, and mutations that resulted in amino acid substitutions into Lysine. In conclusion, this study provides a high-quality genome sequence, updated genome annotation, methylation profile, and mutation spectrum of early ASFV strains in China, thereby providing a reference basis for further studies on the evolution, transmission, and virulence of ASFV.

Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway.

Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-κB), p-IKK, p-IκB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-κB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-κB and NLRP3 pathways.

Prediction of Facial Emotion Recognition Ability in Patients With First-Episode Schizophrenia Using Amplitude of Low-Frequency Fluctuation-Based Support Vector Regression Model.

Objective: There were few studies that had attempted to predict facial emotion recognition (FER) ability at the individual level in schizophrenia patients. In this study, we developed a model for the prediction of FER ability in Chinese Han patients with the first-episode schizophrenia (FSZ). Materials and Methods: A total of 28 patients with FSZ and 33 healthy controls (HCs) were recruited. All subjects underwent resting-state fMRI (rs-fMRI). The amplitude of low-frequency fluctuation (ALFF) method was selected to analyze voxel-level spontaneous neuronal activity. The visual search experiments were selected to evaluate the FER, while the support vector regression (SVR) model was selected to develop a model based on individual rs-fMRI brain scan. Results: Group difference in FER ability showed statistical significance (P < 0.05). In FSZ patients, increased mALFF value were observed in the limbic lobe and frontal lobe, while decreased mALFF value were observed in the frontal lobe, parietal lobe, and occipital lobe (P < 0.05, AlphaSim correction). SVR analysis showed that abnormal spontaneous activity in multiple brain regions, especially in the right posterior cingulate, right precuneus, and left calcarine could effectively predict fearful FER accuracy (r = 0.64, P = 0.011) in patients. Conclusion: Our study provides an evidence that abnormal spontaneous activity in specific brain regions may serve as a predictive biomarker for fearful FER ability in schizophrenia.

Hydroanthraquinones from Nigrospora sphaerica and Their Anti-inflammatory Activity Uncovered by Transcriptome Analysis.

Transcriptome analysis is shown to be an effective strategy to understand the potential function of natural products. Here, it is reported that 11 previously undescribed hydroanthraquinones [nigroquinones A-K (1-11)], along with eight known congeners, were isolated from Nigrospora sphaerica. Their structures were elucidated by interpreting spectroscopic and spectrometric data including high-resolution mass spectra and nuclear magnetic resonance. The absolute configurations of 1-11 were confirmed by electronic circular dichroism calculations. Transcriptome analysis revealed that 3 (isolated in the largest amount) might be anti-inflammatory. Assays based on LPS-induced RAW264.7 macrophages and zebrafish embryos confirmed that some of the isolated hydroanthraquinones attenuated the secretion of pro-inflammatory mediators in vitro and in vivo. Further Western blotting and immunofluorescence experiments indicated that 4 (which showed the most obvious nitric oxide inhibition) could suppress the expression of nuclear factor-kappa-B (NF-κB), phosphorylation of the inhibitor of NF-κB kinase and inhibit the transportation of NF-κB to the nucleus. Hence, the suppression of the NF-κB signaling pathway may be responsible for the anti-inflammatory effect. These results show that bioactivity evaluation on the basis of transcriptome analysis may be effective in the functional exploration of natural products.

Proliferatins suppress lipopolysaccharide-induced inflammation via inhibition of the NF-κB and MAPK signaling pathways.

Three previously undescribed polyketides [proliferatin A-C (1-3)] with anti-inflammatory activity were isolated from Fusarium proliferatum. 1-3 attenuated the production of inflammatory signal messengers including nitric oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the potential anti-inflammatory mechanism of 1-3 involved in the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels revealed that 1-3 can inhibit the phosphorylation of IκB kinase (IKK), the degradation of NF-κB Inhibitor-α (IκBα), the phosphorylation of nuclear factor-κB (NF-κB) and can reduce NF-κB transportation to the nucleus. Interestingly, 1-3 decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. Molecular docking models suggest that binding of 1-3 to TLR4-MD-2 complex may lead to inhibition of NF-κB and MAPK signaling pathways, which was confirmed in vitro by surface plasmon resonance (SPR) assays. 1-3 can thus constitute potential therapeutic candidates for the treatment of inflammation-associated diseases.

The PI3K/AKT signaling pathway: How does it regulate development of Sertoli cells and spermatogenic cells?

The PI3K/AKT signaling pathway is one of the most crucial regulatory mechanisms in animal cells, which can mainly regulate proliferation, survival and anti-apoptosis in cell lines. In the seminiferous epithelium, most studies were concentrated on the role of PI3K/AKT signaling in immature Sertoli cells (SCs) and spermatogonia stem cells (SSCs). PI3K/AKT signaling can facilitate the proliferation and anti-apoptosis of immature Sertoli cells and spermatogenic cells. Besides, in mature Sertoli cells, this pathway can disintegrate the structure of the blood-testis barrier (BTB) via regulatory protein synthesis and the cytoskeleton of Sertoli cells. All of these effects can directly and indirectly maintain and promote spermatogenesis in male testis.

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis.

Background: Excessive inflammation results in severe tissue damage as well as serious acute or chronic disorders, and extensive research has focused on finding new anti-inflammatory hit compounds with safety and efficacy profiles from natural products. As promising therapeutic entities for the treatment of inflammation-related diseases, fusaproliferin and its analogs have attracted great interest. However, the underlying anti-inflammatory mechanism is still poorly understood and deserves to be further investigated. Methods: For the estimation of the anti-inflammatory activity of fusaproliferin (1) and its analogs (2-4) in vitro and in vivo, lipopolysaccharide (LPS)-induced RAW264.7 macrophages and zebrafish embryos were employed. Then, transcriptome analysis was applied to guide subsequent western blot analysis of critical proteins in related signaling pathways. Surface plasmon resonance assays (SPR) combined with molecular docking analyses were finally applied to evaluate the affinity interactions between 1-4 and TLR4 and provide a possible interpretation of the downregulation of related signaling pathways. Results: 1-4 significantly attenuated the production of inflammatory messengers, including nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to reverse LPS stimulation and the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the anti-inflammatory process. Experimental verification at the protein level revealed that 1 can inhibit the activation of inhibitor of NF-κB kinase (IKK), degradation of inhibitor of NF-κB (IκB), and phosphorylation of NF-κB and reduce nuclear translocation of NF-κB. 1 also decreased the phosphorylation of MAPKs, including p38, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 1-4 exhibited affinity for the TLR4 protein with KD values of 23.5-29.3 µM. Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment of inflammation-associated diseases.

Phenolic glycosides from Sanguisorba officinalis and their anti-inflammatory effects.

Two new phenolic glycosides 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-3'-O-(3''-α-L-arabinofuranosyl)-ß-D-glucopyranoside. (1), 4-(4'-hydroxyphenyl)-2-butanone-4''-O-(6-ß-D-xylosyl)-ß-D-glucopyranoside (2), along with two known related analogues 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-3'-O-ß-D-glucopyranoside (3), 4-(4'-hydroxyphenyl)-2-butanone-4'-O-ß-D-glucopyranoside (4) were obtained from the roots of Sanguisorba officinalis. Combined with acid hydrolysis derivatization, the absolute configurations of these new compounds were elucidated by comprehensive analyses of spectroscopic data including nuclear magnetic resonance (NMR), electrospray ionization high resolution mass (HRESIMS) as well as circular dichroism (CD). Compounds 1-4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Aureonitol Analogues and Orsellinic Acid Esters Isolated from Chaetomium elatum and Their Antineuroinflammatory Activity.

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1ß, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

Functional roles of the microbiota-gut-brain axis in Alzheimer's disease: Implications of gut microbiota-targeted therapy.

Increasing scientific evidence demonstrates that the gut microbiota influences normal physiological homeostasis and contributes to pathogenesis, ranging from obesity to neurodegenerative diseases, such as Alzheimer's disease (AD). Gut microbiota can interact with the central nervous system (CNS) through the microbiota-gut-brain axis. The interaction is mediated by microbial secretions, metabolic interventions, and neural stimulation. Here, we review and summarize the regulatory pathways (immune, neural, neuroendocrine, or metabolic systems) in the microbiota-gut-brain axis in AD pathogenesis. Besides, we highlight the significant roles of the intestinal epithelial barrier and blood-brain barrier (BBB) in the microbiota-gut-brain axis. During the progression of AD, there is a gradual shift in the gut microbiota and host co-metabolic relationship, leading to gut dysbiosis, and the imbalance of microbial secretions and metabolites, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs). These products may affect the CNS metabolic state and immune balance through the microbiota-gut-brain axis. Further, we summarize the potential microbiota-gut-brain axis-targeted therapy including carbohydrates, probiotics, dietary measures, and propose new strategies toward the development of anti-AD drugs. Taken together, the data in this review suggest that remodeling the gut microbiota may present a tractable strategy in the management and development of new therapeutics against AD and other neurodegenerative diseases.

Discrimination of Single Living Rat Pancreatic α, ß, δ, and Pancreatic Polypeptide (PP) Cells Using Raman Spectroscopy.

Primary pancreatic α, ß, δ, and pancreatic polypeptide (PP) cells are reliable cell models for diabetes research. However, the separation and purification of these cells in living conditions remains an obstacle for researchers. The interaction of visible light with cellular molecules can produce Raman scattering, which can be analyzed to obtain cellular intrinsic molecular fingerprints. It has been speculated that primary pancreatic α, ß, δ, and PP cells can be identified and separated from each other according to their spectral differences. To test this hypothesis, Raman spectra detection was performed on rat islet cells. Single islet cells identified by Raman scattering under living conditions were verified using immunohistochemistry. Thus, Raman data were acquired from a pure line of islet cells as a training sample and then used to establish the discriminant function. Then, using the principal component analysis-linear discriminate analysis (PCA-LDA) method, the four types of islet cells could be identified and discriminated by Raman spectroscopy. This study provides a label-free and noninvasive method for discriminating islet cell types in a randomly distributed mixed islet cell population via their physical properties rather than by using antibodies or fluorescence labeling.

Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency.

Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA-GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions.

Transcriptome analysis of Gerbera hybrida ray florets: putative genes associated with gibberellin metabolism and signal transduction.

In this study, the transcriptome of the Gerbera hybrida ray floret was constructed using a high-throughput Illumina sequencing platform. All 47,104 UniGenes with an average length of 845 nt and an N50 equaling 1321 nt were generated from 72,688,546 total primary reads after filtering and assembly. A total of 36,693 transcripts were annotated by comparison with non-redundant National Center for Biotechnology Information (NCBI) protein (Nr), non-redundant NCBI nucleotide (Nt), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases after removing exogenous contaminated sequences. The majority of the genes that are associated with gibberellin metabolism and signal transduction were identified. The targets for signal transduction of other plant hormones were also enumerated. Our study provides a systematic overview of the hormone signal transduction genes that are involved in ray floral development in Asteraceae and should facilitate further understanding of the crucial roles of phytohormones in plant growth.

[The studies on the Ku Huang granula technology].

OBJECTIVE: To determine the optimum technology of the Ku Huang granula. METHODS: Making Emodin and Chrysophanol for index, using HPLC, extracturm softening point data and orthogonal design experiment to research the preparatory technology of the Ku Huang granula to screen the optimum technology. RESULTS: The Ku Huang granula was pelletized at 100% dextrin, 170 degrees C- 175 degrees C spray drying and at the conditions of 75% ethylalcohol, 85 degrees C, 4 Hz, 3 hours fluidizing pelletization. CONCLUSION: The optimum condition is reasonable.

[Study on efficiency of nitrogen and phosphorus removal by algal biofilm].

Cultivating algal biofilm on nitrogen (N) and phosphorus (P) in waters presents an alternative to control eutrophication. Under laboratory conditions, efficiency on nitrogen and phosphorus removal from synthetic wastewater, secondary effluent and eutrophic lake water by algal biofilm was assessed. Algal biofilm was mainly composed of blue-green algal species Oscillatoria princeps. During a 5-day treatment, for synthetic wastewater, secondary effluent and eutrophic lake water, removal rates of TN were 57.1%, 94.5% and 93.8%, respectively, removal rates of TP were 93%, 73% and 79%, respectively. The dried algal production were 3.7 - 7.2 g x m(-2)x d(-1), and the TKN and TP of algal biomass were 5.7% - 7.2% and 0.78% - 2.44%, respectively. Recovery of nutrients in harvested algal biomass accounted for about 20% - 39% for N and 65% - 82% for P.