The health and welfare effects of environmental governance: Evidence from China.

Environmental regulations aim to reduce pollution and improve air quality and the health of residents. However, there is a lack of research focusing on the health and welfare effects of low-carbon city pilot policies. In this context, this study takes China's low-carbon city pilot policy as an entry point, focuses on the health effects of public environmental governance, and systematically investigates the effects and mechanisms of low-carbon city development on the health of middle-aged and elderly people by applying the difference-in-differences method. The study finds that low-carbon city (LCC) policy significantly improves the physical and mental health of middle-aged and elderly people, and the main transmission mechanism is the reduction in air pollution and improvement in social capital. These results hold following a series of robustness tests. Furthermore, low-carbon city construction can reduce hospitalization and outpatient costs for people over 45 years old by up to 3 % and 15.5 %, respectively. The findings of this study provide useful policy insights for ensuring sustainable improvement in environmental quality and public health.

Itemized determination of As, Sb, Bi, Se, and Ge in graphite sample by HG-AFS with high-temperature microwave digestion.

In this paper, we optimized a method for fast and accurate determination of five impurity elements (As, Sb, Bi, Se, and Ge) in graphite samples to overcome the shortcomings of existing methods, such as complicated equipment, cumbersome process, multiple-time preparation, separate determination, and large error in results. Graphite samples were digested with HNO3-H2SO4-HClO4-HF in a high-temperature and high-pressure microwave digestion apparatus, and the elements were extracted and determined separately by AFS (atomic fluorescence spectrometry). There is no element loss during the processing and analysis of this method. The spike recoveries (As: 90.30%-102.3%, Sb: 90.73%-110.0%, Bi: 90.00%-99.67%, Se: 93.33%-110.0%, Ge: 92.26%-104.2%) and precision (RSD%; As: 1.34%-8.96%, Sb: 2.67%-7.10%, Bi: 1.83%-4.58%, Se: 0.36%-3.25%, Ge: 4.41%-8.65%) meet the requirements of the corresponding quality specifications. The method has some advantages (such as no elemental loss, fast testing, strong element targeting, and accurate results), and thus can achieve batch determination of graphite samples. The optimized method for graphite sample and final solution preparations can be used for diverse spectrometric technologies, and that for spectrometer conditions have reference value for HG-AFS instruments.

MI-DenseCFNet: deep learning-based multimodal diagnosis models for Aureus and Aspergillus pneumonia.

OBJECTIVE: To build and merge a diagnostic model called multi-input DenseNet fused with clinical features (MI-DenseCFNet) for discriminating between Staphylococcus aureus pneumonia (SAP) and Aspergillus pneumonia (ASP) and to evaluate the significant correlation of each clinical feature in determining these two types of pneumonia using a random forest dichotomous diagnosis model. This will enhance diagnostic accuracy and efficiency in distinguishing between SAP and ASP. METHODS: In this study, 60 patients with clinically confirmed SAP and ASP, who were admitted to four large tertiary hospitals in Kunming, China, were included. Thoracic high-resolution CT lung windows of all patients were extracted from the picture archiving and communication system, and the corresponding clinical data of each patient were collected. RESULTS: The MI-DenseCFNet diagnosis model demonstrates an internal validation set with an area under the curve (AUC) of 0.92. Its external validation set demonstrates an AUC of 0.83. The model requires only 10.24s to generate a categorical diagnosis and produce results from 20 cases of data. Compared with high-, mid-, and low-ranking radiologists, the model achieves accuracies of 78% vs. 75% vs. 60% vs. 40%. Eleven significant clinical features were screened by the random forest dichotomous diagnosis model. CONCLUSION: The MI-DenseCFNet multimodal diagnosis model can effectively diagnose SAP and ASP, and its diagnostic performance significantly exceeds that of junior radiologists. The 11 important clinical features were screened in the constructed random forest dichotomous diagnostic model, providing a reference for clinicians. CLINICAL RELEVANCE STATEMENT: MI-DenseCFNet could provide diagnostic assistance for primary hospitals that do not have advanced radiologists, enabling patients with suspected infections like Staphylococcus aureus pneumonia or Aspergillus pneumonia to receive a quicker diagnosis and cut down on the abuse of antibiotics. KEY POINTS: • MI-DenseCFNet combines deep learning neural networks with crucial clinical features to discern between Staphylococcus aureus pneumonia and Aspergillus pneumonia. • The comprehensive group had an area under the curve of 0.92, surpassing the proficiency of junior radiologists. • This model can enhance a primary radiologist's diagnostic capacity.

Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells.

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.

KNOTTED1-like homeobox (KNOX) transcription factors - Hubs in a plethora of networks: A review.

KNOX (KNOTTED1-like HOMEOBOX) belongs to a class of important homeobox genes, which encode the homeodomain proteins binding to the specific element of target genes, and widely participate in plant development. Advancements in genetics and molecular biology research generate a large amount of information about KNOX genes in model and non-model plants, and their functions in different developmental backgrounds are gradually becoming clear. In this review, we summarize the known and presumed functions of the KNOX gene in plants, focusing on horticultural plants and crops. The classification and structural characteristics, expression characteristics and regulation, interacting protein factors, functions, and mechanisms of KNOX genes are systematically described. Further, the current research gaps and perspectives were discussed. These comprehensive data can provide a reference for the directional improvement of agronomic traits through KNOX gene regulation.

The Circular RNA circFGFR4 Facilitates Resistance to Anti-PD-1 of Triple-Negative Breast Cancer by Targeting the miR-185-5p/CXCR4 Axis.

Purpose: One of the most catastrophic malignant tumors is triple negative breast cancer (TNBC). It is characterized by rapid progression in the clinic. CircRNAs are abnormally expressed in almost all cancers and play important roles in tumor immune evasion. Nevertheless, the biological roles of the circular fibroblast growth factor receptor 4 RNA (circFGFR4) in TNBC remain unclear. Methods: The expression of circFGFR4 in TNBC tissues and paired nontumor tissues was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The role of circFGFR4 in TNBC immune evasion was estimated by analyzing clinical tissues. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore interaction between circFGFR4 and miR-185-5p. Results: Our results indicated that circFGFR4 was significantly overexpressed in TNBC tissues. Upregulated circFGFR4 expression was correlated with decreased CD8+ T cell infiltration in tumor tissues and resistance to anti-programmed cell death 1 (PD-1) immunotherapy in TNBC patients and mice bearing TNBC tumors. Forced circFGFR4 expression inhibited CD8+ T cell infiltration in tissue sections from TNCB tumor bearing mice. Mechanistically, circFGFR4 competitively sponged miR-185-5p and prevented miR-185-5p from decreasing the levels of C-X-C motif chemokine receptor 4 (CXCR4). Conclusion: Ultimately, our results indicated that circFGFR4 plays an important role in immune evasion and anti-PD-1 immunotherapy resistance via regulates miR-185-5p/CXCR4 axis in TNBC, thus suggesting that circFGFR4 has significant potential as a biomarker for predicting sensitivity to anti-PD-1 immunotherapy and as an immunotherapeutic target for TNBC.

Prognostic and predictive values of the grading system of lymph node status in patients with advanced-stage gastric cancer.

Background: Lymph node metastasis is one of the most important prognostic factors of gastric cancer. However, the effect of germinal centers in lymph nodes on the prognosis of patients with gastric cancer has not been reported. This study aimed to investigate the contribution of germinal center generation to prognostic parameters and clinicopathological significance in gastric cancer. Methods: We retrospectively reviewed gastric cancer patients who underwent surgery from October 2012 to June 2022. We analyzed 5484 lymph nodes (210 patients) and calculated the lymph node metastasis rate (LNMR) and the proportion of non-metastatic lymph nodes containing three or more germinal centers (NML-GCP). Results: Using a grading system that incorporated LNMR and NML-GCP. The tumors were classified into three groups based on this system, which was found to be significantly associated with prognosis. The TNM stage and grading system of lymph node status were independent risk factors for overall survival (OS) and disease-free survival (DFS). The 5-year OS rates for patients with advanced gastric cancer were 85.07% (n=50), 58.34% (n=42), and 24.44% (n=21) for Grades 1, 2, and 3, respectively (p<0.0001). The 5-year DFS rates were 65.32% (n=58), 40.85% (n=51), and 5.88% (n=34), respectively (p<0.0001). Patients with Grade 1 advanced gastric cancer had higher 5-year OS and DFS rates compared to those with Grade 2 or 3 in TNM stage II and III. Furthermore, the 5-year OS and DFS rates differed significantly among patients with different grades of advanced gastric cancer who received chemotherapy (p<0.0001). Conclusion: These findings suggest that the grading system may be valuable for predicting prognosis and guiding clinical management in patients with gastric cancer, and provides good prognostic stratification for OS and DFS in patients with TNM stage II and III.

Rubiginosin B selectively inhibits Treg cell differentiation and enhances anti-tumor immune responses by targeting calcineurin-NFAT signaling pathway.

BACKGROUND: The accumulation of CD4+Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment (TME) dampens anti-tumor immune responses and promotes tumor progression. Therefore, the elimination of Tregs has become a strategy to enhance the efficacy of tumor immunotherapy, although it is still a daunting challenge. Rhododendron brachypodum (R. brachypodum) is a perennial shrub mainly distributed in Southwestern China, whereas the chemical constituents in this plant remain elusive. PURPOSE: To identify small-molecule inhibitors of Tregs from R. brachypodum. METHODS: Meroterpenoids in R. brachypodum were isolated by column chromatography under the guidance of LCMS analyses. The structures of isolates were identified by spectroscopic data and quantum calculations. The activities of compounds were first evaluated on CD4+ T cell differentiation by flow cytometry in Th1, Th2, Th17, and Treg polarizing conditions, and then on CT26 and MC38 murine colorectal carcinoma cells-allografted mice models. The mechanism of action was first investigated by determining Foxp3 degradation in Jurkat T cells transfected with pLVX-TetOne-Puro-Foxp3-tGFP, and then through analyses of Foxp3 expression on several pre-transcriptional signaling molecules. RESULTS: Two new prenylated phenolic acids (1 and 2) and a chromane meroterpenoid, rubiginosin B (RGB, 3) were obtained from R. brachypodum. The structure of S-anthopogochromene C (1) was rectified according to the electronic circular dichroism (ECD) experiment, and rhodobrachypodic acid (2) was proposed as the precursor of RGB by photochemical transformation. In this investigation, we first found that RGB (3) selectively suppressed the de novo differentiation of TGFß-induced CD4+Foxp3+ regulatory T cells (iTregs), overcome the immunosuppressive TME, and consequently inhibited the growth of tumor in mouse models. The mechanistic study revealed that RGB could target calcineurin, inhibited the nuclear factor of activated T cells (NFAT) dephosphorylation, and down-regulated Foxp3 expression. The hypothetical binding modes of RGB with calcineurin were predicted by molecular docking, and the interactions were mainly hydrophobic effects and hydrogen bonds. CONCLUSION: These results suggest that RGB enhances anti-tumor immune responses by inhibiting Treg cell differentiation through calcineurin-NFAT signaling pathway, and therefore RGB or its analogs may be used as adjuvant agents meriting further investigation.

Diarylheptanoids with hypoglycemic potency from the rhizomes of Kaempferia galanga.

Five new diarylheptanoids, kaemgalangins A-E (1-5), and seven known ones were isolated from the rhizomes of Kaempferia galanga. The structures of new compounds were identified by spectroscopic analyses involving 1D and 2D NMR, HRESIMS, IR, UV, [α]D, ECD calculations, and chemical methods. All compounds were tested for their hypoglycemic effects against α-glucosidase, Gpa and PTP1B enzymes, and stimulative effects on GLP-1 secretion. Kaemgalangins A (1) and E (5) showed significant inhibition on α-glucosidase with IC50 values of 45.3 and 116.0 µM; renealtin B (8) showed inhibition on GPa with an IC50 value of 68.1 µM; whereas all compounds were inactive to PTP1B. Docking study manifested that 1 well located in the catalytic pocket of α-glucosidase and OH-4″ played important roles in maintaining activity. Moreover, all compounds showed obviously stimulative effects on GLP-1 with promoting rates of 826.9%-1738.3% in NCI-H716 cells. This study suggests that the diarylheptanoids in K. galanga have antidiabetic potency by inhibiting α-glucosidase and Gpa enzymes, and promoting GLP-1 secretion.

Crizotinib-based proteolysis targeting chimera suppresses gastric cancer by promoting MET degradation.

As one of the common malignant cancer types, gastric cancer (GC) is known for late-stage diagnosis and poor prognosis. Overexpression of the receptor tyrosine kinase MET is associated with poor prognosis among patients with advanced stage GC. However, no MET inhibitor has been used for GC treatment. Like other tyrosine kinase inhibitors that fit the "occupancy-driven" model, current MET inhibitors are prone to acquired resistance. The emerging proteolysis targeting chimera (PROTAC) strategy could overcome such limitations through direct degradation of the target proteins. In this study, we successfully transformed the MET-targeted inhibitor crizotinib into a series of PROTACs, recruiting cereblon/cullin 4A E3 ubiquitin ligase to degrade the MET proteins. The optimized lead PROTAC (PRO-6 E) effectively eliminated MET proteins in vitro and in vivo, inhibiting proliferation and motility of MET-positive GC cells. In the MKN-45 xenograft model, PRO-6 E showed pronounced antitumor efficacy with a well-tolerated dosage regimen. These results validated PRO-6 E as the first oral PROTAC for MET-dependent GC.

HOXA5 inhibits the proliferation and metastasis of cervical squamous cell carcinoma by suppressing the ß-catenin/Snail signaling.

HOXA5, as a transcription factor, plays an important role in a variety of malignant tumors. Nevertheless, its biological role in cervical squamous cell carcinoma (CSCC) is largely unknown. In our study, we aimed to explore the function of HOXA5 in CSCC and its molecular mechanism. Immunohistochemistry showed that HOXA5 expression was downregulated in human CSCC tissues and HOXA5 staining was negatively correlated with tumor size and histological grade of CSCC. Ectopic expression of HOXA5 inhibited proliferative and metastatic abilities of CSCC cells in vitro and in vivo. Furthermore, overexpression of HOXA5 inhibited the cell cycle by arresting the S/G2 phase by flow cytometry and that was related to the downregulation of Cyclin A. Further study showed that HOXA5 suppressed EMT by inhibiting the ß-catenin/Snail signaling resulting in reduced metastasis of CSCC cells. Altogether, our results suggested that HOXA5 inhibited the proliferation and metastasis via repression of the ß-catenin/Snail pathway, proposing the potential role of HOXA5 in the prevention and treatment of CSCC.

Expression and immunogenicity of hepatitis E virus-like particles based on recombinant truncated ORF2 capsid protein.

Hepatitis E is an emerging zoonotic disease, posing a severe threat to public health in the world. Since there are no specific treatments available for HEV infection, it is crucial to develop vaccine to prevent this infection. In this study, the truncated ORF2 encoded protein of 439aa∼617aa (HEV3-179) from HEV CCJD-517 isolates was expressed as VLPs in E. coli with diameters of approximate 20 nm. HEV3-179 protein was immunized with mice, and the results showed that a higher titre of antibody was induced in NIH mice in comparison with that of KM mice (P < 0.01) and BALB/c mice (P < 0.01). The induced antibody titer is much higher in subcutaneous immunization mice than that in the mice inoculated via abdominal immunization (P < 0.05) and muscles immunization (P < 0.01). Mice immunized with 12 µg and 6 µg candidate vaccine induced higher level of antibody titer than that of 3 µg dosage group (P < 0.01, P < 0.05). Antibody change curve showed that HEV IgG antibody titer increased from 14 days post immunization (dpi) to 1:262144 and reached the peak level on 42 dpi before gradually retreated with the same level antibody titer with 1:131072 until 84 dpi. Mice inoculated with HEV3-179 produced higher titer of cytokines than the mock group, and the concentration of IL-1ß (P < 0.01) and IFN-γ (P < 0.01) further increased after stimulated by candidate vaccine. The result indicated that HEV3-179 possesses good immunogenicity, which could be used as a potential candidate for future HEV vaccine development.

Artemleucolides A-L, eudesmane-type sesquiterpenoids from Artemisia leucophylla and their antihepatoma cytotoxicity.

Twelve undescribed and 13 known eudesmane-type sesquiterpenoids were obtained from Artemisia leucophylla, and structurally elucidated based on comprehensive analyses of spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculation. The absolute configuration of compound 1 was determined by a single X-ray single crystal diffraction. Chemically, compounds 1-5 featured unprecedented 1,2-seco-1-nor-eudesmane-type skeleton with a cis-fused 6/5 bicyclic system. Antihepatoma evaluation against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1) for all compounds demonstrated that compound 7 displayed the most active cytotoxicity with IC50 values of 35.1, 35.0, and 32.7 µΜ.

[Terpenoids from fruits of Amomum villosum and their hypoglycemic activity].

Eight terpenoids were isolated from the fruits of Amomum villosum by silica gel, Sephadex LH-20, Rp-C_(18), MCI GEL CHP20 P column chromatography, preparative TLC, and HPLC. Their structures were identified by HR-ESI-MS, ~1H and ~(13)C-NMR, IR, UV, [α]_D, and ECD spectroscopic data as kravanhin A 3-O-ß-D-glucopyranoside(1), kravanhin B(2), 6-eudesmene-1ß,4ß-diol(3), oplodiol(4), vicodiol(5),(1R,2S,4R,7S)-vicodiol 9-O-ß-D-glucopyranoside(6),(1R,2S,4S,5R)-angelicoidenol 2-O-ß-D-glucopyranoside(7), and(1S,2S,4R,6S)-bornane-2,6-diol 2-O-ß-D-glucopyranoside(8). Compound 1 was a new compound, and compounds 2-5 were isolated from A. villosum for the first time. Their hypoglycemic activity was tested based on STC-1 cell model and two enzymatic models(GPa and PTP1 B). The results showed that compounds 1, 7, and 8 could stimulate GLP-1 with the secretion rates of 692.8%, 398.6%, and 483.3% at 25.0 µmol·L~(-1), and compound 6 showed inhibitory activity against GPa with an IC_(50) value of 78.6 µmol·L~(-1).

Plasma adsorption in refractory chronic gouty arthritis flare: A case report.

Background: Along with uric acid, which is the primary driving factor of gout, downstream inflammatory mediators have been shown to be involved in the pathogenesis of gouty arthritis flares. Extracorporeal haemadsorption is an emerging technology for the treatment of dysregulated inflammatory states by effectively removing cytokines from the bloodstream. Whether haemadsorption was effective in refractory gout flares has not been reported in the literature. Case summary: We report the case of a 52-year-old male who presented with refractory gouty arthropathy for 30 years. His uric acid levels were poorly controlled due to poor diet and treatment compliance. Tophi were found to have precipitated in multiple joints and subcutaneous tissue. In the last 2 years, his incidents of gouty flares had become more frequent, and resistant to the medications, including colchicine, allopurinol, febuxostat, glucocorticoids, and NSAID analgesics. He had experienced a triad of chills, high fever and arthritis for the past 2 weeks. Therefore, he took 2 mg colchicine twice daily for 2 weeks with no improvement in his pain. Proinflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), were found to be remarkably elevated. Given that conventional treatment was unsuccessful, we tried to employ plasma adsorption (PA) to remove inflammatory cytokines. After 4 sessions, symptoms, such as fever, joint swelling and pain, were greatly improved. Meanwhile, the levels of proinflammatory factors such as IL-6 and TNF-α were found to be decreased, while the anti-inflammatory factor IL-10 remained the same during the course. He was followed up for 8 months and arthritis have flared up twice in response to a high-purine diet. Conclusion: Our study suggests that plasma adsorption (PA) may be a promising and feasible treatment for refractory gout when conventional treatments are unsatisfactory or contraindicated. However, more clinical trials are needed to verify the efficacy and safety of the treatment. Core tip: Chronic gouty arthritis flares are refractory to conventional treatment, such as uric acid-lowering drugs and NSAID analgesics. Due to the involvement of inflammatory cytokines, plasma adsorption was employed to alleviate flares by removing inflammatory mediators. Herein, we report a 52-year-old male who presented with refractory gouty arthropathy for 30 years, manifested with a triad of chills, high fever and arthritis. He underwent several sessions of plasma adsorption, and his symptoms soon improved, along with a drop in inflammatory mediators. We conclude that plasma adsorption may be a promising and feasible treatment for refractory gout when conventional treatments are unsatisfactory or contraindicated.

Association between Serum Oxytocin, Bone Mineral Density and Body Composition in Chinese Adult Females.

Background and Objectives: Oxytocin (OT) is a neuropeptide hormone which is known for its classical effects in pregnancy and lactation. Recently, growing evidence demonstrated a close relation between OT and bone. The present study aimed to explore the relationship between OT, bone and osteoporosis risk in Chinese adult females. Materials and Methods: in total, 149 adult females were enrolled. The serum OT levels were measured using ELISA kits. Bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry (DXA). The study subjects were divided into two groups according to their menopause status and then divided into tertiles based on their serum OT level. Results: Serum OT, serum estradiol and BMD at three skeletal sites were significantly higher in the premenopausal group than in the postmenopausal group (p < 0.001, p = 0.008 and p < 0.001, respectively). In the tertile analysis, relative to tertile 1, significant associations were found for tertile 3 for OT levels and higher BMD in the femoral neck and total hip, in both pre- and postmenopausal groups. Using logistic regression analysis, tertile 3 appeared less likely to have low-BMD osteoporosis than tertile 1 (OR = 0.257, 95% CI = 0.073, 0.910). In multivariate stepwise regression analysis, OT and total lean mass were two positive determinants of BMD in the femoral neck and total hip in the premenopausal group (adjusted R2 for the model = 0.232 and 0.199, respectively; both p < 0.001). Conclusion: Our study demonstrated positive associations between serum OT levels and BMD in a Chinese (non-Caucasian) population. OT appeared to be more strongly associated with hip BMD in premenopausal females. These results may suggest a protective role and potential therapeutic use of OT in osteoporosis, especially for premenopausal women.

Synthesis and biological evaluation of paeoveitol D derivatives as new melatonin receptor agonists with antidepressant activities.

Our previous study demonstrated that paeoveitol D, a benzofuran compound isolated from Paeonia veitchii, displayed activity on MT1 and MT2 receptors with agonistic ratios of 57.5% and 51.6% at a concentration of 1 mM. To explore the structure-activity relationships, 34 paeoveitol D derivatives were synthesized and evaluated for their MT1 and MT2 agonistic activities using the Fluo-8 calcium assay. Among them, 16 and 18 derivatives increased agonistic activities on the MT1 and MT2 receptors, respectively. Compound 18 indicated EC50 values of 21.0 and 298.9 µM on MT1 and MT2 receptors in agonistic dose response curves with Tango assays and shortened immobility time in the forced swim test. The preliminary mechanism-of-action investigation manifested that the antidepressant activity of compound 18 may be mediated by promoting serotonin (5-HT) and dopamine (DA) levels in the mice brain. Compound 18 also showed favorable pharmacokinetic profiles and low toxicity in vivo. These results suggest that compound 18 could be a potential antidepressant agent.

Oligostilbenes from the seeds of Paeonia lactiflora as potent GLP-1 secretagogues targeting TGR5 receptor.

One unusual stilbene trimer-flavonoid hybrid, paeonilactiflobenoid (1), together with six known stilbenes (2-7) were isolated from the seeds of Paeonia lactiflora. The structure of 1 was elucidated with the aid of HRESIMS, 1D and 2D NMR, [α]D spectroscopic data and ECD calculation. Compounds 2-7 showed stimulative effects on GLP-1 secretion with promoting rates of 79.8%-880.4% (25 µM) and 217.6%-1089.4% (50 µM), more potent than the positive control, oleoylethanolamide (250.2% at 50 µM). Moreover, compounds 4 and 6 exhibited agonistic activity on the G protein-coupled receptor (GPCR) TGR5 with stimulative ratios of 40.2% and 40.5% at 50 µM, and 54.2% and 49.1% at 100 µM, respectively. Docking study manifested that 6 well located in the catalytic pocket of TGR5 by hydrogen-bond and hydrophobic interactions. The GLP-1 promotion of 6 could be attenuated by IP3, Ca2+/CaMKII and MEK/ERK pathway inhibitors, suggesting that these pathways played important roles in GLP-1 secretion. Thus, stilbenes in peony seeds maybe regarded as potential GLP-1 secretagogues through TGR5-IP3-Ca2+/CaMKII-MEK/ERK pathways.

Dynamic Response of CFRP Reinforced Steel Beams Subjected to Impact Action Based on FBG Sensing Technology.

The in-situ health condition of carbon fiber reinforced polymer (CFRP) reinforced structures has become an important topic, which can reflect the structural performance of the retrofitted structures and judge the design theory. An optical fiber-based structural health monitoring technique is thus suggested. To check the effectiveness of the proposed method, experimental testing on smart CFRP reinforced steel beams under impact action has been performed, and the dynamic response of the structure has been measured by the packaged FBG sensors attached to the surface of the beam and the FBG sensors inserted in the CFRP plates. Time and frequency domain analysis has been conducted to check the structural feature of the structures and the performance of the installed sensors. Results indicate that the packaged Fiber Bragg Grating (FBG) sensors show better sensing performance than the bare FBG sensors in perceiving the impact response of the beam. The sensors embedded in the CFRP plate show good measurement accuracy in sensing the external excitation and can replace the surface-attached FBG sensors. The dynamic performance of the reinforced structures subjected to the impact action can be straightforwardly read from the signals of FBG sensors. The larger impact energies bring about stronger impact signals.