Compressibility and porosity modulate the mechanical properties of giant gas vesicles.

Gas vesicles used as contrast agents for noninvasive ultrasound imaging must be formulated to be stable, and their mechanical properties must be assessed. We report here the formation of perfluoro-n-butane microbubbles coated with surface-active proteins that are produced by filamentous fungi (hydrophobin HFBI from Trichoderma reesei). Using pendant drop and pipette aspiration techniques, we show that these giant gas vesicles behave like glassy polymersomes, and we discover novel gas extraction regimes. We develop a model to analyze the micropipette aspiration of these compressible gas vesicles and compare them to incompressible liquid-filled vesicles. We introduce a sealing parameter to characterize the leakage of gas under aspiration through the pores of the protein coating. Utilizing this model, we can determine the elastic dilatation modulus, surface viscosity, and porosity of the membrane. These results demonstrate the engineering potential of protein-coated bubbles for echogenic and therapeutic applications and extend the use of the pipette aspiration technique to compressible and porous systems.

A review of the potential involvement of small RNAs in transgenerational abiotic stress memory in plants.

Crop production is increasingly threatened by the escalating weather events and rising temperatures associated with global climate change. Plants have evolved adaptive mechanisms, including stress memory, to cope with abiotic stresses such as heat, drought, and salinity. Stress memory involves priming, where plants remember prior stress exposures, providing enhanced responses to subsequent stress events. Stress memory can manifest as somatic, intergenerational, or transgenerational memory, persisting for different durations. The chromatin, a central regulator of gene expression, undergoes modifications like DNA acetylation, methylation, and histone variations in response to abiotic stress. Histone modifications, such as H3K4me3 and acetylation, play crucial roles in regulating gene expression. Abiotic stresses like drought and salinity are significant challenges to crop production, leading to yield reductions. Plant responses to stress involve strategies like escape, avoidance, and tolerance, each influencing growth stages differently. Soil salinity affects plant growth by disrupting water potential, causing ion toxicity, and inhibiting nutrient uptake. Understanding plant responses to these stresses requires insights into histone-mediated modifications, chromatin remodeling, and the role of small RNAs in stress memory. Histone-mediated modifications, including acetylation and methylation, contribute to epigenetic stress memory, influencing plant adaptation to environmental stressors. Chromatin remodeling play a crucial role in abiotic stress responses, affecting the expression of stress-related genes. Small RNAs; miRNAs and siRNAs, participate in stress memory pathways by guiding DNA methylation and histone modifications. The interplay of these epigenetic mechanisms helps plants adapt to recurring stress events and enhance their resilience. In conclusion, unraveling the epigenetic mechanisms in plant responses to abiotic stresses provides valuable insights for developing resilient agricultural techniques. Understanding how plants utilize stress memory, histone modifications, chromatin remodeling, and small RNAs is crucial for designing strategies to mitigate the impact of climate change on crop production and global food security.

Data-Driven Insights into the Contamination of Polycyclic Aromatic Hydrocarbons in Marine Bays.

The synthesis of polycyclic aromatic hydrocarbon (PAH) data allows us to quantify and gain insights into the spatiotemporal dynamics of PAH contamination in marine bays. Here, a data synthesis framework was developed to understand data-driven insights into the spatiotemporal levels, compositional profiles, and potential sources of PAHs in water and sediment of marine bays. PAHs were detected in 69 bays worldwide, with contamination hotspots located in Asian bays. PAH concentrations in pre-2000 were significantly lower than those in the 2000s and post-2010, while the dominant species in water and sediment were 2-3 ring and 4-6 ring PAHs, respectively. The composition patterns of PAHs included 2-3 ring, 3-5 ring, and 4-5 ring dominant categories, but no significant distance decay relationship was found in the composition similarity due to international energy trade. Temporal dynamic patterns of concentrations included Descending-, Ascending-, and Inverted V-type, whereas over longer time spans, the pattern is more similar to the Inverted V-type owing to the reductions in emission intensity. PAHs were derived from both petrogenic and pyrolytic sources, with combustion from both coal and petroleum being the dominant source. These data-driven discoveries provide quantitative insights into the spatiotemporal patterns in the concentration and composition of PAHs, contributing to the mitigation of PAH contamination.

Physical vapour deposition fabrication of MoO3-based photoanode for water splitting to generate hydrogen.

MoO3 thin film was fabricated on an indium tin oxide substrate using the physical vapor deposition technique. X-ray diffraction and scanning electron microscopy study to investigate surface morphology, grain size, and surface structure, which are critical for absorbing solar spectra in water splitting for hydrogen energy generation. Ultraviolet-visible spectroscopy was used to confirm the absorption of solar spectra and the percentage of transmittance. Fourier-transform infrared analysis provided the functional groups present in the deposited thin film. The Tauc plot was used to determine the thin-film band gap, which allowed for the analysis of charge carrier transitions from the conduction band to the valence band. Electrochemical impedance spectroscopy investigations confirmed the charge transfer processes to the counter electrode and electrolyte interfaces. The observed low curve for MoO3 indicated low resistance and allowed efficient charge transfer. Linear sweep voltammetry analysis was used to measure photocurrent and solar light to hydrogen emission when the thin film was exposed to solar spectra. The thin film's observed hydrogen emission rate was 3731.74 mol g-1 h-1, and the STH% of MoO3 was found to be 0.345% at 0.8 V. These findings highlight the promising potential of MoO3 as a material for hydrogen energy generation using solar light.

Hybrid Precision Floating-Point (HPFP) Selection to Optimize Hardware-Constrained Accelerator for CNN Training.

The rapid advancement in AI requires efficient accelerators for training on edge devices, which often face challenges related to the high hardware costs of floating-point arithmetic operations. To tackle these problems, efficient floating-point formats inspired by block floating-point (BFP), such as Microsoft Floating Point (MSFP) and FlexBlock (FB), are emerging. However, they have limited dynamic range and precision for the smaller magnitude values within a block due to the shared exponent. This limits the BFP's ability to train deep neural networks (DNNs) with diverse datasets. This paper introduces the hybrid precision (HPFP) selection algorithms, designed to systematically reduce precision and implement hybrid precision strategies, thereby balancing layer-wise arithmetic operations and data path precision to address the shortcomings of traditional floating-point formats. Reducing the data bit width with HPFP allows more read/write operations from memory per cycle, thereby decreasing off-chip data access and the size of on-chip memories. Unlike traditional reduced precision formats that use BFP for calculating partial sums and accumulating those partial sums in 32-bit Floating Point (FP32), HPFP leads to significant hardware savings by performing all multiply and accumulate operations in reduced floating-point format. For evaluation, two training accelerators for the YOLOv2-Tiny model were developed, employing distinct mixed precision strategies, and their performance was benchmarked against an accelerator utilizing a conventional brain floating point of 16 bits (Bfloat16). The HPFP selection, employing 10 bits for the data path of all layers and for the arithmetic of layers requiring low precision, along with 12 bits for layers requiring higher precision, results in a 49.4% reduction in energy consumption and a 37.5% decrease in memory access. This is achieved with only a marginal mean Average Precision (mAP) degradation of 0.8% when compared to an accelerator based on Bfloat16. This comparison demonstrates that the proposed accelerator based on HPFP can be an efficient approach to designing compact and low-power accelerators without sacrificing accuracy.

Internet of Vehicles (IoV)-Based Task Scheduling Approach Using Fuzzy Logic Technique in Fog Computing Enables Vehicular Ad Hoc Network (VANET).

The intelligent transportation system (ITS) relies heavily on the vehicular ad hoc network (VANET) and the internet of vehicles (IoVs), which combine cloud and fog to improve task processing capabilities. As a cloud extension, the fog processes' infrastructure is close to VANET, fostering an environment favorable to smart cars with IT equipment and effective task management oversight. Vehicle processing power, bandwidth, time, and high-speed mobility are all limited in VANET. It is critical to satisfy the vehicles' requirements for minimal latency and fast reaction times while offloading duties to the fog layer. We proposed a fuzzy logic-based task scheduling system in VANET to minimize latency and improve the enhanced response time when offloading tasks in the IoV. The proposed method effectively transfers workloads to the fog computing layer while considering the constrained resources of car nodes. After choosing a suitable processing unit, the algorithm sends the job and its associated resources to the fog layer. The dataset is related to crisp values for fog computing for system utilization, latency, and task deadline time for over 5000 values. The task execution, latency, deadline of task, storage, CPU, and bandwidth utilizations are used for fuzzy set values. We proved the effectiveness of our proposed task scheduling framework via simulation tests, outperforming current algorithms in terms of task ratio by 13%, decreasing average turnaround time by 9%, minimizing makespan time by 15%, and effectively overcoming average latency time within the network parameters. The proposed technique shows better results and responses than previous techniques by scheduling the tasks toward fog layers with less response time and minimizing the overall time from task submission to completion.

Synergistic enhancement of maize crop yield and nutrient assimilation via zinc oxide nanoparticles and phosphorus fertilization.

BACKGROUND: Low recovery of conventional fertilizers remains a significant bottleneck for maize production globally. In particular, with phosphate fertilization, zinc (Zn) is prone to precipitation in soil, reducing recovery of both phosphorus (P) and Zn by maize. RESULTS: The present study was designed to investigate the synergistic effect of zinc oxide (ZnO) nanoparticles (NPs) and P on maize crop growth, yield, and nutrient uptake under ZnO seed coating and foliar application in a randomized complete block design. However, plants were subjected to two ZnO NPs levels (0.5 and 12 kg ha-1) amended with two P levels (45 and 90 kg ha-1). ZnO NPs, especially in the form of foliar application, with a P dose of 90 Kg ha-1 significantly (P < 0.05) improved maize crop growth, yield, and nutrient uptake compared with control. In comparison with the control group, plants grown in these conditions absorbed higher levels of Zn and P. Zn uptake rose to 16.34 g ha-1, 137.88 g ha-1, and 166.89 g ha-1 in roots, grains, and stover respectively, and P uptake increased to 0.80 mg kg-1, 10.066 mg kg-1, and 12.17 mg kg-1 respectively. Additionally, seed emergence rate, plant height, and cob length increased by up to 2%, 1177 cm2, and 3.3 cm respectively compared with control. Furthermore, Zn use efficiency was increased up to 38.55% in ZnO NPs foliar application. CONCLUSIONS: Application of ZnO NPs at 0.5 kg ha-1 in the form of foliar application with 90 kg ha-1 P dose produced a more pronounced increment in the parameters studied than ZnO NPs seed coating did. © 2024 Society of Chemical Industry.

Barriers to medical consultation and strategies for enhancing the prevention and reporting of child abuse: A cross-sectional survey of caregivers of paediatric patients at a tertiary care center in Karachi, Pakistan.

Objective: To assess the knowledge of caregivers in a tertiary care setting about child abuse, their perception of potential barriers in the way of seeking medical advice for the victims, and to identify proposed solutions to ensure prevention and reporting of child abuse. METHODS: The cross-sectional study was conducted from June to December 2022 at the paediatric ward of the Aga Khan University Hospital, Karachi, and comprised caregivers who were attendants of inpatients. Data was collected using a predesigned anonymous questionnaire consisting of demographic information and 27 items that were scored on a 6-point Likert scale. Data was analysed using SPSS 20. RESULTS: Of the 144 caregivers, 96(66.6%) were females and 48(33.3%) were males. Overall, 86(59.7%) were aged <35 years, 132(91.7%) were married, and 120(83.3%) were the admitted child's parent. The majority of caregivers 110(76.4%) perceived themselves to possess a high level of knowledge about child abuse. Barriers identified included a lack of trust in police and medicolegal departments 136(94.4%), fear of repercussion from the suspect 120(83.3%) and lack of confidentiality of the victims' identity 116(80.6%). The proposed solutions included spreading awareness among teachers 136(94.4%) and caregivers 131(91.0%) about timely reporting and consultation, and developing proper mechanisms to follow-up on victims 133(92.4%). There were significant associations between some demographic characteristics of the respondents and their self-perceived knowledge and perceptions (p<0.05). Conclusion: There was found a need to enhance public trust, ensure confidentiality, and fostering awareness through targeted strategies for a safer and more facilitative environment for children.

Evaluating the association of childhood sexual abuse with the development of irritable bowel syndrome later in life: A systematic review.

Objective: To review available medical literature to elucidate the association between childhood sexual abuse and the development of irritable bowel syndrome later in life. METHODS: This systematic review was conducted from January to August 2022 and comprised a literature search on Medline (via PubMed), Scopus, Embase, Web of Science, and Google Scholar databases for relevant studies published between 2001 and 2021. The Newcastle-Ottawa scale was used to determine the quality of the studies. Data on the prevalence of irritable bowel syndrome were meta-analysed using a Mantel-Haenszel random-effects model in RevMan 5.4.1. RESULTS: Of the 7 observational studies analyzed in detail, 5 (71.4%) had a case-control design, and 2 (28.6%) were crosssectional studies. Overall, there were 3156 subjects. The prevalence of irritable bowel syndrome in the childhood sexual abuse group was 51.86% (334/644), while it was 36.74% (923/2512) in the non-childhood sexual abuse group. The pooled odds ratio, indicating the association between childhood sexual abuse and irritable bowel syndrome, was 1.87 (95% confidence interval: 1.56-2.26). The study quality was rated as good in 3 (42.8%) cases, fair in 3 (42.8%), and poor in 1 (14.3%). Conclusion: Childhood sexual abuse was found to be significantly associated with the development of irritable bowel syndrome later in life, further strengthening the argument that childhood sexual abuse can lead to long-term detriments extending into adulthood. However, there was no existing literature found that stratified other aspects of irritable bowel syndrome, including symptom severity and childhood sexual abuse being the exclusive cause of irritable bowel syndrome.

Investigation of drought induced biochemical and gene expression changes in carrot cultivars.

BACKGROUND: Carrot is the most important vegetable in Apiaceae family, and it is consumed globally due to its high nutritional quality. Drought stress is major environmental constraint for vegetables especially carrot. Limited data is available regarding the mechanisms conferring drought tolerance in carrot. Methods and Results Eight commercial carrot cultivars were used in this study and subjected to drought stress under semi-controlled greenhouse conditions. Biochemical, antioxidant enzymatic activity and changes in transcript level of drought related genes was estimated, the gene expression analysis was done by using qRT-PCR in comparison with reference gene expression Actin (Act1). Results revealed that cultivars Coral Orange, Tendersweet and Solar Yellow were tolerant to drought stress, which was supported by their higher transcript levels of catalase gene (CAT), superoxide dismutase genes (Cu/ZN-SOD, Cu/Zn-SDC) in these cultivars. The downregulation of PDH1 gene (Proline dehydrogenase 1) was also observed that was associated with upregulation of proline accumulation in carrot plants. Moreover, results also suggested that PRT genes (Proline transporter genes) played a key role in drought tolerance in carrot cultivars. Conclusion Among the cultivars studied, Coral Orange showed overall tolerance to drought stress conditions, whereas cultivars Cosmic Purple and Eregli Black were sensitive based on their biochemical and gene expression levels. According to our knowledge, this is the first comparative study on drought tolerance in several carrot cultivars. It will provide a background for carrot breeding to understand biochemical and molecular responses of carrot plant to drought stress and mechanisms behind it.

Micro(nano)plastics in commercial foods: A review of their characterization and potential hazards to human health.

Micro (nano)plastics (MNPs) are pollutants of worldwide concern for their ubiquitous environmental presence and associated impacts. The higher consumption of MNPs contaminated commercial food can cause potential adverse human health effects. This review highlights the evidence of MNPs in commercial food items and summarizes different sampling, extraction, and digestion techniques for the isolation of MNPs, such as oxidizing digestion, enzymatic digestion, alkaline digestion and acidic digestion. Various methods for the characterization and quantification of microplastics (MPs) are also compared, including µ-Raman spectroscopy, µ-Fourier transform infrared spectroscopy (FTIR), thermal analysis and Scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX). Finally, we share our concerns about the risks of MNPs to human health through the consumption of commercial seafood. The knowledge of the potential human health impacts at a subcellular or molecular level of consuming mariculture products contaminated with MNPs is still limited. Moreover, MNPs are somewhat limited, hard to measure, and still contentious. Due to the nutritional significance of fish consumption, the risk of exposure to MNPs and the associated health effects are of the utmost importance.

Bacteriophage-based techniques for elucidating the function of zebrafish gut microbiota.

Bacteriophages (or phages) are unique viruses that can specifically infect bacteria. Since their discovery by Twort and d'Herelle, phages with bacterial specificity have played important roles in microbial regulation. The intestinal microbiota and host health are intimately linked with nutrient, metabolism, development, and immunity aspects. However, the mechanism of interactions between the composition of the microbiota and their functions in maintaining host health still needs to be further explored. To address the lack of methodology and functions of intestinal microbiota in the host, we first proposed that, with the regulations of special intestinal microbiota and applications of germ-free (GF) zebrafish model, phages would be used to infect and reduce/eliminate the defined gut bacteria in the conventionally raised (CR) zebrafish and compared with the GF zebrafish colonized with defined bacterial strains. Thus, this review highlighted the background and roles of phages and their functional characteristics, and we also summarized the phage-specific infection of target microorganisms, methods to improve the phage specificity, and their regulation within the zebrafish model and gut microbial functional study. Moreover, the primary protocol of phage therapy to control the intestinal microbiota in zebrafish models from larvae to adults was recommended including phage screening from natural sources, identification of host ranges, and experimental design in the animal. A well understanding of the interaction and mechanism between phages and gut bacteria in the host can potentially provide powerful strategies or techniques for preventing bacteria-related human diseases by precisely regulating in vitro and in vivo, which will provide novel insights for phages' application and combined research in the future. KEY POINTS: • Zebrafish models for clarifying the microbial and phages' functions were discussed • Phages infect host bacteria with exquisite specificity and efficacy • Phages can reduce/eliminate the defined gut bacteria to clarify their function.

Validation of catalytic site residues of Ubiquitin Specific Protease 2 (USP2) by molecular dynamic simulation and novel kinetics assay for rational drug design.

Post-translational modifications of proteins such as protein ubiquitination are crucial for regulating conformation, stability and localization of the modified protein. Ubiquitin-specific protease 2 (USP2), a multifunctional cysteine protease is reported to be a key regulator of ubiquitylation events in numerous oncogenic proteins e.g., fatty acid synthetase, Mdm2, EGFR, cyclin A1, and cyclin-D1, etc. Thus targeting USP2 is a promising strategy for cancer therapy. USP2 is characterized by a catalytic triad comprising of cysteine, histidine and aspartic acid residues. Five residues including three from the catalytic triad and two from outside of the catalytic triad have been reported as a catalytic site of USP2 that catalyze hydrolysis and stabilizes the oxyanion formed in the intermediate step of catalysis. Here, we report two more novel residues (L269 and Y558) on USP2 involved in the catalysis of Ubiquitin using computational alanine scanning (CAS) followed by molecular dynamic simulation studies. The results obtained from CAS were further validated by a highly reliable, time- and cost-effective SDS-PAGE-based kinetics assay using UBA52 which is a natural substrate of USP2. Our results showed that mutating L269 and Y558 significantly compromised the catalytic efficiency of USP2 in hydrolyzing UBA52 which can further be extended to rational drug design of USP2 selective inhibitors and to explore the catalytic sites of other USPs. Two novel residues take part in catalytic activity of USP2 which were depicted by MD Simulations and were further validated by novel SDS-PAGE-based reliable time- and cost-effective kinetics assay.

Physical, chemical, microbial, and sensory evaluation and fatty acid profiling of value-added drinking yogurt (laban) under various storage conditions.

Yogurt is defined as a coagulated milk product obtained from the fermentation of lactose into lactic acid. Drinking yogurt (laban) was prepared from buffalo milk, cow milk, and a 50:50 blend (cow + buffalo milks) by adding 0.5% carboxymethyl cellulose to each of the 3 milk treatments. Samples were then refrigerated for 7, 14, and 21 d before determination of physical, microbial, and sensory parameters. Yogurt prepared from buffalo milk had higher fat and protein contents, and better taste, aroma, and overall consumer acceptability compared with laban prepared from cow milk or mixed milk. During storage, protein and total solids contents remained unchanged, whereas milk fat, color, appearance, taste, smell, texture, and overall acceptability of laban decreased in the different treatment groups. The acidity of laban increased with storage time. Bacteria, including coliforms, were not found in any treatment group during storage. In conclusion, overall acceptability of laban prepared from buffalo milk was higher than that made from cow milk or mixed milk, but increased storage time reduced the quality of laban prepared from cow, buffalo, or mixed milk.

Organochlorine pesticides (OCPs) in freshwater resources of Pakistan: A review on occurrence, spatial distribution and associated human health and ecological risk assessment.

The extensive use of organochlorine pesticides (OCPs) has resulted in the widespread contamination of different environmental matrices in Pakistan. Freshwater bodies are also prone to OCPs contamination as they receive agricultural and industrial runoff from different sources. In the present study, the data regarding OCPs' fate and distribution in freshwater resources of Pakistan was reviewed and associated risks to human and ecological health were assessed. Among all the OCPs, DDTs were more prevalent with the highest mean concentration of 2290 ng/L observed in River Ravi (Lahore and Sahiwal District). Human health risk assessment showed a higher risk to the children with high Hazard Quotient (HQ) values ranging between 4.1 × 10-9- 295 for Aldrin. The River Ravi (Lahore and Sahiwal District), the River Sutlej (Kasur & Bahawalpur District), and the River Kabul (Nowshehra District) were categorized as high-risk water bodies based on Hazard Index (HI) and Non-Cancer Risk (CRI) index values > 10. Ecological risk assessment revealed a higher risk posed to invertebrate species from DDT exposure. In summary, this review highlights the occurrence and distribution of OCPs and their associated human health and ecological risks in freshwater bodies of Pakistan and also contributes to signifying the need for proper management and regulation of banned pesticides and future research perspectives.

Comparative transcriptomics of drought stress response of taproot meristem region of contrasting purple carrot breeding lines supported by physio-biochemical parameters.

Carrot is one of the nutritious vegetable crops sensitive to drought stress resulting in loss of quality and yield. There are a lot of studies on detailed molecular mechanisms of drought stress response of main crops; however, very little information available on vegetables, including carrots. Hence, in this study, we investigated root transcriptome profiles from the meristematic region of two contrasting purple carrot (B7262A, drought tolerant; P1129, drought sensitive) lines under varying stress levels (85% and 70%) by using RNA-Seq technique. The morpho-physiological and biochemical response of B7262A line exhibited tolerance behavior to both DS (85% and 70%). RNA-Seq analysis revealed that 15,839 genes were expressed commonly in both carrot lines. The carrot line B7262A showed regulation of 514 genes in response to 85% DS, whereas P1129 showed differential regulation of 622 genes under 70% DS. The B7262A carrot line showed higher upregulation of transcripts that suggested its resilient behavior contrary to P1129 line. Furthermore, validation of transcript gene by qRT-PCR also confirmed the RNA-Seq analysis resulting in elevated expression levels of MYB48 transcription factor, MAPK mitogen-activated protein kinase ANP1, GER geraniol 8-hydroxylase, ABA ABA-induced in somatic embryo 3, FBOX putative F-box protein, FRO ferric reduction oxidase, and PDR probable disease resistance protein. Current study provided unprecedented insights of purple carrot lines that can be potentially exploited for the screening and development of resilient carrot.

Toxicological effects of polystyrene nanoplastics and perfluorooctanoic acid to Gambusia affinis.

Plastic pollution has attracted huge attention from public and scientific community in recent years. In the environment, nanoplastics (NPs, <100 nm) can interact with persistent organic pollutants (POPs) such as perfluorooctanoic acid (PFOA) and may exacerbate associated toxic impacts. The present study aims to explore the single and combined ecotoxicological effects of PFOA and polystyrene nanoplastics (PS-NPs, 80 nm) on the PI3K/AKT3 signaling pathway using a freshwater fish model Gambusia affinis. Fish were exposed individually to PS-NPs (200 µg/L) and PFOA (50, 500, 5000 µg/L) and their chemical mixtures for 96 h. Our results showed that the co-exposure significantly altered the mRNA relative expression of PI3K, AKT3, IKKß and IL-1ß, compared to corresponding single exposure and control groups, indicating that the PFOA-NP co-exposure can activate the PI3K/AKT3 signaling pathway. The bioinformatic analyses showed that AKT3 had more probes and exhibited a significantly sensitive correlation with DNA methylation, compared to other genes (PIK3CA, IKBKB, and IL1B). Further, the mRNA expressions of PIK3CA, AKT3, and IKBKB had a significant correlation with copy number variation (CNV) in human liver hepatocellular carcinoma (LIHC). And PIK3CA had the highest mutation rate among other genes of interest for LIHC. Moreover, AKT3 showed a relatively lower expression in TAM and CAF cells, compared to PIK3CA, IKBKB, and IL1B. Besides, hsa-mir-155-5p was closely correlated with AKT3, PIK3CA, IKBKB, and IL1B. In summary, these results provide evidence that NPs could enhance the carcinogenic effects of POPs on aquatic organisms and highlight possible targets of LIHC induced by PFOA-NP co-exposure.

Toxic effects of polystyrene nanoplastics and polybrominated diphenyl ethers to zebrafish (Danio rerio).

Nanoplastics (NPs) are good carriers of persistent organic pollutants (POPs) such as polybrominated diphenyl ethers (PBDEs), and can alter their bioavailability and toxic impacts to aquatic organisms. This study highlights the single and combined toxic effects of polystyrene nanoplastics (PS-NPs) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, one of the dominant congeners of PBDEs) on zebrafish embryos after an exposure duration of up to 120 hpf. Results showed that PS-NPs and BDE-47 co-exposure exacerbated the morphological deformities in terms of pericardial edema, yolk sac edema and curved tail in zebrafish larvae. Compared to BDE-47 single exposure, the combined exposure caused lower survival rates, shorter body lengths, and accelerated spontaneous movements. Further, PS-NPs were quickly aggregated on the surface of the embryonic chorions covered almost the entire membrane at 12 and 48 hpf, and concentration dependent accumulation was also found in the brain, mouth, trunk, gills, heart, liver and gastrointestinal tract at the larval stages. During the recovery period (7 days), PS-NPs were released from all the organs, with the highest elimination from the gastrointestinal tract. Histopathological examination revealed that co-exposure caused greater damage to retinal structures, muscle fibers and cartilage tissues. Responses of hypothalamic-pituitary-thyroid axis (CRH, TSHß, NIS, TTR, Dio2, TG, TRα and TRß) and reproduction (Esr2 and Vtg1) related genes were also investigated, and results showed that the co-exposure induced more significant upregulated expressions of TSHß, TG, Doi 2, and TRß, compared to BDE-47 single exposure. In conclusion, co-exposure to NPs and BDE-47 exacerbated developmental and thyroid toxicity in zebrafish, generally elucidating the toxicological effects mediated by complex chemical interactions between NPs with POPs in the freshwater environment.

Prospect of Anterior Gradient 2 homodimer inhibition via repurposing FDA-approved drugs using structure-based virtual screening.

Anterior Gradient 2 (AGR2) has recently been reported as a tumor biomarker in various cancers, i.e., breast, prostate and lung cancer. Predominantly, AGR2 exists as a homodimer via a dimerization domain (E60-K64); after it is self-dimerized, it helps FGF2 and VEGF to homo-dimerize and promotes the angiogenesis and the invasion of vascular endothelial cells and fibroblasts. Up till now, no small molecule has been discovered to inhibit the AGR2-AGR2 homodimer. Therefore, the present study was performed to prepare a validated 3D structure of AGR2 by homology modeling and discover a small molecule by screening the FDA-approved drugs library on AGR2 homodimer as a target protein. Thirteen different homology models of AGR2 were generated based on different templates which were narrowed down to 5 quality models sorted by their overall Z-scores. The top homology model based on PDB ID = 3PH9 was selected having the best Z-score and was further assessed by Verify-3D, ERRAT and RAMPAGE analysis. Structure-based virtual screening narrowed down the large library of FDA-approved drugs to ten potential AGR2-AGR2 homodimer inhibitors having FRED score lower than - 7.8 kcal/mol in which the top 5 drugs' binding stability was counter-validated by molecular dynamic simulation. To sum up, the present study prepared a validated 3D structure of AGR2 and, for the first time reported the discovery of 5 FDA-approved drugs to inhibit AGR2-AGR2 homodimer by using structure-based virtual screening. Moreover, the binding of the top 5 hits with AGR2 was also validated by molecular dynamic simulation. A validated 3D structure of Anterior Gradient 2 (AGR2) was prepared by homology modeling, which was used in virtual screening of FDA-approved drugs library for the discovery of prospective inhibitors of AGR2-AGR2 homodimer.

Current understanding of gliomagenesis: from model to mechanism.

Glioma, a kind of central nervous system (CNS) tumor, is hard to cure and accounts for 32% of all CNS tumors. Establishing a stable glioma model is critically important to investigate the underlying molecular mechanisms involved in tumorigenesis and tumor progression. Various core signaling pathways have been identified in gliomagenesis, such as RTK/RAS/PI3K, TP53, and RB1. Traditional methods of establishing glioma animal models have included chemical induction, xenotransplantation, and genetic modifications (RCAS/t-va system, Cre-loxP, and TALENs). Recently, CRISPR/Cas9 has emerged as an efficient gene editing tool with high germline transmission and has extended the scope of stable and efficient glioma models that can be generated. Therefore, this review will highlight the documented evidence about the molecular characteristics, critical genetic markers, and signaling pathways responsible for gliomagenesis and progression. Moreover, methods of establishing glioma models using gene editing techniques and therapeutic aspects will be discussed. Finally, the prospect of applying gene editing in glioma by using CRISPR/Cas9 strategy and future research directions to establish a stable glioma model are also included in this review. In-depth knowledge of glioma signaling pathways and use of CRISPR/Cas9 can greatly assist in the development of a stable, efficient, and spontaneous glioma model, which can ultimately improve the effectiveness of therapeutic responses and cure glioma patients.