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Racemic albuterol is an equimolar mixture of two isomers, (R) and (S). Whether (R) and (S) isomers and the combination of both exert different effects in immune activation is not well defined. We analyzed the effects of (R+S)-albuterol, (R)-albuterol and (S)-albuterol in a murine model of allergic pulmonary inflammation and in activated T cells. Mice (C57BL/6) sensitized and aerosol challenged with the allergen ovalbumin (OVA) or phosphate buffered saline (PBS) were treated with (R)-albuterol, (S)-albuterol or (R+S)-albuterol. Following administration of (R)- albuterol, allergen induced bronchoalveolar lavage eosinophils and IgE showed a decrease, albeit not significantly by ANOVA. As T cells are important in allergic inflammation, we asked whether (R+S), (R) or (S)-albuterol might differ in effects on T cells and on the activity of the inflammatory transcription factor NF-κB. In activated T cells, (R)-albuterol administration decreased levels of inflammatory cytokines and NF-κB activity. These studies suggest that (R)-albuterol decreases cytokine secretion and NF-κB activity in T cells. [ABSTRACT FROM AUTHOR]

Domains play an essential role in determining the piezoelectric properties of polymers. The conventional method for achieving ultrafine piezoelectric domain structures for polymers is multiphase polymerization, which is not the primary choice for industrial-scale applications because of its complex synthesis and weak mechanical properties. In this study, it is demonstrated for the first time that a nanoscale domain design can be achieved in a commercially available polyvinylidene fluoride (PVDF) homopolymer through a simple fabrication method involving cyclic compression and rapid freezing. The domain-engineered PVDF exhibits largely enhanced piezoelectric output with a record-breaking piezoelectric coefficient (d 33 ) of 191.4 picocoulombs per Newton (8.9 times higher than that of PVDF without engineered domain structure) and electromechanical coupling factor (k 33 ) of 77.1%. Moreover, nanoscale domain-induced ferroelectric and dielectric evolutions are revealed. A smaller domain is found to be beneficial for domain switching. An in-depth understanding of the interplay between the domain structure and piezoelectric properties reveals a simple, low-cost method for fabricating high-performance polymeric piezoelectric., (© 2024 Wiley‐VCH GmbH.)

Lightweight flexible piezoelectric polymers are demanded for various applications. However, the low instinctively piezoelectric coefficient (i.e. d33) and complex poling process greatly resist their applications. Herein, we show that introducing dynamic pressure during fabrication is capable for poling polyvinylidene difluoride/barium titanate (PVDF/BTO) composites with d33 of ~51.20 pC/N at low density of ~0.64 g/cm 3 . The melt-state dynamic pressure driven energy implantation induces structure evolutions of both PVDF and BTO are demonstrated as reasons for self-poling. Then, the porous material is employed as pressure sensor with a high output of ~20.0 V and sensitivity of ~132.87 mV/kPa. Besides, the energy harvesting experiment suggests power density of ~58.7 mW/m 2 can be achieved for 10 N pressure with a long-term durability. In summary, we not only provide a high performance lightweight, flexible piezoelectric polymer composite towards sustainable self-powered sensing and energy harvesting, but also pave an avenue for electrical-free fabrication of piezoelectric polymers., (© 2024. The Author(s).)

Reactive oxygen species (ROS) generation to induce cell death is an effective strategy for cancer therapy. In particular, chemodynamic therapy (CDT), using Fenton-type reactions to generate highly cytotoxic hydroxyl radical (•OH), is a promising treatment modality. However, the therapeutic efficacy of ROS-based cancer treatment is still limited by some critical challenges, such as overexpression of enzymatic and non-enzymatic antioxidants by tumor cells, as well as the low tumor targeting efficiency of therapeutic agents. To address those problems, biomimetic CuZn protoporphyrin IX nanoscale coordination polymers have been developed, which significantly amplify oxidative stress against tumors by simultaneously inhibiting enzymatic and non-enzymatic antioxidants and initiating the CDT. In this design, cancer cell membrane camouflaged nanoparticle exhibits an excellent homotypic targeting effect. After being endocytosed into tumor cells, the nanoparticles induce depletion of the main non-enzymatic antioxidant glutathione (GSH) by undergoing a redox reaction with GSH. Afterward, the redox reaction generated cuprous ion (Cu + ) works as a CDT agent for •OH generation. Furthermore, the released Zn protoporphyrin IX strongly inhibits the activity of the typical enzymatic antioxidant heme oxygenase-1. This tetra-modal synergistic strategy endows the biomimetic nanoparticles with great capability for anticancer therapy, which has been demonstrated in both in vitro and in vivo studies., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The self-assembly of mechanoluminochromic polynuclear gold(I) complexes has attracted more and more attention in the field of supramolecular gold(I) chemistry. In this work, we adopted a stepwise self-assembly strategy to precisely synthesize two polynuclear gold(I) supramolecular clusters. Through cooperative Au I ···Au I and Au-N interactions, the gold(I) clusters 1 + •BF 4 - and 2 4+ •4BF 4 - with Au 4 and Au 16 cores, respectively, were successfully constructed. In these supramolecular clusters, (dppm)Au 2 Cl 2 coordination motifs and trithiocyanuric linkers were stepwise assembled via sequential thiolate-chloride/phosphine coordination substitution and Au-S/Au-N coordination bond rearrangement. Two well-defined gold(I) supramolecular clusters displayed intense emission both in the solid state and in solution. Furthermore, the ladder-shaped cluster 2 4+ •4BF 4 - exhibited reversible mechanochromic luminescence behavior in the solid state as well as aggregation-caused redshifted emission in solution. Upon mechanical grinding, the emission of the cluster 2 4+ •4BF 4 - changed from yellow at 582 nm to red at 612 nm. The initial emission could be fully recovered by treatment with acetonitrile.

Objective: To investigate the effect of CD33-targeted bi-specific and tri-specific T-cell engagers on T-cell proliferation and explore their cytotoxicity on leukemia cells. Methods: The CD33-targeted bi-specific T-cell engager (CD33-BiTE) and tri-specific T-cell engager (CD33-TriTE) expression vectors were successfully constructed and expressed through a eukaryotic cell expression system. CD33-BiTE and CD33-TriTE were purified by affinity chromatography. The effects of CD33-BiTE and CD33-TriTE on T cells were analyzed through in vitro experiments. Results: ① CD33-BiTE and CD33-TriTE were successfully constructed and purified and could compete with flow cytometry antibodies for binding to the target cells. ② After 12 days of co-culture with CD33-BiTE and CD33-TriTE, the number of human T cells were expanded to 33.89±19.46 and 81.56±23.62 folds, respectively. CD33-TriTE induced a stronger proliferation of T cells than CD33-BiTE ( P <0.05) . ③ Both CD33-BiTE and CD33-TriTE induced specific dose-dependent cytotoxicity on CD33(+) leukemia cells. ④ Compared to CD33-TriTE, leukemia cells were prone to express PD-L1 when co-cultured with T cells and CD33-BiTE. CD33-TriTE induced powerful cytotoxicity on leukemia cells with high PD-L1 expression. Conclusion: CD33-BiTE and CD33-TriTE expression vectors were constructed, and fusion proteins were expressed in eukaryotic cells. Our results support the proliferative and activating effects of BiTE and TriTE on T cells. Compared to that of CD33-BiTE, CD33-TriTE induced a stronger proliferative effect on T cells and a more powerful cytotoxicity on leukemia cells with high PD-L1 expression.

In the present study, the oral bioavailability of cadmium (Cd) in earthworms and leeches was investigated through in vitro physiologically based extraction test (PBET) digestion/Caco2 and MDKC cell models. We are the first to create an innovative assessment strategy which has capacity to offer a more precise evaluation of Cd-associated health risks in traditional animal medicines (TAMs), by combinational usage of bioavailable Cd levels, the duration and frequency of the exposure to TAMs obtained by questionnaire data, as well as safety factor of TAMs. Our data showed that the percentage of bioavailability for Caco-2 cells in earthworms and leeches ranged from 3.29 to 14.17% and 4.32 to 12.61%, respectively. The percentage of bioavailability of MDCK cells in earthworms and leeches ranged from 4.83 to 15.74% and 6.53 to 15.04%, respectively. After adjusting by the bioavailability of Cd to target hazard quotient (THQ), excitingly, our findings manifested that the health risks induced by the ingestion of earthworms and leeches were acceptable in the clinic. Our key findings suggest that bioavailability characterization cannot be ruled out and health risks should be assessed on the basis of the bioavailable Cd levels rather than total levels. Our novel strategy provides insight into the bio-accumulation of Cd in organisms as well as a more realistic and accurate assessment of Cd-associated health risks in TAMs, with the main purpose of improving public health by scientifically using TAMs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study explored the relations between the social support network of mothers of children with autism spectrum disorder (ASD), perceived social support, and their subjective wellbeing. The participants were mothers of children with ASD in Shanghai. Their social support network structure was explored via the nomination method. Perceived social support was measured using the Revised Social Provisions Scale for Autism (R-SPS-A), and the mothers' subjective wellbeing was assessed using the Index of Wellbeing, Index of General Affect. A significant correlation was observed between the subjective wellbeing of mothers of children with ASD and perceived social support. Meanwhile, perceived social support was significantly correlated with the effectiveness of overall social support. Finally, perceived social support was also significantly correlated with the network size of social support. Moreover, the effectiveness of social support was significantly associated with the network size of social support and was highly significantly associated with the degree of intimacy of social support. Furthermore, the network size of instrumental support has a significant influence on all perceived social support subdimensions. Overall, social support effectiveness plays an important role in the social support network mechanism on perceived social support and subjective wellbeing in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bi, He, Lin and Fan.)

Objective: This study aimed to create a type of CAR-T cells that targets LMP1 antigen and study its immunotherapeutic effect on LMP1-positive hematological malignancies. Methods: To generate LMP1 CAR-T cells, a plasmid expressing LMP1 CAR was created using molecular cloning technology, and T cells were infected with LMP1 CAR lentivirus. The effects of LMP1 CAR-T cells on specific cytotoxicity against LMP1-positive tumor cell lines infected with the EB virus had been confirmed. Results: ① LMP1 protein expressing on EB virus-positive lymphoma cells surface was verified. ② The LMP1 CAR-expressing plasmid was created, and LMP1 CAR-T cells were obtained by infecting T cells with a lentivirus packaging system, with an infection efficiency of more than 80% . ③LMP1 CAR-T cells have a 4∶1 effect-to-target ratio in killing LMP1-positive lymphoma cells. The killing effect of LMP1 CAR-T cells on Raji cells was enhanced after 48 h of coculture, but there was no significant killing effect on Ramos, which are LMP1-negative lymphoma cells. ④After coculture with LMP1-positive lymphoma cells at a ratio of 1∶1 for 5 h, the degranulation effect was enhanced. The proportion of CD107a(+) T cells in the LMP1 CAR-T cell treatment group was significantly higher than that in the vector-T cell group [ (13.25±2.94) % vs (1.55±0.05) % , t =3.972, P =0.017]. ⑤After coculture with LMP1-positive lymphoma cells, the proportion of CD69(+) and CD25(+) T cells in the LMP1 CAR-T cell group was significantly higher than that in vector-T cell group [ (7.40±0.41) % vs (3.48±0.47) % , t =6.268, P =0.003; (73.00±4.73) % vs (57.67±2.60) % , t =2.842, P =0.047]. ⑥After coculture with LMP1-positive lymphoma cells, cytokine secretion in the LMP1 CAR-T cell group was higher than that in the vector-T cell group [interferon-gamma: (703±73) ng/L vs (422±87) ng/L, t =2.478, P =0.068; tumor necrosis factor-alpha: (215±35) ng/L vs (125±2) ng/L, t =2.536, P =0.064]. Conclusion: In this study, we found that the LMP1 protein is only found on the surface of the EBV-positive tumor cell. Simultaneously, we created an LMP1 CAR-expressing plasmid and obtained LMP1 CAR-T cells by infecting T cells with a lentivirus packaging system. Furthermore, we demonstrated that LMP1 CAR-T cells could specifically kill LMP1-positive tumor cells in vitro. The degranulation and activation effects of LMP1 CAR-T cells were enhanced after coculture with LMP1-positive tumor cells, indicating a potential clinical application.

We developed an ultrafast one-step RT-qPCR assay for SARS-CoV-2 detection, which can be completed in only 30 min on benchtop Bio-Rad CFX96. The assay significantly reduces the running time of conventional RT-qPCR: reduced RT step from 10 to 1 min, and reduced the PCR cycle of denaturation from 10 to 1 s and extension from 30 to 1 s. A cohort of 60 nasopharyngeal swab samples testing showed that the assay had a clinical sensitivity of 100% and a clinical specificity of 100%., Competing Interests: There is patent pending on the ultrafast one-step qRT-PCR assay for pathogen detection (US63/178797) method used in this work. S-YZ declares a competing interest in the form of consulting for and equity ownership in Captis Diagnostics. JM and H-ZH are employed by Captis Diagnostics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Milosevic, Lu, Greene, He and Zheng.)

Background: Clozapine is one of the most widely used second-generation antipsychotics in clinic. However, allergy-like symptoms such as rash and angioedema have been reported frequently, and the mechanism is still not clear. Mas-related G protein-coupled receptor X2 (MRGPRX2) expressed on mast cells is a crucial receptor for drug induced pseudo-allergic reactions. Therefore, we explored whether the symptoms induced by clozapine were associated with allergic reaction through MRGPRX2., Methods: The effects of clozapine on pseudo-allergic reactions were evaluated by mast cells degranulation and calcium mobilization assay in vitro , and mice hindpaw swelling, serum histamine detection, avidin and H&E staining assay in vivo . The overexpressed MRGPRX2 cells membrane chromatography (MRGPRX2-HEK293/CMC), MRGPRX2-HEK293 cells calcium mobilization assay and molecular docking were applied to research the correlation between clozapine and MRGPRX2., Results: The study showed that clozapine induced the release of β-hexosaminidase, histamine and monocyte chemoattractant protein-1 (MCP-1), and trigged calcium mobilization in mast cells. In vivo , clozapine induced paw swelling, degranulation and vasodilation. Furthermore, clozapine could activate the calcium mobilization obviously in MRGPRX2-HEK293 cells, not in NC-HEK293 cells. Clozapine also had a good retention characteristic on MRGPRX2-HEK293/CMC column and the K D value is (2.33 ± 0.21)×10 -01 M., Conclusions: Our findings demonstrated that clozapine could induce pseudo-allergic reactions and MRGPRX2 might be the critical receptor for it.

Pancreatic carcinoma (PC) is highly metastatic, and it tends to be detected at advanced stages. Identifying and developing biomarkers for early detection of PC is crucial for a potentially curative treatment. Extracellular vesicles (EVs) are bilayer lipid membrane-structured nanovesicles found in various human bodily fluids, and they play important roles in tumor biogenesis and metastasis. Cancer-derived EVs are enriched with DNA, RNA, protein, and lipid, and they have emerged as attractive diagnostic biomarkers for early detection of PC. In this article, we provided an overview of the cell biology of EVs and their isolation and analysis, and their roles in cancer pathogenesis and progression. Multiplatform analyses of plasma-based exosomes for genomic DNA, micro RNA, mRNA, circular RNA, and protein for diagnosis of PC were critically reviewed. Numerous lines of evidence demonstrate that liquid biopsy with analysis of EV-based biomarkers has variable performance for diagnosis of PC. Future investigation is indicated to optimize the methodology for isolating and analyzing EVs and to identify the combination of EV-based biomarkers and other clinical datasets, with the goal of improving the predictive value, sensitivity, and specificity of screening tests for early detection and diagnosis of PC.

Cell membrane imaging by predesigned molecular and supramolecular photoluminescence probes is of great importance in understanding the nano-biointeractions for potential applications in cellular tracking, drug delivery, cancer diagnosis, and treatment. Herein, we report an effective strategy for cell membrane imaging in both living cell and tissue levels on the basis of a multifunctional nanocage (MOC-16) integrating one-/two-photon active phosphorescence, high charges, balanced hydrophobicity/lipophilicity, and proton sensitivity attributes. The intrinsic optical characters, including strong one-/two-photon excitation and pH-dependent red emission, make MOC-16 powerful optical probes for membrane imaging in living cell and tissue levels under both visible and near-infrared irradiations. Meanwhile, the highly positive charges of +28 endow MOC-16 with adequate water solubility and deprotonation ability while still maintaining its hydrophobicity, thus enabling balanced hydrophobic-lipophilic interactions at the nano-biointerface to facilitate a pH-dependent membrane absorption within the biological pH range of 5.3-7.4. However, the low-charged RuL 3 metalloligand or polyethylene glycol (PEG)-modified MOC-16 PEG with less hydrophobicity cannot offer enough nano-biointeractions for cell membrane tracking. These findings advance the fundamental understanding of nano-biointerface interactions of MOCs with cell membranes and provide further guidance in their biological applications.

A novel and efficient method to synthesize rigid bis-coumarins based on the dimerization of coumarinyl aldehydes was developed. This procedure is additive- and column-free, providing a facile and environment-friendly way to prepare fluorophores. The prepared novel fluorescent bis-coumarins exhibit favorable photophysical properties with good sensitivity and selectivity towards G-quadruplexes (G4s).

Numerous studies have been investigated the potential of biochar (BC) derived from various materials and crop straw (CS) to decrease the bioavailability of heavy metals in soil contaminated with cadmium (Cd), and thereby reduce their potential risk to human health and the ecological environment. However, little attention has been given to the comparison of heavy metal remediation efficiency using BC and CS such as peanut vine (PV) and rice straw (RS), especially in soil contaminated with Cd. Here, we explore if Cd bioavailability is affected in contaminated soil by BC and CS. Peanuts were grown in plastic pots, which contained BC or CS at 5% (dry weight, w/w) in controlled environment mesocosms. The bioavailability of Cd in contaminated soil was measured by Cd concentration in the plant and the concentrations of various forms of Cd in the soil. At the same plant age, growth with BC (compared with PV and RS) led to 13.56% and 8.28% lower rates of Cd content in the aboveground parts, 40.65% and 35.67% lower rates of Cd content in the seeds, yet 9.08% and 7.09% lower rates of Cd content in the roots, yet 35.80% and 28.48% lower rates of exchangeable Cd content in the soil. Moreover, BC amendment enhanced the biomass of peanut and physiological quality. Thus, BC had a greater impact on immobilizing Cd in the soil. The results imply that BC was more significantly (P < 0.05) remarkable in decreasing the Cd bioavailability and improving the biomass of peanut. BC has greater potential for enhancing soil quality and promoting peanut growth. In conclusion, this research demonstrates an understanding of employing BC as a promising inexpensive and eco-friendly amendment to remediate soil contaminated with Cd.

Few studies reported the extent of heavy metal accumulation in traditional Chinese medicines (TCMs). Currently, oral bioaccessibility of lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and copper (Cu) present in traditional animal medicines was investigated with physiologically based extraction test-extracted in vitro model. We are the first to develop a health risk assessment strategy by combinational analysis of bioaccessible heavy metal levels to calculate target hazard quotient (THQ), target hazard index (THI) and cancer risk (CR), which has capacity to evaluate the heavy metal associated heath risk of traditional animal medicines. To precisely acquire a realistic risk assessment, questionnaire data was adopted to measure the frequency and duration of the exposure to traditional animal medicines, and the safety factor was highlighted as well. Our data revealed that the bioaccessibility of Hg was the lowest among the five heavy metals. After the adjustment with the bioaccessibility of each heavy metal to target hazard index (THI) values, excitingly, the results manifested that the consumption of traditional animal medicines might not exert an unacceptable health risk in a broad community. In addition, the CR values of As and Pb indicated that the risk of developing cancers was quite lower than their acceptable levels in the clinic.

* Correspondence: pmhzhe@scut [...].

A series of novel biphenyl-furocoumarin derivatives were synthesized based on the nuclear structure of imperatorin and identified by IR, 1 H NMR, 13 C NMR and MS, and evaluated for their ability to relax vessel on isolated rat mesenteric artery, basilar artery and renal artery, respectively. The majority of compounds demonstrated potent vasodilatation, and compound 8e expressed the highest activity (EC 50  = 0.56 μM) in MA. Compounds with fluorine at 2-position of 5-phenyl get better activity than others with chlorine or bromine, and the compounds containing a bulky structure had relatively low activity, such as 8c (EC 50  = 22.39 μM) in MA. As a follow-up, 8e , 10e, and 8c were docked into L-calcium channel (PDB code: 3G43) to explain the difference in the activity of the compounds.

The western Chongqing region is the main grain-producing area in Chongqing. This region's soils are characterized by light-to-moderate cadmium (Cd) pollution. Two types of typical paddy soils in this area (acidic and calcareous purple soils) were selected for the development of safe rice production techniques using in situ field remediation experiments. These involved a low-Cd-accumulating rice variety (Changliangyou 772) grown either alone or in combination with heavy metal passivators (silicon-calcium fertilizer, iron powder, biochar, and straw organic fertilizer). The results showed that:① all of the passivators except for the Fe powder increased rice yields from both types of soils. Straw organic fertilizer showed the best results for the acidic purple paddy soil, with a rice-yield increase of 47.43%, while biochar performed best for the calcareous paddy soil, increasing yields by 23.95%; ② The low-accumulation rice variety alone could not meet the requirements of safe rice production in the acid purple paddy soil (pH=4.75); however, combined the with passivators (with the exception of the silicon-calcium fertilizer), Cd content in rice grains was reduced by 14.81%-54.88% to within the national safe food standard for rice (0.2 mg·kg -1 , GB 2762-2017). The Cd content of rice grains varied between 0.012 and 0.030 mg·kg -1 in the calcareous purple paddy soil (pH=7.77), under various treatments, which was far lower than the safety standard. The application of passivators (with the exception of biomass charcoal) further reduced the Cd content of rice by 26.67%-59.00% nevertheless; ③ The use of passivators altered Cd transportation and distribution in the rice plant. Taking the acidic soil as an example, silicon-calcium fertilizer inhibited the transport of Cd from the stems to the rice grains, Fe powder and biochar reduced the enrichment of Cd in roots and inhibited the transport of Cd from the stems to the rice grains, and straw organic fertilizer inhibited the transport of Cd from the roots to the stems; ④ The application of passivators promoted the transformation of soil Cd from labile forms into residual form, reduced the bioavailability of Cd in the soil, and, thus, reduced the accumulation of Cd in the rice plants. In the acidic soil, biochar showed the best effect, while straw organic fertilizer performed best in calcareous soils. ⑤ Silicon-calcium fertilizer and straw organic fertilizer significantly increased the pH and organic matter content of acid soils. Consequently, the soil available Cd content decreased by 39.45% and 34.69%, respectively, while no such effects were observed for the calcareous soil.

Nanoscale extracellular vesicles (nEVs) have recently demonstrated potential value in cancer diagnostics and treatment monitoring, but translation has been limited by technical challenges in nEV isolation. Thus, we have developed a one-step nEV isolation platform that utilizes nEV size-matched silica nanostructures and a surface-conjugated lipid nanoprobe with an integrated microfluidic mixer. The reported platform has 28.8% capture efficiency from pancreatic cancer plasma and can sufficiently enrich nEVs for simpler positive identification of point mutations, particularly KRAS, in nEV DNA from the plasma of pancreatic cancer patients.

Little is known about the extent of heavy metal accumulation in traditional Chinese medicines (TCMs). In this study, the levels of lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) in traditional animal medicines were monitored using inductively coupled plasma mass spectroscopy (ICP-MS). Additionally, for the first time, a heavy metal risk assessment strategy was used to evaluate the potential risks of traditional animal medicines by calculating estimated daily intake (EDI), target hazard quotient (THQ), and cancer risk (CR). To obtain a refined risk assessment, the frequency of exposure to traditional animal medicines was determined from questionnaire data, and the safe factor for TCM was applied. Based on the standard levels for leech, it was found that earthworm, hive, scorpion, and leech accumulated high levels of heavy metals. The combined THQ (cTHQ) values indicated that ingestion of most traditional animal medicines would not pose a risk to the health of either male or female human beings. However, it was indicated that attention should be paid to the potential risk associated with cicada slough, earthworm, scorpion, turtle shells, and hive. Among heavy metals, As and Hg contributed to a major extent to the risk to human health. The CR assessment for Pb and As indicated that, with the exception of earthworm, the cancer risk was less than the acceptable lifetime risk for both males and females. Owing to the higher body weight, both THQ and CR were generally lower for males than for females.

Two series of imperatorin analogs were synthesized based on our previous research and evaluated for their vasodilatation activities on in vitro rat mesenteric artery, basilar artery, and renal artery ring models. Target compounds were characterized by infrared, 1 H NMR, and mass spectra. Most derivatives possessed significant vasodilatory activity on the mesenteric artery, and compound 3a exhibited favorable and broad vasodilatation activities on three kinds of rat artery ring models. The pharmacological results indicated that introducing nitrogen-contained ring in side chain or large steric hindrance at the distal end could increase the vasodilatory activity. Further, replacement of oxygen atom (-O-) in the skeleton of furocoumarin derivatives with nitrogen (-NH-) could cause the decrease of vasodilatory activity. The molecular docking also indicated that compound 3a showed a best affinity with α-1C receptor (PDB ID: 3G43). All these results suggested compound 3a would be a potential vasodilatory agent for hypertension.

Objective: To explore the relationship between sugary drinks and diabetes of adults in Wuhai city., Methods: A multiple stage stratified cluster sampling was conducted on 8 131 residents who were between 35 and 79 years by cross-sectional study in Wuhai city. Questionnaires, physical measurements and laboratory tests were used to collect information on demographic information, dietary behavior, health status, blood glucose indicators. Besides, other covariate information was also collected by these ways. The analysis was carried out by chi-square test, trend chi-square test and multifactor Logistic regression., Results: The detection rates of impaired fasting glucose and diabetes of people who were 35 years old and above in Wuhai city were 6.0% and 18.4%, respectively, and they both increased with age (P<0.01, P< 0.01). The detection rates of impaired fasting glucose and diabetes of the men were both far higher than the women (P< 0.01, P< 0.01). For the men, the detection rate of diabetes increased with age (P trend <0.01), but for the women, and the detection rate of impaired fasting glucose and diabetes both increased with age (P trend <0.01, P trend <0.01). The consumption rate of sugary drinks of the people who were 35 years old and above in Wuhai city was 30.2%. And after all the subjects were classified into three groups, A (0- mL/d), B (16- mL/d), and C (237- mL/d) according to the daily different drinking quantities, statistical results found that group A accounted for 75.4%, group B for 21.5%, and group C for 3.1%. In group A, for comparison, the impaired fasting glucose OR values of group B and group C were 1.4 and 2.2, respectively. And diabetes OR values of group B and group C were 1.2 and 2.1 respectively compared with group A, and the trend of OR values increased both had statistical significance (P trend <0.01, P trend < 0.01). Also, after adjusting for other covariates in multifactor Logistic regression, the OR values of impaired fasting glucose in group B and group C were 1.6 and 3.8 respectively, and the OR values of diabetes were 1.9 and 4.9 respectively, compared with group A, and besides, the trend of OR values increased both still had statistical significance (P trend <0.01, P trend < 0.01)., Conclusion: Increased consumption of sugary drinks will increase the risk of impaired fasting glucose and diabetes. Residents in Wuhai city should control their consumption of sugary drinks.

Objective: To analyze associations of sedentary behavior and physical activity with dyslipidemia among residents in Wuhai city., Methods: Data about social demographic characteristics, life style, health status and other covariate required for analysis in this study was obtained from a cross-sectional study on a total of 11 497 18-79 years old residents in Wuhai City by questionnaire, body mea-surement and laboratory examination. In this study, sedentary behavior and physical activity were evaluated using international physical activity questionnaire long version (IPAQ). IPAQ is widely used all over the world, and its reliability and validity have been tested in Chinese population. 2016 Chinese Guideline for the Management of Dyslipidemia in Adults was used to define dyslipidemia in this study., Results: According to IPAQ scoring protocol, 124 participants were excluded as a result of reporting more than 960 min of physical activity per day. 50.58% of 11 373 participants included in the analysis reported more than 4 hours of sedentary behavior per day in this study, thus 49.42% participants reported no more than 4 hours of sedentary behavior per day; the proportions of these 11 373 participants who reached Low level physical activity, Moderate level physical activity and high level physical activity were 23.43%, 37.29% and 39.28% respectively; and the detection ratios of new cases and prevalent cases of dyslipidemia in Wuhai City were 20.46% and 16.13% respectively. After controlling for confounders in this study, we found out that sedentary behavior increased the risk of new cases of dyslipidemia in women (OR=1.17, 95% CI: 1.00-1.36), and increased the risk of prevalent cases of dyslipidemia in both men (OR=1.21, 95% CI: 1.02-1.44) and women (OR=1.24, 95% CI: 1.04-1.48); as for association of physical activity with dyslipidemia, association was found between high level physical activity and prevalent cases of dyslipidemia in men in this study (OR=0.78, 95% CI: 0.62-0.98), suggested that high level physical activity may help to reduce the risk of prevalent cases of dyslipidemia in men., Conclusion: Our results from this cross-sectional study in Wuhai City suggested that sedentary behavior increased the risk of dyslipidemia; by contrast, physical activity may help to reduce the risk of dyslipidemia.

Objective: To observe effect of interleukin(IL)-1β on the expression of signaling pathway of mammalian target of rapamycin(mTOR) of articular cartilage. Methods: Articular cartilage of rats was isolated under sterile technique, cells were digested by type Ⅱ collagenase and trypsin and cultured in vitro, pre-culture the Ⅱ cells for three days, different concentrations of IL-1β were added for 24 hours.The cells were stained with toluidine blue and HE, to observe morphological changes of cells.RT-PCR was used to detect the mRNA expression of typeⅡcollagen gene, aggrecan gene, mTOR gene and P70S6K gene, Western blotting was used to detect the expression of protein related to mTOR. Results: With increasing concentrations of IL-1β, the phenotype of cells appeared polygon into a spindle, the mRNA expression of gene of type Ⅱ collagen (the control group: 0.821±0.014; 1 ng/ml: 0.614±0.014; 10 ng/ml: 0.549±0.009; 100 ng/ml: 0.520±0.008), aggrecan(0.867±0.005; 0.857±0.001; 0.554±0.008; 0.538±0.004) and mTOR(0.845±0.015; 0.785±0.009; 0.569±0.025; 0.518±0.014) reduced, but P70S6K(0.465±0.024; 0.566±0.022; 0.663±0.022; 0.896±0.015) increased by PCR .Expression of protein detected by Western blotting was similar to the trend of PCR. Conclusion: mTOR signaling pathway may play an important role on the degeneration of articular cartilage, regulating mTOR signaling pathway may provides a new idea of delaying the degeneration process of cells.

A hydroponic experiment was conducted to investigate perchlorate (ClO4 (-) ) phytotoxicity in different rice varieties. Considerable variations were observed when 24 rice varieties were treated with ClO4 (-) . The shoot height, root length, and biomass of most varieties were significantly reduced by ClO4 (-) . The roots were more sensitive than the shoots. Hierarchical clustering analysis demonstrated primarily 4 groups: ClO4 (-) -sensitive, medium ClO4 (-) -sensitive, medium ClO4 (-) tolerant, and ClO4 (-) -tolerant. Gannuoxiang (a ClO4 (-) -tolerant variety) and IR65598-112-2 (a ClO4 (-) -sensitive variety) were chosen to explore their antioxidant response when exposed to 0.2 mmol/L, 2.0 mmol/L, and 4.0 mmol/L ClO4 (-) . The results showed that the activities of superoxide dismutase and catalase increased in the shoots and roots of gannuoxiang with increasing doses of ClO4 (-) , but both of them decreased at higher concentrations of ClO4 (-) in IR65598-112-2. The addition of ClO4 (-) led to a significant increase in peroxidase activities for both of the varieties, whereas the increase was more pronounced in gannuoxiang than in IR65598-112-2. No significant difference was found in malondialdehyde (MDA) contents in gannuoxiang, whereas the addition of ClO4 (-) increased the MDA level significantly in IR65598-112-2. The results indicated that gannuoxiang has higher activities of antioxidant enzymes than IR65598-112-2 to cope with oxidative damage caused by ClO4 (-) stress, which may be the main cause of its high tolerance., (© 2015 SETAC.)

A series of luminescent Ir(iii) complexes were synthesised and evaluated for their ability to act as luminescent G-quadruplex-selective probes. The Ir(iii) complex 9 , [Ir(phq) 2 (phen)]PF 6 (where phq = 2-phenylquinoline; phen = 1,10-phenanthroline), exhibited high luminescence in the presence of G-quadruplex DNA compared to dsDNA and ssDNA, and was employed to construct a label-free G-quadruplex-based assay for hepatitis C virus NS3 helicase activity in aqueous solution. Moreover, the application of the assay for screening potential helicase inhibitors was demonstrated. To our knowledge, this is the first G-quadruplex-based assay for helicase activity.

The introduction of a gene, strain, or microbial consortium into an indigenous bacterial population is known as bioaugmentation. This technique has been proposed as an effective strategy for accelerating and enhancing the removal of recalcitrant and toxic compounds during wastewater treatment. In this study, three types of reactors were used to test whether quorum sensing plays an important role in bioaugmented systems. Reverse transcriptase polymerase chain reaction showed that the inoculated strain, HF-1, successfully colonized in the bioaugmented reactor. Meanwhile, no HF-1 colonization was observed in the quorum-quenching and non-bioaugmented reactors. Removal of nicotine in the bioaugmented reactor was almost 100%, and removal of total organic carbon (TOC) was higher than 50%. However, less than 20% of nicotine and 30% of TOC was removed in quorum-quenching and non-bioaugmented reactors. Moreover, the release of acylated homoserine lactones reached the threshold for HF-1 biofilm formation in bioaugmented reactors but not in quorum-quenching or non-bioaugmented reactors. The addition of porcine kidney acylase I, a quenching reagent, to the quorum-quenching reactor hampered the colonization of HF-1. Together, these results demonstrate that quorum sensing plays an important role in HF-1 colonization of bioaugmented systems.

The aim of this study is to compare the effects and complications of InterTAN nail versus Dynamic Hip Screw (DHS) in treatment of femoral intertrochanteric fractures. Between January 2006 and December 2013, a total of 75 patients with femoral intertrochanteric fractures were retrospectively reviewed. There were 16 cases of type A1, 51 cases of type A2, and 8 cases of type A3. 37 patients treated with InterTAN nail, and 38 with DHS. The clinic data of surgical trauma, postoperative function and complications were statistically compared in this study. This results indicated that 31 cases by InterTAN and 30 cases by DHS had obtained follow-up with mean time (11 ± 5.6) months. Operative time of InterTAN group is (23.1 ± 9.2) min, and of DHS group is (55.2 ± 14.5) min (P < 0.05). Intra-operative active blood loss is (70.1 ± 30.7) ml in InterTAN group, and (205.7 ± 40.7) ml in DHS group (P < 0.05). Fluoroscopy frequency of InterTAN group is (16.3 ± 4.4) times, and of DHS group is (25.1 ± 3.1) times (P < 0.05). Complications occurred in 3 cases (9.7%) in InterTAN group compared 6 cases (20%) in DHS group (P < 0.05). Two cases had hip varus in InterTAN group, and three cases in DHS group. One case had deep venous thrombosis (DVT) in InterTAN group, and one case in DHS group. In conclusion, InterTAN significantly reduce the operative time, fluoroscopy frequency, intra-operative active blood loss and postoperative complications. The InterTAN technical features make it applicable to the aged patient with variety of medical basic diseases and cases of osteoporotic and unstable fracture types.

Pseudomonas sp. HF-1 bioaugmented systems were operated to treat tobacco wastewater under pH 5.5 for three cycles and pH 8.0 for the rest, which was suitable for HF-1 biofilm formation. The results showed that, under pH control, the contents of 3-oxo-C6-HSL, C6-HSL and 3-oxo-C8-HSL were significantly higher than HF-1 thresholds for biofilm formation. Compared with non-pH controlled reactors, HF-1 showed greater colonization in pH controlled reactors, primarily owing to the high extracellular polymeric substances secretion induced by quorum sensing. Accordingly, high indigenous community activity and granular sludge were observed. Sludge granulation occurred from the seventh cycle, and the average diameter was greater than 400 μm. These systems were also highly efficient with nearly 100% nicotine degradation and 60% total organic carbon removal. Overall, the results indicate that pH regulation is a new and feasible method for acceleration of releasing of auto-inducers, which is beneficial to construction of HF-1 bioaugmented systems., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A novel luminescent cyclometalated iridium(III) complex-based chemosensor (1) bearing a zinc-specific receptor, tris(2-pyridylmethyl)amine, and the 3-phenyl-1H-pyrazole ligand has been designed and synthesized. Upon the addition of Zn(2+) ions to a solution of iridium(III) complex 1, a pronounced luminescence color change from blue to green can be observed, which may be attributed to the suppression of photoinduced electron transfer upon complexation of complex 1 with Zn(2+) ions. The interaction of iridium(III) complex 1 with Zn(2+) ions was investigated by UV-vis absorption titration, emission titration, and (1)H NMR titration. Furthermore, the iridium(III) complex 1 exhibited good selectivity for Zn(2+) over 13 other common metal ions, including K(+), Ag(+), Na(+), Ni(2+), Fe(3+), Hg(2+), Cd(2+), Mg(2+), Ca(2+), Cu(2+), Mn(2+), Co(2+), and Pb(2+) ions. The practical application of the iridium(III) complex 1 in visualizing intracellular Zn(2+) distribution in live zebrafish was also demonstrated.

A novel iridium(III) complex-based chemosensor bearing the 5,6-bis(salicylideneimino)-1,10-phenanthroline ligand receptor was developed, which exhibited a highly sensitive and selective color change from colorless to yellow and a visible turn-off luminescence response upon the addition of Cu(II) ions. The interactions of this iridium(III) complex with Cu2+ ions and thirteen other cations have been investigated by UV-Vis absorption titration, emission titration, and 1H NMR titration.

A label-free, oligonucleotide-based, switch-on luminescence detection method for T4 polynucleotide kinase activity has been developed using a novel G-quadruplex-selective luminescent Ir(iii) complex probe. The application of the assay for screening potential T4 PNK inhibitors is also demonstrated. To our knowledge, this is the first metal-based assay for PNK activity.

To better construct a bioaugmented system for tobacco wastewater treatment, activated sludge was inoculated with different concentrations of the nicotine-degrading bacterium Pseudomonas sp. HF-1. The results showed that inoculum concentrations of 0.55 ± 0.01 and 1.10 ± 0.03 mg/g (dry weight of strain HF-1/dry weight of activated sludge) were best to ensure strain HF-1 survival and successful bioaugmentation. The release pattern of autoinducer (AI) for quorum sensing in the bioaugmented system was also investigated. During the period of HF-1 inoculation, compared with failed bioaugmented systems, AI-2 was significantly increased in the successful systems, suggesting that AI-2-mediated bacterial communication played an important role in the colonization of HF-1. When inoculation of strain HF-1 was stopped, the amount of AI-2 decreased and leveled out in all systems. Notably, there was a greater than threefold increase of short-chain AHLs in failed bioaugmented systems, but no increase in successful ones, implying that the fluctuation of short-chain AHLs could be an indicator of the failure of bioaugmentation. Thus, AI-2-mediated quorum sensing could be implemented to facilitate HF-1 colonization.

Two new 9-hydroxy-7H-furo[3,2-g]chromen-7-one derivatives were designed, synthesized and evaluated for their in vitro vasodilatory activity. The structures of two compounds were elucidated by infrared, ¹H NMR, and mass spectral data. The in vitro pharmacological evaluation indicated that both of them possessed well vasodilatory activity compared with imperatorin. The molecule docking also showed two target compounds docked well with L-calcium channel (PDB code: 3G43). The result suggested that they would be potential vasodilatory agents for hypertension.

We report herein a luminescent switch-on label-free G-quadruplex-based assay for the rapid and sensitive detection of polymerase proofreading activity using a novel iridium(III) complex as a G-quadruplex-selective probe. The interaction of the iridium(III) complex with the G-quadruplex motif facilitates the highly sensitive switch-on detection of polymerase proofreading activity. Using T4 DNA polymerase (T4 pol) as a model enzyme, the assay achieved high sensitivity and selectivity for T4 pol over other tested enzymes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A parallel G-quadruplex-selective iridium(III) complex has been synthesized and employed as a luminescent probe in a label-free G-quadruplex-based detection assay for Ca(2+) ions in aqueous solution. In this assay, a guanine-rich oligonucleotide (G4, 5'-G4T4G4-3') initially exists in an antiparallel G-quadruplex conformation, resulting in a low luminescence signal. Upon incubation with Ca(2+) ions, the antiparallel G-quadruplex is induced into a parallel G-quadruplex conformation, which greatly enhances the luminescence emission of the iridium(III) probe. This method was highly sensitive for Ca(2+) ions with a limit of detection in the nanomolar range, and was selective for Ca(2+) over other metal ions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A luminescent iridium(III) complex has been discovered to be selective for G-quadruplex DNA, and was employed in a label-free G-quadruplex-based detection assay for 3'→5' exonuclease activity in aqueous solution. A proof-of-concept of this assay has been demonstrated by using prokaryotic exonuclease III (ExoIII) as a model enzyme. In this assay, a G-quadruplex-forming hairpin oligonucleotide (hairpin-G4 DNA, 5'-GAG3TG4AG3TG4A2GCAGA2G2ATA2CT2C4AC3TC4AC3TC-3') initially exists in a duplex conformation, resulting in a low luminescence signal due to the weak interaction between the iridium(III) complex and duplex DNA. Upon digestion by ExoIII, the guanine-rich sequence is released and folds into a G-quadruplex, which greatly enhances the luminescence emission of the iridium(III) probe. This method was highly sensitive for 3'→5' exonuclease over other DNA-modifying enzymes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A label-free G-quadruplex-based luminescent switch-on assay has been developed for the selective detection of micromolar histidine in aqueous solution. In this study, an iridium(III) complex was employed as a G-quadruplex-specific luminescent probe while a guanine-rich oligonucleotide (Pu27, 5'-TG4AG3TG4AG3TG4A2G2-3')/cupric ion (Cu(2+)) ensemble was employed as a recognition unit for histidine. The initial luminescence of the iridium(III) complex in the presence of G-quadruplex DNA is effectively quenched by Cu(2+) ions due to the Cu(2+)-mediated unfolding of the G-quadruplex motif. The addition of histidine sequesters Cu(2+) ions from the ensemble, thereby restoring the luminescence of the system. The assay could detect down to 1 μM of histidine in aqueous media, and also exhibited good selectivity for histidine over other amino acids with the use of the cysteine, masking agent N-ethylmaleimide. Furthermore, the application of the assay for the detection of histidine in diluted urine samples was demonstrated., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We report herein the synthesis and application of a novel G-quadruplex-selective luminescent iridium(III) complex [Ir(ppy)2(bcp)](+) (where ppy = 2-phenylpyridine and bcp = 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline) for the sensitive detection of apurinic/apyrimidinic (AP) endonuclease activity. Using endonuclease IV (Endo IV) as a model enzyme, a duplex DNA substrate containing a G-quadruplex-forming sequence is cleaved by Endo IV at the abasic site. This releases the G-quadruplex sequence, which folds into a G-quadruplex and is recognised by the G-quadruplex-selective iridium(III) complex with an enhanced luminescence response. The assay achieved high sensitivity and selectivity for Endo IV over other tested enzymes.

Objective: To study the effect of transplantation on the growth and oxymatrine content of Sophora flavescens and provide foundation for popularization and cultivation of Sophora flavescens in South China., Methods: Sophora flavescens which was usually planted in North China and Northwest China was planted in a non-traditional location, Zhongshan city, Guangdong Province in South China to test its adaptability. The growth characters, such as plant height, leaf area, dry weight of root, diameter and length of root and so on were measured from 2010 to 2012. The oxymatrine content of one-year old and two-year old root of Sophora flavescens were determined by HPLC. Nine major growth indexes for one-year old Sophora flavescens were comprehensively analyzed and evaluated by the methods of weighted gray relational and hierarchy evaluation of fuzzy mathematics., Results: The weighted relevancy of introduced and reference cultivars was 0.8545. The introduced cultivar was rather adaptable to the geography environment in Zhongshan. Its quality was very close to the reference cultivars. Oxymatrine content of root of one-year old and two-year old Sophora flavescens was 13.2784 mg/g (as much as origin) and 16.4779 mg/g (less than origin 28.67%), respectively. These were 10.65% and 37.32% higher than the quality standard which were set up in the Chinese Pharmacopoeia (2010 edition)., Conclusion: Sophora flavescens performs quite well in the newly introducing region. It is suitable to be cultivated and extended in South China.

Bioaugmentation (BA) using Acinetobacter sp. TW with high nicotine-degrading efficiency was applied in a bioreactor receiving a load of COD (3,200 ± 50 mg/L) and nicotine (1.0 ± 0.1g/L). The results showed that because of the colonization of strain TW, the COD removal was stable at 80-90%, while nicotine removal reached 98% in the BA system. Furthermore, according to PCR-DGGE fingerprinting, compared with the originally activated sludge, more bacteria existed in the BA systems while some bacteria disappeared from the non-BA system. In terms of the quorum sensing, short chain AHLs increased to assist colonization of strain TW, and long chain AHLs were secreted and helped to resist the nicotine toxicity. Compared with the non-BA system, the amounts of ROS, protein carbonyls and 8-OHdG were significant lower in the BA systems, which suggested that strain TW played an important role in eliminating the nicotine toxicity from the bioreactors., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The serendipitous discovery of the anticancer drug cisplatin cemented medicinal inorganic chemistry as an independent discipline in the 1960s. Luminescent metal complexes have subsequently been widely applied for sensing, bio-imaging, and in organic light-emitting diode applications. Transition-metal complexes possess a variety of advantages that make them suitable as therapeutics and as luminescent probes for biomolecules. It is thus highly desirable to develop new luminescent metal complexes that either interact with DNA through different binding modes or target alternative cellular machinery such as proteins as well as to provide a more effective means of monitoring disease progression. In this Review, we highlight recent examples of biologically active luminescent metal complexes that can target and probe a specific biomolecule, and offer insights into the future potential of these compounds for the investigation and treatment of human diseases., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Peaceful coexistence: A double quadruplex composed of an i-motif and a G-quadruplex was constructed within one oligonucleotide strand (see picture). The defined double-quadruplex structure can serve as a NOTIF logic gate on the basis of the fluorescence of crystal violet., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report herein a simple and convenient luminescent assay for detection of base excision repair enzyme activity using an Ir(III) complex as a G-quadruplex selective probe. Using uracil-DNA glycosylase (UDG) as a model enzyme, the assay achieved high sensitivity and selectivity for UDG over other tested enzymes. The utility of the assay for screening potential UDG inhibitors was also demonstrated.