Evaluation of short‐term effectiveness of eight targeted agents combined with chemotherapy for treating esophageal‐gastric junction adenocarcinoma: A network meta‐analysis

This study aimed to evaluate the short‐term effectiveness of eight targeted agents (ramucirumab, bevacizumab, rilotumumab, panitumumab, cetuximab, trebananib, trastuzumab, matuzumab) plus chemotherapy in esophageal‐gastric junction adenocarcinoma (EGJA) by a network meta‐analysis (NMA). PubMed, Embase, and Cochrane Library databases were systematically retrieved for randomized clinical trials (RCTs) concerning targeted agents plus chemotherapy in the treatment of EGJA. This NMA combined both direct and indirect evidence to evaluate odds ratio (OR) and to draw the surface under the cumulative ranking curve (SUCRA). In total 11 RCTs with 3649 EGJA patients (1907 patients treated with targeted agents plus chemotherapy were regarded as the case group, and 1742 patients with placebo plus chemotherapy were assigned into the control group) were enrolled in this study. Targeted agents in terms of stable disease (SD), partial response (PR), disease control rate (DCR), and overall response ratio (ORR) with the SUCRA values of 0.838, 0.807, 0.934, and 0.793, respectively. Cetuximab and trastuzumab, with the SUCRA values of 0.884 and 0.758, came on top as the best outcomes for treating EGJA in terms of progressive disease (PD) and complete response (CR). Cluster analysis results indicated that ramucirumab plus chemotherapy might be the optimal treatment for EGJA. Our findings indicated that ramucirumab plus chemotherapy might be the optimal treatment for EGJA amongst the nine treatment regimens, which provided clinical guidance for clinicians in the treatment of EGJA.     

Efficacy and Toxicity of Different Chemotherapy Regimens in the Treatment of Advanced or Metastatic Pancreatic Cancer: A Network Meta‐Analysis

Objective A network meta‐analysis was conducted to compare the efficacy and toxicity of different chemotherapy regimens in treating advanced or metastatic pancreatic cancer (PC). PubMed, Cochrane Library and EMBASE databases from inception to June 2016 were searched. A combination of direct and indirect evidences was referred to for calculating the weighted mean difference (WMD) or the odds ratio (OR) and to establish surface under the cumulative ranking (SUCRA) curves, so as to evaluate the efficacy and toxicity of different chemotherapy regimens in treating advanced or metastatic PC. Twenty randomized controlled trials were enrolled. Twelve chemotherapy regimens included Gemcitabine, S‐1 (Tegafur), Gemcitabine + Cisplatin, Gemcitabine + Capecitabine, Gemcitabine + S‐1, Gemcitabine + 5‐FU (5‐fluorouracil), Gemcitabine + Exatecan, Gemcitabine + Irinotecan, Gemcitabine + Nab‐paclitaxel, FOLFIRINOX (Oxaliplatin + Irinotecan + Fluorouracil + Leucovorin), Gemcitabine + Oxaliplatin, and Gemcitabine + Pemetrexed. Higher overall response rate (ORR) was observed in patients treated with the gemcitabine + S‐1 and FOLFIRINO regimens. Thrombocytopenia reduced in patients treated with the S‐1 regimen. The Gemcitabine + S‐1 and FOLFIRINO regimens had better short‐ and long‐term efficacies than the other regimens; S‐1 regimen had the lowest hematologic toxicity, while Gemcitabine + Nab‐paclitaxel, FOLFIRINOX, and Gemcitabine + Pemetrexed regimens had higher incidence of non‐hematologic toxicity among twelve chemotherapy regimens. The efficacy of Gemcitabine + S‐1 and FOLFIRINOX regimens may be better in treating patients with advanced or metastatic pancreatic cancer, while FOLFIRINOX and Gemcitabine + Pemetrexed regimens may have relatively higher incidence of toxicity than other regimens. J. Cell. Biochem. 119: 511–523, 2018. © 2017 Wiley Periodicals, Inc.     

Phosphorylation of Dab2 is involved in inhibited VEGF‐VEGFR‐2 signaling induced by downregulation of syndecan‐1 in glomerular endothelial cell

Disabled‐2 (Dab2) and PAR‐3 (partitioning defective 3) are reported to play critical roles in maintaining retinal microvascular endothelial cells biology by regulating VEGF‐VEGFR‐2 signaling. The role of Dab2 and PAR‐3 in glomerular endothelial cell (GEnC) is unclear. In this study, we found that, no matter whether with vascular endothelial growth factor (VEGF) treatment or not, decreased expression of Dab2 could lead to cell apoptosis by preventing activation of VEGF‐VEGFR‐2 signaling in GEnC, accompanied by reduced membrane VEGFR‐2 expression. And silencing of PAR‐3 gene expression caused increased apoptosis of GEnC by inhibiting activation of VEGF‐VEGFR‐2 signaling and membrane VEGFR‐2 expression. In our previous research, we found that the silencing of syndecan‐1 gene expression inhibited VEGF‐VEGFR‐2 signaling by modulating internalization of VEGFR‐2. And our further research demonstrated that downregulation of syndecan‐1 lead to no significant change in the expression of Dab2 and PAR‐3 both at messenger RNA and protein levels in GEnC, while phosphorylation of Dab2 was significantly increased in GEnC transfected with Dab2 small interfering RNA (siRNA) compared with control siRNA. Atypical protein kinase C (aPKC) could induce phosphorylation of Dab2, thus negatively regulating VEGF‐VEGFR‐2 signaling. And we found that decreased expression of syndecan‐1 lead to activation of aPKC, and aPKC inhibitor treatment could block phosphorylation of Dab2 in GEnC. Besides, aPKC inhibitor treatment could activate VEGF‐VGEFR‐2 signaling in GEnC transfected with syndecan‐1 siRNA in a dose‐dependent manner. In conclusion, we speculated that phosphorylation of Dab2 is involved in preventing activation of VEGF‐VEGFR‐2 signaling in GEnC transfected with syndecan‐1 siRNA. This provides a new target for the therapy of GEnC injury and kidney disease.     

Disabled‐2: A modular scaffold protein with multifaceted functions in signaling

Disabled‐2 (Dab2) is a multimodular scaffold protein with signaling roles in the domains of cell growth, trafficking, differentiation, and homeostasis. Emerging evidences place Dab2 as a novel modulator of cell–cell interaction; however, its mode of action has remained largely elusive. In this review, we highlight the relevance of Dab2 function in cell signaling and development and provide the most recent and comprehensive analysis of Dab2's action as a mediator of homotypical and heterotypical interactions. Accordingly, Dab‐2 controls the extent of platelet aggregation through various motifs within its N‐terminus. Dab2 interacts with the cytosolic tail of the integrin receptor blocking inside‐out signaling, whereas extracellular Dab2 competes with fibrinogen for integrin α_IIbβ₃ receptor binding and, thus, modulates outside‐in signaling. An additional level of regulation results from Dab2's association with cell surface lipids, an event that defines the extent of cell–cell interactions. As a multifaceted regulator, Dab2 acts as a mediator of endocytosis through its association with the [FY]xNPx[YF] motifs of internalized cell surface receptors, phosphoinositides, and clathrin. Other emerging roles of Dab2 include its participation in developmental mechanisms required for tissue formation and in modulation of immune responses. This review highlights the various novel mechanisms by which Dab2 mediates an array of signaling events with vast physiological consequences.     

Disabled‐1 is down‐regulated in clinical breast cancer and regulates cell apoptosis through NF‐κB/Bcl‐2/caspase‐9

Disabled‐1 (Dab1) is best known as an adaptor protein regulating neuron migration and lamination during development. However, the exact function of Dab1 in breast cancer is unknown. In this study, we examined the expression of Dab1 in 38 breast cancer paraffin sections, as well as 60 paired frozen breast cancer and their adjacent tissues. Our results showed that Dab1 was reduced in breast cancer, and its compromised expression correlated with triple negative breast cancer phenotype, poor differentiation, as well as lymph node metastasis. Functional analysis in breast cancer cell lines demonstrated that Dab1 promoted cell apoptosis, which, at least partially, depended on its regulation of NF‐κB/Bcl‐2/caspase‐9 pathway. Our study strongly suggests that Dab1 may be a potential tumour suppressor gene in breast cancer.     

Dendritic calcium accumulation regulates wind sensitivity via short‐term depression at cercal sensory‐to‐giant interneuron synapses in the cricket

An in vivo Ca²⁺ imaging technique was applied to examine the cellular mechanisms for attenuation of wind sensitivity in the identified primary sensory interneurons in the cricket cercal system. Simultaneous measurement of the cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and membrane potential of a wind‐sensitive giant interneuron (GI) revealed that successive air puffs caused the Ca²⁺ accumulation in dendrites and diminished the wind‐evoked bursting response in the GI. After tetanic stimulation of the presynaptic cercal sensory nerves induced a larger Ca²⁺ accumulation in the GI, the wind‐evoked bursting response was reversibly decreased in its spike number. When hyperpolarizing current injection suppressed the [Ca²⁺]_i elevation during tetanic stimulation, the wind‐evoked EPSPs were not changed. Moreover, after suprathreshold tetanic stimulation to one side of the cercal nerve resulted in Ca²⁺ accumulation in the GI's dendrites, the slope of EPSP evoked by presynaptic stimulation of the other side of the cercal nerve was also attenuated for a few minutes after the [Ca²⁺]_i had returned to the prestimulation level. This short‐term depression at synapses between the cercal sensory neurons and the GI (cercal‐to‐giant synapses) was also induced by a depolarizing current injection, which increased the [Ca²⁺]_i, and buffering of the Ca²⁺ rise with a high concentration of a Ca²⁺ chelator blocked the induction of short‐term depression. These results indicate that the postsynaptic Ca²⁺ accumulation causes short‐term synaptic depression at the cercal‐to‐giant synapses. The dendritic excitability of the GI may contribute to postsynaptic regulation of the wind‐sensitivity via Ca²⁺‐dependent depression. © 2001 John Wiley & Sons, Inc. J Neurobiol 46: 301–313, 2001     

Role of p38 MAPK in enhanced human cancer cells killing by the combination of aspirin and ABT‐737

Regular use of aspirin after diagnosis is associated with longer survival among patients with mutated‐PIK3CA colorectal cancer, but not among patients with wild‐type PIK3CA cancer. In this study, we showed that clinically achievable concentrations of aspirin and ABT‐737 in combination could induce a synergistic growth arrest in several human PIK3CA wild‐type cancer cells. In addition, our results also demonstrated that long‐term combination treatment with aspirin and ABT‐737 could synergistically induce apoptosis both in A549 and H1299 cells. In the meanwhile, short‐term aspirin plus ABT‐737 combination treatment induced a greater autophagic response than did either drug alone and the combination‐induced autophagy switched from a cytoprotective signal to a death‐promoting signal. Furthermore, we showed that p38 acted as a switch between two different types of cell death (autophagy and apoptosis) induced by aspirin plus ABT‐737. Moreover, the increased anti‐cancer efficacy of aspirin combined with ABT‐737 was further validated in a human lung cancer A549 xenograft model. We hope that this synergy may contribute to failure of aspirin cancer therapy and ultimately lead to efficacious regimens for cancer therapy.     

Limited long‐term effectiveness of roller‐chopping for managing woody encroachment

The encroachment of woody plants into grasslands, woodland, and savanna has increased markedly over the past century, prompting the use of different physical methods to remove woody plants and restore grasses. Roller‐chopping is used extensively in the Americas, but little is known about its long‐term effectiveness for restoration, and whether its effectiveness varies with the intensity of encroachment. We compared the effects of roller‐chopping, under three treatment intensities (control, single treatment, double treatment), on woody plant density, ground cover, and groundstorey plants at sites of low, moderate, and high woody plant density in a semi‐arid eastern Australian woodland over 10 years. Both single and double treatment significantly altered the size distribution of Dodonaea viscosa, which comprised more than 85% of woody plants at all sites. Thus, roller‐chopping changed the size distribution of the community from an even‐size distribution to one dominated by shorter plants, irrespective of initial encroachment level. The effectiveness of roller‐chopping was strongly site‐specific, with significant reductions in density at low‐ and high‐density sites, but no clear trend in relation to the intensity of treatment (i.e. single cf. double treatment). The effectiveness of roller‐chopping was unsustained over the long term, with the suppressive effect on woody density diminishing over time. Grass cover increased with increasing intensity of woody removal, but only at the low‐density site and with some ill‐defined, variable, and short‐term effects on plant composition. Managers should consider that the short‐term effects may not adequately reflect the long‐term results of woody plant removal using the roller‐chopper.     

A rapid procedure to isolate isotopically labeled peptides for NMR studies: application to the Disabled‐2 sulfatide‐binding motif

A procedure for obtaining isotopically labeled peptides, by combining affinity chromatography, urea‐equilibrated gel filtration, and hydrophobic chromatography procedures, is presented using the Disabled‐2 (Dab2) sulfatide‐binding motif (SBM) as a proof of concept. The protocol is designed to isolate unstructured, membrane‐binding, recombinant peptides that co‐purify with bacterial proteins (e.g., chaperones). Dab2 SBM is overexpressed in bacteria as an isotopically labeled glutathione S‐transferase (GST) fusion protein using minimal media containing [¹⁵N] ammonium chloride as the nitrogen source. The fusion protein is purified using glutathione beads, and Dab2 SBM is released from GST using a specific protease. It is then dried, resuspended in urea to release the bound bacterial protein, and subjected to urea‐equilibrated gel filtration. Urea and buffer reagents are removed using an octadecyl column. The peptide is eluted with acetonitrile, dried, and stored at ?80 °C. Purification of Dab2 SBM can be accomplished in 6 days with a yield of ~2 mg/l of culture. The properties of Dab2 SBM can be studied in the presence of detergents using NMR spectroscopy. Although this method also allows for the purification of unlabeled peptides that co‐purify with bacterial proteins, the procedure is more relevant to isotopically labeled peptides, thus alleviating the cost of peptide production. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

Generation of a triple‐gene knockout mammalian cell line using engineered zinc‐finger nucleases

Mammalian cells with multi‐gene knockouts could be of considerable utility in research, drug discovery, and cell‐based therapeutics. However, existing methods for targeted gene deletion require sequential rounds of homologous recombination and drug selection to isolate rare desired events—a process sufficiently laborious to limit application to individual loci. Here we present a solution to this problem. Firstly, we report the development of zinc‐finger nucleases (ZFNs) targeted to cleave three independent genes with known null phenotypes. Mammalian cells exposed to each ZFN pair in turn resulted in the generation of cell lines harboring single, double, and triple gene knockouts, that is, the successful disruption of two, four, and six alleles. All three biallelic knockout events were obtained at frequencies of >1% without the use of selection, displayed the expected knockout phenotype(s), and harbored DNA mutations centered at the ZFN binding sites. These data demonstrate the utility of ZFNs in multi‐locus genome engineering. Biotechnol. Bioeng. 2010; 106: 97–105. © 2009 Wiley Periodicals, Inc.     

Efficacy Comparison of Six Chemotherapeutic Combinations for Osteosarcoma and Ewing's Sarcoma Treatment: A Network Meta‐Analysis

This study aimed to address the insufficiency of traditional meta‐analysis and provide improved guidelines for the clinical practice of osteosarcoma treatment. The heterogeneity of the fixed‐effect model was calculated, and when necessary, a random‐effect model was adopted. Furthermore, the direct and indirect evidence was pooled together and exhibited in the forest plot and slash table. The surface under the cumulative ranking curve (SUCRA) value was also measured to rank each intervention. Finally, heat plot was introduced to demonstrate the contribution of each intervention and the inconsistency between direct and indirect comparisons. This network meta‐analysis included 32 trials, involving a total of 5,626 subjects reported by 28 articles. All the treatments were classified into six chemotherapeutic combinations: dual agent with or without ifosfamide (IFO), multi‐agent with or without IFO, and dual agent or multi‐agent with IFO and etoposide. For the primary outcomes, both overall survival (OS) and event‐free survival (EFS) rates were considered. The multi‐agent integrated with IFO and etoposide showed an optimal performance for 5‐year OS, 10‐year OS, 3‐year EFS, 5‐year EFS, and 10‐year EFS when compared with placebo. The SUCRA value of this treatment was also the highest of these six interventions. However, multi‐drug with IFO alone had the highest SUCRA value of 0.652 and 0.516 when it came to relapse and lung‐metastasis. It was efficient to some extent, but no significant difference was observed in both outcomes. Chemotherapy, applied as induction or adjuvant treatment with radiation therapy or surgery, is able to increase the survival rate of patients, especially by combining multi‐drug with IFO and etoposide, which demonstrated the best performance in both OS and EFS. As for relapse and the lung‐metastasis, multiple agents with IFO alone seemed to have the optimal efficiency, although no significant difference was observed here. J. Cell. Biochem. 119: 250–259, 2018. © 2017 Wiley Periodicals, Inc.     

Proper E‐cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer

We reported that Disabled‐2 (Dab2) is located at the apical membrane in suckling rat intestine. Here, we discovered that, in colon of suckling and adult mouse and of adult human, Dab2 is only at lateral crypt cell membrane and colocalized with E‐cadherin. Dab2 depletion in Caco‐2 cells led to E‐cadherin internalization indicating that its membrane location requires Dab2. In mice, we found that 3 days of dextran sulfate sodium‐induced colitis increased Dab2/E‐cadherin colocalization, which was decreased as colitis progressed to 6 and 9 days. In agreement, Dab2/E‐cadherin colocalization increased in human mild and severe ulcerative colitis and in polyps, being reduced in colon adenocarcinomas, which even showed epithelial Dab2 absence and E‐cadherin delocalization. Epithelial Dab2 decrement preceded that of E‐cadherin. We suggest that Dab2, by inhibiting E‐cadherin internalization, stabilizes adherens junctions, and its absence from the epithelium may contribute to development of colon inflammation and cancer.     

miR‐145 is differentially regulated by TGF‐β1 and ischaemia and targets Disabled‐2 expression and wnt/β‐catenin activity

The effect of wnt/β‐catenin signalling in the response to acute myocardial infarction (AMI) remains controversial. The membrane receptor adaptor protein Disabled‐2 (Dab2) is a tumour suppressor protein and has a critical role in stem cell specification. We recently demonstrated that down‐regulation of Dab2 regulates cardiac protein expression and wnt/β‐catenin activity in mesenchymal stem cells (MSC) in response to transforming growth factor‐β₁ (TGF‐β₁). Although Dab2 expression has been shown to have effects in stem cells and tumour suppression, the molecular mechanisms regulating this expression are still undefined. We identified putative binding sites for miR‐145 in the 3′‐UTR of Dab2. In MSC in culture, we observed that TGF‐β₁ treatment led to rapid and sustained up‐regulation of pri–miR‐145. Through gain and loss of function studies we demonstrate that miR‐145 up‐regulation was required for the down‐regulation of Dab2 and increased β‐catenin activity in response to TGF‐β₁. To begin to define how Dab2 might regulate wnt/β‐catenin in the heart following AMI, we quantified myocardial Dab2 as a function of time after left anterior descending ligation. There was no significant Dab2 expression in sham‐operated myocardium. Following AMI, Dab2 levels were rapidly up‐regulated in cardiac myocytes in the infarct border zone. The increase in cardiac myocyte Dab2 expression correlated with the rapid and sustained down‐regulation of myocardial pri–miR‐145 expression following AMI. Our data demonstrate a novel and critical role for miR‐145 expression as a regulator of Dab2 expression and β‐catenin activity in response to TGF‐β₁ and hypoxia.     

Environmental Assessment of Refuse‐Derived Fuel Co‐Combustion in a Coal‐Fired Power Plant

Municipal residual waste (RW) produced in the Venice area undergoes mechanical‐biological treatment (MBT) in the Fusina plant to produce refuse‐derived fuel (RDF) that is then co‐combusted in a nearby coal‐fired power station. Being the first significant project for RDF co‐firing in power plants in Italy, a number of different testing phases were performed starting in 2003, aimed at evaluating differences between so‐called blank operation (i.e., with only coal feeding) and RDF co‐firing at different feeding rates. The analysis of data gathered during the industrial experimentation shows a savings of 0.7 tonnes (t) of coal per each tonne of co‐fired RDF; stack concentrations of some pollutants (hydrochloric acid [HCl], ammonia [NH₃], carbon monoxide [CO], chromium [Cr], and lead [Pb]) appear slightly higher during co‐combustion compared with blank operation, whereas concentrations of dust, sulfur oxides (SOx), and some metals (manganese [Mn], nickel [Ni], vanadium [V]) are lower. To assess the overall environmental performance of this practice, a life cycle assessment (LCA) study was then performed, where different strategies of energy recovery from RW were compared: production of RDF and its co‐combustion in the Fusina power plant, RW combustion without any pretreatment in a mass‐burn waste‐to‐energy (WTE) plant, and production of RDF and its combustion in a dedicated WTE plant. The LCA results show that co‐combustion of RDF performs better than the other strategies for all impact categories evaluated. The only exception is when the WTE plant operates in combined heat and power mode, with very high overall conversion efficiencies.     

RS‐1 enhances CRISPR‐mediated targeted knock‐in in bovine embryos

Targeted knock‐in (KI) can be achieved in embryos by clustered regularly interspaced short palindromic repeats (CRISPR)‐assisted homology directed repair (HDR). However, HDR efficiency is constrained by the competition of nonhomologous end joining. The objective of this study was to explore whether CRISPR‐assisted targeted KI rates can be improved in bovine embryos by exposure to the HDR enhancer RS‐1. In vitro produced zygotes were injected with CRISPR components (300 ng/µl Cas9 messenger RNA and 100 ng/µl single guide RNA against a noncoding region) and a single‐stranded DNA (ssDNA) repair template (100 ng/µl). ssDNA template contained a 6 bp XbaI site insert, allowing targeted KI detection by restriction analysis, flanked by 50 bp homology arms. Following microinjection, zygotes were exposed to 0, 3.75, or 7.5 µM RS‐1 for 24 hr. No differences were noted between groups in terms of development or genome edition rates. However, targeted KI rates were doubled in the group exposed to 7.5 µM RS‐1 compared to the others (52.8% vs. 25% and 23.1%, for 7.5, 0, and 3.75 µM, respectively). In conclusion, transient exposure to 7.5 µM RS‐1 enhances targeted KI rates resulting in approximately half of the embryos containing the intended mutation, hence allowing direct KI generation in embryos.     

Evidencing Excellent Thermal‐ and Photostability for Single‐Component Organic Solar Cells with Inherently Built‐In Microstructure

Solution‐processed organic solar cells (OSCs) are promising low‐cost, flexible, portable renewable sources for future energy supply. The state‐of‐the‐art OSCs are typically fabricated from a bulk‐heterojunction (BHJ) active layer containing well‐mixed donor and acceptor molecules in the nanometer regime. However, BHJ solar cells suffer from stability problems caused by the severe morphological changes upon thermal or illumination stress. In comparison, single‐component organic solar cells (SCOSCs) based on a double‐cable conjugated polymer with a covalently stabilized microstructure is suggested to be a key strategy for superior long‐term stability. Here, the thermal‐ and photostability of SCOSCs based on a model double‐cable polymer is systematically investigated. It is encouraging to find that under 90 °C & 1 sun illumination, the performance of SCOSCs remains substantially stable. Transport measurements show that charge generation and recombination (lifetime and recombination order) hardly change during the aging process. Particularly, the SCOSCs exhibit ultrahigh long‐term thermal stability with 100% PCE remaining after heating at temperature up to 160 °C for over 400 h, indicating an excellent candidate for extremely rugged applications.     

Assessment of intermittent UMTS electromagnetic field effects on blood circulation in the human auditory region using a near-infrared system

The aim of the present study was to assess the potential effects of intermittent Universal Mobile Telecommunications System electromagnetic fields (UMTS‐EMF) on blood circulation in the human head (auditory region) using near‐infrared spectroscopy (NIRS) on two different timescales: short‐term (effects occurring within 80 s) and medium‐term (effects occurring within 80 s to 30 min). For the first time, we measured potential immediate effects of UMTS‐EMF in real‐time without any interference during exposure. Three different exposures (sham, 0.18 W/kg, and 1.8 W/kg) were applied in a controlled, randomized, crossover, and double‐blind paradigm on 16 healthy volunteers. In addition to oxy‐, deoxy‐, and total haemoglobin concentrations ([O₂Hb], [HHb], and [tHb], respectively), the heart rate (HR), subjective well‐being, tiredness, and counting speed were recorded. During exposure to 0.18 W/kg, we found a significant short‐term increase in Δ[O₂Hb] and Δ[tHb], which is small (≈17%) compared to a functional brain activation. A significant decrease in the medium‐term response of Δ[HHb] at 0.18 and 1.8 W/kg exposures was detected, which is in the range of physiological fluctuations. The medium‐term ΔHR was significantly higher (+1.84 bpm) at 1.8 W/kg than for sham exposure. The other parameters showed no significant effects. Our results suggest that intermittent exposure to UMTS‐EMF has small short‐ and medium‐term effects on cerebral blood circulation and HR. Bioelectromagnetics 33:40–54, 2012. © 2011 Wiley Periodicals, Inc.     

Secreted phosphoprotein‐24 kDa (Spp24) attenuates BMP‐2‐stimulated Smad 1/5 phosphorylation and alkaline phosphatase induction and was purified in a protective complex with alpha2‐Macroglobulins From Serum

Secreted phosphoprotein‐24 kDa (Spp24) binds cytokines of the bone morphogenetic protein/transforming growth factor‐β (BMP/TGFβ) superfamily and is one of the most abundant serum phosphoproteins synthesized by the liver. Little is known about how Spp24 binding affects BMP signal transduction and osteoblastic differentiation or how this labile protein is transported from the liver to remote tissues, such as bone. When Spp24 was administered to W‐20‐17 mesenchymal stem cells with rhBMP‐2, short‐term Smad1/5 phosphorylation was inhibited, intermediate‐term alkaline phosphatase (ALP) induction was blunted, and long‐term mineralization was unaffected. This supports the hypothesis that Spp24 proteolysis restricts the duration of its regulatory effects, but offers no insight into how Spp24 is transported intact from the liver to bone. When Spp24 was immunopurified from serum and subjected to native PAGE and Western blotting, a high molecular weight band of >500 kDa was found. Under reducing SDS–PAGE, a 24 kDa band corresponding to monomeric Spp24 was liberated, suggesting that Spp24 is bound to a complex linked by disulfide bonds. However, such a complex cannot be disrupted by 60 mM EDTA under non‐reducing condition or in purification buffers containing 600 mM NaCl and 0.1% Tween‐20 at pH 2.7–8.5. LC–MS/MS analysis of affinity‐purified, non‐reducing SDS–PAGE separated, and trypsin digested bands showed that the Spp24 was present in a complex with three α₂‐macroglobulins (α₂‐macroglobulin [α₂M], pregnancy zone protein [PZP] and complement C3 [C3]), as well as ceruloplasmin and the protease inhibitor anti‐thrombin III (Serpin C1), which may protect Spp24 from proteolysis. J. Cell. Biochem. 114: 378–387, 2013. © 2012 Wiley Periodicals, Inc.     

Effects of long‐term straw return on soil organic carbon storage and sequestration rate in North China upland crops: A meta‐analysis

Soil organic carbon (SOC) is essential for soil fertility and climate change mitigation, and carbon can be sequestered in soil through proper soil management, including straw return. However, results of studies of long‐term straw return on SOC are contradictory and increasing SOC stocks in upland soils is challenging. This study of North China upland agricultural fields quantified the effects of several fertilizer and straw return treatments on SOC storage changes and crop yields, considering different cropping duration periods, soil types, and cropping systems to establish the relationships of SOC sequestration rates with initial SOC stocks and annual straw C inputs. Our meta‐analysis using long‐term field experiments showed that SOC stock responses to straw return were greater than that of mineral fertilizers alone. Black soils with higher initial SOC stocks also had lower SOC stock increases than did soils with lower initial SOC stocks (fluvo‐aquic and loessial soils) following applications of nitrogen‐phosphorous‐potassium (NPK) fertilizer and NPK+S (straw). Soil C stocks under the NPK and NPK+S treatments increased in the more‐than‐20‐year duration period, while significant SOC stock increases in the NP and NP+S treatment groups were limited to the 11‐ to 20‐year period. Annual crop productivity was higher in double‐cropped wheat and maize under all fertilization treatments, including control (no fertilization), than in the single‐crop systems (wheat or maize). Also, the annual soil sequestration rates and annual straw C inputs of the treatments with straw return (NP+S and NPK+S) were significantly positively related. Moreover, initial SOC stocks and SOC sequestration rates of those treatments were highly negatively correlated. Thus, long‐term straw return integrated with mineral fertilization in upland wheat and maize croplands leads to increased crop yields and SOC stocks. However, those effects of straw return are highly dependent on fertilizer management, cropping system, soil type, duration period, and the initial SOC content.