Characterization and phylogenetic analysis of the complete mitochondrial genome sequence of Photinia serratifolia.

Plant mitochondrial genomes (mitogenomes) are a valuable source of genetic information for a better understanding of phylogenetic relationships. However, no mitogenome of any species in the genus of Photinia has been reported. In this study, using NGS sequencing, we reported the mitogenome assembly and annotation of Photinia serratifolia, which is 473,579 bp in length, contains 38 protein-coding genes, 23 tRNAs, and 6 rRNAs, with 61 genes have no introns. The rps2 and rps11 genes are missing in the P. serratifolia mitogenome. Although there are more editing sites (488) in the P. serratifolia mitogenome than in most angiosperms, fewer editing types were found in the P. serratifolia mitogenome, showing a clear bias in RNA-editing. Phylogenetic analysis based on the mitogenomes of P. serratifolia and 8 other taxa of the Rosaceae family reflected the exact evolutionary and taxonomic status of P. serratifolia. However, Ka/Ks analysis revealed that 72.69% of the protein-coding genes in the P. serratifolia mitogenome had undergone negative selections, reflecting the importance of those genes in the P. serratifolia mitogenome. Collectively, these results will provide valuable information for the evolution of P. serratifolia and provide insight into the evolutionary relationships within Photinia and the Rosaceae family.

Ganoderma lucidum polysaccharide inhibits HSC activation and liver fibrosis via targeting inflammation, apoptosis, cell cycle, and ECM-receptor interaction mediated by TGF-ß/Smad signaling.

BACKGROUND: Ganoderma lucidum polysaccharide (GLP) has many biological properties, however, the anti-fibrosis effect of GLP is unknown at present. PURPOSE: This study aimed to examine the anti-fibrogenic effect of GLP and its underlying molecular mechanisms in vivo and in vitro. STUDY DESIGN: Both CCl4-induced mouse and TGF-ß1-induced HSC-T6 cellular models of fibrosis were established to examine the anti-fibrogenic effect of a water-soluble GLP (25 kDa) extracted from the sporoderm-removed spores of G. lucidum.. METHOD: Serum markers of liver injury, histology and fibrosis of liver tissues, and collagen formation were examined using an automatic biochemical analyzer, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, ELISA, Western blotting, and qRT-PCR. RNA-sequencing, enrichment pathway analysis, Western blotting, qRT-PCR, and flow cytometry were employed to identify the potential molecular targets and signaling pathways that are responsible for the anti-fibrotic effect of GLP. RESULTS: We showed that GLP (150 and 300 mg/kg) significantly inhibited hepatic fibrogenesis and inflammation in CCl4-treated mice as mediated by the TLR4/NF-κB/MyD88 signaling pathway. We further demonstrated that GLP significantly inhibited hepatic stellate cell (HSCs) activation in mice and in TGF-ß1-induced HSC-T6 cells as manifested by reduced collagen I and a-SMA expressions. RNA-sequencing uncovered inflammation, apoptosis, cell cycle, ECM-receptor interaction, TLR4/NF-κB, and TGF-ß/Smad signalings as major pathways suppressed by GLP administration. Further studies demonstrated that GLP elicits anti-fibrotic actions that are associated with a novel dual effect on apoptosis in vivo (inhibit) or in vitro (promote), suppression of cell cycle in vivo, induction of S phase arrest in vitro, and attenuation of ECM-receptor interaction-associated molecule expressions including integrins ITGA6 and ITGA8. Furthermore, GLP significantly inhibited the TGF-ß/Smad signaling in mice, and reduced TGF-ß1 or its agonist SRI-011381-induced Smad2 and Smad3 phosphorylations, but increased Samd7 expression in HSC-T6 cells. CONCLUSION: This study provides the first evidence that GLP could be a promising dietary strategy for treating liver fibrosis, which protects against liver fibrosis and HSC activation through targeting inflammation, apoptosis, cell cycle, and ECM-receptor interactions that are mediated by TGF-ß/Smad signaling.

Laser-Induced Transient Self-Organization of TiNx Nano-Filament Percolated Networks for High Performance Surface-Mountable Filter Capacitors.

Filter capacitors (FCs) are substantial for digital circuits and microelectronic devices, and thus more compact FCs are eternally demanded for system miniaturization. Even though microsupercapacitors are broadly regarded as an excellent candidate for future FCs, yet due to the limitation of available electrode materials, the capacitive performance of reported MSCs drops sharply under high-frequency alternating current. Herein, we present a unique laser-induced transient self-organization strategy, which synergizes pulsed laser energy and multi-physical field controlled coalescence processes, leading to the rapid and controllable preparation of titanium nitride ultrafine nano-filaments (diameter ≈3-5 nm) networks. Their chaotic fractal nanoporous structure, superior specific surface area, and excellent conductivity render these nanostructures promising candidates for FCs. Surface-mounted filter capacitors based on this electrode material exhibit ultra-long cycle-life (2 000 000 cycles) with record ultrahigh volumetric energy density of 9.17 mWh cm-3 at 120 Hz in aqueous electrolyte, displaying advantages in function, size, and integrability compared with the state-of-the-art aluminum electrolytic capacitors. The method here provides a versatile toolbox for designing novel nanostructures with intriguing characteristics and insights for developing advanced and miniaturized filter and power devices.

NAG-1/GDF15 inhibits diabetic nephropathy via inhibiting AGE/RAGE-mediated inflammation signaling pathways in C57BL/6 mice and HK-2 cells.

AIMS: Our previous studies showed that the nonsteroidal anti-inflammatory drug-activated gene-1, or growth differentiation factor-15 (NAG-1/GDF15) inhibits obesity and diabetes in mice. The current study aimed to examine the role and molecular mechanisms of NAG-1/GDF15 in diabetic nephropathy (DN), which is largely unknown. MAIN METHODS: Both male and female wild-type (Wt) C57BL/6 mice and mice overexpressing human NAG-1/GDF15 (transgenic, Tg) were used, which were induced by high-fat diet (HFD)/streptozotocin (STZ) to establish the mouse model of DN. Transcriptome study was performed to identify the underlying molecular mechanisms of NAG-1/GDF15 against DN. In addition, human renal tubular epithelial cells (HK-2) were cultured with high glucose (HG) to establish a DN cellular model and were treated with NAG-1/GDF15 plasmid or the recombinant NAG-1/GDF15 protein for mechanism studies. KEY FINDINGS: Overexpression of NAG-1/GDF15 in Tg mice significantly alleviated HFD/STZ-induced typical symptoms of DN, improved lipid homeostasis, glucose intolerance, and insulin sensitivity. Histopathology of renal tissues revealed that NAG-1/GDF15 mice had significantly reduced renal injury, glycogen deposition, and renal fibrosis. Transcriptome study uncovered inflammation, cell adhesion, and the inflammation-related signaling pathways as major pathways suppressed in the NAG-1/GDF15 mice. Further studies demonstrated that NAG-1/GDF15 overexpression inhibited renal and systematic inflammation, inhibited the AGE/RAGE axis and its associated downstream inflammatory molecules and adhesion molecules, and inhibited the upregulation of TLR4/MyD88/NF-κB signaling pathway in mice. These results were further confirmed in HG-induced HK-2 cells. SIGNIFICANCE: NAG-1/GDF15 plays an important role in the inhibition of the development and progression of DN via targeting AGE/RAGE-mediated inflammation pathways.

Removing the sporoderm from the sporoderm-broken spores of Ganoderma lucidum improves the anticancer and immune-regulatory activity of the water-soluble polysaccharide.

Plant-derived polysaccharides have demonstrated promising anti-cancer effects via immune-regulatory activity. The aim of the current study was to compare the chemical property and the anticancer effects of polysaccharides extracted from the sporoderm-removed spores of the medicinal mushroom Ganoderma lucidum (RSGLP), which removed the sporoderm completely, with polysaccharides extracted from the sporoderm-broken spores of G. lucidum (BSGLP). We found that RSGLP has a higher extraction yield than BSGLP. HPGPC and GC-MS results revealed that both RSGLP and BSGLP are heteropolysaccharides, but RSGLP had a higher molecular weight and a different ratio of monosaccharide composition than BSGLP. MTT and flow cytometry results demonstrated that RSGLP exhibited much higher dose-efficacy in inhibiting cell viability and inducing apoptosis than BSGLP in 8 cancer cell lines representing colon (HCT116 and HT29), liver (HepG2 and Huh-7), breast (MDA-MB-231 and MCF-7), and lung cancers (NCI-H460 and A549). Furthermore, RSGLP is more effective in inhibiting HCT116 and NCI-H460 xenograft tumor growth and inhibiting tumor-induced splenomegaly than BSGLP in nude mice, suggesting a better effect on regulating immunity of RSGLP. Next, we found that RSGLP is more potent in inhibiting the level of serum inflammatory cytokines in nude mice, and in inhibiting the activation of macrophage RAW264.7 and the expression of the inflammatory mediators IL-1ß, TNF-α, iNOS, and COX-2 in vitro. This is the first study to compare the chemical properties, anti-cancer, and immune-regulatory effects of RSGLP and BSGLP using multiple cancer cell lines. Our results revealed that the sporoderm-removed spores of G. lucidum (RSGL) and RSGLP may serve as new anticancer agents for their promising immune-regulatory activity.

Development of a UPLC-MS/MS method for the determination of orelabrutinib in rat plasma and its application in pharmacokinetics.

The aim of the present study was to establish an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of orelabrutinib in rat plasma using futibatinib as internal standard (IS), and to apply it for a pharmacokinetic study in rats. Orelabrutinib was extracted from plasma by protein precipitation and quantitatively analyzed by UPLC-MS/MS. An Acquity UPLC BEH C18 column was used for rapid separation by gradient elution using 0.1% formic acid and acetonitrile as mobile phases. The validation results of bioanalytical methodology showed that the linearity of orelabrutinib in plasma samples was good within the concentration range of 1-2000 ng/ml. The lower limit of quantification (LLOQ) was 1 ng/ml. The precision of orelabrutinib ranged from 1.4% to 11.5%, with intra-day and inter-day accuracy ranging from -5.7% to 7.7% and -0.2% to 12.5%, respectively. The selectivity, stability, matrix effect and recovery of the method all met the requirements of quantitative analysis of biological samples. The method was simple, sensitive, accurate and specific, and had high recovery rate. It also could be successfully applied to the pharmacokinetic study of rats.

Motion correction and its impact on quantification in dynamic total-body 18F-fluorodeoxyglucose PET.

BACKGROUND: The total-body positron emission tomography (PET) scanner provides an unprecedented opportunity to scan the whole body simultaneously, thanks to its long axial field of view and ultrahigh temporal resolution. To fully utilize this potential in clinical settings, a dynamic scan would be necessary to obtain the desired kinetic information from scan data. However, in a long dynamic acquisition, patient movement can degrade image quality and quantification accuracy. METHODS: In this work, we demonstrated a motion correction framework and its importance in dynamic total-body FDG PET imaging. Dynamic FDG scans from 12 subjects acquired on a uEXPLORER PET/CT were included. In these subjects, 7 are healthy subjects and 5 are those with tumors in the thorax and abdomen. All scans were contaminated by motion to some degree, and for each the list-mode data were reconstructed into 1-min frames. The dynamic frames were aligned to a reference position by sequentially registering each frame to its previous neighboring frame. We parametrized the motion fields in-between frames as diffeomorphism, which can map the shape change of the object smoothly and continuously in time and space. Diffeomorphic representations of motion fields were derived by registering neighboring frames using large deformation diffeomorphic metric matching. When all pairwise registrations were completed, the motion field at each frame was obtained by concatenating the successive motion fields and transforming that frame into the reference position. The proposed correction method was labeled SyN-seq. The method that was performed similarly, but aligned each frame to a designated middle frame, was labeled as SyN-mid. Instead of SyN, the method that performed the sequential affine registration was labeled as Aff-seq. The original uncorrected images were labeled as NMC. Qualitative and quantitative analyses were performed to compare the performance of the proposed method with that of other correction methods and uncorrected images. RESULTS: The results indicated that visual improvement was achieved after correction of the SUV images for the motion present period, especially in the brain and abdomen. For subjects with tumors, the average improvement in tumor SUVmean was 5.35 ± 4.92% (P = 0.047), with a maximum improvement of 12.89%. An overall quality improvement in quantitative Ki images was also observed after correction; however, such improvement was less obvious in K1 images. Sampled time-activity curves in the cerebral and kidney cortex were less affected by the motion after applying the proposed correction. Mutual information and dice coefficient relative to the reference also demonstrated that SyN-seq improved the alignment between frames over non-corrected images (P = 0.003 and P = 0.011). Moreover, the proposed correction successfully reduced the inter-subject variability in Ki quantifications (11.8% lower in sampled organs). Subjective assessment by experienced radiologists demonstrated consistent results for both SUV images and Ki images. CONCLUSION: To conclude, motion correction is important for image quality in dynamic total-body PET imaging. We demonstrated a correction framework that can effectively reduce the effect of random body movements on dynamic images and their associated quantification. The proposed correction framework can potentially benefit applications that require total-body assessment, such as imaging the brain-gut axis and systemic diseases.

A chromosome-level genome assembly of Artocarpus nanchuanensis (Moraceae), an extremely endangered fruit tree.

Artocarpus nanchuanensis (Moraceae), which is naturally distributed in China, is a representative and extremely endangered tree species. In this study, we obtained a high-quality chromosome-scale genome assembly and annotation information for A. nanchuanensis using integrated approaches, including Illumina, Nanopore sequencing platform, and Hi-C. A total of 128.71 Gb of raw Nanopore reads were generated from 20-kb libraries, and 123.38 Gb of clean reads were obtained after filtration with 160.34× coverage depth and a 17.48-kb average read length. The final assembled A. nanchuanensis genome was 769.44 Mb with a 2.09 Mb contig N50, and 99.62% (766.50 Mb) of the assembled data was assigned to 28 pseudochromosomes. In total, 39,596 genes (95.10%, 39,596/41,636) were successfully annotated, and 129 metabolic pathways were detected. Plants disease resistance/insect resistance genes, plant-pathogen interaction metabolic pathways, and abundant biosynthesis pathways of vitamins, flavonoid, and gingerol were detected. Unigene reveals the basis of species-specific functions, and gene family in contraction and expansion generally implies strong functional differences in the evolution. Compared with other related species, a total of 512 unigenes, 309 gene families in contraction, and 559 gene families in expansion were detected in A. nanchuanensis. This A. nanchuanensis genome information provides an important resource to expand our understanding of the unique biological processes, nutritional and medicinal benefits, and evolutionary relationship of this species. The study of gene function and metabolic pathway in A. nanchuanensis may reveal the theoretical basis of a special trait in A. nanchuanensis and promote the study and utilization of its rare medicinal value.

The anxiolytic effect of koumine on a predatory sound stress-induced anxiety model and its associated molecular mechanisms.

BACKGROUND: Koumine is the most abundant alkaloid extracted from Gelsemium elegans Benth.. Preliminary studies by our research group have shown that koumine has significant anxiolytic effect, but this needs to be further confirmed. HYPOTHESIS/PURPOSE: To investigate the potential anxiolytic effect of koumine on predatory sound (PS) stress-induced anxiety models and preliminarily explore its therapeutic targets and molecular mechanisms. STUDY DESIGN AND METHODS: The anxiolytic effect of koumine in an animal model of acute PS stress-induced anxiety were determined. Then, neurosteroids levels in the main brain regions involved in anxiety disorders, as well as plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels, were determinated. Finally, to clarify the effect of koumine on translocator protein 18 kDa (TSPO), the affinity between koumine and TSPO was evaluated by surface plasmon resonance (SPR) technology. RESULTS: Koumine treatment mitigated anxiety-like behavior following acute PS stress in the open field test and elevated plus maze test. PS exposure significantly decreased progesterone and allopregnanolone levels in the PFC, Hip, and Amy and increased ACTH and CORT levels in plasma, and koumine administration significantly reversed these effects. Finally, the reliable SPR results showed that the KD of koumine with TSPO was 155.33 ± 11.0 µM, indicating that koumine is a human TSPO high-affinity ligand that has an affinity comparable to typical TSPO ligands. CONCLUSION: Our results show that koumine has obvious anxiolytic effect in the PS-induced anxiety model. Targeting TSPO-neurosteroids-HPA axis may be an important mechanism by which koumine exerts its anxiolytic effect.

Effect of Baicalein on the Pharmacokinetics of Cilostazol and Its Two Metabolites in Rat Plasma Using UPLC-MS/MS Method.

This study aimed to explore the effect of baicalein on the pharmacokinetics of cilostazol (CLZ) and its two metabolites 3,4-dehydro cilostazol (3,4-CLZ) and 4'-trans-hydroxy cilostazol (4'-CLZ) in rats using a newly established ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Ticagrelor was used as an internal standard (IS), then cilostazol and its two metabolites were separated by means of a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm) using gradient elution method with 0.4 ml/min of flow rate. Acetonitrile as organic phase and water with 0.1% formic acid as aqueous phase constructed the mobile phase. Selective reaction monitoring (SRM) mode and positive ion mode were preferentially chosen to detect the analytes. Twelve SD rats were divided into two groups (n = 6) when CLZ was administered orally (10 mg/kg) with or without oral baicalein (80 mg/kg). The selectivity, linearity, recovery, accuracy, precision, matrix effect and stability of UPLC-MS/MS assay were satisfied with the standards of United States Food and Drug Administration guidelines. In control group, AUC0-∞ and Cmax of CLZ were 2,169.5 ± 363.1 ng/ml*h and 258.9 ± 82.6 ng/ml, respectively. The corresponding results were 3,767.6 ± 1,049.8 ng/ml*h and 308.6 ± 87.9 ng/ml for 3, 4-CLZ, 728.8 ± 189.9 ng/ml*h and 100.3 ± 51.3 ng/ml for 4'-CLZ, respectively. After combination with baicalein, AUC0-∞ and Cmax of CLZ were 1.48, 1.38 times higher than the controls. Additionally, AUC0-∞ and Cmax were separately decreased by 36.12 and 19.54% for 3,4-CLZ, 13.11 and 44.37% for 4'-CLZ. Baicalein obviously alters the pharmacokinetic parameters of CLZ, 3,4-CLZ and 4'-CLZ in rats. These results suggested that there was a potential drug-drug interaction between baicalein and CLZ. Therefore, it must raise the awareness when concomitant use of CLZ with baicalein, the dosage regimen of CLZ should be taken into consideration, if this result is confirmed in clinical studies.

Growth differentiation factor-15 overexpression promotes cell proliferation and predicts poor prognosis in cerebral lower-grade gliomas correlated with hypoxia and glycolysis signature.

AIMS: Growth differentiation factor-15 (GDF15) plays complex and controversial roles in cancer. In this study, the prognostic value and the exact biological function of GDF15 in cerebral lower-grade gliomas (LGGs) and its potential molecular targets were examined. MAIN METHODS: Wilcoxon signed-rank test and logistic regression were applied to analyze associations between GDF15 expression and clinical characteristics using the Cancer Genome Atlas (TCGA) database. Overall survival was analyzed using Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) and the hypoxia risk model was conducted to identify the potential molecular mechanisms underlying the effects of GDF15 on LGGs tumorigenesis. The biological function of GDF15 was examined using gain- and loss-of-function experiments, and a recombinant hGDF15 protein in LGG SW1783 cells in vitro. KEY FINDINGS: We found that higher GDF15 expression is associated with poor clinical features in LGG patients, and an independent risk factor for overall survival among LGG patients. GSEA results showed that the poor prognostic role of GDF15 in LGGs is related to hypoxia and glycolysis signatures, which was further validated using the hypoxia risk model. Furthermore, GDF15 overexpression facilitated cell proliferation, while GDF15 siRNA inhibits cell proliferation in LGG SW1783 cells. In addition, GDF15 was upregulated upon CoCl2 treatment which induces hypoxia, correlating with the upregulation of the expressions of HIF-1α and glycolysis-related key genes in SW1783 cells. SIGNIFICANCE: GDF15 may promote LGG tumorigenesis that is associated with the hypoxia and glycolysis pathways, and thus could serve as a promising molecular target for LGG prevention and therapy.

Overexpression of NAG-1/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation.

Mitochondrial dysfunction and oxidative stress-mediated inflammasome activation play critical roles in the pathogenesis of the non-alcoholic fatty liver disease (NAFLD). Non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1), or growth differentiation factor-15 (GDF15), is associated with many biological processes and diseases, including NAFLD. However, the role of NAG-1/GDF15 in regulating oxidative stress and whether this process is associated with absent in melanoma 2 (AIM2) inflammasome activation in NAFLD are unknown. In this study, we revealed that NAG-1/GDF15 is significantly downregulated in liver tissues of patients with steatosis compared to normal livers using the Gene Expression Omnibus (GEO) database, and in free fatty acids (FFA, oleic acid/palmitic acid, 2:1)-induced HepG2 and Huh-7 cellular steatosis models. Overexpression of NAG-1/GDF15 in transgenic (Tg) mice significantly alleviated HFD-induced obesity and hepatic steatosis, improved lipid homeostasis, enhanced fatty acid ß-oxidation and lipolysis, inhibited fatty acid synthesis and uptake, and inhibited AIM2 inflammasome activation and the secretion of IL-18 and IL-1ß, as compared to their wild-type (WT) littermates without reducing food intake. Furthermore, NAG-1/GDF15 overexpression attenuated FFA-induced triglyceride (TG) accumulation, lipid metabolism deregulation, and AIM2 inflammasome activation in hepatic steatotic cells, while knockdown of NAG-1/GDF15 demonstrated opposite effects. Moreover, NAG-1/GDF15 overexpression inhibited HFD- and FFA-induced oxidative stress and mitochondrial damage which in turn reduced double-strand DNA (dsDNA) release into the cytosol, while NAG-1/GDF15 siRNA showed opposite effects. The reduced ROS production and dsDNA release may be responsible for attenuated AIM2 activation by NAG-1/GDF15 upon fatty acid overload. In conclusion, our results provide evidence that other than regulating lipid homeostasis, NAG-1/GDF15 protects against hepatic steatosis through a novel mechanism via suppressing oxidative stress, mitochondrial damage, dsDNA release, and AIM2 inflammasome activation.

NAG-1/GDF15 protects against streptozotocin-induced type 1 diabetes by inhibiting apoptosis, preserving beta-cell function, and suppressing inflammation in pancreatic islets.

The loss of functional insulin-producing ß-cells is a hallmark of type 1 diabetes mellitus (T1DM). Previously, we reported that the non-steroidal anti-inflammatory drug activated gene-1, or growth differentiation factor-15 (NAG-1/GDF15) inhibits obesity and improves insulin sensitivity in both genetic and dietary-induced obese mice. However, the regulatory role of NAG-1/GDF15 in the structure and function of ß-cells and the prevention of T1DM is largely unknown. In the current study, we reported that NAG-1/GDF15 transgenic (Tg) mice are resistant to diabetogenesis induced by multiple low-dose streptozotocin (MLD-STZ) treatment. NAG-1/GDF15 overexpression significantly reduced diabetes incidence, alleviated symptoms of T1DM, and improved MLD-STZ-induced glucose intolerance and insulin resistance. Both the mass and function of pancreatic ß cells were preserved in the NAG-1/GDF15 Tg mice as evidenced by significantly increased islet area and insulin production. The mechanistic study revealed that NAG-1/GDF15 significantly inhibited STZ-induced apoptosis and preserved the reduction of proliferation in the islets of the Tg mice as compared to the wild-type (WT) mice upon MLD-STZ treatment. Additionally, NAG-1/GDF15 significantly reduced both the serum and islet levels of the inflammatory cytokines (IL-1ß, IL-6, and TNFα), and reduced the expression of NF-κB expression and immune cells infiltration in the islets. Collectively, these results indicate that NAG-1/GDF15 is effective in improving STZ-induced glucose intolerance, probably was mediated via suppressing inflammation, inhibiting apoptosis, and preserving ß-cell mass and function.

A method for quantitatively separating the piezoelectric component from the as-received "Piezoelectric" signal.

Polymer-based piezoelectric devices are promising for developing future wearable force sensors, nanogenerators, and implantable electronics, etc. The electric signals generated by them are often assumed as solely coming from the piezoelectric effect. However, triboelectric signals originated from contact electrification between the piezoelectric devices and the contacted objects can produce non-negligible interfacial electron transfer, which is often combined with the piezoelectric signal to give a triboelectric-piezoelectric hybrid output, leading to an exaggerated measured "piezoelectric" signal. Herein, a simple and effective method is proposed for quantitatively identifying and extracting the piezoelectric charge from the hybrid signal. The triboelectric and piezoelectric parts in the hybrid signal generated by a poly(vinylidene fluoride)-based device are clearly differentiated, and their force and charge characteristics in the time domain are identified. This work presents an effective method to elucidate the true piezoelectric performance in practical measurement, which is crucial for evaluating piezoelectric materials fairly and correctly.

Simultaneous measurement of upadacitinib and methotrexate by UPLC-MS/MS and its pharmacokinetic application in rats.

Upadacitinib, as a selective and reversible Janus kinase (JAK) inhibitor, has been widely used in the treatment of atopic dermatitis, ulcerative colitis and other inflammatory bowel diseases and other immune-mediated diseases. The combination of methotrexate and upadacitinib is a common clinical treatment strategy for rheumatoid arthritis (RA) in recent years. In this study, we established an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for quantitative measurement of upadacitinib and methotrexate, by which we successfully determined pharmacokinetic parameters of them in rat plasma. In order to pretreat the samples, we used acetonitrile as the precipitant, and for the internal standard (IS), we chose tofacitinib. The Acquity BEHC18 (2.1 mm × 50 mm, 1.7 µm) column, with acetonitrile and 0.1% formic acid aqueous solution composed mobile phases, was used to separate upadacitinib, methotrexate and tofacitinib. A Xevo TQ-S triple quadrupole tandem mass spectrometer was used as the detecting instrument in the positive ion mode. For upadacitinib, excellent linearity was shown of this assay in the calibration range with 0.1-200 ng/mL, and as for methotrexate, the range was 0.05-100 ng/mL. As the results indicated, the lower limit of quantification (LLOQ) was respectively 0.1 and 0.05 ng/mL for upadacitinib and methotrexate, the intra- and inter-day precision were ≤ 13.3%, and the accuracy of all the analytes ranged from -4.1% to 12.7%. The recovery of each analyte was > 80.2% in this experiment, and matrix effects we observed were unobvious. The establishment of this method and its successful application in rat plasma can provide a theoretical and technical support for the deeper study of pharmacodynamics and the clinical medication strategies.

Ganoderma lucidum polysaccharide modulates gut microbiota and immune cell function to inhibit inflammation and tumorigenesis in colon.

This study investigated the effects of water-soluble polysaccharide extracted from the sporoderm-removed spores of Ganoderma lucidum (GLP) against AOM/DSS-induced inflammation, tumorigenesis, and gut microbiota modification, which has never been reported before. Our data revealed that GLP (200 and 300 mg/kg) decreased AOM/DSS-induced colitis and tumorigenesis, manifested by significantly reduced disease activity index score, and total number and size of tumors. Furthermore, GLP ameliorated AOM/DSS-induced microbiota dysbiosis, increased short-chain fatty acid production, and alleviated endotoxemia by inhibiting TLR4/MyD88/NF-κB signaling. Besides, GLP profoundly improved gut barrier function as evidenced by increased numbers of goblet cells, MUC2 secretion, and tight junction protein expressions. GLP treatment inhibited macrophage infiltration and downregulated IL-1ß, iNOS, and COX-2 expressions. Additionally, GLP inhibited lipopolysaccharides (LPS)-induced inflammation markers and MAPK (JNK and ERK) activation in macrophage RAW264.7, intestinal HT-29, and NCM460 cells. In conclusion, these results indicate that GLP is a promising prebiotic for the treatment of colorectal cancer.

Polysaccharides from sporoderm-removed spores of Ganoderma lucidum induce apoptosis in human gastric cancer cells via disruption of autophagic flux.

The sporoderm-broken spores of Ganoderma lucidum (G. lucidum) polysaccharide (BSGLP) have been demonstrated to inhibit carcinogenesis in several types of cancer. However, to the best of our knowledge, the anticancer effects of polysaccharides extracted from the newly developed sporoderm-removed spores of G. lucidum (RSGLP) have not been assessed. The present study first compared the anticancer effects of RSGLP and BSGLP in three gastric cancer cell lines and it was found that RSGLP was more potent than BSGLP in decreasing gastric cancer cell viability. RSGLP significantly induced apoptosis in AGS cells, accompanied by downregulation of Bcl-2 and pro-caspase-3 expression levels, and upregulation of cleaved-PARP. Furthermore, RSGLP increased LC3-II and p62 expression, indicative of induction of autophagy and disruption of autophagic flux in AGS cells. These results were further verified by combined treatment of AGS cells with the late-stage autophagy inhibitor chloroquine, or early-stage autophagy inducer rapamycin. Adenoviral transfection with mRFP-GFP-LC3 further confirmed that autophagic flux was inhibited by RSGLP in AGS cells. Finally, the present study demonstrated that the RSGLP-induced autophagy and disruption of autophagic flux disruption was, at least in part, responsible for RSGLP-induced apoptosis in AGS cells. The results of the present study demonstrated for the first time that RSGLP is more effective than BSGLP in inhibiting gastric cancer cell viability, and RSGLP may serve as a promising autophagy inhibitor in the management of gastric cancer.

Suppression of obesity and inflammation by polysaccharide from sporoderm-broken spore of Ganoderma lucidum via gut microbiota regulation.

Ganoderma lucidum has been shown to have anti-obesity effects. However, polysaccharide extracted from the sporoderm-broken spores of Ganoderma lucidum (BSGLP) against obesity and its underlying mechanisms have never been reported. In the current study, we showed that BSGLP inhibited high-fat diet (HFD)-induced obesity, hyperlipidemia, inflammation, and fat accumulation in C57BL/6 J mice. BSGLP improved HFD-induced gut microbiota dysbiosis, maintained intestinal barrier function, increased short-chain fatty acids production and GPR43 expression, ameliorated endotoxemia, manifested by reduced serum lipopolysaccharide level, and increased ileum expression of tight junction proteins and antimicrobial peptides. Fecal microbiota transplantation study confirmed that BSGLP-induced microbiota change is responsible, at least in part, for obesity inhibition. Besides, BSGLP notably alleviated HFD-induced upregulation of TLR4/Myd88/NF-κB signaling pathway in adipose tissue. Collectively, our study showed for the first time that BSGLP might be used as a prebiotic agent to inhibit obesity and hyperlipidemia through modulating inflammation, gut microbiota, and gut barrier function.

Broadband laser chaos generation using a quantum cascade laser with optical feedback.

We propose a method to generate broadband laser chaos using a quantum cascade laser (QCL). Through numerical simulation, we give the evidence that the QCL with optical feedback can route to chaos through the quasi-periodic path. Furthermore, we investigate the influence of the feedback intensity and the bias current on the chaos bandwidth. Final results demonstrate that the chaos bandwidth can headily reach 43.1 GHz due to the lack of relaxation oscillation phenomena in QCLs.

Prenatal exposure to koumine results in cognitive deficits and increased anxiety-like behavior in mice offspring.

Koumine (KM) is a major alkaloid monomer in the traditional Chinese medicine herb Gelsemium elegans Benth that has exhibited therapeutic potential in clinical applications. However, the pharmacological toxicological mechanism of this drug has not been fully explored. The purpose of this study was to evaluate the impacts of KM administration at a therapeutic dose in offspring. On gestational day 0, mice were injected with KM once daily for 4 consecutive days. Male and female offspring were subjected to behavioral tests and neuropathological analyses from postnatal day 60. Prenatal KM exposure resulted in cognitive and memory impairments in the Morris water maze, Y-maze test, and novel object recognition test. The open field test and elevated plus maze test indicated that prenatal KM exposure induced anxiety-like behavior in offspring. Electrophysiological experiments demonstrated that KM exposure inhibited hippocampal long-term potentiation. Immunostaining for neurogenesis markers DCX and BrdU demonstrated that KM suppressed adult neurogenesis in the subgranular zone of the dentate gyrus. In addition, prenatal KM exposure induced a significant reduction in dendritic spine density in hippocampal neurons. Synaptic formation-related proteins were decreased in the KM group based on western blot. No sex differences in the effects of KM were observed. Collectively, our results indicate that prenatal KA exposure has detrimental neural effects on offspring. This study provides a preliminary preclinical toxicological assessment of the safety of KM use during pregnancy.