Thyroid disrupting effects and the developmental toxicity of hexafluoropropylene oxide oligomer acids in zebrafish during early development.

As perfluorooctanoic acid (PFOA) alternatives, hexafluoropropylene oxide dimeric acid (HFPO-DA) and hexafluoropropylene oxide trimeric acid (HFPO-TA) have been increasingly used and caused considerable water pollution. However, their toxicities to aquatic organisms are still not well known. Therefore, in this study, zebrafish embryos were exposed to PFOA (0, 1.5, 3 and 6 mg/L), HFPO-DA (0, 3, 6 and 12 mg/L) and HFPO-TA (0, 1, 2 and 4 mg/L) to comparatively investigate their thyroid disrupting effects and the developmental toxicity. Results demonstrated that waterborne exposure to PFOA and its two alternatives decreased T4 contents, the heart rate and swirl-escape rate of zebrafish embryos/larvae. The transcription levels of genes related to thyroid hormone regulation (crh), biosynthesis (tpo and tg), function (trα and trß), transport (transthyretin, ttr), and metabolism (dio1, dio2 and ugt1ab), were differently altered after the exposures, which induced the thyroid disrupting effects and decreased the heart rate. In addition, the transcription levels of some genes related to the nervous system development were also significantly affected, which was associated with the thyroid disrupting effects and consequently affected the locomotor activity of zebrafish. Therefore, HFPO-DA and HFPO-TA could not be safe alternatives to PFOA. Further studies to uncover the underlying mechanisms of these adverse effects are warranted.

MHBase: A comprehensive database of short microhaplotypes for advancing forensic genetic analysis.

Microhaplotypes (MHs) were first recommended by Prof. Kidd for use in forensics because they can improve human identification, kinship analysis, mixture deconvolution, and ancestry prediction. Since their introduction, extensive research has demonstrated the advantages of MHs in forensic applications and provided useful data for different populations. Currently, two databases, ALFRED (ALlele FREquency Database) and MicroHapDB (MicroHaplotype DataBase), house the published MH information and population data. We previously constructed a single nucleotide polymorphism SNP-SNP MH database (D-SNPsDB) of MHs within 50 bp on the whole human genome for 26 populations integrating basic data such as physical genome positions, mapping of variant identifiers (rsIDs), allele frequencies, and basic variant information. Building upon the previous research, we further selected MHs containing at least two variants (SNPs and/or insertions/deletions [InDels]) within a short DNA fragment (≤ 50 bp) in 26 populations based on the 1000 Genomes Project dataset (Phase 3) to construct a more comprehensive database. Subsequently, we established a user-friendly website that allows users to search the MH database (MHBase) based on their research objectives and study population to find suitable loci and provides other functions such as querying reported loci, performing online calculations using the PHASE software, and calculating ancestral-related parameters. The loci in the database are classified as SNP-based MHs, which include only SNPs, and InDel-including MHs, which contain at least one InDel. Here, we provide a detailed overview of the MHBase and an analysis of shared loci at the global and continental levels, ancestral markers, the genetic distance within loci, and mapping with the genome annotation file. The website is an accessible and useful tool for researchers engaged in marker discovery, population studies, assay development, and panel design.

Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer.

BACKGROUND: The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease. RESULT: Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer.

Low-Temperature and Fast-Charge Sodium Metal Batteries.

Low-temperature operation of sodium metal batteries (SMBs) at the high rate faces challenges of unstable solid electrolyte interphase (SEI), Na dendrite growth, and sluggish Na+ transfer kinetics, causing a largely capacity curtailment. Herein, low-temperature and fast-charge SMBs are successfully constructed by synergetic design of the electrolyte and electrode. The optimized weak-solvation dual-salt electrolyte enables high Na plating/stripping reversibility and the formation of NaF-rich SEI layer to stabilize sodium metal. Moreover, an integrated copper sulfide electrode is in situ fabricated by directly chemical sulfuration of copper current collector with micro-sized sulfur particles, which significantly improves the electronic conductivity and Na+ diffusion, knocking down the kinetic barriers. Consequently, this SMB achieves the reversible capacity of 202.8 mAh g-1 at -20 °C and 1 C (1 C = 558 mA g-1 ). Even at -40 °C, a high capacity of 230.0 mAh g-1 can still be delivered at 0.2 C. This study is encouraging for further exploration of cryogenic alkali metal batteries, and enriches the electrode material for low-temperature energy storage.

Optimizing Analytical Thresholds for Low-Template DNA Analysis: Insights from Multi-Laboratory Negative Controls.

When analyzing challenging samples, such as low-template DNA, analysts aim to maximize information while minimizing noise, often by adjusting the analytical threshold (AT) for optimal results. A potential approach involves calculating the AT based on the baseline signal distribution in electrophoresis results. This study investigates the impact of reagent kits, testing quarters, environmental conditions, and amplification cycles on baseline signals using historical records and experimental data on low-template DNA. Variations in these aspects contribute to differences in baseline signal patterns. Analysts should remain vigilant regarding routine instrument maintenance and reagent replacement, as these may affect baseline signals. Prompt analysis of baseline status and tailored adjustments to ATs under specific laboratory conditions are advised. A comparative analysis of published methods for calculating the optimal AT from a negative signal distribution highlighted the efficiency of utilizing baseline signals to enhance forensic genetic analysis, with the exception of extremely low-template samples and high-amplification cycles. Moreover, a user-friendly program for real-time analysis was developed, enabling prompt adjustments to ATs based on negative control profiles. In conclusion, this study provides insights into baseline signals, aiming to enhance genetic analysis accuracy across diverse laboratories. Practical recommendations are offered for optimizing ATs in forensic DNA analysis.

Improving DNA mixtures analysis using compound markers composed of InDels and SNPs screened from the whole genome with next-generation sequencing.

Next-generation sequencing (NGS) allows for better identification of insertion and deletion polymorphisms (InDels) and their combination with adjacent single nucleotide polymorphisms (SNPs) to form compound markers. These markers can improve the polymorphism of microhaplotypes (MHs) within the same length range, and thus, boost the efficiency of DNA mixture analysis. In this study, we screened InDels and SNPs across the whole genome and selected highly polymorphic markers composed of InDels and/or SNPs within 300 bp. Further, we successfully developed and evaluated an NGS-based panel comprising 55 loci, of which 24 were composed of both SNPs and InDels. Analysis of 124 unrelated Southern Han Chinese revealed an average effective number of alleles (Ae ) of 7.52 for this panel. The cumulative power of discrimination and cumulative probability of exclusion values of the 55 loci were 1-2.37 × 10-73 and 1-1.19 × 10-28 , respectively. Additionally, this panel exhibited high allele detection rates of over 97% in each of the 21 artificial mixtures involving from two to six contributors at different mixing ratios. We used EuroForMix to calculate the likelihood ratio (LR) and evaluate the evidence strength provided by this panel, and it could assess evidence strength with LR, distinguishing real and noncontributors. In conclusion, our panel holds great potential for detecting and analyzing DNA mixtures in forensic applications, with the capability to enhance routine mixture analysis.

Metal-Organic Gel Leading to Customized Magnetic-Coupling Engineering in Carbon Aerogels for Excellent Radar Stealth and Thermal Insulation Performances.

Metal-organic gel (MOG) derived composites are promising multi-functional materials due to their alterable composition, identifiable chemical homogeneity, tunable shape, and porous structure. Herein, stable metal-organic hydrogels are prepared by regulating the complexation effect, solution polarity and curing speed. Meanwhile, collagen peptide is used to facilitate the fabrication of a porous aerogel with excellent physical properties as well as the homogeneous dispersion of magnetic particles during calcination. Subsequently, two kinds of heterometallic magnetic coupling systems are obtained through the application of Kirkendall effect. FeCo/nitrogen-doped carbon (NC) aerogel demonstrates an ultra-strong microwave absorption of - 85 dB at an ultra-low loading of 5%. After reducing the time taken by atom shifting, a FeCo/Fe3O4/NC aerogel containing virus-shaped particles is obtained, which achieves an ultra-broad absorption of 7.44 GHz at an ultra-thin thickness of 1.59 mm due to the coupling effect offered by dual-soft-magnetic particles. Furthermore, both aerogels show excellent thermal insulation property, and their outstanding radar stealth performances in J-20 aircraft are confirmed by computer simulation technology. The formation mechanism of MOG is also discussed along with the thermal insulation and electromagnetic wave absorption mechanism of the aerogels, which will enable the development and application of novel and lightweight stealth coatings.

Study of the Protection and Energy Transmission Modes of One Phase Short Circuit to Ground in Inverters.

Research indicates that phase-to-ground short-circuits in a frequency converter can subject the rectifier diode and IGBT to excessive voltage and current, potentially causing damage if the component selection margin during hardware design is insufficient. In order to solve the above problems, this paper studies the design of the LCL filter and ground short circuit problem of the hundred-kilowatt inverter. Firstly, an analytical method for calculating the DC bus capacitance and reactor of the inverter is proposed. The interaction between the DC bus capacitance and the reactor parameters and performance is considered in the implementation process. The parameters of the DC bus capacitor and reactor are given. Secondly, the one-to-ground short circuit of the inverter is studied, and the energy flow mode and mathematical expression of the double boost circuit, considering the influence of the leakage inductance of the power transformer, are given. Based on the above analysis, a method for determining the rectifier diode and IGBT, considering the one-to-ground short circuit of the inverter, is proposed. Finally, a one-hundred-kilowatt inverter is developed, and the corresponding experiments are carried out. The feasibility of the proposed scheme is verified by simulation and experiment.

B-Site Super-Excess Design Sr2V0.4Fe0.9Mo0.7O6-δ-Ni0.4 as a Highly Active and Redox-Stable Solid Oxide Fuel Cell Anode.

In-situ exsolution type perovskites as solid oxide fuel cell (SOFCs) anode materials have received widespread attention because of their excellent catalytic activity. In this study, excessive NiO is introduced to the Sr2V0.4Fe0.9Mo0.7O6-δ (SVFMO) perovskite with the B-site excess design, and in-situ growth of FeNi3 alloy nanoparticles is induced in the reducing atmosphere to form the Sr2V0.4Fe0.9Mo0.7O6-δ-Ni0.4 (SVFMO-Ni0.4) composite anode. Here, with H2 or CH4 as SOFCs fuel gas, the formation of FeNi3 nanoparticles further enhances the catalytic ability. Compared with SVFMO, the maximum power density (Pmax) of Sr2V0.4Fe0.9Mo0.7O6-δ-Ni0.4 (SVFMO-Ni0.4) increases from 538 to 828 mW cm-2 at 850 °C with hydrogen as the fuel gas, and the total polarization resistance (RP) decreases from 0.23 to 0.17 Ω cm2. In addition, the long-term operational stability of the SVFMO-Ni0.4 anode shows no apparent performance degradation for more than 300 h. Compared with SVFMO, the Pmax of SVFMO-Ni0.4 increases from 138 to 464 mW cm-2 with methane as fuel gas, and the RP decreases from 1.21 to 0.29 Ω cm2.

Assessment of ForenSeq mtDNA Whole Genome Kit for forensic application.

Mitochondrial DNA (mtDNA) is an indispensable genetic marker in forensic genetics. The emergence and development of massively parallel sequencing (MPS) makes it possible to obtain complete mitochondrial genome sequences more quickly and accurately. The study evaluated the advantages and limitations of the ForenSeq mtDNA Whole Genome Kit in the practical application of forensic genetics by detecting human genomic DNA standards and thirty-three case samples. We used control DNA with different amount to determine sensitivity of the assay. Even when the input DNA is as low as 2.5 pg, most of the mitochondrial genome sequences could still be covered. For the detection of buccal swabs and aged case samples (bloodstains, bones, teeth), most samples could achieve complete coverage of mitochondrial genome. However, when ancient samples and hair samples without hair follicles were sequenced by the kit, it failed to obtain sequence information. In general, the ForenSeq mtDNA Whole Genome Kit has certain applicability to forensic low template and degradation samples, and these results provide the data basis for subsequent forensic applications of the assay. The overall detection process and subsequent analysis are easy to standardize, and it has certain application potential in forensic cases.

Different Life-Stage Exposure to Hexafluoropropylene Oxide Trimer Acid Induces Reproductive Toxicity in Adult Zebrafish (Danio rerio).

As a novel alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been widely used and has caused ubiquitous water pollution. However, its adverse effects on aquatic organisms are still not well known. In the present study, zebrafish at different life stages were exposed to 0, 5, 50, and 100 µg/L of HFPO-TA for 21 days to investigate reproductive toxicity in zebrafish. The results showed that HFPO-TA exposure significantly inhibited growth and induced reproductive toxicity in zebrafish, including a decrease of the condition factor, gonadosomatic index, and the average number of eggs. Histological section observation revealed that percentages of mature oocytes and spermatozoa were reduced, while those of primary oocytes and spermatocytes increased. In addition, exposure to HFPO-TA at three stages induced a significant decrease in the hatching rate, while the heart rate and normal growth rate of F1 offspring were only significantly inhibited for the exposure from fertilization to 21 days postfertilization (dpf). Compared with the exposure from 42 to 63 dpf, the reproductive toxicity induced by HFPO-TA was more significant for the exposure from fertilization to 21 dpf and from 21 to 42 dpf. Expression of the genes for cytochrome P450 A1A, vitellogenin 1, estrogen receptor alpha, and estrogen receptor 2b was significantly up-regulated in most cases after exposure to HFPO-TA, suggesting that HFPO-TA exhibited an estrogen effect similar to PFOA. Therefore, HFPO-TA might disturb the balance of sex steroid hormones and consequently induce reproductive toxicity in zebrafish. Taken together, the results demonstrate that exposure to HFPO-TA at different life stages could induce reproductive toxicity in zebrafish. However, the underlying mechanisms deserve further investigation. Environ Toxicol Chem 2023;42:2490-2500. © 2023 SETAC.

A chitin deacetylase PsCDA2 from Puccinia striiformis f. sp. tritici confers disease pathogenicity by suppressing chitin-triggered immunity in wheat.

Plants have the ability to recognize the essential chitin molecule present in the fungal cell wall, which stimulates the immune response. Phytopathogenic fungi have developed various strategies to inhibit the chitin-triggered immune response. Here, we identified a chitin deacetylase of Puccinia striiformis f. sp. tritici (Pst), known as PsCDA2, that was induced during the initial invasion of wheat and acted as an inhibitor of plant cell death. Knockdown of PsCDA2 in wheat enhanced its resistance against Pst, highlighting the significance of PsCDA2 in the host-pathogen interaction. Moreover, PsCDA2 can protect Pst urediniospores from being damaged by host chitinase in vitro. PsCDA2 also suppressed the basal chitin-induced plant immune response, including the accumulation of callose and the expression of defence genes. Overall, our results demonstrate that Pst secretes PsCDA2 as a chitin deacetylase involved in establishing infection and modifying the acetyl group to prevent the breakdown of chitin in the cell wall by host endogenous chitinases. Our research unveils a mechanism by which the fungus suppresses plant immunity, further contributing to the understanding of wheat stripe rust control. This information could have significant implications for the development of suitable strategies for protecting crops against the devastating effects of this disease.

Development of specific and rapid detection of human DNA by recombinase polymerase amplification assay for forensic analysis.

The determination of human-derived samples is very important in forensic investigations and case investigation in order to determine vital information on the suspect and the case. In this study, we established a recombinase polymerase amplification (RPA) assay for rapid identification of human-derived components. The sensitivity of the assay was 0.003125 ng, with excellent species specificity, and human-derived DNA could be detected in the presence of non-human-derived components at a ratio of 1:1000. Moreover, the RPA assay had a strong tolerance to inhibitors, in the presence of 800 ng/µL humic acid, 400 ng/µL tannic acid, and 8000 ng/µL collagen. In forensic investigation, common body fluids (blood, saliva, semen, vaginal secretions) are all applicable, and the presence of DNA can be detected from samples after simple alkaline lysis, which greatly shortens the detection time. Four simulation and case samples (aged bones, aged bloodstains, hair, touch DNA) were also successfully applied. The above research results show that the RPA assay constructed in this study can be fully applied to forensic medicine to provide high sensitivity and applicability detection methods.

Evaluation of microhaplotype panels for complex kinship analysis using massively parallel sequencing.

In recent years, microhaplotypes (MHs) have become a research hotspot within the field of forensic genetics. Traditional MHs contain only SNPs that are closely linked within short fragments. Herein, we broaden the concept of general MHs to include short InDels. Complex kinship identification plays an important role in disaster victim identification and criminal investigations. For distant relatives (e.g., 3rd-degree), many genetic markers are required to enhance power of kinship testing. We performed genome-wide screening for new MH markers composed of two or more variants (InDel or SNP) within 220 bp based on the Chinese Southern Han from the 1000 Genomes Project. An NGS-based 67plex MH panel (Panel B) was successfully developed, and 124 unrelated individual samples were sequenced to obtain population genetic data, including alleles and allele frequencies. Of the 67 genetic markers, 65 MHs were, as far as we know, newly discovered, and 32 MHs had effective number of allele (Ae) values greater than 5.0. The average Ae and heterozygosity of the panel were 5.34 and 0.7352, respectively. Next, 53 MHs from a previous study were collected as Panel A (average Ae of 7.43), and Panel C with 87 MHs (average Ae of 7.02) was formed by combining Panels A and B. We investigated the utility of these three panels in kinship analysis (parent-child, full siblings, 2nd-degree, 3rd-degree, 4th-degree, and 5th-degree relatives), with Panel C exhibiting better performance than the two other panels. Panel C was able to separate parent-child, full-sibling, and 2nd-degree relative duos from unrelated controls in real pedigree data, with a small false testing level (FTL) of 0.11% in simulated 2nd-degree duos. For more distant relationships, the FTL was much higher: 8.99% for 3rd-degree, 35.46% for 4th-degree, and 61.55% for 5th-degree. When a carefully chosen extra relative was known, this may enhance the testing power for distant kinship analysis. Two twins from the Q family (2-5 and 2-7) and W family (3-18 and 3-19) shared the same genotypes in all tested MHs, which led to the incorrect conclusion that an uncle-nephew duo was classified as a parent-child duo. In addition, Panel C showed great capacity for excluding close relatives (2nd-degree and 3rd-degree relatives) during paternity tests. Among 18,246 real and 10,000 simulated unrelated pairs, none were misinterpreted as a relative within 2nd-degree at a log10(LR) cutoff of 4. The panels presented herein could provide supplementary power for the analysis of complex kinship.

A prognostic and immunological analysis of 7B-containing Kelch structural domain (KLHDC7B) in pan-cancer: a potential target for immunotherapy and survival.

PURPOSE: KLHDC7B is a member of Kelch family, with a Kelch domain in the C-terminal half, which plays a role in various cellular events, such as cytoskeletal arrangement, protein degradation, gene expression. Although there is increasing evidence supporting KLHDC7B's vital role in tumorigenesis, a systematic analysis of KLHDC7B in cancers remains lacking. Therefore, we intended to investigate the prognostic value for KLHDC7B across 33 cancer types and explore its potential immunological function. METHODS: GEO (Gene Expression Omnibus database) and TCGA (The Cancer Genome Atla) database were used to explore the role of KLHDC7B in 33 cancers. TIMER2, GEPIA2 and Kaplan-Meier plotter were utilized to explore the KLHDC7B expression level and prognostic value in different cancers. The pan cancer genetic variation and DNA methylation of KLHDC7B were analyzed by cBioPortal and MEXPRESS. TIMER2 was employed to investigate the correlation between KLHDC7B expression and immune infiltration. The relationship of KLHDC7B expression with TMB (tumor mutational burden) and MSI (microsatellite instability) were evaluated using Spearman correlation analysis. Finally, by GO and KEGG enrichment analysis, the underlying mechanisms of KLHDC7B in tumor pathophysiology were further investigated. RESULTS: KLHDC7B expression level was related to pathological stages, MSI, TMB, immune checkpoint and immune cell infiltration in most cancers. Especially, we found that the KLHDC7B expression was negatively correlated with the immune infiltration of Myeloid derived suppressor cells into TGCT and GBM. Additionally, survival analysis showed that the expression of KLHDC7B was connected with overall survival (OS) in 3 cancers and disease-free survival (DFS) in 5 cancers. Furthermore, the enrichment analysis revealed that the KLHDC7B collecting genes and binding proteins are related to the function of proteins and immune response. CONCLUSION: KLHDC7B demonstrates strong clinical utility as markers of prognostic and immune response in pan-cancer.

An MPS-Based 50plex Microhaplotype Assay for Forensic DNA Analysis.

Microhaplotypes (MHs) are widely accepted as powerful markers in forensic studies. They have the advantage of both short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs), with no stutter and amplification bias, short fragments and amplicons, low mutation and recombination rates, and high polymorphisms. In this study, we constructed a panel of 50 MHs that are distributed on 21 chromosomes and analyzed them using the Multiseq multiple polymerase chain reaction (multi-PCR) targeted capture sequencing protocol based on the massively parallel sequencing (MPS) platform. The sizes of markers and amplicons ranged between 11-81 bp and 123-198 bp, respectively. The sensitivity was 0.25 ng, and the calling results were consistent with Sanger sequencing and the Integrative Genomics Viewer (IGV). It showed measurable polymorphism among sequenced 137 Southwest Chinese Han individuals. No significant deviations in the Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) were found at all MHs after Bonferroni correction. Furthermore, the specificity was 1:40 for simulated two-person mixtures, and the detection rates of highly degraded single samples and mixtures were 100% and 93-100%, respectively. Moreover, animal DNA testing was incomplete and low depth. Overall, our MPS-based 50-plex MH panel is a powerful forensic tool that provides a strong supplement and enhancement for some existing panels.

Suppression of matrix degradation and amelioration of disc degeneration by a 970-nm diode laser via inhibition of the p38 MAPK pathway in a rabbit model.

Intervertebral disc degeneration (IVDD) mainly manifests as an imbalance between the synthesis and degradation of cellular and extracellular matrix (ECM) components. The cytokine interleukin (IL)-1ß-induced inflammatory response of intervertebral discs causes ECM degradation. The aim of this study was to investigate the effects of a 970-nm diode laser therapy (DLT) on inflammatory cytokine IL-1ß and ECM degradation proteinases in nucleus pulposus (NP) tissues in a puncture-induced rabbit IVDD model. Thirty-six New Zealand white rabbits were randomly divided into six groups: the normal group, IVDD group, laser group, sham laser group, IVDD + anisomycin (p38MAPK signaling pathway agonist), and laser + anisomycin group. Effects of laser on IVDD progression were detected using radiographic and magnetic resonance imaging. Hematoxylin and eosin, Alcian blue, safranin O-fast green staining, western blotting, and immunohistochemistry staining were performed for the histological analysis and molecular mechanism underlying protection against puncture-induced matrix degradation in NP tissues by DLT. DLT reduced the degree of disc degeneration in the gross anatomy of the disc and increased the T2-weighted signal intensity of NP. Inflammatory cytokine IL-1ß levels in the disc were significantly reduced after DLT suppressed the matrix-degrading proteinases MMP13 and ADAMTS-5 and upregulated the protein expression of collagen II and aggrecan. Moreover, it inhibited the p38MAPK signaling pathway in NP tissues in a puncture-induced rabbit IVDD model. DLT reduced puncture-induced overexpression of inflammatory cytokines, mainly IL-1ß, thus inhibiting matrix degeneration of NP tissues and ameliorating IVDD. This may be related to inhibition of the p38 MAPK signaling pathway.

Modelling the octanol-air partition coefficient of aromatic pollutants based on the solvation free energy and the dimer effect.

In this study, generalized predictive models were developed to estimate KOA of four kinds of aromatic pollutants based on the calculated solvation free energy and taking the dimer effect into account. Uncorrected log KOA values, which were directly estimated from the calculated solvation free energy of individual molecules, underestimated experimental values, and the deviation increased with increasing log KOA. Dimers were found to greatly affect the apparent KOA values of these aromatic pollutants, which were driven by π-π interactions. London dispersion and exchange-repulsion terms were identified to be dominant components of the underlying π-π interactions. It is interesting to find that the π-π interactions of polybrominated diphenyl ethers correlate with not only the molecular polarizability but also the size of opposing aromatic surfaces, which leads to a different trend of π-π interactions from other aromatic pollutants. A universal quantitative structure-activity relationship model was developed to estimate the proportion of dimers based on five molecular structural descriptors relevant to the π-π interactions. After calibration with the dimer effect, estimations of log KOA were consistent with experimental values. Therefore, the dimer effect should be taken into consideration when investigating the partition behavior of aromatic pollutants, and the solvation free energy model could be an alternative method for the prediction of KOA.

Establishment of a co-analysis system for personal identification and body fluid identification: a preliminary report.

Analysis of genetic markers can provide clues for case investigation. Short tandem repeat (STR) detection and analysis are widely used for both personal identification and parentage testing. However, DNA analysis currently cannot provide sufficient information for body fluid identification. Tissue or cell sources of samples can be identified by detecting body fluid-specific mRNA markers, which have been studied thoroughly. Integrating STR profiling and mRNA expression patterns can provide more information than conventional methods for investigations and the reconstruction of crime scenes; this can be achieved by DNA/RNA co-extraction technology, which is economical, efficient, and suitable for low-template samples. Here, we propose a co-analysis system based on the PowerPlex 16 kit. This system can simultaneously amplify 25 markers, including 15 STRs, one non-STR amelogenin, and nine mRNA markers (three blood-specific, two saliva-specific, two semen-specific, and two housekeeping gene markers). The specificity and sensitivity of the co-analysis system were determined and aged and degraded samples were used to validate the stability of the co-analysis system. Finally, different DNA/RNA ratios and various carriers were evaluated. The results showed that the DNA/RNA co-analysis system correctly identified different types of body fluid stains. The STR profiles obtained using the co-analysis system were identical to those obtained using the PP16 kit, which demonstrates that the mRNA primers used did not affect STR profiling. Complete STR and mRNA profiles could be obtained from 1/8 portions of buccal swabs, 1/16 portions of swabs of blood and semen samples, 0.1 cm2 of blood samples, 0.25 cm2 of semen samples, and 1.0 cm2 saliva samples. Additionally, our findings indicate that complete STR and mRNA profiles can be obtained with this system from blood and semen samples when the DNA/RNA ratio is 1:1/32. This study suggests that the co-analysis system could be used for simultaneous personal identification and body fluid identification.

Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis.

Curcumin is a natural medicine with a wide range of anti-tumour activities. However, due to ß-diketone moiety, curcumin exhibits poor stability and pharmacokinetics which significantly limits its clinical applications. In this article, two types of dicarbonyl curcumin analogues with improved stability were designed through the calculation of molecular stability by density functional theory. Twenty compounds were synthesised, and their anti-tumour activity was screened. A plurality of analogues had significantly stronger activity than curcumin. In particular, compound B2 ((2E,2'E)-3,3'-(1,4-phenylene)bis(1-(2-chlorophenyl)prop-2-en-1-one)) exhibited excellent anti-lung cancer activity in vivo and in vitro. In addition, B2 could upregulate the level of reactive oxygen species in lung cancer cells, which in turn activated the endoplasmic reticulum stress and led to cell apoptosis and pyroptosis. Taken together, curcumin analogue B2 is expected to be a novel candidate for lung cancer treatment with improved chemical and biological characteristics.