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Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families.Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples.The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients.Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.

Background: Our previous study indicates that Brucea javanica oil (BJO) is beneficial for treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have anti-UC effect.Purpose: The present study aimed to compare the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO), and to explore the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function.Methods: Balb/C mice received 3% (wt/vol) DSS for one weeks to establish the UC model. Different doses of BE-BJO, BF-BJO or BJO were treated. Body weight and colon length were measured. Disease activity index (DAI) and histological analysis were evaluated. The levels of pro-inflammatory cytokines in the colon tissues were measured by enzyme linked immunosorbent assay (ELISA). The expressions of tight junction proteins were tested to investigate the intestinal epithelial barrier function. The effects of BE-BJO on NF-κB and RhoA/ROCK pathways were studied.Results: BE-BJO alleviated DSS-induced loss of body weight, increase of DAI and shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of pro-inflammatory cytokines including TNF-α、 IFN-γ、 IL-6 and IL-1β in the colon tissue, as well as reversed the decreased expressions of ZO-1, Occludin, Claudin-1and E-cadherin induced by DSS, but augmented Claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice.Conclusions: This work demonstrated that BE-BJO could ameliorate DSS-induced UC by preventing colon inflammation and enhancing intestinal epithelial barrier function, probably via suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that quassinoids are active compounds from BJO and suggest the therapeutic potential of quassinoids and BE-BJO in the treatment of UC.

Berberine (BBR), a major active constituent of Rhizoma coptidis, was reported to exert beneficial effects on intestinal mucositis (IM) induced by 5-fluorouracil (5-FU). However, the bioavailability of BBR is extremely low, and its metabolites were perceived to contribute to its prominent pharmacological activities. Oxyberberine (OBB) is a gut metabolite of BBR, which has been reported to have a superior anti-inflammatory effect in experimental colitis. However, its anti-inflammatory effects against 5-FU-induced IM mice have not yet been investigated. Hence, the purpose of this study was to reveal the protective effects of OBB on IM induced by 5-FU and investigate its potential underlying mechanism. The IM mice model was induced by receiving 5-FU (60 mg/kg, i.p.) for five days. Meanwhile, BBR (50 mg/kg) and OBB (12.5, 25, and 50 mg/kg) were given prior to 30 min intraperitoneal injection of 5-FU for seven days. Results indicated that OBB ameliorated body weight loss, anorexia, diarrhea, and histopathological damage in 5-FU-induced IM mice. After OBB administration, the amounts of MDA, SOD, and GSH altered by IM were remarkably restored. OBB was also observed to dramatically decrease the levels of TNF-α, IL-8, IL-6, COX-2, and iNOS and promote the release of IL-10. Besides, OBB distinctly upregulated the mRNA expressions of PCNA, ZO-1, occludin, and mucin-1, which could improve intestinal homeostasis in IM mice. OBB also blocked the activation of the upstream TLR4/MyD88 signaling pathway, and then it inhibited the phosphorylation of the NF-κB and MAPK pathways. Importantly, compared with BBR, OBB displayed a superior therapeutic effect to BBR in alleviating 5-FU-induced IM mice. These results indicated that OBB has considerable potential to become a novel candidate drug against IM.

Phellodendri Chinensis Cortex (PC) is a traditional medicinal material used to treat gout and hyperuricemia (HUA) in China. Berberine (BBR), the main component of PC, possesses anti-hyperuricemic and anti-gout effects. However, BBR exhibits low bioavailability due to its extensive metabolism and limited absorption. Thus, the metabolites of BBR are believed to be the potential active forms responsible for its in vivo biological activities. Berberrubine (BRB), one of the major metabolites of BBR, exhibits appreciable biological activities even superior to BBR. In this work, the anti-hyperuricemic efficacy of BRB was investigated in HUA model mice induced by co-administration with intraperitoneal potassium oxonate (PO) and oral hypoxanthine (HX) for 7 days. Results showed that administration with BRB (6.25, 12.5, and 25.0 mg/kg) significantly decreased the serum levels of uric acid (UA) by 49.70%, 75.35%, and 75.96% respectively, when compared to the HUA group. In addition, BRB sharply decreased the levels of serum creatinine (CRE) (by 19.62%, 28.98%, and 38.72%, respectively) and blood urea nitrogen (BUN) (by 16.19%, 25.07%, and 52.08%, respectively) and reversed the PO/HX-induced renal histopathological damage dose-dependently. Additionally, BRB lowered the hepatic XOD activity, downregulated the expressions of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), upregulated expressions of organic anion transporter 1/3 (OAT1/3) and ATP-binding cassette transporter subfamily G member 2 (ABCG2) at both protein and mRNA levels, and suppressed the activation of the JAK2/STAT3 signaling pathway. In addition, BRB significantly decreased the levels of inflammatory mediators (IL-1β, IL-6, and TNF-α). In conclusion, our study indicated that BRB exerted anti-hyperuricemic effect, at least in part, via regulating the urate transporter expressions and suppressing the JAK2/STAT3 signaling pathway. BRB was believed to be promising for further development into a potential therapeutic agent for HUA treatment.

MicroRNA (miR)‑29b is a key tumor regulator. It can inhibit tumor cell proliferation, induce apoptosis, suppress tumor invasion and migration, thus delaying tumor progression. Our previous studies revealed an increased level of miR‑29b in hepatoma 22 (H22) cells in ascites tumor‑bearing mice. The present study investigated the effect of miR‑29b on proliferation and apoptosis of hepatocellular carcinoma ascites H22 cells and its association with the transforming growth factor‑β1 (TGF‑β1) signaling pathway and p53‑mediated apoptotic pathway. Briefly, H22 cells were transfected with miR‑29b‑3p (hereinafter referred to as miR‑29b) mimic or miR‑29b inhibitor. MTS cell proliferation assay and flow cytometry were used to analyze cell viability and apoptosis. The expression change of the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway were detected by reverse transcription‑quantitative PCR, western blotting and immunofluorescence. Furthermore, cells were treated with exogenous TGF‑β1 and TGF‑β1 small interfering RNA to evaluate the crosstalk between TGF‑β1 and p53 under miR‑29b regulation. The overexpression of miR‑29b decreased cell viability, increased cell apoptosis, activated the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway. Conversely, these effects were reversed by the miR‑29b inhibitor. Moreover, the effect of miR‑29b mimic was further increased after treating cells with exogenous TGF‑β1. The activation of the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway induced by miR‑29b overexpression were reversed by TGF‑β1 inhibition. In summary, these data indicated that miR‑29b has an important role in proliferation and apoptosis of H22 cells by regulating the TGF‑β1 signaling pathway, the p53‑dependent apoptotic pathway, and the crosstalk between TGF‑β1 and p53.

Isorhynchophylline (IRN), an oxindole alkaloid isolated from Uncaria rhynchophylla, elicited distinct antidepressant-like activity in mice. The present study aimed to investigate the antidepressant-like effects of IRN in chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors in mice and to illustrate its possible mechanisms of action. The mice were subjected to CUMS for 6 wk and administered with IRN (20 or 40 mg/kg) daily by oral gavage for 3 wk. The PI3K/protein kinase B (Akt) inhibitor and glycogen synthase kinase-3β (GSK-3β) inhibitors were used to determine the involvement of the PI3K/Akt/GSK-3β pathway in the antidepressant-like effects of IRN in the mice. The results showed that CUMS caused depression-like behaviors in the mice, such as behavioral despair by the forced swim test (FST) and anhedonia by the sucrose preference test. In addition, CUMS could significantly reduce the levels of nerve growth factor and brain-derived neurotrophic factor but markedly increase the release of TNF-α and IL-6 in the hippocampus and cerebral cortex of the mice. Western blotting analysis showed that CUMS markedly suppressed the levels of phosphorylated GSK-3β (Ser9) and phosphorylated Akt (Ser473) but significantly enhanced the translocation of NF-κB p65 from cytosol to nuclei in the hippocampus and cerebral cortex of the mice. CUMS could also significantly increase the NF-κB binding activity in the hippocampus and cerebral cortex of the mice, whereas IRN treatment could significantly reverse the behavioral and biochemical changes induced by CUMS in the mice. Moreover, the antidepressant-like effect of IRN was completely abolished by the PI3K/Akt inhibitor. Combination treatment with IRN and GSK-3β inhibitors in the mice exerted a synergistic anti-immobility action in the FST. The results of mechanistic investigations indicated that the antidepressant-like action of IRN was mediated, at least in part, by enhancing neurotrophins and attenuating neuroinflammation via modulating the PI3K/Akt/GSK-3β pathway.-Xian, Y.-F., Ip, S.-P., Li, H.-Q., Qu, C., Su, Z.-R., Chen, J.-N., Lin, Z.-X. Isorhynchophylline exerts antidepressant-like effects in mice via modulating neuroinflammation and neurotrophins: involvement of the PI3K/Akt/GSK-3β signaling pathway.

A modified sodium bentonite geosynthetic clay liner (GCL) designed for acid-and-alkaline resistance was evaluated for its potential application in the containment of bauxite residue leachate. A modified fluid loss test was employed to quickly evaluate the hydraulic conductivity (k) of the GCL using distilled water, tap water, and four bauxite liquors (BLs, leachate from bauxite residue reservoirs). The effects of swelling capacity of bentonite, prehydration, hydraulic gradient (i), ionic strength (I), and relative abundance of monovalent and multivalent cations (RMD) on the hydraulic conductivity of the GCL were analyzed. The results indicated that the BLs significantly decreased free swell index of the bentonite. As compared to increasing i, prehydration obviously enhanced hydraulic performance of the GCL. The four BLs increased k of the GCL by a factor of 4-12 relative to the tap water permeation condition, and the resultant k exceeded upper limit of 5.0 × 10

Qiaoping Li,1,* Ziwei Huang,2,* Defu Liu,3 Jingna Zheng,1 Jianhui Xie,4– 6 Jiannan Chen,1 Huifang Zeng,2 Ziren Su,1 Yucui Li1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 3School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 4The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 5State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yucui Li; Ziren SuGuangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of ChinaTel +86 20 39358517Fax +86 20 39358390Email liyucui@gzucm.edu.cn; suziren@gzucm.edu.cnPurpose: Berberine (BBR) is an active component of Phellodendri Cortex (PC), which is a traditional Chinese medicine that has been prescribed clinically for hyperuricemia (HUA) for hundreds of years. Many studies reported the anti-inflammatory and nephroprotective properties of BBR and PC; however, the therapeutic effects of BBR on HUA have not been explored. This study aims to investigate the efficacy and mechanism of BBR for treating HUA.Methods: The mechanism of BBR in the treatment of HUA were predicted by network pharmacology. A mouse model of HUA established by potassium oxonate and hypoxanthine was used to verify the prediction. The levels of serum uric acid (UA), urea nitrogen (BUN) and creatinine (CRE) were determined by biochemical test kits. Hematoxylin and eosin staining of kidney tissues was used to observe the kidney damage. ELISA kits were applied to detect the levels of interleukin (IL)-1β and IL-18 in serum and kidney tissues. Quantitative real-time PCR and Western blotting were adopted to analyze the expression of NLRP3, ASC, Caspase1, IL-1β and URAT1. The expressions of URAT1 in the kidney tubules were visualized by immunohistochemical staining. Molecular docking was used to assess the interaction between URAT1 and BBR.Results: The network pharmacology screened out 82 genes and several inflammation-related signaling pathways related to the anti-hyperuricemia effect of BBR. In the in vivo experiment, BBR substantially decreased the level of UA, BUN and CRE, and alleviated the kidney damage in mice with HUA. BBR reduced IL-1β and IL-18, and downregulated expressions of NLRP3, ASC, Caspase1 and IL-1β. BBR also inhibited expression of URAT1 and exhibited strong affinity with this target in silico docking.Conclusion: BBR exerts anti-HUA and nephroprotective effects via inhibiting activation of NLRP3 inflammasome and correcting the aberrant expression of URAT1 in kidney. BBR might be a novel therapeutic agent for treating HUA.Keywords: berberine, hyperuricemia, URAT1, NLRP3 signaling pathway

Non-alcoholic steatohepatitis (NASH), an extreme progressive subtype of metabolic associated fatty liver disease, is well characterized by hepatic steatosis, injury and inflammation. It causes irreversible hepatic damage and there are no approved interventions for it. β-PAE, a representatively pharmacological active substance isolated from Pogostemon cablin, has been indicated to alleviate hepatic steatosis and injury through modulating lipid metabolism in rats with simple steatosis. However, its protection against NASH remains unclear. Here, this study explored the potential effect of β-PAE against high-fat diet-induced NASH in rats. The results displayed that β-PAE significantly reduced the gains of body weight and epididymal adipose tissue, liver index and attenuated liver histological damages in NASH rats. It also markedly alleviated hepatic inflammation by inhibiting NLRP3 inflammasome activation. In NASH, the active NLRP3 inflammasome is caused by hepatic lipid abnormal accumulation-induced oxidative stress. Excessive oxidative stress results in hepatic histanoxia, which exacerbates lipid metabolism disorders by elevating CD36 to suppress AMPK signalling pathways. Moreover, the lipid accumulation led by lipid metabolism dysfunction intensifies oxidative stress. A vicious circle is formed among oxidative stress, histanoxia and lipid accumulation, eventually, but β-PAE effectively interrupted it. Interestingly, soluble CD36 (sCD36) was tightly associated not only with hepatic steatosis and injury but also with inflammation. Collectively, β-PAE exerted a positive effect against NASH by interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation, and sCD36 may be a promising non-invasive tool for NASH diagnosis.

We have numerically studied the evolution of the heavy ions that expand in a cold background plasma at a large scale. Two typical collective behaviors of the heavy ions are identified with the conditions where only the traversing heavy ion's initial total mass is different. Our work has demonstrated that a difference in the initial total mass of the moving heavy ions is able to induce completely different collective behaviors of the plasma. The simulation is performed via the hybrid model, in which the ions and electrons are treated as classical particles and mass-less fluid, respectively. Due to the imbalance of the electric and magnetic force on the heavy ions, these particles will evolve into different collective patterns at the later time. These patterns manifest a rather different stopping behavior of the moving ions and an opposite drifting direction of the electron fluid at the rim of the expanding plasma. Further numerical and analytical calculations show that the imbalance depends not only on the number densities of the plasma ions, but also on the spatial variations of the magnetic fields. Our work reveals that the collective behavior of the heavy ions is highly non-linear, and the non-linearity is able to induce different phenomena in the evolution of the system at a large scale., 8 pages, 8 figures

We have implemented a GPU version of the Jefimenko's equations -- JefiGPU. Given the proper distributions of the source terms $\rho$ (charge density) and $\mathbf{J}$ (current density) in the source volume, the algorithm gives the electromagnetic fields in the observational region (not necessarily overlaps the vicinity of the sources). To verify the accuracy of the GPU implementation, we have compared the obtained results with that of the theoretical ones. Our results show that the deviations of the GPU results from the theoretical ones are around 5\%. Meanwhile, we have also compared the performance of the GPU implementation with a CPU version. The simulation results indicate that the GPU code is significantly faster than the CPU version. Finally, we have studied the parameter dependence of the execution time and memory consumption on one NVIDIA Tesla V100 card. Our code can be consistently coupled to RBG (Relativistic Boltzmann equations on GPUs) and many other GPU-based algorithms in physics., Comment: 21 pages, 8 figures, 4 tables

Non-alcoholic fatty liver disease (NAFLD) has been a leading cause of chronic metabolic disease, seriously posing healthy burdens to the public, whereas interventions available for it are limited to date. Patchouli oil had been reported to attenuate hepatic steatosis in our previous study. β-patchoulene (β-PAE) is a representative component separated from patchouli oil with multiple activities, but its effect against NAFLD is still unknown. To investigate the effect and potential mechanism of β-PAE on NAFLD, we used high fat diet (HFD) in vivo and free fatty acid (FFA) in vitro to induce hepatic steatosis in rats and L02 cells, respectively. Histological examination was evaluated via Hematoxylin-eosin and oil red O staining. The parameters for hepatic steatosis were estimated via biochemical kits, western blotting and quantitative real-time PCR. Compound C, the inhibitor of AMPK, was applied further to examine the precise mechanism of β-PAE on NAFLD. Our results indicated that β-PAE significantly attenuated HFD-induced weight gain, hepatic injury, lipid deposition in serum and hepatic tissue as well as FFA induced-lipid accumulation. Besides, β-PAE markedly improved the expression of AMP-activated protein kinase (AMPK) and its downstream factors which correlate with hepatic lipid synthesis and oxidation in vivo and in vitro. Nevertheless, Compound C abrogated the benefits derived from β-PAE in L02 cells. In conclusion, these results suggest that β-PAE exerts AMPK agonist-like effect to regulate hepatic lipid synthesis and oxidation, eventually prevent NAFLD progression.

Berberine (BBR) is a promising anti-diabetic isoquinoline alkaloid from Rhizoma coptidis, while its bioavailability was extremely low. Here, the existing form and pharmacokinetics of BBR were comparatively characterized in conventional and antibiotic-induced pseudo germ-free (PGF) rats. Furthermore, we comparatively investigated the antidiabetic effect and potential mechanism of BBR and its intestinal oxidative metabolite oxyberberine (OBB) in STZ-induced diabetic rats. Results showed that BBR and OBB existed mainly as protein-bound form in blood, while protein-bound OBB was significantly depleted in PGF rats. Treatment with OBB and BBR effectively decreased clinical symptoms of diabetic rats, reduced blood glucose level, ameliorated the pancreatic damage, and mitigated oxidative stress and inflammatory markers. However, the anti-diabetes effect of BBR was obviously compromised by antibiotics. In addition, OBB exerted superior anti-diabetes effect to BBR of the same dose, significantly up-regulated the mRNA expression of Nrf2 signaling pathway and substantially promoted the pancreatic levels of PI3K/Akt signaling pathway. In conclusion, BBR and its absorbed oxidative metabolite OBB were mainly presented and transported in the protein-bound form in vivo. The gut microbiota may play an important role in the anti-diabetes effect of BBR through transforming itself into the superior hypoglycemic metabolite OBB. OBB possessed favorable hypoglycemic and pancreatic β-cells protective effects, which may stand a huge potential to be further developed into a promising anti-diabetes candidate.

Background Berberine (BBR) has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The metabolites of BBR were believed to contribute significantly to its pharmacological effects. Oxyberberine (OBB), a gut microbiota-mediated oxidative metabolite of BBR, has been firstly identified in our recent work. Purpose Here, we aimed to comparatively investigate the anti-NAFLD properties of OBB and BBR. Methods The anti-NAFLD effect was evaluated in high-fat diet-induced obese NAFLD rats with biochemical/ELISA tests and histological staining. The related gene and protein expressions were detected by qRT-PCR and Western blotting respectively. Molecular docking and dynamic simulation were also performed to provide further insight. Results Results indicated OBB remarkably and dose-dependently attenuated the clinical manifestations of NAFLD, which (100 mg/kg) achieved similar therapeutic effect to metformin (300 mg/kg) and was superior to BBR of the same dose. OBB significantly inhibited aberrant phosphorylation of IRS-1 and up-regulated the downstream protein expression and phosphorylation (PI3K, p-Akt/Akt and p-GSK-3β/GSK-3β) to improve hepatic insulin signal transduction. Meanwhile, OBB treatment remarkably alleviated inflammation via down-regulating the mRNA expression of MCP-1, Cd68, Nos2, Cd11c, while enhancing Arg1 mRNA expression in white adipose tissue. Moreover, OBB exhibited closer affinity with AMPK in silicon and superior hyperphosphorylation of AMPK in vivo, leading to increased ACC mRNA expression in liver and UCP-1 protein expression in adipose tissue. Conclusion Taken together, compared with BBR, OBB was more capable of maintaining lipid homeostasis between liver and WAT via attenuating hepatic insulin pathway and adipocyte inflammation, which was associated with its property of superior AMPK activator.

Ulcerative colitis (UC), as an autoimmune disease, has been troubling human health for many years. Up to now, the available treatments remain unsatisfactory. Rhizoma Coptidis has been widely applied to treat gastrointestinal diseases in China for a long time, and coptisine (COP) is identified as one of its major active components. This study aimed to evaluate the bioactivity of COP on dextran sulfate sodium (DSS)-induced mice colitis and clarify the potential mechanism of action. The results revealed that COP treatment markedly alleviated DSS-induced clinical symptoms by relieving body weight loss and the disease activity index (DAI) score. Specifically, the colon length in the COP (50 and 100 mg/kg) groups were obviously longer than that in the DSS group (7.21 ± 0.34, 8.59 ± 0.45 cm vs. 6.71 ± 0.59 cm, P 0.01). HE staining analysis revealed that COP treatment significantly protected the integrity of intestinal barrier and alleviated inflammatory cells infiltration. Western blot assay confirmed that COP notably improved the intestinal epithelial barrier function by enhancing the expressions of colonic tight junction proteins and inhibited the expressions of apoptosis-related proteins. In addition, COP treatment remarkably suppressed the levels of colonic myeloperoxidase (MPO), adhesion molecules and pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6 and IL-17), while enhanced IL-10 and TGF-β. The mechanism anti-inflammatory of COP might be related to inhibiting the phosphorylation of IκBα, and the translocation of NF-κB p65 from cytoplasm to nucleus. In summary, the study indicated that COP ameliorated DSS-induced colitis, at least partly through maintaining the integrity of intestinal epithelial barrier, inhibiting apoptosis and inflammatory response.

Background As a prevalent type of cryptogenic fibrotic disease with high mortality, idiopathic pulmonary fibrosis (IPF) still lacks effective therapeutic drugs. The compounds extracted from buds and flowers of Chrysanthemum indicum Linné with supercritical-carbon dioxide fluid (CISCFE) has been confirmed to have antioxidant, anti-inflammatory, and lung-protective effects. This paper aimed to clarify whether CISCFE could treat IPF induced by bleomycin (BLM) and elucidate the related mechanisms. Methods Rats (Sprague-Dawley, male) were separated into the following groups: normal, model, pirfenidone (50 mg/kg), CISCFE-L, −M, and -H (240, 360, and 480 mg/kg/d, i.g., respectively, for 4 weeks). Rats were given BLM (5 mg/kg) via intratracheal installation to establish the IPF model. A549 and MRC-5 cells were stimulated by Wnt-1 to establish a cell model and then treated with CISCFE. Haematoxylin-eosin (H&E) and Masson staining were employed to observe lesions in the lung tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were performed to observe changes in genes and proteins connected with the Wnt/β-catenin pathway. Results CISCFE inhibited the proliferation of MRC-5 cells (IC50: 2.723 ± 0.488 μg/mL) and A549 cells (IC50: 2.235 ± 0.229 μg/mL). In rats, A549 cells, and MRC-5 cells, BLM and Wnt-1 obviously induced the protein expression of α-smooth muscle actin (α-SMA), vimentin, type I collagen (collagen-I), and Nu-β-catenin. The mRNA levels of matrix metalloproteinase-3 (MMP-3) and − 9 (MMP-9), two enzymes that degrade and reshape the extracellular matrix (ECM) were also increased while those of tissue inhibitor of metalloproteinase 1 (TIMP-1) were decreased. However, CISCFE reversed the effects of BLM and Wnt-1 on the expression pattern of these proteins and genes. Conclusion These findings showed that CISCFE could inhibit IPF development by activating the Wnt/β-catenin pathway and may serve as a treatment for IPF after further investigation.

Brusatol occurs as a characteristic bioactive principle of Brucea javanica (L.) Merr., a traditional medicinal herb frequently employed to tackle cancer in China. This work endeavored to unravel the potential anti-cancer activity and action mechanism of brusatol against non-small cell lung cancer (NSCLC) cell lines. The findings indicated that brusatol remarkably inhibited the growth of wild-type NSCLC cell lines (A549 and H1650) and epidermal growth factor receptor-mutant cell lines (PC9 and HCC827) in a dose- and time-related fashion, and profoundly inhibited the clonogenic capability and migratory capacity of PC9 cells. Treatment with brusatol resulted in significant apoptosis in PC9 cells, as evidenced by Hoechst 33342 staining and flow cytometric analysis. The apoptotic effect was closely related to induction of G0-G1 cell cycle arrest, stimulation of reactive oxygen species (ROS) and malondialdehyde, decrease of glutathione levels and disruption of mitochondrial membrane potential. Furthermore, pretreatment with N-acetylcysteine, a typical ROS scavenger, markedly ameliorated the brusatol-induced inhibition of PC9 cells. Western blotting assay indicated that brusatol pronouncedly suppressed the expression levels of mitochondrial apoptotic pathway-associated proteins Bcl-2 and Bcl-xl, accentuated the expression of Bax and Bak, and upregulated the protein expression of XIAP, cleaved caspase-3/pro caspase-3, cleaved caspase-8/pro caspase-8, and cleaved PARP/total PARP. In addition, brusatol significantly suppressed the expression of Nrf2 and HO-1, and abrogated tBHQ-induced Nrf2 activation. Combinational administration of brusatol with four chemotherapeutic agents exhibited marked synergetic effect on PC9 cells. Together, the inhibition of PC9 cells proliferation by brusatol might be intimately associated with the modulation of ROS-mediated mitochondrial-dependent pathway and inhibition of Nrf2-mediated antioxidant response. This novel insight might provide further evidence to buttress the antineoplastic efficacy of B. javanica, and support a role for brusatol as a promising anti-cancer candidate or adjuvant to current chemotherapeutic medication in the therapy of EGFR-mutant NSCLC.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.

Inflammatory bowel disease (IBD), majorly include Crohn’s disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Pal (50 and 100 mg kg−1) and the positive drug Sulfasalazine (SASP, 200 mg kg−1) were orally administered for 7 days. Disease activity index (DAI) was evaluated on day 8, and colonic tissues were collected for biochemistry analysis. The fecal microbiota was characterized by high-throughput Illumina MiSeq sequencing. And plasma metabolic changes were detected by UPLC-MS. Our results showed that Pal treatment significantly reduced DAI scores and ameliorated colonic injury in mice with DSS-induced colitis. Mucosal integrity was improved and cell apoptosis was inhibited. Moreover, gut microbiota analysis showed that mice received Pal-treatment have higher relative abundance of Bacteroidetes and Firmicutes, but reduced amount of Proteobacteria. Moreover, Pal not only suppressed tryptophan catabolism in plasma, but also decreased the protein expression of indoleamine 2,3-dioxygenase 1 (IDO-1, the rate-limiting enzyme of tryptophan catabolism) in colon tissue. This is consolidated by molecular docking, which suggested that Pal is a potent IDO-1 inhibitor. Taken together, our findings demonstrate that Pal ameliorated DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis, and regulating tryptophan catabolism, which indicated that Pal has great therapeutic potential for colitis.

The attitude control problem is addressed for a quadrotor system subject to the modeling uncertainties and unknown disturbances. A novel attitude control scheme is proposed based on nonsingular fast terminal sliding mode (NFTSM) technique. First, the tracking differentiator (TD) is designed to obtain the smooth tracking signal and its derivative. Then, the extended state observer (ESO) is constructed to provide the estimate of the modeling uncertainties and unknown disturbances. With the designed TD and ESO, a novel NFTSM controller is developed such that tracking error converges to zero in finite time. The transient-state and the steady-state performances are both achieved with the new controller. Finally, the simulation and real experiment results verify the effectiveness and superiority of the proposed control method.

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used as effective anti-inflammatory agents. However, their clinical application brings about inevasible gastrointestinal side effects. Pogostemon cablin is a traditional herbal medicine used for the treatment of gastrointestinal diseases in China. One of its representative components, the tricyclic triterpenoid β-patchoulone (β-PAE) has demonstrated great anti-inflammatory activity and gastroprotective effect against ethanol-induced gastric injury, but its protective effect against gastric ulcer induced by indomethacin is still unknown. Purpose To assess the protective effect of β-PAE against ulcer produced by indomethacin and reveal the underlying pharmacological mechanism. Study design We used an indomethacin-induced gastric ulcer model of rats in vivo. Methods Gastroprotective activity of β-PAE (10, 20, 40 mg/kg, i.g.) was estimated via indomethacin-induced gastric ulcer model in rats. Histopathological and histochemical assessment of ulcerated tissues were performed. Protein and mRNA expression were determined by Elisa, Western blotting and qRT-PCR. Results β-PAE could inhibit ulcer formation. Histopathological and histochemical assessment macroscopically demonstrated that β-PAE alleviates indomethacin-induced gastric ulceration in dose-dependent manner. After administration of β-PAE, elevated tumor necrosis factor -α level was significantly decreased and the phosphorylation of JNK and IκB was markedly inhibited. β-PAE suppressed the levels of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule and monocyte chemoattractant protein 1, as well as myeloperoxidase. Meanwhile, β-PAE increased cyclooxygenase enzyme activities (COX-1 and COX-2) to enhance the production of prostaglandin E2. Proangiogenic protein, vascular endothelial growth factor and its receptor fms-like tyrosine kinase-1 mRNA expression were promoted while anti-angiogenic protein, endostatin-1 and its receptor ETAR mRNA expression were decreased. Conclusion β-PAE may provide gastroprotection in indomethacin-induced gastric ulcer in rats by reducing inflammatory response and improving angiogenesis.

Excessive alcohol consumption can cause serious hepatic injury which is associated with oxidative stress and fatty metabolic disturbance. Patchouli oil (PO) is a sort of food supplement with high medicinal value in hepatoprotection, but its ability against ethanol-induced liver failure has not been demonstrated. Thus, this study aimed to investigate the potential hepatoprotection of PO through an ethanol-induced hepatotoxicity rat model. Our results showed that PO pretreatment could dramatically decrease the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in serum, paralleled by an improvement of histopathology alterations. Additionally, PO could markedly suppress the content of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), free fatty acid (FFA), and triglyceride (TG), while enhancing the activities of glutathione (GSH), glutathione reductase (GR), and superoxide dismutase (SOD) as well as the ratio of glutathione to oxidized glutathione (GSH/GSSG) in liver. The protective effect of PO against oxidative stress was interrelated with restraining the mRNA and protein expression of hepatic microsomal enzyme cytochrome P450 2E1 (CYP2E1). What's more, PO pretreatment could also accelerate lipometabolism via up-regulating expressions of adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPAR-α), and carnitine palmitoyltransferase 1 (CPT-1) and down-regulating expressions of nuclear factor-kappaB (NF-κB) p65, sterol regulatory element-binding protein 1 (SREBP-1c), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD-1). To conclude, PO showed potent effect against ethanol-induced hepatotoxicity by relieving oxidative stress and preventing lipid accumulation.

Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to mice. In summary, the study successfully demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing inflammation, maintaining the integrity of intestinal epithelial barrier, inhibiting cell death signaling, and suppressing tryptophan catabolism. The results provided valuable information and guidance for using PA in treatment of UC.

This study was designed to explore how supercritical fluid CO2 extract of Ligusticum chuanxiong Hort (CX) protects mouse liver and kidney from d-galactose-induced injury. The antioxidant capacity of CX was confirmed both in vitro and in vivo. The d-galactose-induced malondialdehyde increase was attenuated by CX, as well as the increase in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine level. In addition, the activities of antioxidant enzymes were markedly renewed, and the gene expressions of these enzymes were upregulated in CX groups. The results of histological analysis suggested that CX could effectively attenuate the d-galactose-induced structure damage. Furthermore, results of Western blotting analysis showed that CX significantly inhibited the upregulation of nuclear factor protein expression caused by d-galactose. In conclusion, CX could attenuate the liver and kidney injury in d-galactose-treated mice, and the mechanism might be associated with attenuating oxidative stress and inflammatory response.

In this work, we successfully demonstrate a fast method to determine the fish freshness by using a sensing system containing an ultrasensitive amine gas sensor to detect the volatile amine gas from the raw fish meat. When traditional titration method takes 4 h and complicated steps to test the total volatile basic nitrogen (TVB-N) as a worldwide standard for fish freshness, our sensor takes 1 min to deliver an electrical sensing response that is highly correlated with the TVB-N value. When detecting a fresh fish with a TVB-N as 18 mg/100 g, the sensor delivers an effective ammonia concentration as 100 ppb. For TVB-N as 28-35 mg/100 g, a well-accepted freshness limit, the effective ammonia concentration is as 200-300 ppb. The ppb-regime sensitivity of the sensor and the humidity control in the sensing system are the keys to realizing fast and accurate detection. It is expected that the results in this report enable the development of on-site freshness detection and real-time monitoring in a fish factory.

Confined round jet impingement cooling of a flat plate at constant heat flux with carbon dioxide at supercritical pressures was investigated numerically. The pressure ranged from 7.8 to 10.0 MPa, which is greater than the critical pressure of carbon dioxide, 7.38 MPa. The inlet temperature varied from 270 to 320 K and the heat flux ranged from 0.6 to 1.6 MW/m2. The shear-stress transport turbulence model was used and the numerical model was validated by comparison with experimental results for jet impingement heating with hot water at supercritical pressures. Radial conduction in the jet impingement plate was also considered. The sharp variations of the thermal-physical properties of the fluid near the pseudocritical point significantly influence heat transfer on the target wall. For a given heat flux, the high specific heat near the wall for the proper inlet temperature and pressure maximizes the average heat transfer coefficient. For a given inlet temperature, the heat transfer coefficient remai...

Livistona chinensis fruit is a traditional Chinese medicine widely used for treating hepatitis, but its protective effect against hepatitis remains unknown. This study investigated the hepatoprotective effect and mechanism of flavonoids from Livistona chinensis fruit (FLCF). Mice received FLCF pre-treatment for 7 days and induced liver injury with LPS+D-GalN. RAW264.7 cells were triggered inflammation by LPS and received FLCF for 24 h. The result showed that FLCF ameliorated the liver pathology in mice, decreased the levels of AST, ALT, MDA, but increased SOD and GSH. Moreover, FLCF inhibited TLR4/NF-κB signaling, while activated Nrf2/HO-1 signaling in LPS+D-GalN mice. These effects were consistent with the in vitro data revealing that FLCF suppressed TLR4/NF-κB signaling, while promoting Nrf2/HO-1 signaling in RAW264.7 cell. The effects of FLCF were neutralized by Nrf2 siRNA. Taken together, these results demonstrated that FLCF has a protective role against acute liver injury and supports its use as a dietotherapy.

Isorhynchophylline (IRN), an oxindole alkaloid isolated from

Dihydroberberine (DHB), a hydrogenated derivative of berberine (BBR), has been firstly identified in Phellodendri Chinese Cortex (PC) by HPLC-ESI-MS/MS. Nowadays most researches on PC focus on its main components like BBR, however, the role of its naturally-occurring derivatives remains poorly defined heretofore. The present work aimed to comparatively evaluate the in vivo anti-inflammatory properties and mechanisms of DHB and BBR in three typical inflammatory murine models. The results showed that DHB effectively mitigated acetic acid-induced vascular permeability, xylene-elicited ear edema and carrageenan-caused paw edema. Meanwhile, DHB markedly attenuated the inflammatory cell infiltration in pathological sections of ears and paws. DHB was also observed to significantly decrease the production and mRNA expression levels of IL-6, IL-1β, TNF-α, NO (iNOS) and PGE2 (COX-2), increase the release of IL-10, and inhibit the activation of NF-κB and MAPK signaling pathways. The anti-inflammatory effect of DHB was weaker than that of BBR. The results might further contribute to unraveling the pharmacodynamic basis of PC and support its ethnomedical use in the treatment of inflammatory diseases. DHB possesses good potential to be further developed into a promising anti-inflammatory alternative, and can serve as a lead template for novel anti-inflammatory candidate.

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn’s disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.

Brucea javanica oil (BJO), one of the main products of Brucea javanica, has been widely used in treating different kinds of malignant tumors. Quassinoids are the major category of anticancer phytochemicals of B. javanica. However, current researches on the anti-cancer effect of BJO mainly focused on oleic acid and linoleic acid, the common major components of dietary edible oils, essential and characteristic components of B. javanica like quassinoids potentially involved remained unexplored. In the current investigation, we developed an efficient HPLC method to detect brusatol, a characteristic quassinoid, and comparatively scrutinized the anti-hepatocellular carcinoma (anti-HCC) effect of BJO, brusatol-free BJO (BF-BJO), and brusatol-enriched BJO (BE-BJO) against hepatoma 22 (H22) in mice. High-performance liquid chromatography (HPLC) was utilized to identify the components in BJO. BE-BJO was extracted with 95 % ethanol. The anti-tumor effect of BJO, BF-BJO and BE-BJO was comparatively investigated, and the potential underlying mechanism was explored in H22 ascites tumor-bearing mice. The results indicated that BJO and BE-BJO significantly prolonged the survival time of H22 ascites tumor-bearing mice, while BF-BJO exhibited no obvious effect. BJO and BE-BJO exhibited pronounced anti-HCC activity by suppressing the growth of implanted hepatoma H22 in mice, including ascending weight, abdominal circumference, ascites volume and cancer cell viability, with a relatively wide margin of safety. BJO and BE-BJO significantly induced H22 cell apoptosis by upregulating the miRNA-29b gene level and p53 expression. Furthermore, BJO and BE-BJO treatment substantially downregulated Bcl-2 and mitochondrial Cytochrome C protein expression, and upregulated expression levels of Bax, Bad, cytosol Cytochrome C, caspase-3 (cleaved), caspase‑9 (cleaved), PARP and PARP (cleaved) to induce H22 cells apoptosis. Brusatol was detected in BJO and found to be one of its major active anti-HCC components, rather than fatty acids including oleic acid and linoleic acid. The anti-HCC effect of BJO and BE-BJO was intimately associated with the activation of miRNA-29b, p53-associated apoptosis and mitochondrial-related pathways. Our study gained novel insight into the material basis of BJO in the treatment of HCC, and laid a foundation for a novel specific standard for the quality evaluation of BJO and its commercial products in terms of its anti-cancer application.

Ulcerative colitis (UC) often occurs accompanied by colonic leakage and flora imbalance, resulting in secondary liver injury (SLI). SLI, in turn, aggravates UC, so the treatment of UC should not ignore it. β-patchoulene (β-PAE), a tricyclic sesquiterpene isolated from Pogostemon cablin, has been reported to exert a protective effect in gastrointestinal disease in our previous studies. However, its protection against UC and SLI remains unknown. Here we explored the protective effect and underlying mechanism of β-PAE against dextran sulfate sodium-induced UC and SLI in mice. The results indicated that β-PAE significantly reduced disease activity index, splenic index and attenuated the shortening of colonic length in UC mice. It alleviated colonic pathological changes and apoptosis through protecting tight junctions, reducing neutrophil aggregation, and inhibiting the release of pro-inflammatory cytokines and adhesion molecules. These effects of β-PAE were associated with the inhibition of TLR4/MyD88/NF-κB and ROCK1/MLC2 signalling pathway. UC-induced colonic leakage caused abnormally high LPS levels to result in SLI, and β-PAE markedly inhibited it. β-PAE simultaneously ameliorated SLI with reduced biomarker levels of endotoxin exposure and hepatic inflammation. High levels of LPS were also associated with flora imbalance in UC mice. However, β-PAE restored the diversity of gut microbiota and altered the relative abundance of characteristic flora of UC mice. Escherichia-dominated gut microbiota of UC mice was changed to Oscillospira-dominated after β-PAE treatment. In conclusion, pharmacological effects of β-PAE on UC and SLI were mainly contributed by suppressing colonic leakage and flora imbalance. The findings may have implications for UC treatment that not neglect the treatment of SLI.

We demonstrate an extremely sensitive ammonia gas sensor based on vertical organic diode to exhibit a 1 ppb detection limit. Using phenyl-C61-butyric acid methyl ester (PCBM) as the sensing layer, the nano-porous structure enlarges the surface to volume ratio and hence realizes the ppb-regime sensitivity. The proposed vertical nano-junction (VNJ) organic diode is then investigated by changing the semiconducting materials (i.e. sensing material). In addition to a pure n-type or p-type sensing material, the blend of n/p organic semiconductor (PCBM/P3HT) is used to react with gas. Changing the n/p blending ratio from 0 to 100% delivers a tunable gas response to ammonia and nitric oxide, hence demonstrating a sensing map concept with good selectivity.

Pogostone, a chemical constituent of patchouli oil, has been confirmed to possess favorable anti-inflammatory property. In the present study, we investigated the possible anti-photoaging potential of pogostone and the underlying mechanism against UV-induced skin damage in mice. The macroscopic and histopathological lesions were significantly ameliorated by pretreatment of pogostone as compared to the VC group. Furthermore, topical application of pogostone markedly increased the activities of the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observably decreased malonaldehyde (MDA) level. Analysis of inflammatory cytokines showed obvious down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) in the pogostone groups. In addition, pogostone pretreatment evidently inhibited the abnormal expression of matrix metalloproteinases (MMP-1 and MMP-3). Taken together, pogostone exhibited prominent photo-protective activity mainly by its antioxidative and anti-inflammatory properties, promising it as an effective alternative pharmaceutical therapy for photoaging.