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Due to inherent differences in cellular composition and metabolic behavior with host cells, tumor-harbored bacteria can discriminatorily affect tumor immune landscape. However, the mechanisms by which intracellular bacteria affect antigen presentation process between tumor cells and antigen-presenting cells (APCs) are largely unknown. The invasion behavior of attenuated Salmonella VNP20009 (VNP) into tumor cells is investigated and an attempt is made to modulate this behavior by modifying positively charged polymers on the surface of VNP. It is found that non-toxic chitosan oligosaccharide (COS) modified VNP (VNP@COS) bolsters the formation of gap junction between tumor cells and APCs by enhancing the ability of VNP to infect tumor cells. On this basis, a bacterial biohybrid is designed to promote in situ antigen cross-presentation through intracellular bacteria induced gap junction. This bacterial biohybrid also enhances the expression of major histocompatibility complex class I molecules on the surface of tumor cells through the incorporation of Mdivi-1 coupled with VNP@COS. This strategic integration serves to heighten the immunogenic exposure of tumor antigens; while, preserving the cytotoxic potency of T cells. A strategy is proposed to precisely controlling the function and local effects of microorganisms within tumors., (© 2024 Wiley‐VCH GmbH.)

As an emerging cancer treatment strategy, ferroptosis is greatly restricted by excessive glutathione (GSH) in tumor microenvironment (TME) and low reactive oxygen species (ROS) generation efficiency. Here, this work designs self-assembled copper-alanine nanoparticles (CACG) loaded with glucose oxidase (GOx) and cinnamaldehyde (Cin) for in situ glutathione activated and enzymatic cascade-enhanced ferroptosis and immunotherapy. In response to GSH-rich and acidic TME, CACG allows to effectively co-deliver Cu 2+ , Cin, and GOx into tumors. Released Cin consumes GSH through Michael addition, accompanying with the reduction of Cu 2+ into Cu + for further GSH depletion. With the cascade of Cu + -catalyzed Fenton reactions and enzyme-catalyzed reactions by GOx, CACG could get rid of the restriction of insufficient hydrogen peroxide in TME, leading to a robust and constant generation of ROS. With the high efficiency of GSH depletion and ROS production, ferroptosis is significantly enhanced by CACG in vivo. Moreover, elevated oxidative stress triggers robust immune responses by promoting dendritic cells maturation and T cell infiltration. The in vivo results prove that CACG could efficiently inhibit tumor growth in 4T1 tumor-bearing mouse model without causing obvious systemic toxicity, suggesting the great potential of CACG in enhancing ferroptosis and immunotherapy for effective cancer treatment., (© 2023 Wiley-VCH GmbH.)

The chemotherapy efficacy of nanodrugs is restricted by poor tumor targeting and uptake. Here, an engineered biohybrid living material (designated as EcN@HPB) is constructed by integrating paclitaxel and BAY-876 bound human serum albumin nanodrugs (HPB) with Escherichia coli Nissle 1917 (EcN). Due to the inherent tumor tropism of EcN, EcN@HPB could actively target the tumor site and competitively deprive glucose through bacterial respiration. Thus, albumin would be used as an alternative nutrient source for tumor metabolism, which significantly promotes the internalization of HPB by tumor cells. Subsequently, BAY-876 internalized along with HPB nanodrugs would further depress glucose uptake of tumor cells via inhibiting glucose transporter 1 (GLUT1). Together, the decline of glucose bioavailability of tumor cells would activate and promote the macropinocytosis in an AMP-activated protein kinase (AMPK)-dependent manner, resulting in more uptake of HPB by tumor cells and boosting the therapeutic outcome of paclitaxel.

The differential tumor environment guides various antitumor drug delivery strategies for efficient cancer treatment. Here, based on the special bacteria-enriched tumor environment, we report a different drug delivery strategy by targeting bacteria inhabiting tumor sites. With a tissue microarray analysis, it was found that bacteria amounts displayed significant differences between tumor and normal tissues. Bacteria-targeted mesoporous silica nanoparticles decorated with bacterial lipoteichoic acid (LTA) antibody (LTA-MSNs) could precisely target bacteria in tumors and deliver antitumor drugs. By the intravenous administration of bacteria-targeted nanoparticles, we showed in mice with colon cancer, lung cancer, and breast cancer that LTA-MSNs exhibited a high tumor-targeting ability. As a proof-of-concept study, tumor microbes as some of the characteristics of a tumor environment could be utilized as potential targets for tumor targeting. This bacteria-guided tumor-targeting strategy might have great potential in differential drug delivery and cancer treatment.

Clinical treatment efficacy of oral bacterial therapy has been largely limited by insufficient gut retention of probiotics. Here, we developed a bioorthogonal-mediated bacterial delivery strategy for enhancing probiotics colonization by modulating bacterial adhesion between probiotics and gut inhabitants. Metabolic amino acid engineering was applied to metabolically incorporate azido-decorated d-alanine into peptidoglycans of gut inhabitants, which could enable in situ bioorthogonal conjugation with dibenzocyclooctyne (DBCO)-modified probiotics. Both in vitro and in vivo studies demonstrated that the occurrence of the bioorthogonal reaction between azido- and DBCO-modified bacteria could result in obvious bacterial adhesion even in a complex physiological environment. DBCO-modified Clostridium butyricum ( C. butyricum ) also showed more efficient reservation in the gut and led to obvious disease relief in dextran sodium sulfate-induced colitis mice. This strategy highlights metabolically modified gut inhabitants as artificial reaction sites to bind with DBCO-decorated probiotics via bioorthogonal reactions, which shows great potential for enhancing bacterial colonization., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Degradation of pro-inflammatory macrophage-mediated connexin 43 (Cx43) plays an important role in post-myocardial infarction (MI) arrhythmogenesis, microRNA (miR)-155 produced by macrophages has been shown to mediate post-MI effects. We hypothesized that miR-155 inhibition attenuated MI-induced Cx43 degradation by reducing pro-inflammatory macrophage activation., Methods: MI was induced by permanent ligation of the left anterior descending coronary artery in male C57BL/6 mice. Lipopolysaccharide (LPS)-stimulated mice bone marrow-derived macrophages (BMDMs) and hypoxia-induced neonatal rat cardiomyocytes (NRCMs) were used in vitro models. qRT-PCR, Western-blot and immunofluorescence were used to analyze relevant indicators., Results: The expression levels of miR-155, interleukin-1 beta (IL-1β), and matrix metalloproteinase (MMP)7 were higher in MI mice and LPS-treated BMDMs than in the sham/control groups, treatment with a miR-155 antagomir reversed these effects. Moreover, miR-155 inhibition reduced ventricular arrhythmias incidence and improved cardiac function in MI mice. Cx43 expression was decreased in MI mice and hypoxia-exposed NRCMs, and hypoxia-induced Cx43 degradation in NRCMs was reduced by application of conditioned medium from LPS-induced BMDMs treated with the miR-155 antagomir, but increased by conditioned medium from BMDMs treated with a miR-155 agomir. Importantly, NRCMs cultured in conditioned medium from LPS-induced BMDMs transfected with small interfering RNA against IL-1β and MMP7 showed decreased hypoxia-mediated Cx43 degradation, and this effect also was diminished by BMDM treatment with the miR-155 agomir. Additionally, siRNA-mediated suppressor of cytokine signaling 1 (SOCS1) knockdown in LPS-induced BMDMs promoted Cx43 degradation in hypoxia-exposed NRCMs, and the effect was reduced by the miR-155 inhibition., Conclusions: MiR-155 inhibition attenuated post-MI Cx43 degradation by reducing macrophage-mediated IL-1β and MMP7 expression through the SOCS1/nuclear factor-κB pathway., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-21-743/coif). All authors report that this work was supported by the Joint Construction Project of Medical Science and Technology of Henan Province (Grant Nos. LHGJ20200072, LHGJ20200071 and LHGJ20200077) and the Medical Science and Technology Project of Henan Province (No. SBGJ202002030). The authors have no other conflicts of interest to declare., (2022 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP)., Methods: Self-administered GA was compared to provider's assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar's test was used to detect differences between PA and GA., Results: One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of 356 abnormalities in 96 patients; of which, 223 required interventions. African American and widowed/single patients were more likely to have abnormalities identified by GA. On average, across 100 patients, PA did not detect 25.5% of GA-detected abnormalities, mostly in functional status, social support, nutrition, and cognition. These differences were less pronounced among providers with more clinical experience. Patients with abnormal Timed Up and Go tests more likely had additional abnormalities in other domains, and more abnormalities that were not identified by PA. Providers were "surprised" by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 39% of patients based on GA findings., Conclusions: Including a GA in the care of OA-MBC in CP is beneficial for the detection of multiple abnormalities not detected by routine PA., (© The Author(s) 2022. Published by Oxford University Press.)

Ammonia inhibition easily affects the performance of anaerobic digestion (AD) for municipal sludge and the oxidization of volatile fatty acids (VFAs) is the rate-limiting step of this process. Bioaugmentation is considered to be an effective method to alleviate ammonia inhibition of AD, but most study used the hydrogenotrophic methanogens as the bioaugmentation culture. In this study, bioaugmentation of mesophilic AD (MAD) and thermophilic AD (TAD) under ammonia inhibition with syntrophic acetate and propionate oxidizing consortia was investigated. The results showed that the bioaugmented reactors recovered earlier than control reactors with 20 (MAD) and 8 (TAD) days, respectively. The high-throughput 16S rRNA gene sequencing indicated that the relative abundance of carbohydrates fermenter (Lentimicrobium), syntrophic VFAs-oxidizing bacteria (Rikenellaceae_DMER64, Smithella and Syntrophobacter) and acetoclastic and hydrogenotrophic methanogens (Methanosaeta, Methanolinea and Methanospirillum) increased in MAD after bioaugmentation. However, part of the bioaugmentation culture could not adapt to the high free ammonia (FAN) concentration in MAD and the effect was weakened. In TAD, proteolytic bacteria (Keratinibaculum and Tepidimicrobium), syntrophic VFAs-oxidizing bacteria (Syntrophomonas) and hydrogenotrophic methanogen (Methanosarcina) were strengthened. The effect of bioaugmentation in TAD was durable even at higher organic loading rate (OLR), due to its positive influence on microbial community. These results suggested that the different bioaugmentation mechanism occurred in MAD and TAD, which are derived from the synergetic effects of ammonia tolerance and microbial interactions. Our study revealed the VFAs-oxidizing consortia as bioaugmented culture could be the potential strategy to alleviate the ammonia stress of AD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Because a host's immune system is affected by host-microbiota interactions, means of modulating the microbiota could be leveraged to augment the effectiveness of cancer therapies. Here we report that patients with oral squamous cell carcinoma (OSCC) whose tumours contained higher levels of bacteria of the genus Peptostreptococcus had higher probability of long-term survival. We then show that in mice with murine OSCC tumours injected with oral microbiota from patients with OSCCs, antitumour responses were enhanced by the subcutaneous delivery of an adhesive hydrogel incorporating silver nanoparticles (which inhibited the growth of bacteria competing with Peptostreptococcus) alongside the intratumoural delivery of the bacterium P. anaerobius (which upregulated the levels of Peptostreptococcus). We also show that in mice with subcutaneous or orthotopic murine OSCC tumours, combination therapy with the two components (nanoparticle-incorporating hydrogel and exogenous P. anaerobius) synergized with checkpoint inhibition with programmed death-1. Our findings suggest that biomaterials can be designed to modulate human microbiota to augment antitumour immune responses., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The excessive lactate in the tumor microenvironment always leads to poor therapeutic outcomes of chemotherapy. In this study, a self-driven bioreactor (defined as SO@MDH, where SO is Shewanella oneidensis MR-1 and MDH is MIL-101 metal-organic framework nanoparticles/doxorubicin/hyaluronic acid) is rationally constructed via the integration of doxorubicin (DOX)-loaded metal-organic framework (MOF) MIL-101 nanoparticles with SO to sensitize chemotherapy. Owing to the intrinsic tumor tropism and electron-driven respiration of SO, the biohybrid SO@MDH could actively target and colonize hypoxic and eutrophic tumor regions and anaerobically metabolize lactate accompanied by the transfer of electrons to Fe 3+ , which is the key component of the MIL-101 nanoparticles. As a result, the intratumoral lactate would undergo continuous catabolism coupled with the reduction of Fe 3+ to Fe 2+ and the subsequent degradation of MIL-101 frameworks, leading to an expeditious drug release for effective chemotherapy. Meanwhile, the generated Fe 2+ will be promptly oxidized by the abundant hydrogen peroxide in the tumor microenvironment to reproduce Fe 3+ , which is, in turn, beneficial to circularly catabolize lactate and boost chemotherapy. More importantly, the consumption of intratumoral lactic acid could significantly inhibit the expression of multidrug resistance-related ABCB1 protein (also named P-glycoprotein (P-gp)) for conquering drug-resistant tumors. SO@MDH demonstrated here holds high tumor specificity and promising chemotherapeutic efficacy for suppressing tumor growth and overcoming multidrug resistance, confirming its potential prospects in cancer therapy.

Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-β1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-β1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-β1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Objective: To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT)., Methods: A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated., Results: We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score ( p = 0.364) or occur-to-treatment time ( p = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; p = 0.016). We further found significantly lower plasma S100-β ( p = 0.007) and higher vascular endothelial growth factor ( p = 0.003) levels in the RIPC group than in the control group., Conclusions: Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS., Clinicaltrialsgov Identifier: NCT03218293., Classification of Evidence: This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days., (© 2020 American Academy of Neurology.)

Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.

Accumulating evidence indicates that colonized microbes play a crucial role in regulating health and disease in the human body. Detecting microbes should be essential for understanding the relationship between microbes and diseases, as well as increasing our ability to detect diseases. Here, a combined metabolic labeling strategy was developed to identify different bacterial species and microbiota by the use of three different fluorescent metabolite derivatives emitting red, green, and blue (RGB) fluorescence. Upon co-incubation with microbes, these fluorescent metabolite derivatives are incorporated into bacteria, generating unique true-color fingerprints for different bacterial species and different microbiota. A portable spectrometer was also fabricated to automate the colorimetric analysis in combination with a smartphone to conveniently identify different bacterial species and microbiota. Herein, the effectiveness of this system was demonstrated by the identification of certain bacterial species and microbiota in mice with different diseases, such as skin infections and bacteremia. By analyzing the microbiota fingerprints of saliva samples from clinical patients and healthy people, this system was proved to precisely distinguish oral squamous cell carcinoma (OSCC, n = 29) samples from precancerous ( n = 10) and healthy ( n = 5) samples., (This journal is © The Royal Society of Chemistry 2020.)

Background: A standard approach to treating resectable esophageal adenocarcinoma is chemoradiotherapy (CRT) followed by surgery; however, recurrence is common. To improve this, we designed a single-arm, phase II trial that added an epidermal growth factor receptor (EGFR) inhibitor, cetuximab (C), to CRT, with the hypothesis that EGFR inhibition would improve pathologic complete response (pCR) rate., Materials and Methods: We aimed to increase the pCR rate from 25% to 45%. A Simon two-stage design (α and β of 0.10) required pCR/enrolled 5/18 for stage 1 and 14/40 total. CRT: oxaliplatin 85 mg/m 2 days 1, 15, and 29; infusional 5-fluorouracil 180 mg/m 2 /24 hours × 35 days; C 400 mg/m 2 day 1 then 250 mg/m 2 days 8, 15, 22, and 29 and radiation (intensity modulated radiotherapy [IMRT] allowed) 180 cGy/day × 25 fractions (Monday through Friday). Following esophagectomy, adjuvant chemotherapy (CT): weekly docetaxel 35 mg/m 2 and C 250 mg/m 2 5 out of 6 weeks for two cycles., Results: Of 21 eligible patients enrolled, 17 had surgery; 4 died before operation (due to pulmonary embolism 4 days after CRT, G3 diarrhea, progressive disease during CRT, sepsis/hypoxia during CRT, and acute respiratory distress syndrome [ARDS]). pCR = 7/17. Three postoperative deaths due to ARDS resulted in seven total study-related deaths. Of the 14 remaining patients, 12 started and completed adjuvant CT. Two of seven patients with pCR died, both of ARDS. Out of the 21 eligible subjects in this study, 13 have died and 8 remain alive. The use of IMRT did not correlate with ARDS., Conclusion: This regimen demonstrated promising activity. Toxicity was significant, with seven study-related deaths leading to closure after stage 1. All postoperative deaths were due to ARDS. This regimen is not recommended., Implications for Practice: Esophageal cancer is a disease with a high death rate. The current treatment involves giving chemotherapy plus radiation followed by surgery, but this cures only a quarter of patients. In order to improve survival, better treatments are needed. This trial evaluated the addition of a novel drug, cetuximab, to chemotherapy plus radiation. Unfortunately, the side effects were too great and the study was stopped early., (© AlphaMed Press 2019.)

Phosphorus (P) deficiency is an important factor that limits the agricultural production potential in acidic soils. The bacterial phoC gene encodes non-specific acid phosphatase (ACP), which participates in the mineralization of soil organic P and is therefore important for the improvement of soil P availability. However, the function and community population of phoC -harboring bacteria and their driving factors in acidic soil remain largely unknown. For this study, 51 soil samples and 207 plant samples were collected from four locations in the acidic soil region of southern China. Quantitative PCR and high-throughput sequencing were employed to analyze abundance and community composition of phoC -harboring bacteria. The results showed that soil P availability was the important nutrient element limiting the growth of both plants and soil bacteria. Soil ACP activity was clearly higher than alkaline phosphatase, indicating the important effect of phoC -harboring bacteria in acidic soils. ACP activity and phoC gene abundance showed a significant positive correlation, and both were closely related to soil available P, total carbon, and total nitrogen. The dominant genera of phoC -harboring bacteria involved Cupriavidus , Stenotrophomonas , and Xanthomonas . Compared to land-use pattern, sampling location, and soil parent material, soil property played a more important role in affecting phoC -harboring bacterial community structure, where N-related variables including soil NO 3 - -N, NH 4 + -N, and C/N ratio appeared to be the main factors. These findings suggest that phoC -harboring bacteria should provide an important contribution to soil P availability in acidic soil, and its function and community composition were strongly associated with soil nutrients., (Copyright © 2019 Zheng, Wang, Li, Song and Shen.)

Chan, APC, Yang, Y, Wong, FKW, Yam, MCH, Wong, DP, and Song, W-F. Reduction of physiological strain under a hot and humid environment by a hybrid cooling vest. J Strength Cond Res 33(5): 1429-1436, 2019-Cooling treatment is regarded as one of good practices to provide safe training conditions to athletic trainers in the hot environment. The present study aimed to investigate whether wearing a commercial lightweight and portable hybrid cooling vest that combines air ventilation fans with frozen gel packs was an effective means to reduce participants' body heat strain. In this within-subject repeated measures study, 10 male volunteers participated in 2 heat-stress trials (one with the cooling vest-COOL condition, and another without-CON condition, in a randomized order) inside a climatic chamber with a controlled ambient temperature 33° C and relative humidity (RH) 75% on an experimental day. Each trial included a progressively incremental running test, followed by a 40-minute postexercise recovery. Core temperature (Tc), heart rate (HR), sweat rate (SR), rating of perceived exertion (RPE), exercise duration, running distance, and power output were measured. When comparing the 2 conditions, a nonstatistically significant moderate cooling effect in rate of increase in Tc (0.03 ± 0.02° C·min for COOL vs. 0.04 ± 0.02° C·min for CON, p = 0.054, d = 0.57), HR (3 ± 1 b·min·min for COOL vs. 4 ± 1 b·min·min for CON, p = 0.229, d = 0.40), and physiological strain index (PSI) (0.20 ± 0.06 unit·min for COOL vs. 0.23 ± 0.06 unit·min for CON, p = 0.072, d = 0.50) was found in the COOL condition during exercise. A nonstatistically significant (p > 0.05) trivial cooling effect (d < 0.2) was observed between the COOL and CON conditions for measures of exercise duration, running distance, power output, SR, and RPE. It is concluded that the use of the hybrid cooling vest achieved a moderate cooling effect in lowering the rate of increase in physiological strain without impeding the performance of progressively incremental exercise in the heat.

A star-shaped molecularly imprinted coating was prepared starting from octavinyl-modified polyhedral oligomeric silsesquioxanes (Ov-POSS). It possesses a relatively open structure and has good site accessibility and a larger capacity even at lower cross-linking. The imprinted coating was prepared from S-amlodipine (S-AML) as the template and analyte, Ov-POSS as the cross-linker, and methacrylic acid as the functional monomer. The preparation and chromatographic parameters were optimized, including ratio of template to functional monomer, apparent cross-linking degree, pH value, ACN content and salt concentration in the mobile phase. The best resolution in enantiomer separation by means of capillary electrochromatography reaches a value of 33. A good recognition ability (α = 2.60) was obtained and the column efficiency for S-AML was 54,000 plates m -1 . The use of Ov-POSS as a cross-linker significantly improves the column capacity and thus the detection sensitivity. The results show that Ov-POSS is an effective cross-linker for the preparation of imprinted polymers with good accessibility and large capacity. Graphical abstract Schematic presentation of the preparation of star-shaped imprinted polymer using octavinyl-modified polyhedral oligomeric silsesquioxanes (Ov-POSS) and by using methacrylic acid (MAA) as functional monomer. The best enantiometric resolution (33) for amlodipine (AML) can be achieved in capillary chromatography (CEC).

An inorganic-organic hybrid monolith incorporated with stellated mesoporous silica nanoparticles (SMSNs) was prepared. Using binary solvents, deep eutectic solvents and room temperature ionic liquids, an SMSN-incorporated poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith demonstrated uniform structure with good column permeability. A systematic investigation of preparation parameter was performed, including SMSN content, crosslinking monomer content, and the component of binary solvent. The optimized monoliths were characterized by field emission scanning electron microscopy, transmission electron microscopy, area scanning energy dispersive spectrometry, and nitrogen adsorption. Column performance was tested by separating four groups of analytes (alkylbenzenes, anilines, naphthalenes and phenols) by capillary electrochromatography (CEC). Baseline separation of all analytes was obtained with column efficiencies of up to 266,000 plates m -1 . The performance of the resulting monolith was further investigated in detail by separating mixtures of polycyclic aromatic hydrocarbons (PAHs), nonsteroidal antiinflammatory drugs (NSAIDs), and hydroxybenzoic acid isomers. Compared with the corresponding SMSN-free monolith, the CEC performance was improved by about six times. Successful extraction of PAHs and quinolones (QNs) were also performed using this capillary. Improved extraction efficiency (20.2%) for complex samples, lake water, was also found when the material was applied to solid phase microextraction of fluoranthene. Graphical abstract A poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith incorporated with stellated mesoporous silica nanoparticles was prepared. It demonstrated column efficiency up to 266,000 plates m -1 in capillary electrochromatography and ability as solid phase microextraction for organic small molecules with good column permeability.

Objective: Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown., Data Sources: This review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS.", Study Selection: The original articles and reviews including the topics were the primary references., Results: Based on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival., Conclusions: At present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs., Competing Interests: There are no conflicts of interest

Objective: The provision of appropriate personal cooling vests is recognized as an effective measure to combat heat stress. However, personal cooling vests are not widely implemented in the Hong Kong industries. The current study aims to evaluate the usability of a hybrid cooling vest that is associated with the success of its application in industrial settings., Methods: A self-administrated questionnaire focusing on 10 subjective attributes of cooling effect, ergonomic design and usability of a hybrid cooling vest was administered with 232 occupational workers in the construction, horticultural and cleaning, airport apron services and kitchen and catering industries., Results: A structural equation model estimated by analysis of moment structures was constructed to evaluate the usability of the cooling vest, as influenced by cooling effect and ergonomic design. Results showed that cooling effect (path coefficient = 0.69, p < 0.001) and ergonomic design (path coefficient = 0.55, p < 0.001) significantly affect the usability of the cooling vest., Conclusions: The structural equation model is feasible to examine the complex nature of the structural relationships among the subjective perceptions of personal cooling vests. The empirical findings furnish sound evidence for further optimization of the hybrid cooling vest in terms of cooling effect and ergonomic design for occupational workers.

Light environments have long been known to influence grape ( Vitis vinifera L.) berry development and biosynthesis of phenolic compounds, and ultimately affect wine quality. Here, the accumulation and compositional changes of hydroxycinnamic acids (HCAs) and flavonoids, as well as global gene expression were analyzed in Cabernet Sauvignon grape berries under sunlight exposure treatments at different phenological stages. Sunlight exposure did not consistently affect the accumulation of berry skin flavan-3-ol or anthocyanin among different seasons due to climatic variations, but increased HCA content significantly at véraison and harvest, and enhanced flavonol accumulation dramatically with its timing and severity degree trend. As in sunlight exposed berries, a highly significant correlation was observed between the expression of genes coding phenylalanine ammonia-lyase, 4-coumarate: CoA ligase, flavanone 3-hydroxylase and flavonol synthase family members and corresponding metabolite accumulation in the phenolic biosynthesis pathway, which may positively or negatively be regulated by MYB, bHLH, WRKY, AP2/EREBP, C2C2, NAC, and C2H2 transcription factors (TFs). Furthermore, some candidate genes required for auxin, ethylene and abscisic acid signal transductions were also identified which are probably involved in berry development and flavonoid biosynthesis in response to enhanced sunlight irradiation. Taken together, this study provides a valuable overview of the light-induced phenolic metabolism and transcriptome changes, especially the dynamic responses of TFs and signaling components of phytohormones, and contributes to the further understanding of sunlight-responsive phenolic biosynthesis regulation in grape berries.

Objective: To estimate the safety and feasibility of flexible laryngeal mask airway (FLMA) for lumbar vertebral surgery in prone position., Methods: In the study, 120 adult patients scheduled for lumbar vertebral surgery under intravenous general anesthesia were divided into group FLMA and reinforced tracheal tube (RTT) group at random. Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded at the beginning of anesthesia induction (T0) and on the time of artificial airway intubation (T1), 1 min after intubation (T2), extubation (T3), 1 min after extubation (T4) as well. The number and time required for intubation were recorded. Peak airway pressure (P PEAK ), airway sealing pressure (P AS ) in group FLMA and fiberoptic bronchoscopy scale (FBS) were recorded after artificial airway intubation, turned over into prone position and after the operation started, as well as on the time of 1 hour after the operation started, 2 hours after operation started and when the operation stopped. Finally, respiratory complications after extubation, including hypoxemia, laryngospasm, coughing, vomiting, hoarseness, and pharyngalgia, were observed and whether there was blood or sewage inside and outside the artificial airway was recorded., Results: There was no difference in the number and time required for intubation between the two groups (P>0.05). There was no difference in P PEAK and FBS between the two groups, and also the same at the different time points in each group (P>0.05). P AS in group FLMA was the same at the diverse time points during anesthesia (P>0.05) and always higher than P PEAK in the perioperative period. In group FLMA, there was no difference in HR, SBP and DBP between the time points of T2 and T1, also of T4 and T3 (P>0.05). In group RTT, HR, SBP and DBP were significantly higher between the time points of T2 and T1 (P<0.01); SBP was significantly higher between the time points of T4 and T3 (P<0.01), DBP and HR were higher between the time points of T4 and T3 (P<0.05). SBP in group FLMA was significantly lower than in group RTT at T2 (P<0.01), HR and DBP were lower than those in group RTT simultaneously (P<0.05). On the time point of T4, SBP, DBP and HR in group FLMA were lower than those in group RTT (P<0.05). The incidence of coughing and pharyngalgia after extubation was significantly lower in group FLMA than in group RTT (P<0.01), with the incidence of hoarseness was lower in group FLMA than in group RTT (P<0.05). There was no difference in the incidence of hypoxemia, vomiting and blood seen outside the cuff between the two groups (P>0.05) while no laryngospasm and sewage seen outside the artificial airway in each group., Conclusion: For suitable patients, FLMA can be used in mechanical ventilation forlumbar vertebral surgery in prone position with more stable circulation and less respiratory complications than RTT. Further clinical validation is needed for the safety of FLMA.

While continuous cooling strategies may induce some ergonomic problems to occupational workers, cooling between work bouts may be an alternative for cooling them down in hot environments. The purpose of this study was to assess the effects of wearing a newly designed hybrid cooling vest (HCV) between two bouts of exercise. Inside a climatic chamber set at an air temperature of 37°C and a relative humidity of 60%, twelve male participants underwent two bouts of intermittent exercise interspersed with a 30min between-bout recovery session, during which HCV or a passive rest without any cooling (PAS) was administered. The results indicated that thermoregulatory, physiological, and perceptual strains were significantly lower in HCV than those in PAS during the recovery session (p≤0.022), which were accompanied with a large effect of cooling (Cohen's d=0.84-2.11). For the second exercise bout, the exercise time following HCV (22.13±12.27min) was significantly longer than that following PAS (11.04±3.40min, p=0.005, d=1.23) During this period, core temperature T c was significantly lower by 0.14±0.0.15°C in HCV than that in PAS. The heart rate drift over time was declined by 2±2bpmmin -1 (p=0.001, d=1.00) and the rise in physiological strain index was reduced by 0.11±0.12unitmin -1 (p=0.010, d=0.96) following the use of HCV. These findings suggested that using HCV could accelerate between-bout recovery and improve subsequent exercise performance by the enlarged body core temperature margin and blunted cardiovascular drift., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced clinical stage in pancreatic cancer patients. EZH2 knockdown in pancreatic cancer cell lines inhibited cell migration and invasion, but did not alter cell proliferation. Silencing of EZH2 also increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with EZH2 expression in pancreatic cancer tissue samples. Patients with high EZH2 and low E-cadherin expression had the worst prognosis. RIP and ChIP assays suggest that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer.

Previous studies have revealed that wearers had low skin temperatures and cold and pain sensations in the feet, when using sleeping bags under defined comfort and limit temperatures. To improve wearers' local thermal comfort in the feet, a novel heating sleeping bag (i.e., MARHT) was developed by embedding two heating pads into the traditional sleeping bag (i.e., MARCON) in this region. Seven female and seven male volunteers underwent two tests on different days. Each test lasted for three hours and was performed in a climate chamber with a setting temperature deduced from EN 13537 (2012) (for females: comfort temperature of -0.4 °C, and for males: the limit temperature of -6.4 °C). MARHT was found to be effective in maintaining the toe and feet temperatures within the thermoneutral range for both sex groups compared to the linearly decreased temperatures in MARCON during the 3-hour exposure. In addition, wearing MARHT elevated the toe blood flow significantly for most females and all males. Thermal and comfort sensations showed a large improvement in feet and a small to moderate improvement in the whole body for both sex groups in MARHT. It was concluded that MARHT is effective in improving local thermal comfort in the feet.

Plants challenged with abiotic stress show enhanced polyamines levels. Here, we show that the polyamine putrescine (Put) plays an important role to alleviate Fe deficiency. The adc2-1 mutant, which is defective in Put biosynthesis, was hypersensitive to Fe deficiency compared with wild type (Col-1 of Arabidopsis [Arabidopsis thaliana]). Exogenous Put decreased the Fe bound to root cell wall, especially to hemicellulose, and increased root and shoot soluble Fe content, thus alleviating the Fe deficiency-induced chlorosis. Intriguingly, exogenous Put induced the accumulation of nitric oxide (NO) under both Fe-sufficient (+Fe) and Fe-deficient (-Fe) conditions, although the ferric-chelate reductase (FCR) activity and the expression of genes related to Fe uptake were induced only under -Fe treatment. The alleviation of Fe deficiency by Put was diminished in the hemicellulose-level decreased mutant-xth31 and in the noa1 and nia1nia2 mutants, in which the endogenous NO levels are reduced, indicating that both NO and hemicellulose are involved in Put-mediated alleviation of Fe deficiency. However, the FCR activity and the expression of genes related to Fe uptake were still up-regulated under -Fe+Put treatment compared with -Fe treatment in xth31, and Put-induced cell wall Fe remobilization was abolished in noa1 and nia1nia2, indicating that Put-regulated cell wall Fe reutilization is dependent on NO. From our results, we conclude that Put is involved in the remobilization of Fe from root cell wall hemicellulose in a process dependent on NO accumulation under Fe-deficient condition in Arabidopsis., (© 2016 American Society of Plant Biologists. All Rights Reserved.)

Stable isotope techniques provide a new approach to study soil water movement. The precipitation and the soil water from 0 to 100 cm soil layer in 4 kinds of typical vegetation types (forest, shrub forest, grassland and non-forest land) over the water source area of Yuanyang terrace were sampled, and their isotope compositions were analyzed, aimed to understand the characteristics of stable isotopes in different depth of the soil water. The results showed that the meteoric water line in the water source area of Yuanyang terrace was δD = 6.838 4δ(18)O-5.6921 (R2 = 0.8787, n = 20), the slope and intercept were less than the global atmospheric precipitation. The hydrogen and oxygen stable isotopes in the soil water of the 4 kinds of typical types was lower than the local meteoric water line side and the fluctuation of isotope value on surface soil profile was greater. With the increasing soil depth, the fluctuation of delta 18O value was smaller and smaller, especially in the 80-100 cm soil layer which was the most obvious. The delta 18O values of the deep soil water in forest and grassland were higher than that in the surface soil. while it was on the contrary in shrub forest and non-forest land.

The relative efficacy and safety of first-line metastatic colorectal cancer (mCRC) treatment regimens, capecitabine with irinotecan (CAPIRI) and 5-fluorouracil/leucovorin plus irinotecan (FOLFIRI), are not well defined. We identified and subsequently examined seven independent, randomized controlled clinical trials, performing a meta-analysis to compare these two treatment regimens. Using Medline, EMBASE, Cochrane Library (CENTRAL), and the American Society of Clinical Oncology Annual Meeting to search available literature until February 2014, we identified seven studies comparing safety and efficacy of CAPIRI and FOLFIRI in mCRC patients. These studies were pooled and evaluated for rates of progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and diarrhea. CAPIRI and FOLFIRI demonstrated similar efficacy outcomes, though CAPIRI was associated with a higher incidence of diarrhea. CAPIRI and FOLFIRI are equally effective options for first-line treatment of mCRC.

Intergeneric crop plant hybrid lines with small-segment chromosome translocations are very useful in plant genetic research and breeding. In this study, to create small-segment chromosome translocations with beneficial agronomic characters, the progeny of wheat-rye substitution lines 5R/5A and 6R/6A were selected from generations F 2 to F 5 for rye-specific characteristics. A PCR primer and specific simple sequence repeat marker for rye were used in F 5 populations to detect rye chromatin and to amplify a specific chromosome band in six translocation lines (06-6-5, 06-6-6, 06-6-9, 6-26-1, 7-23, and 7-33). Fragment pSc119.1 cloned from 7-33 had 99% homology with the big ear gene sequence (GenBank AF512607.1) in wheat. The six lines were further characterized via pollen mother cell meiosis analysis for genetic stability, and chromosome C-banding and genomic in situ hybridization for rye chromatin. The results show that line 7-33 was still within the 5R/5A substitution lines and possessed the big ear gene. The other lines all contained small-segment rye chromosome translocations. The results indicated that substitution line hybridization is an effective method for creating small-segment chromosome translocations with useful agronomic traits. Trials for these six wheat-rye translocation lines are justified because they possess many important stably-inherited agronomic characters, including disease resistance and improved yield.

Aim: We retrospectively investigated the relationship between IVS14+1 G > A genotype of the dihydropyrimidine dehydrogenase (DPD) gene with plasma concentration of 5-fluorouracil (5-FU) as well as adverse reactions in 80 patients with locally advanced or metastatic colorectal cancer., Patients and Methods: Eighty patients with un-resectable locally advanced or metastatic colorectal cancer were treated with Folfox-6 regimen, which repeated every two weeks for at least three cycles. Single nucleotide polymorphisms for DPD gene were analyzed before chemotherapy by high-resolution melting (HRM) analysis. The plasma concentration of fluorouracil was measured by high performance liquid chromatography (HPLC) after continuous infusion of fluorouracil over 12 h in each cycle. The average values of plasma concentrations in each cycle were calculated, and the factors related to plasma concentration of 5-FU were screened by stepwise regression., Results: All patients were divided into three groups according to the predictive confidence interval of plasma concentration of 5-FU, and the average plasma concentrations of fluorouracil in each cycle of these three groups were less than or equal to 26.83 mg/L, 26.83-40.62 mg/L, and more than 40.62 mg/L, respectively. Stepwise regression analysis showed that the plasma concentration of fluorouracil was associated with myelosuppression, hand-foot syndrome, diarrhea, overall survival (OS) and DPD genotype. In efficacy, the median progression-free survival PFS (mPFS) and OS (mOS) of group 2 and group 3 were both significantly higher than those of group 1., Conclusions: Among the advanced colorectal cancer patients receiving fluorouracil-based chemotherapy, those with plasma concentration of 5-FU above 26.83 mg/L can obtain better survival; for patients with heterozygous DPD IVS14+1 mutation, 5-FU dose should be appropriately reduced according to last plasma concentration to reduce adverse reactions, while the homozygous ones should avoid application of 5-FU and its derivatives.

Objective: To clarify the effect of aluminum exposure on the cognitive function in electrolytic workers and the prevalence of mild cognitive impairment (MCI) among them by prevalence survey, and to investigate its influential factors., Methods: Sixty-six retired workers from the electrolysis workshop of an electrolytic aluminum plant were selected as an aluminum exposure group, while 70 retired workers from a flour mill in the same region were selected as a control group. MCI patients were screened out by Mini-Mental State Examination (MMSE); the blood aluminum level was measured by inductively coupled plasma-mass spectrometry; multivariate statistical analysis was used to investigate the influential factors for MMSE scores and the correlation between blood aluminum level and MCI prevalence., Results: The aluminum exposure group showed a significantly higher blood aluminum level than the control group (25.18 ± 2.65 µg/L vs 9.97 ± 2.83 µg/L, P < 0.01). The total MMSE score of the aluminum exposure group (26.13 ± 2.57) was significantly lower than that of the control group (27.89 ± 1.91) (P < 0.05), particularly the scores on time and place orientation, short-term memory, calculation ability, and language skill (P < 0.05). The detection rate of MCI was significantly higher in the aluminum exposure group (18.2%) than in the control group (5.7%) (P < 0.01). The main influential factors for MMSE scores were gender, age, education level, and blood aluminum level. The logistic regression analysis indicated that the MCI prevalence was significantly correlated with blood aluminum level in the study population (OR = 1.168, P < 0.01)., Conclusion: Long-term exposure to aluminum can cause cognitive disorders in electrolytic workers and may be one of the risk factors for MCI. Advanced age, male, low education level, and high blood aluminum level may be high-risk factors for cognitive impairment.

Background and Aims: MicroRNA-21 (miR-21) is reported to be overexpressed and to contribute to proliferation, apoptosis and gemcitabine resistance in pancreatic ductal adenocarcinomas (PDACs). The aims of this study were to explore regulation of miR-21 expression by epigenetic change and its impact on chemoresistance and malignant properties of of pancreatic cancer., Materials and Methods: We retrospectively collected 41 cases of advanced pancreatic cancer patients who were sensitive or resistant to gemcitabine and assessed levels of serum circulating miR-21 for correlation with cytotoxic activity. Histone acetylation in the miR-21 promoter was also studied in gemcitabine-sensitive and gemcitabine-resistant PDAC cells. Gemcitabine-resistant HPAC and PANC-1 cells were transfected with pre-miR-21 precursors (pre-miR-21) and antisense oligonucleotides (anti-miR-21), and were treated with TSA. Finally, invasion and metastasis assays were performed and alteration in mir-21, PTEN, AKT and pAKT level was evaluated in these cells., Results: Serum miR-21 levels were increased in gemcitabine- resistant PDAC patients compared with gemcitabine-sensitive subjects. The miR-21 levels were increased in 6 PDAC cells treated with gemcitabine significantly, associated with 50% inhibitory concentrations (IC50s). Histone acetylation levels at miR-21 promoter were increased in PDAC cells after treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21 expression, decreased PTEN, elevated pAKT level were demonstrated in gemcitabine-resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAKT levels in these two lines. In contrast, anti-miR-21 transfection could reverse invasion and metastasis, and PTEN and pAKT expressions induced by gemcitabine., Conclusions: MiR-21 upregulation induced by histone acetylation in the promoter zone is associated with chemoresistance to gemcitabine and enhanced malignant potential in pancreatic cancer cells.

Objective: To investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer, and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy., Methods: Eighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil): group 1 (plasma concentration of fluorouracil < 25 ng/ml), group 2 (25 - 35 ng/ml) and group 3 (> 35 ng/ml). The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h). The relationship between the drug plasma concentration, therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively., Results: The average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml, (31.47 ± 2.33) ng/ml and (39.89 ± 3.87) ng/ml, respectively (P < 0.01). As for therapeutic efficacy, the median OS of the groups 2 and 3 were 18.0 and 17.5 months, significantly higher than that in the group 1 (13.0 months, P < 0.01). The PFS were 4.5, 7.5 and 8.0 months, respectively (P < 0.01). In terms of adverse reactions, the incidences of bone marrow suppression, mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P = 0.02, P = 0.04 and P = 0.02)., Conclusions: The patients with local advanced and metastatic colorectal cancer, receiving fluorouracil-based chemotherapy, and with an average plasma concentration of fluorouracil between 25 - 35 mg/L have a better prognosis, and lower incidence of adverse reactions such as bone marrow suppression, mucositis and diarrhea.

Objective: To analyze the chemical compositions of Dalbergia odorifera essential oils extacted by CO2-supercritical-fluid-extraction (SFE-CO2) and steam distillation extraction (SD)., Methods: The essential oils of Dalbergia odorifera were extracted by steam distillation extraction and SFE-CO2. The chemical components were separated and analyzed by gas chromatography-mass spectrometry., Results: 12 compounds were identified in SFE sample. The major components from essential oils were 2-propenoic acid-3(4-methoxyphenyl)-ethyl ester (14.53%), nerolidol (14.95%), ageratochromene (1.33%). 9 compounds were identified in SD sample. The major components from essential oils were nerolidol (26.61%), cedrol (1.65%)., Conclusion: The SFE method is better than the SD method in reliability stability and reproducibility, and suitable for essential oils extraction of Dalbergia odorifera.

Objective: To detect central obesity and related adverse cardiovascular disease risk factors by waist-to-height ratio (WHR) among normal weight adults in Chongqing area., Methods: A total of 20 000 participants aged 18 - 59 from one hour economic cycle of Chongqing area were selected by group sampling method. We measured the height, waist circumference (WC), body weight, blood pressure, blood lipid and blood sugar. Body Mass Index (BMI) and WHR were computed. We analyzed the differences of the correlated indexes between non-central obesity group (WHR < 0.5) and central obesity group (WHR ≥ 0.5) of those had normal weight (18.5 ≤ BMI (kg/m(2)) < 24). And we used logistic regression method to analyze the relation between central obesity and related adverse cardiovascular risk factors., Results: Among 11 612 normal weight subjects, 1801 (15.51%) participants were normal weight central obesity. Of non-central obesity group and central obesity group, the levels of waist WC were (73.71 ± 5.91) and (84.47 ± 4.58) cm (F = 328.74, P < 0.01); diastolic blood pressure levels were (72.85 ± 10.30) and (78.22 ± 11.90) mm Hg (1 mm Hg = 0.133 kPa, F = 23.62, P < 0.01); triglyceride levels were (1.22 ± 0.95), (1.97 ± 1.91) mmol/L (F = 114.70, P < 0.01); total cholesterol levels were (4.66 ± 0.84) and (5.04 ± 0.92) mmol/L (F = 13.10, P < 0.01); high density lipoprotein levels were (1.41 ± 0.31), (1.25 ± 0.29) mmol/L (F = 29.44, P < 0.01); low density lipoprotein levels were (2.65 ± 0.74) and (3.03 ± 0.77) mmol/L (F = 9.98, P < 0.01); glycemia levels were (4.94 ± 0.82) and (5.25 ± 1.37) mmol/L (F = 47.21, P < 0.01). The results of the logistic regression analysis showed the central obesity normal weight group was 1.28 (1.02 - 1.60), 1.49 (1.20 - 1.84), 2.24 (1.92 - 2.60), 1.77 (1.53 - 2.05), 1.58 (1.15 - 2.16) and 1.31 (1.06 - 1.63) times more likely than the normal group to have significantly elevated levels of systolic blood pressure, diastolic blood pressure, triglyceride, high density lipoprotein, low density lipoprotein and blood glucose., Conclusion: WHR can effectively reflect the normal weight central obesity and the risk factors of cardiovascular disease;the adverse cardiovascular disease risk was high among normal weight central obesity adults.

In the title complex, {[Ag(C(8)H(7)N(5))]ClO(4)·H(2)O}(n), the multidentate dipyrazin-2-ylamine acts as a μ(2)-bridging link with an anti-syn configuration, assembling the Ag(I) ions into a zigzag chain structure. The Ag(I) ion is linearly coordinated by two dipyrazin-2-ylamine ligands through two pyrazine N atoms. (ClO(4) (-))⋯π(pyrazine) [O⋯centroid distances of 3.612 (3) and 3.664 (1) Å] and π-π inter-actions [centroid-centroid distance = 3.518 (2) Å] as well as O-H⋯O and N-H⋯O hydrogen-bonds assemble the chains into a three-dimensional supra-molecular aggregation.

The main mol-ecule of the title compound, C(45)H(30)N(6)·CH(3)OH, has a non-planar core: the dihedral angles between the benzimidazole rings and the central benzene ring are 20.19 (10), 34.57 (8), and 44.59 (8)°, while the dihedral angles between the peripheral phenyl rings and the attached benzimidazole rings are 84.57 (7), 62.71 (6) and 51.73 (6)°. The tri-substituted benzene mol-ecule is connected to the methanol solvent mol-ecule through an O-H⋯N hydrogen bond, forming a 1:1 solvate. In the crystal structure, no significant π-π inter-actions are present, and the mol-ecules are associated through weak C-H⋯N and C-H⋯O(methanol) contacts.

Airway and alveolar fluid clearance is mainly governed by vectorial salt movement via apically located rate-limiting Na(+) channels (ENaC) and basolateral Na(+)/K(+)-ATPases. ENaC is regulated by a spectrum of protein kinases, i.e. protein kinase A (PKA), C (PKC), and G (PKG). However, the molecular mechanisms for the regulation of ENaC by cGMP/PKG remain to be elucidated. In the present study, we studied the pharmacological responses of native epithelial Na(+) channels in human Clara cells and human alphabetagammadelta ENaCs expressed in oocytes to cGMP. 8-pCPT-cGMP increased amiloride-sensitive short-circuit current (I(sc)) across H441 monolayers and heterologously expressed alphabetagammadelta ENaC activity in a dose-dependent manner. Similarly, 8-pCPT-cGMP (a PKGII activator) but not 8-Br-cGMP (a PKGI activator) increased amiloride-sensitive whole cell currents in H441 cells in the presence of CFTRinh-172 and diltiazem. In all cases, the cGMP-activated Na(+) channel activity was inhibited by Rp-8-pCPT-cGMP, a specific PKGII inhibitor. This was substantiated by the evidence that PKGII was the sole isoform expressed in H441 cells at the protein level. Importantly, intratracheal instillation of 8-pCPT-cGMP in BALB/c mice increased amiloride-sensitive alveolar fluid clearance by approximately 30%, consistent with the in vitro results. We therefore conclude that PKGII is an activator of lung epithelial Na(+) channels, which may expedite the resolution of oedematous fluid in alveolar sacs.

Objective: To explore the patterns of Cx43 and Pax3 protein expressions in the small intestinal muscular layers of human embryo during early development., Methods: Immunohistochemistry with SABC method was employed to examine the expression of Cx43 and Pax3 proteins in the muscular layers of the small intestine in early human embryos in the second to fourth months of gestation., Results: In the second month of gestation, the muscle layer of the small intestine was negative for Cx43 and Pax3 protein expressions. In the third month, Cx43 and Pax3 expressions were negative in the inner circular muscle layer, but some positive cells were found in the longitudinal muscle layer and the myenteric plexus. In the fourth month, positive expression of Cx43 and Pax3 proteins were seen in the entire muscle layer., Conclusion: Cx43 and Pax3 proteins are closely related to the growth and development of the cells and tissues in the small intestinal muscle layer in human embryos.