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Objective: To investigate the influence of different post-filter ionic calcium (Ca 2+ ) gradients (0.25-0.35 mmol/L vs>0.35-0.50 mmol/L) on the extracorporeal lifetime of local citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT). Methods: Patients who underwent CRRT with RCA at West China Hospital of Sichuan University from March 2021 to June 2022 were retrospectively selected. The basic information and the values of post-filter Ca 2+ at 0, 2, and 6 hours after the start of treatment and every 6 hours thereafter were collected. The patients were divided into low concentration group (0.25-0.35 mmol/L mmol/L) and high concentration group (>0.35-0.50 mmol/L) according to the mean value of Ca 2+ concentration per treatment, and propensity score matching was performed in a 1∶1 ratio to evaluate the effect of post-filter [iCa 2+ ] on the duration of extracorporeal circulation in different groups. Results: A total of 232 patients (147 males and 85 females) aged (58.2±16.9) years were enrolled. There were 431 cases treated with CRRT for 12 592 h, including 317 cases (73.5%) in the low concentration group and 114 cases (26.5%) in the high concentration group. The baseline data of the two groups were matched and analyzed. Coagulation events occurred in 54.9% (62/113) and 54.0% (61/113) in the low and high concentration groups, respectively ( P =0.894). The median survival on extracorporeal circulation was 65.0 (29.0, 72.0) h and 68.0 (31.5, 72.0) h in the two groups, respectively ( P =0.805). Multivariate Cox regression analyses showed that post-filter [iCa 2+ ] had no effect on extracorporeal life expectancy ( HR =0.99, 95% CI :0.55-1.79). Conclusion: During CRRT treatment with RCA, the desired anticoagulant effect can still be achieved when the post-filter [iCa 2+ ] target was set to 0.25-0.50 mmol/L.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe 3 O 4 @Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab 1 -CEA, Ab 1 -AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL -1 -100 ng·mL -1 with detection limits of 33.34 and 17.02 fg·mL -1 ( S / N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

The detailed dynamics of small molecular nonvolatile chemical and bacterial diversities, as well as their relationship are still unclear in the manufacturing process of Keemun black tea (KMBT). Herein, mass spectrometry-based untargeted metabolomics, Feature-based Molecular Networking (FBMN) and bacterial DNA amplicon sequencing were used to investigate the dense temporal samples of the manufacturing process. For the first time, we reveal that the pyrogallol-type catechins are oxidized asynchronously before catechol-type catechins during the black tea processing. Rolling is the key procedure for forming the small molecular nonvolatile metabolite profile (SMNMetProf), increasing the metabolite richness, and then shaping the bacterial community structure in the KMBT manufacturing process, which decreases both molecular weight and molecular polarity of the small molecular nonvolatile metabolites. The SMNMetProf of black tea is formed by the endogenous enzymatic oxidation of tea leaves, rather than bacterial fermentation., 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 © 2024 Elsevier Ltd. All rights reserved.)

Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL -1 to 10 ng mL -1 ), low detection limit (14.52 fg mL -1 ), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCβ), cellular cGMP, and phosphorylation of VASP ser239 . Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated β-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded β-catenin expression. As β-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with β-catenin function through the activation of a PDE5/cGMP functional axis.

Epidural electrical stimulation is a new treatment method for spinal cord injury (SCI). Its efficacy and safety have previously been reported. Rehabilitation treatment after epidural electrical stimulation is important to ensure and improve the postoperative efficacy of epidural electrical stimulation in patients with SCI. Considering that electromyography (EMG)-induced rehabilitation treatment can accurately match the muscle contraction of patients with SCI, we designed a study protocol for a prospective, randomized controlled trial. In this trial, on the premise of adjusting the spinal cord electrical stimulator to obtain the maximum EMG signal of the target muscle, patients with SCI receiving epidural electrical stimulation will undergo EMG-induced rehabilitation treatment. Recovery of muscle strength of key muscles, quality of life, safety and therapeutic effects will be monitored. Twenty patients with SCI who are scheduled to undergo epidural electrical stimulation in Shanghai Ruijin Rehabilitation Hospital will be randomly divided into two groups with 10 patients per group. The control group will receive conventional rehabilitation treatment. The EMG-induced rehabilitation group will receive EMG-induced rehabilitation treatment of the target muscles of the upper and lower limbs based on conventional rehabilitation treatment. After rehabilitation treatment, follow up for all patients will occur at 2 weeks and 1, 3 and 6 months. The primary outcome measure of this trial will be evaluation of target muscle recovery using the Manual Muscle Testing grading scale. Secondary outcome measures will include modified Barthel Index scores, integrated EMG values, the visual analogue scale, Spinal Cord Independence Measure scores, and modified Ashworth scale scores. The safety indicator will be the incidence of adverse events. This trial will collect data regarding the therapeutic effects of EMG-induced rehabilitation in patients with SCI receiving epidural electrical stimulation for 6 months after rehabilitation treatment. Findings from this trial will help develop rehabilitation methods in patients with SCI after epidural electrical stimulation. This study protocol was approved by Ethics Committee of Shanghai Ruijin Rehabilitation Hospital (Approval No. RKIRB2022-12) on February 15, 2022 and was registered with Chinese Clinical Trial Registry (registration number: ChiCTR2200061674; date: June 30, 2022). Study protocol version: 1.0., Competing Interests: None

Fibrosis and fibroblast activation usually occur in the tissues surrounding a malignant tumor; therefore, anti-fibrotic drugs are used in addition to chemotherapy. A reliable technique for evaluating the combined effects of anti-fibrotic drugs and anticancer drugs would be beneficial for the development of an appropriate treatment strategy. In this study, we manufactured a three-dimensional (3D) co-culture system of fibroblasts and lung cancer cell spheroids in Matrigel supplemented with fibrin (fibrin/Matrigel) that simulated the tissue microenvironment around a solid tumor. We compared the efficacy of an anticancer drug (cisplatin) with or without pretreatments of two anti-fibrotic drugs, nintedanib and pirfenidone, on the growth and invasion of cancer cells co-cultured with fibroblasts. The results showed that the addition of nintedanib improved cisplatin's effects on suppressing the growth of cancer cell spheroids and the invasion of cancer cells. In contrast, pirfenidone did not enhance the anticancer activity of cisplatin. Nintedanib also showed higher efficacy than pirfenidone in reducing the expression of four genes in fibroblasts associated with cell adhesion, invasion, and extracellular matrix degradation. This study demonstrated that the 3D co-cultures in fibrin/Matrigel would be useful for assessing the effects of drug combinations on tumor growth and invasion., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

In the biosynthesis of the iron-guanylylpyridinol (FeGP) cofactor, 6-carboxymethyl-5-methyl-4-hydroxy-2-pyridinol (1) is 3-methylated to form 2, then 4-guanylylated to form 3, and converted into the full cofactor. HcgA-G proteins catalyze the biosynthetic reactions. Herein, we report the function of two radical S-adenosyl methionine enzymes, HcgA and HcgG, as uncovered by in vitro complementation experiments and the use of purified enzymes. In vitro biosynthesis using the cell extract from the Methanococcus maripaludis ΔhcgA strain was complemented with HcgA or precursors 1, 2 or 3. The results suggested that HcgA catalyzes the biosynthetic reaction that forms 1. We demonstrated the formation of 1 by HcgA using the 3 kDa cell extract filtrate as the substrate. Biosynthesis in the ΔhcgG system was recovered by HcgG but not by 3, which indicated that HcgG catalyzes the reactions after the biosynthesis of 3. The data indicated that HcgG contributes to the formation of CO and completes biosynthesis of the FeGP cofactor., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

[Fe]-hydrogenase, the third type of natural hydrogenase, is capable to heterolytically activate hydrogen molecule and transfer the resulting hydride to an unsaturated substrate, making it a promising hydrogenation catalyst. Over the last three decades, fruitful results on this enzyme have been achieved. In this review, we have summarized the major progresses about this enzyme including its structural characterisation, catalytic mechanism, cofactor biosynthesis, mimetic model development as well as artificial enzymes construction. In the meanwhile, challenges and opportunities of this enzyme and its mimetic systems in the application of synthetic chemistry and others are discussed., (© 2022 Wiley-VCH GmbH.)

Background: Tunneling nanotubes (TNTs) are special membrane structures for intercellular communications. Vital cargoes (such as mitochondria) could be delivered from healthy cells to rescue damaged ones through TNTs. The TNTs could be utilized for the purpose of systematic delivery of therapeutic agents between cells. However, there are insufficient studies on the controlled enhancement of TNT formations. The purpose of this study is to understand how macrophages influence the TNT formation in cancer cells., Results: Here we compared the capabilities of inducing TNTs in human pancreatic cancer cells (PANC-1) of the media conditioned by M0, M1 and M2 macrophages derived from THP-1 cells. The M0 and M1 macrophage conditioned media promoted TNT formation. Using a focused ion beam to cut through a TNT, we observed tunnel-like structures inside dense cytoskeletons with scanning electron microscopy. The TNT formation correlated with raised motility, invasion, and epithelial-mesenchymal transition in the PANC-1 cells. Mitochondria and lysosomes were also found to be transported in the TNTs., Conclusions: These results suggest that TNT formation could be one of the responses to the immune stress in pancreatic cancer cells caused by M0 and M1 macrophages. This finding is valuable for the development of macrophage-targeting cancer therapy., (© 2022. The Author(s).)

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.

In the FeGP cofactor of [Fe]-hydrogenase, low-spin Fe II is in complex with two CO ligands and a pyridinol derivative; the latter ligates the iron with a 6-acylmethyl substituent and the pyridinol nitrogen. A guanylylpyridinol derivative, 6-carboxymethyl-3,5-dimethyl-4-guanylyl-2-pyridinol (3), is produced by the decomposition of the FeGP cofactor under irradiation with UV-A/blue light and is also postulated to be a precursor of FeGP cofactor biosynthesis. HcgC and HcgB catalyze consecutive biosynthesis steps leading to 3. Here, we report an in vitro biosynthesis assay of the FeGP cofactor using the cell extract of the ΔhcgBΔhcgC strain of Methanococcus maripaludis, which does not biosynthesize 3. We chemically synthesized pyridinol precursors 1 and 2, and detected the production of the FeGP cofactor from 1, 2 and 3. These results indicated that 1, 2 and 3 are the precursors of the FeGP cofactor, and the carboxy group of 3 is converted to the acyl ligand., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

To investigate the efficacy and value of optical genome mapping (OGM) in detecting chromosomal structural variations. In a clinical study about high-precision analysis of genomic structural variation for complex genetic diseases, a retrospective study was performed on the cases with karyotyping at the department of Obstetrics and Gynecology, and Endocrinology of Peking Union Medical College Hospital from January to December 2021. Ten cases with abnormal karyotype was detected by OGM. Partial cases were verified by fluorescence in situ hybridization (FISH), SNP array or CNV-seq. Results of ten cases, nine were detected with abnormality by OGM, including unbalanced chromosomal rearrangements ( n =3), translocation ( n =5) and paracentric inversion ( n =1), and the results were in concordance with other standard assays. However, one case with breakpoint and reconnected at centromere has not been detected. In conclusion, ten samples were comprehensively analyzed by karyotyping, FISH, SNP array or CNV-seq, and OGM, and results demonstrated that optical genome mapping as a new technology can not only detect unbalanced rearrangements such as copy number variants as well as balanced translocations and inversions, but more importantly, it can refine breakpoints and orientation of duplicated segments or insertions. So it can contribute to the diagnosis of genetic diseases and prevent birth defect. However, the current technology is not yet capable of detecting breakpoints of balanced structural variations lying within unmapped regions.

A unique ratiometric MALDI-MS strategy is proposed for the convenient and reliable quantitation of alkaline phosphatase based on the homogeneous enzymatic cleavage of a coded phosphopeptide (CPP)-triggered double-signal output. The dynamic range can be tuned by simply adjusting the primary concentration of CPP. The proposed strategy is also capable of being challenged by real human serum, and thus it may offer a wonderful approach for the convenient identification and quantitation of various enzyme activities in clinical diagnosis.

We present herein an unprecedented diastereoconvergent synthesis of vicinal diamines from diols through an economical, redox-neutral process. Under cooperative ruthenium and Lewis acid catalysis, readily available anilines and 1,2-diols (as a mixture of diastereomers) couple to forge two C-N bonds in an efficient and diastereoselective fashion. By identifying an effective chiral iridium/phosphoric acid co-catalyzed procedure, the first enantioconvergent double amination of racemic 1,2-diols has also been achieved, resulting in a practical access to highly valuable enantioenriched vicinal diamines., (© 2021 Wiley-VCH GmbH.)

The reconstitution of [Mn]-hydrogenases using a series of Mn I complexes is described. These complexes are designed to have an internal base or pro-base that may participate in metal-ligand cooperative catalysis or have no internal base or pro-base. Only Mn I complexes with an internal base or pro-base are active for H 2 activation; only [Mn]-hydrogenases incorporating such complexes are active for hydrogenase reactions. These results confirm the essential role of metal-ligand cooperation for H 2 activation by the Mn I complexes alone and by [Mn]-hydrogenases. Owing to the nature and position of the internal base or pro-base, the mode of metal-ligand cooperation in two active [Mn]-hydrogenases is different from that of the native [Fe]-hydrogenase. One [Mn]-hydrogenase has the highest specific activity of semi-synthetic [Mn]- and [Fe]-hydrogenases. This work demonstrates reconstitution of active artificial hydrogenases using synthetic complexes differing greatly from the native active site., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Pulau Tioman is a famous tourist island off Peninsular Malaysia with beautiful coral reefs. This study aims to assess the health of the coral reefs surrounding Pulau Tioman based on the application of the Foraminifera in Reef Assessment and Monitoring Index (FI). Ten sampling sites around Pulau Tioman were studied with a total of 30 samples. Eight orders, 41 families, 80 genera, and 161 species of benthic foraminifera were identified. The agglutinated type of foraminifera constituted 2-8% of the total assemblages. Calcareous hyaline and porcelaneous groups represented 79% and 19% of the total assemblages, respectively. Symbiont-bearing taxa were the most common foraminifera. The results indicate that most of the sampling sites are conducive for coral reef growth with good recoverability from future stress to the ecosystem. However, several areas with higher coastal development and tourism have reduced water and sediment quality. Therefore, the limit on the number of visitors and tourists should be revised to enable coral growth and health. The FI values in this study showed a positive correlation with good water qualities and a negative correlation with organic matter enrichment. The FI is a good measure to assess the health of a coral reef and can be applied to other reef ecosystems around Malaysia.

We investigated the effects of cigarette smoke extract (CSE) on lung fibroblasts and found that the invasiveness of lung cancer cells was facilitated by the conditioned medium from CSE-treated fibroblasts. CSE induced autophagy in fibroblasts and increased the expression of autophagy-related proteins, including optineurin and Ras-related protein Rab1B. Afterward, the fibroblasts produced high levels of interleukin-8 (IL-8), which promoted cancer cell invasion. The inhibition of either optineurin or Rab1B abrogated a rise in microtubule-associated protein 1 light chain 3 β and a decrease in p62 protein, as well as the production of IL-8, in CSE-treated fibroblasts. A three-dimensional invasion assay using cancer cell spheroids revealed that the invasion of cancer cells alone and the fibroblast-led cancer cell invasion were both enhanced by the conditioned media from CSE-treated fibroblasts. These results suggest that cigarette smoke may induce autophagy and IL-8 secretion in lung fibroblasts and modify the microenvironment to favor invasion of lung cancer cells., (© 2020 UICC.)

Background: Hypo-fractionation radiotherapy (HFRT) was considered to be an important treatment for non-small cell lung cancer (NSCLC), but the radiobiological effects of HFRT on NSCLC remain unclear. The aim of this study was to investigate specific biological effect of HFRT on tumor angiogenesis, compared with conventional radiotherapy (CRT)., Methods: The subcutaneous xenograft models and the dorsal skinfold window chamber (DSWC) models of nude mice bearing H460 and HCC827 NSCLC cells were irradiated with doses of 0 Gy (sham group), 22 Gy delivered into 11 fractions (CRT group) or 12 Gy delivered into 1 fraction (HFRT group). At certain time-points after irradiation, the volumes, hypoxic area, coverage rate of pericyte and micro-vessel density (MVD) of the subcutaneous xenograft models were detected, and the tumor vasculature was visualized in the DSMC model. The expressions of phosphorylated signal transducer and activator of transcription (p-STAT3), hypoxia-inducible factor 1-α (HIF-1α), CXCL12 and VEGFA were detected., Results: Compared with the CRT groups, HFRT showed more-efficient tumor growth-suppression, accompanied by a HFRT-induced window-period, during which vasculature was normalized, tumor hypoxia was improved and MVD was decreased. Moreover, during the window-period, the signal levels of p-STAT3/HIF-1α pathway and the expressions of its downstream angiogenic factors (VEGFA and CXCL12) were inhibited by HFRT., Conclusion: Compared with CRT, HFRT induced tumor vasculature normalization by rendering the remaining vessels less tortuous and increasing pericyte coverage of tumor blood vessels, thereby ameliorating tumor hypoxia and enhancing the tumor-killing effect. Moreover, HFRT might exert the aforementioned effects through p-STAT3/HIF-1α signaling pathway., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Objectives: Women with terminal cancer are assumed to choose hospice care over aggressive treatment at the end of life. With new chemotherapy and target therapy options, it becomes more difficult to decide between hospice care and aggressive management. It is also crucial to consider the cost increases leading to severe financial burdens on healthcare systems. To better understand treatment options at the individual level, this study set out to describe trends in end-of-life care for the four leading cancers in women in Taiwan., Study Design: This was a population-based retrospective cohort study., Methods: The data source was obtained between January 1, 2000, and December 31, 2013, from Taiwan's National Health Insurance Research Database. We identified 98,575 women with a diagnosis of breast (18,596), colorectal (23,734), liver and biliary (28,795) or lung (27,450) cancer who had died during the study period. Hospital data for services provided in the last 6 months of life, including hospice services and aggressive managements (chemotherapy, frequent hospitalisation, emergency room [ER] visits, intensive care unit [ICU] admission and endotracheal intubation), were collected., Results: Hospice utilisation increased over the study period, with 25.85%, 25.34%, 21.23% and 26.55% of female patients with breast, colorectal, liver and biliary, and lung cancer receiving hospice care, respectively. However, the number of women undergoing aggressive treatments in the last 6 months of life remained high, with the breast cancer group having the highest chemotherapy rate, the colorectal cancer group having frequent hospitalisation and the liver and biliary cancer group having frequent ER visits and ICU admissions., Conclusions: Increasing hospice utilisation among women with the four most common cancers in Taiwan indicates that hospice services have gradually become well accepted over the past 13 years; however, the real focus is on the ineffective treatment preceding hospice care, and late referral was also a notable problem., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

We report herein an unprecedented highly efficient Guerbet-type reaction at room temperature (catalytic TON up to >6000). This β-alkylation of secondary methyl carbinols with primary alcohols has significant advantage of delivering higher-order secondary alcohols in an economical, redox-neutral fashion. In addition, the first enantioselective Guerbet reaction has also been achieved using a commercially available chiral ruthenium complex to deliver secondary alcohols with moderate yield and up to 92 % ee. In both reactions, the use of a traceless ketone promoter proved to be beneficial for the catalytic efficiency., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

[Fe]-hydrogenase is an efficient biological hydrogenation catalyst. Despite intense research, Fe complexes mimicking the active site of [Fe]-hydrogenase have not achieved turnovers in hydrogenation reactions. Herein, we describe the design and development of a manganese(I) mimic of [Fe]-hydrogenase. This complex exhibits the highest activity and broadest scope in catalytic hydrogenation among known mimics. Thanks to its biomimetic nature, the complex exhibits unique activity in the hydrogenation of compounds analogous to methenyl-H 4 MPT + , the natural substrate of [Fe]-hydrogenase. This activity enables asymmetric relay hydrogenation of benzoxazinones and benzoxazines, involving the hydrogenation of a chiral hydride transfer agent using our catalyst coupled to Lewis acid-catalyzed hydride transfer from this agent to the substrates., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: Childhood obesity is prevalent in southern Taiwan and lifestyle interventions for the management of childhood obesity are challenging. How to overcome the barriers of implementation programs is crucial. We offered lunchtime education and integrated it into education programs. Finally, we evaluated whether such an intervention could change unhealthy behaviors and reduce obesity tendency among elementary students., Methods: This was a prospective cohort study, conducted at an elementary school from September 2015 to July 2018. We distributed a lifestyle questionnaire to assess the students' dietary habits and physical activities before our intervention. We offered class-based interactive nutrition programs and record the behavior and weight change each semester. The body mass index (BMI) of the students were obtained each semester, and they were categorized as underweight, normal, overweight, and obese according to the age-specific BMI., Results: In total, 279 students were followed for 3 consecutive years. The most prevalent unhealthy dietary habit was the consumption of sweetened beverages in approximately 76% of the students. At the end of the study, the percentage of normal weight increased and the overall percentage of overweight/obesity decreased in both groups. At the end of the study, the BMI-time curve became flatter than that of Kaohsiung (regional) city and approached the national standard. It indicates that the increase in average BMI was effectively delayed with our intervention., Conclusions: Lunchtime education is an innovative way to provide class-based education programs in school that yielded behavior changes and are effective approaches for delaying childhood obesity., (Copyright © 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

In the past ten years, the application of artificial intelligence (AI) in biomedicine has increased rapidly, which roots in the rapid growth of biomedicine data, the improvement of computing performance, and the development of deep learning methods. At present, there are great difficulties in front of AI for solving complex and comprehensive medical problems. Ontology can play an important role in how to make machines have stronger intelligence and has wider applications in the medical field. By using ontologies, (meta) data can be standardized so that data quality is improved and more data analysis methods can be introduced, data integration can be supported by the semantics relationships which are specified in ontologies, and effective logic expression in nature language can be better understood by machine. This can be a pathway to stronger AI. Under this circumstance, the Chinese Conference on Biomedical Ontology and Terminology was held in Beijing in autumn 2019, with the theme "Making Machine Understand Data". The success of this conference further improves the development of ontology in the field of biomedical information in China, and will promote the integration of Chinese ontology research and application with the international standards and the findability, accessibility, interoperability, and reusability(FAIR) Data Principle.

A novel nickel pincer cofactor was recently discovered in lactate racemase. Reported here are three synthetic nickel pincer complexes that are both structural and functional models of the pincer cofactor in lactate racemase. DFT computations suggest the ipso-carbon atom of the pyridinium pincer ligands act as a hydride acceptor for lactate isomerization, whereas an organometallic pathway involving nickel-mediated β-hydride elimination is less favored., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the past ten years, the application of artificial intelligence (AI) in biomedicine has increased rapidly, which roots in the rapid growth of biomedicine data, the improvement of computing performance, and the development of deep learning methods. At present, there are great difficulties in front of AI for solving complex and comprehensive medical problems. Ontology can play an important role in how to make machines have stronger intelligence and has wider applications in the medical field. By using ontologies, (meta) data can be standardized so that data quality is improved and more data analysis methods can be introduced, data integration can be supported by the semantics relationships which are specified in ontologies, and effective logic expression in nature language can be better understood by machine. This can be a pathway to stronger AI. Under this circumstance, the Chinese Conference on Biomedical Ontology and Terminology was held in Beijing in autumn 2019, with the theme "Making Machine Understand Data". The success of this conference further improves the development of ontology in the field of biomedical information in China, and will promote the integration of Chinese ontology research and application with the international standards and the findability, accessibility, interoperability, and reusability(FAIR) Data Principle.

Nature carefully selects specific metal ions for incorporation into the enzymes that catalyse the chemical reactions necessary for life. Hydrogenases, enzymes that activate molecular H 2 , exclusively utilize Ni and Fe in [NiFe]-, [FeFe]- and [Fe]-hydrogeanses. However, other transition metals are known to activate or catalyse the production of hydrogen in synthetic systems. Here, we report the development of a biomimetic model complex of [Fe]-hydrogenase that incorporates a Mn, as opposed to a Fe, metal centre. This Mn complex is able to heterolytically cleave H 2 as well as catalyse hydrogenation reactions. The incorporation of the model into an apoenzyme of [Fe]-hydrogenase results in a [Mn]-hydrogenase with an enhanced occupancy-normalized activity over an analogous semi-synthetic [Fe]-hydrogenase. These findings demonstrate a non-native metal hydrogenase that shows catalytic functionality and that hydrogenases based on a manganese active site are viable.

Objective: To investigate the gene mutation types and distribution features of α- and β-thalassemia in reproductive population of Xing bin district of Guangxi Lai bin city so as to provide the scientific basis for formulating the preventive and control measures., Methods: The high risk population with thalassemia in 6 498 people of child-bearing age admited in department of antenatal care of our hospital from January 2017 to December 2017 were screened by blood cell test and hemoglobin electrophoresis. The gene mutation types and mutation frequency in αandβthalassemia positive cases were diagnosed and analyzied by Gap-PCR and PCR-RDB., Results: The inital screening showed that there were 1 432 cases of thalassemia positive accounting for 22.04%; the gene diagnoses showed that there were 920 cases of thalassemia gene positive accounting for 14.16%. Among 920 cases, 593 cases were α-thalassemia accounting for 64.45% (593/920); the gene mutation types were 19 kinds. The α-deletion type gene was mainly -- SEA (47.22%), the α-mutatin type gene was mainly -α cs α(13.66%); 260 cases were the β-thalassemia accounting for 28.26%, (260/920), the gene mutation types were 9 kinds, out of which the β41-42 βN was main (50.38%), followed by β17/βN (38.08%)，there were 2 kinds of gene mutation types accounted for 88.46%; the αβ-thalassemia numbered 67 cases (7.28%), the mutation types were mainly -- SEA /β41-42 (17.91%) and -α3.7/β41-42 (17.91%)., Conclusion: The α-and β-thalassemia mostly observed in the childbearing population of Laibin city Xinbin district possess the gene comblexity and diversity as well as the significant genetic heterogeneily.The results of this study provide the reference basis for the prevention of thalassemia and eugenic works.

Background: Tamoxifen is commonly used to prevent breast cancer recurrence. Studies have confirmed the association between tamoxifen and nonalcoholic fatty liver disease (NAFLD), with the results indicating the need for aggressive management of this side effect. We assessed the potential risk factors for and identified the possible protective factors of tamoxifen-related fatty liver., Materials and Methods: We enrolled patients with a history of breast cancer, aged 20 to 70 years, who had received with tamoxifen treatment within the past 5 years. We obtained the initial data and performed a follow-up blood test and ultrasound examination to compare the differences before and after tamoxifen treatment. The patients were divided into relatively normal and fatty liver groups., Results: Of the 266 enrolled tamoxifen-treated patients, 143 (53.8%) and 123 (46.2%) were in the relatively normal and fatty liver groups, respectively. The initial body weight (57.6 ± 9.3 kg vs. 60.9 ± 10.3 kg; P = .006) and body mass index (BMI; 23.4 ± 3.8 kg/m 2 vs. 25.0 ± 4.2 kg/m 2 ; P < .001) were lower in the relatively normal group. An initial BMI of ≥ 22 kg/m 2 was a potential risk factor for tamoxifen-related NAFLD (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.00-2.48; P = .048). In contrast, a weekly exercise duration of ≥ 150 minutes reduced the risk (HR, 0.47; 95% CI, 0.31-0.69; P < .001)., Conclusion: The results from our study suggest that a BMI of ≥ 22 kg/m 2 is a potential risk factor for tamoxifen-related fatty liver and exercise is a possible protective factor., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the antioxidative effect and mechanism of luteolin on rat cardiomyocytes and isolated hearts followed by simulated ischemia/reperfusion (SI/R) injury., Methods: The left ventricular cardiomyocytes and the isolated hearts from adult rats were subjected to SI/R injury. The experiment groups included control, SI/R, luteolin + SI/R (Lut + SI/R), vitamin E (Vit E) + SI/R, and LY294002 + luteolin + SI/R (LY + Lut + SI/R) groups. Cell viability, shortening amplitude, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity, the production of reactive oxygen species (ROS) and malondialdehyde (MDA), expression levels of Akt, phosphorylated Akt, NOX2 (gp91phox), NOX2 mRNA, mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38MAPK were all measured after 3-h simulated ischemia and 2-h simulated reperfusion procedure in cardiomyocytes. Vit E was used as a standard control. The contractile function of isolated hearts was further observed after they were subjected to 30-min global ischemia and 120-min reperfusion., Results: Pretreatment with 8-μmol/L luteolin substantially increased cell viability and shortening amplitude, while reducing evidence of oxidative stress-induced damage in the cells. In addition, the expression of NOX2, NOX2 mRNA and phosphorylation of p38MAPK were all downregulated. Furthermore, pretreatment with 40-μmol/L luteolin improved the recovery of myocardial contractile function following SI/R-induced injury, and luteolin markedly increased phosphorylation of Akt. However, all of the above effects were partially inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002., Conclusions: Luteolin prevents SI/R-induced myocardial damage by reducing oxidative stress-induced injury in isolated rat hearts and cardiomyocytes, and the cardioprotection induced by luteolin was partially mediated by the PI3K/Akt pathway.

To explore the inhibitory effect of timosaponin AⅢ on the proliferation of human glioblastoma cell line U87MG and investigate its related mechanism. As compared with the model group, the tumor weight was significantly reduced in timosaponin AⅢ-treated group. Timosaponin AⅢinhibited the proliferation of U87MG cell line in a dose-dependent manner. It up-regulated the gene and protein expression levels of p21, meanwhile inhibited the protein expression levels of β-Catenin, Cyclin D1 and Bcl-2. It also inhibited the translocation of β-Catenin into nucleus, suppressed the phosphorylation expression of ERK, but increased the phosphorylation expression of p38 and JNK. Combined use of JNK inhibitor SP600125 and p38 inhibitor SB203580 could decrease p21 and increase β-Catenin protein expressions. Timosaponin AⅢ inhibited the proliferation of human glioblastoma cell line U87MG partly by intervening MAPK and Wnt/β-Catenin signal pathways., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The mechanical characteristics presented in cancer microenvironment are known to have pivotal roles in cancer metastasis, which accounts for the leading cause of death from malignant tumors. However, while a uniformly distributed high interstitial fluid pressure (IFP) is a common feature in solid tumors, the effects of high IFP on the motility and invasiveness of cancer cells remain obscure. Using cell-culture devices that simulated increased IFP conditions by applying hydrostatic pressure (HP) ranging from 0 to 20 mm Hg to the cells, we found that the elevated HPs increased the migration speeds, invasiveness, cell volume, filopodial number and aquaporin-1 (AQP1), Snail and vinculin expression levels, as well as phosphorylation of caveolin-1 and extracellular signal-regulated kinase1/2 (ERK1/2), in the lung cancer cells CL1-5 and A549. The increases of migration speed and cell volume correlated temporally with the increase of AQP1 expression. The elevated HP-induced migration acceleration was hindered by AQP1 knockdown using small interfering RNA (siRNA) transfection. Inhibition of ERK1/2 phosphorylation using the mitogen-activated protein kinase kinase inhibitor PD98059 abrogated the elevated HP-induced AQP1 upregulation and migration acceleration in the cancer cells. Caveolin-1 knockdown by siRNA transfection attenuated the HP-induced, ERK1/2-depedent AQP1 upregulation and migration acceleration. Further biochemical studies revealed that the caveolin-1 activation-driven ERK1/2 signaling is mediated by Akt1/2 phosphorylation. By contrast, the elevated HPs had negligible effects on the migration speed and volume of normal bronchial epithelial cells. These results disclose a novel mechanism relating high IFP to the invasiveness of cancer cells and highlight potential targets to impede cancer spreading.

Background: Excessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells., Methods: Of 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010. Of 1198 women who delivered, 1116 eligible mothers (147 with hyperandrogenism and 969 normal) were recruited. 1216 children (156 children born to mothers with hyperandrogenism and 1060 born to normal mother) were followed up their glycometabolism in mean age of 5years. Imprinting genes of oocyte from mothers and lymphocytes from children were examined. A pregestational hyperandrogenism rat model was also established., Findings: Children born to women with hyperandrogenism showed increased serum fasting glucose and insulin levels, and were more prone to prediabetes (adjusted RR: 3.98 (95%CI 1.16-13.58)). Oocytes from women with hyperandrogenism showed increased insulin-like growth factor 2 (IGF2) expression. Lymphocytes from their children also showed increased IGF2 expression and decreased IGF2 methylation. Treatment of human oocytes with dihydrotestosterone upregulated IGF2 and downregulated DNMT3a levels. In rat, pregestational hyperandrogenism induced diabetic phenotypes and impaired insulin secretion in offspring. In consistent with the findings in human, hyperandrogenism also increased Igf2 expression and decreased DNMT3a in rat oocytes. Importantly, the same altered methylation signatures of Igf2 were identified in the offspring pancreatic islets., Interpretation: Pregestational hyperandrogenism may predispose offspring to glucose metabolism disorder via epigenetic oocyte inheritance. Clinical trial registry no.: ChiCTR-OCC-14004537; www.chictr.org., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

The influence of the alcohol, as the hydrogen donor, on the efficiency and selectivity of the asymmetric transfer hydrogenation (ATH) of imines is reported for the first time. This discovery not only leads to a highly enantioselective access to N-aryl and N-alkyl amines, but also provides new insight into the mechanism of the ATH of imines. Both experimental and computational studies provide support for the reaction pathway involving an iridium alkoxide as the reducing species., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An iron-catalyzed transfer hydrogenation of N-aryl and N-alkyl imines using isopropanol as the hydrogen donor is reported for the first time. A combination of two iron complexes serving different roles is the key for the success of this catalytic system. As a result, an environmentally friendly and precious metal-free transfer hydrogenation of imines has been developed. The use of a suitable co-catalyst as an activator not only led to efficient transfer hydrogenation, but also showed potential in enantioselective transformation.

Background/purpose: For estrogen-receptor positive breast cancer cases, tamoxifen has been the most important adjuvant hormonal therapy for the purpose of reducing recurrence rates and prolonging disease free survival. However, several side effects have been noticed, and fatty liver is one of the most common side effects among them. Since fatty liver is a common problem in the general population, we wanted to examine the effects of tamoxifen under pre-existing fatty liver conditions and evaluate the prevalence of tamoxifen-related impaired liver function., Methods: We recruited breast cancer cases at ages 20-70 years and divided them into tamoxifen or control groups. Personal information was collected, and fasting blood tests and abdominal ultrasound were performed. The changes of fatty liver degree between the initial and follow-up ultrasound were divided into five categories., Results: Of the 406 enrolled participants, 266 were in the tamoxifen group and 140 were in the control group. The tamoxifen group had a higher risk of newly developed fatty liver [hazard ratio (HR) = 3.69; 95% confidence interval (CI) 1.67-8.13), lower rate of improved fatty liver (HR = 0.33; 95% CI 0.15-0.75), and higher rate of worsened fatty liver (HR = 2.11; 95% CI 1.02-4.35)., Conclusion: The current study suggests that tamoxifen treatment is associated with the risk of fatty liver either by increasing the risk of newly developed fatty liver conditions or worsening previous fatty liver conditions, and even retarding fatty liver improvement., (Copyright © 2015. Published by Elsevier B.V.)

Aim: We have shown that rutaecarpine extracted from the dried fruit of Chinese herb Evodia rutaecarpa (Juss) Benth (Wu Zhu Yu) promotes glucose consumption and anti-inflammatory cytokine expression in insulin-resistant primary skeletal muscle cells. In this study we investigated whether rutaecarpine ameliorated the obesity profiles, lipid abnormality, glucose metabolism and insulin resistance in rat model of hyperlipidemia and hyperglycemia., Methods: Rats fed on a high-fat diet for 8 weeks, followed by injection of streptozotocin (30 mg/kg, ip) to induce hyperlipidemia and hyperglycemia. One week after streptozotocin injection, the fat-fed, streptozotocin-treated rats were orally treated with rutaecarpine (25 mg·kg(-1)·d(-1)) or a positive control drug metformin (250 mg·kg(-1)·d(-1)) for 7 weeks. The body weight, visceral fat, blood lipid profiles and glucose levels, insulin sensitivity were measured. Serum levels of inflammatory cytokines were analyzed. IRS-1 and Akt/PKB phosphorylation, PI3K and NF-κB protein levels in liver tissues were assessed; pathological changes of livers and pancreases were examined. Glucose uptake and AMPK/ACC2 phosphorylation were studied in cultured rat skeletal muscle cells in vitro., Results: Administration of rutaecarpine or metformin significantly decreased obesity, visceral fat accumulation, water consumption, and serum TC, TG and LDL-cholesterol levels in fat-fed, streptozotocin-treated rats. The two drugs also attenuated hyperglycemia and enhanced insulin sensitivity. Moreover, the two drugs significantly decreased NF-κB protein levels in liver tissues and plasma TNF-α, IL-6, CRP and MCP-1 levels, and ameliorated the pathological changes in livers and pancreases. In addition, the two drugs increased PI3K p85 subunit levels and Akt/PKB phosphorylation, but decreased IRS-1 phosphorylation in liver tissues. Treatment of cultured skeletal muscle cells with rutaecarpine (20-180 μmol/L) or metformin (20 μmol/L) promoted the phosphorylation of AMPK and ACC2, and increased glucose uptake., Conclusion: Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating IRS-1/PI3K/Akt signaling pathway in liver and AMPK/ACC2 signaling pathway in skeletal muscles.

The aim of the present study was to compare differential impacts of bariatric surgery and exercise-induced weight loss on excessive abdominal and cardiac fat deposition.Excessive fat accumulation around the heart may play an important role in the pathogenesis of cardiovascular disease. Recent evidences have suggested that bariatric surgery results in relatively less decrease in epicardial fat compared with abdominal visceral fat and paracardial fat.Sixty-four consecutive overweight or obese subjects were enrolled in the study. Clinical characteristics and metabolic profiles were recorded. The volumes of abdominal visceral adipose tissue (AVAT), abdominal subcutaneous adipose tissue (ASAT), epicardial (EAT), and paracardial adipose tissue (PAT) were measured by computed tomography in the bariatric surgery group (N = 25) and the exercise group (N = 39) at baseline and 3 months after intervention. Subjects in both the surgery and exercise groups showed significant reduction in body mass index (15.97%, 7.47%), AVAT (40.52%, 15.24%), ASAT (31.40, 17.34%), PAT (34.40%, 12.05%), and PAT + EAT (22.31%, 17.72%) (all P < 0.001) after intervention compared with baseline. In both the groups, the decrease in EAT was small compared with the other compartments (P < 0.01 in both groups). Compared with the exercise group, the surgery group had greater loss in abdominal and cardiac visceral adipose tissue (AVAT, ASAT, PAT, EAT+PAT) (P < 0.001), but lesser loss in EAT (P = 0.037).Compared with the exercise group, bariatric surgery results in significantly greater percentage loss of excessive fat deposits except for EAT. EAT, but not PAT, was relatively preserved despite weight reduction in both the groups. The physiological impact of persistent EAT deserves further investigation.

Background: Cell membranes exhibit abundant types of responses to external stimulations. Intuitively, membrane topography should be sensitive to changes of physical or chemical factors in the microenvironment. We employed the non-interferometric wide-field optical profilometry (NIWOP) technique to quantify the membrane roughness of living neuroblastoma cells under various treatments that could change the mechanical properties of the cells., Results: The membrane roughness was reduced as the neuroblastoma cell was treated with paclitaxel, which increases cellular stiffness by translocating microtubules toward the cell membranes. The treatment of positively charged gold nanoparticles (AuNPs) showed a similar effect. In contrast, the negatively charged AuNPs did not cause significant changes of the membrane roughness. We also checked the membrane roughness of fixed cells by using scanning electron microscopy (SEM) and confirmed that the membrane roughness could be regarded as a parameter reflecting cellular mechanical properties. Finally, we monitored the temporal variations of the membrane roughness under the treatment with a hypertonic solution (75 mM sucrose in the culture medium). The membrane roughness was increased within 1 h but returned to the original level after 2 h., Conclusions: The results in the present study suggest that the optical measurement on membrane roughness can be regarded as a label-free method to monitor the changes in cell mechanical properties or binding properties of nanoparticles on cell surface. Because the cells were left untouched during the measurement, further tests about cell viability or drug efficacy can be done on the same specimen. Membrane roughness could thus provide a quick screening for new chemical or physical treatments on neuronal cells.

An efficient Lewis acid-assisted, iron-catalyzed amination of alcohols using borrowing hydrogen methodology was developed. In particular, silver fluoride was identified to be a highly effective additive to overcome the low efficiency in the amination of secondary alcohols catalyzed by Knölker's complex.

We used a spatial light modulator to project an optical micropattern of 473 nm light with a quartic intensity gradient on a single lung cancer cell. We observed that the intracellular amounts of reactive oxygen species (ROS) of the cancer cells were proportional to the intensity of the blue light, and the blue light intensity gradients could drive directional cell migration. This optically induced directional cell migration was inhibited by a ROS scavenger in the culture medium in a dose-dependent manner. In contrast, the ROS levels in fibroblasts were saturated by the blue light at low intensity and therefore the fibroblasts did not exhibit directional migration in the intensity gradient.

The first dynamic kinetic asymmetric amination of alcohols via borrowing hydrogen methodology is presented. Under the cooperative catalysis by an iridium complex and a chiral phosphoric acid, α-branched alcohols that exist as a mixture of four isomers undergo racemization by two orthogonal mechanisms and are converted to diastereo- and enantiopure amines bearing adjacent stereocenters. The preparation of diastereo- and enantiopure 1,2-amino alcohols is also realized using this catalytic system.

We employed a microfluidic device to study the effects of hydraulic pressure on cardiomyoblast H9c2. The 170 mm Hg pressure increased the cellular area and the expression of atrial natriuretic peptide. With the same device, we demonstrated that the effects of hydraulic pressure on the cardiomyoblast could be reduced by the inhibitor of focal adhesion kinase. This mechanical-chemical antagonism could lead to a potential therapeutic strategy of hypertension-induced cardiac hypertrophy.

The complete mitochondrial sequence of the capped langur (Trachypithecus pileatus) has been determined using long amplification polymerase chain reaction (LA-PCR). The total sequence length is 16,526 bp and includes 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 D-loop locus. The base composition of H-strand is 31.9% A, 29.1% T, 26.2% C and 12.8% G, with an AT content of 55.3%. The arrangement of genes in T. pileatus is identical to that of other primate species. All genes are encoded on the heavy strand with the exception of ND6 and eight tRNA genes. The mitochondrial genome of T. pileatus presented here will contribute to a better understanding of the species' population genetics, helping to protect its genetic diversity and resolve phylogenetic relationships within the family.

The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95-2.21) μmol/kg]>propranolol [9.21 (9.08-9.42) μmol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012 μmol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012 μmol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012 μmol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia., (Copyright © 2014 Elsevier B.V. All rights reserved.)