A Coupled Statistical and Deterministic Model for Forecasting Climate-Driven Dengue Incidence in Selangor, Malaysia.

The mosquito-borne dengue virus remains a major public health concern in Malaysia. Despite various control efforts and measures introduced by the Malaysian Government to combat dengue, the increasing trend of dengue cases persists and shows no sign of decreasing. Currently, early detection and vector control are the main methods employed to curb dengue outbreaks. In this study, a coupled model consisting of the statistical ARIMAX model and the deterministic SI-SIR model was developed and validated using the weekly reported dengue data from year 2014 to 2019 for Selangor, Malaysia. Previous studies have shown that climate variables, especially temperature, humidity, and precipitation, were able to influence dengue incidence and transmission dynamics through their effect on the vector. In this coupled model, climate is linked to dengue disease through mosquito biting rate, allowing real-time forecast of dengue cases using climate variables, namely temperature, rainfall and humidity. For the period chosen for model validation, the coupled model can forecast 1-2 weeks in advance with an average error of less than 6%, three weeks in advance with an average error of 7.06% and four weeks in advance with an average error of 8.01%. Further model simulation analysis suggests that the coupled model generally provides better forecast than the stand-alone ARIMAX model, especially at the onset of the outbreak. Moreover, the coupled model is more robust in the sense that it can be further adapted for investigating the effectiveness of various dengue mitigation measures subject to the changing climate.

Design, synthesis, and antifungal activity of novel pyrazole carboxamide derivatives containing benzimidazole moiety as potential SDH inhibitors.

To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.

Carrier Modulation in 2D Transistors by Inserting Interfacial Dielectric Layer for Area-Efficient Computation.

2D materials with atomic thickness display strong gate controllability and emerge as promising materials to build area-efficient electronic circuits. However, achieving the effective and nondestructive modulation of carrier density/type in 2D materials is still challenging because the introduction of dopants will greatly degrade the carrier transport via Coulomb scattering. Here, a strategy to control the polarity of tungsten diselenide (WSe2 ) field-effect transistors (FETs) via introducing hexagonal boron nitride (h-BN) as the interfacial dielectric layer is devised. By modulating the h-BN thickness, the carrier type of WSe2 FETs has been switched from hole to electron. The ultrathin body of WSe2 , combined with the effective polarity control, together contribute to the versatile single-transistor logic gates, including NOR, AND, and XNOR gates, and the operation of only two transistors as a half adder in logic circuits. Compared with the use of 12 transistors based on static Si CMOS technology, the transistor number of the half adder is reduced by 83.3%. The unique carrier modulation approach has general applicability toward 2D logic gates and circuits for the improvement of area efficiency in logic computation.

Internal phosphorus recycling promotes rich and complex dynamics in an algae-phosphorus model: Implications for eutrophication management.

Internal phosphorus recycling in lakes is an important nutrient source that promotes algal growth. Its persistence impedes the effort to improve water quality and thus poses a challenge to the management of eutrophication in lakes, especially in shallow lakes where the occurrence of internal phosphorus recycling is reportedly more common. This paper aims to provide crucial insights on the effects of internal phosphorus recycling on eutrophication dynamics for effective management of lake eutrophication. For this purpose, a mathematical model for lake eutrophication, comprising two compartments of algae and phosphorus, is first formulated for application to a eutrophic tropical lake named Tasik Harapan in Universiti Sains Malaysia. Numerical bifurcation analysis of the model is then performed to assess the combined influences of internal phosphorus recycling, algal mortality and external phosphorus loading on Tasik Harapan eutrophication dynamics. Specifically, co-dimension one bifurcation analysis of algal mortality rate is carried out by means of XPPAUT for various external phosphorus loading rates. The emergence of limit cycle for a certain range of algal mortality rate could be related to the hydra effect (i.e., algal concentration increases in response to greater algal mortality) and the paradox of enrichment (i.e., destabilization of algae in nutrient rich environment). To trace the locus of co-dimension one bifurcation, co-dimension two bifurcation analysis is performed by means of MatCont. The analysis demonstrated that the inclusion of the internal phosphorus recycling term induces rich and complex dynamics of the model. These dynamics include saddle-node bifurcation, cusp, Bogdanov-Takens bifurcation, Generalized Hopf bifurcation and limit point bifurcation of cycles. The results suggest that high internal phosphorus recycling rate promotes bistability and catastrophic shift in a shallow and tropical lake like Tasik Harapan. Hence, the key to effective management of eutrophication in shallow and tropical lakes is the control of internal phosphorus recycling.

The type of previous abortion modifies the association between air pollution and the risk of preterm birth.

BACKGROUND: Air pollution and previous abortion have been reported to be related to preterm birth (PTB). But rare study examined the effect of air pollution on PTB risk among mothers with previous abortion. OBJECTIVE: To estimate the effect of air pollution on PTB and the potential effect modification of previous abortion on such an association in rural part of Henan province (China). METHOD: Based on National Free Preconception Health Examination Project (NFPHEP), information from the medical records of 57,337 mothers with previous abortion were obtained. An inverse distance-weighted model was used to estimate exposure levels of air pollutants. The effect of air pollution on the risk of PTB was estimated with a multiple logistic regression model. Stratified and interaction analyses were undertaken to explore the potential effect modification of previous abortion on this association. RESULTS: The risk of PTB was positively associated with exposure to levels of nitrogen dioxide (NO2; OR: 1.03; 95%CI: 1.02-1.04)], and sulfur dioxide (SO2; 1.04; 1.02-1.07), and negatively associated with ozone (O3) exposure (0.97; 0.97-0.98) during the entire pregnancy. Besides, we observed a positive effect of carbon monoxide (CO) exposure during the third trimester of pregnancy on PTB (1.14; 1.01-1.29). The type of previous abortion could modify the effect of air pollution on the PTB risk (P-interaction < 0.05). Compared with mothers with previous induced abortion, mothers with previous spontaneous abortion carried a higher risk of PTB induced by NO2, CO, and O3. CONCLUSIONS: The risk of PTB was positively associated with levels of NO2, SO2 and CO, and negatively associated with the O3 level. The types of previous abortion could modify the effect of air pollution on PTB. Mothers who had an abortion previously, especially spontaneous abortion, should avoid exposure to air pollution to improve their pregnancy outcome.

Effects of ambient temperature on the risk of preterm birth in offspring of adolescent mothers in rural henan, China.

BACKGROUND: A number of studies have explored the association between ambient temperature and preterm birth (PTB), but rarely among adolescent mothers. OBJECTIVES: To estimate the effects of ambient temperature on the risk of PTB and gestational age of newborns delivered by adolescent mothers in rural areas of Henan province. METHODS: We obtained 5394 medical records of adolescent mothers with results of pre-pregnancy physical examination and pregnancy outcomes from the National Free Preconception Health Examination Project (NFPHEP) in Henan province. Meteorological information was obtained from the China Meteorological Data Sharing Service System. Individual exposure levels were evaluated with an inverse distance-weighted model. A multiple logistic regression model and multiple linear regression model were used to estimate the effects of ambient temperature on the risk of PTB and gestational age, respectively. Stratified and interaction analyses were also performed. RESULTS: Of newborns in this study, 3.45% (186/5394) were PTB. Mean, maximum and minimum temperature during the entire pregnancy, especially the last 1-4 weeks of pregnancy, were positively associated with the risk of PTB and negatively associated with gestational age (P < 0.05). Nevertheless, a masking effect was observed that gestational age was positively associated with ambient temperature during the first trimester of pregnancy, due to the strongly inverse correlation between ambient temperature during the early and late stages of pregnancy. Stratified analyses showed that increasing temperature during the last 1-4 weeks of pregnancy increased the risk of PTB and decreased gestational age in newborns born in the cold season (P < 0.05). Furthermore, interaction analyses showed that birth season modified the effects of temperature on the gestational age (Pinteraction < 0.10). CONCLUSIONS: Elevated ambient temperature can decrease gestational age and increase the risk of PTB in offspring of adolescent mothers in rural areas. The birth season may modify the effects of temperature on gestational age.

Genome-wide identification and expression analysis of the calmodulin-binding transcription activator (CAMTA) gene family in wheat (Triticum aestivum L.).

BACKGROUND: Plant calmodulin-binding transcription activator (CAMTA) proteins play important roles in hormone signal transduction, developmental regulation, and environmental stress tolerance. However, in wheat, the CAMTA gene family has not been systematically characterized. RESULTS: In this work, 15 wheat CAMTA genes were identified using a genome-wide search method. Their chromosome location, physicochemical properties, subcellular localization, gene structure, protein domain, and promoter cis-elements were systematically analyzed. Phylogenetic analysis classified the TaCAMTA genes into three groups (groups A, B, and C), numbered 7, 6, and 2, respectively. The results showed that most TaCAMTA genes contained stress-related cis-elements. Finally, to obtain tissue-specific and stress-responsive candidates, the expression profiles of the TaCAMTAs in various tissues and under biotic and abiotic stresses were investigated. Tissue-specific expression analysis showed that all of the 15 TaCAMTA genes were expressed in multiple tissues with different expression levels, as well as under abiotic stress, the expressions of each TaCAMTA gene could respond to at least one abiotic stress. It also found that 584 genes in wheat genome were predicted to be potential target genes by CAMTA, demonstrating that CAMTA can be widely involved in plant development and growth, as well as coping with stresses. CONCLUSIONS: This work systematically identified the CAMTA gene family in wheat at the whole-genome-wide level, providing important candidates for further functional analysis in developmental regulation and the stress response in wheat.

Transcriptome analysis of activated charcoal-induced growth promotion of wheat seedlings in tissue culture.

BACKGROUND: Activated charcoal (AC) is highly adsorbent and is often used to promote seedling growth in plant tissue culture; however, the underlying molecular mechanism remains unclear. In this study, root and leaf tissues of 10-day-old seedlings grown via immature embryo culture in the presence or absence of AC in the culture medium were subjected to global transcriptome analysis by RNA sequencing to provide insights into the effects of AC on seedling growth. RESULTS: In total, we identified 18,555 differentially expressed genes (DEGs). Of these, 11,182 were detected in the roots and 7373 in the leaves. In seedlings grown in the presence of AC, 9460 DEGs were upregulated and 7483 DEGs were downregulated in the presence of AC as compared to the control. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed 254 DEG-enriched pathways, 226 of which were common between roots and leaves. Further analysis of the major metabolic pathways revealed that AC stimulated the expression of nine genes in the phenylpropanoid biosynthesis pathway, including PLA, CYP73A, COMT, CYP84A, and 4CL, the protein products of which promote cell differentiation and seedling growth. Further, AC upregulated genes involved in plant hormone signaling related to stress resistance and disease resistance, including EIN3, BZR1, JAR1, JAZ, and PR1, and downregulated genes related to plant growth inhibition, including BKI1, ARR-B, DELLA, and ABF. CONCLUSIONS: Growth medium containing AC promotes seedling growth by increasing the expression of certain genes in the phenylpropanoid biosynthesis pathway, which are related to cell differentiation and seedling growth, as well as genes involved in plant hormone signaling, which is related to resistance.

Investigation of the mechanism of overall water splitting in UV-visible and infrared regions with SnC/arsenene vdW heterostructures in different configurations.

Monolayer arsenene presents good stability and high photogenic carrier mobility. However, a high photogenic electron and hole pair recombination rate seriously reduces its photocatalytic activity. The photocatalytic activity can be effectively improved by building type II heterostructures. In this work, SnC/arsenene heterostructures in three configurations are studied using first-principles calculations. Their structure, stability, and electronic and photocatalytic properties are investigated. It is found that all SnC/arsenene heterostructures are stable, and form type-II band edges, which effectively promote the transfer of photogenerated electrons from the SnC monolayer to the arsenene sheet. The charge transfer between SnC and arsenene leads to a built-in electric field in the interface region, which is favorable for inhibiting photogenic electron and hole pair recombination. Compared with the monolayer arsenene, the photocatalytic activity is greatly improved and the absorption spectrum of SnC/arsenene heterostructures is expanded. Attractively, these three heterostructures present two different photocatalytic mechanisms. H1 and H3 configurations were taken as examples to study their photocatalytic properties for overall water splitting at varying pH values and external strains. We found that alkaline conditions were more favorable for photocatalysis of SnC/arsenene heterostructures. In particular, H3 can still achieve full photocatalytic water decomposition in the near infrared region. These results show that the SnC/arsenene heterostructures are a prospective material for photocatalysis application.

Study of the GaAs/SiH van der Waals type-II heterostructure: a high efficiency photocatalyst promoted by a built-in electric field.

The application of two-dimensional (2D) materials to construct van der Waals (vdW) heterostructures in photocatalysis has attracted extensive attention recently. However, exploration of ways to enhance the photocatalytic efficiency at the interface is relatively limited. In this study, using density functional theory, we prove that GaAs/SiH formed a standard type-II heterojunction with a 2.17 eV direct band gap. The charge transfer across the interface was investigated by the charge density difference and Bader charge analysis. Due to the difference in the work functions, the relative positions of the conduction band (CB) and valence band (VB) of GaAs and SiH present a significant change after the heterostructure is formed. Furthermore, the built-in electric field, formed by charge transfer at the interface of the GaAs/SiH heterojunction, promotes photogenerated carrier separation. The band edge position and the absorption spectrum were calculated and the photocatalytic performance of the GaAs/SiH vdW heterostructure in the visible light region was evaluated. Strong absorption is observed, which predicts promising application in photonic detection across the visible and the UV region. Excitingly, GaAs/SiH has a significant advantage for improving the photocatalytic efficiency under visible light irradiation. Our work can provide guidance for the design of other highly efficiency heterostructures.

The role of maternal methylation in the association between prenatal meteorological conditions and neonatal H19/H19-DMR methylation.

Meteorological conditions during pregnancy can affect birth outcome, which has been linked to the H19/H19-differentially methylated region (DMR). However, the detailed mechanisms underlying this association are unclear. This was investigated in the present study to provide epidemiological evidence for elucidating the pathogenesis of adverse birth outcomes. A total of 550 mother-newborn pairs were recruited in Zhengzhou, China from January 2010 to January 2012. Meteorological data including temperature (T), relative humidity (RH), and sunshine duration (SSD) were obtained from the China Meteorological Data Sharing Service System. Bisulfite sequencing PCR was performed to determine the methylation levels of H19/H19-DMR using genomic DNA extracted from maternal peripheral and umbilical cord blood. The results showed that H19-DMR methylation status in cord blood was positively associated with that in maternal blood. Neonatal H19-DMR methylation was negatively associated with T and RH during the first trimester and positively associated with these variables during the third trimester. There was a positive correlation between neonatal H19-DMR methylation and SSD during the second trimester and a negative correlation during the third trimester. Similar associations were observed between maternal H19-DMR methylation and prenatal meteorological conditions. We also observed significant interaction effects of maternal H19/H19-DMR methylation and most prenatal meteorological factors on neonatal methylation, and found that changes in the methylation status of maternal H19-DMR were responsible for the effects of prenatal meteorological conditions on neonatal methylation. In summary, neonatal H19-DMR methylation was significantly associated with prenatal meteorological conditions, which was modified and mediated by maternal H19-DMR methylation changes. These findings provide insights into the relationship between meteorological factors during pregnancy and adverse birth outcomes or disease susceptibility in offspring, and can serve as a reference for environmental policy-making.

[Association between vitamin D deficiency and Toxoplasma gondii infection in women of childbearing age].

OBJECTIVE: To explore the association between the risk of vitamin D deficiency and the infection of Toxoplasma gondii in women of childbearing age. METHODS: Based on a Women's Reproductive Health Cohort Study performed from 2007 to 2010 in four counties of Henan Province, Toxoplasma gondii infection were tested by enzyme linked immunosorbent assay(ELISA). A total of 1151 women with pregnancy outcomes were followed up and pre-pregnancy vitamin D level was measured with serum samples. Case-control study was used to examine the association between the risk of vitamin D deficiency and Toxoplasma infection. RESULTS: The prevalence of vitamin D deficiency was 61. 5%(95% CI 59. 2%-64. 9%) and Toxoplasma infection was 9. 6%(95% CI 7. 9%-11. 4%), among which IgG positive, IgM positive and both positive were 7. 6%, 2. 3% and 0. 3%, respectively. After adjusting confounding factors, including education, family annual income, and dietary intake frequencies. , it was found that the risk of vitamin D deficiency in women infected with Toxoplasma gondii recently or previously was 1. 75 times higher than that of uninfected women(95% CI 1. 11-2. 77). CONCLUSION: There is association between the risk of vitamin D deficiency and the infection of Toxoplasma gondii in women of childbearing age.

Pollution patterns and characteristics of perfluorinated compounds in surface water adjacent potential industrial emission categories of Shanghai, China.

Perfluorinated compounds (PFCs) have received increasing attention worldwide recently because of potential risk to aquatic environment and living organisms. Herein, occurrence and spatial distributions of 17 selected PFCs were investigated in surface water adjacent to potential industrial emission categories in Shanghai. The results showed the distributions of PFCs in the ambient rivers were greatly affected by those industrial sources. Perfluorooctanoic acid (PFOA) and other short-chain PFCs such as perfluoropentanoic acid (PFPeA) and perfluorooctanesulfonate (PFBS) were detected as the predominant species in all samples. Specifically, the total concentrations of PFCs (∑PFCs) near the airport ranged from 142 to 264ngL-1, with PFOA, PFPeA, and PFBS as most prevalent. While near the fluorochemical plant and metal plating, concentrations of ∑PFCs ranged from 200 to 2143ngL-1 and 211ngL-1 to 705ngL-1; and PFOA was the predominant individual PFCs, with the highest concentration of 1985ngL-1. However, concentrations of PFOS were found at relatively low level, which ranged from < 0.06 to 4.44ngL-1. The Spearman correlation analysis of concentration of individual PFCs showed that PFOA and perfluorohexanoic acid (PFHxA) was positive, while the correlation between PFOA and perfluorohexansulfonate (PFHxS) was negative near the airport, indicating PFOA and PFHxA may share common sources. Preliminary ecological risk evaluation of PFCs in adjacent water of the industrial emission areas suggested these emission categories posed higher risks than other area, although the risk level was still relatively safe.

Allospecific CD4(+) T cells retain effector function and are actively regulated by Treg cells in the context of transplantation tolerance.

Although donor-specific transfusion (DST) plus CD154 blockade represents a robust protocol for inducing transplantation tolerance, the underlying mechanisms are incompletely understood. In a murine T-cell adoptive transfer model, we have visualized alloantigen-specific, TCR-transgenic for H2-A(b) /H2-K(d) 54-68 epitope (TCR75) CD4(+) T cells with indirect allospecificity during the course of tolerance induction. Three main observations were made. First, although the majority of TCR75 CD4(+) T cells were deleted following DST plus CD154 blockade, the surviving TCR75 CD4(+) T cells were capable of making IL-2, upregulating CD44, and undergoing cell division, suggesting that they were functionally active. Indeed, residual TCR75 CD4(+) T cells reisolated from the primary recipients given DST plus CD154 blockade were fully capable of rejecting allografts upon secondary transfer. Second, in tolerant mice, TCR75 CD4(+) T cells were not induced to express Foxp3 in the graft-draining lymph node. TCR75 CD4(+) T cells were also absent in accepted graft tissues in which endogenous Treg cells were enriched. Finally, DST plus CD154 blockade resulted in an abortive expansion of TCR75 CD4(+) T cells, a process that required the presence of endogenous Treg cells. Collectively, surviving TCR75 CD4(+) T cells are immunocompetent but kept in check by an endogenous immunosuppressive network induced by DST plus CD154 blockade.

Transitional-2 B cells acquire regulatory function during tolerance induction and contribute to allograft survival.

In humans, tolerance to renal transplants has been associated with alterations in B-cell gene transcription and maintenance of the numbers of circulating transitional B cells. Here, we use a mouse model of transplantation tolerance to investigate the contribution of B cells to allograft survival. We demonstrate that transfer of B cells from mice rendered tolerant to MHC class I mismatched skin grafts can prolong graft survival in a dose-dependent and antigen-specific manner to a degree similar to that afforded by graft-specific regulatory T (Treg) cells. Tolerance in this model was associated with an increase in transitional-2 (T2) B cells. Only T2 B cells from tolerized mice, not naïve T2 nor alloantigen experienced T2, were capable of prolonging skin allograft survival, and suppressing T-cell activation. Tolerized T2 B cells expressed lower levels of CD86, increased TIM-1, and demonstrated a preferential survival in vivo. Furthermore, we demonstrate a synergistic effect between tolerized B cells and graft-specific Treg cells. IL-10 production by T2 B cells did not contribute to tolerance, as shown by transfer of B cells from IL-10(-/-) mice. These results suggest that T2 B cells in tolerant patients may include a population of regulatory B cells that directly inhibit graft rejection.

Intranasal peptide-induced tolerance and linked suppression: consequences of complement deficiency.

A role for complement, particularly the classical pathway, in the regulation of immune responses is well documented. Deficiencies in C1q or C4 predispose to autoimmunity, while deficiency in C3 affects the suppression of contact sensitization and generation of oral tolerance. Complement components including C3 have been shown to be required for both B-cell and T-cell priming. The mechanisms whereby complement can mediate these diverse regulatory effects are poorly understood. Our previous work, using the mouse minor histocompatibility (HY) model of skin graft rejection, showed that both C1q and C3 were required for the induction of tolerance following intranasal peptide administration. By comparing tolerance induction in wild-type C57BL/6 and C1q-, C3-, C4- and C5-deficient C57BL/6 female mice, we show here that the classical pathway components including C3 are required for tolerance induction, whereas C5 plays no role. C3-deficient mice failed to generate a functional regulatory T (Treg) -dendritic cell (DC) tolerogenic loop required for tolerance induction. This was related to the inability of C3-deficient DC to up-regulate the arginine-consuming enzyme, inducible nitric oxide synthase (Nos-2), in the presence of antigen-specific Treg cells and peptide, leading to reduced Treg cell generation. Our findings demonstrate that the classical pathway and C3 play a critical role in the peptide-mediated induction of tolerance to HY by modulating DC function.

The T-cell receptor is not hardwired to engage MHC ligands.

The bias of αß T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that engagement with MHC ligands during thymocyte selection and peripheral T-cell activation imposes remarkably little constraint over TCR structure. Such versatility is more consistent with an opportunist, rather than a predetermined, mode of interface formation. This hypothesis was experimentally confirmed by expressing a hybrid TCR containing TCR-γ chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.

[DUOX2 mutations in children with congenital hypothyroidism].

OBJECTIVE: To study the features of DUOX2 mutations and genotype-phenotype relationship in children with congenital hypothyroidism (CH), in order to provide evidence for gene diagnosis and gene treatment of CH. METHODS: Blood samples were collected from 10 CH children with thyromegaly. Genomic DNA was extracted from peripheral blood leukocytes. All exons of DUOX2 gene were analyzed using PCR and direct sequencing. RESULTS: G3632A mutation in the exon 28 of DUOX2 that may result in arginine to histidine substitution at codon 1211 was found in one patient. T2033C mutation in the exon 17 of DUOX2 that may result in histidine to arginine substitution at codon 678 was found in three patients. They were all heterozygous mutations. CONCLUSIONS: Heterozygous mutations in DUOX2 may affect protein function and cause CH. The relationship between DUOX2 genotypes and clinical phenotypes is unclear and needs further studies.

Molecular cloning and expression of glutathione S-transferases involved in propargite resistance of the carmine spider mite, Tetranychus cinnabarinus (Boisduval).

The carmine spider mite (CSM) Tetranychus cinnabarinus has become a serious pest in China and has developed resistance to acaricide propargite as it is used to control mites worldwide including T. cinnabarinus. In this study, a resistant colony of T. cinnabarinus, PRR34 (37.78-fold resistant ratio), was established after 34 generations of propargite selection, and cross-resistance patterns of 7 other acaricides were determined in comparison with a susceptible strain (SS). The contribution of detoxification enzymes to propargite tolerance were investigated using biological, biochemical and molecular approaches. Enzyme inhibitor synergist tests suggested glutathione S-transferases (GST) involvement in propargite-resistance of PRR34, and GST activity against 1-chloro-2,4-dinitrobenzene (CDNB) was correlated with the development of resistance. Eight novel GST genes (TcGSTd1, TcGSTd2, TcGSTm1, TcGSTm2, TcGSTm3, TcGSTm4 and TcGSTm5) were cloned, and phylogenetic analysis showed that the eight GST genes were most closely related to GST family delta and mu from Tetranychusurticae. Quantitative RT-PCR revealed that the expression level of GSTs in PPR34 strain increased in larvae, nymphs and adults, while decreased in eggs compared with that of SS. Collectively, these results support a role of GSTs in mediating resistance to propargite in the PRR34 strain. TcGSTd1,TcGSTd2 and TcGSTm2 genes might play significant roles in propargite resistance of CSM, especially at adult stage. This is the first attempt to define specific genes involved in GST mediated propargite resistance of T. cinnabarinus at the transcriptional level.

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors.

The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 µg/mL that was superior to that of the agricultural fungicide boscalid (2.2 µg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 µM that was superior to that of boscalid (7.9 µM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.