Search

Junctions between the ER and plasma membrane (PM) are implicated in calcium homeostasis, non-vesicular lipid transfer, and other cellular functions. Two ER proteins that function both as tethers to the PM via a polybasic C-terminus motif and as phospholipid transporters are brain-enriched TMEM24 (C2CD2L) and its paralog C2CD2. We report that both proteins also form a complex with band 4.1 family members, which in turn bind PM proteins including cell adhesion molecules such as SynCAM 1. This complex enriches TMEM24 and C2CD2 containing ER/PM junctions at sites of cell contacts. Dynamic properties of TMEM24-dependent ER/PM junctions are impacted when band 4.1 is part of the junction, as TMEM24 at cell-adjacent ER/PM junctions is not shed from the PM by calcium rise, unlike TMEM24 at non-cell adjacent junctions. Lipid transport between the ER and the PM by TMEM24 and C2CD2 at sites where cells, including neurons, contact other cells may participate in adaptive responses to cell contact-dependent signaling., (© 2024 Johnson et al.)

In this review, we delineate the unique set of characteristics associated with cryosphere environments (namely, ice and permafrost) which present both challenges and opportunities for studying ancient environmental microbiomes (AEMs). In a field currently reliant on several assumptions, we discuss the theoretical and empirical feasibility of recovering microbial nucleic acids (NAs) from ice and permafrost with varying degrees of antiquity. We also summarize contamination control best practices and highlight considerations for the latest approaches, including shotgun metagenomics, and downstream bioinformatic authentication approaches. We review the adoption of existing software and provide an overview of more recently published programs, with reference to their suitability for AEM studies. Finally, we summarize outstanding challenges and likely future directions for AEM research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, and recent evidence suggests that pathogenesis may be in part mediated by inflammatory processes, the molecular and cellular architectures of which are largely unknown. To identify and characterize selectively vulnerable brain cell populations in PD, we performed single-nucleus transcriptomics and unbiased proteomics to profile the prefrontal cortex from postmortem human brains of six individuals with late-stage PD and six age-matched controls. Analysis of nearly 80,000 nuclei led to the identification of eight major brain cell types, including elevated brain-resident T cells in PD, each with distinct transcriptional changes in agreement with the known genetics of PD. By analyzing Lewy body pathology in the same postmortem brain tissues, we found that α-synuclein pathology was inversely correlated with chaperone expression in excitatory neurons. Examining cell-cell interactions, we found a selective abatement of neuron-astrocyte interactions and enhanced neuroinflammation. Proteomic analyses of the same brains identified synaptic proteins in the prefrontal cortex that were preferentially down-regulated in PD. By comparing this single-cell PD dataset with a published analysis of similar brain regions in Alzheimer's disease (AD), we found no common differentially expressed genes in neurons but identified many shared differentially expressed genes in glial cells, suggesting that the disease etiologies, especially in the context of neuronal vulnerability, in PD and AD are likely distinct.

An extensive mosquito survey was carried out in Hong Kong from September to October 2022, employing a variety of collection methods. Specimens were identified using a combination of morphology and mitochondrial cytochrome C oxidase subunit 1 (COI) barcode sequences. Twenty-nine species, including three new records, i.e., Culex bicornutus (Theobald), Culex cinctellus Edwards, and Lutzia chiangmaiensis Somboon & Harbach, were collected. Phylogenetic analysis of COI sequences of Culex annulus Theobald and Culex vishnui Theobald collected in Hong Kong and elsewhere revealed that the sequences of the two nominal species are genetically very similar and are included in the same clade. Consequently, the synonymy of Cx. annulus with Cx. vishnui is reinstated. Lutzia halifaxii (Theobald) is removed from the list of species in Hong Kong and is replaced with Lutzia vorax Edwards, the identification of which is confirmed in the present study. The record of Culex spiculothorax Bram recorded in Hong Kong is replaced with the senior synonym Culex sasai Kano, Nitahara & Awaya. The occurrence of Anopheles fluviatilis James and Aedes aegypti (Linnaeus) is discussed. Finally, an updated checklist of the mosquitoes of Hong Kong, which now includes 76 species representing 14 genera, is provided, with notation of those species that vector pathogens of human diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Given the increasing use of cannabis in the US, there is an urgent need to better understand the drug's effects on central signaling mechanisms. Extracellular vesicles (EVs) have been identified as intercellular signaling mediators that contain a variety of cargo, including proteins. Here, we examined whether the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), alters EV protein signaling dynamics in the brain. We first conducted in vitro studies, which found that THC activates signaling in choroid plexus epithelial cells, resulting in transcriptional upregulation of the cannabinoid 1 receptor and immediate early gene c-fos, in addition to the release of EVs containing RNA cargo. Next, male and female rats were examined for the effects of either acute or chronic exposure to aerosolized ('vaped') THC on circulating brain EVs. Cerebrospinal fluid was extracted from the brain, and EVs were isolated and processed with label-free quantitative proteomic analyses via high-resolution tandem mass spectrometry. Interestingly, circulating EV-localized proteins were differentially expressed based on acute or chronic THC exposure in a sex-specific manner. Taken together, these findings reveal that THC acts in the brain to modulate circulating EV signaling, thereby providing a novel understanding of how exogenous factors can regulate intercellular communication in the brain.

Polyadenylation controls mRNA biogenesis, nucleo-cytoplasmic export, translation and decay. These processes are interdependent and coordinately regulated by poly(A)-binding proteins (PABPs), yet how PABPs are themselves regulated is not fully understood. Here, we report the discovery that human nuclear PABPN1 is phosphorylated by mitotic kinases at four specific sites during mitosis, a time when nucleoplasm and cytoplasm mix. To understand the functional consequences of phosphorylation, we generated a panel of stable cell lines inducibly over-expressing PABPN1 with point mutations at these sites. Phospho-inhibitory mutations decreased cell proliferation, highlighting the importance of PABPN1 phosphorylation in cycling cells. Dynamic regulation of poly(A) tail length and RNA stability have emerged as important modes of gene regulation. We therefore employed long-read sequencing to determine how PABPN1 phospho-site mutants affected poly(A) tails lengths and TimeLapse-seq to monitor mRNA synthesis and decay. Widespread poly(A) tail lengthening was observed for phospho-inhibitory PABPN1 mutants. In contrast, expression of phospho-mimetic PABPN1 resulted in shorter poly(A) tails with increased non-A nucleotides, in addition to increased transcription and reduced stability of a distinct cohort of mRNAs. Taken together, PABPN1 phosphorylation remodels poly(A) tails and increases mRNA turnover, supporting the model that enhanced transcriptome dynamics reset gene expression programs across the cell cycle., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2., Methods: Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis., Results: A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2-59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. Streptococcus parasanguinis (log 10 LDA score = 2.38, p = 0.003; relative abundance of 2.97 × 10 -5 vs. 0.03%, p = 0.001), Bacteroides stercoris (log 10 LDA score = 4.29, p = 0.024; relative abundance of 0.14% vs. 2.40%, p = 0.014) and Haemophilus parainfluenzae (log 10 LDA score = 2.15, p = 0.022; relative abundance of 0.01% vs. 0, p = 0.010) were enriched in low responders. Bifidobacterium pseudocatenulatum (log 10 LDA score = 2.99, p = 0.048; relative abundance of 0.09% vs. 0.36%, p = 0.049) and Clostridium leptum (log 10 LDA score = 2.38, p = 0.014; relative abundance of 1.2 × 10 -5 % vs. 0, p = 0.044) were enriched in high responders. S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log 10 LDA score = 2.63), which contributes to inflammation and antibody production. H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log 10 LDA score = 2.14)., Conclusion: Among three-dose BNT162b2 recipients, S. parasanguinis , B. stercoris and H. parainfluenzae were associated with poorer immunogenicity at one year, while B. pseudocatenulatum and C. leptum was associated with a better response.

Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially because of subventricular zone contact. Despite this, cross-talk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. In addition, GBM brain tumor-initiating cells (BTICs) increase expression of cathepsin B (CTSB) upon interaction with NPCs. Lentiviral knockdown and recombinant protein experiments reveal that both cell-intrinsic and soluble CTSB promote malignancy-associated phenotypes in BTICs. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Last, we show LV-proximal CTSB up-regulation in patients, showing the relevance of this cross-talk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM.

A large number of studies on organophosphate esters (tri-OPEs) in marine organisms have not assessed the simultaneous occurrence of tri-OPEs and their metabolites (di-OPEs) in these species. This research investigated the concentration and geographical distribution of 15 tri-OPEs and 7 di-OPEs in 172 samples of Pampus argenteus that were collected annually from 2021 to 2023 at three distinct locations along the Vietnamese coast. As a result, tri-OPEs and di-OPEs were detected in numerous fish samples, indicating their widespread spatial and temporal occurrence in marine fish and pointing out the importance of monitoring their levels. The tri-OPEs and di-OPEs ranged within 2.1-38.9 ng g -1 dry weight (dw) and 3.2-263.4 ng g -1 dw, respectively. The mean concentrations of tri-OPEs ranged from 0.4 (TIPrP) to 5.4 ng g -1 dw (TBOEP), with TBOEP and TEHP having the highest mean values. In addition, the profiles of tri-OPEs in fish exhibited a descending order: Σalkyl OPEs > ΣCl-alkyl OPEs > Σaryl OPEs. The di-OPEs, namely BEHP and DMP, had the highest mean levels, measuring 33.4 ng g -1 dw and 23.8 ng g -1 dw, respectively. Furthermore, there have been significant findings of strong positive correlations between di-OPEs and tri-OPE pairs (p < 0.05). It is worth noting that there is a noticeable difference in the composition of tri-OPEs between the North and other regions. Despite these findings, the presence of OPE-contaminated fish did not pose any health risks to Vietnam's coastal population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Influenza A/H9 viruses circulate worldwide in wild and domestic avian species, continuing to evolve and posing a zoonotic risk. A substantial increase in human infections with A/H9N2 subtype avian influenza viruses (AIVs) and the emergence of novel reassortants carrying A/H9N2-origin internal genes has occurred in recent years. Different names have been used to describe the circulating and emerging A/H9 lineages. To address this issue, an international group of experts from animal and public health laboratories, endorsed by the WOAH/FAO Network of Expertise on Animal Influenza, has created a practical lineage classification and nomenclature system based on the analysis of 10,638 hemagglutinin sequences from A/H9 AIVs sampled worldwide. This system incorporates phylogenetic relationships and epidemiologic characteristics designed to trace emerging and circulating lineages and clades. To aid in lineage and clade assignment, an online tool has been created. This proposed classification enables rapid comprehension of the global spread and evolution of A/H9 AIVs.

The unprecedentedly large size of the global SARS-CoV-2 phylogeny makes any computation on the tree difficult. Lineage identification (e.g. the PANGO nomenclature for SARS-CoV-2) and assignment are key to track the virus evolution. It requires annotating clade roots of lineages to unlabeled ancestral nodes in a phylogenetic tree. Then the lineage labels of descendant samples under these clade roots can be inferred to be the corresponding lineages. This is the ancestral lineage annotation problem, and matUtils (a package in pUShER) and PastML are commonly used methods. However, their computational tractability is a challenge and their accuracy needs further exploration in huge SARS-CoV-2 phylogenies. We have developed an efficient and accurate method, called "F1ALA", that utilizes the F1-score to evaluate the confidence with which a specific ancestral node can be annotated as the clade root of a lineage, given the lineage labels of a set of taxa in a rooted tree. Compared to these methods, F1ALA achieved roughly an order of magnitude faster yet with ∼12% of their memory usage when annotating 2277 PANGO lineages in a phylogeny of 5.26 million taxa. F1ALA allows real-time lineage tracking to be performed on a laptop computer. F1ALA outperformed matUtils (pUShER) with statistical significance, and had comparable accuracy to PastML in tests on empirical and simulated data. F1ALA enables a tree refinement by pruning taxa with inconsistent labels to their closest annotation nodes and re-inserting them back to the pruned tree to improve a SARS-CoV-2 phylogeny with both higher log-likelihood and lower parsimony score. Given the ultrafast speed and high accuracy, we anticipated that F1ALA will also be useful for large phylogenies of other viruses. Codes and benchmark datasets are publicly available at https://github.com/id-bioinfo/F1ALA., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Ticks, as critical vectors of a variety of pathogens, pose a significant public health challenge globally. In Southeast Asia (SEA), ticks are responsible for transmitting a diverse array of pathogens affecting humans and animals. The geographical and ecological diversity of SEA provides a unique environment that supports a wide range of tick species, which complicates the management and study of tick-borne diseases (TBDs)., Methodology/principal Findings: This article synthesizes findings from the first international symposium on ticks and TBDs in Southeast Asia, held in Phnom Penh on June 22 and 23, 2023. It highlights regional efforts to understand tick ecology and pathogen transmission. This paper proposes to present a summary of the various presentations given during the symposium following 3 main parts. The first one is devoted to the state of knowledge regarding ticks and TBDs in SEA countries, with presentations from 6 different countries, namely Cambodia, Indonesia, Laos, Malaysia, Thailand, and Vietnam. The second part focuses on the development of new research approaches on tick-borne pathogens (TBPs) and TBDs. The last part is a summary of the round table discussion held on the final day, with the aim of defining the most important challenges and recommendations for researches on TBP and TBD in the SEA region., Conclusions/significance: Key topics discussed include advancements in diagnostic tools, such as MALDI-TOF MS and proteomics, and the development of sustainable strategies for tick management and disease prevention. The symposium facilitated the exchange of knowledge and collaborative networks among experts from various disciplines, promoting a unified approach to tackling TBDs in the region. The symposium underscored the need for enhanced surveillance, diagnostics, and inter-regional cooperation to manage the threat of TBDs effectively. Recommendations include the establishment of a regional database for tick identification and the expansion of vector competence studies. These initiatives are crucial for developing targeted interventions and understanding the broader implications of climate change and urbanization on the prevalence of TBDs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing., Results: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG., Conclusions: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract., (© 2024. The Author(s).)

Liquid Chromatography Mass Spectrometry (LC-MS) is a powerful method for profiling complex biological samples. However, batch effects typically arise from differences in sample processing protocols, experimental conditions, and data acquisition techniques, significantly impacting the interpretability of results. Correcting batch effects is crucial for the reproducibility of omics research, but current methods are not optimal for the removal of batch effects without compressing the genuine biological variation under study. We propose a suite of Batch Effect Removal Neural Networks (BERNN) to remove batch effects in large LC-MS experiments, with the goal of maximizing sample classification performance between conditions. More importantly, these models must efficiently generalize in batches not seen during training. A comparison of batch effect correction methods across five diverse datasets demonstrated that BERNN models consistently showed the strongest sample classification performance. However, the model producing the greatest classification improvements did not always perform best in terms of batch effect removal. Finally, we show that the overcorrection of batch effects resulted in the loss of some essential biological variability. These findings highlight the importance of balancing batch effect removal while preserving valuable biological diversity in large-scale LC-MS experiments., (© 2024. The Author(s).)

To identify proteins by the bottom-up mass spectrometry workflow, enzymatic digestion is essential to break down proteins into smaller peptides amenable to both chromatographic separation and mass spectrometric analysis. Trypsin is the most extensively used protease due to its high cleavage specificity and generation of peptides with desirable positively charged N- and C-terminal amino acid residues that are amenable to reverse phase HPLC separation and MS/MS analyses. However, trypsin can yield variable digestion profiles and its protein cleavage activity is interdependent on trypsin source and quality, digestion time and temperature, pH, denaturant, trypsin and substrate concentrations, composition/complexity of the sample matrix, and other factors. There is therefore a need for a more standardized, general-purpose trypsin digestion protocol. Based on a review of the literature we delineate optimal conditions for carrying out trypsin digestions of complex proteomes from bulk samples to limiting amounts of protein extracts. Furthermore, we highlight recent developments and technological advances used in digestion protocols to quantify complex proteomes from single cells. SIGNIFICANCE: Currently, bottom-up MS-based proteomics is the method of choice for global proteome analysis. Since trypsin is the most utilized protease in bottom-up MS proteomics, delineating optimal conditions for carrying out trypsin digestions of complex proteomes in samples ranging from tissues to single cells should positively impact a broad range of biomedical research., Competing Interests: Declaration of competing interest The authors declare there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Uncomplicated urinary tract infections (uUTIs) in women are common infections encountered in primary care. Evidence suggests that rapid point-of-care tests (POCTs) to detect bacteria and erythrocytes in urine at presentation may help primary care clinicians to identify women with uUTIs in whom antibiotics can be withheld without influencing clinical outcomes. This pilot study aims to provide preliminary evidence on whether a POCT informed management of uUTI in women can safely reduce antibiotic use., Methods and Analysis: This is an open-label two-arm parallel cluster-randomised controlled pilot trial. 20 general practices affiliated with the Bavarian Practice-Based Research Network (BayFoNet) in Germany were randomly assigned to deliver patient management based on POCTs or to provide usual care. POCTs consist of phase-contrast microscopy to detect bacteria and urinary dipsticks to detect erythrocytes in urine samples. In both arms, urine samples will be obtained at presentation for POCTs (intervention arm only) and microbiological analysis. Women will be followed-up for 28 days from enrolment using self-reported symptom diaries, telephone follow-up and a review of the electronic medical record. Primary outcomes are feasibility of patient enrolment and retention rates per site, which will be summarised by means and SDs, with corresponding confidence and prediction intervals. Secondary outcomes include antibiotic use for UTI at day 28, time to symptom resolution, symptom burden, number of recurrent and upper UTIs and re-consultations and diagnostic accuracy of POCTs versus urine culture as the reference standard. These outcomes will be explored at cluster-levels and individual-levels using descriptive statistics, two-sample hypothesis tests and mixed effects models or generalised estimation equations., Ethics and Dissemination: The University of Würzburg institutional review board approved MicUTI on 16 December 2022 (protocol n. 109/22-sc). Study findings will be disseminated through peer-reviewed publications, conferences, reports addressed to clinicians and the local citizen's forums., Trial Registration Number: ClinicalTrials.gov NCT05667207., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac., Methods: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors., Results: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9-56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. Eubacterium rectale (log 10 LDA score = 4.15, p = 0.001; relative abundance of 1.4% vs. 0, p = 0.002), Collinsella aerofaciens (log 10 LDA score = 3.31, p = 0.037; 0.39% vs. 0.18%, p = 0.038), and Streptococcus salivarius (log 10 LDA score = 2.79, p = 0.021; 0.05% vs. 0.02%, p = 0.022) were enriched in low responders. The aOR of high immune response with E. rectale, C. aerofaciens , and S. salivarius was 0.03 (95% CI: 9.56 × 10 -4 -0.32), 0.03 (95% CI: 4.47 × 10 -4 -0.59), and 10.19 (95% CI: 0.81-323.88), respectively. S. salivarius had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log 10 LDA score = 2.23). C. aerofaciens similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions., Conclusion: E. rectale, C. aerofaciens , and S. salivarius correlated with poorer long-term immunogenicity following three doses of CoronaVac.

Parabens (p-hydroxybenzoic acid esters) commonly used preservatives (in cosmetics, pharmaceuticals, and foods) can pose potential effects on environmental health. In this study, seven parabens were quantified in marine fish samples using an ultra-high performance liquid chromatography triple quadrupole mass spectrometer (UHPLC-MS/MS) system. Parabens in the fish samples were extracted and purified by a rapid, simple, and effective procedure comprising sample homogenization with solvent, solid-phase extraction clean-up, and solvent evaporation. Results demonstrated that the recoveries of seven compounds (with relative standard deviation < 15%) were 88-103% in matrix-spike samples and 86-105% in surrogate standards. The method detection limits and method quantification limits of seven parabens were 0.015-0.030 and 0.045-0.090 ng/g-ww (wet weight), respectively. The optimized method was applied to measure the concentration of parabens in the 37 marine fish samples collected from Vietnam coastal waters. The concentration ranges of seven parabens found in round scad and greater lizardfish samples were 6.82-25.3 ng/g ww and 6.21-17.2 ng/g-ww, respectively. Among parabens, methylparaben accounted for the highest contribution in both fish species (43.2 and 44.9%, respectively). Based on the measured concentrations of parabens in marine fish samples, the estimated daily intake was calculated for children and adults with the corresponding values of 0.0477 µg/kg/day and 0.0119 µg/kg/day, respectively. However, the presence of parabens in Vietnamese marine fish may not pose a significant risk to human health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Organelle transporters define metabolic compartmentalization, and how this metabolite transport process can be modulated is poorly explored. Here, we discovered that human SLC25A39, a mitochondrial transporter critical for mitochondrial glutathione uptake, is a short-lived protein under dual regulation at the protein level. Co-immunoprecipitation mass spectrometry and CRISPR knockout (KO) in mammalian cells identified that mitochondrial m-AAA protease AFG3L2 is responsible for degrading SLC25A39 through the matrix loop 1. SLC25A39 senses mitochondrial iron-sulfur cluster using four matrix cysteine residues and inhibits its degradation. SLC25A39 protein regulation is robust in developing and mature neurons. This dual transporter regulation, by protein quality control and metabolic sensing, allows modulating mitochondrial glutathione level in response to iron homeostasis, opening avenues for exploring regulation of metabolic compartmentalization. Neuronal SLC25A39 regulation connects mitochondrial protein quality control, glutathione, and iron homeostasis, which were previously unrelated biochemical features in neurodegeneration., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Opioid use disorder (OUD) is a public health crisis currently being exacerbated by increased rates of use and overdose of synthetic opioids, primarily fentanyl. Therefore, the identification of novel biomarkers and treatment strategies to reduce problematic fentanyl use and relapse to fentanyl taking is critical. In recent years, there has been a growing body of work demonstrating that the gut microbiome can serve as a potent modulator of the behavioral and transcriptional responses to both stimulants and opioids. Here, we advance this work to define how manipulations of the microbiome drive fentanyl intake and fentanyl-seeking in a translationally relevant drug self-administration model. Depletion of the microbiome of male rats with broad spectrum antibiotics leads to increased drug administration on increased fixed ratio, progressive ratio, and drug seeking after abstinence. Utilizing 16S  sequencing of microbiome contents from these animals, specific populations of bacteria from the gut microbiome correlate closely with levels of drug taking. Additionally, global proteomic analysis of the nucleus accumbens following microbiome manipulation and fentanyl administration to define how microbiome status alters the functional proteomic landscape in this key limbic substructure. These data demonstrate that an altered microbiome leads to marked changes in the synaptic proteome in response to repeated fentanyl treatment. Finally, behavioral effects of microbiome depletion are reversible by upplementation of the microbiome derived short-chain fatty acid metabolites. Taken together, these findings establish clear relevance for gut-brain signaling in models of OUD and lay foundations for further translational work in this space., (Copyright © 2024 Hofford et al.)

Massive sequencing of SARS-CoV-2 genomes has urged novel methods that employ existing phylogenies to add new samples efficiently instead of de novo inference. 'TIPars' was developed for such challenge integrating parsimony analysis with pre-computed ancestral sequences. It took about 21 seconds to insert 100 SARS-CoV-2 genomes into a 100k-taxa reference tree using 1.4 gigabytes. Benchmarking on four datasets, TIPars achieved the highest accuracy for phylogenies of moderately similar sequences. For highly similar and divergent scenarios, fully parsimony-based and likelihood-based phylogenetic placement methods performed the best respectively while TIPars was the second best. TIPars accomplished efficient and accurate expansion of phylogenies of both similar and divergent sequences, which would have broad biological applications beyond SARS-CoV-2. TIPars is accessible from https://tipars.hku.hk/ and source codes are available at https://github.com/id-bioinfo/TIPars., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A multiple-input-multiple-output (MIMO) antenna system with low-profile and small element spacing characteristics is presented in this paper. This antenna contains multiple elements arranged in both E-plane and H-plane configurations. The original strong coupling between the MIMO elements can be suppressed by exciting orthogonal operating modes. To achieve this, a half-wavelength microstrip line and a quarter-wavelength grounded stub are utilized to decouple the H- and E-plane MIMO arrays. A 2 × 2 antenna prototype is fabricated and measured to demonstrate the decoupling concept's feasibility. The measured impedance bandwidth is from 4.78 to 4.81 GHz. Across this band, the isolation is better than 15 dB with extremely small edge-to-edge distances of 0.032λ and 0.026λ in the E- and H-plane, respectively. Featuring the simple decoupling structure, small element spacing, and the capability of extending to a large-scale 2 × N array, the proposed antenna can be used for 5G Internet of Things (IoT) applications operating at the N79 frequency band., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tran-Huy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Coronaviruses (CoVs) pose a major risk to global public health due to their ability to infect diverse animal species and potential for emergence in humans. The CoV spike protein mediates viral entry into the cell and plays a crucial role in determining the binding affinity to host cell receptors. With particular emphasis on α- and β-coronaviruses that infect humans and domestic animals, current research on CoV receptor use suggests that the exploitation of the angiotensin-converting enzyme 2 (ACE2) receptor poses a significant threat for viral emergence with pandemic potential. This review summarizes the approaches used to study binding interactions between CoV spike proteins and the human ACE2 (hACE2) receptor. Solid-phase enzyme immunoassays and cell binding assays allow qualitative assessment of binding but lack quantitative evaluation of affinity. Surface plasmon resonance, Bio-layer interferometry, and Microscale Thermophoresis on the other hand, provide accurate affinity measurement through equilibrium dissociation constants (K D ). In silico modeling predicts affinity through binding structure modeling, protein-protein docking simulations, and binding energy calculations but reveals inconsistent results due to the lack of a standardized approach. Machine learning and deep learning models utilize simulated and experimental protein-protein interaction data to elucidate the critical residues associated with CoV binding affinity to hACE2. Further optimization and standardization of existing approaches for studying binding affinity could aid pandemic preparedness. Specifically, prioritizing surveillance of CoVs that can bind to human receptors stands to mitigate the risk of zoonotic spillover., Competing Interests: We declare that all authors have read and approved the final version of the manuscript. We declare that the manuscript has not been published before and is not under consideration for publication elsewhere. We declare no conflicts of interest., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

The release of endocrine-disrupting chemicals (EDCs) into the aquatic environment, specifically the oceans, is increasing, leading to adverse effects on the marine ecosystem. Using optimized QuEChERS extraction methods, the study created the first contamination profiles of 44 EDCs, including organic ultraviolet compounds, pharmaceutically active compounds, hormones, and phthalate esters, in 114 fish muscle samples from five species collected along the Vietnamese coast. The study found that largehead hairtail exhibited the highest total EDCs at 208.3 ng g -1 lipid weight (lw), while Indian catfish displayed the lowest concentration at 105.5 ng g -1 lw. Besides, the study observed notable variations in the total EDCs across distinct fish species. This study hypothesized that the marine economic characteristics of each research location have a significant role in shaping the pollution profile of EDCs found in fish specimens taken from the corresponding area. As a result, a notable disparity in the composition of organic ultraviolet compounds has been observed among the three regions of North, Central, and South Vietnam (Mann-Whitney U test, p < 0.05). Despite these findings, EDC-contaminated fish did not pose any health risks to Vietnam's coastal population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Spillovers of viruses from animals to humans occur more frequently under warmer conditions, particularly arboviruses. The invasive tick species Haemaphysalis longicornis, the Asian longhorned tick, poses a significant public health threat due to its global expansion and its potential to carry a wide range of pathogens. We analyzed meta-transcriptomic data from 3595 adult H. longicornis ticks collected between 2016 and 2019 in 22 provinces across China encompassing diverse ecological conditions. Generalized additive modeling revealed that climate factors exerted a stronger influence on the virome of H. longicornis than other ecological factors, such as ecotypes, distance to coastline, animal host, tick gender, and antiviral immunity. To understand how climate changes drive the tick virome, we performed a mechanistic investigation using causality inference with emphasis on the significance of this process for public health. Our findings demonstrated that higher temperatures and lower relative humidity/precipitation contribute to variations in animal host diversity, leading to increased diversity of the tick virome, particularly the evenness of vertebrate-associated viruses. These findings may explain the evolution of tick-borne viruses into generalists across multiple hosts, thereby increasing the probability of spillover events involving tick-borne pathogens. Deep learning projections have indicated that the diversity of the H. longicornis virome is expected to increase in 81.9% of regions under the SSP8.5 scenario from 2019 to 2030. Extension of surveillance should be implemented to avert the spread of tick-borne diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

The FMS-like tyrosine kinase 3 (FLT3) gene encodes a class III receptor tyrosine kinase that is expressed in hematopoietic stem cells. The mutations of FLT3 gene found in 30% of acute myeloid leukemia (AML), leads to an abnormal constitutive activation of FLT3 kinase of the receptor and results in immature myeloblast cell proliferation. Although small molecule drugs targeting the FLT3 kinase have been approved, new FLT3 inhibitors are needed owing to the side effects and drug resistances arising from kinase domain mutations, such as D835Y and F691L. In this study, we have developed benzimidazole-indazole based novel inhibitors targeting mutant FLT3 kinases through the optimization of diverse chemical moieties substituted around the core skeleton. The most optimized compound 22f exhibited potent inhibitory activities against FLT3 and FLT3/D835Y, with IC 50 values of 0.941 and 0.199 nM, respectively. Furthermore, 22f exhibited strong antiproliferative activity against an AML cell line, MV4-11 cells with a GI 50 of 0.26 nM. More importantly, 22f showed single-digit nanomolar GI 50 values in the mutant FLT kinase expressed Ba/F3 cell lines including FLT-D835Y (GI 50  = 0.29 nM) and FLT3-F691L (GI 50  = 2.87 nM). Molecular docking studies indicated that the compound exhibits a well-fitted binding mode as a type 1 inhibitor in the homology model of active conformation of FLT3 kinase., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Testing hospital wastewater (HWW) is potentially an effective, long-term approach for monitoring trends in antimicrobial resistance (AMR) patterns in health care institutions. Over a year, we collected wastewater samples from the clinical and non-clinical sites of a tertiary hospital and from a downstream wastewater treatment plant (WWTP). We focused on the extent of carbapenem resistance among Enterobacteriaceae isolates given their clinical importance. Escherichia coli and Klebsiella spp. were the most frequently isolated Enterobacteriaceae species at all sampling sites. Additionally, a small number of isolates belonging to ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), except K. pneumoniae, were detected. Of the 232 Klebsiella spp. isolates, 100 (43.1 %) were multi-drug resistant (MDR), with 46 being carbapenem-resistant. Most of these carbapenem-resistant isolates were K. quasipneumoniae (CRKQ) (n = 44). All CRKQ isolates were isolated from the wastewater of a clinical site that includes intensive care units, which also yielded significantly more multi-drug resistant isolates compared to all other sampling sites. Among the CRKQ isolates, bla GES-5 genes (n = 42) were the primary genetic determinant of carbapenem resistance. Notably, three different CRKQ isolates, collected within the same month in HWW and the influent and effluent flow of the WWTP, shared >99 % sequence similarity between their bla GES-5 genes and between their flanking regions and upstream integron-integrase region. The influent isolate was phylogenetically close to K. quasipnuemoniae isolates from wastewater collected in Japan. Its bla GES-5 gene and surrounding sequences were > 99 % identical to bla GES-24 genes found in the Japanese isolates. Our results suggest that testing samples from sites located closer to hospitals could support antibiotic stewardship programs compared to samples collected further downstream. Moreover, testing samples collected regularly from WWTPs may reflect the local and global spread of pathogens and their resistances., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Parabens have emerged as the primary preservative of choice in numerous consumer goods, prompting growing apprehension regarding their potential for human exposure. The study employed the optimized QuEChERs sample extraction method and the UHPLC-Q-Orbitrap HRMS system to generate the initial contamination profiles of seven parabens and their four metabolites in a total of 114 fish samples found along the coastline of Vietnam. The findings of the study indicated that methylparaben was the predominant substance detected, exhibiting the highest concentration in the largehead hairtail (Trichiurus lepturus) species at 32.8 ng g -1 dry weight (dw). Additionally, the metabolites with the highest detectable concentrations in the largehead hairtail were found to be 4-HB and 3,4-DHB, with levels of 8822.0 ng g -1 dw and 3490.8 ng g -1 dw, respectively. Besides, the study reveals notable variations in paraben concentrations across three distinct regions in Vietnam, namely the Central, North, and South (Mann-Whitney U test, p < 0.05). The trophic magnification factors (TMF) for methylparaben, ethylparaben, ethyl protocatechuate, and 4-hydroxybenzoic acid exhibited values exceeding 1, indicating substantial biomagnification of these substances within the marine food web of Vietnam. Additionally, noteworthy positive associations have been observed between methylparaben and ethylparaben, as well as their respective metabolites. Based on the findings of the study, it can be concluded that there is no direct impact of seafood consumption on human health in Vietnam., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Between January 2015 and October 2022, 38 patients with culture-confirmed melioidosis were identified in the Kowloon West (KW) Region, Hong Kong. Notably, 30 of them were clustered in the Sham Shui Po (SSP) district, which covers an estimated area of 2.5 km 2 . Between August and October 2022, 18 patients were identified in this district after heavy rainfall and typhoons. The sudden upsurge in cases prompted an environmental investigation, which involved collecting 20 air samples and 72 soil samples from residential areas near the patients. A viable isolate of Burkholderia pseudomallei was obtained from an air sample collected at a building site five days after a typhoon. B. pseudomallei DNA was also detected in 21 soil samples collected from the building site and adjacent gardening areas using full-length 16S rRNA gene sequencing, suggesting that B. psuedomallei is widely distributed in the soil environment surrounding the district. Core genome-multilocus sequence typing showed that the air sample isolate was phylogenetically clustered with the outbreak isolates in KW Region. Multispectral satellite imagery revealed a continuous reduction in vegetation region in SSP district by 162,255 m 2 from 2016 to 2022, supporting the hypothesis of inhalation of aerosols from the contaminated soil as the transmission route of melioidosis during extreme weather events. This is because the bacteria in unvegetated soil are more easily spread by winds. In consistent with inhalational melioidosis, 24 (63.2%) patients had pneumonia. Clinicians should be aware of melioidosis during typhoon season and initiate appropriate investigation and treatment for patients with compatible symptoms.

Protein posttranslational modifications (PTMs) arise in a number of normal cellular biological pathways and in response to pathology caused by inflammation and/or infection. Indeed, a number of PTMs have been identified and linked to specific autoimmune responses and metabolic pathways. One particular PTM, termed isoaspartyl (isoAsp or isoD) modification, is among the most common spontaneous PTM occurring at physiological pH and temperature. Herein, we demonstrate that isoAsp modifications arise within the ZAP70 protein tyrosine kinase upon T-cell antigen receptor (TCR) engagement. The enzyme protein L -isoaspartate O -methyltransferase (PCMT1, or PIMT, EC 2.1.1.77) evolved to repair isoaspartyl modifications in cells. In this regard, we observe that increased levels of isoAsp modification that arise under oxidative stress are correlated with reduced PIMT activity in patients with systemic lupus erythematosus (SLE). PIMT deficiency leads to T cell hyper-proliferation and hyper-phosphorylation through ZAP70 signaling. We demonstrate that inducing the overexpression of PIMT can correct the hyper-responsive phenotype in lupus T cells. Our studies reveal a phenotypic role of isoAsp modification and phosphorylation of ZAP70 in lupus T cell autoimmunity and provide a potential therapeutic target through the repair of isoAsp modification.

Background and Objectives: Epilepsy may result from various brain injuries, including stroke (ischemic and hemorrhagic), traumatic brain injury, and infections. Identifying shared common biological pathways and biomarkers of the epileptogenic process initiated by the different injuries may lead to novel targets for preventing the development of epilepsy. We systematically reviewed biofluid biomarkers to test their association with the risk of post-brain injury epilepsy., Methods: We searched articles until January 25, 2022, in MEDLINE, Embase, PsycInfo, Web of Science, and Cochrane. The primary outcome was the difference in mean biomarker levels in patients with and without post-brain injury epilepsy. We used the modified quality score on prognostic studies for risk of bias assessment. We calculated each biomarker's pooled standardized mean difference (SMD) and 95% CI. Molecular interaction network and enrichment analyses were conducted in Cytoscape (PROSPERO CRD42021297110)., Results: We included 22 studies with 1,499 cases with post-brain injury epilepsy and 7,929 controls without post-brain injury epilepsy. Forty-five biomarkers in the blood or CSF were investigated with samples collected at disparate time points. Of 22 studies, 21 had a moderate-to-high risk of bias. Most of the biomarkers (28/45) were investigated in single studies; only 9 provided validation data, and studies used variable definitions for early-onset and late-onset seizures. A meta-analysis was possible for 19 biomarkers. Blood glucose levels in 4 studies were significantly higher in patients with poststroke epilepsy (PSE) than those without PSE (SMD 0.44; CI 0.19-0.69). From individual studies, 15 biomarkers in the blood and 7 in the CSF were significantly associated with post-brain injury epilepsy. Enrichment analysis identified that the significant biomarkers (interleukin [IL]-6, IL-1β]) were predominantly inflammation related., Discussion: We cannot yet recommend using the reported biomarkers for designing antiepileptogenesis trials or use in the clinical setting because of methodological heterogeneity, bias in the included studies, and insufficient validation studies. Although our analyses indicate the plausible role of inflammation in epileptogenesis, this is likely not the only mechanism. For example, an individual's genetic susceptibilities might contribute to his/her risk of epileptogenesis after brain injury. Rigorously designed biomarker studies with methods acceptable to the regulatory bodies should be conducted., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

This paper shows an effective method to significantly enhance the isolation of a closely spaced two-port patch antenna, which can be deployed for full-duplex transceivers as well as multiple-input-multiple-output (MIMO) systems. Two rectangular microstrip patches are arranged in the E-plane configuration. To achieve high isolation, a grounded stub is positioned between the radiating patches. For validation of the proposed concept, an antenna prototype is fabricated for measurements. The measured data demonstrates that the port-to-port mutual coupling can be suppressed to -50 dB, which is useful in self-interference cancellation for full-duplex communication systems. Compared with the coupled design, the isolation is significantly enhanced by 43 dB with an inter-element spacing of 0.034λc, where λc is a free-space wavelength at the center operating frequency. Regarding MIMO metrics, the antenna also shows good MIMO diversity performance based on an envelope correlation coefficient and a diversity gain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Colon cancer is the third leading cause of cancer death globally. Although early screenings and advances in treatments have reduced mortality since 1970, identification of novel targets for therapeutic intervention is needed to address tumor heterogeneity and recurrence. Previous work identified aldehyde dehydrogenase 1B1 (ALDH1B1) as a critical factor in colon tumorigenesis. To investigate further, we utilized a human colon adenocarcinoma cell line (SW480) in which the ALDH1B1 protein expression has been knocked down by 80% via shRNA. Through multi-omics (transcriptomics, proteomics, and untargeted metabolomics) analysis, we identified the impact of ALDH1B1 knocking down (KD) on molecular signatures in colon cancer cells. Suppression of ALDH1B1 expression resulted in 357 differentially expressed genes (DEGs), 191 differentially expressed proteins (DEPs) and 891 differentially altered metabolites (DAMs). Functional annotation and enrichment analyses revealed that: (1) DEGs were enriched in integrin-linked kinase (ILK) signaling and growth and development pathways; (2) DEPs were mainly involved in apoptosis signaling and cellular stress response pathways; and (3) DAMs were associated with biosynthesis, intercellular and second messenger signaling. Collectively, the present study provides new molecular information associated with the cellular functions of ALDH1B1, which helps to direct future investigation of colon cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ying Chen, Vasilis Vasiliou reports financial support was provided by National Institutes of Health., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Rates of Cannabis Use Disorder (CUD) are highest amongst young adults. Paucity of brain tissue samples limits the ability to examine the molecular basis of cannabis related neuropathology. Proteomic studies of neuron-derived extracellular vesicles (NDEs) isolated from the biofluids may reveal markers of neuropathology in CUD., Methods: NDEs were extracted using ExoSORT, an immunoaffinity method to enrich NDEs from plasma samples from patients with young onset CUD and matched controls. Differential proteomic profiles were explored with Label Free Quantification (LFQ) mass spectrometry. Selected proteins were validated using orthogonal methods., Results: A total of 231 (±10) proteins were identified in NDE preparations from CUD and controls of which 28 were differentially abundant between groups. The difference in abundance of properdin ( CFP gene) was statistically significant. SHANK1 ( SHANK1 gene), an adapter protein at the post-synaptic density, was nominally depleted in the CUD NDE preparations., Conclusion: In this pilot study, we noted a decrease in SHANK1 protein, involved in the structural and functional integrity of glutamatergic post-synapse, a potential peripheral signature of CUD neuropathology. The study shows that LFQ mass spectrometry proteomic analysis of NDEs derived from plasma may yield important insights into the synaptic pathology associated with CUD.

14 new gold(I) NHC complexes of the type [AuX( i Pr 2 -bimy)] ( i Pr 2 -bimy = 1,3-diisopropylbenzimidazolin-2-ylidene) have been prepared and fully characterized. These complexes and their reported analogues were used to systematically compare and rank the donating abilities of overall 34 anionic X-type donors by 13 C NMR spectroscopy. Specifically, the carbene chemical shift of the i Pr 2 -bimy ligand was found to be responsive to the ligand X spanning an overall range Δδ > 37 ppm between the strongest and weakest donor in this study.

Repetitive DNA elements are packaged in heterochromatin, but many require bursts of transcription to initiate and maintain long-term silencing. The mechanisms by which these heterochromatic genome features are transcribed remain largely unknown. Here, we show that DOT1L, a conserved histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), has a specialized role in transcription of major satellite repeats to maintain pericentromeric heterochromatin and genome stability. We find that H3K79me3 is selectively enriched relative to H3K79me2 at repetitive elements in mouse embryonic stem cells (mESCs), that DOT1L loss compromises pericentromeric satellite transcription, and that this activity involves possible coordination between DOT1L and the chromatin remodeler SMARCA5. Stimulation of transcript production from pericentromeric repeats by DOT1L participates in stabilization of heterochromatin structures in mESCs and cleavage-stage embryos and is required for preimplantation viability. Our findings uncover an important role for DOT1L as a bridge between transcriptional activation of repeat elements and heterochromatin stability, advancing our understanding of how genome integrity is maintained and how chromatin state is set up during early development., (© 2023 The Authors.)

Substance use disorders are associated with disruptions in sleep and circadian rhythms that persist during abstinence and may contribute to relapse risk. Repeated use of substances such as psychostimulants and opioids may lead to significant alterations in molecular rhythms in the nucleus accumbens (NAc), a brain region central to reward and motivation. Previous studies have identified rhythm alterations in the transcriptome of the NAc and other brain regions following the administration of psychostimulants or opioids. However, little is known about the impact of substance use on the diurnal rhythms of the proteome in the NAc. We used liquid chromatography coupled to tandem mass spectrometry-based quantitative proteomics, along with a data-independent acquisition analysis pipeline, to investigate the effects of cocaine or morphine administration on diurnal rhythms of proteome in the mouse NAc. Overall, our data reveal cocaine and morphine differentially alter diurnal rhythms of the proteome in the NAc, with largely independent differentially expressed proteins dependent on time-of-day. Pathways enriched from cocaine altered protein rhythms were primarily associated with glucocorticoid signaling and metabolism, whereas morphine was associated with neuroinflammation. Collectively, these findings are the first to characterize the diurnal regulation of the NAc proteome and demonstrate a novel relationship between the phase-dependent regulation of protein expression and the differential effects of cocaine and morphine on the NAc proteome. The proteomics data in this study are available via ProteomeXchange with identifier PXD042043.

Halogenated organic pollutants (HOPs), including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and chlorophenols (CPs), were identified in three marine fish species in Vietnam. Total PCBs, OCPs, and CPs concentrations ranged from 4.5 to 711.6 ng g -1 lipid weight (lw), 69.9-2360 ng g -1 lw, and 208.1-3941.2 ng g -1 lw, respectively. CPs were the most frequently detected pollutants in the marine environment of Vietnam of the three HOPs studied, followed by OCPs and PCBs. There are significant differences in HOPs between three types of seafood in Vietnam, including yellowstripe scad, Indian mackerel, and silver pomfret in this study. Notably, the types and amounts of HOPs found in the fish were differently influenced by the economic and industrial activities of the sampled areas. Despite these findings, the consumption of HOP-contaminated fish from the study areas was found not to pose any significant health risks to Vietnam's coastal population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Although influenza A viruses of several subtypes have occasionally infected humans, to date only those of the H1, H2, and H3 subtypes have led to pandemics and become established in humans. The detection of two human infections by avian H3N8 viruses in April and May of 2022 raised pandemic concerns. Recent studies have shown the H3N8 viruses were introduced into humans from poultry, although their genesis, prevalence, and transmissibility in mammals have not been fully elucidated. Findings generated from our systematic influenza surveillance showed that this H3N8 influenza virus was first detected in chickens in July 2021 and then disseminated and became established in chickens over wider regions of China. Phylogenetic analyses revealed that the H3 HA and N8 NA were derived from avian viruses prevalent in domestic ducks in the Guangxi-Guangdong region, while all internal genes were from enzootic poultry H9N2 viruses. The novel H3N8 viruses form independent lineages in the glycoprotein gene trees, but their internal genes are mixed with those of H9N2 viruses, indicating continuous gene exchange among these viruses. Experimental infection of ferrets with three chicken H3N8 viruses showed transmission through direct contact and inefficient transmission by airborne exposure. Examination of contemporary human sera detected only very limited antibody cross-reaction to these viruses. The continuing evolution of these viruses in poultry could pose an ongoing pandemic threat. IMPORTANCE A novel H3N8 virus with demonstrated zoonotic potential has emerged and disseminated in chickens in China. It was generated by reassortment between avian H3 and N8 virus(es) and long-term enzootic H9N2 viruses present in southern China. This H3N8 virus has maintained independent H3 and N8 gene lineages but continues to exchange internal genes with other H9N2 viruses to form novel variants. Our experimental studies showed that these H3N8 viruses were transmissible in ferrets, and serological data suggest that the human population lacks effective immunological protection against it. With its wide geographical distribution and continuing evolution in chickens, other spillovers to humans can be expected and might lead to more efficient transmission in humans., Competing Interests: The authors declare no conflict of interest.

Hexagonal NaYF4:Tm, Yb upconversion (UC) phosphors with excellent UC luminescence quantum efficiency and chemical stability meet demands for applications in bioimaging and anti-counterfeiting printing. In this work, a series of NaYF4:Tm, Yb upconversion microparticles (UCMPs) with different concentrations of Yb were synthesized by a hydrothermal method. Then, the UCMPs become hydrophilic through surface oxidation of the oleic acid (C-18) ligand to azelaic acid (C-9) using the Lemieux-von Rodloff reagent. The structure and morphology of UCMPs were investigated by X-ray diffraction and scanning electron microscopy. The optical properties were studied using diffusion reflectance spectroscopy and photoluminescent spectroscopy under 980 nm laser irradiation. The emission peaks of the Tm 3+ ions are 450, 474, 650, 690, and 800 nm, attributed to the transitions from the excited state to ground state 3 H 6 . These emissions are the results of two or three photon absorption through multi-step resonance energy transfer from excited Yb 3+ , confirmed via a power-dependent luminescence study. The results show that the crystal phases and luminescence properties of the NaYF4:Tm, Yb UCMPs are controlled by changing the Yb doping concentration. The printed patterns are readable under the excitation of a 980 nm LED. Moreover, the zeta potential analysis shows that the UCMPs after surface oxidation are water dispersible. In particular, the naked eye can observe the enormous upconversion emissions in UCMPs. These findings indicated that this fluorescent material is an ideal candidate for anti-counterfeiting and biological applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The widely distributed antibiotic resistance genes (ARGs) were unevenly proliferated in various habitats. Great endeavors are needed to resolve the resistome features that can differentiate or connect different habitats. This study retrieved a broad spectrum of resistome profiles from 1723 metagenomes categorized into 13 habitats, encompassing industrial, urban, agricultural, and natural environments, and spanning most continents and oceans. The resistome features (ARG types, subtypes, indicator ARGs, and emerging mobilizable ARGs: mcr and tet(X)) in these habitats were benchmarked via a standardized workflow. We found that wastewater and wastewater treatment works were characterized to be reservoirs of more diverse genotypes of ARGs than any other habitats including human and livestock fecal samples, while fecal samples were with higher ARG abundance. Bacterial taxonomy composition was significantly correlated with resistome composition across most habitats. Moreover, the source-sink connectivities were disentangled by developing the resistome-based microbial attribution prediction model. Environmental surveys with standardized bioinformatic workflow proposed in this study will help comprehensively understand the transfer of ARGs in the environment, thus prioritizing the critical environments with high risks for intervention to tackle the problem of ARGs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Sensitive detection of Mycobacterium tuberculosis (TB) in small percentages in metagenomic samples is essential for microbial classification and drug resistance prediction. However, traditional methods, such as bacterial culture and microscopy, are time-consuming and sometimes have limited TB detection sensitivity. Oxford nanopore technologies (ONT) MinION sequencing allows rapid and simple sample preparation for sequencing. Its recently developed adaptive sequencing selects reads from targets while allowing real-time base-calling to achieve sequence enrichment or depletion during sequencing. Another common enrichment method is PCR amplification of the target TB genes. In this study, we compared both methods using ONT MinION sequencing for TB detection and variant calling in metagenomic samples using both simulation runs and those with synthetic and patient samples. We found that both methods effectively enrich TB reads from a high percentage of human (95%) and other microbial DNA. Adaptive sequencing with readfish and UNCALLDE achieved a 3.9-fold and 2.2-fold enrichment compared to the control run. We provide a simple automatic analysis framework to support the detection of TB for clinical use, openly available at https://github.com/HKU-BAL/ONT-TB-NF . Depending on the patient's medical condition and sample type, we recommend users evaluate and optimize their workflow for different clinical specimens to improve the detection limit., (© 2023. The Author(s).)

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid (aa) residues of PC1 in two Pkd1-KO orthologous murine models of ADPKD suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase (NNT). This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function, and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD., (© 2023. The Author(s).)