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Simple Summary: It is important to know exactly the difference in changes in Complement C5a Receptor 1 (C5aR1) levels at onset and in Immunoglobulin G (IgG) levels after recovery between severe and non-severe coronavirus disease 2019 (COVID-19) patients to reduce the severity of the disease and prevent reinfection with severe acute respiratory syndrome coronavirus 2. We found that some of these changes in C5aR1 and IgG levels over time were dependent on their initial levels and not suitable for analysis by conventional statistical tests. We developed new t-tests that correctly examine the above changes. Our new t-test suggested a greater increase in C5aR1-levels at onset and a smaller decrease in IgG-levels after recovery in COVID-19 patients than non-COVID-19 patients, which were not detected by conventional statistical tests. Thus, the clinical trials should be analyzed with not only conventional statistical tests but also our new t-test. (1) Background: It is our purpose to identify the differences in the changes in Complement C5a receptor 1 (C5aR1) levels showing the degree of inflammation at onset and Immunoglobulin G (IgG) levels showing the extent of survival of the virus fragments after recovery between coronavirus disease 2019 (COVID-19) and pneumonia coronavirus disease (non-COVID-19) for saving patients' lives. (2) Methods: First, the studies showing these markers' levels in individual patients before and after the passage of time were selected from the PubMed Central® databases with the keywords (((COVID-19) AND individual) NOT review) AND C5a/IgG. Then, no changes in these markers' levels with conventional analyses were selected from the studies. Finally, the no changes were reexamined with our new two-tailed t-test using the values on the regression line between initial levels and changed levels instead of the mean or median of changed levels as the expected values of changed levels. (3) Results: Not conventional analyses but our new t-test suggested a greater increase in C5aR1-levels at onset and a smaller decrease in IgG-levels after recovery in COVID-19 patients than non-COVID-19 patients. (4) Conclusion: Our new t-test also should be used in clinics for COVID-19 patients. [ABSTRACT FROM AUTHOR]

• Discovery of sandwiched beam systems for topological phase transition. • Development of the spectral element method for such sandwiched beam systems. • Determination of geometric phases for explaining the underlying mechanism of phase transition. • Investigation of effects of various outer fields on frequency behaviors. • Analysis of the robustness of topologically protected interface states. Topological phononic crystals (PnCs) have attracted tremendous research attention in recent years. A significant hallmark of these structures is that these crystals can support interface modes that are robust to structural disturbance and protected by topology. In this study, we propose a new type of active sandwiched PnC beam for inducing topological geometric phase transition and topologically protected interface modes (TPIMs) for one-dimensional (1D) systems. The layered system comprises two commonly used active materials, i.e., barium titanate (BaTiO 3) and cobalt ferric oxide (CoFe 2 O 4). Analytical modeling for this layered system is derived in the framework of linearly constitutive relations of a magneto-electro-elastic (MEE) material with temperature effects. Two analytical approaches, i.e., the spectral element method (SEM) and the plane wave expansion (PWE) method, are applied to derive the theoretical band structure of the system and excellent agreement is reported. A numerical analysis based on the finite element method (FEM) is adopted for further validation. The influence of outer fields in the bandgap frequency is examined and the size-dependent properties are also analyzed. Moreover, the transmission response is determined via analytical modeling and numerical analysis. It is found that the robust TPIMs are immune to defects and disorders. Conclusively, this study puts forward a new type of beam system for inducing topological phase transition. It can be readily extended to more complex systems and higher-order models. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction Cereals are an important source of food, feed and fuel with a rapidly increasing global demand. However, cereal seeds contain high levels of starch and polysaccharides, making the isolation of high quality RNA extremely difficult. Objective To develop a novel method for extracting high quality total RNA from various starch- and polysaccharides-rich cereal seeds, such as maize, rice, sorghum and wheat. Methodology We developed a modified sodium dodecyl sulphate (SDS)/TRIzol method. The combined use of a Tris buffer (pH 9.0) and SDS before TRIzol extraction effectively resolved the problem of seed homogenate solidification in such a buffer. A high concentration of SDS was used separately, not only to promote cell lysis but also to effectively dissolve seed sample containing high levels of starch. Moreover, acid phenol saturated with 0.1 m citrate buffer (pH 4.3) was used to separate RNA from DNAs, proteins and high levels of starch. This rapid protocol was compared with other RNA isolation methods preferentially used for plants rich in polysaccharides and secondary metabolites. Results Gel electrophoresis analysis indicated that the extracted total RNA had good integrity without apparent DNA contamination. Furthermore, an A260/280 ratio of approximately 2.0, an A260/230 ratio of more than 2.0 and RIN values of more than 8.6 indicated that the isolated RNA was of high purity. The isolated RNA was suitable for subsequent molecular manipulations, such as reverse-transcription polymerase chain reaction (PCR), rapid amplification of cDNA ends (RACE) and real-time PCR. Conclusion The study has described an easy, efficient and highly reproducible method for RNA isolation from various cereal seeds. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Expansins are unique plant cell wall proteins that possess the ability to induce immediately cell wall extension in vitro and cell expansion in vivo. To investigate the biological functions of expansins that are abundant in wood-forming tissues, we cloned two expansin genes from the differentiating xylem of Chinese fir ( Cunninghamia lanceolata (Lamb.) Hook). Phylogenetic reconstruction indicated that they belong to α-expansin (EXPA), named ClEXPA1 and ClEXPA2. Expression pattern analysis demonstrated that they are preferentially expressed in the cambium region. Overexpression of ClEXPA1 and ClEXPA2 in tobacco plants yielded pleiotropic phenotypes of plant height, stem diameter, leaf number and seed pod. The height and diameter growth of the 35S: ClEXPA1 and 35S: ClEXPA2 transgenic plants were increased drastically, exhibiting an enlargement of pith parenchyma cell size. Isolated cell walls of ClEXPA1 and ClEXPA2 overexpressors contained 30%-50% higher cellulose contents than the wild type, accompanied by a thickening of the cell walls in the xylem region. Both ClEXPA1 and ClEXPA2 are involved in plant growth and development, with a partially functional overlap. Expansins are not only able to induce cell expansion in different tissues/organs in vivo, but they also can act as a potential activator during secondary wall formation by directly or indirectly affecting cellulose metabolism, probably in a cell type-dependent manner. [ABSTRACT FROM AUTHOR]

[Display omitted] Determining strong robustness in flexural wave propagation in beam systems has always been a promising achievement with various real-life applications such as energy harvesting and waveguiding. In this manuscript, the bending characteristics of a phononic crystal beam on periodically alternated linear elastic support systems with topologically protected wave propagation are proposed. Based on the Timoshenko beam theory, general solutions of this periodic beam-foundation topological system are obtained. Subsequently, by applying the Bloch theory, the dispersion relation is obtained using the transfer matrix method. Comparing with finite element numerical solutions, excellent agreement is observed with only a minor difference due to the assumptions in the Timoshenko beam theory. Generally, any breaking of spatial symmetry in beam systems can be achieved by changing geometry of beam cross-sections or tuning the material properties of substructures. We herein propose a new approach to break the spatial symmetry, i.e., tuning the elastic stiffnesses of the periodically alternated elastic supports. It is found that beam bending on an infinite continuously distributed elastic foundation leads to a band-crossing point. After tuning the elastic support stiffness in a periodic manner, the band-crossing point is broken and a new bandgap appears due to the breaking of structural symmetry. Further, a mode shape inversion and Zak phase transition are captured. Based on a unit cell analysis, we examine the topologically protected interface modes in an array constructed with periodically arranged unit cells with two corresponding phase states. Furthermore, several numerical examples are used to demonstrate the defect- and disorder-immune properties in this one-dimensional topological system. This new proposed general mechanism can be extended to establish topological phase transitions in other mechanical and dynamic systems. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO2) enhanced oil recovery (EOR) is considered to be an effective measure to increase oil productivity by injecting CO2 into reservoirs. Nevertheless, the injection of CO2 can potentially induce instability in discontinuities such as faults and fractures within the reservoir, influencing the safety and efficiency of the operation. Qualitative analysis of fault stability was implemented in the integrated process of CO2-EOR, by integrating fluid dynamics models, in-situ stress conditions and rock mechanics parameters. The results show that there is a pressure decreasing region around the oil producer, and CO2 injection has a prominent influence on reservoir pressure maintenance. The reservoir pressure and liquid flow of oil producer is slightly higher from the beginning of CO2 injection. The minimum effective normal stress and the maximum slip tolerance of the faults are aligned with the axis between the CO2 injector and the oil producer. The fault friction angle is the primary factor in discontinuity stability analysis, influencing the slip rate and mode during CO2-EOR. The larger the friction angle, the fewer faults are in the critical slip state. Fault stability analysis is a complete assessment, indicating that a fault may remain stable even if certain parts reach a critical state. [ABSTRACT FROM AUTHOR]

• Analysis of band structures of phononic crystal beams resting on elastic foundation. • Discovery of topological properties by capitalizing the negative capacitance. • Investigation of the effects of elastic foundation on the system. • Tunable frequency range of the topologically protected interface mode. This work presents the active control effects on a piezoelectric phononic crystal beam resting on elastic foundation. The bending of passive periodic beams that rest on elastic foundation can exhibit distinguished applications for geotechnical and railroad structures. Generally, elastic waves propagate in these structures in a certain frequency range and these structures are able to block the other input waves outside this range. These two frequency ranges are usually called the pass band and the bandgap of structures. With periodic attachment of piezoelectric patches having negative capacities, the structural band properties can be easily tuned to a wider range. However, the beam system with negative capacities is always restricted by the presence of electrical boundary conditions in the structural stability response. It leads to tuning inconvenience and tuning disabilities of the structures. In view of these tuning shortcomings, this study proposes to capitalize the effects of elastic foundation or elastic supports to improve the active control of piezoelectric beams for bandgap generation in wave propagation. By artificially positioning periodic negative capacities and piezoelectric patches, the system sub-structure is designed as an A-B-A phononic crystal beam. Further, the plane wave expansion method is applied to the governing equation to derive analytical solutions and to compare with numerical solutions. The topologically protected phase transition is observed by analyzing mode shapes of the specific cases and the Zak phase across the Brillouin zone. The topologically protected interface modes are also captured in this system and the topologically protected manner provides a new paradigm for manipulating wave propagations in the bending of beam system resting on the elastic foundation. Finally, the efficiency of electrical parameters and foundation stiffness on system tuning is examined. The controllable system is further justified to allow operation in a wider frequency range. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The traditional ip-iq harmonic detection method is widely used in APF, but it sacrifices the response speed and detection accuracy of the APF system due to the limitations of the traditional phase-locked loop and LPF. Therefore, in order to make APF both higher detection accuracy and faster response speed, a harmonic detection method based on dual second-order sliding-window discrete Fourier transform (DS-SDFT) is proposed, which can accurately detect harmonics with DSOGI-PLL and greatly reduce the computational effort by using half-cycle sliding-window iterative discrete Fourier transform, solving the inherent defects of traditional phase-locked loops and LPFs. Meanwhile, in order to compensate the harmonics better, the model predictive control with stronger dynamic response capability is used in the current compensation control. Finally, the APF based on this harmonic detection method and current control strategy is fast in response and high in detection accuracy, which is proved by the simulation and experimental results, and the effectiveness of the detection method is verified. [ABSTRACT FROM AUTHOR]

Understanding the dynamic mechanical behaviors and microstructural properties of outburst-prone coal is significant for preventing coal and gas outbursts during underground mining. In this paper, the split Hopkinson pressure bar (SHPB) tests were completed to study the strength and micro-structures of outburst-prone coal subjected to compressive impact loading. Two suites of coals—outburst-prone and outburst-resistant—were selected as the experimental specimens. The characteristics of dynamic strength, failure processes, fragment distribution, and microstructure evolution were analyzed based on the obtained stress-strain curves, failed fragments, and scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR) images. Results showed that the dynamic compressive strength inclined linearly with the applied strain rate approximately. The obtained dynamic stress-strain responses could be represented by a typical curve with stages of compression, linear elasticity, microcrack evolution, unstable crack propagation, and rapid rapture. When the loading rate was relatively low, fragments fell in tension. With an increase in loading rates, the fragments fell predominantly in shear. The equivalent particle size of coal fragments decreased with the applied strain rate. The Uniaxial compressive strength (UCS) of outburst-prone coal was smaller than that of resistant coal, resulting in its smaller equivalent particle size of coal fragments. Moreover, the impact loading accelerated the propagation of fractures within the specimen, which enhanced the connectivity within the porous coal. The outburst-prone coal with behaviors of low strength and sudden increase of permeability could easily initiate gas outbursts. [ABSTRACT FROM AUTHOR]

The classical model predictive control (MPC) usually aims to minimize the current error at the end of the control period. This method is equivalent to minimizing the current total harmonic distortion (THD) when the control period tends to be infinitely small. However, due to the limitations of hardware in practice, the optimization effect of current THD is not obvious. Aiming at the above problem, an improved double-vector model predictive control method is proposed for the single-phase active-neutral-point-clamped five-level (ANPC-5L) inverter. Two voltage vectors in each control cycle are used in this method to reduce the current THD by minimizing the area enclosed by the actual and reference current. In addition, a capacitor voltage control method is designed for the problem of multiple control objectives coupling in this structure. In this method, an idea of hierarchy is designed for voltage jump and switching transition limits, neutral point (NP) voltage, and flying capacitor (FC) voltage, achieving the effect of weightless factor and good dynamic and static performance. Finally, the effectiveness of the proposed method is verified by simulation and experimental results. [ABSTRACT FROM AUTHOR]

Summary Genomic imprinting is an epigenetic phenomenon occurring in mammals and flowering plants, causing genes to be expressed depending on their parent of origin. In plants, genomic imprinting is mainly confined to the endosperm, a nutritive tissue supporting embryo growth, similar to the placenta in mammals. Here, we show that the paternally expressed imprinted gene PEG2 transcript sequesters the transposable element (TE)-derived small interfering RNA (siRNA) siRNA854 in the endosperm. siRNA854 is present in the vegetative cell of pollen and transferred to the central cell of the female gametophyte after fertilization, where it is captured by PEG2. Depletion of siRNA854 as a consequence of increased PEG2 transcript levels establishes a reproductive barrier and prevents successful hybridizations between plants differing in chromosome number (ploidy). Thus, the balance of a male gamete accumulating TE-derived siRNA and a paternally expressed imprinted gene regulate triploid seed viability, revealing a transgenerational speciation mechanism. Highlights • The imprinted gene PEG2 acts as a sponge for the transposon-derived siRNA854 • Depletion of siRNA854 in the endosperm causes triploid seed abortion • siRNA854 is generated in pollen and acts transgenerationally in the endosperm • Regulation of UBP1b by siRNA854 is causally connected to triploid seed viability Hybridizations of plants that differ in chromosome number (ploidy) frequently lead to seed abortion. Wang et al. show that the imprinted gene PEG2 acts as a sponge for the transposon-derived siRNA854 in the endosperm. Increased dosage of PEG2 depletes siRNA854 , causing triploid seed abortion. [ABSTRACT FROM AUTHOR]

Purpose: As for vibrating screen, the separation of granular materials is a very complicated process, particularly the screening with a swing trace. To study the characteristics of stratification and penetration in the swing vibrating screen, a three-dimensional numerical model was developed to simulate the screening process. Design/methodology/approach: The discrete element method (DEM) was used to perform the numerical simulation, and the kinetic model of the swing screening was established. The regions of stratification and penetration were defined, and the mathematical functions relating fine particle ratio of stratification and penetration to time were presented using the least squares method. Findings: The results show that the low value of frequency (5 and 10 Hz) has a limited effect on the stratification, while the obvious effect can be found at high frequency. A low frequencies or small swing angles may enhance the particle penetration. By studying the vibration parameters affecting the stratification and penetration rate, it is found that the frequency has more influence than the swing angle. Originality/value: The higher screening efficiency and processing capacity can be further obtained for the swing vibrating screen by comparing with the linear vibrating screen. These results reveal the fundamental characteristics of particle motion in the swing screening, which will provide reliable guidance for studying the design optimization of vibrating screen. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) imaging is pervasively utilized for detecting tumors and internal body injuries. CT image retargeting means to horizontally/vertically shrink the semantically non-salient regions (e.g , the normal organs) while preserving the salient ones (e.g. , the diseased organs) inside a CT image, as exemplified in Fig. 1. In practice, retargeting can substantially facilitate CT image displaying, which can benefit the subsequent medical treatment. In this work, we propose a bio-inspired CT image retargeting pipeline by mimicking human gaze behavior. More specifically, for each CT image, we extract the gaze shifting path (GSP) to capture human gaze distribution during the visual perception toward each CT image. Afterward, a multi-attribute binary hashing (MABH) is formulated to exploit the semantics of these GSPs. Thereby, each graphlet can be converted into the binary hash codes. Finally, the hash codes corresponding to GSP from each CT image are quantized into a feature vector, which is leveraged to learn a Gaussian mixture model (GMM) that guides CT image shrinking. In the experiments, to evaluate how gaze allocation influencing CT image retargeting, a user study is designed to compare the GSPs produced by normal observers and Alzheimer's patients respectively. Besides, a comparative study has verified the superiority of our method. • A new multi-attribute binary hashing with an iterative solution. • A novel fast and accurate CT image retargeting model. • A comprehensive user study with 33 Alzheimer's patients. [ABSTRACT FROM AUTHOR]

In this study, ordinary bamboo charcoal was activated at 750 °C with a steam flow rate of 6.25 L/min for 1.5 h. The effects of triglyceride adsorption by activated bamboo charcoal were investigated using an orthogonal design, and the adsorption mechanism was explored through molecular dynamics. Experimental results revealed that the adsorption capacity of activated bamboo charcoal for triglycerides reached 27.0%. The activated bamboo charcoal exhibited a specific surface area of 560.0 m2/g. The average pore diameter of activated bamboo charcoal was 1.6 nm, whereas that of ordinary bamboo charcoal was 7.2 nm. Molecular dynamics simulations revealed an interaction energy of − 145.12 kcal/mol between the molecular layers of activated bamboo charcoal and the triglyceride molecules, as well as an interaction energy of − 132.73 kcal/mol between the molecular layers of ordinary bamboo charcoal and the triglyceride molecules. The quantity of triglyceride molecules adsorbed by activated bamboo charcoal per gram was estimated to be 1.77 × 1021 while ordinary bamboo charcoal could adsorb merely 1.56 × 1019 triglyceride molecules per gram. This stark contrast in adsorption capacity underscores the superior performance of activated bamboo charcoal than its counterpart. [ABSTRACT FROM AUTHOR]

The transformation between Cr(III) and Cr(VI) occurs in Cr-contaminated soil, which can be regulated by root-soil interactions, under natural conditions. In situ investigation of the effectiveness of different reductants in reducing Cr(VI) to Cr(III), and thereby the reoccurrence risk in reduced Cr-contaminated soil, can improve the understanding of Cr biogeochemistry and toxicity. Traditional and high-resolution diffusive gradients in thin films (DGT) were used to measure Cr(VI) availability and rhizosphere effect controlling the chemical behaviors of Cr(VI) in the rice rhizosphere microdomain. The Cr(VI) concentration in the soil solution (Csoln) of the rhizosphere region varied according to the reductant type and followed the order: Molasses > CaS4 >Fe(II). Rice root activity increased the Csoln in the rhizosphere region by 2.16 μg/L, 1.90 μg/L, and 1.08 μg/L for Fe(II), CaS4, and Molasses treatments, respectively. The Cr(VI) concentration measured by DGT (CDGT) in the reduced Cr-contaminated soils increased from 0.96–1.17 μg/L in the bulk region to 1.23–1.76 μg/L in rhizosphere region. The variation in the effective concentration of Cr(VI) (CE) was similar to that of Csoln in the rice rhizosphere microdomain. Csoln accounted for 14.71–19.36% of the CE, further suggesting that bioavailable Cr(VI) mainly originated from the replenishment from the solid phase. The sequence of the average Cr(VI) flux in the reduced Cr-contaminated soil was Molasses, CaS4, and Fe(II). Except for Molasses, there was no obvious Cr(III) in Fe(II) and CaS4. For Fe(II), a higher phosphate flux in the rhizosphere microdomain hindered Cr(VI) uptake. High-resolution imaging provides a theoretical basis for the bioavailability evaluation and remediation of Cr-contaminated soil. Compared with CaS4 and Molasses, Fe(II) was the most effective reductant for remediating Cr-contaminated soils. [ABSTRACT FROM AUTHOR]

Plasma membrane-associated abscisic acid (ABA) signal transduction is an integral part of ABA signaling. The C2-domain ABA-related (CAR) proteins play important roles in the recruitment of ABA receptors to the plasma membrane to facilitate ABA signaling. However, how CAR proteins are regulated remains unclear. In this study, we conducted a genetic screen for mutants with altered leaf transpiration and identified an uncharacterized protein, LOWER TEMPERATURE 1 (LOT1), which regulates the dynamic localization and stability of CAR proteins. The lot1 mutant had a lower leaf temperature as compared with the wild type due to higher transpiration. We found that LOT1 physically interacts with CAR9 , and ABA reduces LOT1–CAR9 interaction in the nucleus, likely via Ca2+, resulting in increased localization of CAR9 to the plasma membrane. We further found that the stability of CAR9 is affected by LOT1 less CAR9 proteins were accumulated and more were ubiquitinated in lot1. While the lot1 , car9 and lot1 car9 mutants were hyposensitive to ABA, the hyposensitive phenotype of lot1 could be rescued by CAR9 overexpression. Collectively, our study reveals that LOT1 regulates plant tolerance to drought stress by affecting ABA signaling through regulating the stability and dynamic localization of CAR9. CAR proteins play important roles in plasma membrane-associated ABA signal transduction by recruiting ABA receptors to the plasma membrane, yet how CAR proteins are regulated remains unclear. This study identified an uncharacterized protein, LOT1, which regulates plant tolerance to drought stress by affecting ABA signaling through regulating the stability and localization of CAR9. [ABSTRACT FROM AUTHOR]

In contrast to mammals, genomic imprinting primarily occurs in the endosperm in flowering plants. Nevertheless, the imprinting drivers and functions of imprinted genes remain poorly understood. Batista et al. identified the type I MADS-box transcription factor (TF) PHERES1 (PHE1) as a key regulator of some imprinted and nonimprinted genes required for endosperm development. [ABSTRACT FROM AUTHOR]

The industrial robot, due to its flexibility, is considered as a promising option to accomplish the fine boring work of the aircraft intersection holes. However, the robot has a relatively low stiffness and is easily subjected to chatter vibration in the boring process, resulting in difficulty in guaranteeing the machining quality. In this article, the mechanism of the vibration in the robotic boring process is analyzed, and a novel vibration suppression method based on the pressure foot is proposed. First, a robotic boring system is presented. Based on its cutting characteristics and stiffness characteristics, the mechanism of the vibration is analyzed, followed by the study of the tool path during the boring operation. It is found that in the robotic boring process it is the robot itself vibrates rather than the boring bar, which usually vibrates in the traditional CNC machine tools. And the type of the vibration is found to be a forced vibration with a displacement feedback. Furthermore, a novel method making use of the pressure foot is proposed to suppress the vibration of the robot. Finally, large numbers of boring experiments have been conducted and the results verify the correctness of the vibration mechanism and the effectiveness of the vibration suppression method. [ABSTRACT FROM AUTHOR]

During adaptive radiation, mitochondria have co-evolved with their hosts, leading to gain or loss of subunits and assembly factors of respiratory complexes. Plant mitochondrial complex I harbors ∼40 nuclear- and 9 mitochondrial-encoded subunits, and is formed by stepwise assembly during which different intermediates are integrated via various assembly factors. In mammals, the mitochondrial complex I intermediate assembly (MCIA) complex is required for building the membrane arm module. However, plants have lost almost all of the MCIA complex components, giving rise to the hypothesis that plants follow an ancestral pathway to assemble the membrane arm subunits. Here, we characterize a maize crumpled seed mutant, crk1 , and reveal by map-based cloning that CRK1 encodes an ortholog of human complex I assembly factor 1, zNDUFAF1, the only evolutionarily conserved MCIA subunit in plants. zNDUFAF1 is localized in the mitochondria and accumulates in two intermediate complexes that contain complex I membrane arm subunits. Disruption of zNDUFAF1 results in severe defects in complex I assembly and activity, a cellular bioenergetic shift to aerobic glycolysis, and mitochondrial vacuolation. Moreover, we found that zNDUFAF1, the putative mitochondrial import inner membrane translocase ZmTIM17-1, and the isovaleryl-coenzyme A dehydrogenase ZmIVD1 interact each other, and could be co-precipitated from the mitochondria and co-migrate in the same assembly intermediates. Knockout of either ZmTIM17-1 or ZmIVD1 could lead to the significantly reduced complex I stability and activity as well as defective seeds. These results suggest that zNDUFAF1, ZmTIM17-1 and ZmIVD1 probably form an MCIA-like complex that is essential for the biogenesis of mitochondrial complex I and seed development in maize. Our findings also imply that plants and mammals recruit MCIA subunits independently for mitochondrial complex I assembly, highlighting the importance of parallel evolution in mitochondria adaptation to their hosts. An MCIA-like complex is required for mitochondrial complex I assembly and seed development in maize, revealing parallel evolution of complex I membrane arm module assembly in plants and mammals. [ABSTRACT FROM AUTHOR]

Rerouting the starch biosynthesis pathway in maize can generate specialty types, like sweet corn and waxy corn, with a drastically increasing global demand. Hence, a fine-tuning of starch metabolism is relevant to create diverse maize cultivars for end-use applications. Here, we characterized a new maize brittle endosperm mutant, referred to as bt1774 , which exhibited decreased starch content but a dramatic increase of soluble sugars at maturity. Both endosperm and embryo development was impaired in bt1774 relative to the wild-type (WT), with a prominently arrested basal endosperm transfer layer (BETL). Map-based cloning revealed that BRITTLE ENDOSPERM2 (Bt2), which encodes a small subunit of ADP-glucose pyrophosphorylase (AGPase), is the causal gene for bt1774. A MuA2 element was found to be inserted into intron 2 of Bt2 , leading to a severe decrease of its expression, in bt1774. This is in line with the irregular and loosely packed starch granules in the mutant. Transcriptome of endosperm at grain filling stage identified 1,013 differentially expressed genes in bt1774 , which were notably enriched in the BETL compartment, including ZmMRP1 , Miniature1 , MEG1 , and BETLs. Gene expression of the canonical starch biosynthesis pathway was marginally disturbed in bt1774. Combined with the residual 60 % of starch in this nearly null mutant of Bt2 , this data strongly suggests that an AGPase-independent pathway compensates for starch synthesis in the endosperm. Consistent with the BETL defects, zein accumulation was impaired in bt1774. Co-expression network analysis revealed that Bt2 probably has a role in intracellular signal transduction, besides starch synthesis. Altogether, we propose that Bt2 is likely involved in carbohydrate flux and balance, thus regulating both the BETL development and the starchy endosperm filling. • A new maize brittle endosperm mutant, referred to as bt1774 was mapped and cloned, which encodes a small subunit of ADP-glucose pyrophosphorylase (AGPase). • RNA-seq and co-expression network analysis suggested that Bt2 probably has a role in intracellular signal transduction, as well as, starch and zein accumulation. • Bt2 is likely involved in carbohydrate flux and balance, thus regulating the BETL development and starchy endosperm filling. [ABSTRACT FROM AUTHOR]

Depression is a kind of mood disorder. The incidence of depressed patients has demonstrated an upward trend in recent years. Symptoms may improve with treatments such as pharmacotherapy and cognitive-behavioral therapy, but such approaches may exert strong side effects, and therapeutic effects can be slow. We studied how acupuncture stimulation would affect depression as a method to reduce side effects. Mild depression was induced in rats by 1-week water-immersion stress. We treated these mildly depressed rats with either acupuncture stimulation at the “Bai-Hui” (GV 20) and “Yintáng” (Ex-HN3) points, or antidepressants. We then measured the immobile time and serum corticosterone level in rats. Immobile time and serum corticosterone level decreased on stimulation with acupuncture or antidepressants. These findings suggest that mild depression in rats was improved by stimulation with acupuncture The mechanisms underlying such improvement may effect HPA system activated by this stress, and inhibit the response to lead to the disorder of the hippocampal nerve cell. [ABSTRACT FROM AUTHOR]

Small molecule compound tyrphostin A9 (A9), an inhibitor of platelet-derived growth factor (PDGF) receptor, was previously reported by our group to stimulate extracellular signal-regulated kinase 1 (ERK1) and 2 (ERK2) in neuronal cells in a PDGF receptor-irrelevant manner. The study aimed to investigate whether A9 could protect axons in experimental autoimmune encephalomyelitis through activation of ERKs. A9 treatment on the protection on neurite outgrowth in SH-SY5Y neuroblastoma cells and primary substantia nigra neuron cultures from the neurotoxin MPP+ were analyzed. Then, clinical symptoms as well as ERK1/2 activation, axonal protection induction, and the abundance increases of the regeneration biomarker GAP-43 in the CNS in the relapsing-remitting experimental autoimmune encephalomyelitis (EAE) model were verified. A9 treatment could stimulate neurite outgrowth in SH-SY5Y neuroblastoma cells and protect primary substantia nigra neuron cultures from the neurotoxin MPP+. In the relapsing-remitting EAE model, oral administration of A9 successfully ameliorated clinical symptoms, activated ERK1/2, induced axonal protection, and increased the abundance of the regeneration biomarker GAP-43 in the CNS. Interestingly, gene deficiency of ERK1 or ERK2 disrupted the beneficial effects of A9 in MOG-35-55-induced EAE. These results demonstrated that small molecule compounds that stimulate persistent ERK activation in vitro and in vivo may be useful in protective or restorative treatment for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Picophytoplankton are essential components of phytoplankton in the oligotrophic South China Sea (SCS). Understanding the variation in the picophytoplankton community structure will provide important information about primary production and the biogeochemical cycling of carbon in the SCS. Based on a field dataset from the SCS , we developed empirical algorithms using the absorption coefficient of phytoplankton at 443 nm [ a ph (443)] as the input to estimate the cell abundances of picophytoplankton, including Prochlorococcus (Pro), Synechococcus (Syn), and autotrophic picoeukaryotes (PE), in the SCS. Evaluation of algorithm performances demonstrated good agreement with field measurements. The root mean square errors and the mean absolute errors (MAE s) between the algorithm derivations and measurements were 0.44, 0.35, and 0.29, and 2.67, 2.02, and 1.88 for the cell abundances of Pro , Syn , and PE , respectively. The match-up comparisons showed that the satellite-derived cell abundances of picophytoplankton (e.g., MAE s ranged from 1.73 to 2.76) also agreed with the field data. We also analyzed the influences of both temperature and nutrient concentration on algorithm performance. The influence of temperature on the algorithms was not significant because the data were mainly collected in the summer, and the analysis should be repeated in the future with data from other seasons. The algorithm for estimating cell abundance of Syn was sensitive to variations in nutrient levels and herbivory pressure in coastal waters where nano- or microphytoplankton dominated. The input of our algorithms, a ph (443), was easily obtained from field measurements and remote sensing. These algorithms provide a relatively easy way to estimate the cell abundances of picophytoplankton and provide data for studying the picophytoplankton community structure in the SCS. • We developed new empirical algorithms for remote cell abundances of picophytoplankton estimations in the South China Sea. • The influences of temperature on the algorithms were not significant as the data were mainly collected in summer. • The nutrient and herbivory pressure had a certain influence on the Synechococcus algorithm. • The 10-years averaged distributions of cell abundances of picophytoplankton in the SCS were explored using MODIS images. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) are intricate compounds that pose significant challenges in bioanalytical characterization. Therefore, multiple bioanalytical methods are required to comprehensively elucidate their pharmacokinetic (PK) profiles. In this study, we investigated DS001, an ADC consisting of a humanized monoclonal antibody (hRS7), a cleavable chemical linker, and the microtubule inhibitor monomethyl auristatin E (MMAE), with a drug-to-antibody ratio (DAR) of 8. This study established a rapid and sensitive hybrid immunoaffinity liquid-chromatography-tandem-mass-spectrometry (LC-MS/MS) approach for the simultaneous quantification of the total antibody and the enzymatically cleavable conjugated payload of DS001. This method is capable of monitoring fluctuations in average DAR values during PK assessments. The sample preparation procedure involved immunocapture, denaturation, trypsin digestion, papain digestion, and termination, all completed within a total processing time of less than 4 h. The method demonstrated linearity for the total antibody in the range of 100 ng/mL (lower-limit-of-quantification, LLOQ) to 100,000 ng/mL, and for the conjugated payload from 3.495 ng/mL (LLOQ) to 3495 ng/mL in rat serum. Both analytes exhibited standard curve correlation coefficients (r) greater than 0.990 within their respective linear ranges. The precision and accuracy of the method were within ± 15% (± 20% for LLOQ). The verified LC-MS/MS approach was successfully employed in the PK analysis following intravenous administration of 0.2 mg/kg DS001 in rats via tail vein injection., Competing Interests: Declarations. Conflict of Interest: The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this article., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

We previously demonstrated that glycyrrhizin (GL) suppressed inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer (CC). In this study, we found an accumulation of regulatory T cells (Tregs) in the spleen and suppression by GL in model mice. ICR mice were divided into four groups: Control, GL, CC, and GL-treated CC (CC+GL), and were sacrificed 20 weeks after AOM/DSS treatment. We measured spleen weight, areas of white and red pulp, and CD8+ T cells (cytotoxic T lymphocytes, CTL), and CD11c-positive cells (dendritic cells) in splenic tissues and forkhead box protein 3 (FoxP3)-positive cells (Tregs) in colorectal and splenic tissues. In all cases, the CC group showed a significant increase compared with those in Control group, and GL administration significantly attenuated this increase. These results indicate that Tregs accumulated in the spleen may participate in inflammation-related carcinogenesis by suppressing CTL. We also suggest that GL which binds to high-mobility group box 1 (HMGB1), suppresses carcinogenesis with decreasing Tregs in the spleen. Furthermore, there was an expression of FoxP3 in cancer cells, indicating that it may be involved in the malignant transformation of cancer cells., Competing Interests: Author N.Y. was employed by a company Cokey Co., Ltd., operating licorice-related business. N.Y. ’s position, etc. does not alter our adherence to PLOS ONE policies on sharing data and materials. Also, there are no restrictions from Cokey Co. Ltd, on all steps of this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Humanization is typically adopted to reduce the immunogenicity of murine antibodies generated by hybridoma technology when used in humans., Methods: Two different strategies of antibody humanization are popularly employed, including "complementarity determining region (CDR) grafting" and "framework (FR) shuffling" to humanize a murine antibody against human programmed death-1 (PD-1), XM PD1. In CDR-grafting humanization, the CDRs of XM PD-1, were grafted into the human FR regions with high homology to the murine FR counterparts, and back mutations of key residues were performed to retain the antigen-binding affinities. While in FR-shuffling humanization, a combinatorial library of the six murine CDRs in-frame of XM PD-1 was constructed to a pool of human germline FRs for high-throughput screening for the most favorable variants. We evaluated many aspects which were important during antibody development of the molecules obtained by the two methods, including antibody purity, thermal stability, binding efficacy, predicted humanness, and immunogenicity, along with T cell epitope prediction for the humanized antibodies., Results: While the ideal molecule was not achieved through CDR grafting in this particular instance, FR-shuffling proved successful in identifying a suitable candidate. The study highlights FR-shuffling as an effective complementary approach that potentially increases the success rate of antibody humanization. It is particularly noted for its accessibility to those with a biological rather than a computational background., Discussion: The insights from this comparison are intended to assist other researchers in selecting appropriate humanization strategies for drug development, contributing to broader application and understanding in the field., Competing Interests: Author Y-LC was employed by the companies Shanghai Mabstone Biotechnologies, Ltd and Dartsbio Pharmaceuticals Ltd. Author CW was employed by the company Dartsbio Pharmaceuticals Ltd. Author CW received compensation from Dartsbio Pharmaceuticals Ltd. Author QJ was employed by the company Shanghai Genechem Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chen, Xu, Rana, Tan, He, Jing, Wang, Wang, Xie and Wang.)

Wild soybean ( Glycine soja L.), drought-tolerant cultivar Tiefeng 31 ( Glycine max L.), and drought-sensitive cultivar Fendou 93 ( Glycine max L.) were used as materials to investigate the drought tolerance mechanism after 72 h 2.5 M PEG 8000 (osmotic potential -0.54 MPa)-simulated drought stress at the seedling stage. The results indicated that the leaves of the G. soja did not wilt under drought stress. However, both the drought-tolerant and drought-sensitive cultivated soybean cultivars experienced varying degrees of leaf wilt. Notably, the drought-sensitive cultivated soybean cultivars exhibited severe leaf wilt after the drought stress. Drought stress was determined to have a significant impact on the dry matter of the above-ground part of the drought-sensitive cultivar Fendou 93 , followed by the drought-tolerant cultivar Tiefeng 31 , with the lowest reduction observed in G. soja . Furthermore, the presence of drought stress resulted in the closure of leaf stomata. G. soja exhibited the highest proportion of stomatal opening per unit area, followed by the drought-tolerant cultivar Tiefeng 31 , while the drought-sensitive cultivar Fendou 93 displayed the lowest percentage. Photosynthesis-related indexes, including photosynthetic rate, intercellular CO 2 , transpiration rate, and stomatal conductance, decreased in Fendou 93 and Tiefeng 31 after drought stress, but increased in G. soja . In terms of the antioxidant scavenging system, lower accumulation of malondialdehyde (MDA) was observed in G. soja and Tiefeng 31 , along with higher activities of superoxide dismutase (SOD, EC 1.15.1.1) and catalase (CAT, EC 1.11.1.6) to counteract excess reactive oxygen species and maintain cell membrane integrity. In contrast, the drought-sensitive cultivar Fendou 93 had higher MDA content and higher activities of ascorbate peroxidase (APX, EC 1.11.1.11) and peroxidase (POD, 1.11.1.7). G. soja and Tiefeng 31 also exhibited less accumulation of osmolytes, including soluble sugar, soluble protein, and free proline content. The activities of δ-OAT, ProDH, and P5CS, key enzymes in proline anabolism, showed an initial increase under drought stress, followed by a decrease, and then an increase again at the end of drought stress in G. soja . Before drought stress, Tiefeng 31 had higher activities of ProDH and P5CS, which decreased with prolonged drought stress. Fendou 93 experienced an increase in the activities of δ-OAT, ProDH, and P5CS under drought stress. The δ-OAT gene expression levels were up-regulated in all three germplasms. The expression levels of the P5CS gene in Fendou 93 and Tiefeng 31 were down-regulated, while G. soja showed no significant change. The expression of the P5CR gene and ProDH gene was down-regulated in Fendou 93 and Tiefeng 31 , but up-regulated in G. soja . This indicates that proline content is regulated at both the transcription and translation levels.

Chronic obstructive pulmonary disease (COPD) is characterized by dyspnea caused by airflow limitation. Further development may lead to decreased lung function and other lung diseases. Pyroptosis is a type of programmed cell death that involves multiple pathways. For example, the pathway induced by the NLR family pyrin domain containing 3 (NLRP3) inflammasome is closely associated with COPD exacerbation. Therefore, in this study, various machine learning algorithms were applied to screen for diagnostically relevant pyroptosis-related genes from the GEO dataset, and the results were verified using external datasets. The results showed that deep neural networks and logistic regression algorithms had the highest AUC of 0.91 and 0.74 in the internal and external test sets, respectively. Here, we explored the immune landscape of COPD using diagnosis-related genes. We found that the infiltrating abundance of dendritic cells significantly differed between the COPD and control groups. Finally, the communication patterns of each cell type were explored based on scRNA-seq data. The critical role of significant pathways involved in communication between DCS and other cell populations in the occurrence and progression of COPD was identified., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

With the development of high-throughput experimental technologies, large-scale RNA sequencing (RNA-Seq) data have been and continue to be produced, but have led to challenges in extracting relevant biological knowledge hidden in the produced high-dimensional gene expression matrices. Here, we develop easyMF ( https://github.com/cma2015/easyMF ), a web platform that can facilitate functional gene discovery from large-scale transcriptome data using matrix factorization (MF) algorithms. Compared with existing MF-based software packages, easyMF exhibits several promising features, such as greater functionality, flexibility and ease of use. The easyMF platform is equipped using the Big-Data-supported Galaxy system with user-friendly graphic user interfaces, allowing users with little programming experience to streamline transcriptome analysis from raw reads to gene expression, carry out multiple-scenario MF analysis, and perform multiple-way MF-based gene discovery. easyMF is also powered with the advanced packing technology to enhance ease of use under different operating systems and computational environments. We illustrated the application of easyMF for seed gene discovery from temporal, spatial, and integrated RNA-Seq datasets of maize (Zea mays L.), resulting in the identification of 3,167 seed stage-specific, 1,849 seed compartment-specific, and 774 seed-specific genes, respectively. The present results also indicated that easyMF can prioritize seed-related genes with superior prediction performance over the state-of-art network-based gene prioritization system MaizeNet. As a modular, containerized and open-source platform, easyMF can be further customized to satisfy users' specific demands of functional gene discovery and deployed as a web service for broad applications., (© 2022. International Association of Scientists in the Interdisciplinary Areas.)

Antibody-drug conjugates (ADCs) are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies. In this study, we report the generation of a monoclonal antibody against monomethyl auristatin E (MMAE) and the development, validation, and application of sensitive and high-throughput enzyme-linked immunosorbent assays (ELISA) to measure the concentrations of MMAE-conjugated ADCs and total antibodies (tAb, antibodies in ADC plus unconjugated antibodies) in cynomolgus monkey sera. These assays were successfully applied to in vitro plasma stability and pharmacokinetic (PK) studies of SMADC001, an MMAE-conjugated ADC against trophoblast cell surface antigen 2 (TROP-2). The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit, Lys (m-dPEG24)-Cit, and Val-Cit linkers. The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation between serum concentrations and the OD 450 values, with R 2 at 1.000, and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL, respectively; the intra- and inter-assay accuracy bias% ranged from -12.2% to -5.2%, precision ranged from -12.4% to -1.4%, and the relative standard deviation (RSD) was less than 6.6% and 8.7%, respectively. The total error was less than 20.4%. The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters, which suggested that these can be applied to quantify MMAE-conjugated ADCs, as well as in PK studies. Furthermore, these assays can be easily adopted for development of other similar immunoassays., (© 2021 The Authors.)

Taurine (2-aminoethanesulfonic acid) is a natural amino acid that is found widely in all mammalian tissues. Several studies have demonstrated that taurine has anti-inflammatory, antioxidant, and hypoglycemic effects. Recently, taurine not only mitigates the side effects of chemotherapy in cancer but also possesses antitumor properties, including inhibiting cancer cell proliferation and inducing apoptosis in certain cancers by differential regulating proapoptotic and antiapoptotic proteins. Antitumor studies of taurine are still in their infancy, and the mechanism of its antitumor effect is not fully understood. In this regard, it is worthwhile to study the antitumor mechanism of taurine, which may provide clues to develop new synthetic therapeutic molecules. In this mini review, we summarize the main effects of taurine that have shown suppressing actions in the initiation and progression of cancers. The underlying molecular mechanism also suggested that taurine can be a potential clinical application in tumor therapy. In addition, with the in-depth study of different biological functions of taurine, we found that many systemic diseases are associated with taurine. In this review, the research progress of taurine's antitumor effect is briefly summarized including the in vivo and in vitro studies in our laboratory., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2., (© 2021. The Author(s).)

Main Conclusion: The information on core components in maize polycomb repressive complex 2 (PRC2) are updated at a genome-wide scale, and the protein-protein interaction networks of PRC2 components are further provided in maize. The evolutionarily conserved polycomb group (PcG) proteins form multi-subunits polycomb repressive complexes (PRCs) that repress gene expression via chromatin condensation. In Arabidopsis, three distinct PRC2s have been identified, each determining a specific developmental program with partly functional redundancy. However, the core components and biological functions of PRC2 in cereals remain obscure. Here, we updated the information on maize PRC2 components at a genome-wide scale. Maize PRC2 subunits are highly duplicated, with five MSI1, three E(z), two ESC and two Su(z)12 homologs. ZmFIE1 is preferentially expressed in the endosperm, whereas the remaining are broadly expressed in many tissues. ZmCLF/MEZ1 and ZmFIE1 are maternally expressed imprinted genes, in contrast to the paternal-dominantly expression of ZmFIE2 in the endosperm. In maize, E(z) members likely provide a scaffold for assembling PRC2 complexes, whereas Su(z)12 and p55/MSI1-like proteins together reinforce the complex; ESC members probably determine its specificity: FIE1-PRC2 regulates endosperm cell development, whereas FIE2-PRC2 controls other cell types. The duplicated Brassicaceae-specific MEA and FIS2 also directly interact with maize PRC2 members. Together, this study establishes a roadmap for protein-protein interactions of maize PRC2 components, providing new insights into their functions in the growth and development of cereals.

The 26S proteasome, an essential protease complex of the ubiquitin-26S proteasome system (UPS), controls many cellular events by degrading short-lived regulatory proteins marked with polyubiquitin chains. The 20S proteolytic core protease (CP), the catalytic core of the 26S proteasome, is a central enzyme in the UPS. Its biogenesis proceeds in a multistep and orderly fashion assisted by a series of proteasome assembly chaperones. In this study, we identified a novel maize ( Zea mays ) kernel mutant named defective kernel40 ( dek40 ), which produces small, collapsed kernels and exhibits delayed embryo and endosperm development. Dek40 was identified by map-based cloning and confirmed by transgenic functional complementation. Dek40 encodes a putative cytosol-localized proteasome biogenesis-associated chaperone4 (PBAC4) protein. DEK40 participates in the biogenesis of the 20S CP by interacting with PBAC3. Loss-of-function of DEK40 substantially affected 20S CP biogenesis, resulting in decreased activity of the 26S proteasome. Ubiquitylome analysis indicated that DEK40 influences the degradation of ubiquitinated proteins and plays an essential role in the maintenance of cellular protein homoeostasis. These results demonstrate that Dek40 encodes a PBAC4 chaperone that affects 20S CP biogenesis and is required for 26S proteasome function and seed development in maize., (© 2019 American Society of Plant Biologists. All Rights Reserved.)

Hepatitis C virus (HCV) infection and its related liver disease have constituted a heavy burden worldwide. It had been reported that Drinking coffee could decrease mortality risk of HCV infected patients. Caffeic Acid (CA), the Coffee-related organic acid could inhibit HCV replication, however, the detailed mechanism of CA against HCV is unclear. In this study, we showed that CA could notably inhibit HCV replication. Mechanism study demonstrated that CA could induce HO-1 expression, which would trigger the IFNα antiviral response, and the antiviral effect of CA was attenuated when HO-1 activity was inhibited by SnPP (an HO-1 inhibitor). CA could also increase erythroid 2-related factor 2 (Nrf2) expression. When Nrf2 was knocked down by specific siRNA, HO-1 expression was concomitantly decreased while HCV expression was restored. Further study indicated that kelch-like ECH-associated protein 1 (keap1) expression was decreased by CA through p62/Sequestosome1 (p62)-mediated autophagy, which would lead to the stabilization and accumulation of Nrf2. The decrease of keap1 was restored when p62 was silenced by specific p62 siRNA and when autophagy was inhibited, suggesting p62-mediated autophagy was required for CA-mediated keap1 downregulation. Taken together, the results demonstrated that CA could modulate Keap1/Nrf2 interaction via increasing p62 expression, leading to stabilization of Nrf2 and HO-1 induction, and elicit IFNα antiviral response to suppress HCV replication., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Seeds provide up to 70% of the energy intake of the human population, emphasizing the relevance of understanding the genetic and epigenetic mechanisms controlling seed formation. In flowering plants, seeds are the product of a double fertilization event, leading to the formation of the embryo and the endosperm surrounded by maternal tissues. Analogous to mammals, plants undergo extensive epigenetic reprogramming during both gamete formation and early seed development, a process that is supposed to be required to enforce silencing of transposable elements and thus to maintain genome stability. Global changes of DNA methylation, histone modifications, and small RNAs are closely associated with epigenome programming during plant reproduction. Here, we review current knowledge on chromatin changes occurring during sporogenesis and gametogenesis, as well as early seed development in major flowering plant models., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ribosome biogenesis is a fundamental cellular process in all cells. Impaired ribosome biogenesis causes developmental defects; however, its molecular and cellular bases are not fully understood. We cloned a gene responsible for a maize (Zea mays) small seed mutant, dek* (for defective kernel), and found that it encodes Ribosome export associated1 (ZmReas1). Reas1 is an AAA-ATPase that controls 60S ribosome export from the nucleus to the cytoplasm after ribosome maturation. dek* is a weak mutant allele with decreased Reas1 function. In dek* cells, mature 60S ribosome subunits are reduced in the nucleus and cytoplasm, but the proportion of actively translating polyribosomes in cytosol is significantly increased. Reduced phosphorylation of eukaryotic initiation factor 2α and the increased elongation factor 1α level indicate an enhancement of general translational efficiency in dek* cells. The mutation also triggers dramatic changes in differentially transcribed genes and differentially translated RNAs. Discrepancy was observed between differentially transcribed genes and differentially translated RNAs, indicating distinct cellular responses at transcription and translation levels to the stress of defective ribosome processing. DNA replication and nucleosome assembly-related gene expression are selectively suppressed at the translational level, resulting in inhibited cell growth and proliferation in dek* cells. This study provides insight into cellular responses due to impaired ribosome biogenesis., (© 2016 American Society of Plant Biologists. All Rights Reserved.)

In maize, a series of seed mutants with starchy endosperm could increase the lysine content by decreased amount of zeins, the main storage proteins in endosperm. Cloning and characterization of these mutants could reveal regulatory mechanisms for zeins accumulation in maize endosperm. Opaque7 (o7) is a classic maize starchy endosperm mutant with large effects on zeins accumulation and high lysine content. In this study, the O7 gene was cloned by map-based cloning and confirmed by transgenic functional complementation and RNAi. The o7-ref allele has a 12-bp in-frame deletion. The four-amino-acid deletion caused low accumulation of o7 protein in vivo. The O7 gene encodes an acyl-activating enzyme with high similarity to AAE3. The opaque phenotype of the o7 mutant was produced by the reduction of protein body size and number caused by a decrease in the α-zeins concentrations. Analysis of amino acids and metabolites suggested that the O7 gene might affect amino acid biosynthesis by affecting α-ketoglutaric acid and oxaloacetic acid. Transgenic rice seeds containing RNAi constructs targeting the rice ortholog of maize O7 also produced lower amounts of seed proteins and displayed an opaque endosperm phenotype, indicating a conserved biological function of O7 in cereal crops. The cloning of O7 revealed a novel regulatory mechanism for storage protein synthesis and highlighted an effective target for the genetic manipulation of storage protein contents in cereal seeds.

A serum-specific protein 'fingerprint' model was established which is capable of evaluating the effect of chemotherapy (gemcitabine) of pancreatic adenocarcinoma. We used SELDI-TOF-MS coupled with CM10 chips and bioinformatics tools to analyze a total of 45 mouse serum samples from three groups: the healthy control group, the pancreatic cancer model group (orthotopic transplantation model of human pancreatic adenocarcinoma) and the gemcitabine-treated group to establish diagnostic models. As a result, the test set yielded a specificity of 95.0% and a sensitivity of 95.0% for pattern 1, which distinguished pancreatic adenocarcinoma from healthy individuals and a specificity of 95.0% and a sensitivity of 75.0% for pattern 3, which distinguished healthy controls, PC model group and gemcitabine-treated group, as evaluated by leave-one-out cross-validation. We concluded from this study that the SELDI-TOF-MS technique combined with bioinformatics approaches can facilitate evaluating the effect of chemotherapy (gemcitabine) for pancreatic adenocarcinoma and could be used as a potential prognostic monitoring method.