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Buried interface modification is promising for preparing high-performance perovskite solar cells (PSCs) by improving the film quality and adjusting the interfacial energy level alignment. In this work, multifunctional ethylenediaminetetraacetic acid diammonium (EAD)-modulated ZnO is employed as an effective buried interface to regulate the interplay between SnO 2 and CsPbI 2 Br in carbon-based inorganic PSCs (C-IPSCs). The burying of EAD into the ZnO interlayer not only enhances the photoelectric properties of ZnO by passivating oxygen defects but also adjusts the energy level alignment of the buried interface. More importantly, the perovskite quality is optimized and the buried interface defects are passivated due to the formation of coordination and hydrogen bondings. Benefiting from such a robust and efficient charge transfer configuration, a maximum power conversion efficiency of 14.58% is achieved in the optimized device, which represents the highest performance reported among those of low-temperature CsPbI 2 Br C-IPSCs. In addition, the unencapsulated device demonstrates better long-term and thermal stability.

Fe-mediated nickel organic framework nanoarrays (NiFe-MOFs NAs) on carbon cloth were successfully constructed from ultrathin nanosheets via an etching effect. This strategy also combined the dissolution and coordination effect of acidic ligand (2,6-naphthalenedicarboxylic acid, NDC) to a self-sacrificial template of Ni(OH) 2 NAs. Benefiting from the strong Fe etching effect, dense and thick brick-like Ni-NDC nanoplates were tailored into loose and ultrathin NiFe-NDC nanosheets with abundant squamous nanostructures, which were still tightly attached to carbon cloth. As a consequence, more coordinatively unsaturated metal sites (CUMSs) that served as active centers were exposed to accelerate oxygen production. Meanwhile, the electronic structure of active Ni centers was modulated by the incorporation of Fe atoms. The charge density redistribution between Ni and Fe ultimately optimized the energy barrier of the adsorption/desorption of oxygenated intermediates, promoting the kinetics for water oxidation.

The charge recombination resulting from bulk defects and interfacial energy level mismatch hinders the improvement of the power conversion efficiency (PCE) and stability of carbon-based inorganic perovskite solar cells (C-IPSCs). Herein, a series of small molecules including ethylenediaminetetraacetic acid (EDTA) and its derivatives (EDTA-Na and EDTA-K) are studied to functionalize the zinc oxide (ZnO) interlayers at the SnO 2 /CsPbI 2 Br buried interface to boost the photovoltaic performance of low-temperature C-IPSCs. This strategy can simultaneously passivate defects in ZnO and perovskite films, adjust interfacial energy level alignment, and release interfacial tensile stress, thereby improving interfacial contact, inhibiting ion migration, alleviating charge recombination, and promoting electron transport. As a result, a maximum PCE of 13.94% with a negligible hysteresis effect is obtained, which is one of the best results reported for low-temperature CsPbI 2 Br C-IPSCs so far. Moreover, the optimized devices without encapsulation demonstrate greatly improved operational stability., (© 2022 Wiley-VCH GmbH.)

Insect infestation and weed interference have a seriously negative impact on the growth, yield, and grain quality of maize. In this study, transgenic maize plants harboring three exogenous genes, cry2Ab , vip3A , and cp4epsps , that were constructed into a single T-DNA were developed for protection against insects and weeds. The transgene integration sites on the chromosomes in two transgenic maize events, CVC-1 and CVC-2, were determined using whole genome sequencing and specific PCR detection. As revealed by laboratory insect bioassays, these two transgenic events exhibited strong insecticidal toxicity against three major species of Lepidoptera insects, including Mythimna separata , Helicoverpa armigera , and Spodoptera frugiperda , with mortality rates exceeding 96%, 100%, and 100%, respectively, after six days of infestation. In addition, CVC-1 exhibited a high tolerance to glyphosate under field conditions. The successful expressions of cry2Ab , vip3A , and cp4epsps in various tissues at different developmental stages of CVC-1 were validated at the transcriptional and translational levels using quantitative real-time reverse transcription PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. These findings demonstrated that the transgenic maize CVC-1 developed using this triple gene construct has excellent insect resistance and herbicide tolerance, which may provide a valuable germplasm resource and data support for future maize breeding of insect and weed control.

High-efficiency electromagnetic interference (EMI) shielding and heat dissipation synergy materials with flexible, robust, and environmental stability are urgently demanded in next-generation integration electronic devices. In this work, we report the lamellar MXene/Aramid nanofiber (ANF) composite films, which establish a nacre-like structure for EMI shielding and heat dissipation by using the intermittent filtration strategy. The MXene/ANF composite film filled with 50 wt % MXene demonstrates enhanced mechanical properties with a strength of 230.5 MPa, an elongation at break of 6.2%, and a toughness of 11.8 MJ·m 3 (50 wt % MXene). These remarkable properties are attributed to the hydrogen bonding and highly oriented structure. Furthermore, due to the formation of the MXene conductive network, the MXene/ANF composite film shows an outstanding conductivity of 624.6 S/cm, an EMI shielding effectiveness (EMI SE) of 44.0 dB, and a superior specific SE value (SSE/ t ) of 18847.6 dB·cm 2 /g, which is better than the vacuum filtration film. Moreover, the MXene/ANF composite film also shows a great thermal conductivity of 0.43 W/m·K. The multifunctional MXene/ANF composite films with high-performance EMI shielding, heat dissipation, and joule heating show great potential in the field of aerospace, military, microelectronics, microcircuit, and smart wearable electronics.

Background Vascular calcification (VC), associated with enhanced cardiovascular morbidity and mortality, is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells. Inflammation promotes VC initiation and progression. Interleukin (IL)-29, a newly discovered member of type III interferon, has recently been implicated in the pathogenesis of autoimmune diseases. Here we evaluated the role of IL-29 in the VC process and underlying inflammatory mechanisms. Methods and Results The mRNA expression of IL-29 was significantly increased and positively associated with an increase in BMP2 (bone morphogenetic protein 2) mRNA level in calcified carotid arteries from patients with coronary artery disease or chronic kidney disease. IL-29 and BMP2 proteins are colocalized in human calcified arteries. IL-29 binding to its specific receptor IL-28Rα (IL-28 receptor α) (IL-29/IL-28Rα) inhibited the proliferation of rat vascular smooth muscle cells without altering cell apoptosis or migration. IL-29 promoted the calcification of rat vascular smooth muscle cells and their osteogenic transdifferentiation in vitro as well as the rat aortic ring calcification ex vivo, induced by the calcification medium or osteogenic medium. The procalcification effect of IL-29 was reduced by pharmacological inhibition of IL-29/IL-28Rα binding as well as suppression of janus kinase 2/signal transducer and activator of transcription pathway activation, accompanied by decreased BMP2 expression in the cultured rat vascular smooth muscle cells. Conclusions These results suggest an important role of IL-29 in VC development, at least partly, via activating the janus kinase 2/signal transducer and activator of transcription 3 signaling. Inhibition of IL-29 or its specific receptor, IL-28Rα, may provide a novel strategy to reduce VC in patients with vascular diseases.

Routine examination for intraoperative histopathologic assessment is lengthy and laborious. Here, we present the dark-field reflectance ultraviolet microscopy (DRUM) that enables label-free imaging of unprocessed and thick tissues with subcellular resolution and a high signal-to-background ratio. To the best of our knowledge, DRUM provides image results for pathological assessment with the shortest turnaround time (2-3 min in total from sample preparation to tissue imaging). We also proposed a virtual staining process to convert DRUM images into pseudo-colorized images and enhance the image familiarity of pathologists. By imaging various tissues, we found DRUM can resolve cell nuclei and some extranuclear features, which are comparable to standard H&E images. Furthermore, the essential diagnostic features of intraoperatively excised tumor tissues also can be revealed by DRUM, demonstrating its potential as an additional aid for intraoperative histopathology., Competing Interests: S. Ye, H. Li, and W. Zheng have applied for patents (Chinese Patent Application No.: CN202211224969.8 and CN202222637881.0) related to the work reported in this article., (© 2022 The Authors.)

Native mass spectrometry coupled to ion mobility (IM-MS) combined with collisional activation (CA) of ions in the gas phase ( in vacuo ) is an important method for the study of protein unfolding. It has advantages over classical biophysical and structural techniques as it can be used to analyze small volumes of low-concentration heterogeneous mixtures while maintaining solution-like behavior and does not require labeling with fluorescent or other probes. It is unclear, however, whether the unfolding observed during collision activation experiments mirrors solution-phase unfolding. To bridge the gap between in vacuo and in-solution behavior, we use unbiased molecular dynamics (MD) to create in silico models of in vacuo unfolding of a well-studied protein, the N-terminal domain of ribosomal L9 (NTL9) protein. We utilize a mobile proton algorithm (MPA) to create 100 thermally unfolded and coulombically unfolded in silico models for observed charge states of NTL9. The unfolding behavior in silico replicates the behavior in-solution and is in line with the in vacuo observations; however, the theoretical collision cross section (CCS) of the in silico models was lower compared to that of the in vacuo data, which may reflect reduced sampling.

MicroRNAs (miRNAs) play key regulatory roles in seed development and emerge as new key targets for engineering grain size and yield. The Zma-miRNA169 family is highly expressed during maize seed development, but its functional roles in seed development remain elusive. Here, we generated zma-miR169o and ZmNF-YA13 transgenic plants. Phenotypic and genetic analyses were performed on these lines. Seed development and auxins contents were investigated. Overexpression of maize miRNA zma-miR169o increases seed size and weight, whereas the opposite is true when its expression is suppressed. Further studies revealed that zma-miR169 acts by negatively regulating its target gene, a transcription factor ZmNF-YA13 that also plays a key role in determining seed size. We demonstrate that ZmNF-YA13 regulates the expression of the auxin biosynthetic gene ZmYUC1, which modulates auxin levels in the early developing seeds and determines the number of endosperm cells, thereby governing maize seed size and ultimately yield. Overall, our present study has identified zma-miR169o and ZmNF-YA13 that form a functional module regulating auxin accumulation in maize seeds and playing an important role in determining maize seed size and yield, providing a set of novel molecular tools for yield improvement in molecular breeding and genetic engineering., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Key Message: An R2R3-MYB transcription factor FOUR LIPS associated with B-type Cyclin-Dependent Kinase 1;1 confers salt tolerance in rice. The Arabidopsis FOUR LIPS (AtFLP), an R2R3 MYB transcription factor, acts as an important stomatal development regulator. Only one orthologue protein of AtFLP, Oryza sativa FLP (OsFLP), was identified in rice. However, the function of OsFLP is largely unknown. In this study, we conducted RNA-seq and ChIP-seq to investigate the potential role of OsFLP in rice. Our results reveal that OsFLP is probably a multiple functional regulator involved in many biological processes in growth development and stress responses in rice. However, we mainly focus on the role of OsFLP in salt stress response. Consistently, phenotypic analysis under salt stress conditions showed that osflp exhibited significant sensitivity to salt stress, while OsFLP over-expression lines displayed obvious salt tolerance. Additionally, Yeast one-hybrid assay and electrophoretic mobility shift assay (EMSA) showed that OsFLP directly bound to the promoter region of Oryza sativa B-type Cyclin-Dependent Kinase 1;1 (OsCDKB1;1), and the expression of OsCDKB1;1 was repressed in osflp. Disturbing the expression of OsCDKB1;1 remarkably enhanced the tolerance to salt stress. Taken together, our findings reveal a crucial function of OsFLP regulating OsCDKB1;1 in salt tolerance and largely extend the knowledge about the role of OsFLP in rice., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Designing and fabricating well-aligned metal-organic framework nanoarrays (MOF NAs) with high electrocatalytic activity and durability for water oxidation at large current density remain huge challenges. Here the vertical NiFc-MOF NAs constructed from agaric-like nanosheets were fabricated by introducing a ligand containing an exotic Fe atom to coordinate with Ni ion using Ni(OH) 2 NAs as a self-sacrificing template. The NiFc-MOF NAs exhibited superior water oxidation performance with a very low overpotential of 161 mV at the current density of 10 mA cm -2 . Chronoamperometry was tested at an overpotential of 250 mV, which delivered an initial industrial-grade current density of 702 mA cm -2 and still remained at 694 mA cm -2 after 24 h. Furthermore, it possessed fast reaction kinetics with a small Tafel slope of 29.5 mV dec -1 . The superior electrocatalytic performance can be ascribed to the structural advantage of vertically grown agaric-like NAs and the synergistic electron coupling between Ni and Fe atoms, namely, electron transfer from Ni to Fe atoms in NiFc-MOF NAs. The exposed density and valence state of active Ni sites were synchronously increased. Furthermore, the energy barrier for the adsorption/desorption of oxygenated intermediates was ultimately optimized for water oxidation. This work provides a novelty orientation to accelerate electrocatalytic performance of MOF NAs by introducing self-sacrificing templates containing one metal and synergistic ligand containing dissimilar metal.

Background: Climate change caused by environmental pollution is the most important one of many environmental health hazards currently faced by human beings. In particular, the extreme temperature is an important risk factor for death from respiratory and circulatory diseases. This study aims to explore the meteorological-health effect and find out the vulnerable individuals of extreme temperature events in a less developed city in western China., Method: We collected the meteorological data and data of death caused by respiratory and circulatory diseases in Mianyang City from 2013 to 2019. The nonlinear distributed lag model and the generalized additive models were combined to study the influence of daily average temperature (DAT) on mortality from respiratory and circulatory diseases in different genders, ages., Results: The exposure-response curves between DAT and mortality from respiratory and circulatory diseases presented a nonlinear characteristic of the "V" type. Cumulative Relative Risk of 30 days (CRR 30 ) of deaths from respiratory diseases with 4.48 (2.98, 6.73) was higher than that from circulatory diseases with 2.77 (1.96, 3.92) at extremely low temperature, while there was no obvious difference at extremely high temperature. The health effects of low temperatures on the respiratory system of people of all ages and genders were persistent, while that of high temperatures were acute and short-term. The circulatory systems of people aged < 65 years were more susceptible to acute effects of cold temperatures, while the effects were delayed in females and people aged ≥65 years., Conclusion: Both low and high temperatures increased the risk of mortality from respiratory and circulatory diseases. Cold effects seemed to last longer than heat did., (© 2022. The Author(s).)

Salt stress significantly reduces the productivity of crop plants including maize (Zea mays). miRNAs are major regulators of plant growth and stress responses, but few studies have examined the potential impacts of miRNAs on salt stress responses in maize. Here, we show that ZmmiR169q is responsive to stress-induced ROS signals. After detecting that salt stress and exogenous H2O2 treatment reduced the accumulation of ZmmiR169q, stress assays with transgenic materials showed that depleting ZmmiR169q increased seedling salt tolerance whereas overexpressing ZmmiR169q decreased salt tolerance. Helping explain these observations, we found that ZmmiR169q repressed the transcript abundance of its target NUCLEAR FACTOR YA8 (ZmNF-YA8), and overexpression of ZmNF-YA8 in maize improved salt tolerance, specifically by transcriptionally activating the expression of the efficient antioxidant enzyme PEROXIDASE1. Our study reveals a direct functional link between salt stress and a miR169q-NF-YA8 regulatory module that plants use to manage ROS stress and strongly suggests that ZmNF-YA8 can be harnessed as a resource for developing salt-tolerant crop varieties., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Proteins fold on relatively smooth free energy landscapes which are biased toward the native state, but even simple topologies which fold rapidly can experience roughness on their free energy landscape. The details of these interactions are difficult to elucidate experimentally. Closely related to the problem of deciphering the details of the free energy landscape is the problem of defining the interactions in the denatured state ensemble (DSE) which is populated under native conditions, that is, under conditions where the native state is stable. The DSE of many proteins deviates from random coil models, but quantifying and defining the energetics of the transiently populated interactions in this ensemble is extremely challenging. Characterization of the DSE of proteins which fold to compact structures is also relevant to studies of intrinsically disordered proteins (IDPs) since interactions in the dynamic ensemble populated by IDPs can modulate their behavior. Here we show how experimental thermodynamic and p K a measurements can be combined with computational thermodynamic integration to quantify interactions in the DSE. We show that non-native side chain interactions can stabilize native backbone structure in the DSE and demonstrate that that even rapidly folding proteins can form energetically significant non-native interactions in their DSE. As an example, we characterize a non-native salt bridge that stabilizes local native backbone structure in the DSE of a widely studied fast-folding protein, the villin headpiece helical domain. The combined computational experimental approach is applicable to other protein unfolded states and provides insight that is impossible to obtain with either method alone.

Objectives: Glioma is the most common tumor of the central nervous system. In this review, we outline the immunobiological factors that interact with glioma cells and tumor microenvironment (TME), providing more potential targets for clinical inhibition of glioma development and more directions for glioma treatment., Content: Recent studies have shown that glioma cells secrete a variety of immune regulatory factors and interact with immune cells such as microglial cells, peripheral macrophages, myeloid-derived suppressor cells (MDSCs), and T lymphocytes in the TME. In particular, microglia plays a key role in promoting glioma growth. Infiltrating immune cells induce local production of cytokines, chemokines and growth factors. Further leads to immune escape of malignant gliomas., Summary and Outlook: The complex interaction of tumor cells with the TME has largely contributed to tumor heterogeneity and poor prognosis. We review the immunobiological factors, immune cells and current immunotherapy of gliomas, provide experimental evidence for future research and treatment of gliomas., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2020 Houminji Chen et al., published by De Gruyter, Berlin/Boston.)

Ultrasound stimulation has recently emerged as a non-invasive method for modulating brain activity in animal and human studies with healthy subjects. Whether brain diseases such as Alzheimer's disease, epilepsy, and depression can be treated using ultrasound stimulation still needs to be explored. Recent studies have reported that ultrasound stimulation suppressed epileptic seizures in a rodent model of epilepsy. These findings raise the crucial question of whether ultrasound stimulation can inhibit seizures in non-human primates with epilepsy. Here, we addressed this critical question. We confirmed that ultrasound stimulation significantly reduced the frequency of seizures in acute epileptic monkeys. Furthermore, the results showed that the number and duration of seizures were reduced, whereas the inter-seizure interval was increased after ultrasound stimulation. Besides, no significant brain tissue damage was observed by T2-weighted MR imaging. Our results are of great importance for future clinical applications of ultrasound neuromodulation in patients with epilepsy., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Although the clinical outcomes continue to be scrutinized, there are a few data summarizing the changes in perfusion parameters in postoperative patients. The objective was to undertake a systematic literature review and perform a meta-analysis to assess the effects of cerebral perfusion changes in cognitive and functional status., Methods: A systematic search was conducted in July 2018 identifying articles comparing perfusion parameter changes before and after carotid revascularization in patients with carotid artery stenosis. Combined overall effect sizes were calculated using random-effects models., Results: The literature search identified 1031 unique articles eligible for analysis. Sixteen studies including 755 patients were identified. The studies were different for many methodological factors, for example, sample size, type of patients, statistical measure, type of test, timing of assessment, and so on. There were no differences in cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO 2 ), and relative cerebral blood volume (rCBV) between preintervention and postintervention, but there was a significant increase of cerebral blood flow (CBF) (95% confidence interval [CI] standardized mean difference [Std. MD] : -0.83 [-1.27, -0.40]; P = 0.0002; I 2  = 68%) and relative cerebral blood flow (rCBF) (95% CI Std. MD: -0.72 [-1.61, -0.27]; P < 0.0001; I 2  = 48%) after operation. In addition, the perfusion of mean transit time (MTT) (95% CI Std. MD: 1.26 [0.62, 1.90]; P = 0.0001; I 2  = 84%), oxygen extraction fraction (OEF) (95% CI Std. MD: 0.78 [0.24, 1.33]; P = 0.005; I 2  = 0%), time to peak (TTP) (95% CI Std. MD: 0.46 [0.16, 0.77]; P = 0.003; I 2  = 47%), and relative mean transit time (rMTT) (95% CI Std. MD: 0.41 [0.33, 0.50]; P < 0.00001; I 2  = 67%) was higher before than after operation., Conclusions: The increase in changes in CBF and rCBF and the decrease in MTT, OEF, TTP, and rMTT after operation may indicate the improvement of cognition in the short term. Intraoperative perfusion parameters could be an important adjuvant monitoring method in neurocognitive changes after carotid revascularization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Islet amyloid polypeptide (IAPP), a 37 residue polypeptide, is the main protein component of islet amyloid deposits produced in the pancreas in Type 2 diabetes. Human IAPP contains five serine residues at positions 19, 20, 28, 29, and 34. Models of the IAPP amyloid fibril indicate a structure composed of two closely aligned columns of IAPP monomers with each monomer contributing to two intermolecular β-strands. Ser 19 and Ser 20 are in the partially ordered β-turn region, which links the two strands, whereas Ser 28, Ser 29, and Ser 34 are in the core region of the amyloid fibril. Ser 29 is involved in contacts between the two columns of monomers and is the part of the steric zipper interface. We undertook a study of individual serine substitutions with the hydrophobic isostere 2-aminobutyric acid (2-Abu) to examine the site-specific role of serine side chains in IAPP amyloid formation. All five variants formed amyloid. The Ser 19 to 2-Abu mutant accelerates amyloid formation by a factor of 3 to 4, while the Ser 29 to 2-Abu mutation modestly slows the rate of amyloid formation. 2-Abu replacements at the other sites had even smaller effects. The data demonstrate that the cross-column interactions made by residue 29 are not essential for amyloid formation and also show that cross-strand networks of hydrogen-bonded Ser side chains, so called Ser-ladders, are not required for IAPP amyloid formation. The effect of the Ser 19 to 2-Abu mutant suggests that residues in this region are important for amyloid formation by IAPP., (© 2019 The Protein Society.)

Intrinsically disordered proteins (IDPs) play important roles in biology, but little is known about the energetics of their inter-residue interactions. Methods that have been successfully applied to analyze the energetics of globular proteins are not applicable to the fluctuating partially ordered ensembles populated by IDPs. A combined computational experimental strategy is introduced for analyzing the energetic role of individual residues in the free state of IDPs. The approach combines experimental measurements of the binding of wild-type and mutant IDPs to their partners with alchemical free energy calculations of the structured complexes. These data allow quantitative information to be deduced about the free state via a thermodynamic cycle. The approach is validated by the analysis of the effects of mutations upon the binding free energy of the ovomucoid inhibitor third binding domain to its partners and is applied to the C-terminal domain of the measles virus nucleoprotein, a 125-residue IDP involved in the RNA transcription and replication of measles virus. The analysis reveals significant inter-residue interactions in the unbound IDP and suggests a biological role for them. The work demonstrates that advances in force fields and computational hardware have now led to the point where it is possible to develop methods, which integrate experimental and computational techniques to reveal insights that cannot be studied using either technique alone.

In the framework of the 2018 Drug Design Data Resource grand challenge 4, blinded predictions on relative binding free energy were performed for a set of 39 ligands of the Cathepsin S protein. We leveraged the GPU-accelerated thermodynamic integration of Amber 18 to advance our computational prediction. When our entry was compared to experimental results, a good correlation was observed (Kendall's τ: 0.62, Spearman's ρ: 0.80 and Pearson's R: 0.82). We designed a parallelized transformation map that placed ligands into several groups based on common alchemical substructures; TI transformations were carried out for each ligand to the relevant substructure, and between substructures. Our calculations were all conducted using the linear potential scaling scheme in Amber TI because we believe the softcore potential/dual-topology approach as implemented in current Amber TI is highly fault-prone for some transformations. The issue is illustrated by using two examples in which typical preparation for the dual-topology approach of Amber TI fails. Overall, the high accuracy of our prediction is a result of recent advances in force fields (ff14SB and GAFF), as well as rapid calculation of ensemble averages enabled by the GPU implementation of Amber. The success shown here in a blinded prediction strongly suggests that alchemical free energy calculation in Amber is a promising tool for future commercial drug design.

In rice, and other major cereal grass crops, stomata are arranged in linear files parallel to the long growth axis of leaves. Each stomatal unit comprises two dumbbell-shaped guard cells flanked by two subsidiary cells. These morphological and developmental characteristics enable grass stomata to respond to environmental changes more efficiently. Cyclin-dependent kinases (CDKs) and their cyclin partners co-ordinate cell proliferation and differentiation during the development of multicellular organisms. In contrast to animals, plants have many more types and members of cyclins. In Arabidopsis, four A2-type cyclins (CYCA2s) function redundantly in regulating CDKB1 activity to promote the asymmetric division for stomatal initiation and the symmetric division of guard mother cells (GMCs). In this study, we examine the function of the single A2-type cyclin in rice, OsCYCA2;1, as well the single B1-type CDK, OsCDKB1;1. Cross-species complementation tests demonstrated that OsCYCA2;1 and OsCDKB1;1 could complement the defective stomatal phenotypes of Arabidopsis cyca2 and cdkb1 mutants, but also could suppress DNA endoduplication and cell enlargement. The early asymmetric divisions that establish the stomatal lineages are often missing within the stomatal cell files of OsCYCA2;1-RNAi rice transgenic lines, leading to a significantly reduced stomatal production. However, GMC divisions are not disrupted either in OsCYCA2;1-RNAi or in OsCDKB1;1-RNAi rice transgenic lines as expected. Our results demonstrate a conserved but diverged function and behavior of rice A2-type cyclins, which might be associated with the distinct stomatal development pathways between rice and Arabidopsis.

The rational and predictable enhancement of protein stability is an important goal in protein design. Most efforts target the folded state, however stability is the free energy difference between the folded and unfolded states thus both are suitable targets. Strategies directed at the unfolded state usually seek to decrease chain entropy by introducing cross-links or by replacing glycines. Cross-linking has led to mixed results. Replacement of glycine with an l-amino acid, while reducing the entropy of the unfolded state, can introduce unfavorable steric interactions in the folded state, since glycine is often found in conformations that require a positive φ angle such as helical C-capping motifs or type I' and II″ β-turns. l-Amino acids are strongly disfavored in these conformations, but d-amino acids are not. However, there are few reported examples and conflicting results have been obtained when glycines are replaced with d-Ala. We critically examine the effect of Gly-to-d-Ala substitutions on protein stability using experimental approaches together with molecular dynamics simulations and free energy calculations. The data, together with a survey of high resolution structures, show that the vast majority of proteins can be stabilized by substitution of C-capping glycines with d-Ala. Sites suitable for substitutions can be identified via sequence alignment with a high degree of success. Steric clashes in the native state due to the new side chain are rarely observed, but are likely responsible for the destabilizing or null effect observed for the small subset of Gly-to-d-Ala substitutions which are not stabilizing. Changes in backbone solvation play less of a role. Favorable candidates for d-Ala substitution can be identified using a rapid algorithm based on molecular mechanics.

Purpose: To examine the safety, feasibility, and mid-term efficacy of the chimney technique for aortic arch pathologies., Methods: From February 2011 to December 2014, a total of 35 patients (30 men; mean age 54.3 ± 14.1 years) with aortic arch pathologies underwent thoracic endovascular aortic repair combined with chimney stents. The indication was a proximal landing zone <1.5 cm. Follow-up was performed at 3, 6, and 12 months and then yearly thereafter., Results: A total of 36 chimney stents were deployed (innominate artery, n = 1; left common carotid artery, n = 9; right subclavian artery, n = 1; left subclavian artery, n = 25). The technical success rate was 94.3 % (33/35). Immediate type Ia endoleaks (ELIa) were observed in two patients (8.6 %, 2/35). Twenty-five patients were successfully followed-up for a median period of 29.3 months (range, 6-48 months). One patient died due to aortic dissection aneurysm rupture at 36 months (mortality rate of 4 %, 1/25). Three late ELIa were observed and no reinterventions were performed. The overall incidence of ELIa was 20 % (5/25). During follow-up, the patency rate for chimney stents was 92 % (23/25)., Conclusion: Our limited experience demonstrates that the chimney technique is a viable and relatively safe treatment for patients with challenging thoracic aortic pathologies at least in the mid-term follow-up period.

Background: SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear., Methods: The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 µmol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting., Results: Over expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-κB p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-κB p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05)., Conclusions: Upregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.