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Copper-chlorophyllin is a water-soluble derivative of chlorophylls and shows low cytotoxicity and antimutagenic properties in cultured cells. It has multiple applications, including its use as a photosensitizer in photothermal therapy because of its green light-activated photothermal performance. In this work, it was copolymerized with a poly(ethylene glycol) methacrylic monomer to yield random copolymers by free radical polymerization, which showed dual temperature- and pH-dependent phase transitions in aqueous solutions. The cloud points of the copolymer solutions were raised by lowering the pH of the aqueous solutions due to the protonation of the carboxylic groups on the chlorophyllin moieties, which decreased the overall hydrophilicity of the polymers. At low pH values, complete protonation of the carboxylic acid groups of the chlorophyllin moieties led to an irreversible aggregation of the copolymers in water. The incorporation of chlorophyllin in the copolymer improved its stability over its single molecular form.

Four undescribed sesquiterpene-shikimates (1-4), eight undescribed monoterpene-shikimates (5-12), together with two known ones were isolated and identified from the 95% ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Capitalensis A (1) was identified as the first sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid degradation product, while capitalensis B (2) is a sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid with a unique D-ring formed by a C-2-O-C-9' connection. The structures of these previously undescribed compounds were elucidated by multiple techniques, including IR, HR-ESI-MS, and NMR analysis. Furthermore, their absolute configurations were established through the comprehensive approach that involved the calculations of ECD spectra, optical rotation values, and single-crystal X-ray analysis. Moreover, the anti-inflammatory activity of all isolated compounds was evaluated using a lipopolysaccharide (LPS)-induced inflammation model in BV2 microglial cells. Meanwhile, these compounds exhibited activity in inhibiting NO production. Four compounds, capitalensis C (3), capitalensis D (4), 15-hydroxyl tricycloalternarene 5b (13) and guignarenone A (14) showed strong inhibitory effects with IC 50 values of 21.6 ± 1.33, 12.2 ± 1.08, 18.6 ± 1.27, and 15.8 ± 1.20 μM, respectively. In addition, the structure-activity relationship of the anti-inflammatory activity of the compounds was discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal cation channel that is activated by electrophilic irritants, oxidative stress, cold temperature, and GPCR signaling. TRPA1 expression has been primarily identified in subsets of nociceptive sensory afferents and is considered a target for future analgesics. Nevertheless, TRPA1 has been implicated in other cell types including keratinocytes, epithelium, enterochromaffin cells, endothelium, astrocytes, and CNS neurons. Here, we developed a knock-in mouse that expresses the recombinase Flp O in TRPA1-expressing cells. We crossed the TRPA1 Flp mouse with the R26 ai65f mouse that expresses tdTomato in a Flp-sensitive manner. We found tdTomato expression correlated well with TRPA1 mRNA expression and sensitivity to TRPA1 agonists in subsets of TRPV1 (transient receptor potential vanilloid receptor type 1)-expressing neurons in the vagal ganglia and dorsal root ganglia (DRGs), although tdTomato expression efficiency was limited in DRG. We observed tdTomato-expressing afferent fibers centrally (in the medulla and spinal cord) and peripherally in the esophagus, gut, airways, bladder, and skin. Furthermore, chemogenetic activation of TRPA1-expressing nerves in the paw evoked flinching behavior. tdTomato expression was very limited in other cell types. We found tdTomato in subepithelial cells in the gut mucosa but not in enterochromaffin cells. tdTomato was also observed in supporting cells within the cochlea, but not in hair cells. Lastly, tdTomato was occasionally observed in neurons in the somatomotor cortex and the piriform area, but not in astrocytes or vascular endothelium. Thus, this novel mouse strain may be useful for mapping and manipulating TRPA1-expressing cells and deciphering the role of TRPA1 in physiological and pathophysiological processes., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Patil et al.)

Purpose: Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide. Mounting evidence suggests that even mild TBI injuries, which comprise >75% of all TBIs, can cause chronic post-concussive neurological symptoms, especially when experienced repetitively (rTBI). The most common post-concussive symptoms include auditory dysfunction in the form of hearing loss, tinnitus, or impaired auditory processing, which can occur even in the absence of direct damage to the auditory system at the time of injury. The mechanism by which indirect damage causes loss of auditory function is poorly understood, and treatment is currently limited to symptom management rather than preventative care. We reasoned that secondary injury mechanisms, such as inflammation, may lead to damage of the inner ear and parts of the brain used for hearing after rTBI. Herein, we established a model of indirect damage to the auditory system induced by rTBI and characterized the pathology of hearing loss., Methods: We established a mouse model of rTBI in order to determine a timeline of auditory pathology following multiple mild injuries. Mice were subject to controlled cortical impact at the skull midline once every 48 h, for a total of 5 hits. Auditory function was assessed via the auditory brainstem response (ABR) at various timepoints post injury. Brain and cochleae were collected to establish a timeline of cellular pathology., Results: We observed increased ABR thresholds and decreased (ABR) P1 amplitudes in rTBI vs sham animals at 14 days post-impact (dpi). This effect persisted for up to 60 days (dpi). Auditory temporal processing was impaired beginning at 30 dpi. Spiral ganglion degeneration was evident at 14 dpi. No loss of hair cells was detected at this time, suggesting that neuronal loss is one of the earliest notable events in hearing loss caused by this type of rTBI., Conclusions: We conclude that rTBI results in chronic auditory dysfunction via damage to the spiral ganglion which occurs in the absence of any reduction in hair cell number. This suggests early neuronal damage that may be caused by systemic mechanisms similar to those leading to the spread of neuronal death in the brain following TBI. This TBI-hearing loss model provides an important first step towards identifying therapeutic targets to attenuate damage to the auditory system following head injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the research described in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Frontal polymerization (FP) was used to prepare poly(ethylene glycol) methyl ether acrylate (PEGMA) fluorescent polymer hydrogels containing pyrenebutyl pendant groups as fluorescent probes. The polymerization procedure was carried out under solvent-free conditions, with different molar quantities of pyrenebutyl methyl ether methacrylate (PybuMA) and PEGMA, in the presence of tricaprylmethylammonium (Aliquat 336 ® ) persulfate as a radical initiator. The obtained PEGPy hydrogels were characterized by FT-IR spectroscopy, confirming the effective incorporation of the PybuMA monomer into the polymer backbone. The thermal properties of the hydrogels were determined using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). After immersing the hydrogels in deionized water at 25 °C and pH = 7, their swelling behavior was investigated by mass gain at different pH and temperature values. The introduction of PybuMA comonomer into the hydrogel resulted in a decreased swelling ability due to the hydrophobicity of PybuMA. The optical properties of PEGPy were determined by UV-visible absorption and fluorescence spectroscopies. Both monomer and excimer emission bands were observed at 379-397 and 486 nm, respectively, and the fluorescence spectra of the PEGPy hydrogel series were recorded in different solvents to explore the coexistence of monomer and excimer emissions.

GEN-0828, a proposed clinical candidate for hemophilia and trauma hemorrhage treatment, is a novel recombinant activated human factor VII (rFVIIa). The purpose of this paper is to compare the pharmacokinetics and pharmacodynamics of GEN-0828 in hemophilia B mice with those of NovoSeven®, the only marketed rFVIIa product worldwide., GEN-0828 and NovoSeven® showed similar affinity bioactivity to recombinant tissue factor (rTF) in vitro. Pharmacodynamics data indicated a generally similar hemostatic efficacy (ED 50 ) of GEN-0828 (10.91 KIU·kg -1 ) and NovoSeven® (18.91 KIU·kg -1 ) at the doses studied in hemophilia B mice, while GEN-0828 represented a lower initial effective dosage compared with that of NovoSeven® in terms of both blood loss and APTT. GEN-0828 exhibited linear pharmacokinetic profiles in hemophilia B mice at the 30-338 KIU·kg -1 dose range, the comparative pharmacokinetic study with NovoSeven® indicated better characteristics than NovoSeven® in terms of the appropriate higher maximal concentration (C max ) and area under the plasma concentration-time curve (AUC last ) and longer mean residence time (MRT). In conclusion, GEN-0828 was a promising new type of rFVIIa compound with favourable pharmacokinetic and pharmacodynamic profiles., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

At present, whole-brain radiation therapy/stereotactic radiosurgery is one of the main local treatments for brain metastasis of non-small-cell lung cancer (NSCLC). Currently, it has been proved that radiotherapy (RT) can regulate the immune response, and small-sample studies have shown that patients with NSCLC brain metastases (BMs) can benefit from RT combined with immunotherapy (IO). However, the efficacy and safety of the combination treatment have not been deeply elaborated. Notably, as a challenge that is still being explored, the timing of RT combined with IO is likely to be an important factor affecting efficacy and prognosis. This article reviews the current application and challenges of RT combined with IO from the perspectives of molecular mechanism, combination timing, safety, and efficacy. The purpose is to provide information on clinical evidence-based medicine of combination between RT with IO. For further investigation, we also discuss the major challenges and prospects of RT combined with IO in NSCLC BMs., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Gonadotropin-releasing hormone analogs (GnRHas) are used for treating central precocious puberty (CPP). However, their roles in the regulation of immune cells especially regulatory T cells (Tregs) remains elusive. Therefore, we characterized buserelin-induced phenotypical and functional changes of Tregs., Methods: A rat CPP model was established followed by administration of buserelin acetate. Flow cytometry was used to evaluate the expression of functional molecules in splenic Tregs. The suppressive activity of Tregs was determined by the suppression assay. GnRHR expression in Tregs was assessed by flow cytometry analysis and Immunoblotting. Normal Tregs were then stimulated and treated with buserelin acetate in vitro . After that, Foxp3 expression, Treg proliferation, and cytokine production were analyzed by flow cytometry. Intracellular signaling was evaluated by Immunoblotting, and Treg function was determined by the suppression assay., Results: After in vivo buserelin treatment, the frequency of splenic Tregs was decreased, with the reduction in the expression of Foxp3, IL-10, and TGF-β. The suppressive activity of Tregs was weakened. Buserelin down-regulated Foxp3 expression while promoting the expression of RORγt and IL-17 in Tregs through activating the protein kinase A (PKA) pathway in vitro . The PKA inhibitor H-89 abolished the effect of buserelin and enhanced Treg function., Conclusion: Buserelin impaired the immunosuppressive activity of Tregs through the PKA signal pathway. Buserelin-induced activation of PKA signaling down-regulated Foxp3 expression while promoting RORγt expression in Tregs, and subsequently weakened Treg function. Our study indicates the necessity of monitoring Treg activity in CPP patients to avoid potential autoimmunity or inflammation.

The proactive change behavior of an employee is the key to promoting organizational innovation. However, the proactive change has a certain risk, and many employees are unwilling to implement initiatively. How to promote the occurrence of a proactive change behavior of an employee has become a hot issue in the theoretical and practical areas. Based on the self-disclosure theory, this study uses the questionnaire survey method, containing a total of 32 items, and uses the 5-point Likert scale (1 = strongly disagree and 5 = strongly agree), with the Mplus and SPSS statistical software to analyze the impact mechanism of work-related information sharing of supervisors on the proactive change behavior of employees through the structural equation model. The regulatory effect of non-work information sharing of leaders is analyzed using the latent regulatory structural equation method. The conclusions are as follows: work-related information sharing positively of supervisors influences the family-like employee-organization relationship of employees; the family-like employee-organization relationship and relationship energy play serial mediating roles in the relationship between work-related information sharing of supervisors and the proactive change behavior of employees; non-work information sharing of supervisors moderates the serial mediating path by enhancing the positive influence of work-related information sharing of supervisors on the family-like employee-organization relationship. Theoretically, this study has complemented and enriched the research on the influence mechanism between the information sharing of supervisors and the proactive change behavior of employees. Practically, this study has important implications for supervisors to promote the proactive change behavior of employees by sharing work-related information and non-work information with employees., 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 © 2021 Zhu, Li, Wang, Liu and Xia.)

The aim of this study was to identify the effects of melatonin on acute gouty inflammation and to investigate the underlying mechanisms. We found significantly lower serum melatonin levels in gout patients in the acute phase than in those in the remission phase or in normal individuals. The mRNA expression of melatonin receptor 2 (MT2) was also lower in gout patients than in normal individuals. To verify the in-vivo role of melatonin, a gouty arthritis model was established by intraarticular injection of monosodium urate (MSU, 1 mg) crystals into the paws of C57BL/6 mice. Joint inflammation in the mouse model was evaluated by measuring the thickness of the right paw/left paw, and the inflammation index was determined by examining infiltrating neutrophils with haematoxylin and eosin (H&E) staining. Melatonin was found to reduce both paw thickness and the inflammation index in the mouse model, and melatonin also reduced the mRNA levels of interleukin-1 beta (IL-1β), IL-6 and NLR family pyrin domain containing 3 (NLRP3) inflammasome. To mimic gouty inflammation in vitro, mouse peritoneal macrophages were stimulated with lipopolysaccharides (LPS) plus MSU. Melatonin was revealed to reduce IL-1β secretion by stimulated macrophages. The mRNA expression levels of IL-1β and IL-6 were also inhibited by melatonin. Western blot analysis showed that the expression of NLRP3, caspase-1 and pro-IL-1β was also inhibited by melatonin. In conclusion, our study demonstrated that melatonin alleviated gouty inflammation in vivo and in vitro, and the underlying mechanism may involve inhibiting the assembly of the NLRP3 inflammasome., (© 2021. Huazhong University of Science and Technology.)

The conformational study of dendritic platforms containing multiple β-cyclodextrin (βCD) units in the periphery is relevant to determine the availability of βCD cavities for the formation of inclusion complexes in aqueous biological systems. In this work, we performed a detailed conformational analysis in D 2 O, via 1D and 2D NMR spectroscopy of a novel class of phosphorus dendritic compounds of the type P 3 N 3 -[O-C 6 H 4 -O-(CH 2 ) n -βCD] 6 (where n = 3 or 4). We unambiguously demonstrated that a functionalized glucopyranose unit of at least one βCD unit undergoes a 360° tumbling process, resulting in a deep inclusion of the spacer that binds the cyclodextrin to the phosphorus core inside the cavity, consequently limiting the availability of the inner cavities. In addition, we confirmed through NMR titrations that this tumbling phenomenon can be reversed for all βCD host units using a high-affinity guest, namely 1-adamantanecarboxylic acid (AdCOOH). Our findings have demonstrated that it is possible to create a wide variety of multi-functional dendritic platforms.

The toxicity of the poly(amidoamine) dendrimers (PAMAM) caused by the peripheral amino groups has been a limitation for their use as drug carriers in clinical applications. In this work, we completely modified the periphery of PAMAM dendrimer generation 1 (PAMAM G1) with β-cyclodextrin (β-CD) units through the Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) to obtain the PAMAM G1-β-CD dendrimer with high yield. The PAMAM G1-β-CD was characterized by 1 H- and 13 C-NMR and mass spectrometry studies. Moreover, the PAMAM G1-β-CD dendrimer showed remarkably higher water solubility than native β-CD. Finally, we studied the toxicity of PAMAM G1-β-CD dendrimer in four different cell lines, human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa) and pig kidney epithelial cells (LLC-PK1). The PAMAM G1-β-CD dendrimer did not present any cytotoxicity in cell lines tested which shows the potentiality of this new class of dendrimers., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Objective: To assess the value of contrast-enhanced ultrasound (CEUS) and color Doppler ultrasound (DUS) on hemodynamic changes and cerebral perfusion quantitative analyses in Sprague-Dawley (SD) rats with focal permanent ischemic stroke., Methods: Sixteen SD rats with thin skulls were subjected to establish middle cerebral artery occlusion (MCAO) model. CEUS images were performed before modeling (T 0 ), immediately after modeling (5-15 min after modeling, T 1 ), 3 h after modeling (T 2 ), followed by the measurement of bilateral middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA) using DUS. The peak systolic velocity (PSV), end-diastolic velocity (EDV) and mean velocity (MV) of these arteries were obtained. The brain time-intensity curve was taken as interest region of the whole right brain, and the quantitative parameters of CEUS were obtained, including peak intensity (PI), area under the curve ( AUC ), wash in slope (WIS), time to peak (TTP), rise time (RT) and time from peak to one half (TPH). The modified neurological deficit score (mNSS) of the rats was performed 3 h after the modeling, and the data of the rats with a score of 9-11 were statistically analyzed., Results: A total of 12 rats were successfully modeled and completed with mNSS score 9-11. No blood flow signals were observed on the right MCA and ACA in the 12 rats at T 1 and T 2 . From T 0 to T 1 , PI, AUC and WIS of the right hemisphere decreased sharply with TTP and RT significantly prolonged, and the differences were statistically significant. However, there was no significant difference in hemodynamic parameters at that period of time. From T 1 to T 2 , there were no significant changes in CEUS quantitative parameters (except AUC and TPH), while PSV, EDV, MV of LMCA and bilateral PCA showed significant acceleration, and the differences were statistically significant., Conclusion: CEUS and DUS can reveal the intracranial hemodynamics and brain tissue perfusion trends of MCAO rats, which could be new methods in assessment of ischemic stroke model at multiple time points., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Background: Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs., Methods: We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model., Results: Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE., Conclusions: The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

Background: Chronic spontaneous urticaria (CSU) is a skin disorder with an important immunologic profile. S100A8, S100A9, and S100A12 are the members of S100 family that have been reported to play important role in autoimmune diseases, but the characteristics of these three S100 members have not been defined in CSU., Aims: This study was performed to investigate the levels of these three S100s in patients with CSU and to study whether they were associated with the severity and clinical characteristics of CSU., Materials and Methods: The levels of plasma S100A8, S100A9, and S100A12 were measured in 51 CSU patients and 20 healthy controls using enzyme linked immunosorbent assay kits. The values in the patient group and that of the healthy controls were statistically compared. The relationships between the different markers were evaluated by correlation analysis., Results: The plasma levels of S100A8, S100A9, and S100A12 were significantly higher in CSU patients than those in controls. Interestingly, the level of S100A12 was significantly correlated with S100A8 and S100A9 in CSU patients ( P < 0.05 and P < 0.001, respectively). In addition, S100A8, S100A9, and S100A12 were all significantly inversely correlated with blood basophil percentage., Conclusions: Plasma S100A8, S100A9, and S100A12 levels were elevated in CSU patients. They might be useful biomarkers of CSU, with the potential role in the pathogenesis of CSU., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Dermatology.)

Objective: To determine the value of applying multimodal ultrasound (mUS) in SD rats of cerebral ischemic model at super early stage (5-15 min after modeling)., Methods: Fifteen focal cerebral ischemic models were established in SD rats with thinning skulls using the suture method. Gray-scale ultrasound, contrast-enhanced ultrasound, and enhanced color Doppler (CECDUS) were performed before and immediately after the modeling to observe the location of the in-cranial suture, perfusion of the right hemisphere, and color flow signal of the middle cerebral artery and the anterior cerebral artery, respectively.A modified neurological deficit score (mNSS) and 2, 3, 5-triphenyltetrazolium chloride (TTC) stains were obtained three hours later to confirm the successful modeling as the gold standard. The positive rate detected by mUS was compared with the gold standard using McNemar tests., Results: One rat died and 14 rats completed the experiment.mUS imaging detected 71% (10/14) positive signals, no significant difference compared with the gold standard (64%, 9/14) ( P >0.05). A hyperechoic double-line at the bottom of the right brain and focal hypoperfused areas in the right hemisphere were observed by gray scale ultrasound and contrast-enhanced ultrasound in the successfully modeled rats, respectively. The CECDUS found no blood flow in the anterior and middle cerebral arteries. Time intensity curve (TIC) analyses indicated significant changes in peak intensity (PI), area under the curve (AUC), wash in slope (WIS), and time to peak (TTP) after successful modeling., Conclusion: Multimodal ultrasound can assess modeling success quickly and accurately immediately after the establishment of ischemic model of SD rats., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

To improve the quality of the tailings water from a wastewater treatment plant (WWTP), a denitrification biofilter (DNBF) with a composite filler composed of a new slow-release organic-carbon source (SOC-F), sponge iron, and activated carbon was tested. Studies were conducted in the combined process of DNBF-O 3 -GAC to explore the efficiency of the advanced removal of nitrogen, phosphorus, and microbial metabolite by using synthetic effluent made from running water and chemicals. Corresponding comparative studies were conducted by using the secondary effluent from the WWTP. The microbial population structure in the biofilm of the denitrification biofilter was analyzed by adopting MiSeq high-throughput sequencing technologies. The results indicated that the combination process achieved high efficiency removal of nitrogen, phosphorus, and microbial metabolite. The average removal rate of NO 3 - -N in the simulated and actual water period reached 88.87% and 79.99%, respectively; the average removal rate of TP reached 87.67% and 65.51%, respectively; and the average removal rate of UV 254 reached 45.51% and 49.23%, respectively. Each processing unit had different functions. The changes in NO 3 - -N, TN, TP, and TFe mainly occurred in the denitrification biofilter, and the removal of UV 254 and the change in the three-dimensional fluorescence intensity mainly occurred in the ozone-activated carbon reactor. The cluster analysis at the genus level indicated that the denitrification system had sulfur autotrophic denitrifying bacteria and heterotrophic denitrifying bacteria. Sulfur autotrophic denitrification increased obviously in the actual water period when relatively lack of carbon sources, and the proportion of Thiobacillus increased from 7.44% to 29.62%. The complementary effect of sulfur autotrophic denitrification and heterotrophic denitrification had extended the use of the new slow-release carbon source.

In order to investigate the effect of temperature on the cellulose-degrading bacteria and denitrifying bacteria, the denitrification and phosphorus removal of solid carbon source of cellulose corncob+sulfur/sponge iron nitrogen and phosphorus removal composite system, abbreviated as SCSC-S/Fe, was analyzed under different temperature conditions, and the surface structure and microbial properties of corncob before and after reaction were analyzed by scanning electron microscope (SEM) and MiSeq high-throughput sequencing technologies. The results indicated that when temperature increased from 15, 20, 25 to 30℃, the average TN removal rate of the system increased from 78.88% to 92.70%, the average removal rate of TP increased from 82.58% to 89.15%;microbial properties showed that the surface reaction after corncob was dominated by spherical and rod-shaped microorganisms; the proportion of cellulose-degrading bacteria was 11.01% higher at 30℃ than 20℃, and the proportion of denitrifying bacteria decreased by 21.26%. It can be seen that the cellulose -degrading bacteria were more sensitive to the temperature than the denitrification bacteria, and more obviously affected by the temperature.

Background: Oral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis., Methods: Based on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated., Findings: Our results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema - patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89., Interpretation: Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

To obtain materials useful for the biomedical field, toxic catalysts should be removed from the synthetic route of polymerization reactions and of their precursors. Lipase-catalyzed ring-opening polymerization and the synthesis of cyclic precursors can be performed with the same catalyst under different conditions. Here, we highlight the use of lipases as catalysts and optimization of their performance for both ring-closing and ring-opening polymerization, via varying parameters such as ring size, concentration, substrate molar ratio, temperature, and solvent. While the conditions for ring-closing reactions and ring-opening polymerizations of small molecules, such as ε-caprolactone, have been extensively explored using Candida antarctica lipase B (CALB), the optimization of macrocyclization, especially for more bulky substrates is surveyed here. Finally, recent methods and polymer architectures are summarized with an emphasis on new procedures for more sustainable chemistry, such as the use of ionic liquids as solvents and recycling of polyesters by enzymatic pathways., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In order to improve the phosphorus removal effect in the denitrification and phosphorus synchronous removal process by sulfur/sponge iron composite fillers, the phosphorus removal effect by different fillers with the coupling microorganisms was studied to analyze the denitrifying phosphorus removal mechanism of the microbial coupling sulfur/sponge iron composite fillers. The research result showed that the phosphorus removal ratio of sponge iron/sulfur composite fillers was over 95%, which was increased by 30% as compared to only sponge iron filler. In addition, the effluent TP concentration was reduced to less than 0.1 mg·L -1 . The analysis of X-ray diffraction(XRD)and total iron concentration indicated that the main phosphorus removal system products which were produced in the corrosion and phosphorus removal process of sponge iron were FeOOH, FeS and Fe 4 (PO 4 ) 3 (OH) 3 deposits and dissolved iron ions; FeS and FeOOH which were the hydrolysis products of Fe 2+ and Fe 3+ converted PO 4 3- to Fe 4 (PO 4 ) 3 (OH) 3 by adsorption and deposition so that phosphorus removal could be achieved. After the reactor of microbial coupling sulfur/sponge iron carbon composite fillers became stable, the removal efficiency of TN and TP could reach 90% and more than 83%, respectively; Corrosion of sponge iron and phosphorus removal process could also be promoted by biological iron and H + that was produced in the sulfur autotrophic denitrification process, the system could realize the combination of "heterotrophic synergy autotrophic" composite denitrification and chemical phosphorus removal, and efficient denitrifying denitrification synchronous phosphorus removal process could be achieved in the urban sewage treatment plant.

Silent information regulator T1 (SIRT1) plays several key roles in the regulation of lipid and glucose homoeostasis. In this study, we investigated the potential role of SIRT1 in hyperuricemia and explored possible mechanisms. Significant hyperuricemia was detected in C57BL/6 mice treated with oxonate and yeast polysaccharide. Resveratrol (RSV), a specific SIRT1 activator, was administered to the mice. SIRT1 suppressed the increased serum uric acid level but up-regulated the expression of urate transporter ATP-binding cassette subfamily G member 2 (ABCG2) in the ileum of hyperuricemic mice. In a human colon carcinoma cell line, SIRT1 promoted ABCG2 production through the deacetylation of peroxisome proliferator-activated receptor (PPAR) γ co-activator 1α (PGC-1α), which then activated the effectors of PPARγ. Interestingly, the SIRT1-induced up-regulation of ABCG2 was significantly inhibited when PGC-1α or PPARγ was blocked by siRNA transfection. Our data demonstrated that SIRT1 and its activator, RSV, have clear anti-hyperuricemia functions in this mouse model. One possible mechanism is the activation of ABCG2 in the ileum through the PGC-1α/PPARγ pathway.

To study the effects of sulfur/sponge iron ratio on denitrification and phosphorus removal, a series of static experiments were conducted using different ratios of sulfur and sponge iron. The results showed that the denitrification and phosphorus removal effect of sulfur/sponge iron composite fillers was significantly higher than that of single filler, and sulfur/sponge iron ratio was one of the key factors influencing nitrogen and phosphorus removal by composite fillers. When the volume ratio was equal to or greater than 1:1, the removal efficiency of TN and TP reached 85% and 97%, respectively. The denitrification and phosphorus removal process of the composite fillers both fitted second-order kinetic equation, the denitrification was dependent on heterotrophic denitrification and sulfur autotrophic denitrification; the phosphorus removal was mainly chemical phosphorus removal caused by sponge iron corrosion.

Aim: SCT800 is a new third-generation recombinant FVIII agent that is undergoing promising preclinical study. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles of SCT800 in hemophilia A mice., Methods: After hemophilia A mice were intravenously injected with single dose of SCT800 (80, 180, and 280 IU/kg) or the commercially available product Xyntha (280 IU/kg), pharmacokinetics profiles were evaluated based on measuring plasma, Fviii: C. For pharmacodynamics study, dose-response curves of SCT800 and Xyntha (1-200 IU/kg) were constructed using a tail bleeding model monitoring both bleeding time and blood loss., Results: Pharmacokinetics profile analysis showed a dose independency of SCT800 ranging from 80 to 280 IU/kg and comparable pharmacokinetic profiles between SCT800 and Xyntha at the doses tested. Pharmacodynamics study revealed comparable ED50 values of SCT800 and Xyntha in the tail bleeding model: 14.78 and 15.81 IU/kg for bleeding time, respectively; 13.50 and 13.58 IU/kg for blood loss, respectively. Moreover, at the doses tested, the accompanying dose-related safety evaluation in the tail bleeding model showed lower hypercoagulable tendency and wider dosage range potential for SCT800 than Xyntha., Conclusion: In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties.

Background: This study aims to evaluate the efficacy of Xiaoyaosan (XYS) for treatment of major depressive disorder (MDD) and to review the studies on antidepressant mechanisms of XYS., Methods: The China Knowledge Resource Integrated Database (1998-2014), VIP Journal Integration Platform (1989-2009), and PubMed (1950-2014) were used to search for and collect scientific publications related to XYS and MDD. Clinical trials for "MDD" and "xiaoyao" were screened. Papers that used the original prescription of XYS for treatment and in combination with Western medicines were included, while papers describing modified XYS were excluded. Four investigators read and screened the resulting publications independently, evaluated the associated scientific results and evidence., Results: There were no conclusive results to support the efficacy of XYS for treatment of MDD, owing to limited sample sizes, flaws in blinding and randomization, and lack of multi-centered clinical trials. Among the experimental studies on the effects of XYS possible involvement of 5-hydroxytryptamine, hypothalamic-pituitary-adrenal axis function, and neuroinflammation were possibly involved demonstrated., Conclusions: The effectiveness of XYS for treatment of MDD is uncertain.

Objective(s): This article was undertaken to investigate the association between tumor necrosis factor-α (TNF-α) G308A polymorphism and interferon-γ (INF-γ) A874T polymorphism and risk of preterm birth (PTB) by performing a meta-analysis of available studies., Study Design: Articles were chosen based on PubMed, EMBASE, Web of science, and China Biology Medicine (CBM) databases with no language restriction from their inceptions to 1 March, 2014. Specific inclusion criteria were used to evaluate articles. Meta-analysis was performed by using a random or fixed effect model with STATA 11.0 software. We estimated the summary odds ratios (ORs) with its corresponding 95% confidence interval (95%CI) to assess the association., Results: 21 eligible case-control studies with a total of 2103 cases and 5070 controls were finally included into this meta-analysis. Pooled analysis showed that A allele of TNF-α G308A was not associated with increased PTB risk (OR=0.84, 95%CI: 0.65-1.07, p=0.167 for G vs. A). Stratifying analysis for ethnicity and different definition of PTB also indicated that A allele was not associated with increased PTB risk. However, the meta-analysis showed that INF-γ A874T polymorphism was associated with the increased risk of PTB (OR=1.14, 95%CI: 1.11-1.73, p=0.004 for A vs. T). Stratifying analysis was not performed due to the small sample size., Conclusion(s): TNF-α G308A polymorphism was not associated with an increased risk of PTB, but INF-γ A874T polymorphism may contribute to increasing susceptibility to PTB. Detection of polymorphism of INF-γ A874T might be a promising biomarker for the diagnosis and prognosis of preterm delivery., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Epidemiological studies demonstrate a linkage between morbidity and mortality and particulate matter (PM), particularly fine particulate matter (PM2.5) that can readily penetrate into the lungs and are therefore more likely to increase the incidence of respiratory and cardiovascular diseases. The present study investigated the compositions of cooking oil fume (COF)-derived PM2.5, which is the major source of indoor pollution in China. Furthermore, oxidative stress, cytotoxicity, apoptosis, and cell cycle arrest induced by COF-derived PM2.5 in primary fetal alveolar type II epithelial cells (AEC II cells) were also detected. N-acetyl-L-cysteine (NAC), a radical scavenger, was used to identify the role of oxidative stress in the abovementioned processes. Our results suggested that compositions of COF-derived PM2.5 are obviously different to PM2.5 derived from other sources, and COF-derived PM2.5 led to cell death, oxidative stress, apoptosis, and G0/G1 cell arrest in primary fetal AEC II cells. Furthermore, the results also showed that COF-derived PM2.5 induced apoptosis through the endoplasmic reticulum (ER) stress pathway, which is indicated by the increased expression of ER stress-related apoptotic markers, namely GRP78 and caspase-12. Besides, the induction of oxidative stress, cytotoxicity, apoptosis, and cell cycle arrest was reversed by pretreatment with NAC. These findings strongly suggested that COF-derived PM2.5-induced toxicity in primary fetal AEC II cells is mediated by increased oxidative stress, accompanied by ER stress which results in apoptosis.

As a widespread phenomenon in living system, molecular self-assembly has become the meeting point of multidisciplinary research including chemistry, biology, materials science and medicine. In recent years, the rapid development in molecular self-assembly of peptide technology is showing a great potential in the application of tissue engineering, drug delivery, bionic medicine, cosmetology field, optical and electronic product development, etc. Especially, the remarkable hemostatic effect of self-assembling peptides (SAP) on organs, nerves and brain wounds successfully promoted its application to the material science and clinical medicine. This review focuses on the hemostatic effects and characteristics of SAP on different bleeding wound models, action mechanism, its benefits and limitations as well as its adrancing trends.

Objective: To evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients., Methods: A prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment., Results: After three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P > 0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P < 0.05]. Scores for CM syndromes, BASDAI, night pain index, spinal pain index, PGA, CRP were improved in the BSG group (P < 0.05, P < 0.01). The incidence of adverse events in the BSG group was lower than that of the control group., Conclusion: BSG based on Shen supplementing, Du-channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.

Background: To investigate whether monosodium urate (MSU) crystals induce interleukin (IL)-1β in human fibroblast-like synoviocytes (FLS), and whether the NLRP3 inflammasome is involved in the inflammatory mechanism., Methods: Human FLS isolated from explants of synovial tissue were stimulated with MSU crystals (0.001 to 0.5 mg/ml) for different time course (6 hours to 48 hours). The expressions of IL-1β, IL-6, TNF-α and NLRP3 were evaluated with ELISA, Western blot and quantitative real-time PCR., Results: Exposure of FLS to MSU crystals transiently induced a significant increase in IL-1β expression in culture medium with a peak at 6 h. The mRNA level of IL-1β in the FLS cells had a similar pattern at this time point. Changes in IL-6 and TNF-α expression were not observed. Simultaneously, intercellular pro-IL-1β was detected at 6 h. Furthermore, MSU crystals also induced NLRP3 mRNA and protein expression at 6 h to 48 h after MSU treatment., Conclusions: MSU crystals directly increased IL-1β and intercellular NLRP3 expression in FLS cells. It is suggested that the NLRP3 inflammasome may be associated with IL-1β in FLS treated with MSU. Altogether, MSU could induce production and release of IL-1β through the NLRP3 inflammasome in human synoviocytes.

The Ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) is a candidate risk gene for Parkinson' disease (PD), and a function SNP (rs5030732) in the coding region of this gene has been studied for the association with the disease extensively among worldwide populations, but the results were inconsistent and controversial. Here, to estimate the association between UCHL1 S18Y polymorphism and risk of PD in general population, we conducted a systematic meta-analysis by combining all available case-control subjects in Asian, European, and American populations, with a total of 7742 PD cases and 8850 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for UCHL1 S18Y polymorphism and PD were calculated using the Mantel-Haenszel method with a fixed- or random-effects model. Subgroup analysis was also performed in different onset age-matched groups. Among high-quality studies, UCHL1 S18Y polymorphism was moderately associated with the risk of PD (allele contrasts, OR = 1.063, 95% CI 1.008-1.122; p = 0.024; regressive genetic model, OR = 1.078, 95% CI 1.005-1.157; p = 0.035). When stratifying for ethnicity, none association were observed in subgroups. Analysis of early-onset PD (EOPD) and late-onset PD (LOPD) revealed that the polymorphism was not associated with the risk of PD. In conclusion, our meta-analysis suggests that UCHL1 S18Y polymorphism is moderately associated with susceptibility to PD, and more studies are needed to confirm our conclusion.

Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion., Materials and Methods: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors., Results: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643)., Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.

Purpose: Several studies have reported that excessive amounts of plasminogen activator inhibitor-1(PAI-1) might increase the incidence of polycystic ovary syndrome(PCOS), but so far the published results were inconsistent. The aim of this study was to further investigate the association between PAI-1 gene polymorphism and the susceptibility to PCOS by performing a meta-analysis., Methods: A comprehensive literature search for relevant studies was conducted on google scholar, PubMed, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM). This meta-analysis was performed using the STATA 11.0 software and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated., Results: Ten case-control studies were included in this meta-analysis with a total of 2,079 cases and 1,556 controls. The results showed that PAI-1 -675 4G/5G polymorphism may increase the risk of PCOS, especially among Asian populations. However, there was no statistically significant association between the polymorphism and PCOS risk in Caucasians., Conclusion: Our meta-analysis suggests that PAI-1 -675 4G/5G polymorphism may contribute to increasing susceptibility to PCOS in Asians. Detection of the PAI-1 gene polymorphism might be a promising biomarker for the susceptibility of PCOS.

S100A8 and S100A9 play important roles in immune and inflammatory disorders. The role of the two proteins in systemic sclerosis (SSc) remains unknown. Fifty-seven diffuse cutaneous SSc (dcSSc) patients, 31 limited cutaneous SSc (lcSSc) patients were recruited in the present study. The expression of S100A8 and S100A9 in plasma was measured using an enzyme-linked immunosorbent assay and the mRNA levels in peripheral blood were assessed using reverse transcriptase quantitative PCR. The expression and distribution of S100A8, S100A9, and receptor for advanced glycation end products (RAGE), in skin tissues was analyzed by immunohistochemistry. The plasma concentrations of S100A8 and S100A9 were significantly higher in dcSSc patients than in normal controls and lcSSc patients. Both S100A8 and S100A9 levels were significantly increased in dcSSc patients with lung or kidney involvement. Increased plasma levels of S100A8 and S100A9 in dcSSc patients were associated with several autoantibodies. Transcription levels of S100A8 and S100A9 in peripheral blood were found elevated in both dcSSc and lcSSc patients than normal controls. Immunohistochemistry demonstrated higher S100A8 and S100A9 expression in sclerotic skin than in normal skin. The number of S100A8, S100A9, or RAGE positive fibroblasts was also significantly increased. Highly elevated expression of both S100A8 and S100A9 was found in dcSSc patients. There was close correlation with disease severity and serological abnormalities, suggesting that the two proteins may play important roles in the development of systemic sclerosis.

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

The purpose of this study was to investigate the effect of paclitaxel in combination with 20(s)-ginsenoside Rg3 on its anti-tumour effect in nude mice. In the Caco-2 transport assay, the apparent permeability from the apical side to the basal side (P(app)) (A-B) and P(app) (B-A) of paclitaxel were measured when co-incubated with different concentrations of 20(s)-ginsenoside Rg3. The results indicated that the penetration of paclitaxel through the Caco-2 monolayer from the apical side to the basal side was facilitated by 20(s)-ginsenoside Rg3 in a concentration-dependent manner. Meanwhile, 20(s)-ginsenoside Rg3 inhibited P-glycoprotein (P-gp), and the maximum inhibition was achieved at 80 µM (p < 0.05). The pharmacokinetic parameters of paclitaxel after oral co-administration of paclitaxel (40 mg/kg) with various doses of 20(s)-ginsenoside Rg3 in rats were investigated by an in vivo pharmacokinetic experiment. The results showed that the AUC of paclitaxel co-administered with 20(s)-ginsenoside Rg3 was significantly higher (p < 0.001 at 10 mg/kg) compared with the control. The relative bioavailability (RB) % of paclitaxel with 20(s)-ginsenoside Rg3 was 3.4-fold (10 mg/kg) higher than that of the control. The effect of paclitaxel orally co-administered with 20(s)-ginsenoside Rg3 against human tumour MCF-7 xenografts in nude mice was also evaluated. Paclitaxel (20 mg/kg) co-administered with 20(s)-ginsenoside Rg3 (10 mg/kg) exhibited an effective anti-tumour activity with the relative tumor growth rate (T/C) values of 39.36% (p <0.05). The results showed that 20(s)-ginsenoside Rg3 enhanced the oral bioavailability of paclitaxel in rats and improved the anti-tumour activity in nude mice, indicating that oral co-administration of paclitaxel with 20(s)-ginsenoside Rg3 could provide an effective strategy in addition to the established i.v. route., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: To explore the iodine level in the environment and the iodine status among the general population as well as the prevalence of thyroid nodules in Hangzhou city. Relationship between the prevalence of thyroid nodules and the policy of universal salt iodization in Hangzhou was also analyzed., Methods: Questionnaire, a 3-day weighed dietary record method, and 3 days' 24-hour dietary recall method were used to understand the iodine nutrition status and dietary intake of iodine among the general population in the city. Drinking water, edible salt and morning urine were collected to determine iodine content. All objects under survey underwent the thyroid B ultrasonic examination. Statistical analysis was done by SPSS 13.0 and SAS 9.1., Results: (1) In total, 12 620 effective questionnaires were available, with 221 water samples, 12 730 urine samples, and 3593 salt samples collected. 12 515 objects underwent B ultrasonic examination, and 1848 received dietary investigation. (2) Water iodine level of Hangzhou was in the range of 0.20 - 5.99 µg/L, with the median level as 2.58 µg/L. (3) Average daily dietary intake of iodine for adult males in Hangzhou was 289.2 µg/d. The contribution of iodine intake from iodized salt was 74.4%. (4) The median of Hangzhou residents' urinary iodine was 178.80 µg/L, with the urinary iodine levels at 100 µg/L-, 200 µg/L-, < 100 µg/L, and ≥ 300 µg/L groups were 37.14%, 23.11%, 21.05%, and 18.69% respectively. Urinary iodine of pregnant women was 141.0 µg/L. (5) Incidence of thyroid nodules in females (28.6%) was higher than that of males (20.1%). The detection rate increased with age (6.4% at group 6-, 10.9% at 12-, 12.0% at 18-, 24.4% at 40-, and 38.8% at 65-); with the highest in urban area (29.8%), followed by suburbs (23.3%) and in rural area it showed the least (20.3%). Urinary iodine level was found lower among the population who had been detected with thyroid nodules (160.36 µg/L) than those among the undetected population (182.00 µg/L)., Conclusion: Hangzhou appeared to be an area where the environmental was iodine deficient. Iodized salt was the major source of iodine intake. The iodine status among the general population seemed to be safe and suitable, but the iodine level for pregnant women was not sufficient. There was still no evidence indicating that the universal salt iodization policy in Hangzhou was associated with the prevalence of thyroid nodules.

This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in rat > in dog > in human > in monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

Objective: to study the correlation of polymorphisms of CYP1A1 MspI, GSTM1 null genotype, cooking oil fumes independently and in combination with the risk of non-smoking lung cancer in females., Methods: one hundred and sixty female non-smoking patients with primary lung cancer and 160 controls were enrolled from Xiangya Hospital of Central South University. PCR-RELP and PCR were used to detect the distribution of CYP1A1 MspI and GSTM1 genotypes respectively. The correlation of these genes and cooking oil fumes with the susceptibility to lung cancer was analyzed., Results: There was a significant difference in the frequencies of cooking oil fumes exposure between cancer cases and controls (χ(2) = 10.734, P < 0.01);but there was no statistical difference in CYP1A1 MspI polymorphisms between the 2 groups (χ(2) = 3.731, P > 0.05). The combination of CYP1A1 polymorphisms and cooking oil fumes significantly increased the risk of lung cancer. The frequencies of GSTM1 null genotype was significantly different between cancer cases and controls (χ(2) = 0.518, P < 0.05). The risk of lung cancer was higher in those with the GSTM1 null genotype and the OR was 1.697 (95%CI 1.090 - 2.640). Individuals with both GSTM1 null genotype and exposure to cooking fumes had a higher risk of cancer than those with only one of them, the OR being 3.617 (95%CI 1.899 - 6.891). The combination of the two genes significantly increased the risk of lung cancer., Conclusions: cooking oil fumes exposure was a risk factor for non-smoking lung cancer in females. The combination of CYP1A1 with cooking oil fume increased the risk of female lung cancer. GSTM1 null genotype was associated with risk of lung cancer in non-smoking females. The combination of GSTM1 null genotype and cooking oil fumes significantly increased the risk of female lung cancer. The combination of CYP1A1 and GSTM1 significantly increased the risk of lung cancer.

The paper is to report the pharmacokinetic character of a series of chemical compounds in vitro and in vivo. Metabolism stability of a series of chemical compounds was screened by using rat liver microsomes. The samples of different chemical compounds were combined and then simultaneously detected by LC-MS/MS. Compounds y13, y12 and y11 were screened out by microstability assay in vitro. The pharmacokinetics of compounds y11, y12 and y13 was evaluated by using SD rat. The plasma samples were pooled at the same time. The plasma concentrations were determined by LC-MS/MS. The pharmacokinetic character of two compounds y13, y11 was good by screening in vivo, so they were developed for further research. High-throughput screening of drug candidates in vitro and in vivo was effective, to provide information for the chemical structure information and lower the drug development risk.

Objective: To explore the risk factors of injuries among school aged children from migrant workers' families, in Hangzhou., Methods: A cross-sectional survey on 3582 students from eight separate schools in which, four were set for migrant workers' families and the other four were for families of permanent residents. Stratified cluster random sampling method was used. Data was analyzed by unconditional univariate and multivariate logistic regression methods under SPSS 13.0., Results: The incidence rate of injury did not show statistical difference between children of migrant workers or from the permanent residents. The incidence rate of multiple injuries was higher in children from the migrant workers' families. The incidence rates on electric shock occurred at the primary school, drowning among boys at the secondary school and scald/crash/cutting by knives in girls at secondary schools were seen higher among children from the of migrant workers. Results from multivariate analysis showed that factors as gender (OR = 1.20), age (6 - 9 years: OR = 0.70, 10 - 12 years: OR = 1.45), fond of playing Pingpong (OR = 1.35), history of injuries by pets (OR = 1.41), skills on swimming (OR = 1.22), no history of being threatened (OR = 0.68), having harmonious family relations (OR = 0.69) and owning a house by family (OR = 0.76) appeared to be the major one that related to the occurrence of injury., Conclusion: Personal behavior as well as family and social environment seemed to be factors affecting the occurrence of injuries among children from the migrant workers' families.

Objective: To explore the correlation of the expressions of metastatic tumor antigen 1 (MTA1) and hypoxia-inducible-factor l alpha (HIF-1alpha) to the clinical features of lung cancer., Methods: The expressions of MTA1 and HIF-1alpha proteins in 59 lung cancer patients were detected by immunohistochemistry., Results: Positive staining of MTA1 and HIF-1alpha was found in 54.24% and 50.85% of the patients, respectively. MTA1 expression was not found to correlated to any of the clinical parameters. HIF-1alpha expression was significantly lower in poorly differentiated than in moderately and well differentiated lung cancer (P<0.05), and a positive association between the expressions of MTA1 and HIF-17alpha were noted (P<0.05)., Conclusion: MTA1 and HIF-1alpha overexpression occurs in lung cancer possibly as an important factor of lung carcinogenesis. MTA1 may promote lung carcinogenesis by enhancing HIF-1alpha protein activity.

A novel method concerning the coding technology of polystyrene beads with Si encapsulated quantum dot (QD) particles (Si@QDs particles) is studied in this paper. In the reverse microemulsion system containing tetraethoxysilane (TEOS), water-soluble QDs (emission peak at 600 nm) were enveloped within the silica shell, forming Si@QDs particles. The Si@QDs particles were characterized by TEM, showing good uniform size, with an average diameter of about 167.0 nm. In comparison with the pure water-soluble QDs, the encapsulation of water-soluble QDs in the silica shell led to an enhancement in anti-photobleaching by providing inert barriers for the QDs. Images presented by SEM and confocal laser scanning microscopy demonstrated that the Si@QDs particles were equably coated on the surface of carboxyl functionalized polystyrene (PS) beads. Then, with the assistance of ethyl-3-(dimethyl aminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), human IgG could be successfully crosslinked to Si@QDs particle coated PS-COOH beads. Furthermore, the Si@QDs coated PS-COOH beads with human IgG were examined in immunoassay experiments, and the results indicated that these beads could be applied in the specific recognition of goat-anti-human IgG in solution. This investigation is expected to provide a new route to bead coding in the field of suspension microarrays, based on the use of QDs.

This study was purposed to verify the binding part of human complement C3 to complement receptor III (CRIII) in monocytes, the peptide rC3B, including the binding-site, was expressed, purified and identified. rC3B, the binding part of human complement C3 to CRIII, was selected by computer-aided modeling and summarizing researches published. Then, rC3B gene fragment was amplified by PCR, and cloned into prokaryotic vector pQE30a. The fusion protein rC3B was expressed in E.coli M15 and purified by Ni(2+)-chelating affinity chromatography. The activity of rC3B was identified by Western blot and adherence assay with monocytes. The results showed that rC3B fragment was obtained, and a prokaryotic expression vector pQE30-rC3B was constructed. rC3B was efficiently expressed and purified. In Western blot, the target protein showed the activity of binding with C3 antibody, while the purified protein showed the activity of adherence with monocytes. It is concluded that the recombinant C3B was obtained and identified, and this study lay the basis for the further functional analysis of C3.

Objective: To study the pathological basis of radiological reaction types of radiation-induced liver disease on multiphasic CT scans., Methods: Three pigs (tagged with A, B, and C) were subjected to single-dose radiation of 40, 40 and 30 Gy on the right or left lobe of the liver, respectively. At 42, 56, 133, and 168 days after irradiation, all pigs were examined with non-enhanced scan and contrast-enhanced scans at different time points after contrast injection. Hounsfield units (HU) were measured in each CT study to evaluate the density of irradiated and non-irradiated liver tissue to determine the reaction type. Liver tissues in the irradiation area obtained by needle biopsy with CT guidance were examined with electron microscopy, and specimens of the tissue corresponding to the region of interest on CT were obtained from necropsies for pathological examination., Results: Radiologically, the 3 pig models presented with 3 reaction types on the multiphasic CT scans on days 133, 56, and 168 after radiation, respectively. Type 1 presented constant low-density change in all phases, the pathological basis of which was radiation hepatitis; type 2 showed pre-contrast phase isodense, arterial phase hyperdense, portal phase isodense and later phase hyperdense changes; type 3 was characterized by pre-contrast phase isodense, arterial phase hyperdense, portal phase hypodense and later phase hyperdense changes. The pathological basis of the last two radiological reaction types was radiation cirrhosis (postnecrotic cirrhosis)., Conclusions: Different radiological reaction types of radiation liver injury on multiphase CT have different pathological basis, and multiphase contrast-enhanced CT may help distinguish the radiation reactions from tumor recurrence.