Cell-free DNA test for fetal chromosomal abnormalities in multiple pregnancies.

INTRODUCTION: This study aimed to report the screening performance of cell-free DNA (cfDNA) testing for chromosomal abnormalities in twins, triplets, and vanishing twin pregnancies. MATERIAL AND METHODS: Data were obtained from pregnant women with a multiple pregnancy or a vanishing twin pregnancy at ≥10 weeks' gestation who requested self-financed cfDNA testing between May 2015 and December 2021. Those that had positive screening results had diagnostic confirmatory procedures after counseling and consent. The performance of screening of the cfDNA test was determined by calculating confirmation rate and combined false-positive rate (cFPR). RESULTS: Data from 292 women were included after exclusion of those lost to follow-up, with no-result on cfDNA testing, or had reductions. Of the 292 pregnancies, 10 (3.4%) were triplets, including no cases of trisomy 21 and trisomy 18; 249 (85.3%) were twins, including 3 cases of trisomy 21 and no cases of trisomy 18 and 13; and 33 (11.3%) were vanishing twins, including 3 cases of trisomy 21 and 1 case of trisomy 18. The median (IQR) maternal age was 34 years (31-37). For triplet pregnancies, the initial no-result rate was 10.3% (95% confidence interval [CI] 3.6-26.4), all with results after redraw. For twin pregnancies, the initial no-result rate was 12.9% (95% CI 9.6-17.0), and the no-result rate after redraw was 1.6% (95% CI 0.7-3.6). For vanishing twins, there were no cases with no-result. All triplets had low-risk cfDNA results. The confirmation rate for trisomy 21 was 100% with a FPR at 0% due to the small number of positive cases for twins. For vanishing twins, one high-risk case for trisomy 21 and the only high-risk case for trisomy 18 were confirmed with a cFPR of 8.3% (n = 2/24; 95% CI 2.3-25.9). CONCLUSIONS: cfDNA testing in twin pregnancies has sufficient screening performance for trisomy 21 but the number of affected cases for other conditions is limited to draw any meaningful conclusion. The use of cfDNA testing in triplet pregnancies and vanishing twins remains an area for further research.

Chemical Speciation, Leaching Behavior, and Environmental Risk Assessment of Trace Elements in the Bottom Ash from Biomass Power Plant.

Biomass combustion for power generation stands as a pivotal method in energy utilization, offering a promising approach for renewable energy utilization. However, the substantial volume of slag produced by biomass burning plants poses environmental challenges, impeding sustainable energy practices. This article systematically studies the characteristics of ash generated from typical biomass direct combustion power plant ash and analyzes the chemical composition, trace element content characteristics, leaching characteristics, and chemical forms of biomass bottom ash. Furthermore, it assesses the environmental ecology and bioavailability of trace elements in bottom ash using the ecological risk assessment method and RAC method. The results demonstrate that the biomass bottom ash contains plant nutrients, such as K, Ca, Mg, and P, while the content of harmful trace elements is lower than the relevant Chinese standards. In dissolution experiments, the leaching rate of nearly all elements remains exceptionally low, primarily due to the distribution of trace elements within the lattice structure of stable minerals. Trace elements predominantly exist in the residual phase, Cu and Zn primarily found in organic compounds and sulfide bound states, while other elements mostly exist in the form of iron manganese oxide bound states. Ecological risk assessment indicates a significant risk level for Cd, contrasting with the slight risk associated with other elements. RAC results indicated no ecological risk of all of the trace elements. Consequently, the utilization of bottom ash in agricultural and forestry soils is deemed to be viable. These findings serve as a crucial foundation for biomass bottom ash resource utilization and underpin the sustainable utilization of biomass energy.

ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Structural analysis of lignite-derived humic acid and its microscopic interactions with heavy metal ions in aqueous solution.

Understanding heavy metal environmental behavior with humic acid (HA) is critical. There is currently a lack of information on the control of its structure organization on its reactivity to metals. The difference in HA structures under non-homogeneous conditions is critical for revealing its micro-interaction with heavy metals. The heterogeneity of HA was reduced using the fractionation method in this study, the chemical properties of HA fractions were analyzed using py-GC/MS, and the structural units of HA were proposed. Pb2+ was used as a probe to investigate the difference in the adsorption capacity of HA fractions. The microscopic interaction of structures with heavy metal was investigated and validated by structural units. The results show that as molecular weight increased, the oxygen content and the number of aliphatic chains decreased, but the opposite was true for aromatic and heterocyclic rings. The adsorption capacity for Pb2+ was as follows: HA-1 > HA-2 > HA-3. According to the linear analysis of the influencing factors of maximum adsorption capacity and possibility factors, the adsorption capacity was positively correlated with the contents of acid groups, carboxyl groups, phenolic hydroxyl groups, and the number of aliphatic chains. The phenolic hydroxyl group and the aliphatic-chain structure have the greatest impact. Therefore, structural differences and the number of active sites play an important role in adsorption. The binding energy of HA structural units to Pb2+ was calculated. It was found that the chain structure is easier to bind to heavy metals than aromatic rings, and the affinity of-COOH to Pb2+ is greater than that of -OH. These findings can help improve the adsorbent design.

A pilot investigation of low-pass genome sequencing identifying site-specific variation in chromosomal mosaicisms by a multiple site sampling approach in first-trimester miscarriages.

STUDY QUESTION: Can multiple-site low-pass genome sequencing (GS) of products of conception (POCs) improve the detection of genetic abnormalities, especially heterogeneously distributed mosaicism and homogeneously distributed mosaicism in first-trimester miscarriage? SUMMARY ANSWER: Multiple-site sampling combined with low-pass GS significantly increased genetic diagnostic yield (77.0%, 127/165) of first-trimester miscarriages, with mosaicisms accounting for 17.0% (28/165), especially heterogeneously distributed mosaicisms (75%, 21/28) that are currently underappreciated. WHAT IS KNOWN ALREADY: Aneuploidies are well known to cause first-trimester miscarriage, which are detectable by conventional karyotyping and next-generation sequencing (NGS) on a single-site sampling basis. However, there are limited studies demonstrating the implications of mosaic genetic abnormalities in first-trimester miscarriages, especially when genetic heterogeneity is present in POCs. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional cohort study carried out at a university-affiliated public hospital. One hundred seventy-four patients diagnosed with first-trimester miscarriage from December 2018 to November 2021 were offered ultrasound-guided manual vacuum aspiration (USG-MVA) treatment. Products of conception were subjected to multiple-site low-pass GS for the detection of chromosomal imbalances. PARTICIPANTS/MATERIALS, SETTING, METHODS: For each POC, multiple sites of villi (three sites on average) were biopsied for low-pass GS. Samples with maternal cell contamination (MCC) and polyploidy were excluded based on the quantitative fluorescence polymerase chain reaction (QF-PCR) results. The spectrum of chromosomal abnormalities, including mosaicism (heterogeneously distributed and homogeneously distributed) and constitutional abnormalities was investigated. Chromosomal microarray analysis and additional DNA fingerprinting were used for validation and MCC exclusion. A cross-platform comparison between conventional karyotyping and our multiple-site approach was also performed. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred sixty-five POCs (corresponding to 490 DNA samples) were subjected to low-pass GS. Genetic abnormalities were detected in 77.0% (127/165) of POCs by our novel approach. Specifically, 17.0% (28/165) of cases had either heterogeneously distributed mosaicism (12.7%, 21/165) or homogeneously distributed mosaicism (6.1%, 10/165) (three cases had both types of mosaicism). The remaining 60.0% (99/165) of cases had constitutional abnormalities. In addition, in the 71 cases with karyotyping performed in parallel, 26.8% (19/71) of the results could be revised by our approach. LIMITATIONS, REASONS FOR CAUTION: Lack of a normal gestational week-matched cohort might hinder the establishment of a causative link between mosaicisms and first-trimester miscarriage. WIDER IMPLICATIONS OF THE FINDINGS: Low-pass GS with multiple-site sampling increased the detection of chromosomal mosaicisms in first-trimester miscarriage POCs. This innovative multiple-site low-pass GS approach enabled the novel discovery of heterogeneously distributed mosaicism, which was prevalent in first-trimester miscarriage POCs and frequently observed in preimplantation embryos, but is currently unappreciated by conventional single-site cytogenetic investigations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported partly by Research Grant Council Collaborative Research Fund (C4062-21GF to K.W.C), Science and Technology Projects in Guangzhou (202102010005 to K.W.C), Guangdong-Hong Kong Technology Cooperation Funding Scheme (TCFS), Innovation and Technology Fund (GHP/117/19GD to K.W.C), HKOG Direct Grant (2019.050 to J.P.W.C), and Hong Kong Health and Medical Research Fund (05160406 to J.P.W.C). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Shear polaritons from transformation optics.

Natural in-plane hyperbolic crystals (such as α-MoO3) and natural monoclinic crystals (such as ß-Ga2O3) have recently drawn great research focus. Despite their obvious similarities, however, these two kinds of materials are usually studied as separate topics. In this Letter, we explore the intrinsic relationship between materials like α-MoO3 and ß-Ga2O3 under the framework of transformation optics, providing another perspective to understand the asymmetry of hyperbolic shear polaritons. It is worth mentioning that we demonstrate this novel, to the best of our knowledge, method from theoretical analysis and numerical simulations, which maintain a high degree of consistency. Our work not only combines natural hyperbolic materials with the theory of classical transformation optics, but also opens new avenues for future studies of various natural materials.

Calcium-doped magnetic humic acid nano particles for the efficient removal of heavy metals from wastewater: the role of Ca.

Ca doping is an effective method for improving the adsorption capacity of HA-Fe aggregates and regulating their structures. Understanding the structural characteristics of Ca-HA-Fe aggregates can help explore their microscopic adsorption effect on heavy metals. However, the heterogeneity of HA results in an incomplete understanding of the structural characteristics of the ternary system of Ca-HA-Fe aggregates and adsorption of the quaternary system of Ca-HA-Fe-Pb/Cu/Cd. In this study, interactions between Ca-HA-Fe ternary and Ca-HA-Fe-Pb/Cu/Cd quaternary systems were discussed from a molecular perspective. The structures of the basic structural units of HA were identified. Density functional theory (DFT) was employed to calculate the stable states of basic structural units of HA and Ca2+. The results showed that hydroxyl and carboxyl groups exhibited the highest capacity to bind with Ca2+. The interactions among Ca, HA, and Fe led to the formation of network aggregates. The binding energies of functional groups for heavy metals and the feasibility of ion exchange were calculated by the method of experiment and DFT. According to the contribution of functional group complexation and ion exchange, the ion exchange values for Pb2+, Cu2+, and Cd2+ were 66.71%, 62.87%, and 60.79%, respectively, which indicated that Ca2+ ion exchange showed considerable potential in enhancing the adsorption capacity of heavy metals.

A Sandwich Structure of Fulvic Acid and PMIDA-Modified LDHs for the Simultaneous Removal of Cu2+ and Aniline in Multicomponent Solutions.

The coexistence of organic and inorganic pollutants in industrial wastewater has emerged as a concerning environmental issue worldwide due to the critical levels of biological toxicity of these pollutants. In this context, the present study proposes a sandwich structure of fulvic acid and PMIDA-modified LDHs (FA/PMIDA-LDHs) for the simultaneous removal of Cu2+ and aniline from wastewater. The specific structure was synthesized using a combination of coprecipitation and impregnation methods. Abundant benzene rings and oxygen-containing functional groups greatly increased the number of sites for the adsorption of both Cu2+ and aniline. The maximum adsorption capacity of Cu2+ and aniline in solution with initial pH 5.0 at 25 °C could reach 221.24 and 132.28 mg/g, respectively. Cu2+ could be chelated by the functional groups in the FA/PMIDA-LDHs structure, and a coupled reduction-complexation mechanism was proposed for this process. The uptake of aniline on FA/PMIDA-LDHs was demonstrated to be a result of the combination of coordination forces, hydrophobic effects, π-π interactions, and hydrogen bonds. In a multicomponent solution, FA/PMIDA-LDHs exhibited excellent salt tolerance of up to 1000 mg/L of Na+ or Ca2+. The effects of Fe3+, Ni2+, Cl-, Cr2O72-, SO42-, and H2PO4- on the uptakes of Cu2+ and aniline were also investigated.

Remediation of the soil contaminated by heavy metals with nano-hydroxy iron phosphate coated with fulvic acid.

Heavy metals pose a serious threat and damage to ecological health when released into the environment. n-HFP is usually used to remediate soils contaminated with heavy metals, but its ability to solidify heavy metals is limited. FA has good ability to trap heavy metals due to its abundant oxygen-containing functional groups. However, the solubility of FA in water limits its application in the field of heavy metal removal. In this paper, n-HFP@FA was prepared by co-precipitation method. Through FT-IR and BET analysis, the oxygen-containing functional groups and specific surface area of n-HFP@FA increased due to the addition of FA. The adsorption behaviour of n-HFP@FA on Pb, Cd, and Cu followed the pseudo-second-order and Langmuir isotherm models. In addition, the maximum adsorption capacities of n-HFP@FA for Pb, Cd, and Cu were 371.1, 190.5, and 129.75 mg/g, respectively. As shown by FT-IR and XPS analysis, the main mechanisms of Pb, Cd and Cu removal by n-HFP@FA are: complexation, electrostatic and precipitation. The n-HFP@FA showed high removal rates of Pb, Cd, and Cu in soil leachates of different pH. In the soil remediation experiments, the BCR method and Pearson correlation analysis showed that the acid-soluble, reducible and oxidizable fractions of Pb, Cd, and Cu in the soil were effectively converted into a more stable residual fraction. This study opens up a prospect for the application of n-HFP@FA composites in the remediation of contaminated soil.

Mate-pair genome sequencing reveals structural variants for idiopathic male infertility.

Currently, routine genetic investigation for male infertility includes karyotyping analysis and PCR for Y chromosomal microdeletions to provide prognostic information such as sperm retrieval success rate. However, over 85% of male infertility remain idiopathic. We assessed 101 male patients with primary infertility in a retrospective cohort analysis who have previously received negative results from standard-of-care tests. Mate-pair genome sequencing (large-insert size library), an alternative long-DNA sequencing method, was performed to detect clinically significant structural variants (SVs) and copy-number neutral absence of heterozygosity (AOH). Candidate SVs were filtered against our in-house cohort of 1077 fertile men. Genes disrupted by potentially clinically significant variants were correlated with single-cell gene expression profiles of human fetal and postnatal testicular developmental lineages and adult germ cells. Follow-up studies were conducted for each patient with clinically relevant finding(s). Molecular diagnoses were made in 11.1% (7/63) of patients with non-obstructive azoospermia and 13.2% (5/38) of patients with severe oligozoospermia. Among them, 12 clinically significant SVs were identified in 12 cases, including five known syndromes, one inversion, and six SVs with direct disruption of genes by intragenic rearrangements or complex insertions. Importantly, a genetic defect related to intracytoplasmic sperm injection (ICSI) failure was identified in a patient with non-obstructive azoospermia, illustrating the additional value of an etiologic diagnosis in addition to determining sperm retrieval rate. Our study reveals a landscape of various genomic variants in 101 males with idiopathic infertility, not only advancing understanding of the underlying mechanisms of male infertility, but also impacting clinical management.

Invisible devices with natural materials designed by evolutionary optimization.

It is a longstanding dream to put on a cloak and escape from sight. Transformation optics (TO) and artificial metamaterials turn this circumstance into reality, but the requirements for inhomogeneous and anisotropic materials make it almost impossible in practical realization. Furthermore, invisibility can only be constructed at a narrow frequency regime in previous studies and depends critically on the inescapable material losses. Here, the authors propose the multifrequency isotropic invisible devices and natural hyperbolic invisible devices using realistic materials, such as microwave materials and van der Waals (vdW) materials. The inherent material losses are taken into account in the optimization process, bringing the concept of invisibility closer to realistic conditions. To verify the stability of the proposed method, full-wave numerical simulations and analytical calculations are performed, and both obtained excellent invisibility performance. Due to the combined advantages of the simple two-layer core-shell configuration and natural materials, our work provides a promising platform for fabricating invisible devices at low cost and paves the way for new implementations of intelligent photonics beyond the limitations of TO.

Genome-Wide Cell-Free DNA Test for Fetal Chromosomal Abnormalities and Variants: Unrestricted Versus Restricted Reporting.

This study aimed to compare the screening performance of genome-wide cfDNA testing for chromosomal abnormalities between two periods where additional findings were reported and not reported. Data were obtained from consecutive pregnant women with a singleton pregnancy at ≥10 weeks who requested cfDNA testing during 2015-2019. The performance of screening of the cfDNA test was determined by calculating the concordance rate, detection rate, and false-positive rate. Data from 3981 women were included. The no-result rates were similar between the two reporting periods (2.04% vs. 2.08%). Concordance rates for trisomy 21 and 18 were 100% and 100%, respectively. There were two cases tested high risk for trisomy 13, with a concordance rate of 0%. In total, 12 cases were high risk for any sex chromosome aneuploidy with an overall concordance of 75%, and 15 cases tested high risk for any rare autosomal trisomy, with a 13.3% concordance rate. The detection rates for trisomy 21 and 18 were 100% and 100%, respectively. For any SCA, the detection rate was 90%. For the two reporting periods, the combined false-positive rates were 0.93% and 0.17%, which were significantly different (p = 0.002). Restricting the reporting of additional findings from genome-wide cfDNA analysis has reduced the false-positive rate but without a reduction in the no-result rate.

Tunable Cherenkov radiation based on a van der Waals semiconductor α-MoO3 and graphene hybrid.

In this Letter, we explore the Cherenkov radiation properties of α-phase molybdenum trioxide (α-MoO3). We demonstrate that the asymmetric, forward, and reverse Cherenkov radiation can simultaneously exist by rotating the α-MoO3 slab at the same working frequency and structure. In addition, thanks to the tunable functionalities of graphene, the conversion of forward and reverse Cherenkov radiation can be actualized by altering the Fermi level of graphene. These dynamically adjustable features provide a novel, to the best of our knowledge, and intuitive way for tunable Cherenkov radiation in the mid-infrared range, which opens up new opportunities in designing and manufacturing tunable radiation sources in future.

Investigation of Chromosomal Structural Abnormalities in Patients With Undiagnosed Neurodevelopmental Disorders.

Background: Structural variations (SVs) are various types of the genomic rearrangements encompassing at least 50 nucleotides. These include unbalanced gains or losses of DNA segments (copy number changes, CNVs), balanced rearrangements (such as inversion or translocations), and complex combinations of several distinct rearrangements. SVs are known to play a significant role in contributing to human genomic disorders by disrupting the protein-coding genes or the interaction(s) with cis-regulatory elements. Recently, different types of genome sequencing-based tests have been introduced in detecting various types of SVs other than CNVs and regions with absence of heterozygosity (AOH) with clinical significance. Method: In this study, we applied the mate-pair low pass (∼4X) genome sequencing with large DNA-insert (∼5 kb) in a cohort of 100 patients with neurodevelopmental disorders who did not receive informative results from a routine CNV investigation. Read-depth-based CNV analysis and chimeric-read-pairs analysis were used for CNV and SV analyses. The region of AOH was indicated by a simultaneous decrease in the rate of heterozygous SNVs and increase in the rate of homozygous SNVs. Results: First, we reexamined the 25 previously reported CNVs among 24 cases in this cohort. The boundaries of these twenty-five CNVs including 15 duplications and 10 deletions detected were consistent with the ones indicated by the chimeric-read-pairs analysis, while the location and orientation were determined in 80% of duplications (12/15). Particularly, one duplication was involved in complex rearrangements. In addition, among all the 100 cases, 10% of them were detected with rare or complex SVs (>10 Kb), and 3% were with multiple AOH (≥5 Mb) locating in imprinting chromosomes identified. In particular, one patient with an overall value of 214.5 Mb of AOH identified on 13 autosomal chromosomes suspected parental consanguinity. Conclusion: In this study, mate-pair low-pass GS resolved a significant proportion of CNVs with inconclusive significance, and detected additional SVs and regions of AOH in patients with undiagnostic neurodevelopmental disorders. This approach complements the first-tier CNV analysis for NDDs, not only by increasing the resolution of CNV detection but also by enhancing the characterization of SVs and the discovery of potential causative regions (or genes) contributory to could be complex in composition NDDs.

Population dynamics under climate change: persistence criterion and effects of fluctuations.

The present paper is devoted to the investigation of population dynamics under climate change. The evolution of species is modelled by a reaction-diffusion equation in a spatio-temporally heterogeneous environment described by a climate envelope that shifts with a time-dependent speed function. For a general almost-periodic speed function, we establish the persistence criterion in terms of the sign of the approximate top Lyapunov exponent and, in the case of persistence, prove the existence of a unique forced wave solution that dominates the population profile of species in the long run. In the setting for studying the effects of fluctuations in the shifting speed or location of the climate envelope, we show by means of matched asymptotic expansions and numerical simulations that the approximate top Lyapunov exponent is a decreasing function with respect to the amplitude of fluctuations, yielding that fluctuations in the shifting speed or location have negative impacts on the persistence of species, and moreover, the larger the fluctuation is, the more adverse the effect is on the species. In addition, we assert that large fluctuations can always drive a species to extinction. Our numerical results also show that a persistent species under climate change is invulnerable to mild fluctuations, and becomes vulnerable when fluctuations are so large that the species is endangered. Finally, we show that fluctuations of amplitude less than or equal to the speed difference between the shifting speed and the critical speed are too weak to endanger a persistent species.

Histamine Sensitization of the Voltage-Gated Sodium Channel Nav1.7 Contributes to Histaminergic Itch in Mice.

Itch, a common clinical symptom of many skin diseases, severely impairs the life quality of patients. Nav1.7, a subtype of voltage-gated sodium channels mainly expressed in primary sensory neurons, is responsible for the amplification of threshold currents that trigger action potential (AP) generation. Gain-of-function mutation of Nav1.7 leads to paroxysmal itch, while pharmacological inhibition of Nav1.7 alleviates histamine-dependent itch. However, the crosstalk between histamine and Nav1.7 that leads to itch is unclear. In the present study, we demonstrated that in the dorsal root ganglion (DRG) neurons from histamine-dependent itch model mice induced by compound 48/80, tetrodotoxin-sensitive (TTX-S) but not TTX-resistant Na+ currents were activated at more hyperpolarized membrane potentials compared to those on DRG neurons from vehicle-treated mice. Meanwhile, bath application of histamine shifted the activation voltages of TTX-S Na+ currents to the hyperpolarized direction, increased the AP frequency, and reduced the current threshold required to elicit APs. Further mechanistic studies demonstrated that selective activation of H1 but not H2 and H4 receptors mimicked histamine effect on TTX-S Na+ channels in DRG neurons. The protein kinase C (PKC) inhibitor GO 8963, but not the PKA inhibitor H89, normalized histamine-sensitized TTX-S Na+ channels. We also demonstrated that histamine shifted the activation voltages of Na+ currents to the hyperpolarized direction in Chinese hamster ovary (CHO) cells expressing Nav1.7. Importantly, selective inhibition of Nav1.7 by PF-05089771 significantly relieved the scratching frequency in a histamine-dependent itch model induced by compound 48/80. Taken together, these data suggest that activation of H1 receptors by histamine sensitizes Nav1.7 channels through the PKC pathway in DRG neurons that contributes to histamine-dependent itch.

Removal of Antimony in Wastewater by Antimony Tolerant Sulfate-Reducing Bacteria Isolated from Municipal Sludge.

Antimony (Sb), a global and priority controlled pollutant, causes severe environmental issues. Bioremediation by microbial communities containing sulfate-reducing bacteria (SRB) is considered to be among the safest, economical, and environmentally friendly methods to remove Sb from wastewater. However, the roles of SRB species in these communities remain uncertain, and pure cultures of bacteria that may be highly efficient have not yet been developed for Sb removal. In this study, an Sb tolerant community was enriched from municipal sludge, and molecular ecological analysis showed that Escherichia (40%) and Desulfovibrio (15%) were the dominant bacteria. Further isolation and identification showed that the enriched SRB strains were closely related to Cupidesulfovibrio oxamicus, based on the molecular analyses of 16S rRNA and dsrB genes. Among them, a strain named SRB49 exhibited the highest activity in removal of Sb(V). SRB49 was able to remove 95% of Sb(V) at a concentration of 100 mg/L within 48 h under optimum conditions: a temperature of 37-40 °C, an initial pH value of 8, 4 mM of sulfate, and an initial redox potential of 145-229 mV. SEM-EDX analysis showed that SRB49 did not adsorb Sb(V) but reduced and precipitated Sb(V) via the formation of Sb2S3. The results demonstrated the potential roles that pure cultures of SRB species may play in Sb removal and the use of Sb-tolerant SRB strains for Sb remediation.

Binding interaction of a ring-hydroxylating dioxygenase with fluoranthene in Pseudomonas aeruginosa DN1.

Pseudomonas aeruginosa DN1 can efficiently utilize fluoranthene as its sole carbon source, and the initial reaction in the biodegradation process is catalyzed by a ring-hydroxylating dioxygenase (RHD). To clarify the binding interaction of RHD with fluoranthene in the strain DN1, the genes encoding alpha subunit (RS30940) and beta subunit (RS05115) of RHD were functionally characterized through multi-technique combination such as gene knockout and homology modeling as well as molecular docking analysis. The results showed that the mutants lacking the characteristic alpha subunit and/or beta subunit failed to degrade fluoranthene effectively. Based on the translated protein sequence and Ramachandran plot, 96.5% of the primary amino-acid sequences of the alpha subunit in the modeled structure of the RHD were in the permitted region, 2.3% in the allowed region, but 1.2% in the disallowed area. The catalytic mechanism mediated by key residues was proposed by the simulations of molecular docking, wherein the active site of alpha subunit constituted a triangle structure of the mononuclear iron atom and the two oxygen atoms coupled with the predicted catalytic ternary of His217-His222-Asp372 for the dihydroxylation reaction with fluoranthene. Those amino acid residues adjacent to fluoranthene were nonpolar groups, and the C7-C8 positions on the fluoranthene ring were estimated to be the best oxidation sites. The distance of C7-O and C8-O was 3.77 Å and 3.04 Å respectively, and both of them were parallel. The results of synchronous fluorescence and site-directed mutagenesis confirmed the roles of the predicted residues during catalysis. This binding interaction could enhance our understanding of the catalytic mechanism of RHDs and provide a solid foundation for further enzymatic modification.

Calcium-Modified Fe3O4 Nanoparticles Encapsulated in Humic Acid for the Efficient Removal of Heavy Metals from Wastewater.

Ca-modified Fe3O4 nanoparticles encapsulated in humic acid (HA-Ca/Fe3O4) were produced using a co-precipitation method. Furthermore, the adsorption performance of HA-Ca/Fe3O4 as well as the effect of coexisting ions and mechanisms were evaluated. A good description of the adsorption process was given using pseudo-second-order kinetic and Langmuir models. The adsorption capacities of HA-Ca/Fe3O4 for Pb2+, Cu2+, and Cd2+ were 208.33, 98.33, and 99.01 mg g-1, respectively. The 0.02-0.1 times concentrations in alkali and alkaline-earth metals promoted Pb2+ and Cd2+ adsorption; however, any concentration of alkali and alkaline-earth metals inhibited Cu2+-ion adsorption, probably owing to the differences in ionic radii between the interfering and heavy-metal ions. Pb2+, Cu2+, and Cd2+ removal using HA-Ca/Fe3O4 occurred via ion exchange, complexation of O-containing functional groups, mineral precipitation, and π-electron coordination. A method was proposed to calculate the contribution of these mechanisms to the adsorption process. In practice, HA-Ca/Fe3O4 can remove 99% Pb2+ and 91% Cu2+ and Cd2+ from real wastewater samples. Following five adsorption-desorption cycles, HA-Ca/Fe3O4 adsorption capacity did not change significantly. The aforementioned results indicated that HA-Ca/Fe3O4 presented a good potential in removing heavy metals in wastewater.