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Members of the tumor necrosis factor receptor superfamily (TNFRSF) are important therapeutic targets that can be activated to induce death of cancer cells or stimulate proliferation of immune cells. Although it has long been implicated that these receptors assemble preligand associated states that are required for dominant interference in human disease, such states have so far eluded structural characterization. Here, we find that the ectodomain of death receptor 5 (DR5-ECD), a representative member of TNFRSF, can specifically self-associate when anchored to lipid bilayer, and we report this self-association structure determined by nuclear magnetic resonance (NMR). Unexpectedly, two non-overlapping interaction interfaces are identified that could propagate to higher-order clusters. Structure-guided mutagenesis indicates that the observed preligand association structure is represented on DR5-expressing cells. The DR5 preligand association serves an autoinhibitory role as single-domain antibodies (sdAbs) that partially dissociate the preligand cluster can sensitize the receptor to its ligand TRAIL and even induce substantial receptor signaling in the absence of TRAIL. Unlike most agonistic antibodies that require multivalent binding to aggregate receptors for activation, these agonistic sdAbs are monovalent and act specifically on an oligomeric, autoinhibitory configuration of the receptor. Our data indicate that receptors such as DR5 can form structurally defined preclusters incompatible with signaling and that true agonists should disrupt the preligand cluster while converting it to signaling-productive cluster. This mechanism enhances our understanding of a long-standing question in TNFRSF signaling and suggests a new opportunity for developing agonistic molecules by targeting receptor preligand clustering.

Background: Inborn errors of immunity have been implicated in causing immune dysregulation, including allergic diseases. STAT6 is a key regulator of allergic responses. Objectives: This study sought to characterize a novel gain-of-function STAT6 mutation identified in a child with severe allergic manifestations. Methods: Whole-exome and targeted gene sequencing, lymphocyte characterization, and molecular and functional analyses of mutated STAT6 were performed. Results: This study reports a child with a missense mutation in the DNA binding domain of STAT6 (c.1114G>A, p.E372K) who presented with severe atopic dermatitis, eosinophilia, and elevated IgE. Naive lymphocytes from the affected patient displayed increased TH2- and suppressed TH1- and TH17-cell responses. The mutation augmented both basal and cytokine-induced STAT6 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reversed STAT6 hyperresponsiveness to IL-4, normalized TH1 and TH17 cells, suppressed the eosinophilia, and improved the patient\"s atopic dermatitis. Conclusions: This study identified a novel inborn error of immunity due to a STAT6 gain-of-function mutation that gave rise to severe allergic dysregulation. Janus kinase inhibitor therapy could represent an effective targeted treatment for this disorder.

Magnolia bark is an edible traditional Chinese medicine that has antibacterial activity against Staphylococcus aureus. In the present study, interactions between S. aureus DNA and raw magnolia bark (RMB) and ginger mix-fried magnolia bark (GMB) aqueous extracts were determined via spectroscopic methods. Fluorescence spectroscopy and Stern-Volmer constants showed that S. aureus DNA quenched the fluorescence of the extracts by static quenching. UV-Vis spectroscopy and iodide quenching experiments indicated that the interactions between S. aureus DNA and the fluorescent substances might involve groove binding or electrostatic interactions. In 4', 6-diamidino-2-phenylindole competitive assays, the fluorescence intensity at decreased as the extract amount was increased. This indicates that groove binding is responsible for the fluorescence quenching. The antibacterial activity of GMB aqueous extract treated under light, cold, heat and cycling hot-cold conditions decreased by 13.99, 9.31, 10.89 and 14.40%, respectively, whereas that of RMB aqueous extract treated under the same conditions decreased by 8.91, 14.99, 14.99 and 13.70%, respectively. The results indicate that S. aureus DNA quenches the fluorescence of GMB and RMB aqueous extracts by grooving interactions. Additionally, the antibacterial activities of GMB and RMB extracts are sensitive to light and temperature, respectively.

The B-cell antigen receptor (BCR) is composed of a membrane-bound immunoglobulin (mIg) of class M, D, G, A or E for antigen recognition and a disulfide-linked heterodimer between Igα and Igβ (Igα/β, also known as CD79A and CD79B) that functions as the signalling entity. The organizing principle of BCR assembly remains elusive. Here we report the cryo-electron microscopy structures of the intact IgM class BCR at 8.2 Å resolution and its Fab-deleted form (IgM BCRΔFab) at 3.6 Å resolution. At the ectodomain (ECD), Igα and Igβ position their respective Ig folds roughly in parallel with an approximate 2-fold symmetry, which is distinct from structures of Igβ/β homodimers. Unlike previous predictions, the BCR structure displays an asymmetric arrangement, in which the Igα/β ECD heterodimer mainly uses Igα to associate with Cµ3-Cµ4 domains of one heavy chain (µHC) while leaving the other heavy chain (µHC’) empty. The transmembrane domain (TMD) helices of the two µHCs also deviate from the 2-fold symmetry of the Cµ3-Cµ4 domain dimer and form together with the TMD helices of the Igα/β heterodimer a tight 4-helix bundle. The asymmetry at the TMD helices prevents the recruitment of two Igα/β heterodimers. Surprisingly, the connecting peptides (CPs) between the ECD and TMD are braided together through striking charge complementarity, resulting in intervening of the CP of µHC in between those of Igα and Igβ and crossover of the TMD relative to ECD for the Igα/β heterodimer, to guide the TMD assembly. Interfacial analyses suggest that the IgM BCR structure we present here may represent a general organizational architecture of all BCR classes. Our studies thus provide a structural platform for understanding B-cell signalling and for designing rational therapies against BCR-mediated diseases.

Inflammasomes are molecular machines that carry out inflammatory responses on challenges by pathogens and endogenous dangers. Dysregulation of inflammasome assembly and regulation is associated with numerous human diseases from autoimmunity to cancer. In recent years, significant advances have been made in understanding the mechanism of inflammasome signaling using structural approaches. Here, we review inflammasomes formed by the NLRP1, NLRP3, and NLRC4 sensors, which are well characterized structurally, and discuss the structural and functional diversity among them.

Background Acne is a multifactorial skin disorder frequently observed during adolescence with different grades of severity. The crucial factors of acne are the increase of lipids secretion and the change of composition on the skin surface lipid (SSL). However, there are no studies on the changes of lipid composition and content between different grades of adolescent acne in lesional skin and nonlesionsal skin. Aims This study was to investigate correlation in the composition of SSL and different grades in order to understand the tendency of SSL alterations in this disease for successful acne management and prevention. Methods A powerful analytical technique, UPLC-QTOF-MS, and multivariate data analysis were used to investigate SSL variations of lipid main classes, subclasses, and species. Results The results indicated that sphinganine, triradylglycerols (TG), and phytosphingosine were important in adolescent acne development. The average fatty acids (FAs) chain length in patients with acne showed significantly shortened trend from mild to moderate adolescent acne. Additionally, the relative average content of TG, diglyceride (DG), FA, ceramides (Cers), and the level of unsaturated FAs significantly increased from mild to moderate adolescent acne. Interestingly, our results demonstrated that the phytosphingosine and sphinganine showed an increasing trend in mild acne groups, but decreasing trend in lesional skin of moderate group. Conclusions Lipidomics analysis suggested that the variation of TG, phytosphingosine, and sphinganine was closely related to the occurrence severity of acne in adolescent.

Background There are a number of hypotheses about the link between sensitive skin and skin microbiota, but so far there have been no studies to confirm these. Objective To answer whether the sensitive skin microbiome is distinct from that of no-sensitive skin. Method By bacterial 16s rRNA gene sequencing, analyzed the difference of microbial composition cheek skin in young women aged 18 to 25 years old between sensitive and non-sensitive skin. Result On the whole, there was no significant difference in skin bacterial diversity (Shannon index) and richness (sobs and Chao index) between SS group and NS group (p > 0.05). However, further analysis showed that the relative abundance of Staphylococcus decreased significantly in SS group. The abundance of Staphylococcus is second only to Propionibacterium in facial cheeks of normal and sensitive skin. The results of species level analysis showed that, the abundance of Staphylococcus aureus limited increased, while that of Staphylococcus epidermidis decreased significantly in SS group. Conclusion The occurrence of sensitive skin is related to the weak microbial barrier associated with the significant decrease of Staphylococcus epidermidis.

Objective. Ultrasound is a practical imaging modality for screening and identification of anomalies in the organs. This study used ultrasonography to examine the association between body parameters and dimensions of the normal liver, spleen, and kidney in adolescents based on ultrasound examination results. Methods. A total of 300 junior and senior high school teenagers receiving routine health check-ups in our hospital from January 2020 to January 2021 were included. Their height and weight were measured, and their body surface area (BSA) and body mass index (BMI) were calculated. Ultrasound imaging was employed to obtain information such as the length and volume of the liver, gallbladder, spleen, and kidney. Besides, the correlation of body parameters such as gender, age, height, weight, BSA, and BMI with visceral dimension was investigated using the Pearson test and multiple regression analysis, respectively. Results. We observed that the abdominal organs of adolescents were enlarged with age. The span and volume of the liver and the length and volume of the right kidney were significantly larger in boys than in girls. The age, BSA, and BMI were positively correlated with the liver span and spleen length, as well as the left and right kidney lengths. Additionally, age, BSA, and BMI were identified as important predictors for dimensions of the spleen, liver, and kidney. Conclusions. Body parameters are notably associated with the dimensions of the liver, spleen, and kidney and could be utilized as predicting factors for the liver, spleen, and kidney dimensions.

In this work, two different types of ZnAl-layered double hydroxide (LDH) mixed metal-oxide composites (CeO

Maoli Lake is the water source for local residents and a national nature protected area. However, due to intensive agriculture development, the water quality has deteriorated over the past decades. An effective measure to improve water quality is to control the agricultural non-point source (NPS) pollution through elaborate schemes based on eco-compensation. In order to develop such eco-compensation schemes, three scenarios of agricultural activity adjustment were designed: S1 (halving fertilization every year), S2 (fallow every other year), and S3 (returning agricultural land to forest). A Soil and Water Assessment Tool (SWAT) model was adopted to simulate runoff, total nitrogen, and total phosphorus. Based on SWAT results, a multi-criteria spatial evaluation model considering the environmental, economic, and social effects of eco-compensation was created for best scenario decision. The results reveal the following: (1) the total nutrients loss of agricultural land reduces in all scenarios, but S2 has more reduction compared to S1 and S3, (2) from the comprehensive perspective of environment–economy–society effects, S2 is the best scenario for rice land and dry land, (3) the comprehensive effect of eco-compensation at the grid scale has a significant spatial difference, and therefore, we highlight the necessity and significance of controlling agricultural NPS pollution by eco-compensation on a precise spatial scale. This study can broaden the application field of the SWAT model and provide a scientific basis and experience for the evaluation and spatial design of agriculture eco-compensation.

Background: Atopic dermatitis (AD) is a chronic, recurrent skin condition with recently increased incidence in younger children. AD development has been correlated with the skin microbiome, and Staphylococcus aureus enrichment causes significant increases in skin lesions. Objective: Our objectives were to compare the microbial diversity of the cheek skin of children with or without AD aged 0–1 years in China, and to determine whether 4 types of skin-isolated bacteria could inhibit S. aureus in vitro. Methods: The skin microbial samples of cheek skin of children were sequenced by 16S rRNA V1-V2 region. Four skin isolated bacterial fermentation supernatants were tested for effects on S. aureus growth, membrane formation, and induction of cytokine secretion from HaCaT cells. Results: Bacterial diversity decreased significantly in skin with severe AD compared to healthy skin (p < 0.01). Seven phyla had content >1%, 4 of which differed in AD (p < 0.05). 38 genera had content >1%, 15 differed (p < 0.05). Differences in 8 species were observed (p < 0.05). In vitro antibacterial and cellular experiments showed that S. aureus growth, biofilm formation, and induction of interleukin (IL)-1α and IL-6 secretion from HaCaT cells were significantly inhibited by Klebsiella oxytoca, Kocuria rhizophila, and Staphylococcus epidermidis culture supernatants (p < 0.05). Conclusion: Skin microbiome changes in children varied with age and with AD. There were complex interactions between skin isolated bacteria and S. aureus which could inhibit S. aureus growth and biofilm formation in vitro, suggesting that these microorganisms could be used in AD treatment.

Background The microbiological basis of diaper dermatitis has not been clearly elucidated; however, a better understanding of microbial colonization may be vital for developing appropriate therapies. Methods Using 16S-rRNA gene sequencing technology, we characterized and compared the bacterial communities obtained from the buttock skin sites of children with diaper dermatitis and from healthy controls. Bacterial diversity in the buttock lesion area and subsequent recovery after emollient treatment have been discussed herein. Results In buttock skin of children with or without diaper dermatitis, Staphylococcus and Anaerococcus were predominant in the total skin microbiome. Compared with the healthy group, the overall skin bacterial richness and diversity were higher in children with diaper dermatitis, with the abundance of Proteobacteria being significantly higher. In the diaper dermatitis group, the richness of Enterococcus, Erwinia and Pseudomonas was significantly higher, and the levels of Clostridium and Actinomyces were significantly lower than those in healthy children. Richness of Staphylococcus aureus was significantly higher in the diaper dermatitis group, whereas that of Staphylococcus epidermidis and Bifidobacterium longum was lower. Staphylococcus epidermidis and Staphylococcus haemolyticus, the dominant species found in buttock skin, were observed to recover earlier after the disease had improved through emollient treatment. Conclusion Staphylococcus epidermidis, as skin probiotic bacterium, and B longum, Clostridium butyricum and Lactobacillus ruminis, which are intestinal probiotic bacteria, are significantly decreased in diaper dermatitis lesions. These changes in the buttock skin microflora indicate an imbalance in the microflora and suggest that the intestinal microflora may be undergoing dynamic changes. The results of this study suggest that probiotic bacterial supplementation may be useful in the treatment and prevention of diaper dermatitis.

Background Skin microbiota are involved in the skin physiological functions and are also affected by the skin physiological characteristics. Objective To better understand the skin microbial characteristics of facial cheek skin and the relationship with skin physiological characteristics. Methods By bacterial 16S rRNA gene sequencing, the authors studied the facial cheek skin microbial characteristics of 85 cases of young women aged 18-25 years. Results Healthy young woman's cheek skin bacterial composition was relatively stable. Dry skin has high bacterial diversity and richness, and oily skin has low bacterial diversity and richness. Cutibacterium was significantly enriched in oily skin and was significantly negatively correlated with other genera such as Streptococcus (r > 0.5). There were significant positive correlations among other genera of enrichment in dry and neutral skin such as Streptococcus and Rothia (r > 0.8). Skin sebum level was significantly negatively correlated with bacterial alpha diversity index. The combined abundance of Cutibacterium acnes and Staphylococcus epidermidis was significantly positively correlated with sebum secretion (r > 0.5). Conclusions The skin sebum secretion and bacterial interaction were the important factors driving the young females' cheek skin bacterial community structure.

SummaryAutophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargoes to the membrane bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we discover a selective autophagy pathway for protein condensates formed by endocytic proteins. In this pathway, the endocytic yeast protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and mediate phase separation into condensates. Both properties are necessary for an Ede1-dependent autophagy pathway for endocytic proteins, which differs from regular endocytosis, does not involve other known selective autophagy receptors, but requires the core autophagy machinery. Cryo-electron tomography of Ede1-containing condensates – at the plasma membrane and in autophagic bodies – shows a phase-separated compartment at the beginning and end of the Ede1-mediated selective autophagy pathway. Our data suggest a model for autophagic degradation of membraneless compartments by the action of intrinsic autophagy receptors.HighlightsEde1 is a selective autophagy receptor for aberrant CME protein assembliesAberrant CME assemblies form by liquid-liquid phase separationCore autophagy machinery and Ede1 are important for degradation of CME condensatesUltrastrucural view of a LLPS compartment at the PM and within autophagic bodies

Lipidation of Atg8-family ubiquitin-like proteins (UBLs) plays important roles in macroautophagy/autophagy. This process is catalyzed by an E1-E2-E3 trienzyme cascade, in which an E1 enzyme, Atg7, directs Atg8 to its E2 enzyme, Atg3, forming a thioester bond-linked Atg3~ Atg8 intermediate; then the composite E3, Atg12–Atg5-Atg16, interacts with the Atg3~ Atg8 intermediate and promotes Atg8 transfer from the catalytic cysteine of Atg3 to the head group of phosphatidylethanolamine (PE) lipids. Despite progress that has been made toward understanding the Atg8 lipidation pathway, the molecular mechanism of Atg3 as it orchestrates between the E1 and E3 remains unclear. Here we summarize our recent work reporting an element in Atg3, termed the E1, E2, and E3-interacting region (E123IR), is an allosteric switch: in the absence of other binding partners, the E123IR restrains Atg3′s catalytic loop, while the E1 or E3 enzyme directly binds this region to remove this brace and thereby conformationally activate Atg3 to elicit Atg8 lipidation in vitro and in vivo.

Electrochemical oxidation has attracted vast interest as a promising alternative to traditional chemical processes in fine chemical synthesis owing to its fast and sustainable features. An electrocatalytic membrane reactor (ECMR) with a three-dimensional (3D) electrode has been successfully designed for the selective oxidation of alcohols with high current efficiency to the corresponding acids or ketones. The anode electrode was fabricated by the in situ loading of one-dimensional (1D) Co3O4 nanowires (NWs) on the conductive porous Ti membrane (Co3O4 NWs/Ti) via the combination of a facile hydrothermal synthesis and subsequent thermal treatment. The electrocatalytic oxidation (ECO) results of alcohols exhibited superior catalytic performance with a higher current efficiency on the Co3O4 NWs/Ti membrane compared with those of Co3O4 nanoparticles on the Ti membrane (Co3O4 NPs/Ti). Even under low reaction temperatures such as 0 °C, it still displayed a very high ECO activity for alcohol oxidation in the ECMR...

In this study, the antibacterial mechanisms of vine tea aqueous extract (VTE) and 2R, 3R-Dihydromyricetin (DMY) against Escherichia coli (E. coli) were investigated. The results showed they had good antibacterial activities on E. coli, and affected cell membrane and nucleoid. The minimum bactericidal concentrations of VTE and DMY were 3.2 and 1.25 mg/mL, respectively. The constituent leakage tests showed VTE and DMY caused significant increases of extracellular alkaline phosphatase (24.4 ± 0.4% and 5.3 ± 0.1%) and β-Galactosidase (27.6 ± 1.0% and 13.6 ± 0.5%), indicating the membrane integrity might be damaged. The lipids studies showed the ratio of unsaturated fatty acids to saturated fatty acids in treated groups were significant decrease (P

Members of the LC3/GABARAP family of ubiquitin-like proteins function during autophagy by serving as membrane linked protein-binding platforms. Their C-termini are physically attached to membranes through covalent linkage to primary amines on lipids such as phosphatidylethanolamine, while their ubiquitin-like fold domains bind "LIR" (LC3-Interacting Region) sequences found within an extraordinarily diverse array of proteins including regulators of autophagy, adaptors that recruit ubiquitinated cargoes to be degraded, and even proteins controlling processes at membranes that are not associated with autophagy. Recently, LC3/GABARAP proteins were found to bind the ubiquitin E3 ligase NEDD4 to influence ubiquitination associated with autophagy in human cell lines. Here, we use purified recombinant proteins to define LC3B interactions with a specific LIR sequence from NEDD4, present a crystal structure showing atomic details of the interaction, and show that LC3B-binding can steer intrinsic NEDD4 E3 ligase activity. The data provide detailed molecular insights underlying recruitment of an E3 ubiquitin ligase to phagophores during autophagy.

Development of efficient catalysts with low cost for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) has been a long-term pursuit because of their vital role in renewable-energy technologies including fuel cells and water splitting. Herein, based on polymerizable ionic liquids (PILs) functionalized with nitrate groups as pore former and precursor of C and N, a facile one-pot thermal treatment method was developed to construct a hybrid electrocatalyst consisting of earth-abundant materials, which was made of Co-based nanoparticles (NPs) grown on 2 D N-doped and macroporous carbon nanosheets (pCNs) of approximately 20–50 nm thickness, that is, Co–N-pCNs. The obtained Co–N-pCNs catalyst manifests enhanced catalytic performance for both ORR and OER, even compared with the best-known commercial catalysts, such as Pt/C and IrO2. The enhanced catalytic activity arises from the 2 D nanosheets and porous structures, well-dispersed Co-based NPs on the carbon sheets, the introduction of electron-rich nitrogen, and the stability by the carbon protection of Co-based NPs between the interlayers of nanosheets. Our present work supplies a novel opportunity for exploring 2 D non-precious-metal catalysts for ORR and OER.

Atopic dermatitis (AD), a chronic relapsing inflammatory pruritic skin disorder with a unique pathophysiology, has a high incidence in the perioral zone among infants. This study aimed to analyze the association of skin microfloral dynamics with disease severity and treatment of AD in 0–1-year-old infants. Based on the eczema area and severity index, subjects were divided into five groups, i.e., mild, moderate, severe, and severe post-treatment, with a healthy control group, and bacterial density at the perioral lesion, disease severity, and treatment were assessed in 0–1-year-old infants with AD. The perioral lesions were colonized predominantly by Firmicutes, followed in abundance by Proteobacteria, Actinobacteria, and Bacteroidetes. In the phylum Firmicutes, Streptococcus was the most predominant genus. In AD infants, the abundance of Bacteroidetes and Fusobacterium decreased significantly with an increase in disease severity (p

Autophagy depends on the E2 enzyme, Atg3, functioning in a conserved E1-E2-E3 trienzyme cascade that catalyzes lipidation of Atg8-family ubiquitin-like proteins (UBLs). Molecular mechanisms underlying Atg8 lipidation remain poorly understood despite association of Atg3, the E1 Atg7, and the composite E3 Atg12–Atg5-Atg16 with pathologies including cancers, infections and neurodegeneration. Here, studying yeast enzymes, we report that an Atg3 element we term E123IR (E1, E2, and E3-interacting region) is an allosteric switch. NMR, biochemical, crystallographic and genetic data collectively indicate that in the absence of the enzymatic cascade, the Atg3E123IR makes intramolecular interactions restraining Atg3′s catalytic loop, while E1 and E3 enzymes directly remove this brace to conformationally activate Atg3 and elicit Atg8 lipidation in vitro and in vivo. We propose that Atg3′s E123IR protects the E2~UBL thioester bond from wayward reactivity toward errant nucleophiles, while Atg8 lipidation cascade enzymes induce E2 active site remodeling through an unprecedented mechanism to drive autophagy., Autophagy mediated by the conjugation pathway for ubiquitin-like proteins plays a key role in controlling homeostasis in eukaryotic cells. Here the authors provide a molecular basis for allosteric activation of the E2 ligase Atg3, uncovering the mechanism underlying Atg8 lipidation and a novel mechanism regulating E1-E2-E3-mediated ubiquitin-like protein conjugation.

The MADS box transcription factor Arabidopsis (Arabidopsis thaliana) AGAMOUS-LIKE15 (AGL15) and a putative ortholog from soybean (Glycine max), GmAGL15, are able to promote somatic embryogenesis (SE) in these plants when ectopically expressed. SE is an important means of plant regeneration, but many plants, or even particular cultivars, are recalcitrant for this process. Understanding how (Gm)AGL15 promotes SE by identifying and characterizing direct and indirect downstream regulated genes can provide means to improve regeneration by SE for crop improvement and to perform molecular tests of genes. Conserved transcription factors and the genes they regulate in common between species may provide the most promising avenue to identify targets for SE improvement. We show that (Gm)AGL15 negatively regulates auxin signaling in both Arabidopsis and soybean at many levels of the pathway, including the repression of AUXIN RESPONSE FACTOR6 (ARF6) and ARF8 and TRANSPORT INHIBITOR RESPONSE1 as well as the indirect control of components via direct expression of a microRNA-encoding gene. We demonstrate interaction between auxin and gibberellic acid in the promotion of SE and document an inverse correlation between bioactive gibberellic acid and SE in soybean, a difficult crop to transform. Finally, we relate hormone accumulation to transcript accumulation of important soybean embryo regulatory factors such as ABSCISIC ACID INSENSITIVE3 and FUSCA3 and provide a working model of hormone and transcription factor interaction in the control of SE.

Several physiological functions have been attributed to class III peroxidases (PRXs) in plants, but the in planta role of most members of this family still remains undetermined. Here, we report the first functional characterization of PRX17 (At2g22420), one of the 73 members of this family in Arabidopsis thaliana. Localization of PRX17 was examined by transient expression in Nicotiana benthamiana. Loss- and gain-of-function mutants in A. thaliana were studied. Regulation at the gene and protein levels was analyzed using β-glucuronidase (GUS) activity, quantitative reverse transcriptase (qRT)-PCR, zymography, and chromatin immunoprecipitation. Phenotypes were characterized including lignin and xylan contents. PRX17 was expressed in various tissues, including vascular tissues, and PRX17 was localized to the cell wall. In prx17, the lignin content was reduced in the stem and siliques and bolting was delayed, while the opposite phenotype was observed in 35S:PRX17 plants, together with a significant increase of lignin and xylan immunofluorescence signal. Finally, we demonstrated that the transcription factor AGAMOUS-LIKE15 (AGL15) binds to the PRX17 promoter and regulates PRX17 expression level. This converging set of structural, transcriptomic and physiological data suggests that PRX17, under the control of AGL15, contributes to developmental programs by playing an essential role in regulating age-dependent lignified tissue formation, including changes in cell wall properties.

There has been a lack of socioeconomic status (SES) disparity analysis on women in China with only one child, the family planning target population. In 2008, the National Research Institute for Family Planning of China conducted a study investigating the relationship between SES and fertility intentions among 17,093 women in China who already had one child. A questionnaire was used to collect information on SES and fertility intentions, and logistic regression models were used to estimate the odds ratios and 95% CIs of fertility intentions according to SES. Compared with female farmers, women in other occupations intended to have fewer children (p 0.05). Additionally, compared with women with low educational level (illiterate/primary), women with secondary and postsecondary education intended to have fewer children (p 0.05) (OR = 0.70; 95% CI: 0.61-0.81 and OR = 0.56; 95% CI 0.47-0.66). A mother's education level was significantly and negatively associated with fertility intentions after adjustment for potential confounders (p 0.05). Among Chinese women who had one child, the women with higher SES (e.g. higher educational level) had lower fertility intentions. There is an SES disparity in the fertility intention among Chinese women who already have one child. China's policy-makers should consider increasing high SES women's fertility intention.

Internet use has seriously affected individual health in potential and subtle ways. Past research on the subject mainly concentrated on the mental health caused by addictive use, e.g., impulse control disorders and obsessive-compulsive disorder. With the constant development of cyber technology, Internet has been an indispensable element of living and working, which can provide more convenient and efficient support and help. At the same time, the effects of Internet use more than Internet addiction on individual health cannot be ignored in living and working. This paper aims to identify the most common physical complaints associated with Internet use, and further investigate the association between the frequency of Internet use and individual physical health. Five hundred and thirteen participants completed the questionnaires by online or offline manner, which covers demographic questions and questions concerning Internet use and physical complaints. The most common complaints were involving dry eyes, decreased vision, and cervical pain. The positive pearson correlation coefficient were found between the level of physical complaints and the frequency of Internet use, place of residence and education. Especially, the higher amount of time for the Internet use is strongly associated with a higher level of physical complaints.

The present work investigate the green synthesis of zinc oxide nanoparticles (ZnO NPs) using Anacardium occidentale leaf extract by an eco-friendly method. ZnO NPs were synthesized by boiling the mixture of 10 ml of Anacardium occidentale leaf extract and 30 ml 0.1 M zinc nitrate (ZnNO3) at 60 °C for 3 h. The obtained nanoparticles were studied using spectroscopic and microscopic techniques such as Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and ultraviolet-visible spectroscopy (UV–Vis).X-ray diffraction results showed the hexagonal structure of the ZnO NPs. TEM results confirmed the hexagonal NPs with average particle size of 33 nm. Further the prepared nanoparticles were studied for their cytotoxicity against human pancreatic cancer cells. The cytotoxicity results have confirmed that the fabricated ZnO NPs exhibited the concentration-dependent cytotoxicity against pancreatic cancer cell lines.

Electrochemical oxidation has attracted vast interest as a promising alternative to traditional chemical processes in fine chemical synthesis owing to its fast and sustainable features. An electrocatalytic membrane reactor (ECMR) with a three-dimensional (3D) electrode has been successfully designed for the selective oxidation of alcohols with high current efficiency to the corresponding acids or ketones. The anode electrode was fabricated by the in situ loading of one-dimensional (1D) Co

Smart worlds begin with smart things, such as smart objects, smart cities, smart manufacturing, and smart systems, are overlaid with sensing and actuation, many embedded in things, and eventually encompass all aspects of the cyber, physical, social, and thinking hyperspace. In the future, human beings will live in a smart environment where both life and work are well addressed by technology, whereas humans will be responsible only for providing creativity. For this purpose, we have organized the first 2015 Smart World Congress, including five IEEE International Conferences. Specifically, a variety of challenges are presented in the field of smart world. Therefore, an open forum on the top ten challenges (Top10Cs) for smart worlds was held under the congress to identify the main challenges through collecting the intelligence existing particularly in crowd wisdom. Top10Cs and related works, as a crowdsourcing approach, discuss and analyze the top challenges for smart worlds based on the selective results of the crowd and experts via an online platform. Moreover, we summarize the experiences obtained in organizing the Top10Cs forum.

A facile, convenient, and green method for the synthesis of BAgNPs by using basalin is proposed in this work. The capping of the basalin on the surface of BAgNP was confirmed by the zeta potential and FTIR findings. Further, we have injected prepared BAgNPs into oxaliplatin-treated mice to alleviate neuropathic pain. The aluminum levels in the DRG were reduced by the chelating activity of BAgNPs. Moreover, behavioral analyses also manifested that the accumulation of aluminum on the DRG might be a reason for neuropathic hyperalgesia. These findings also recommended that the chelation of aluminum by AgNPs could provide an effective remedy to alleviate the symptoms of oxaliplatin-induced neuropathic pain in cancer patients.

Autophagosome formation and specific substrate recruitment during Autophagy require ligation of the ubiquitin-like protein (UBL) Atg8 to the head group of the lipid phosphatidylethanolamine (PE). Atg8 lipidation is mediated by distinctive UBL cascades involving autophagy-specific E1, E2, and E3 enzymes that differ substantially in sequence from components of other UBL conjugation cascades. Structural studies are important for elucidating the roles of Atg proteins that regulate multiple steps involved in autophagy. This chapter describes methods to prepare and crystallize selected proteins and complexes involved in autophagy UBL conjugation pathways, as a guide for strategies for structural and biochemical characterization of Atg proteins.

Multiple factors, including the MADS-domain proteins AGAMOUS-LIKE15 (AGL15) and AGL18, contribute to the regulation of the transition from vegetative to reproductive growth. AGL15 and AGL18 were previously shown to act redundantly as floral repressors and upstream of FLOWERING LOCUS T (FT) in Arabidopsis (Arabidopsis thaliana). A series of genetic and molecular experiments, primarily focused on AGL15, was performed to more clearly define their role. agl15 agl18 mutations fail to suppress ft mutations but show additive interactions with short vegetative phase (svp) mutations in ft and suppressor of constans1 (soc1) backgrounds. Chromatin immunoprecipitation analyses with AGL15-specific antibodies indicate that AGL15 binds directly to the FT locus at sites that partially overlap those bound by SVP and FLOWERING LOCUS C. In addition, expression of AGL15 in the phloem effectively restores wild-type flowering times in agl15 agl18 mutants. When agl15 agl18 mutations are combined with agl24 svp mutations, the plants show upward curling of rosette and cauline leaves, in addition to early flowering. The change in leaf morphology is associated with elevated levels of FT and ectopic expression of SEPALLATA3 (SEP3), leading to ectopic expression of floral genes. Leaf curling is suppressed by sep3 and ft mutations and enhanced by soc1 mutations. Thus, AGL15 and AGL18, along with SVP and AGL24, are necessary to block initiation of floral programs in vegetative organs.

Humans express several orthologs of yeast Atg8, in the LC3 and GABARAP families, which play crucial roles in autophagy through their covalent ligation to lipids, typically phosphatidylethanolamine (PE), in a process known as lipidation. Lipidation of LC3 and GABARAP regulates numerous facets of the autophagy process, including regulating expansion of the phagophore membrane, recruiting selected cargoes for degradation, and providing an autophagosome membrane-bound platform mediating dynamic interactions with other regulatory proteins. LC3 and GABARAP are families of related ubiquitin-like proteins (UBLs) (referred to here collectively as LC3/GABARAP), and their lipidation involves a divergent UBL conjugation cascade including ATG7, ATG3, and ATG12~ATG5-ATG16L1 acting as E1, E2, and E3 enzymes, respectively. ATG7 initiates LC3/GABARAP conjugation by catalyzing their C-terminal adenylation and conjugation to the catalytic cysteine of ATG3. Ultimately, the ATG12~ATG5-ATG16L1 complex catalyzes LC3/GABARAP ligation to a primary amino group on PE or other acceptor lipids. This chapter describes methods for expressing and purifying human LC3 or GABARAP, ATG7, ATG3, and the ATG12~ATG5-ATG16L1 complex for in vitro studies of LC3/GABARAP lipidation.

Somatic embryogenesis (SE) is an important avenue for regeneration of many plants. Although documented over half a century ago, the process of SE remains poorly understood and many factors impact upon competence for SE. We recently reported that a Glycine max ortholog of a MADS-domain transcription factor that promotes SE in Arabidopsis also enhances SE in soybean. We recently assessed transcriptomes in 35Spro:GmAGL15 compared to control during an early time-course of SE and in response to 35Spro:AtAGL15. We expand here upon discussion of the types of genes regulated by overexpression of AGL15 and characterize the step of SE that may be affected by altered accumulation of AGL15.

Several physiological functions have been attributed to class III peroxidases (PRXs) in plants, but the in planta role of most members of this family still remains undetermined. Here, we report the first functional characterization of PRX17 (At2g22420), one of the 73 members of this family in Arabidopsis thaliana. Localization of PRX17 was examined by transient expression in Nicotiana benthamiana. Loss- and gain-of-function mutants in A. thaliana were studied. Regulation at the gene and protein levels was analyzed using β-glucuronidase (GUS) activity, quantitative reverse transcriptase (qRT)-PCR, zymography, and chromatin immunoprecipitation. Phenotypes were characterized including lignin and xylan contents. PRX17 was expressed in various tissues, including vascular tissues, and PRX17 was localized to the cell wall. In prx17, the lignin content was reduced in the stem and siliques and bolting was delayed, while the opposite phenotype was observed in 35S:PRX17 plants, together with a significant increase of lignin and xylan immunofluorescence signal. Finally, we demonstrated that the transcription factor AGAMOUS-LIKE15 (AGL15) binds to the PRX17 promoter and regulates PRX17 expression level. This converging set of structural, transcriptomic and physiological data suggests that PRX17, under the control of AGL15, contributes to developmental programs by playing an essential role in regulating age-dependent lignified tissue formation, including changes in cell wall properties.

Objective: Induced abortion is widely practiced in China. However, the information on induced abortion is limited. A national cross-sectional survey was designed to determine the risk factors of induced abortion among Chinese women with one child. Methods: We sampled 16,881 Chinese women with one living child for the study. A structured questionnaire was used to collect induced abortion and related health information. The National Research Institute for Family Planning of China conducted a cross-sectional study among women who had delivered a baby between 2006 and 2008. Information was collected in relation to demographic characteristics (age, ethnicity, region, area etc.), social economic status (education level and occupation), marriage, and the attitude towards potential child’s gender. Multi-logistic regression was used to test potential predictors for conducting abortion stratified by consistency between gender preference and current infants’ gender, and indicating adjusted estimation on selected models of risk factors for abortion. Results: The mean age of participants was 27.96 ± 4.10 years (median 27 years). Among those women, the prevalence of induced abortion was 8.13 %. In the final model, females living in rural areas (OR = 1.21, 95 %CI: 1.04-1.39), individuals ages 18-25 (OR = 0.84, 95% CI: 0.72-0.99), individuals ages 30 or older (OR = 1.63, 95% CI: 1.42-1.86), and single individuals (OR = 1.72, 95% CI: 1.05-2.83) were more likely to experience induced abortion. Wife gender preference (OR = 0.66, 95 %CI: 0.53-0.83), husband gender preference (Boy: OR = 1.33, 95 %CI: 1.10-1.63; Girl: OR = 1.5, 95% CI: 1.22-1.86), and the area where the individuals were located were significantly associated with the reporting of induced abortion. Conclusion: The prevalence of induced abortion is high among married women with child in China. There are also socio-demographic characteristics associated with induced abortion in China.

Objective: although numerous studies have reported the association between birth season and sex ratio, few studies have been conducted in subtropical regions in a non-Western setting. The present study assessed the effects of pregnancy season on birth sex ratio in China. Methods: We conducted a national population-based retrospective study from 2006–2008 with 3175 children-parents pairs enrolled in the Northeast regions of China. Demographics and data relating to pregnancy and birth were collected and analyzed. A multiple logistical regression model was fitted to estimate the regression coefficient and 95% confidence interval (CI) of refractive error for mother pregnancy season, adjusting for potential confounders. Results: After adjusting for parental age (cut-off point was 30 years), region, nationality, mother education level, and mother miscarriage history, there is a significant statistical different mother pregnancy season on birth-sex. Compared with mothers who were pregnant in spring, those pregnant in summer or winter had a high probability of delivering girls (p < 0.05). The birth-sex ratio varied with months. Conclusions: Our results suggested that mothers pregnant in summer and winter were more likely to deliver girls, compared with those pregnant in spring. Pregnancy season may play an important role in the birth-sex.

Many of the regulatory processes occurring during plant embryogenesis are still unknown. Relatively few cells are involved, and they are embedded within maternal tissues, making this developmental phase difficult to study. Somatic embryogenesis is a more accessible system, and many important regulatory genes appear to function similar to zygotic development, making somatic embryogenesis a valuable model for the study of zygotic processes. To better understand the role of the Arabidopsis (Arabidopsis thaliana) MADS factor AGAMOUS-Like15 (AGL15) in the promotion of somatic embryogenesis, direct target genes were identified by chromatin immunoprecipitation-tiling arrays and expression arrays. One potential directly up-regulated target was At5g61590, which encodes a member of the ethylene response factor subfamily B-3 of APETALA2/ETHYLENE RESPONSE FACTOR transcription factors and is related to Medicago truncatula SOMATIC EMBRYO-RELATED FACTOR1 (MtSERF1), which has been shown to be required for somatic embryogenesis in M. truncatula. Here, we report confirmation that At5g61590 is a directly expressed target of AGL15 and that At5g61590 is essential for AGL15’s promotion of somatic embryogenesis. Because At5g61590 is a member of the ETHYLENE RESPONSE FACTOR family, effects of ethylene on somatic embryogenesis were investigated. Precursors to ethylene stimulate somatic embryogenesis, whereas inhibitors of ethylene synthesis or perception reduce somatic embryogenesis. To extend findings to a crop plant, we investigated the effects of ethylene on somatic embryogenesis in soybean (Glycine max). Furthermore, we found that a potential ortholog of AGL15 in soybean (GmAGL15) up-regulates ethylene biosynthesis and response, including direct regulation of soybean orthologs of At5g61590/MtSERF1 named here GmSERF1 and GmSERF2, in concordance with the M. truncatula nomenclature.