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Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medications and highlight potential targets for new drug development. Human neuronal-like (NT2-N) cells were treated with either lamotrigine, lithium, quetiapine, valproate or vehicle for 24 h. Genome-wide mRNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs with lncRNAs. Functional enrichment analysis and hub lncRNA identification was conducted on key co-expressed modules associated with the drug response. We constructed lncRNA-mRNA co-expression networks and identified key modules underlying these treatments, as well as their enriched biological functions. Processes enriched in key modules included synaptic vesicle cycle, endoplasmic reticulum-related functions and neurodevelopment. Several lncRNAs such as GAS6-AS1 and MIR100HG were highlighted as driver genes of key modules. Our study demonstrates the key role of lncRNAs in the mechanism(s) of action of BD drugs. Several lncRNAs have been suggested as major regulators of medication effects and are worthy of further investigation as novel drug targets to treat BD.

The positive transcription elongation factor b (P-TEFb) is a critical coactivator for transcription of most cellular and viral genes, including those of HIV. While P-TEFb is regulated by 7SK snRNA in proliferating cells, P-TEFb is absent due to diminished levels of CycT1 in quiescent and terminally differentiated cells, which has remained unexplored. In these cells, we found that CycT1 not bound to CDK9 is rapidly degraded. Moreover, productive CycT1:CDK9 interactions are increased by PKC-mediated phosphorylation of CycT1 in human cells. Conversely, dephosphorylation of CycT1 by PP1 reverses this process. Thus, PKC inhibitors or removal of PKC by chronic activation results in P-TEFb disassembly and CycT1 degradation. This finding not only recapitulates P-TEFb depletion in resting CD4+ T cells but also in anergic T cells. Importantly, our studies reveal mechanisms of P-TEFb inactivation underlying T cell quiescence, anergy, and exhaustion as well as proviral latency and terminally differentiated cells.

The nanoparticles of bentonite can be easily synthesized by hydrothermal treatment with microwave-assisted method. The products were characterized by XRD, FTIR, BET, SEM, EDS, and DLS. Results have revealed that the nano-bentonite was in nanometer scale with particles size of 200–300 nm. The SEM analysis of the nano-bentonite dispersion showed that a decrease in agglomeration and surface roughness. The nano-bentonite possessed high surface area (152.4 m ^2 .g ^−1 ) and pore volume (0.25 cm ^3 .g ^−1 ). Additionally, nanocomposite hydrogels (NB/PAA) were synthesized through the free-radical polymerization of acrylic acid (PAA) in the presence of the as-synthesized nano-bentonite (NB). The presence of NB in hydrogel matrix may improve the tensile strength of hydrogel. The tensile strength of the hydrogel increases from 0.294 to 1.609 MPa when NB content was 1.0% (NB10/PAA). Under the optimum conditions, the nanocomposite hydrogels (NB10/PAA) exhibited high water absorption capacity of 420.0 ${g}_{water}.{g}_{hydrogel}^{-1}.$ These findings contribute to the sustainable development and green chemistry.

Copper (I) chloride (CuCl) modified graphene oxide with different copper (Cu) content were prepared by ‘ion implantation’ method using CuCl as Cu source. The samples were characterized by x-ray Powder Diffraction-XRD, FTIR, BET, SEM, TEM, EDS and x-ray photoelectron spectroscopy-XPS. From TEM images and EDS elemental mapping, it showed the CuCl particles of 30–50 nm with high dispersion on graphene oxide surface. From XPS result, it revealed the presence of both Cu ^+ and Cu ^2+ ions but Cu ^+ ion amount was predominant. CO adsorption on CuCl modified graphene oxide with different Cu content was tested. Among tested CuCl modified GO samples, 2CuCl/GO sample exhibited the highest CO gas adsorption capacity of 2.9 mmol g ^−1 at 20 °C which was 7.5 times higher than that of pristine GO (0.38 mmol g ^−1 ). High CO adsorption performance on CuCl modified GO can be explained by the formation of π –complexation between CO molecules and Cu(I) ions. From CO adsorption on CuCl modified GO, it showed that the experimental data fit well with Langmuir- Freundlich model.

T cell antigen receptor stimulation induces tyrosine phosphorylation of downstream signaling molecules and the phosphatidylinositol, Ras, MAPK, and PI3 kinase pathways, leading to T cell activation. Previously, we reported that the G-protein-coupled human muscarinic receptor could bypass tyrosine kinases to activate the phosphatidylinositol pathway and induce interleukin-2 production in Jurkat leukemic T cells. Here, we demonstrate that stimulating G-protein-coupled muscarinic receptors (M1 and synthetic hM3Dq) can activate primary mouse T cells if PLCβ1 is coexpressed. Resting peripheral hM3Dq+PLCβ1 (hM3Dq/β1) T cells did not respond to clozapine, an hM3Dq agonist, unless they were preactivated by TCR and CD28 stimulation which increased hM3Dq and PLCβ1 expression. This permitted large calcium and phosphorylated ERK responses to clozapine. Clozapine treatment induced high IFN-γ, CD69, and CD25 expression, but surprisingly did not induce substantial IL-2 in hM3Dq/β1 T cells. Importantly, costimulation of both muscarinic receptors plus the TCR even led to reduced IL-2 expression, suggesting a selective inhibitory effect of muscarinic receptor costimulation. Stimulation of muscarinic receptors induced strong nuclear translocation of NFAT and NFκB and activated AP-1. However, stimulation of hM3Dq led to reduced IL-2 mRNA stability which correlated with an effect on the IL-2 3'UTR activity. Interestingly, stimulation of hM3Dq resulted in reduced pAKT and its downstream pathway. This may explain the inhibitory impact on IL-2 production in hM3Dq/β1T cells. Moreover, an inhibitor of PI3K reduced IL-2 production in TCR-stimulated hM3Dq/β1 CD4 T cells, suggesting that activating the pAKT pathway is critical for IL-2 production in T cells.

Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant intra-tumoral B to plasma cell differentiation in lymphoid aggregates in MBM. MBM harbored larger fractions of monocyte-derived macrophages and dysfunctional TOX+CD8+ T cells with distinct expression of immune checkpoints. This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration.

The positive transcription elongation factor b (P-TEFb) is a critical coactivator for transcription of most cellular and viral genes, including those of HIV. While P-TEFb is regulated by 7SK snRNA in proliferating cells, P-TEFb is absent due to diminished levels of CycT1 in quiescent and terminally differentiated cells, which has remained unexplored. In these cells, we found that CycT1 not bound to CDK9 is rapidly degraded. Moreover, productive CycT1:CDK9 interactions are increased by PKC-mediated phosphorylation of CycT1 in human cells. Conversely, dephosphorylation of CycT1 by PP1 reverses this process. Thus, PKC inhibitors or removal of PKC by chronic activation results in P-TEFb disassembly and CycT1 degradation. This finding not only recapitulates P-TEFb depletion in resting CD4+ T cells but also in anergic T cells. Importantly, our studies reveal mechanisms of P-TEFb inactivation underlying T cell quiescence, anergy, and exhaustion as well as proviral latency and terminally differentiated cells.

Transcription factors are key players underlying cancer formation, growth, survival, metastasis and treatment resistance, yet few drugs exist to directly target them. Here, we characterized the in vitro and in vivo anti-cancer efficacy of novel synthetic cell-penetrating peptides (Bpep and Dpep) designed to interfere with the formation of active leucine-zipper-based dimers by CEBPB and CEBPD, transcription factors implicated in multiple malignancies. Both peptides similarly promoted apoptosis of multiple tumor lines of varying origins, without such effects on non-transformed cells. Combined with other treatments (radiation, Taxol, chloroquine, doxorubicin), the peptides acted additively to synergistically and were fully active on Taxol-resistant cells. The peptides suppressed expression of known direct CEBPB/CEBPD targets IL6, IL8 and asparagine synthetase (ASNS), supporting their inhibition of transcriptional activation. Mechanisms by which the peptides trigger apoptosis included depletion of pro-survival survivin and a required elevation of pro-apoptotic BMF. Bpep and Dpep significantly slowed tumor growth in mouse models without evident side effects. Dpep significantly prolonged survival in xenograft models. These findings indicate the efficacy and potential of Bpep and Dpep as novel agents to treat a variety of cancers as mono- or combination therapies.

Staphylococcus aureus is a major human pathogen that causes a wide range of infections by producing an arsenal of cytotoxins. We found that passive immunization with either a monoclonal antibody (MAb) neutralizing alpha-hemolysin or a broadly cross-reactive MAb neutralizing Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysins HlgAB and HlgCB conferred only partial protection, whereas the combination of those two MAbs conferred significant protection in a rabbit model of necrotizing pneumonia caused by the USA300 methicillin-resistant S. aureus epidemic clone.

Pseudomonas aeruginosa is a challenge for clinicians due to increasing drug resistance and dwindling treatment options. We report on the activity of MEDI3902, an antibody targeting type 3 secretion protein PcrV and Psl exopolysaccharide, in rabbit bloodstream and lung infection models. MEDI3902 prophylaxis or treatment was protective in both acute models and exhibited enhanced activity when combined with a subtherapeutic dose of meropenem. These findings further support MEDI3902 for the prevention or treatment of serious P. aeruginosa infections.

The Malaria Box collection includes 400 chemically diverse small molecules with documented potency against malaria parasite growth, but the underlying modes of action are largely unknown. Using complementary phenotypic screens against Plasmodium falciparum and Toxoplasma gondii, we report phenotype-specific hits based on inhibition of overall parasite growth, apicoplast segregation, and egress or host invasion, providing hitherto unavailable insights into the possible mechanisms affected. First, the Malaria Box library was screened against tachyzoite stage T. gondii and the half-maximal effective concentrations (EC50s) of molecules showing ≥80% growth inhibition at 10 µM were determined. Comparison of the EC50s for T. gondii and P. falciparum identified a subset of 24 molecules with nanomolar potency against both parasites. Thirty molecules that failed to induce acute growth inhibition in T. gondii tachyzoites in a 2-day assay caused delayed parasite death upon extended exposure, with at least three molecules interfering with apicoplast segregation during daughter cell formation. Using flow cytometry and microscopy-based examinations, we prioritized 26 molecules with the potential to inhibit host cell egress/invasion during asexual developmental stages of P. falciparum. None of the inhibitors affected digestive vacuole integrity, ruling out a mechanism mediated by broadly specific protease inhibitor activity. Interestingly, five of the plasmodial egress inhibitors inhibited ionophore-induced egress of T. gondii tachyzoites. These findings highlight the advantage of comparative and targeted phenotypic screens in related species as a means to identify lead molecules with a conserved mode of action. Further work on target identification and mechanism analysis will facilitate the development of antiparasitic compounds with cross-species efficacy. IMPORTANCE The phylum Apicomplexa includes many human and animal pathogens, such as Plasmodium falciparum (human malaria) and Toxoplasma gondii (human and animal toxoplasmosis). Widespread resistance to current antimalarials and the lack of a commercial vaccine necessitate novel pharmacological interventions with distinct modes of action against malaria. For toxoplasmosis, new drugs to effectively eliminate tissue-dwelling latent cysts of the parasite are needed. The Malaria Box antimalarial collection, managed and distributed by the Medicines for Malaria Venture, includes molecules of novel chemical classes with proven antimalarial efficacy. Using targeted phenotypic assays of P. falciparum and T. gondii, we have identified a subset of the Malaria Box molecules as potent inhibitors of plastid segregation and parasite invasion and egress, thereby providing early insights into their probable mode of action. Five molecules that inhibit the egress of both parasites have been identified for further mechanistic studies. Thus, the approach we have used to identify novel molecules with defined modes of action in multiple parasites can expedite the development of pan-active antiparasitic agents.

Previous studies with mice lacking secreted IgM (sIgM) due to a deletion of the μs splice region (μs-/- ) had shown sIgM involvement in normal B cell development and in support of maximal Ag-specific IgG responses. Because of the changes to B cell development, it remains unclear to which extent and how sIgM directly affects B cell responses. In this study, we aimed to explore the underlying mechanisms of sIgM-mediated IgG response regulation during influenza virus infection. Generating mice with normally developed μs-deficient B cells, we demonstrate that sIgM supports IgG responses by enhancing early Ag-specific B cell expansion, not by altering B cell development. Lack of FcμR expression on B cells, but not lack of Fcα/μR expression or complement activation, reduced antiviral IgG responses to the same extent as observed in μs-/- mice. B cell-specific Fcmr-/- mice lacked robust clonal expansion of influenza hemagglutinin-specific B cells early after infection and developed fewer spleen and bone marrow IgG plasma cells and memory B cells, compared with controls. However, germinal center responses appeared unaffected. Provision of sIgM rescued plasma cell development from μs-/- but not Fcmr-/- B cells, as demonstrated with mixed bone marrow chimeric mice. Taken together, the data suggest that sIgM interacts with FcμR on B cells to support early B cell activation and the development of long-lived humoral immunity.

The FcμR receptor for the crystallizable fragment (Fc) of immunoglobulin M (IgM) can function as a cell-surface receptor for secreted IgM on a variety of cell types. We found here that FcμR was also expressed in the trans-Golgi network of developing B cells, where it constrained transport of the IgM-isotype BCR (IgM-BCR) but not of the IgD-isotype BCR (IgD-BCR). In the absence of FcμR, the surface expression of IgM-BCR was increased, which resulted in enhanced tonic BCR signaling. B-cell-specific deficiency in FcμR enhanced the spontaneous differentiation of B-1 cells, which resulted in increased serum concentrations of natural IgM and dysregulated homeostasis of B-2 cells; this caused the spontaneous formation of germinal centers, increased titers of serum autoantibodies and excessive accumulation of B cells. Thus, FcμR serves as a critical regulator of B cell biology by constraining the transport and cell-surface expression of IgM-BCR.

Most serum immunoglobulin M (IgM) is "natural IgM", which is produced apparently spontaneously by a distinct subset of B cells requiring no exogenous antigenic or microbial stimuli. Natural IgM is an evolutionarily conserved molecule and reacts with a variety of epitopes expressed on both self- and non-self antigens. It has long been understood that secreted (s) IgM contributes to the removal of altered self-antigens, such as apoptotic and dying cells. As we outline in this review, it is thought that this sIgM housekeeping function removes potential triggers of autoresponse induction. However, we recently demonstrated an unexpected and distinct role for sIgM in the control of autoreactive B cells: the regulation of bone marrow B cell development. The absence of sIgM blocked pro- to pre- B-cell transition and greatly altered the BCR repertoire of the developing B cells and the peripheral B-cell pools in genetically engineered mice. This finding strongly suggests that IgM is critical for B-cell central tolerance induction. Given that treatment of sIgM-deficient mice with polyclonal IgM corrected these developmental defects, therapeutic application of IgM could be of clinical relevance in the treatment of some B-cell-mediated autoimmune diseases.

Mouse B-1 cells are not only major producers of steady-state natural antibodies but also rapid responders to infections and inflammation. These discrete functions may be the outcomes of distinct environmental or developmental triggers that drive B-1 cells toward IgM production or an effector cell fate. Alternatively, distinct B-1 cell subsets may exist, which differ in their functional plasticity. In this paper, we summarize existing data suggesting that B-1 cells form a heterogeneous group of cells with distinct developmental requirements and nonoverlapping functions. Most spleen B-1 cells differ in development from that of bone marrow and peritoneal cavity B-1 cells, in that they develop in the absence of natural IgM. Functional heterogeneity is revealed by findings that B-1 cells in the bone marrow and spleen, but not the peritoneal cavity, generate natural serum IgM, while the latter are rapid responders to inflammatory and infectious insults, resulting in their relocation to secondary lymphoid tissues. A clearer understanding of the developmental and functional differences within the B-1 cell pool may reveal how they might be harnessed for prophylaxis or therapy.

It is unclear why selective deficiency in secreted (s)IgM causes Ab-mediated autoimmunity. We demonstrate that sIgM is required for normal B cell development and selection. The CD5(+) B cells that were previously shown to accumulate in body cavities of sIgM(-/-) mice are not B-1a cells, but CD19(int), CD43(-), short-lived, BCR signaling-unresponsive anergic B-2 cells. Body cavity B-1 cells were >10-fold reduced, including VH11(+) and phosphotidylcholine-specific B-1a cells, whereas splenic B-1 cells were unaffected and marginal zone B cells increased. Follicular B cells had higher turnover rates, survived poorly after adoptive transfer, and were unresponsiveness to BCR stimulation in vitro. sIgM bound to B cell precursors and provided a positive signal to overcome a block at the pro/pre-B stage and during IgVH repertoire selection. Polyclonal IgM rescued B cell development and returned autoantibody levels to near normal. Thus, natural IgM deficiency causes primary autoimmune disease by altering B cell development, selection, and central tolerance induction.

Abstract Background Jars, tanks, and drums provide favorable rearing/breeding sites for Aedes aegypti in Vietnam. However, the use of insecticides to control mosquitoes at such breeding sites has not been approved in Vietnam since they are also often sources of drinking water, making larval vector control difficult. Mosquito nets pre-treated with long-lasting insecticide treated nets (LLITNs) form an effective measure for malaria control. We examined changes in the abundance of immature Aedes aegypti to evaluate the efficacy of covering ceramic jars with lids comprising one type of LLITN, Olyset® Net, in inhibiting oviposition by adult females, and to evaluate the effect of treating other breeding containers, such as flower vases, inside and around the outside of houses with a slow-release pyriproxyfen formulation to kill pupae. Methods We selected 313 households for the trial and 363 households for the control in Tan Chanh, Long An province, Vietnam. In the trial area, Olyset® Net lids were used to cover five major types of water container (ceramic jars, cylindrical concrete tanks, other concrete tanks, plastic drums, and plastic buckets), while pyriproxyfen was used to treat flower vases and ant traps. We also monitored dengue virus transmission by measuring anti-dengue IgM and IgG levels in healthy residents in both control and trial areas to estimate the effectiveness of Olyset® Net at controlling the dengue vector, Aedes aegypti. Results The container-index and house-index for immature Ae. aegypti fell steeply one month after treatment in the trial area. Lids with Olyset® Net that fit container openings clearly seemed to reduce the presence of immature Ae. aegypti as the density of pupae decreased 1 month after treatment in the trial area. Pyriproxyfen was also effective at killing pupae in the water containers in the trial area. Although the dengue seroconversion rate was not influenced by Olyset® Net, it was lower in two-five year old children when compared to older children and adults in both control and trial areas. Conclusions Our study showed that the treatment by Olyset® Net and pyriproxyfen had a strong negative effect on the prevalence of immature Ae. aegypti, which persisted for at least 5 months after treatment.

AbstractObjectivesMethodsResultsConclusionsFocal adhesions and their dynamic nature are essential for various physiological processes, including the formation of neurites, synaptic function and plasticity. Alterations in these processes have been associated with schizophrenia and bipolar disorder.This study aimed to explore the impact of pharmacological treatments used for bipolar disorder and schizophrenia on the expression of genes involved in the focal adhesion pathway, addressing a gap in understanding the interaction between medication effects and disease pathophysiology.NT2-N (neuron-like) cells were exposed to treatment with amisulpride, aripiprazole, chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone, or vehicle for 24 h. Genome-wide mRNA expression was analysed using gene set enrichment analysis.The analysis revealed that seven out of the eight drugs widely prescribed for bipolar disorder and schizophrenia downregulate the expression of genes associated with the focal adhesions pathway. Focal adhesion was the pathway with the most negative normalised enrichment score across all treatments.Our results support the hypothesis that focal adhesion pathways may play a role in the pathophysiology of bipolar disorder and schizophrenia. Moreover, the data underscore the importance of differentiating medication effects from disease mechanisms in psychiatric research, a challenge compounded by the medicated state of most study participants. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hemodynamic factors significantly influence the onset, progression, and rupture of intracranial aneurysms (IAs). Current rupture risk prediction scores focus primarily on the clinical, anatomic, and morphologic aspects. This study aimed to investigate the hemodynamic characteristics differences between ruptured and unruptured IAs., Materials and Methods: Conducted from July 2021 to July 2022, this prospective cohort study involved patients with ruptured and unruptured IAs undergoing DSA. Hemodynamic characteristics were assessed by using the AneurysmFlow tool. Hemodynamic, clinical, anatomic, and morphologic parameters were compared between ruptured and unruptured IA groups., Results: The study included 127 patients with 135 aneurysms (67 ruptured, 68 unruptured). Complex flow patterns (type 3 and 4) were observed more frequently in ruptured aneurysms compared with unruptured aneurysms (OR, 5.57; 95% CI, 2.49-12.45; P < .001) in univariate analysis, and were also more common in unruptured aneurysms associated with daughter sac features ( P = .015). The mean aneurysm flow amplitude (MAFA) was lower in ruptured aneurysms, and associated with lower flow velocity in the parent artery related to vasospasm. MAFA in the aneurysmal dome or any additional daughter sacs was lowest compared with other regions inside the aneurysms. The technical failure rate of AneurysmFlow measurements was 8.5% (12 of 139 patients). Additionally, hypertension (OR, 0.42; 95% CI, 0.30-0.54; P < .001), bifurcation location (anterior communicating artery/anterior cerebral artery/MCA/posterior communicating artery/posterior circulation) (OR, 0.17; 95% CI, 0.05-0.29; P = .005), and irregular shape (OR, 0.19; 95% CI, 0.05-0.35; P = .012) were identified as independently associated with rupture., Conclusions: Complex flow patterns identified on the AneurysmFlow tool are significantly more common in ruptured and unruptured aneurysms associated with daughter sac features. The lowest MAFA in the aneurysmal dome and daughter sacs likely indicates specific pathophysiologic changes within the aneurysm wall associated with rupture incidence. Hypertension, bifurcation location, and an irregular shape are independently associated with the risk of rupture. Further multicenter studies with larger sample sizes are needed to validate these findings., (© 2025 by American Journal of Neuroradiology.)

Background: Pre-exposure prophylaxis with tixagevimab-cilgavimab significantly reduced severe COVID-19 outcomes in high-risk individuals during the pre-Omicron era (PROVENT trial). However, efficacy in patients with haematological malignancies (HM) was underreported. The rapid emergence of Omicron strains in 2021 showed reduced neutralizing activity in preclinical data, but real-world data remains limited due to short follow-up., Patients and Methods: We aimed to evaluate the effectiveness and safety of tixagevimab-cilgavimab in 86 HM patients during the early Omicron wave, including the BA.2, BA.5, and XBB.1 sublineages. These patients received PrEP between February and August 2022 due to impaired vaccine response (72%) and B-cell depletion (46.5%). They were followed prospectively until April 2023, with a median follow-up of 297 days., Results: Breakthrough SARS-CoV-2 infections occurred in 32.6% of patients, with 22.1% within six months. Infections within six months were milder and shorter. B-cell depletion within six (p = 0.035) and twelve months (p = 0.016) was identified as risk factor for breakthrough infections. No new safety events were reported., Conclusion: Our data showed that tixagevimab-cilgavimab prophylaxis effectively reduces severe COVID-19 outcomes in patients with HM, particularly within the first six months, even during the Omicron era. However, those with recent B-cell depletion (within 12 months) remained at high risk., (© 2025 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Objectives: To determine the additional detection rate (DR) and the residual risk (RR) of combined cell-free DNA (cfDNA) screening for aneuploidies (not including copy number variants) and 25 dominant single-gene disorders (SGD) in pregnancies with sonographic abnormalities., Method: One hundred sixteen singleton pregnant women with abnormal fetal ultrasounds from week 12 were included in the study. They underwent combined cfDNA analysis, while exome sequencing and karyotyping were performed as reference standards. The results of the cfDNA analysis were compared with diagnostic genetic tests., Results: The positive rate of cfDNA analysis was 15/116 (12.9%), with a positive predictive value of 13/15 (86.7%). The incremental DR of combined cfDNA screening for aneuploidies and 25 SGD compared with cfDNA testing for aneuploidies in fetuses with sonographic anomalies was 22.9%. The RR of cfDNA analysis for aneuploidies and pathogenic/likely pathogenic gene variants, after excluding cfDNA testing-detectable findings, was 2/101 (2.0%). The DR of cfDNA analysis for genetic aberrations in pregnancies with abnormal ultrasound was 13/35 (37.1%) compared with diagnostic testing., Conclusion: In fetuses with sonographic anomalies, the additional DR of combined cfDNA analysis for aneuploidies and 25 SGD was remarkable at 22.9% compared with cfDNA testing for aneuploidies; the overall RR of combined cfDNA analysis was approximately 2.0%. It is essential to provide detailed genetic counseling before using cfDNA analysis in these pregnancies., (© 2024 John Wiley & Sons Ltd.)

The purpose of this study was to investigate the application of an innovative extrusion-based 3D food printing (3DFOODP) technique in developing rice protein-starch (RP-S) gel-based products. The effects of 3DFOODP conditions were examined, which included variations in the concentrations of rice protein (RP) and corn starch (S) (15, 17.5, and 20 wt.%), nozzle size (0.8, 1.5, and 2.5 mm), printing temperature (40°C, 60°C, and 80°C), and ingredient flow speed (5.7, 6.3, and 6.9 mL/min). A hollow cylindrical model was chosen as a test object to determine the printability of RP-S gels. The best 3D printability was achieved using an RP concentration of 17.5% and an S concentration of 15% at 60°C printing temperature with a nozzle size of 1.5 mm, and ingredient flow speed of 6.3 mL/min. With increasing the RP concentration, a rise in apparent viscosity, loss, and storage moduli was observed. The recovery test showed the gels' rapid and reversible response. The freeze-dried 3D-printed RP-S gels showed a porous granular structure, depending on the printing temperature. No chemical interactions between the RP and S were observed as analyzed by FTIR. Overall, RP, in combination with S, provides a new opportunity for the 3DFOODP and their utilization by the alternative protein industry., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Introduction: No longitudinal study has investigated the impact of cigarette tax increases on retail prices in Vietnam. This study aims to describe changes in the purchase price of cigarettes following an excise tax increase from 70% to 75% in January 2019., Methods: Data were collected from people who currently smoke cigarettes in the longitudinal ITC Vietnam surveys: 1870 participants in Wave 1 (pre-increase), 1564 in Wave 2 (post-increase), and 1308 in Wave 3 (post-increase). Weighted mean self-reported prices of a cigarette pack (with standard error) were calculated for participants who were successfully followed up across three waves. These mean prices were calculated for domestic and international brands, categorized by specific cigarette brands. Percentage changes in mean prices were also measured, and significant differences in mean prices between follow-up waves (Waves 2 and 3) and the baseline (Wave 1) were assessed using paired t-tests. For brands with very small sample sizes, we used non-parametric tests, specifically the Wilcoxon signed-rank test instead of paired t-tests., Results: The weighted mean price of a cigarette pack remained low and stable: VND 12330 (US$0.54) in 2018, VND 12700 (US$0.55) in 2019, and VND 12120 (US$0.53) in 2020 (1000 Vietnamese Dongs about US$0.04345, at 2018). International brands were substantially more expensive than domestic brands, but prices for both remained constant across all waves. Among domestic brands, Thang Long and Sai Gon showed slight price increases of around 3% and 5%, respectively (p<0.05). Among international brands, no statistically significant increase in mean prices was observed., Conclusions: The retail price of cigarettes remains low, indicating that the slight tax increase was insufficient to raise the current retail price significantly. Therefore, a substantial increase in cigarette prices by adding a specific tax is necessary., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Tran T.P.T. et al.)

Introduction: Shortage of ear, nose, and throat specialists in public hospitals can result in delays in the detection and management of otitis media. This study introduced a new hospital-based telehealth service, named the Ear Portal, and investigated its role in improving access to specialist care., Methods: The study included 87 children (aged 6 months to 6 years) referred to a tertiary children's hospital due to otitis media-related concerns. A specialist multidisciplinary team met fortnightly to review pre-recorded data and provide care plans., Results: The service resulted in a median waiting time of 28 days to receive a diagnosis and care plan by the multidisciplinary team, compared to a mean waiting time of 450 days for a reference group receiving standard healthcare services. Most children (90.3%) received bilateral ear diagnosis. Normal findings were found in 43.9%. However, the majority required further ear, nose, and throat with or without audiology face-to-face follow-up due to a diagnosis of middle-ear disease, unknown hearing status, or concerns not related to ears. The mean time required for clinical assessments completion by research assistants and multidisciplinary team review was 37.6 and 5.1 min per participant, respectively., Discussion: Children in the Ear Portal service received a diagnosis and care plan in a median of 28 days, which is within the clinically recommended timeframes. With sufficient clinical information, this service can provide faster access to specialist care than the standard healthcare pathway. The service can reduce the time required by the specialist to provide a diagnosis and care plan which may help increase the specialists' capacity., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intussusception is a common pediatric emergency that causes significant morbidity and mortality, particularly in low- to middle-income countries. The laparoscopic management of intussusception following failed non-invasive methods remains a topic of debate. This study aims to evaluate the long-term outcomes of minimally invasive approaches for intussusception. A retrospective analysis was conducted on patients who underwent minimally invasive surgery for intussusception between January 2016 and December 2020 at our institution. Data on patient demographics, pre-operative and intra-operative variables, immediate postoperative complications, length of hospital stay, and long-term results were collected. A total of 181 patients underwent minimally invasive surgery, including 117 boys (64.6%) and 64 girls (35.4%), with a median age of 8 months (range: 2-134). The median hospital stay was 4 days. Thirty-nine patients underwent trans-umbilical mini-open reduction (MO group), while 142 had laparoscopic exploration after failed air enema reduction. Among them, 40 had successful laparoscopic reduction (LAP group), and 102 required conversion to laparoscopic-assisted mini-open reduction (LAMO group). No intra-operative or immediate postoperative complications were observed. Recurrence occurred in 13 patients (7.2%) after a median follow-up of 43 months, with 6 patients (3.3%) requiring laparoscopic adhesiolysis due to bowel adhesions. In conclusion, minimally invasive surgery for intussusception is a safe and feasible approach with excellent long-term outcomes., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Seeing portrayals of tobacco and alcohol in music videos (MVs) may reduce perceived risks, increase susceptibility, and lead to the initiation of tobacco and alcohol use among adolescents and young adults. Previous studies have predominantly concentrated on assessing tobacco and alcohol contents in English-language MVs within Western countries. However, many other countries have not only been influenced by the English music market but have also produced music in their native languages, and this content remains underexamined., Objective: This study aims to investigate the prevalence of tobacco- and alcohol-related content in top Vietnamese MVs on YouTube from 2013 to 2021, to describe how tobacco and alcohol are portrayed in these MVs, and to examine associations between these portrayals and MV characteristics., Methods: A total of 410 Vietnamese MVs, including the top 40 or 50 most viewed released each year between 2013 and 2021, were analyzed. General information, such as the song name, its release date and ranking, age restriction, musical genre, and type of MV, was collected. We examined tobacco and alcohol content in the MVs, with specific details such as tobacco types, their brands, as well as the number, age, sex, and roles of individuals smoking or drinking., Results: Among the 410 MVs, 36 (8.8%) contained tobacco-related content and 136 (33.2%) featured alcohol-related content. Additionally, 28 (6.8%) out of 410 MVs included both tobacco and alcohol content. The prevalence of videos with tobacco and alcohol content fluctuated over the years. In MVs with tobacco-related content, a higher proportion of hip-hop or rap songs contained tobacco-related content (n=6, 30%) compared to other music genres. In MVs with tobacco-related content, cigarettes were the most frequently shown product (n=28, 77.8%), and smoking scenes were often depicted at parties (n=13, 36.1%) and during dancing and singing scenes (n=12, 33.3%). Among the 31 MVs portraying actual tobacco use, tobacco use was typically depicted with 1 person, often a young adult male, while 38.7% (n=12) showed singer(s) smoking. For MVs with alcohol-related content, there was a high proportion showing alcohol images at parties, bars, or pubs (n=96, 70.6%). Among 87 MVs containing drinking scenes, 60.9% (n=53) involved groups of young adults of both sexes, and 64% (n=56) depicted singers drinking. Additionally, only 2 (5.6%) MVs included health warnings about tobacco harm, and 2 MVs (1.5%) included warnings about drinking restricted to individuals 18 years and above., Conclusions: The notable prevalence of tobacco and alcohol content in leading Vietnamese YouTube MVs raises concerns, especially as most of this content is portrayed without any warnings. The study underscores a regulatory gap in addressing such content on the internet, emphasizing the urgent need for stricter regulations and age restrictions on platforms such as YouTube., (©Thi Phuong Thao Tran, Thu Trang Vu, Yachao Li, Lucy Popova. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.11.2024.)

Women living with HIV/AIDS (WLHA) encounter numerous challenges, such as stigma and gender disparities, that hinder their access to care, especially in patriarchal societies like Vietnam. We developed a hybrid intervention with online and offline (in-person) components to empower WLHA in Vietnam. The intervention was pilot tested with 91 WLHA in Hanoi. During baseline and 4-month, study investigators delivered two in-person sessions, one Zoom session, and 15 weeks of Zalo (social media platform) discussions to enhance positive coping strategies, treatment utilization and adherence, and engagement of support from family and peers. The participants continued their Zalo discussions from 4-month to 6-month without investigators' involvement. Intervention outcomes, including active coping and perceived barriers to care, were evaluated at baseline, 4-, and 6-month surveys. Mixed-effects regression models showed that the participants' active coping significantly increased from baseline (50.5 ± 9.4) to 4-month (53.8 ± 6.2; p = 0.0001), although there was a slight decrease at 6-month (52.8 ± 7.2), the change from 4-month to 6-month was not significantly significant (p = 0.3256). There was a significant reduction in participants' perceived barriers to care, from 19.8 ± 5.2 at baseline to 17.4 ± 5.2 at 4-month (p < 0.0001), which remained stable at 17.8 ± 4.3 at 6-month (p < 0.0001 compared to baseline). This intervention presents a promising model to empower WLHA in Vietnam and potentially in similar global contexts. Future interventions could benefit from leveraging natural peer leaders and adopting a more person-centered approach to meet WLHA's varying needs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Women living with HIV/AIDS (WLHA) in Vietnam encounter challenges stemming from HIV-related stigma and gender disparities. This study delves into the intersectionality of HIV-related stigma and gender disparities as perceived by WLHA. A cross-sectional survey was conducted among 91 WLHA in Hanoi, Vietnam. Two sets of identically worded scales were used to measure awareness, agreement, and application of stigma towards people living with HIV/AIDS (PLHA) and WLHA. A larger difference between stigma scores towards WLHA and that of PLHA represents a higher level of female-specific stigma. Univariate analyses and multiple regressions were conducted to identify demographic and psycho-social factors associated with the gendered differences in stigma measures. Multiple linear regression showed that WLHA who were currently married were more likely to apply stigma concepts to themselves due to gender identity (adjusted beta coefficient (aBeta Coef) = 0.223). Psychological capital was negatively associated with awareness of stigma towards female identity (aBeta Coef = -0.261). A higher perceived norm in women's equity and power was associated with less self-application of female-specific stigma (aBeta Coef = -0.294). Our findings underscore the importance of addressing psychological well-being and promoting gender equity norms as essential components in the efforts to reduce female-specific HIV-related stigma in WLHA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microbial exopolysaccharides (EPSs) are receiving growing interest today, owing to their diversity in chemical structure and source, multiple functions, and immense potential applications in many food and non-food industries. Their health-promoting benefits for humans deserve particular attention because of their various biological activities and physiological functions. The aim of this paper is to provide a comprehensive review of microbial EPSs, covering (1) their chemical and biochemical diversity, including composition, biosynthesis, and bacterial sources belonging mainly to lactic acid bacteria (LAB) or probiotics; (2) their technological and analytical aspects, especially their production mode and characterization; (3) their biological and physiological aspects based on their activities and functions; and (4) their current and future uses in medical and pharmaceutical fields, particularly for their prebiotic, anticancer, and immunobiotic properties, as well as their applications in other industrial and agricultural sectors.

In this work, ZnO nanoplates and Fe 2 O 3 nanospindles were successfully fabricated via a simple hydrothermal method using inorganic salts as precursors. The ZnO/Fe 2 O 3 hybrid was fabricated using a mechanical mixture of two different ZnO : Fe 2 O 3 weight ratios to investigate the effect of weight ratio on catalytic properties. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images showed that ZnO nanoplates (NPls) are about 20 nm thick with lateral dimensions of 100 × 200 nm, and Fe 2 O 3 nanospindles (NSs) are about 500 nm long and 50 nm wide. X-ray diffraction (XRD) patterns revealed the successful formation of the ZnO, Fe 2 O 3 , and ZnO/Fe 2 O 3 samples and indicated that their crystallite sizes varied from 20 to 29 nm depending on the ZnO : Fe 2 O 3 weight ratio. Ultraviolet-visible (UV-vis) spectra showed that the bandgap energies of ZnO and Fe 2 O 3 were 3.15 eV and 2.1 eV, respectively. Energy dispersive X-ray spectroscopy (EDS) results revealed the successful combination of ZnO and Fe 2 O 3 . Photocatalytic activity of the materials was evaluated through the degradation of methylene blue (MB) in aqueous solution under green light-emitting diode (GLED) irradiation. The results indicated that the ZnO/Fe 2 O 3 composite showed a remarkable enhanced degradation capacity compared to bare ZnO NPls and Fe 2 O 3 NSs. The ZnO : Fe 2 O 3 = 3 : 2 sample demonstrated the best performance among all samples under identical conditions with a degradation efficiency of 99.3% for MB after 85 min. The optimum photocatalytic activity of the sample with ZnO : Fe 2 O 3 = 3 : 2 was nearly 3.6% higher than that of the pure ZnO sample and 1.12 times more than that of the pristine Fe 2 O 3 sample. Moreover, the highest photo-degradation was obtained at a photocatalyst dosage of 0.25 g l -1 in dye solution., Competing Interests: The authors declare that they have no competing financial interests in this paper., (This journal is © The Royal Society of Chemistry.)

Objective: Many clinicians are unfamiliar with a diagnosis of lacertus syndrome (LS). We investigated the value of the lacertus notch sign in diagnosing LS., Methods: We included 56 consecutive patients (112 upper extremities) who had neuropathic pain and neurological symptoms of the hand. The presence of LS and the lacertus notch sign in each upper extremity was assessed., Results: Of the 83 upper extremities with LS, 54 (65.1%) had a lacertus notch sign, whereas 29 (34.9%) did not. Of the 29 upper extremities without LS, 9 (31.0%) and 20 (69.0%) had and did not have a lacertus notch sign, respectively. The rates of lacertus notch presence in upper extremities with and without LS were significantly different. Of the 63 upper extremities with a lacertus notch sign, 54 (85.7%) were diagnosed with LS, whereas 9 (14.3%) were not. Of the 49 upper extremities without a lacertus notch sign, 20 (40.8%) were diagnosed with LS, and 29 (59.2%) were not. We observed significant differences in the rates of LS in upper extremities with and without lacertus notch., Conclusions: The presence of the lacertus notch sign is useful for diagnosing LS. When patients with neuropathic pain and neurological symptoms present with a lacertus notch sign, clinicians should consider the possibility of LS., (© 2024 World Institute of Pain.)

Bacterial exopolysaccharides (EPS) are biopolymers of carbohydrates, often released from cells into the extracellular environment. Due to their distinctive physicochemical properties, biocompatibility, biodegradability, and non-toxicity, EPS finds applications in various industrial sectors. However, the need for alternative EPS has grown over the past few decades as lactic acid bacteria's (LAB) low-yield EPS is unable to meet the demand. In this case, rhizosphere bacteria with the diverse communities in soil leading to variations in composition and structure, are recognized as a potential source of EPS applicable in various industries. In addition, media components and cultivation conditions have an impact on EPS production, which ultimately affects the quantity, structure, and biological functions of the EPS. Therefore, scientists are currently working on manipulating bacterial EPS by developing cultures and applying abiotic and biotic stresses, so that better production of exopolysaccharides can be attained. This review highlights the composition, biosynthesis, and effects of environmental factors on EPS production along with the potential applications in different fields of industry. Ultimately, an overview of potential future paths and tactics for improving EPS implementation and commercialization is pointed out., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Three-dimensional cell spheroids show promise for the reconstruction of native tissues. Herein, we report a sophisticated, uniform, and highly reproducible spheroid culture system for tissue reconstruction. A mesh-integrated culture system was designed to precisely control the uniformity and reproducibility of spheroid formation. Furthermore, we synthesized hexanoyl glycol chitosan, a material with ultralow cell adhesion properties, to further improve spheroid formation efficiency and biological function. Our results demonstrate improved biological function in various types of cells and ability to generate spheroids with complex structures composed of multiple cell types. In conclusion, our spheroid culture system offers a highly effective and widely applicable approach to generating customized spheroids with desired structural and biological features for a variety of biomedical applications., (Creative Commons Attribution license.)

CuCoFe-LDO/BCD was successfully synthesized from CuCoFe-LDH and biochar derived from durian shell (BCD). Ciprofloxacin (CFX) degraded more than 95% mainly by O 2 •- and 1 O 2 in CuCoFe-LDO/BCD(2/1)/PMS system within 10 min with a rate constant of 0.255 min -1 , which was 14.35 and 2.66 times higher than those in BCD/PMS and CuCoFe-LDO/PMS systems, respectively. The catalytic system exhibited good performance over a wide pH range (3-9) and high degradation efficiency of other antibiotics. Built-in electric field (BIEF) driven by large difference in the work function/Fermi level ratio between CuCoFe-LDO and BCD accelerated continuous electron transfer from CuCoFe-LDO to BCD to result in two different microenvironments with opposite charges at the interface, which enhanced PMS adsorption and activation via different directions. As a non-radical, 1 O 2 was mainly generated via PMS activation by C=O in BCD. The presence of C=O in BCD resulted in an increase in atomic charge of C in C=O and redistributed the charge density of other C atoms. As a result, strong adsorption of PMS at C atom in C=O and other C with a high positive charge was favorable for 1 O 2 generation, whereas an enhanced adsorption of PMS at negatively charged C accounted for the generation of • OH and SO 4 •- . After adsorption, electrons in C of BCD became deficient and were fulfilled with those transferred from CuCoFe-LDO driven by BIEF, which ensured the high catalytic activity of CuCoFe-LDO/BCD. O 2 •- , on the other hand, was generated via several pathways that involved in the transformation of • OH and SO 4 •- originated from PMS activation by the transition of metal species in CuCoFe-LDO and negatively charged C in BCD. This study proposed a new idea of fabricating a low-cost metal-LDH and biomass-derived catalyst with a strong synergistic effect induced by BIEF for enhancing PMS activation and antibiotic degradation., 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.)

Phosphate-solubilising fungi (PSF) are beneficial microorganisms that play a pivotal role in plant growth by increasing the availability of phosphorus (P) in soil. Although phosphorus is an essential nutrient for plants, it often becomes inaccessible as it binds into insoluble forms. PSF effectively facilitate the release of this bound phosphorus through diverse mechanisms. Numerous fungal species demonstrate the ability to solubilise various types of phosphate compounds. Among the commonly researched PSF are Penicillium, Aspergillus, Rhizopus, Fusarium, Trichoderma, and Sclerotium. Moreover, yeasts such as Saccharomyces cerevisiae can potentially be leveraged as PSF. PSF secrete organic acids that chelate phosphate ions, thereby increasing their solubility in the soil. Moreover, PSF contribute to the decomposition of organic phosphorus compounds in soil by employing enzymes such as phosphatases, phytases, and phosphonatases. Furthermore, PSF can interact with other soil microorganisms, including nitrogen-fixing bacteria and arbuscular mycorrhizal fungi (AM-fungi), fostering synergistic effects that further enhance plant growth and nutrient absorption. The utilisation of PSF as biofertilisers offers numerous advantages over chemical fertilisers, including environmental friendliness, cost-effectiveness, and enhanced fertiliser utilisation efficiency. Furthermore, PSF can prove beneficial in challenging environments characterised by high phosphate sorption. Hence, this review serves as an updated study aimed at broadening the understanding of PSF and its potential applications in P solubilisation. This review also focuses on the diversity of PSF, the mechanisms underlying solubilisation, ecological roles of PSF in soil microbiome, and the benefits of sustainable agriculture. By delving into the ecological roles of PSF and their potential as biofertilisers, this study contributes to a deeper understanding of sustainable agriculture practices and addresses challenges in phosphate-scarce environments., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Two BODIPY-C 60 -peptide assemblies were synthesized by CuAAC reactions of BODIPY-C 60 dyads and a helical peptide functionalized with a terminal alkyne group and an azide group, respectively. The helical peptide within these assemblies was functionalized at its other end by a disulfide group, allowing formation of self-assembled monolayers (SAMs) on gold surfaces. Characterizations of these SAMs, as well as those of reference molecules (BODIPY-C 60 -alkyl, C 60 -peptide and BODIPY-peptide), were carried out by PM-IRRAS and cyclic voltammetry. BODIPY-C 60 -peptide SAMs are more densely packed than BODIPY-C 60 -alkyl and BODIPY-peptide based SAMs. These findings were attributed to the rigid peptide helical conformation along with peptide-peptide and C 60 -C 60 interactions within the monolayers. However, less dense monolayers were obtained with the target assemblies compared to the C 60 -peptide, as the BODIPY entity likely disrupts organization within the monolayers. Finally, electron transfer kinetics measurements by ultra-fast electrochemistry experiments demonstrated that the helical peptide is a better electron mediator in comparison to alkyl chains. This property was exploited along with those of the BODIPY-C 60 dyads in a photo-current generation experiment by converting the resulting excited and/or charge separated states from photo-illumination of the dyad into electrical energy., (© 2024 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)