Bioactivity responses to changes in mucus-associated bacterial composition between healthy and bleached Porites lobata corals.

This study aims to investigate how bioactivities of the coral surface mucus layer (SML) respond to changes in mucus-associated bacterial communities between bleached and healthy Porites lobata corals in Nha Trang Bay, Vietnam. The findings suggested that significant shifts in the mucus-associated bacterial communities were related to changes in coral health states from bleached to healthy P. lobata colonies (p < 0.05), while bacterial compositions were not significantly different across seasons and locations (p > 0.05). Of which 8 genera, Shewanella, Fusibacter, Halodesulfovibrio, Marinifilum, Endozoicomonas, Litoribacillus, Algicola, and Vibrio were present only in the SML of bleached coral while absent in the SML of the healthy one. As compared with the bleached SML, the healthy SML demonstrated stronger antibacterial activity against a coral bleaching pathogen, V. coralliilyticus, higher antitumor activity against HCT116 cell accompanied with increased induction of cleaved PARP and accelerated cell nucleic apoptosis and cycle arrest at S and G2/M phases exhibiting several typical characteristics, cell shrinkage, lost cell contact, and apoptotic body formation. Moreover, putative compounds detected at 280 nm in the healthy SML were obviously higher than those in the bleached one, probably they could be bioactive molecules responsible for competitively exclusion of pathogens, Algicola and Vibrio, from the healthy SML.

Friendly Environmental Strategies to Recycle Zinc-Carbon Batteries for Excellent Gel Polymer Electrolyte (PVA-ZnSO4-H2SO4) and Carbon Materials for Symmetrical Solid-State Supercapacitors.

In this report, we introduce a novel idea to prepare a redox additive in a gel polymer electrolyte system of PVA-ZnSO4-H2SO4 based on zinc-carbon battery recycling. Here, zinc cans from spent zinc-carbon batteries are dissolved completely in 1 M H2SO4 to obtain a redox additive in an aqueous electrolyte of ZnSO4-H2SO4. Moreover, carbon nanoparticles and graphene nanosheets were synthesized from carbon rod and carbon powder from spent zinc-carbon batteries by only one step of washing and electrochemical exfoliation, respectively, which have good electrochemical capability. The three-electrode system using a ZnSO4-H2SO4 electrolyte with carbon nanoparticles and graphene nanosheets as working electrodes shows high electrochemical adaptability, which points out its promising application in supercapacitor devices. Thus, the symmetrical solid-state supercapacitor devices based on the sandwich structure of graphene nanosheets/PVA-ZnSO4-H2SO4/graphene nanosheets illustrated the highest energy density of 39.17 W h kg-1 at a power density of 1700 W kg-1. While symmetrical devices based on carbon nanoparticles/PVA-ZnSO4-H2SO4/carbon nanoparticles exhibited a maximum energy density of 35.65 W h kg-1 at a power density of 1700 W kg-1. Moreover, these devices illustrate strong durability after 5000 cycles, with approximately 90.2% and 73.1% remaining, respectively. These results provide a promising strategy for almost completely recycling zinc-carbon batteries, one of the most popular dry batteries.

New diterpene lactone derivatives from Aphanamixis polystachya leaves inhibit nitric oxide production in RAW 264.7 cells.

Phytochemical studies on Aphanamixis plants have attracted considerable attention over the past few decades due to the structural diversities and significant biological activities of terpenoids produced by these plants. In the present study, five new acyclic diterpene lactone derivatives, aphanamixionolides A-E (1-5), and three known tirucallane-type triterpenes, namely, piscidinol A (6), hispidone (7), and bourjotinolone A (8), were isolated from the leaves of Aphanamixis polystachya. Their structures were elucidated by comprehensive analyses of HR-ESI-MS and NMR spectroscopic data and by comparison with those reported in the literature. Absolute configurations of the new compounds were determined by experimental and TD-DFT calculated ECD spectra. Compounds 1-8 inhibited NO production with IC50 values of 10.2-37.7 µM, which are comparable to positive control l-NMMA (IC50: 31.5 µM).

Uterocervical angle and cervical length measurements for spontaneous preterm birth prediction in low-risk singleton pregnant women: a prospective cohort study.

PURPOSE: Preterm birth is the leading cause of early neonatal morbidity and mortality. Strategies to predict preterm birth risk can help improve pregnancy outcomes. Even pregnant women without known risk factors for preterm birth can also experience it. This study aimed to evaluate the ability of the uterocervical angle and cervical length to predict spontaneous preterm birth in low-risk singleton pregnant women. METHODS: A prospective study on 1107 singleton pregnant women between 16+0 and 23+6 weeks gestation at low risk for spontaneous preterm birth who were treated at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, between September 2020 and September 2021 was conducted. A single sonographer assessed the cervical length and the uterocervical angle using transvaginal ultrasonography. The patients were followed up until delivery to determine the main pregnancy outcome (spontaneous preterm birth before 37 weeks gestation). The cut-off points for the uterocervical angle and cervical length were established by analyzing the receiver operating characteristic curve. The sensitivity, specificity, likelihood ratio, positive and negative predictive values, and accuracy of the uterocervical angle and cervical length for predicting spontaneous preterm birth were determined. RESULTS: A uterocervical angle ≥ 99° predicted spontaneous preterm birth at < 37 weeks, with a sensitivity and specificity of 91% and 76%, respectively. A cervical length ≤ 33.8 mm predicted preterm birth at < 37 weeks with a sensitivity and specificity of 25% and 66%, respectively. A uterocervical angle ≥ 99° combined with a cervical length ≤ 33.8 mm yielded the sensitivity, specificity, positive predictive value, likelihood ratio, and accuracy of spontaneous preterm birth prediction of 66%, 93%, 36%, 9, and 91%, respectively; thus provided a significant increase of specificity with an acceptable reduction of sensitivity as compared to cervical length alone. CONCLUSION: Besides the cervical length, the uterocervical angle can be considered a valuable ultrasound parameter for predicting spontaneous preterm birth in low-risk singleton pregnant women. Combining the uterocervical angle and cervical length yielded stronger spontaneous preterm birth prediction values.

The splicing factor CCAR1 regulates the Fanconi anemia/BRCA pathway.

The twenty-three Fanconi anemia (FA) proteins cooperate in the FA/BRCA pathway to repair DNA interstrand cross-links (ICLs). The cell division cycle and apoptosis regulator 1 (CCAR1) protein is also a regulator of ICL repair, though its possible function in the FA/BRCA pathway remains unknown. Here, we demonstrate that CCAR1 plays a unique upstream role in the FA/BRCA pathway and is required for FANCA protein expression in human cells. Interestingly, CCAR1 co-immunoprecipitates with FANCA pre-mRNA and is required for FANCA mRNA processing. Loss of CCAR1 results in retention of a poison exon in the FANCA transcript, thereby leading to reduced FANCA protein expression. A unique domain of CCAR1, the EF hand domain, is required for interaction with the U2AF heterodimer of the spliceosome and for excision of the poison exon. Taken together, CCAR1 is a splicing modulator required for normal splicing of the FANCA mRNA and other mRNAs involved in various cellular pathways.

High Prevalence of Highly Pathogenic Avian Influenza: A Virus in Vietnam's Live Bird Markets.

Background: In recent years, Vietnam has suffered multiple epizootics of influenza in poultry. Methods: From 10 January 2019 to 26 April 2021, we employed a One Health influenza surveillance approach at live bird markets (LBMs) and swine farms in Northern Vietnam. When the COVID-19 pandemic permitted, each month, field teams collected oral secretion samples from poultry and pigs, animal facility bioaerosol and fecal samples, and animal worker nasal washes at 4 LBMs and 5 swine farms across 5 sites. Initially samples were screened with molecular assays followed by culture in embryonated eggs (poultry swabs) or Madin-Darby canine kidney cells (human or swine swabs). Results: Many of the 3493 samples collected had either molecular or culture evidence for influenza A virus, including 314 (37.5%) of the 837 poultry oropharyngeal swabs, 144 (25.1%) of the 574 bioaerosol samples, 438 (34.9%) of the 1257 poultry fecal swab samples, and 16 (1.9%) of the 828 human nasal washes. Culturing poultry samples yielded 454 influenza A isolates, 83 of which were H5, and 70 (84.3%) of these were highly pathogenic. Additionally, a positive human sample had a H9N2 avian-like PB1 gene. In contrast, the prevalence of influenza A in the swine farms was much lower with only 6 (0.4%) of the 1700 total swine farm samples studied, having molecular evidence for influenza A virus. Conclusions: This study suggests that Vietnam's LBMs continue to harbor high prevalences of avian influenza A viruses, including many highly pathogenic H5N6 strains, which will continue to threaten poultry and humans.

Early improvement with cariprazine as a predictor of antidepressant, anxiolytic, and antimanic response in bipolar I mania and depression: A pooled post hoc analysis of randomized cariprazine trials.

BACKGROUND: Early symptomatic improvement may predict treatment response in bipolar I disorder. Cariprazine has demonstrated early treatment effects in bipolar I depression and mania studies; therefore, we assessed whether early improvement with cariprazine predicts eventual treatment response. METHODS: Post hoc analyses used pooled data from randomized, double-blind, placebo-controlled bipolar I depression (NCT02670538, NCT02670551) and mania (NCT00488618, NCT01058096, NCT01058668) trials. In depression studies (cariprazine 1.5 mg/d, 3 mg/d, or placebo), early improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) total scores (≥25 % improvement at day 15) and subsequent depressive/anxiety symptom response status (≥50 % improvement at week 6) were assessed. In mania studies (cariprazine 3-12 mg/d or placebo), early improvement in Young Mania Rating Scale (YMRS) total scores (≥25 % improvement at day 7) and manic symptom response status (≥50 % improvement at week 3) were assessed. RESULTS: Patients with bipolar I depression and early MADRS improvement were approximately 4- to 6-times as likely to achieve MADRS or HAM-A response than those without early improvement; patients with early HAM-A improvement were approximately 3- to 4-times as likely to achieve MADRS or HAM-A response. A subset of patients without early improvement with cariprazine 1.5 mg/d (20 %-31 %) subsequently responded following up-titration. Patients with mania and early YMRS improvement were approximately 5 times more likely to have manic symptom response than those without early improvement. LIMITATIONS: Post hoc analysis; relatively short study durations; flexible-dosing (mania studies). CONCLUSIONS: Early symptom improvement with cariprazine may inform therapeutic decisions for patients with bipolar I disorder.

Crosstalk between genomic variants and DNA methylation in FLT3 mutant acute myeloid leukemia.

Acute myeloid leukemia (AML) is a type of blood cancer with diverse genetic variations and DNA methylation alterations. By studying the interaction of gene mutations, expression, and DNA methylation, we aimed to gain valuable insights into the processes that lead to block differentiation in AML. We analyzed TCGA-LAML data (173 samples) with RNA sequencing and DNA methylation arrays, comparing FLT3 mutant (48) and wild-type (125) cases. We conducted differential gene expression analysis using cBioPortal, identified DNA methylation differences with ChAMP tool, and correlated them with gene expression changes. Gene set enrichment analysis (g:Profiler) revealed significant biological processes and pathways. ShinyGo and GeneCards were used to find potential transcription factors and their binding sites among significant genes. We found significant differentially expressed genes (DEGs) negatively correlated with their most significant methylation probes (Pearson correlation coefficient of -0.49, P-value <0.001) between FLT3 mutant and wild-type groups. Moreover, our exploration of 450 k CpG sites uncovered a global hypo-methylated status in 168 DEGs. Notably, these methylation changes were enriched in the promoter regions of Homebox superfamily gene, which are crucial in transcriptional-regulating pathways in blood cancer. Furthermore, in FLT3 mutant AML patient samples, we observed overexpress of WT1, a transcription factor known to bind homeobox gene family. This finding suggests a potential mechanism by which WT1 recruits TET2 to demethylate specific genomic regions. Integrating gene expression and DNA methylation analyses shed light on the impact of FLT3 mutations on cancer cell development and differentiation, supporting a two-hit model in AML. This research advances understanding of AML and fosters targeted therapeutic strategy development.

Expression of SUMO and NF-κB genes in hepatitis B virus-associated hepatocellular carcinoma patients: An observational study.

Alterations in signaling pathways and modulation of cell metabolism are associated with the pathogenesis of cancers, including hepatocellular carcinoma (HCC). Small ubiquitin-like modifier (SUMO) proteins and NF-κB family play major roles in various cellular processes. The current study aims to determine the expression profile of SUMO and NF-κB genes in HCC tumors and investigate their association with the clinical outcome of HCC. The expression of 5 genes - SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 - was quantified in tumor and adjacent non-tumor tissues of 58 HBV-related HCC patients by real-time quantitative PCR and was analyzed for the possible association with clinical parameters of HCC. The expression of SUMO2 was significantly higher in HCC tumor tissues compared to the adjacent non-tumor tissues (P = .01), while no significant difference in SUMO1, SUMO3, NF-κB p65, and NF-κB p50 expression was observed between HCC tumor and non-tumor tissues (P > .05). In HCC tissues, a strong correlation was observed between the expression of SUMO2 and NF-κB p50, between SUMO3 and NF-κB p50, between SUMO3 and NF-κB p65 (Spearman rho = 0.83; 0.82; 0.772 respectively; P < .001). The expression of SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 was decreased in grade 3 compared to grades 1 and 2 in HCC tumors according to the World Health Organization grades system. Our results highlighted that the SUMO2 gene is upregulated in tumor tissues of patients with HCC, and is related to the development of HCC, thus it may be associated with the pathogenesis of HCC.

Time-course cross-species transcriptomics reveals conserved hepatotoxicity pathways induced by repeated administration of cyclosporine A.

Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity mechanism. This study aimed to capture the alterations in genome-wide expression over time and the subsequent perturbations of corresponding pathways across species. Six data from humans, mice, and rats, including animal liver tissue, human liver microtissues, and two liver cell lines exposed to CsA toxic dose, were used. The microtissue exposed to CsA for 10 d was analyzed to obtain dynamically differentially expressed genes (DEGs). Single-time points data at 1, 3, 5, 7, and 28 d of different species were used to provide additional evidence. Using liver microtissue-based longitudinal design, DEGs that were consistently up- or down-regulated over time were captured, and the well-known mechanism involved in CsA toxicity was elucidated. Thirty DEGs that consistently changed in longitudinal data were also altered in 28-d rat in-house data with concordant expression. Some genes (e.g. TUBB2A, PLIN2, APOB) showed good concordance with identified DEGs in 1-d and 7-d mouse data. Pathway analysis revealed up-regulations of protein processing, asparagine N-linked glycosylation, and cargo concentration in the endoplasmic reticulum. Furthermore, the down-regulations of pathways related to biological oxidations and metabolite and lipid metabolism were elucidated. These pathways were also enriched in single-time-point data and conserved across species, implying their biological significance and generalizability. Overall, the human organoids-based longitudinal design coupled with cross-species validation provides temporal molecular change tracking, aiding mechanistic elucidation and biologically relevant biomarker discovery.

Single-stranded DNA Gap Accumulation is a Functional Biomarker for USP1 Inhibitor Sensitivity.

Recent studies suggest that PARP inhibitors and POLQ inhibitors confer synthetic lethality in BRCA1-deficient tumors by accumulation of single-stranded DNA (ssDNA) gaps at replication forks. Loss of USP1, a deubiquitinating enzyme, is also synthetic lethal with BRCA1 deficiency, and USP1 inhibitors are now undergoing clinical development for these cancers. Here, we show that USP1 inhibitors also promote the accumulation of ssDNA gaps during replication in BRCA1-deficient cells, and this phenotype correlates with the drug sensitivity. USP1 inhibition increased monoubiquitinated PCNA at replication forks, mediated by the ubiquitin ligase RAD18, and knockdown of RAD18 caused USP1 inhibitor resistance and suppression of ssDNA gaps. USP1 inhibition overcame PARP inhibitor resistance in a BRCA1-mutated xenograft model and induced ssDNA gaps. Furthermore, USP1 inhibition was synergistic with PARP and POLQ inhibition in BRCA1-mutant cells, with enhanced ssDNA gap accumulation. Finally, in patient-derived ovarian tumor organoids, sensitivity to USP1 inhibition alone or in combination correlated with the accumulation of ssDNA gaps. Assessment of ssDNA gaps in ovarian tumor organoids therefore represents a rapid approach for predicting response to USP1 inhibition in ongoing clinical trials.

Deconwolf enables high-performance deconvolution of widefield fluorescence microscopy images.

Microscopy-based spatially resolved omic methods are transforming the life sciences. However, these methods rely on high numerical aperture objectives and cannot resolve crowded molecular targets, limiting the amount of extractable biological information. To overcome these limitations, here we develop Deconwolf, an open-source, user-friendly software for high-performance deconvolution of widefield fluorescence microscopy images, which efficiently runs on laptop computers. Deconwolf enables accurate quantification of crowded diffraction limited fluorescence dots in DNA and RNA fluorescence in situ hybridization images and allows robust detection of individual transcripts in tissue sections imaged with ×20 air objectives. Deconvolution of in situ spatial transcriptomics images with Deconwolf increased the number of transcripts identified more than threefold, while the application of Deconwolf to images obtained by fluorescence in situ sequencing of barcoded Oligopaint probes drastically improved chromosome tracing. Deconwolf greatly facilitates the use of deconvolution in many bioimaging applications.

Changes in the levels of serum glial fibrillary acidic protein and the correlation with outcomes in severe traumatic brain injury patients.

Purpose: Glial fibrillary acidic protein serves as a biomarker indicative of astroglial injury, particularly following instances of severe traumatic brain injury. This study aims to evaluate variations in serum glial fibrillary acidic protein levels within the first 3 days and their correlation with outcomes in patients with severe traumatic brain injury. Subjects and methods: Thirty-nine patients with severe traumatic brain injury were enrolled in the study. Their blood samples were collected at six distinct time points: T0 (upon admission), T1, T2, T3, T4, and T5 (6-, 12-, 24-, 48-, and 72-h post-admission, respectively). The blood samples were run for the quantification of serum glial fibrillary acidic protein levels and other biochemical tests. All patients were closely watched and the outcomes at discharge were evaluated. Results: Glial fibrillary acidic protein levels tend to increase gradually from the time of admission to 48 h post-admission and then decrease at 72 h post-admission. Glial fibrillary acidic protein T2 is correlated with Acute Physiology and Chronic Health Evaluation II score, lactate, Simplified Acute Physiology Score II score and outcome. Glial fibrillary acidic protein max correlated with lactate, Acute Physiology and Chronic Health Evaluation II score, Simplified Acute Physiology Score II score, and outcome. Glasgow Coma Score at admission and glial fibrillary acidic protein T2 (OR = 1.034; p = 0.025), T3 (OR = 1.029; p = 0.046), T4 (OR = 1.006; p = 0.032), T5 (OR = 1.012; p = 0.048) and glial fibrillary acidic protein max (OR = 1.005; p = 0.010) were independent factors that have significant prognostic value in mortality in patients with severe traumatic brain injury. The predictive model in predicting mortality had the highest area under the curve based on glial fibrillary acidic protein T2 and Glasgow Coma Score T0 with an area under the curve of 0.904 and p < 0.001. In the multivariable regression model, glial fibrillary acidic protein max was associated with Glasgow score (p < 0.001; VIF = 1.585), lactate T0 (p = 0.024; VIF = 1.163), Acute Physiology and Chronic Health Evaluation II score (p = 0.037; VIF = 1.360), and Rotterdam score (p = 0.044; VIF = 1.713). Conclusion: Glial fibrillary acidic protein levels tend to increase gradually from the time of admission to 48 h post-admission then decreases at 72 h post-admission. Glial fibrillary acidic protein T2, T3, T4, T5, and glial fibrillary acidic protein max were independent factors with significant prognostic mortality values in patients with severe traumatic brain injury.

QMix: An Efficient Program to Automatically Estimate Multi-Matrix Mixture Models for Amino Acid Substitution Process.

The single-matrix amino acid (AA) substitution models are widely used in phylogenetic analyses; however, they are unable to properly model the heterogeneity of AA substitution rates among sites. The multi-matrix mixture models can handle the site rate heterogeneity and outperform the single-matrix models. Estimating multi-matrix mixture models is a complex process and no computer program is available for this task. In this study, we implemented a computer program of the so-called QMix based on the algorithm of LG4X and LG4M with several enhancements to automatically estimate multi-matrix mixture models from large datasets. QMix employs QMaker algorithm instead of XRATE algorithm to accurately and rapidly estimate the parameters of models. It is able to estimate mixture models with different number of matrices and supports multi-threading computing to efficiently estimate models from thousands of genes. We re-estimate mixture models LG4X and LG4M from 1471 HSSP alignments. The re-estimated models (HP4X and HP4M) are slightly better than LG4X and LG4M in building maximum likelihood trees from HSSP and TreeBASE datasets. QMix program required about 10 hours on a computer with 18 cores to estimate a mixture model with four matrices from 200 HSSP alignments. It is easy to use and freely available for researchers.

An Automated Robotic Interface for Assays: Facilitating Machine Learning in Drug Discovery by the Automation of Physicochemical Property Assays.

Measuring the physicochemical properties of molecules is an iterative but integral process in the drug development process. A strategy to overcome the challenges in maximizing assay throughput relies on the usage of in silico machine learning (ML) prediction models trained on experimental data. Consequently, the performance of these in silico models are dependent on the quality of the utilized experimental data. To improve the data quality, we have designed and implemented an automated robotic system to prepare and run physicochemical property assays (Automated Robotic Interface for Assays, ARIA) with an increase in sample throughput of 6 to10-fold. Through this process, we overcame major challenges and achieved consistent reproducible assay data compared to semiautomated assay preparation.

Design principles and therapeutic applications of novel synthetic WNT signaling agonists.

Wingless-related integration site or Wingless and Int-1 or Wingless-Int (WNT) signaling is crucial for embryonic development, and adult tissue homeostasis and regeneration, through its essential roles in cell fate, patterning, and stem cell regulation. The biophysical characteristics of WNT ligands have hindered efforts to interrogate ligand activity in vivo and prevented their development as therapeutics. Recent breakthroughs have enabled the generation of synthetic WNT signaling molecules that possess characteristics of natural ligands and potently activate the pathway, while also providing distinct advantages for therapeutic development and manufacturing. This review provides a detailed discussion of the protein engineering of these molecular platforms for WNT signaling agonism. We discuss the importance of WNT signaling in several organs and share insights from the initial application of these new classes of molecules in vitro and in vivo. These molecules offer a unique opportunity to enhance our understanding of how WNT signaling agonism promotes tissue repair, enabling targeted development of tailored therapeutics.

Chemical composition and the anti-inflammatory effect of volatile compounds from Anaxagorea luzonensis A. Gray.

Anaxagorea luzonensis A. Gray, a member of the Annonaceae family, has been used to treat a variety of illnesses for a long time. For the first time, A. luzonensis volatile compounds (ALVCs) were extracted from the leaves, and the components were identified using gas chromatography-mass spectrometry (GC-MS). Further, the main compositions of ALVCs were also assessed for their ability to bind with anti-inflammatory proteins using a docking model. In addition, in vitro tests e.g. inhibition of protein degradation and the inhibition of nitric oxide release using RAW264.7 macrophage cells were utilized for evaluating the anti-inflammatory activity. The results showed that the principal compounds of ALVCs were bulnesol (34.1 %), cubitene (17.8 %), ß-eudesmol (10.4 %), epi-longipinanol (5.9 %), and (Z)-nerolidyl acetate (5.5 %). Three compounds viz. bulnesol, cubitene, and ß-eudesmol bound firmly to cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), as shown by the in silico analysis, similar to the positive control diclofenac. ALVCs effectively inhibited protein degradation with the IC50 of 31 ± 2.3 µg/mL and inhibited nitric oxide production with the IC50 of 43.30 ± 3.37 µg/mL. These findings showed that ALVCs might have a promising anti-inflammatory effect by blocking several inflammatory proteins.

Doping-control of excitons and magnetism in few-layer CrSBr.

Magnetism in two-dimensional materials reveals phenomena distinct from bulk magnetic crystals, with sensitivity to charge doping and electric fields in monolayer and bilayer van der Waals magnet CrI3. Within the class of layered magnets, semiconducting CrSBr stands out by featuring stability under ambient conditions, correlating excitons with magnetic order and thus providing strong magnon-exciton coupling, and exhibiting peculiar magneto-optics of exciton-polaritons. Here, we demonstrate that both exciton and magnetic transitions in bilayer and trilayer CrSBr are sensitive to voltage-controlled field-effect charging, exhibiting bound exciton-charge complexes and doping-induced metamagnetic transitions. Moreover, we demonstrate how these unique properties enable optical probes of local magnetic order, visualizing magnetic domains of competing phases across metamagnetic transitions induced by magnetic field or electrostatic doping. Our work identifies few-layer CrSBr as a rich platform for exploring collaborative effects of charge, optical excitations, and magnetism.

Mental health nurses' attitudes towards consumers with co-existing mental health and drug and alcohol problems: Adescriptive study.

WHAT IS KNOWN ON THE SUBJECT?: Dual diagnosis is one of the leading causes of disability globally. There is limited evidence on mental health nurses' attitudes towards consumers with dual diagnosis. WHAT DOES THE PAPER ADD TO EXISTING KNOWLEDGE?: Mental health nurses have positive attitudes towards consumers with dual diagnosis. A positive attitude at work is influenced by various factors, including feeling that one's role is appropriate and legitimate. This also includes receiving support in that role, being motivated to work, having confidence in completing tasks and feeling satisfied with one's job. ABSTRACT: BACKGROUND: Dual diagnosis is a global health concern. This descriptive research assessed mental health nurses' attitudes towards consumers with dual diagnosis in Australian mental health settings. The research question was: What is the attitude of mental health nurses towards consumers with co-existing mental health and drug and alcohol problems? MATERIALS AND METHODS: This cross-sectional survey included 103 mental health nurses who work with consumers with dual diagnosis. Participants were recruited from various mental health settings through convenience sampling. The Comorbidity Problems Perceptions Questionnaire was used to assess attitudes. Descriptive data and multiple regression analyses were conducted. We utilized the consensus-based checklist for reporting results of this study. RESULTS: Mental health nurses positively perceived consumers with dual diagnosis. Factors associated with a positive attitude were a higher level of work experience, feeling that one's role is adequate, perceiving one's role as legitimate, receiving increased support in one's position, having high work motivation, possessing high task-specific self-esteem and experiencing higher levels of work satisfaction. Work experience predicted role adequacy. Position predicted role support. The work sector predicted role-related self-esteem. CONCLUSIONS: As mental health nurses gain work experience; they develop positive attitudes that boost their self-esteem and sense of importance towards consumers with dual diagnosis. This constructive mindset also positively affects their work motivation and job satisfaction towards consumers with dual diagnosis. Conducting interventional studies is necessary to examine how clinical experiences, work environments, and job positions can impact attitudes, aiming to improve mental health nursing interventions towards consumers with dual diagnosis. IMPLICATIONS TO PRACTICE: The study found that mental health nurses' positive attitudes towards consumers with dual-diagnosis are influenced by their experience and knowledge. Moreover, mental health nurses who feel supported, motivated and confident in their roles are more likely to provide high-quality care to consumers with dual diagnosis. Mental health nurses could provide better care and support if they took a proactive approach and addressed the challenges associated with this consumer population. To be successful in their roles, mental health nurses require access to resources and support from healthcare organizations. As a result, their job satisfaction and attitudes towards consumers with dual diagnosis will be enhanced. In this way, consumers as well as healthcare organizations will benefit.

Neuraminidase inhibition promotes the collective migration of neurons and recovery of brain function.

In the injured brain, new neurons produced from endogenous neural stem cells form chains and migrate to injured areas and contribute to the regeneration of lost neurons. However, this endogenous regenerative capacity of the brain has not yet been leveraged for the treatment of brain injury. Here, we show that in healthy brain chains of migrating new neurons maintain unexpectedly large non-adherent areas between neighboring cells, allowing for efficient migration. In instances of brain injury, neuraminidase reduces polysialic acid levels, which negatively regulates adhesion, leading to increased cell-cell adhesion and reduced migration efficiency. The administration of zanamivir, a neuraminidase inhibitor used for influenza treatment, promotes neuronal migration toward damaged regions, fosters neuronal regeneration, and facilitates functional recovery. Together, these findings shed light on a new mechanism governing efficient neuronal migration in the adult brain under physiological conditions, pinpoint the disruption of this mechanism during brain injury, and propose a promising therapeutic avenue for brain injury through drug repositioning.