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The properties of polyethylene are highly dependent on the variety and quantity of substitutions. Generally, polyethylene can only be fully substituted with fluorine atoms, mainly e. g., polytetrafluoroethylene and nafion, because atomic radius of fluorine atom is small enough. The preparation of fully substituted polyethylene analogues (FSPEA) and their non-traditional intrinsic luminescence (NTIL) are attractive, especially for substitutions with relatively larger atomic radii than a fluorine atom. Here, Barbier polymerization-induced emission (PIE) is demonstrated as a universal method for the molecular design of NTIL type FSPEAs with intriguing aggregation-induced emission (AIE) behaviors. Through Barbier polymerization of diphenyldichloromethane and different peroxyesters in the presence of Mg in one pot, a series of FSPEAs, including polytriphenylethanol (PTPE), polydiphenylfurylethanol (PDPFE), polydiphenylthiophenylethanol (PDPTE) and polydiphenylnaphthylethanol (PDPNE) have been successfully prepared. Further potential applications for explosive detection, artificial light-harvesting system and white phosphor-converted light-emitting diode are investigated. Therefore, this work opens up a new approach for the molecular design of FSPEA with non-conjugated luminescence, which may cause inspirations to different research fields like polyolefin and luminescent materials., (© 2023 Wiley-VCH GmbH.)

Incorporating graphite/graphene into a Mg alloy matrix is a promising approach for developing lightweight heat dissipation materials. However, carbon material is inherently incompatible with Mg because of their distinctly different surface characteristics, resulting in the challenge of composite fabricating and interface controlling. Herein, a new strategy of in situ interfacial modification was proposed to achieve excellent thermal conductivity and mechanical properties in graphite/Mg composites. A super-nano CaCO 3 interfacial layer was reported in this paper. The detailed interfacial structure, reaction thermodynamics and kinetics, and interface strengthening mechanisms were analyzed and discussed. Several preferential epitaxial relationships of the Mg/CaCO 3 interface were revealed, which are conducive to minimize the interfacial energy, stabilize and strengthen the interface. Moreover, strong ionic bond of graphite/CaCO 3 interface was demonstrated. The strong chemical interface bonding of graphite-Mg via in situ interface modification facilitates both the interfacial cohesion and interfacial thermal conduction, which endows the graphite/Mg composites with superior strength-thermal conductivity synergy., Competing Interests: 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., (© 2023 The Author(s).)

Stimuli-responsive opposite emission (A)/absorption (B) polymer material (A∪B = Ω and A∩B = Ø) represents a novel polymer material that is difficult to prepare. Here, we demonstrate a one-pot strategy for the molecular design of stimuli-responsive opposite emission/absorption polymer material with intriguing properties of opposite emission/absorption and aggregation-induced emission (AIE) type nontraditional intrinsic luminescence (NTIL) in the visible region, through reversible addition-fragmentation chain transfer polymerization-induced emission (PIE) of the N , N -dimethyl-triphenylmethanol moiety. Investigations reveal that NTIL is due to the through-space conjugation effect caused by polymer chain entanglement, when increasing the repeating unit number. The corresponding stimuli-responsive opposite emission/absorption properties are derived from the carbocation-quinoid mechanism, which enables the fluorescence encryption capability. This work therefore demonstrates the proof of concept of a novel opposite emission/absorption polymer material that might cause inspiration in different fields.

Background: Neuroinflammation and oxidative stress after traumatic brain injury (TBI) can further lead to neuronal apoptosis, which plays a crucial role in the process of neuron death. Curcumin, which is derived from the rhizome of the Curcuma longa plant, has multiple pharmacological effects., Objective: The objective of this study was to investigate whether curcumin treatment has neuroprotective effects after TBI, and to elucidate the underlying mechanism., Methods: A total of 124 mice were randomly divided into 4 groups: Sham group, TBI group, TBI+Vehicle group, and TBI+Curcumin group. The TBI mice model used in this study was constructed with TBI device induced by compressed gas, and 50 mg/kg curcumin was injected intraperitoneally 15 minutes after TBI. Then, the blood-brain barrier permeability, cerebral edema, oxidative stress, inflammation, apoptosis-related protein, and behavioral tests of neurological function were utilized to evaluate the protective effect of curcumin after TBI., Results: Curcumin treatment markedly alleviated post-trauma cerebral edema and blood-brain barrier integrity, and suppressed neuronal apoptosis, reduced mitochondrial injury and the expression of apoptosis-related proteins. Moreover, curcumin also attenuates TBI-induced inflammatory response and oxidative stress in brain tissue and improves cognitive dysfunction after TBI., Conclusion: These data provide substantial evidence that curcumin has neuroprotective effects in animal TBI models, possibly through the inhibition of inflammatory response and oxidative stress., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups., Methods: The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages., Results: A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups., Conclusions: The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.

Luminescent polymer materials have gained considerable research efforts in the past decades and are generally molecular designed by extending the π system of the polymer main chain or by incorporating chromophores into the polymer chain, which suffer from poor solubility, difficult synthesis, or multi-step procedures. Meanwhile, according to the step-growth polymerization theory, synthesis of hyperbranched polymers from an AB-type monomer is still challenging. Herein, we report a one-pot synthesis of nonconjugated luminescent hyperbranched polymer material via Barbier hyperbranching polymerization-induced emission (PIE) from an AB-type monomer. The key step in the realization of the hyperbranched polymer is bi-functionalization of a mono-functional group. Through a Barbier reaction between an organohalide and an ester group in one pot, bi-functionalization of mono-functional ester is realized through two-step nucleophilic additions, resulting in hyperbranched polytriphenylmethanols (HPTPM). Attributed to through-space conjugation and inter- and intramolecular charge-transfer effects induced by polymer chain, nonconjugated HPTPMs are PIEgens, which are tunable by monomer structure and polymerization time. When all phenyl groups are rotatable, HPTPM is aggregation-induced emission type PIEgen. Whereas, it is aggregation-caused quenching type PIEgen if some phenyl groups are rotation forbidden. Further potential applications of PIEgen are in the fields of explosive detection and artificial light harvesting systems. This work, therefore, expands the monomer library and molecular design library of hyperbranched polymers through "bi-functionalization of mono-functional group" strategy, which eventually expands the preparation library of nonconjugated luminescent polymer materials through one-pot PIE from nonemissive monomer., (© 2022 Wiley-VCH GmbH.)

Objectives: To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve., Methods: A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves., Results: A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities., Conclusions: The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.

Objectives: To develop the birth weight curve of singleton neonates with a gestational age of 24-42 weeks, and to investigate the regional differences of the birth weight curve., Methods: A total of 11 maternal and child health hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Shenzhen, Liuzhou, Guilin, Quanzhou, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live singleton neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves., Results: A total of 93 720 singleton neonates with a gestational age of 24-42 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of singleton neonates for the total of the 11 cities and for each of the 11 cities were established, and the birth weight percentile curves were drawn. The birth weight curve level of singleton neonates in Shenzhen and Quanzhou was almost the same as the average level of the 11 cities; the birth weight curve level of singleton neonates in Haikou, Guangzhou, Guilin, and Liuzhou was slightly lower than the average level of the 11 cities; the birth weight curve level of singleton neonates in Chongqing, Chengdu, and Changsha was slightly higher than the average level of the 11 cities; the birth weight curve level of singleton neonates in Ningbo and Lianyungang was higher than the average level of the 11 cities. The average birth weight curve level of singleton neonates in the 11 cities were very close to that of China Neonatal Cooperation Network in 2011-2014., Conclusions: The reference values of the 3rd-97th percentiles of birth weight of singleton neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of singleton neonates in the region. The level of intrauterine growth of neonates in some cities is different from the national level.

The developments of the living alkene polymerization method have achieved great progress and enabled the precise synthesis of important polyalkenes with controlled molecular weight, molecular weight distribution, and architecture through an anionic, cationic or radical strategy. However, it is still challenging to develop a living alkene polymerization method through an all-in-one strategy where anionic and radical characteristics are merged into one polymerization species. Here, a versatile living polymerization method is reported by introducing a well-established all-in-one covalent-anionic-radical Barbier strategy into a living polymerization. Through this living covalent-anionic-radical Barbier polymerization (Barbier CARP), narrow distributed polystyrenes, with Đ as low as 1.05, are successfully prepared under mild conditions with a full monomer conversion by using wide varieties of organohalides, for example, alkyl, benzyl, allyl, and phenyl halides, as initiators with Mg in one pot. This living covalent-anionic-radical polymerization via a Barbier strategy expands the methodology library of polymer chemistry and enables living polymerization with an unconventional polymerization mode.

Background: Although previous studies have made significant contributions to establishing animal traumatic brain injury (TBI) models for simulation of human TBI, the accuracy, controllability, and modeling efficiency of animal TBI models need to be further improved. This study established a novel high-efficiency graded mouse TBI model induced by shock wave., Methods: A total of 125 mice were randomly divided into sham, 0.7 mm, 0.6 mm, and 0.5 mm groups according to the depth of the cross groove of the aluminum sheets. The stability and repeatability of apparatus were evaluated, and the integrity of the blood-brain barrier, cerebral edema, neuropathologic immunohistochemistry, apoptosis-related protein, and behavioral tests of neurologic function were used to validate this new model., Results: The results showed that 4 mice were injured simultaneously in 1 experiment. They received the same intensity of shock waves. Moreover, the mortality rates caused by 3 different aluminum sheets were consistent with the mortality rates of mild TBI, moderate TBI, and severe TBI. Compared with the sham group, mice in different injured groups significantly increased brain water content, blood-brain barrier permeability, and neuronal apoptosis. And the mice in all injured groups showed poor motor ability, balancing, spatial learning, and memory abilities., Conclusions: The novel TBI apparatus has advantages in its small size, simple operation, high repeatability, high efficiency, and graded severity. Our TBI apparatus provides a novel tool to investigate the neuropathologic changes and underlying mechanisms of TBI with various levels of severities., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The conventional rolling of magnesium alloy with a single pass and large reduction will cause severe edge cracking. The sheet without cracks can be achieved by limited width rolling. The microstructure evolution of the sheet with cracks after conventional rolling and the sheet without cracks after limited width rolling is explored, and an effective mechanism for solving edge cracks is proposed. Conventional rolling can fully develop twin evolution due to high deformation, and three stages of twinning evolution can be observed and the secondary twins easily become the nucleation points of micro cracks, resulting in a large number of cracks propagating along the twin lamellae. Cracks terminate at dislocation accumulation because the accumulation of a large number of dislocations can hinder propagation. Dislocation shearing of twins to eliminate the high localization caused by twins and induce the tensile twins to weaken the basal surface texture provides an effective plastic deformation mechanism of crack inhibition, which is useful for expanding the engineering application of magnesium alloy rolled sheets.

To better control the quality of synthetic vanillin obtained by using the guaiacol synthesis method, the olfactory impacts of byproducts on the aroma of the synthetic vanillin samples were evaluated and their optimum concentration ranges were determined. Four byproducts (guaiacol, ortho-vanillin, 5-methyl-vanillin, and 5-formyl-vanillin) were identified by gas chromatography-mass spectrometry (GC-MS) and quantified by gas chromatography-flame ionization detection (GC-FID) in the synthetic vanillin samples with different degrees of purity. The aroma intensities (AIs) of the four byproducts obtained by gas chromatography-olfactometry (GC-O) were: guaiacol (AI: 3.5-4.0, smoke), ortho-vanillin (AI: 1.6-2.5, almond), 5-methyl-vanillin (AI: 2.5-3.3, aldehyde), and 5-formyl-vanillin (AI: 3.2-3.8, green). The aroma perceptual interactions of the four byproducts and the vanillin in the synthetic vanillin samples were determined by S-curve analysis. Guaiacol and 5-methyl-vanillin showed synergistic effects by Feller's additive model. Combined with the results of an addition experiment, when the contents of guaiacol, ortho-vanillin, 5-methyl-vanillin, and 5-formyl-vanillin were within 50, 10, 400, and 1,000 mg/kg respectively, the byproducts had no effects on the aroma quality of the synthetic vanillin samples. PRACTICAL APPLICATION: Synthetic vanillin is one of the most commonly used food additives. Currently, the purity of synthetic vanillin can reach 99.9%, but trace byproducts are still present. Continuing to improve the purity of synthetic vanillin will significantly increase its production costs. Therefore, it is necessary to determine whether the presence of these byproducts affects the aroma quality of the synthetic vanillin samples or not. If they have a negative effect on its aroma, it will be important to reduce their content. If they have no influence or positive role, there is no need to control the content of these byproducts to very low levels. This study determined the content of the byproducts produced during the synthesis of vanillin by guaiacol glyoxylic acid method, judged the perceptual interaction between the byproducts and the vanillin in the synthetic vanillin samples, and determined the optimum range within which the byproducts had no effects on the aroma quality. This study provides a theoretical basis for improving the aroma quality of synthetic vanillin while controlling the production costs., (© 2021 Institute of Food Technologists®.)

Cognitive impairment is a significant sequela of traumatic brain injury (TBI) especially blast induced traumatic brain injury (bTBI), which is characterized by rapid impairments of learning and memory ability. Although several neuroprotective agents have been postulated as promising drugs for bTBI in animal studies, very few ideal therapeutic options exist to improve cognitive impairment following bTBI. Thymosin α1(Tα1), a 28-amino-acid protein that possesses immunomodulatory functions, has exhibited beneficial effects in the treatment of infectious diseases, immunodeficiency diseases and cancers. However, it remains unclear whether Tα1 has a therapeutic role in bTBI. Thus, we hypothesized that Tα1 administration could reverse the outcomes of bTBI. The blast induced TBI (bTBI) rat model was established with the compressed gas driven blast injury model system. A consecutive Tα1 therapy (in 1 ml saline, twice a day) at a dose of 200 µg/kg or normal saline (NS) (1 ml, twice a day) for 3 days or 2 weeks was performed. Utilizing our newly designed bTBI model, we investigated the beneficial effects of Tα1 therapy on rats exposed to bTBI including: cognitive functions, general histology, regulatory T (Treg) cells, edema, inflammation reactions and the expression and phosphorylation level of tau via Morris Water Maze test (MWM test), HE staining, flow cytometry, brain water content (BWC) calculation, IL-6 assay and Western blotting, respectively. Tα1 treatment seemed to reduce the 24-hour mortality, albeit with no statistical significance. Moreover, Tα1 treatment markedly improved cognitive dysfunction by decreasing the escape latency in the acquisition phase, and increasing the crossing numbers in the probe phase of MWM test. More interestingly, Tα1 significantly inhibited tau phosphorylation at the Thr205 epitope, but not at the Ser404 and Ser262 epitopes. Tα1 increased the percentage of Treg cells and inhibited plasma IL-6 production on 3d post bTBI. Moreover, Tα1 suppressed brain edema as demonstrated by decrease of BWC. However, there was a lack of obvious change in histopathology in the brain upon Tα1 treatment. This is the first study showing that Tα1 improves neurological deficits after bTBI in rats, which is potentially related to the inhibition of tau phosphorylation at the Thr205 epitope, increased Treg cells and decreased inflammatory reactions and brain edema., 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 © 2020. Published by Elsevier B.V.)

The supported chitosan (CS) adsorbent (FZCS) was successfully prepared by load CS on the BSCS supporter in this work. The adsorbent was characterized by elemental analysis, FT-IR, XRD, TGA, SEM and N 2 adsorption-desorption techniques. The results showed the FZCS sorbent displayed the high removal rate (97.95%) for Titan Yellow (TY) anionic dye in aqueous solutions owing to its properties combining amino active functional amino group from the CS itself and higher specific surface area and mesoporous structure from the BSCS support. Isotherm data conform to the Langmuir isothermal model with a maximum adsorption capacity of 120.48 mg/g at 30 °C, suggesting monolayer adsorption of TY on the FZCS sorbent. The data were very well fitted to the pseudo-second-order kinetics. The adsorption capacity of FZCS could maintain about 70% after six cycles. The research indicated that FZCS would be a promising, eco-friendly and effective sorbent for anionic dye wastewater treatment in the near future., (Copyright © 2020. Published by Elsevier B.V.)

Improvised explosive devices (IEDs) represent the leading causes for casualties among civilians and soldiers in the present war (including counter-terrorism). Traumatic brain injury (TBI) caused by IEDs results in different degrees of impairment of cognition and behavior, but the exact brain pathophysiological mechanism following exposure to blast has not been clearly investigated. Here, we sought to establish a rat model of closed-head blast injury using compressed gas to deliver a single blast only to the brain without systemic injuries. The cognitive functions of these bTBI models were assessed by Morris Water Maze test (MWM test). The HE staining, flow cytometry, ELISA and Western Blotting were used to measure the effects of shock wave on general histology, regulatory T (Treg) cells percentage, inflammatory reactions, the expression and phosphorylation level of tau, respectively. In addition, the brain water content and 24 -h mortality were also assessed. As the distance from the blast source increased, the input pressure did not change, the overpressure decreased, and the mortality decreased. Receiver operating characteristic (ROC) curves for predicting 24 -h mortality using peak overpressure fits with the following areas under ROC curves: 0.833. In 2 weeks after blast injury, cognitive tests revealed significantly decreased performance at 20 cm distance from the blast (about 136.44 kPa) as demonstrated by increased escape latency in the acquisition phase, and decreased crossing numbers in the probe phase of MWM test. Interestingly, a single blast exposure (at 20 cm) lead to significantly increased tau phosphorylation at the Thr205 epitope but not at the Ser404 and Ser262 epitopes at 12 h, 24 h, 3d, and 7d after blast injury. Blast decreased the percentage of CD4+T cells, CD8+T cells, Treg cells and lymphocytes at different time points after blast injury, and blast increased the percentage of neutrophils at 12 h after blast injury and significantly increased IL-6 production at 12 h, 24 h and 3d after blast injury. In addition, blast lead to an increase of brain edema at 24 h and 3d after blast injury. However, no obvious alterations in brain gross pathology were found acutely in the blast-exposed rats. In conclusion, we established a rat model of simple craniocerebral blast injury characterized by impairment of cognitive function, Thr205 phosphorylation of tau, decreased Treg cells and increased inflammatory reactions and brain edema. We expect this model may help clarify the underlying mechanism after blast injury and possibly serve as a useful animal model in the development of novel therapeutic and diagnostic approaches., Competing Interests: Declaration of Competing Interest The authors have declared no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Four [Ag-Ag] 2+ unit-encapsulated trimetallic cages 1-4 were synthesized from one new tripodal ligand L and silver salts in different solvent systems by a one-pot method. The formation of coordination cages occurred simultaneously with the condensation of amino groups and ketone. The remarkable structural feature of cages 1-4 is their spontaneous incorporation of [Ag-Ag] 2+ cationic units. Moreover, the argentophilic interactions are modulated by the uncoordinated amino substituents. The study herein shows that modification and subtle changes of the cage structures could be realized by a one-pot synthetic method.

Background: Spinal neurosyphilis manifesting as a solitary syphilitic gumma is exceedingly rare. There are non-specific imaging findings and challenges in the diagnosis of spinal syphilitic gumma, which could be easily misdiagnosed as tumor lesions and require surgical resection or biopsy., Clinical Presentation: We report the case of a 45-year-old female patient who was diagnosed with Spinal syphilitic gumma. Our case is the first reported case of spinal cord syphilitic gumma with intradural-extramedullary and intramedullary involvement., Conclusion: Spinal syphilitic gumma exhibits diverse clinical manifestations, lacks specific imaging features, accompanied by the patient's history deliberately concealed. Since clinicians do not have sufficient knowledge about such rare cases, misdiagnosis and missed diagnosis will be likely. When there is clinical suspicion for spinal syphilitic gumma, clinicians should pay close attention to relevant medical history, carry out a comprehensive physical examination and specific serological tests and cerebrospinal fluid (CSF) analysis. In summary, in cases with stable neurologic conditions, a trial administration of intravenous penicillin with follow-up imaging may be the optimal treatment option, and in cases with rapid progression or acute exacerbation, a surgical resection together with systemic antibiotic treatment for syphilis after surgery may be the best treatment strategy., (© 2019 by the Association of Clinical Scientists, Inc.)

A limited number of studies have explored whether the role of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathogenesis of acute myocardial infarction (AMI) is sex specific. The purpose of the present study was to examine sex differences in plasma PCSK9 in Chinese patients with AMI. In this study, a total of 281 records from patients presenting with AMI were analyzed.We compared hospital data and plasma PCSK9 levels by sex difference for inpatients presenting with AMI. After 1 year of follow-up, major adverse cardiac events(MACE) were recorded. A Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. We found that, compared with male groups, PCSK9 levels were higher in female patients not only for overall patients with AMI but also for patients with ST-elevation myocardial infarction (STEMI) (median: 273.6 [215.6-366.8] vs. 325.1 [247.5-445.3] ng/ml, P = 0.0136; 273.4 [215.6-369.7] vs. 317.1 [249.6-450.1], P = 0.0275, respectively). The cumulative incidence of cardiac death and 1-year MACE were significantly higher in the female group compared with male group (10% vs. 2.74%, P = 0.025; 15% vs. 4.11%, P = 0.0054, respectively). On multivariate Cox regression analysis, female sex, total triglyceride, glycosylated hemoglobin A, and homocysteic acid were independent risk factors of 1-year MACE. There was no significant correlation between PCSK9 and 1-year MACE in total AMI patients. In conclusion, PCSK9 levels and 1-year MACE were higher in women with AMI than in men with AMI, however, female sex but not PCSK9 were significant correlated with the 1-year MACE. The clinical implications of this finding are worthy of further investigations and must be confirmed in larger cohorts.

Selenoprotein K (SELENOK) is primarily observed in the endoplasmic reticulum, and serves to maintain the normal physiological functions of skeletal muscle. Skeletal muscle development and regeneration are associated with significant changes in the expression of specific microRNAs (miRNAs). Downregulated SELENOK expression is observed in chicken muscles deficient of Se. However, the mechanisms of miRNA regulation of SELENOK expression remain elusive. Here, deep sequencing was used to detect the miRNA profiles of muscle in Se deficient (-Se group) and normal (C group) chickens. A dual-luciferase reporter assay was adopted to verify the relationship between SELENOK and gga-let-7f-3p. In addition, gga-let-7f-3p was either overexpressed or knocked-down in chicken myoblasts. Furthermore, the cells were treated with N-acetyl-l-cysteine (NAC) or hydrogen peroxide (H2O2) in order to probe the factors involved in oxidative stress, endoplasmic reticulum stress (ERS) and apoptosis, respectively. Relative to the C group, there were 132 differentially expressed miRNAs (including 57 upregulated and 75 downregulated) in the muscles of the -Se group. The dual-luciferase reporter assay showed that SELENOK was a primary target of gga-let-7f-3p. It was also observed that the overexpression or knock-down of gga-let-7f-3p significantly influenced the SELENOK expression. Moreover, NAC blocked mimics of ga-let-7f-3p, thus inducing oxidative stress, ERS and apoptosis. Simultaneously, gga-let-7f-3p inhibitors blocked the stimulant effects caused by H2O2 in chicken myoblasts. Furthermore, Se deficiency downregulated the SELENOK protein expression and induced oxidative stress, ERS and apoptosis in chicken muscles. In conclusion, the gga-let-7f-3p-SELENOK pathway played a pivotal role in Se deficiency mediated muscle injuries through the induction of oxidative stress and ERS, ultimately promoting apoptosis.

Porous chitin sorbents (PChs) with different content of chitin, ranging from 0.9% to 3.5%, were prepared by gel method with CaBr 2 ·xH 2 O/CH 3 OH solution and characterized by FT-IR, XRD and SEM. The adsorption isotherms and kinetic analysis of methylene blue (MB) onto PChs were studied. Experimental results illustrated lower crystallinity and more pores of PChs containing 3.5% chitin displayed higher adsorption capacity, the removal of MB was 79.8%. The adsorption equilibrium isotherm curve of MB onto PChs adsorbents conformed to the Freundlich equation. The PFO, PSO and Weber-Morris models were applied to fit with the adsorption kinetics. The results demonstrated the adsorption of MB might be the mass transfer of heterogeneous system and involve multiple diffusion steps. The adsorption capacity of PChs with 3.5% chitin can maintain 65% removal ratio of MB after being used six adsorption-desorption cycles. It was supposed that PChs may be a promising, cheap, environmentally friendly and efficient adsorbent for some dye wastewater treatment in the near future., (Copyright © 2018. Published by Elsevier B.V.)

Objects The aim of this trial was to evaluate the effect of short-term high-dose atorvastatin therapy on levels of high-sensitivity C-reactive protein (hs-CRP), malonaldehyde (MDA), endothelin-1(ET-1), matrix metalloproteinases (MMPs), and left ventricular (LV) remodeling in patients with first time attack of acute anterior myocardial infarction (AAMI) .Methods A hundred and three patients with first time attack of AAMI who underwent successful primary percutaneous coronary intervention were randomized to receive atorvastatin 40 mg once daily for 1 week followed by 20 mg once daily (intensive treatment group, IT group, n=49), or atorvastatin 20 mg once daily (standard treatment group, ST group, n=54). Plasma levels of hs-CRP, MDA, ET-1, MMP-2 and MMP-9 were measured on admission, at 1 week, 2 weeks and 6 months follow up and compared between the IT group and ST group. Echocardiography was performed on admission, at 2 week, and 1 year follow up. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were measured at each echocardiographic examination and compared between the IT group and ST group.Results Plasma levels of hs-CRP (F=7.718, P=0.009), ET-1 (F=7.882, P=0.006), MMP-9 (F=4.834, P=0.028) and pro-BNP (F=4.603, P=0.032) were significantly lower at 1 week after initial onset of AAMI in the IT group compared with the ST group. The changes of LVEDV, LVESV, and LVEF at the 1 year follow-up from the admission did not differ between the IT group and the ST group (t=0.722, P=0.444; t=1.228, P=0.221; t=1.354, P=0.187, repectively).Conclusions Short-term high-dose atorvastatin treatment for AAMI was associated with lower hs-CRP, ET-1 and MMP-9 levels compared to the standard dose treatment. However, this beneficial effect is not likely to related to the left ventricular remodeling.

Composite polymeric and ionic liquid (IL) electrolytes are some of the most promising electrolyte systems for safer battery technology. Although much effort has been directed towards enhancing the transport properties of polymer electrolytes (PEs) through nanoscopic modification by incorporating nano-fillers, it is still difficult to construct ideal ion conducting networks. Here, a novel class of three-dimensional self-assembled polymeric ionic liquid (PIL)-functionalized cellulose nano-crystals (CNC) confining ILs in surface-grafted PIL polymer chains, able to form colloidal crystal polymer electrolytes (CCPE), is reported. The high-strength CNC nano-fibers, decorated with PIL polymer chains, can spontaneously form three-dimensional interpenetrating nano-network scaffolds capable of supporting electrolytes with continuously connected ion conducting networks with IL being concentrated in conducting domains. These new CCPE have exceptional ionic conductivities, low activation energies (close to bulk IL electrolyte with dissolved Li salt), high Li + transport numbers, low interface resistances and improved interface compatibilities. Furthermore, the CCPE displays good electrochemical properties and a good battery performance. This approach offers a route to leak-free, non-flammable and high ionic conductivity solid-state PE in energy conversion devices., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid receptor, whose exact role in anxiety remains unknown. The present study was conducted to explore the possible mechanisms by which GPR55 regulates anxiety and to evaluate the effectiveness of O-1602 in the treatment of anxiety-like symptoms. Mice were exposed to two types of acute stressors: restraint and forced swimming. Anxiety behavior was evaluated using the elevated plus maze and the open field test. We found that O-1602 alleviated anxiety-like behavior in acutely stressed mice. We used lentiviral shRNA to selective ly knockdown GPR55 in the medial orbital cortex and found that knockdown of GPR55 abolished the anxiolytic effect of O-1602. We also used Y-27632, a specific inhibitor of ROCK, and U73122, an inhibitor of PLC, and found that both inhibitors attenuated the effectiveness of O-1602. Western blot analysis revealed that O-1602 downregulated the expression of GluA1 and GluN2A in mice. Taken together, these results suggest that GPR55 plays an important role in anxiety and O-1602 may have therapeutic potential in treating anxiety-like symptoms.

Objective: To investigate the impact of symptom onset to first medical contact (SO-to-FMC)time on the prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI). Methods: The clinical data of 341 consecutive STEMI patients, who were hospitalized to our hospital and received primary percutaneous coronary intervention(PCI) from August 2011 to April 2016, were retrospectively analyzed. The patients were divided into ≤90 min group (201 cases) and >90 min group (140 cases) according to the SO-to-FMC time. The treatment time, mortality and incidence of major adverse cardiac and cerebro-vascular events(MACCE) were analyzed. The risk factor of 1-year mortality after PCI and 1-year incidence of MACCE during the post-discharge follow-up period were analyzed by binary logistic regression analysis. The predictor of 4.5-year mortality after PCI was analyzed by multivariate Cox regression analysis. Methods The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P =0.023), first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P =0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P <0.001)were all significantly shorter in the ≤90 min group than i n >90 min group. The 30-day mortality (2.99% (6/201) vs. 7.86%(11/140), P =0.042), 1-year mortality (2.89 (5/173) vs. 9.57(11/115), P =0.015), 1-year incidence of MACCE during the post-discharge follow-up period(1.16%(2/173) vs. 6.96%(8/115), P =0.021), and 4.5-year cumulative mortality(3.00% vs. 11.20%, P =0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P =0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P =0.071). Results: The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P =0.023) , first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P =0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P <0.001) were all significantly shorter in the ≤90 min group than in >90 min group. The 30-day mortality(2.99% (6/201) vs. 7.86%(11/140), P =0.042), 1-year mortality (2.89(5/173) vs. 9.57(11/115), P =0.015), 1-year incidence of MACCE during the post-discharge follow-up period (1.16%(2/173) vs. 6.96%(8/115), P =0.021), and 4.5-year cumulative mortality (3.00% vs. 11.20%, P =0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P =0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P =0.071). Results of binary logistic regression analysis showed that the SO-to-FMC time >90 min was the risk factor of 1-year mortality( OR =2.90, 95% CI 1.22-6.92, P =0.016) and 1-year incidence of MACCE ( OR =5.19, 95% CI 1.21-22.20, P =0.026) during the post-discharge follow-up period. Multivariate Cox regression analysis demonstrated that the SO-to-FMC time >90 min was the risk factor of 4.5-year mortality after PCI in patients with STEMI ( HR =2.88, 95% CI 1.10-7.53, P =0.031). Conclusion: Shorting the SO-to-FMC time can significantly reduce the treatment time of STEMI patients, short and long-term mortalities and the incidence of MACCE, and improve the prognosis of patients with STEMI.

In addition to debilitating sensory and motor deficits, patients with spinal cord injury (SCI) may experience chronic hyperpathic pain (SCI-pain). Recent studies have revealed that translocator protein (TSPO) is involved in repairing neural cells as well as reducing anxiety and depression. However, the role of TSPO in SCI-pain and pain-induced depression remains unknown. The present study aimed to determine the effects of a new TSPO ligand, ZBD-2, on SCI-pain and consequent pain-induced depressive-like behaviors in mice. Treatment with ZBD-2 at either dose significantly attenuated the symptoms of chronic SCI-pain and pain-induced depressive-like behaviors. ZBD-2 reversed SCI-induced elevation of serum corticosterone levels, an index of hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, administration of ZBD-2 inhibited decreases in the expression of synaptic plasticity-related signaling proteins, including brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding protein (CREB). Moreover, ZBD-2 administration reversed chronic, SCI-induced gliocyte activation at the lesion site. Therefore, ZBD-2 may improve chronic SCI-pain and pain-induced depressive-like behaviors via suppression of gliocyte activation and restoration of the synaptic plasticity-related signaling systems., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Huntington's disease (HD) is an autosomal dominant inherited disease characterized by movement, psychiatric, and cognitive disorders. Previous research suggests that Praeruptorin C (Pra-C), an effective component in the root of Peucedanum praeruptorum dunn, a traditional Chinese medicine, may function in neuroprotection. The present study was conducted to evaluate the effectiveness of Pra-C in the treatment of HD-like symptoms in a 3-nitropropionic acid (3-NP) mouse model, and to explore the possible mechanism of the drug's activity. We treated 3-NP-injected mice with two different doses of Pra-C (1.5 and 3.0mg/kg) for 3 days. Motor behavior was tested using the open field test (OFT) and rotarod test, while psychiatric symptoms were tested using the forced swimming test (FST) and tail suspension test (TST). We found that Pra-C alleviated the motor deficits and depression-like behavior in the 3-NP-treated mice, and protected neurons from excitotoxicity. Western blot analysis revealed that Pra-C upregulated BDNF, DARPP32, and huntingtin protein in the striatum of 3-NP mice. These results taken together suggest that Pra-C may have therapeutic potential with respect to the movement, psychiatric, and cognitive symptoms of HD., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: To construct a recombinant lentiviral expression vectors carrying MEG3 and to evaluate its effects on XG-7 cell apoptosis., Methods: A full-length genomic fragment of human MEG3 was cloned from the pcDNA3.0-MEG3 packaging plasmid and was amplified by PCR. New restriction sites were introduced to be blunted with T4 DNA Ligase. The sequence of the amplified segments was sub-cloned into lentivirus expression vector pCDH-EF1-MCS-T2A-copGFP.The recombined lentiviral expression vector was transfected into 293T cells. FACS was used to detect the effect of MEG3 on XG-7 cell apoptosis after being infected by optimized MOI., Results: The recombined lentiviral expression vector pCDH-EF1-MEG3-copGFP was constructed successfully. The results showed that pCDH-EF1-MEG3-copGFP could increase the mRNA expression of MEG3 dramatically, its transfection efficiency was more than 90%. The apoptosis rate in XG-7 cells (26.8±2.8%) was very significantly higher than that of the control group (P<0.01)., Conclusion: The recombined lentiviral LncRNA expression vector targeting MEG3, pCDH-EF1-MEG3-copGFP, has been successfully constructed, the pCDH-EF1-MEG3-copGFP can induce the cell apoptosis in human myeloma cell lines. This study set up a basis to further explore the relationship between human myeloma cells and LncRNA-MEG3 gene.

Necrophoric behaviour is critical sanitation behaviour in social insects. However, little is known about the necrophoric responses of workers towards different developmental stages in a colony as well as its underlying mechanism. Here, we show that Solenopsis invicta workers display distinct necrophoric responses to corpses of workers and pupae. Corpses of workers killed by freezing (dead for <1 h) were carried to a refuse pile, but pupal corpses would take at least 1 day to elicit workers' necrophoric response. Metarhizium anisopliae-infected pupal corpses accelerated the necrophoric behaviour of resident workers, with 47.5% of unaffected corpses and 73.8% infected corpses discarded by 1 day post-treatment). We found that fungus-infected pupal corpses had a higher concentration of fatty acids (palmitic acid, oleic acid and linoleic acid) on their surface. We experimentally confirmed that linoleic and oleic acids would elicit a necrophoric response in workers. The appearance of linoleic and oleic acids appeared to be chemical signals involved in recognition of pupal corpses, and M. anisopliae infection could promote the accumulation of fatty acids on surface of pupal corpses resulting in accelerated necrophoric responses of workers.

Background: Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions. Plasmacytoid dendritic cells (pDCs) have been found to participate in the progression of atherosclerosis mainly through interferon α (IFN-α) production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation of pDCs in vitro in this study., Methods: Peripheral blood mononuclear cells isolated by Ficoll centrifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naïve T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively., Results: Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α (TNF-α) production from pDCs in a dose-dependent manner. In addition, the ability of priming naïve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment., Conclusion: Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.

Cystic fibrosis transmembrane conductance regulator (CFTR) has been demonstrated to be expressed in mature spermatozoa and correlated with sperm quality. Sperm CFTR expression in fertile men is higher than that in infertile men suffering from teratospermia, asthenoteratospermia, asthenospermia and oligospermia, but it is unknown whether CFTR is correlated with sperm parameters when sperm parameters are normal. In this study, 282 healthy and fertile men with normal semen parameters were classified into three age groups, group (I): age group of 20-29 years (98 cases, 27.1 ± 6.2), group (II): age group of 30-39 years (142 cases, 33.7 ± 2.6) and group (III): age group of more than or equal to 40 years (42 cases, 44.1 ± 4.6). Sperm concentration, total count and progressive motility were analysed by computer-assisted sperm analysis. Sperm morphology was analysed by modified Papanicolaou staining. Sperm CFTR expression was conducted by indirect immunofluorescence staining. There was a significant positive correlation (P < 0.001) between CFTR expression and sperm progressive motility (r = 0.221) and normal morphology (r = 0.202), but there were no correlations between sperm CFTR expression and semen volume, sperm concentration, sperm total count as well as male age (P > 0.05). Our findings show that CFTR expression is associated with sperm progressive motility and normal morphology in healthy and fertile men with normal sperm parameters, but not associated with the number of spermatozoa and male age., (© 2013 Blackwell Verlag GmbH.)

Background: G-quadruplexes are promising therapeutic targets for small molecules. In general, the introduction of steady positive charges through the in situ alkylation of nitrogen atoms within potential G-quadruplex ligands can significantly improve their quadruplex binding and stabilization abilities. However, our previous studies on bisaryldiketene derivatives showed that the derivative M4, whose central piperidone moiety is quaternized, exhibits a poor G-quadruplex stabilization ability., Methods: To clarify this unusual finding, CD, ITC, UV and NMR analyses were performed to determine the binding behaviors of M4 and its non-quaternized analog M2 to G-quadruplex DNA [d(TGGGT)]4. Molecular modeling approaches were also employed to help illustrate ligand-quadruplex DNA interactions., Results: The CD melting and ITC analyses revealed that M2 exhibited much stronger stabilization and binding abilities to [d(TGGGT)]4 compared to M4. Moreover, the CD and ITC analyses in combination with UV, NMR and MD simulations revealed that M2 tended to be end-stacked on the G-quartet, whereas M4 tended to be bound in the groove region. Analysis of the electrostatic potential showed that the charged surface of M4 was more positive than that of M2 and other reported ligands that bind to the G-quadruplex via end-stacking interactions., Conclusions: The results indicated that the different positively charged surfaces of M2 and M4 might be the key reason for their different binding modes. These different binding modes also lead to different binding affinities and stabilization abilities for [d(TGGGT)]4., General Significance: These results provide new clues for the rational design of G-quadruplex-binding small molecules with steady positive charges., (© 2013.)

κ-opioid receptor (κ-OR) activation with U50,488H, a selective κ-OR agonist, has been previously demonstrated to prevent against cardiac arrhythmias via stabilizing the synthesis and degradation of an integral membrane protein, Cx43, in gap junctions. However, the exact prevention mechanism remains unclear. The present study tested the hypothesis that the kappa OR agonist U50,488H mediates the prevention of arrhythmia through the regulation of intracellular calcium leading to the preservation of Cx43 protein. By performing electrocardiogram monitoring and immunoblotting in isolated Langendorff-perfused rat hearts, high concentrations of calcium-perfused rat hearts exhibited increased cardiac arrhythmias. Diminished expression of Cx43 protein was observed. The utilization of a whole-cell patch clamp technique revealed that U50,488H inhibited L-type calcium current in single ventricular myocytes in a dose-dependent manner. These effects were blocked by nor-binaltorphimine, potent and selective κ-OR antagonists. Administration of U50,488H before myocardial ischemia resulted in an attenuated of total arrhythmia scores. The attenuation effect was blocked by nor-binaltorphimine. The attenuation effect was antagonized both by Bay K8644, a L-type calcium channel agonist, and also by the Cx43 uncoupler heptanol. Finally, immunoblotting data demonstrated that the preservation of Cx43 protein conferred by U50,488H was reversed in the presence of Bay K8644. In summary, the present study demonstrates κ-OR activation with U50,488H may confer antiarrhythmic effects via modulation of the calcium-Cx43 pathway.

Impairment of pulmonary endothelium function in the pulmonary artery is a direct result of chronic hypoxia. This study is to investigate the vasculoprotective effects of U50,488H (a selective κ-opioid receptor agonist) and its underlying mechanism in hypoxia-induced pulmonary artery endothelial functional injury. Chronic hypoxia was simulated by exposing the rats to 10% oxygen for 2 wk. After hypoxia, right ventricular pressure (RVP) and right ventricular hypertrophy index (RVHI) were measured. The pulmonary vascular dysfunction, effect of nitric oxide synthase inhibitor (l-NAME) on the relaxation of U50,488H, and level of nitric oxide (NO) were determined. In vitro, the signaling pathway involved in the anti-apoptotic effect of U50,488H was investigated. Cultured endothelial cells were subjected to simulated hypoxia, and cell apoptosis was determined by TUNEL staining. U50,488H (1.25 mg/kg) significantly reduced RVP and RVHI in hypoxia. U50,488H markedly improved both pulmonary endothelial function (maximal vasorelaxation in response to ACh: 74.9 ± 1.8%, n = 6, P <0.01 vs. hypoxia for 2 wk group) and increased total NO production (1.65 fold). U50,488H relaxed the pulmonary artery rings of the hypoxic rats. This effect was partly abolished by l-NAME. In cells, U50,488H both increased NO production and reduced hypoxia-induced apoptosis. Moreover, pretreatment with nor-binaltorphimine (nor-BNI, a selective κ-opioid receptor antagonist), PI3K inhibitor, Akt inhibitor or l-NAME almost abolished anti-apoptotic effect exerted by U50,488H. U50,488H resulted in increases in Akt and eNOS phosphorylation. These results demonstrate that pretreatment with U50,488H attenuates hypoxia-induced pulmonary vascular endothelial dysfunction in an Akt-dependent and NO-mediated fashion.

Study Question: Does adjudin disrupt chloride ion (Cl⁻) ion transport function in human sperm and impede sperm capacitation and fertilizing ability in vitro?, Summary Answer: In this study the results indicate that adjudin is a potent blocker of Cl⁻ channels: disrupting Cl⁻ ion transport function results in a decline in sperm capacitation and fertilizing ability in humans in vitro., What Is Known Already: Although our previous studies have demonstrated that adjudin exerts its effect by disrupting sertoli-germ cell adhesion junctions, most notably apical ectoplasmic specialization by targeting testin and actin filament bundles that disrupts the actin-based cytoskeleton in sertoli cells, it remains unclear whether adjudin impedes Cl⁻ ion transport function in the human sperm., Study Design, Size and Duration: Semen samples were obtained from 45 fertile men (aged 25-32). Spermatozoa were isolated from the semen in the human tube fluid (HTF) medium by centrifugation through a discontinuous Percoll gradient, and incubated with adjudin at 10 nM-10 µM and/or other reagents under capacitating conditions for 0-5 h., Participants/materials, Setting, Methods: We evaluated the effect of adjudin and different reagents on sperm functions with which they were incubated at 37 °C. Sperm motility and hyperactivation were analyzed by a computer-assisted sperm analysis (CASA) system. Sperm capacitation and the acrosome reaction were assessed by chlortetracycline fluorescence staining. Sperm fertilizing ability was evaluated by sperm penetration of zona-free hamster egg assay, and cellular cAMP levels in spermatozoa were quantified by the EIA kit. The proteins tyrosine, serine and threonine phosphorylation in the presence or absence of adjudin were analyzed by means of a immunodetection of spermatozoa, especially, compared the effect of adjudin on sperm hyperactivation and capacitation in the complete HTF medium with the Cl⁻-deficient HTF medium as well as the various Cl⁻ channel blockers., Main Results and the Role of Chance: Adjudin significantly inhibited sperm hyperactivation but not sperm motility. Adjudin-induced inhibition of sperm capacitation was reversible, and it was found to block the rhuZP₃β- and progesterone-induced acrosome reaction in a dose-dependent manner. Adjudin also blocked sperm penetration of zona-free hamster eggs, and significantly inhibited both forskolin-activated transmembrane adenylyl cyclase and soluble adenylyl cyclase activities leading to a significant decline in the cellular cAMP levels in human spermatozoa. Adjudin failed to reduce sperm protein tyrosine phosphorylation but it did prevent sperm serine and threonine protein phosphorylation. Interestingly, adjudin was found to exert its inhibitory effects on sperm capacitation and capacitation-associated events only in the complete Cl⁻-HTF medium but not Cl⁻-deficient medium, illustrating the likely involvement of Cl⁻. Adjudin inhibits the fertility capacity of human sperm is mediated by disrupting chloride ion and its transport function., Limitations, Reasons for Caution: This study has examined the effect of adjudin only on human sperm capacitation and fertilizing ability in vitro and thus has some limitations. Further investigations in vivo are needed to confirm adjudin is a potent male contraceptive., Wider Implications of the Findings: Our studies demonstrated that adjudin inhibition of capacitation is reversible and its toxicity is low, opening the door for the examination of adjudin as a mediator of male fertility control. Adjudin may be a safe, efficient and reversible male antifertility agent and applicable to initial clinical trials of adjudin as a male antifertility agent in humans. STUDING FUNDING/COMPETING INTEREST(S): This work was supported by the National Basic Research Program of China (2006CB504002), the Nature Science Foundation of China (Nos. 81000244 and 81170554), Zhejiang Project of Science and Technology (2011C23046), the Nature Science Fund of Zhejiang province (Nos.Y2100058 and Y2090236), the key Science and Technology Innovation Team of Zhejiang Province (No.2012R10048-07) and the National Institutes of Health (NICHD U54 HD029990 project 5), USA. The authors declare no conflict of interest.

In addressing the challenge of the low survival rates of rats with myocardial ischaemia, we developed a novel respiratory mask. We tested this mask on the rat model. We gave attention to several features of the mask: (1) shape, (2) size, (3) inlet, (4) outlet, (5) compatibility between rat head and the mask, (6) connection between mask and ventilator. We found certain features, especially to influence mask efficacy. These features include: mask shape, mask inlet and outlet, mask connection to the respiratory machine, mask mount on the rat head. We examined the rat mask in a model of chronic myocardial ischaemia; our model was the ligation of the coronary artery. The rats with the masks experienced an increase in survival by a factor of 50-90% compared with rats deprived of the masks. Towards the examination of myocardial ischaemia, our new mask may offer a platform replete with both efficiency and stability.

Phospholipase A2 (PLA(2)) plays a major role during acrosomal exocytosis (AE) in mammalian spermatozoa, but the identity of PLA(2) subtypes present in spermatozoa remains elusive. This study explored whether secretory PLA(2) Group IID (sPLA(2)-IID) isoform is present in human spermatozoa and whether it is involved in AE. Localization and expression of sPLA(2)-IID in human spermatozoa were explored by immunofluorescence staining and Western blot analysis. Occurrence of AE was evaluated by triple staining, and arachidonic acid (AA) levels were quantified by gas chromatography-mass spectrometry. Sperm motion parameters and hyperactivation were analyzed by computer-assisted sperm analysis. sPLA(2)-IID was localized in the postacrosomal region of the head and the midpiece of tail in human sperm. A 16-kd protein band was detected by Western blotting in sperm extracts. Progesterone-induced AE was significantly inhibited in a concentration-dependent manner using a sPLA(2)-IID neutralizing antibody. The increase in AA levels seen during progesterone-stimulated exocytosis was significantly abrogated by the antibody. The sPLA(2)-IID antibody significantly inhibited hyperactivation, sperm curvilinear velocity, and amplitude of lateral head displacement, but it did not affect the proportion of motile sperm. In conclusion, sPLA(2)-IID is present at the head and midpiece in the human sperm, and activation of such sPLA(2)-IID seems to be involved in AE. Therefore, sPLA(2)-IID isoform plays a functional role during the AE in human sperm.

Our previous studies have shown that the cystic fibrosis transmembrane conductance regulator (CFTR) was important for capacitation and fertilisation in mouse, guinea pig and human spermatozoa. However, it is unclear whether CFTR is correlated with ovum fertilisation rate. The present study was to test the possible relationship between spermatozoa CFTR protein expression rate in healthy men and ovum fertilisation rate during in vitro fertilisation. Ninety-four couples for female factor infertility for IVF-ET treatments were retrospectively studied. All the patients were divided into three groups based on the fertilisation rate of ovum in vitro. It was performed to explore whether there were differences in sperm CFTR protein expression rate among the three groups and the relevance between CFTR protein expression rate and ovum fertilisation rate. Our study showed that there was no significant differences in sperm CFTR protein expression rate among the three groups (F = 0.614, P = 0.544), and the relevance between spermatozoa CFTR protein expression rate and ovum fertilisation rate was not significantly different (r = 0.013, P = 0.904). These results further suggest that CFTR protein expression rate in healthy men spermatozoa was not associated with ovum fertilisation rate and thus we cannot predict ovum fertilisation results by sperm CFTR protein expression rate., (© 2011 Blackwell Verlag GmbH.)

The aim of this study was to investigate the underlying mechanism that dynorphin, an endogenous kappa opioid receptor (κ-OR) agonist, triggers antiapoptotic effect of postconditioning (Postcon). In addition to vehicle treatment, Sprague Dawley rats (n = 6) underwent a 30-minute left anterior descending occlusion followed by 2 hours of reperfusion with or without a Postcon stimulus. The selective κ-OR antagonist nor-binaltorphimine (Nor-BNI) was administered intravenously 5 minutes before reperfusion. Infarct size was determined by using 2,3,5-triphenyltetrazolium chloride staining. Blood plasma concentrations of creatine kinase (CK) and lactate dehydrogenase (LDH) and myocardial caspase-3 activity were analyzed spectrophotometrically. Myocardial apoptosis was analyzed by the detection of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling. Immunoreactive dynorphin in blood serum and myocardium was measured by means of an antigen-competitive enzyme-linked immunosorbent assay. Infarction size, caspase-3 activity, apoptotic index, and CK and LDH levels were significantly higher in the ischemic/reperfusion group than in the vehicle group (P < 0.01). Postcon significantly reduced infarction size, caspase-3 activity, apoptotic index, CK and LDH levels (P < 0.01 vs. ischemic/reperfusion). Dynorphin content significantly increased after Postcon (P < 0.01). All the effects described above were abolished by Nor-BNI, with the exception of dynorphin content. We found that cardiac protection and antiapoptotic effect of Postcon is mediated by the activation of κ-OR. Effect of Postcon is mediated, at least partially, by enhanced dynorphin expression.

In the journey from the male to female reproductive tract, mammalian sperm experience a natural osmotic decrease (e.g., in mouse, from ~415 mOsm in the cauda epididymis to ~310 mOsm in the uterine cavity). Sperm have evolved to utilize this hypotonic exposure for motility activation, meanwhile efficiently silence the negative impact of hypotonic cell swelling. Previous physiological and pharmacological studies have shown that ion channel-controlled water influx/efflux is actively involved in the process of sperm volume regulation; however, no specific sperm proteins have been found responsible for this rapid osmoadaptation. Here, we report that aquaporin3 (AQP3) is a sperm water channel in mice and humans. Aqp3-deficient sperm show normal motility activation in response to hypotonicity but display increased vulnerability to hypotonic cell swelling, characterized by increased tail bending after entering uterus. The sperm defect is a result of impaired sperm volume regulation and progressive cell swelling in response to physiological hypotonic stress during male-female reproductive tract transition. Time-lapse imaging revealed that the cell volume expansion begins at cytoplasmic droplet, forcing the tail to angulate and form a hairpin-like structure due to mechanical membrane stretch. The tail deformation hampered sperm migration into oviduct, resulting in impaired fertilization and reduced male fertility. These data suggest AQP3 as an essential membrane pathway for sperm regulatory volume decrease (RVD) that balances the "trade-off" between sperm motility and cell swelling upon physiological hypotonicity, thereby optimizing postcopulatory sperm behavior.

Cystic fibrosis (CF) is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB) expression in the testes of CFTR knockout mice. The involvement of CFTR in HCO(3) (-) transport and the expression of the HCO(3) (-) sensor, soluble adenylyl cyclase (sAC), are demonstrated for the first time in the primary culture of rat Sertoli cells. Inhibition of CFTR or depletion of HCO(3) (-) could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. Decreased CFTR and CREB expression are also observed in human testes with azoospermia. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various CF-related diseases.

Background: Our previous studies have demonstrated the cystic fibrosis transmembrane conductance regulator (CFTR) is important for capacitation and male fertility in mouse and guinea pig spermatozoa. However, the exact function of CFTR on human sperm fertilizing capacity, and correlation with sperm quality has not been established. The present study may shed light on some unexplained male infertility, and on a possible new method for diagnosis of male infertility and strategy for male contraception., Methods: To assess the effect of CFTR on human sperm fertilizing capacity, we examined sperm capacitation and the acrosome reaction using chlortetracycline staining, analyzed sperm hyperactivation by computer-assisted semen analysis (CASA), measured intracellular cAMP levels using ElA and evaluated sperm penetration of zona-free hamster eggs assay in fertile men. The percentage of spermatozoa expressing CFTR from fertile, healthy and infertile men (mainly teratospermic, asthenoteratospermic, asthenospermic and oligospermic) was conducted by indirect immunofluorescence staining., Results: Progesterone significantly facilitated human sperm capacitation and ZP3 triggered the acrosome reaction, both were significantly inhibited by CFTR inhibitor-172 (CFTRinh-172; 10 nM-1 microM) in a dose-dependent manner. The presence of 100 nM CFTRinh-172 markedly depressed intracellular cAMP levels, sperm hyperactivation and sperm penetration of zona-free hamster eggs. In addition, the percentage of spermatozoa expressing CFTR in the fertile men was significantly higher than healthy and infertile men categories (P < 0.01)., Conclusions: CFTR is essential for human sperm fertilizing capacity and the impairment of CFTR expression in spermatozoa is correlated with a reduction of sperm quality. These results suggest that defective expression of CFTR in human sperm may lead to the reduction of sperm fertilizing capacity.

Capacitation requires removal of proteins secreted by the cauda epididymis. Previously, we isolated and cloned the HongrES1 gene from rat cauda epididymis and found that it was exclusively expressed there. Here we report that HongrES1 mRNA is also expressed in the guinea pig cauda epididymis using Northern blot analysis, and the molecular weight of its cognate protein is approximately 48 kDa by Western blot analysis. Therefore, we investigated whether HongrES1 was involved in regulation of sperm capacitation in guinea pig. The results show that HongrES1 antisera (HA) significantly enhances sperm capacitation with maximal stimulation at a dilution of 1:500. Capacitation was reversed when capacitated spermatozoa were re-exposed to HongrES1 protein (HP, 0.25 microg/ml). In other words, HP acted as a decapacitation factor. HA accelerated the onset of capacitation and promoted a sperm hyperactivated motility response. Sperm capacitation was accelerated by HA stimulation of extracellular calcium influx while HP prevented extracellular calcium from influxing. Indirect immunofluorescence staining finds HP localized over the acrosomal anterior region of the sperm head, which exfoliates gradually during capacitation incubation, and completely disappeared after the acrosome reaction. Thus, HongrES1 expressed by the cauda epididymis is a novel molecule that regulates the physiology of guinea pig sperm prior to fertilization., ((c) 2009 Wiley-Liss, Inc.)

This study was designed to determine whether HCO(3)(-) and Cl(-) are required for the activation of the GABA(A) receptor/Cl(-) channel (GBRC) by GABA and the subsequent capacitation of rat sperm. Spermatozoa from adult Sprague Dawley rats were incubated in four different media: modified complete rat fertilization medium (mRFM), Cl(-)-deficient (Cl(-)-DF) mRFM, HCO(3)(-)-DF mRFM, and Cl(-)-DF HCO(3)(-)-DF mRFM, with or without GBRC agonists (GABA and progesterone) or GBRC antagonists (bicuculline and picrotoxin) for 0-6 h under capacitating conditions. Sperm capacitation and hyperactivation were assessed by chlortetracycline staining and computer-assisted sperm analysis, respectively. The results showed that GABA added to the mRFM accelerated capacitation and hyperactivation, followed by increase in the acrosome reaction, reaching maximum value after 5 h. Progesterone also accelerated sperm capacitation and hyperactivation. Bicuculline and picrotoxin, antagonists of GABA, blocked the effects of both GABA and progesterone acceleration of sperm capacitation and hyperactivation. Sperm capacitation required both Cl(-) and HCO(3)(-). These results indicate that activation of GBRC may contribute to sperm capacitation and hyperactivation, and that both HCO(3)(-) and Cl(-) are essential. This is the first report of a close relationship between HCO(3)(-)/Cl(-) transport and the activation of GBRC in rat sperm capacitation and hyperactivation.

Our previous study demonstrated the involvement of cystic fibrosis transmembrane conductance regulator (CFTR) in transporting bicarbonate that is necessary for sperm capacitation; however, whether its involvement is direct or indirect remains unclear. The present study investigated the possibility of a Cl-/HCO3- exchanger (solute carrier family 26, number 3 [SLC26A3]) operating with CFTR during guinea pig sperm capacitation. Incubating sperm in media with various concentrations of Cl- resulted in varied percentages of capacitated sperm in a concentration-dependent manner. Depletion of Cl-, even in the presence of HCO3-, abolished sperm capacitation and vice versa, indicating the involvement of both anions in the process. Capacitation-associated HCO3--dependent events, including increased intracellular pH, cAMP production, and protein tyrosine phosphorylation, also depend on Cl- concentrations. Similar Cl- dependence and inhibitor sensitivity were observed for sperm-hyperactivated motility and for sperm-egg fusion. The expression and localization of CFTR and SLC26A3 were demonstrated using immunostaining and Western blot analysis. Taken together, our results indicate that Cl- is required for the entry of HCO3- that is necessary for sperm capacitation, implicating the involvement of SLC26A3 in transporting HCO3-, with CFTR providing the recycling pathway for Cl-.

Objective: This study examined the relationship between the ultrastructural alterations of alveolar epithelial cells type II (AEC-II) and pulmonary surfactant protein A (SP-A) levels in the lung tissue of young rats with acute lung injury (ALI) in order to explore the possible mechanism of ALI., Methods: Forty-eight young Sprague-Dawley rats were randomly divided into control and ALI groups. The rats in the ALI group were intraperitoneally injected with 4 mg/kg of lipopolysaccharide (LPS) in order to induce ALI. The control subjects were injected with the same volume of normal saline. Rats were sacrificed at 24, 48 and 72 hrs after LPS or NS injection. Lung samples were obtained from the lower parts of the left lung and fixed with 2.5% glutaraldehyde for transmission electron microscope examination and for Western blot test of SP-A., Results: The microvilli of AEC-II disappeared 24 hrs after LPS injection. After 24 and 48 hrs of LPS injection, lamellar body (Lb) increased in number, enlarged in size and reduced in density, and the ring-like arrangement of Lb was present. By 48 hrs after LPS injection, giant Lb with vacuole-like deformity appeared. The contents of lung SP-A in the ALI group 24 hrs (6.52+/-0.62 vs 5.02+/-0.35; P<0.01) and 48 hrs (6.65+/-0.62 vs 5.01+/-0.36; P<0.01) after LPS injection were significantly higher than those in the control group. By 72 hrs after LPS injection, Lbs ruptured and were reduced in number. The shape of the nuclei was irregular and the border was blurred. The content of lung SP-A was greatly reduced in the ALI group 72 hrs after LPS injection compared with that in the control group (3.87+/-0.50 vs 5.22+/-0.36; P<0.01)., Conclusions: The alterations of AEC-II and lung SP-A were time-dependent in young rats with ALI induced by LPS. In the early stage of ALI, the lung SP-A content showed a compensatory increase. With the increasing injury of AEC-II cells, the secretion of SP-A presented with a decompensation and the lung SP-A content decreased. This may be one possible mechanism for the development of ARD.

Objective: To determine the contents of tetramethylpyrazine (TMP) and ferulic acid in Ligusticum chuanxiong from different producing areas and seasons., Methods: The contents of TMP and ferulic acid were determined by HPLC, and then analyzed by Chromatographic Fingerprints., Results: The contents of TMP and ferulic acid from different seasons were obviously different from each other. It was much higher in "laoxiong" than that in "naixiong". The similarity of fingerprints was high if the samples were collected from the same season, or the same areas, but not different seasons., Conclusions: The contents of TMP and ferulic acid were different from different producing areas. The evident variety of Ligusticum chuanxiong's fingerprints from different collecting seasons, Laoxiong and Naixiong, was not relevant for clinical use as the same medicine.

Objective: To investigate the advantages of using the preoperative computer-aided design system (CAD) in total hip replacement (THR)., Methods: From March 2002 to September 2005, 182 patients who underwent primary THR were screened and divided into 2 groups randomly. CAD and traditional preoperative templating were used in preoperative planning respectively., Results: In group using CAD, the migration of the center of acetabulum was smaller, and the discrepancy of the limb length and the abductor force lever arm were fewer. All the differences above were significantly different., Conclusions: CAD helps remove much of the guesswork during surgery, and the implant can be more precise fitting to the patient. And equal limb lengths and balanced abductor force can be restored more accurately.