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Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAAreceptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN’s protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.

The levels of serum uric acid (UA) and creatinine in the first trimester of pregnant women were significantly lower than healthy non-pregnant women, probably because of the increase of glomerular filtration.Serum UA concentration in the first trimester was significantly higher in women with gestational diabetes mellitus (GDM) than in women with normal glucose tolerance (NGT). The association of serum UA in the first trimester and GDM were observed when serum UA was above 240 μmol/l, and the association was stronger in women aged over 35 years old and preBMI ≥ 24 kg/m2.To prevent GDM, healthy lifestyle intervention should be taken since early pregnancy to control serum UA concentration, especially in older and heavier pregnant women.

ABSTRACTAutophagy, an evolutionally conserved cellular degradation process, plays critical roles in plant development and stress response. Despite the wealth of information on the vital role of autophagy in responses to environmental stresses, little is known about the regulation of autophagy. In this study, we demonstrated that spermidine (Spd), a kind of polyamine, was involved in the regulation of salt tolerance through activating the expression of ATG(autophagy-related) genes and the formation of autophagosomes in cucumber under salt stress. Furthermore, NADPH oxidase-derived apoplastic H2O2-mediated Spd-induced salt tolerance and autophagy. Exogenous Spd significantly increased the tolerance to salt stress and inhibited the accumulation and ubiquitination of insoluble proteins. Foliar application of Spd promoted the transcript levels of ATGgenes and autophagosomes formation. Besides, Spd induced the expression of RBOH(respiratory burst oxidase homolog), and the accumulation of H2O2both in leaves and roots. However, either pretreatment with dimethylthiourea (DMTU, an H2O2scavenger) or diphenyleneiodonium chloride (DPI, an inhibitor of NADPH oxidase) reduced Spd-induced accumulation of apoplastic H2O2. Importantly, Spd-induced salt tolerance and autophagy were compromised when plants were pretreated with DMTU or DPI. Furthermore, the silencing of ATG4and ATG7reduced Spd-induced salt tolerance and autophagosomes formation. Taken together, these results revealed that RBOH-dependent H2O2mediated the Spd-induced autophagy and salt tolerance in cucumber.Abbreviations: Asat: light-saturated rate of CO2assimilation; ATG: autophagy-related; DCF-DA: 2, 7-dichlorofluorescein diacetate; DMTU: dimethylthiourea; DPI: diphenyleneiodonium chloride; DW: dry weight; EL: electrolyte leakage; FW: fresh weight; Fv/Fm: the maximum quantum yield of photosystem II; GFP: green fluorescent protein; MDC: monodansylcadaverine; PDS: phytoene desaturase; PE: phosphatidylethanolamine; PLD: phospholipase D; RBOH: respiratory burst oxidase homolog; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SIN1: salt induced NAC1; Spd: spermidine; TOR: target of rapamycin; VIGS: virus-induced gene silencing.

To achieve long-term effective protection of food by continuously controlling the release of active substances in an active film, IRMOF-3 was post-synthetic modified with benzoic acid (BA) to obtain BA-IRMOF-3. This modification enhanced the loading capacity of carvacrol (CA) and slowed down its release rate. Research on IRMOF-3 synthesis has found that increasing the proportion of metal nodes can improve its crystallinity. The post-synthesis modification of IRMOF-3 through amide reaction successfully enhanced the binding energy with CA from −5.1 kcal/mol to −6 kcal/mol, resulting in an improved CA loading rate of 28.62% ± 0.15% and delayed release. Furthermore, the BA-IRMOF-3/CA assembly was added to the sodium alginate matrix to prepare the active film BMC@SA, which improved the mechanical and physical properties of the film. The release and antibacterial/antioxidant properties were investigated. The results demonstrated that the active film BMC@SA exhibited significant sustained-release properties and antibacterial/antioxidant activities, reducing the growth of E. coliand S. aureusby 61.95% and 49.33% respectively. In refrigerated pork experiments, the film BMC@SA slowed down the color, weight, pH changes and inhibited microbial growth of fresh pork effectively, and extended the shelf life of pork from 6 d to 12 d, which demonstrated the potential application of active film BMC@SA in food preservation.

Discovering new low-dimensional magnetic materials is of paramount importance in spintronics. We report on a new ferrimagnetic (FiM) compound, Nb6Mn1–xIr6+xB8(x= 0.25), the structure of which contains Mn chains embedded in stacked planar B6rings. Its crystal structure, which was determined by combined single-crystal X-ray and neutron diffraction studies, contains three Mn chains (intrachain distance is 3.30 Å) building a triangular network with an interchain distance of 9.28 Å, indicating stronger intrachain interactions than interchain ones. Density functional theory (DFT) calculations proposed ferrimagnetic ordering for the new phase resulting from three nonequivalent, triangularly arranged ferromagnetic (FM) Mn chains with two in spin-up and one in spin-down. Magnetization measurements confirmed the presence of not only strong FM interactions (high Curie temperature of 250 K) but also weak antiferromagnetic (AFM) ones (small and negative Weiss constant of −70 K), thus confirming the proposed FiM ordering.

Inhibition of the serine protease enteropeptidase (EP) opens a new avenue to the discovery of chemotherapeutics for the treatment of metabolic diseases. Camostat has been used clinically for treating chronic pancreatitis in Japan; however, the mechanistic basis of the observed clinical efficacy has not been fully elucidated. We demonstrate that camostat is a potent reversible covalent inhibitor of EP, with an inhibition potency (kinact/KI) of 1.5 × 104M−1s−1. High-resolution liquid chromatography-mass spectrometry (LC-MS) showed addition of 161.6 Da to EP after the reaction with camostat, consistent with insertion of the carboxyphenylguanidine moiety of camostat. Covalent inhibition of EP by camostat is reversible, with an enzyme reactivation half-life of 14.3 hours. Formation of a covalent adduct was further supported by a crystal structure resolved to 2.19 Å, showing modification of the catalytic serine of EP by a close analog of camostat, leading to formation of the carboxyphenylguanidine acyl enzyme identical to that expected for the reaction with camostat. Of particular note, minor structural modifications of camostat led to changes in the mechanism of inhibition. We observed from other studies that sustained inhibition of EP is required to effect a reduction in cumulative food intake and body weight, with concomitant improved blood glucose levels in obese and diabetic leptin-deficient mice. Thus, the structure-activity relationship needs to be driven by not only the inhibition potency but also the mechanistic and kinetic characterization. Our findings support EP as a target for the treatment of metabolic diseases and demonstrate that reversible covalent EP inhibitors show clinically relevant efficacy.

Atomic and/or vacancy ordering has proven to be important in understanding some unexpected properties in perovskites, leading to the formulation of double perovskites (oxides or halides) as a subclass of these compounds. Intermetallic double perovskite borides (IDPBs) have been described structurally, but the study of their physical properties is still in its infancy. In this work, we have investigated the mechanical hardness and microstructure of the series Sc2Ir6–xPdxB for the first time. We found that the hardness decreases until x= 5, and then it levels off. This transition coincides with the change in structure from ordered to disordered. A detailed microstructure analysis reveals that the order–disorder transition at x= 5 is accompanied by the precipitation of small amounts of a boron-rich side phase. Interestingly, the hardness trend in the IDPBs (x= 0–4) is accurately reproduced by crystal orbital Hamilton populations (COHP) analysis, especially the total integrated COHP (iCOHP) which measures the bond strength in each compound. Furthermore, it is found that more antibonding states are occupied if Ir is replaced by alioelectronic Pd, thereby reducing the total iCOHP and thus explaining the reduced hardness with increasing Pd concentration.

Ovarian cancer is among the most prevalent gynecological malignancies around the globe. Nonetheless, chemoresistance continues to be one of the greatest obstacles in the treatment of ovarian cancer. Therefore, understanding the mechanisms of chemoresistance and identifying new treatment options for ovarian cancer patients is urgently required. In this study, we found that the mRNA and protein expression levels of PRDX1 were significantly increased in cisplatin resistant A2780/CDDP cells. Cell survival assays revealed that PRDX1 depletion substantially increased ovarian cancer cell sensitivity to cisplatin, docetaxel, and doxorubicin. Additionally, PRDX1 significantly increased GSTP1 activity, resulting in multidrug resistance. Biochemical experiments showed that PRDX1 interacted with GSTP1 through Cysteine 83, which regulated GSTP1 activity as well as chemotherapy resistance in ovarian cancer cells. Our findings indicate that the molecular chaperone activity of PRDX1 is a promising new therapeutic target for ovarian cancer.

Materials “design” is increasingly gaining importance in the solid-state materials community in general and in the field of magnetic materials in particular. Density functional theory (DFT) predicted the competition between ferromagnetic (FM) and antiferromagnetic (AFM) ground states in a ruthenium-rich Ti3Co5B2-type boride (Hf2MnRu5B2) for the first time. Vienna ab initio simulation package (VASP) total energy calculations indicated that the FM model was marginally more stable than one of the AFM models (AFM1), indicating very weak interactions between magnetic 1D Mn chains that can be easily perturbated by external means (magnetic field or composition). The predicted phase was then synthesized by arc-melting and characterized as Hf2Mn1–xRu5+xB2(x= 0.27). Vibrating-scanning magnetometry shows an AFM ground state with TN≈ 20 K under low magnetic field (0.005 T). At moderate-to-higher fields, AFM ordering vanishes while FM ordering emerges with a Curie temperature of 115 K. These experimental outcomes confirm the weak nature of the interchain interactions, as predicted by DFT calculations.

This study aims to provide new insight on the association between the development of wooden breast myopathy and mitochondrial and glycolytic activity under oxidative stress. Myopathic muscle had higher oxidative stress together with altered glycolytic metabolism and tricarboxylic acid (TCA) cycle. This was evidenced by significantly elevated antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase), decreased citrate synthase activity and postmortem glycolytic potential with increasing wooden breast severity. In addition, affected muscles also exhibited higher initial and ultimate pH values as well as reduced total glucose and lactate contents. Citrate synthase activity was negatively correlated to antioxidant enzyme activities. Taken together, we propose that the development of the wooden breast lesion is a chronic process that may be related to the failure of muscle fibers to defend against the excessively generated oxidative products promoted by mitochondrial damage accompanied by impaired TCA cycle. Furthermore, there was a positive correlation between citrate synthase activity and glycolytic potential, which suggests that the wooden breast condition is linked to the overall altered energy metabolism of the muscle, including the oxidative phosphorylation and glycolytic pathways.

Ever since the social networks became the focus of a great number of researches, the privacy risks of published network data have also raised considerable concerns. To evaluate users’ privacy risks, researchers have developed methods to de-anonymize the networks and identify the same person in the different networks. However, the existing solutions either require high-quality seed mappings for cold start, or exhibit low accuracy without fully exploiting the structural information, and entail high computation expense. In this paper, we propose a fast and effective seedless network de-anonymization approach simply relying on structural information, named RoleMatch. RoleMatch equips with a new pairwise node similarity measure and an efficient node matching algorithm. Through testing RoleMatch with both real and synthesized social networks, which are anonymized by several popular anonymization algorithms, we demonstrate that the RoleMatch receives superior performance compared with existing de-anonymization algorithms.

Na2Au3Al, the first experimentally prepared compound in the ternary Na–Au–Al system, crystallizes in the cubic crystal system with space group P4132 (a= 771.42(2) pm). It can be described as a P-centered ternary ordered variant of the F-centered Laves phase MgCu2and is isostructural to Mo3Al2C. A phase width was found for the series Na2Au4–xAlxallowing a successive substitution of Au by Al. The primitive structure forms for x≥ 0.5. Na2Au3Al is diamagnetic at room temperature but metallic in nature, as seen from susceptibility and electrical resistivity measurements. Band structure calculations and X-ray photoelectron spectroscopy confirm the metallic nature of the title compound as states are found at the Fermi level of the DOS, along with its “auride” character. 23Na and 27Al solid-state-NMR investigations show the existence of both a disordered (x= 0.5 and 0.75) and a fully ordered (x= 1.0) representative within this series. Both COHP and Bader charge analyses suggest the presence of strong Au–Al interactions forming an anionic [Au3Al]δ−network, with the Na cations occupying the cavities.

Microplastics (MPs) are abundant in air, but evidence of their deposition in the respiratory tract is limited. We conducted a prospective case series to investigate the deposition of microplastics in bronchoalveolar lavage fluid (BALF) and determine the internal dose of MPs via inhalation. Eighteen never-smokers aged 32–74 years who underwent fiberoptic bronchoscopy with BALF were recruited from Zhuhai, China. Control samples were obtained by performing the same procedure using isotonic saline instead of BALF. Laser direct infrared spectroscopy combined with scanning electron microscopy detected the presence and characteristics of MPs and quantitatively analyzed the microplastic in BALF and control samples. Concentrations of total and specific MPs in BALF and control samples were compared using the Wilcox test. Thirteen types of MPs were observed in 18 BALF samples. Polyethylene (PE, 86.1%) was the most abundant in BALF, followed by poly(ethylene terephthalate) (PET, 7.5%) and polypropylene (PP, 1.9%). Compared with the control samples, BALF had significantly higher concentrations of PE (median [IQR] of

Ischemic heart disease is the leading cause of mortality in industrialized countries. Cell transplantation could restore function of the ischemic heart likely through the mechanism of cell-induced angiogenesis. We have previously shown that cells isolated from uteri increase angiogenesis and alleviate cardiac dysfunction when transplanted after MI. However, which uterine cell type contributes to angiogenesis is unknown. Here we report that uterine-derived CD11b cells significantly increase vasculogenesis and promote myocardial healing in ischemic cardiomyopathy. We have established a novel and simple methodology for uterine CD11b cell isolation and enrichment and demonstrate that this technique can be used for purifying and establishing viable CD11b cell cultures in rats. The isolated fresh CD11b cells were transplanted into ischemic rat hearts 5 days after injury. Following transplantation, vasculogenesis significantly increased in ischemic cardiac tissue, which reduced infarct size and restored myocardial function and perfusion compared with controls. Thus, uterine CD11b cells have the potential to promote functional healing when implanted after ischemic cardiomyopathy. Importantly, we have demonstrated a novel means by which CD11b cells can be easily purified and cultured for cell transplantation.

Spin-frustrated chains of Cr3triangles are found in the new metal boride TiCrIr2B2by synergistic experimental and theoretical investigations. Although magnetic ordering is found at 275 K, competing ferro- and anti-ferromagnetic interactions coupled with spin frustration induce a rather small total magnetic moment (0.05 μBat 5 T), and density functional theory (DFT) calculations propose a canted, nonlinear magnetic ground-state ordering in the new phase. TiCrIr2B2crystallizes in the hexagonal Ti1+xOs2–xRuB2structure type (space group P6̅2m, No. 189, Pearson symbol hP18). The structure contains trigonal planar B4boron fragments with B–B distances of 1.76(3) Å alternating along the c-direction with Cr3triangles with intra- and intertriangle Cr–Cr distances of 2.642(9) and 3.185(1) Å, respectively. Magnetization measurements of TiCrIr2B2reveal ferrimagnetic behavior and a large, negative Weiss constant of −750 K. DFT calculations demonstrate a strong site preference of Cr for the triangle sites, as well as magnetic frustration due to indirect anti-ferromagnetic interactions within the Cr3triangles.

Biogenic amines, ATP-related compounds, sensory attributes, total volatile basic nitrogen, microbial flora (total viable bacteria, Pseudomonas, Aeromonas,and H2S-producing bacteria), and free amino acids were determined in common carp (Cyprinus carpiovar. Jian)stored at 20 and 0°C. Pseudomonasand H2S-producing bacteria became the dominant bacteria in carp stored at 20 and 0°C, whereas Aeromonasrapidly increased only in carp stored at 0°C. Inosine monophosphate, which is responsible for flavor and freshness, increased to a maximum of 2.37 μmol/g after 12 h at 20°C and to 4.72 μmol/g after 3 days at 0°C. Putrescine and cadaverine were the dominant amines in carp and their concentrations were significantly correlated (P <0.05) with total volatile basic nitrogen and sensory scores in all samples during the storage. Significant correlations also were observed between histamine and total volatile basic nitrogen and sensory scores only in samples stored at 20°C. Arginine decreased while putrescine increased in all samples. A significant decrease (P< 0.05) in histidine was observed after 24 h of storage, which coincided with an increase in histamine after 36 h in samples stored at 20°C. Hypoxanthine concentrations were significantly correlated with the microbial species (P< 0.01) and sensory scores (P< 0.05) and seems to be a reliable marker for quality of carp fillets stored at 20 and 0°C.

The electronic and magnetic structures of the tetragonal and hexagonal MnFeAs were examined using density functional theory to understand the reported magnetic orderings and structural change induced by high-pressure synthesis. The reported magnetic ground states were confirmed using VASP total energy calculations. Effective exchange parameters for metal–metal contacts obtained from SPRKKR calculations indicate indirect exchange couplings are dominant in tetragonal MnFeAs. Weak direct exchange couplings for adjacent Fe–Fe and Fe–Mn contacts cause the coexistence of several low-energy magnetic structures in tetragonal MnFeAs and result in a near zero magnetic moment on the Fe atoms. On the other hand, the nearest-neighbor Fe–Fe and Fe–Mn interactions in hexagonal MnFeAs are a combination of direct and indirect exchange couplings. In addition, indirect exchange couplings in tetragonal MnFeAs are rationalized by both RKKY and superexchange mechanisms. Finally, to probe the high-pressure-induced phase transition, total energy changes with the change of volume was studied on both tetragonal and hexagonal MnFeAs.

Autologous stem cell therapy has not been as effective as forecasted from preclinical studies. Patient age was reported as an important contributing factor. The goal of this study was to uncover age-dependent mechanisms of stem cell dysfunction and to investigate possible means to restore the cellular function. Bone marrow mesenchymal stem cells (MSCs) were isolated from cardiovascular patients. Cell proliferation and number of colonies were inversely correlated with patient age. Myogenic differentiation of MSCs in culture was induced with 5-azacytidine. Differentiation correlated with age, with less differentiation in MSCs from aged patients. We performed real-time PCR to identify genes in the WNT/β-catenin signaling network and found that transcript levels of CTNNB1, LEF1, FZD8, WNT3A, and SFRP4were negatively correlated with age, whereas FOSL1, LRP6,and FZD6were positively correlated with age. Protein evaluation showed that β-catenin nuclear translocation correlated with age and was lower in aged MSCs. Aged MSCs treated with lithium chloride—to increase the bioavailability of β-catenin—recovered their capacity for myogenic differentiation through myocyte enhancer factor 2C but not with the knockdown of β-catenin using small-interfering RNA. This study may be the first to relate reduced nuclear β-catenin bioavailability in MSCs from aged patients. Most important, this abnormality was potentially recoverable, providing a target for improving the function of bone marrow stem cells and their clinical utility in aged patients.

Stem cells exhibit long-term self-renewal by asymmetric division and multipotent differentiation. During embryonic development, cell fate is determined with predictable orientation, differentiation, and partitioning to form the organism. This includes the formation of a hemangioblast from which 2 derivative cell clusters commit to either a hematopoietic or an endothelial lineage. Frequently, it is not clear whether tissue resident stem cells in the adult originate from the bone marrow. Here, we show that blast colony-forming cells exhibiting bilineage (hematopoietic and vascular) potential and long-term self-renewal originate from the uterus in the mouse. This is the first in vitro and in vivo evidence of an adult hemangioblast retained from development in the uterus. Our findings offer new understanding of uterine cell renewal and turnover and may provide insights and opportunities for the study of stem cell maintenance.

Polymethylsilazanes (PMS) were synthesized and used to cure silicone resins at ambient temperature. The curing degree of the silicone resins depends on the structure of PMS and its concentration in the resin. Silicone resins of different structure and different silanol content can be cured to a satisfactory degree, if the concentration of the PMS is high enough. Silicone resins cured with PMS showed improved thermal stability in nitrogen, compared with that of the heat-cured counterparts. The mechanism of thermal decomposition of the silicone resins is discussed. The improvement of heat resistance using PMS as the curing agent is accounted for by diminished thermal rearrangement and degradation of the polysiloxane network initiated by silanol groups in the resins. © 2003 Wiley Periodicals, J Appl Polym Sci 89: 1702–1707, 2003

A hyperbranched polyol with long flexible chains on the molecule surface was synthesized and characterized. The effect of the hyperbranched polyol as flexibilizer and chain-transfer agent on cationic UV curing was investigated. It was found the hyperbranched polyol could markedly improve the mechanical properties of cured film. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 1353–1356, 2000