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Heavy metal (HM) pollution in soils and sediment is a significant concern, yet its levels and ecological risks in peatland areas remain unexplored. This study evaluates these aspects in three peatland regions of the Long An province in Vietnam. Comparisons of HM concentrations in peatland sediments from Tan Thanh, Thanh Hoa, and Duc Hue provinces in the study locations revealed highest values in the Tan Thanh region. Specifically, Cu and Ni were found in sediments at levels two to three times higher than the threshold effects level (TEL) and the effects range median (ERL) guidelines. The main sources of HM pollution in the study area are predicted to include the production and use of fertilizers and pesticides, metal surface processing, mechanical engineering and electronics manufacturing, and chemical plants. Further, positive correlations between HM concentrations and factors such as pH, total organic carbon (TOC), and clay-silt ratio in the sediments were identified through Spearman correlation analysis. The results obtained from the correlation analysis were further corroborated by Bayesian network analysis, which was also applied in this study. In addition, the contamination factor (CF) index indicated that Ni has a pollution level of "moderate degree" in Thanh Hoa (CF = 1.3) and "considerable degree" in Tan Thanh (CF = 3.2), whereas, Cu has a pollution level of "moderate degree" in both Thanh Hoa (CF = 1.3) and Tan Thanh (CF = 2.4). The modified degree of contamination (mCd) ranked the areas as Tan Thanh > Thanh Hoa > Duc Hue, with mCd indexes of 1.3, 0.7, and 0.4, respectively. The potential ecological risk index (RI) indicated a "low risk" level, with an average RI of 35.6 across all sites. These findings address knowledge gaps in HM pollution in peatlands but also contribute to the development of strategies for the protection of peatlands., 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 © 2025. Published by Elsevier Inc.)

Diclofenac has a relatively low oral bioavailability (50-60 %) and is quickly metabolized with a half-life of less than 1 h. Therefore, the oral therapeutic effect of diclofenac is not optimal. This research developed polyvinylpyrrolidone K30-functionalized silk fibroin nanoparticles as an effective delivery system for diclofenac (FNPs-PVP-DC). The FNPs-DC and FNPs-PVP-DC were formulated by two methods of adsorption and solvent exchange. Depending on the formulation factors, the obtained particles exhibited different properties of nano-scale sizes (400-800 nm), narrow size distribution, negatively charged surfaces (-17 to -19 mV), high PVP K30 incorporation (23 %-50 %), pHpzc of ~6.6, and appropriate chemical interactions. Interestingly, particles formulated by the adsorption method showed low drug encapsulation efficiencies of <15 %, whereas the solvent exchange method yielded moderate results of ~40 %. The FNPs-DC possessed aggregated patterns, while the FNPs-PVP-DC were more uniformly distributed. All formulations limited diclofenac release (<20 %) under gastric conditions and sustained its release in the intestinal environment. In in-vivo carrageenan-induced paw edema mice model, the FNPs-PVP-DC demonstrated a 20-30 % higher anti-inflammatory effect and a faster onset of action (within 1 h) compared to pure diclofenac at the same dose (5 mg/kg). These findings suggest that FNPs-PVP-DC have promising potential as novel oral anti-inflammatory products., (© 2024 Wiley-VCH GmbH.)

Early childhood caries (ECC) is the most common noncommunicable childhood disease-an important health problem with known environmental and social/behavioral influences lacking consensus genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multiancestry population of U.S. preschool-age children ( N  = 6,103) ages 3 to 5 y participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used International Caries Detection and Assessment System criteria to measure ECC; the primary trait was the number of primary tooth surfaces with caries experience (i.e., dmfs index). We estimated heritability and concordance rates and conducted genome-wide association analyses to estimate overall genetic effects as well as stratified by sex, household water fluoride, and dietary sugar and leveraged combined gene/gene-environment effects using 2-degree-of-freedom joint tests. Common genetic variants explained 24% of ECC phenotypic variance among unrelated individuals, while concordance rates were 0.64 (95% confidence interval [CI] = 0.42-0.79) among monozygotic twins and 0.44 (95% CI = 0.34-0.53) among first-degree relatives. Across all analyses, we identified 21 novel nonoverlapping genome-wide significant loci ( P  < 5 × 10 -8 ) and 1 genome-wide significant gene ( TAAR6 ) associated with ECC. The taste receptor activity gene set, with known roles in chemosensing, bacterial recognition, and innate immunity in the oral cavity, was strongly associated with ECC. While no locus remained significant after studywise multiple-testing correction, 3 loci were nominally significant ( P  < 0.05) and directionally consistent in external cohorts of 285,248 adults (rs1442369, DLGAP1 and rs74606067, RP11-856F16.2 ) and 18,994 children (rs71327750, SLC41A3 ). Meanwhile, the strongest marker known to be associated with adult caries (rs1122171, tagging the long noncoding RNA PITX1-AS1 ) was nominally significant ( P  = 0.01) and directionally consistent with ECC in our study. Taken together, the results of this study add to the genomics knowledge base for early childhood caries, offer several plausible candidates for future mechanistic studies, and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: During the preparation of this manuscript, J.S. Preisser served on a data safety and monitoring board of a study funded by the National Institute of Dental and Craniofacial Research (NIDCR). The remaining authors declare no competing interests.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMGCS2D) is a rare metabolic disorder that impairs the body's ability to produce ketone bodies and regulate energy metabolism. Diagnosing HMGCS2D is challenging because patients typically remain asymptomatic unless they experience fasting or illness. Due to the absence of reliable biochemical markers, genetic testing has become the definitive method for diagnosing HMGCS2D. This study included 19 patients from 14 unrelated families diagnosed with HMGCS2D in our department between October 2018 and October 2024. The clinical presentations, biochemical findings, molecular characteristics, and management strategies were systematically summarized and analyzed. Of the 19 cases studied, 16 were symptomatic, and 3 were asymptomatic. The onset of the first acute episode occurred between 10 days and 28 months of age. Triggers for the initial crisis in the symptomatic cases included poor feeding (93.8%), vomiting (56.3%), diarrhea (25.0%), and fever (18.8%). Clinical manifestations during the first episode were lethargy/coma (81.3%), rapid breathing (68.8%), hepatomegaly (56.3%), shock (37.5%), and seizures (18.8%). The biochemical abnormalities observed included elevated plasma transaminases (100%), metabolic acidosis (75%), hypoglycemia (56.3%), and elevated plasma ammonia levels (31.3%). Additionally, low free carnitine levels were found in seven cases, elevated C2 levels were found in one case, dicarboxylic aciduria was found in two cases, and ketonuria was found in two cases. Abnormal brain MRI findings were detected in three patients. Genetic analysis revealed seven HMGCS2 gene variants across the 19 cases. Notably, a novel variant, c.407A>T (p.D136V), was identified and has not been reported in any existing databases. Two common variants, c.559+1G>A and c.1090T>A (p.F364I), were present in 11 out of 19 cases (57.9%) and 10 out of 19 cases (55.5%), respectively. The implementation of a high glucose infusion and proactive management strategies-such as preventing prolonged fasting and providing enteral carbohydrate/glucose infusion during illness-effectively reduced the rate of acute relapses following accurate diagnosis. Currently, all 19 patients are alive, with ages ranging from 5 months to 14 years, and exhibit normal physical development. To the best of our knowledge, this study represents the first reported cases of HMGCS2D in Vietnamese patients. Our findings contribute to a broader understanding of the clinical phenotype and expand the known spectrum of HMGCS2 gene variants, enhancing current knowledge of this rare metabolic disorder.

Aim: To determine the rate of prediabetes among and the pre-transplant plasma high-sensitivity C-reactive protein (hs-CRP) value predictive of prediabetes in patients during their first year post-living donor kidney transplant., Methods: A total of 538 patients underwent living donor kidney transplantation between January 2018 and December 2020, 413 of whom met the inclusion criteria for this study. All patients underwent oral glucose tolerance tests (OGTTs) with 75 g glucose/200 mL solution, starting 3 months post-transplant and repeating the test every 3 months for the first year. Clinical and paraclinical indicators and plasma hs-CRP concentrations were quantified the day prior to the transplant. Prediabetes was diagnosed according to the American Diabetes Association 2018 criteria as a 2-h OGTT result between 140 mg/dL (7.8 mmol/L) and 199 mg/dL (11.0 mmol/L)., Results: The rate of prediabetes among the study subjects was 38.3 % (158/413). Body mass index (BMI) and pre-transplant plasma triglycerides, high-density lipoprotein cholesterol (HDLC), and hs-CRP levels were related factors predictive of prediabetes in patients within the first year post-kidney transplant based on multivariate logistic regression and receiver operative characteristic curve models. Hs-CRP was the factor with the best predictive value (area under the curve = 0.89; p < 0.001)., Conclusions: Pre-transplant plasma hs-CRP levels were a good predictor of prediabetes in the first year post-living donor kidney transplant., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2024. Published by Elsevier B.V.)

Several studies have now described instances where G-rich sequences in promoters and enhancers regulate gene expression through forming G-quadruplex (G4) structures. Relatedly, our group recently identified 301 long genomic stretches significantly enriched for minimal G4 motifs (LG4s) in humans and found the majority of these overlap annotated enhancers, and furthermore, that the promoters regulated by these LG4 enhancers are similarly enriched with G4-capable sequences. While the generally accepted model for enhancer:promoter specificity maintains that interactions are dictated by enhancer- and promoter-bound transcriptional activator proteins, the current study tested an alternative hypothesis: that LG4 enhancers interact with cognate promoters via a direct G4:G4 DNA-based mechanism. This work establishes the nuclear proximity of LG4 enhancer:promoter pairs, biochemically demonstrates the ability of individual LG4 single-stranded DNAs (ssDNAs) to directly interact target promoter ssDNAs, and confirms that these interactions, as well as the ability of LG4 enhancers to activate target promoters in culture, are mediated by G4 DNA., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background : Sitosterolemia is a rare autosomal recessive disorder characterized by diverse clinical manifestations ranging from asymptomatic cases to the development of xanthomas, hypercholesterolemia, premature atherosclerosis, or even sudden death during childhood. It results from homozygous or compound heterozygous pathogenic variants in the ABCG5 or ABCG8 genes. Prompt detection and intervention are essential to managing this condition and preventing severe outcomes. Methods : This study aims to retrospectively analyze the phenotype, genotype, treatment, and outcomes of 14 children-seven boys and seven girls-all of Vietnamese origin, diagnosed with sitosterolemia at the Vietnam National Children's Hospital between March 2015 and July 2024. Results : The median ages at disease onset and diagnosis were 5.7 years (range: 1.5-17.9) and 7.2 years (range: 1.7-17.9), respectively. Xanthomas were observed in 85.7% of patients (12/14), arthralgia in 14.3% (2/14), and anemia in 7.1% (1/14), with no cases of thrombocytopenia. At diagnosis, all patients exhibited elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), with considerably higher levels in patients with xanthomas compared to those without. Mutations in the ABCG5 gene were identified in 71.4% (10/14) of the patients, while 28.6% (4/14) had mutations in the ABCG8 gene. Fourteen variants were detected, nine in ABCG5 and five in ABCG8 , with five variants reported for the first time in sitosterolemia patients. Initial management for all patients involved dietary modifications. After three months, 10 patients with persistently elevated TC and LDL-C received ezetimibe or cholestyramine treatment. Among the eight patients who continued treatment for over three months, the median TC and LDL-C concentrations decreased by 54.9% and 67.3%, respectively. Conclusions : Among Vietnamese patients with sitosterolemia, variants in the ABCG5 gene were more prevalent than those in the ABCG8 gene. Patients showed a positive response to ezetimibe or cholestyramine treatment. Genetic testing is essential for establishing a diagnosis of sitosterolemia and guiding accurate management strategies.

Metastatic prostate cancer remains incurable. Though significant progress has been made in the field, the search for agents that improve outcomes for patients is ongoing. Several clinical trials have explored the benefit of combining PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPIs) for metastatic castrate resistant prostate cancer (mCRPC), especially those cancers with alterations in homologous recombination repair (HRR) genes. Niraparib, a highly selective inhibitor of PARP1 and PARP2, has been shown to confer a radiographic progression-free survival benefit in the treatment of mCRPC with HRR-associated gene alterations, particularly BRCA1 and BRCA2 ( BRCA1/2 ), when combined with abiraterone acetate plus prednisolone (AAP). This combination has recently been approved in the USA, Canada and Europe for patients with mCRPC and a BRCA1/2 gene mutation. This review summarizes the evidence with regards to the pharmacologic activity and clinical efficacy of niraparib with a specific focus on its efficacy in combination with AAP in mCRPC patients with HRR alterations.

The Type V secretion system, or "autotransporter", is a secretion system that enables bacteria to directly export proteins from the cell interior to the extracellular membrane. mCherry is a second-generation monomeric red fluorescent protein that has an improvement in photostability compared to the first generation of RFP. In this research, we conducted the fusion of the mRFP into the C-terminal domain of EhaA - the translocation domain of the autotransporter protein transport system - to investigate the expression of mRFP on the surface of Escherichia coli , a model organism commonly utilized in recombinant protein research. The induction of the mRFP-EhaA C-terminal domain complex expression was achieved using isopropyl β-D-1-thiogalactopyranoside (IPTG) and confirmed through SDS-PAGE stained with Coomassie Brilliant Blue and Western blotting using anti-6X His tag antibodies. The surface expression of the mRFP-EhaA C-terminal complex protein was validated through the fluorescent properties of mRFP and further confirmed using fluorescent microscopy. This study laid the groundwork for surface expression on cost-effective Gram-negative bacteria, E. coli ., Competing Interests: The authors declare that they have no conflict of interest.

In recent years, surface-enhanced Raman scattering (SERS) based on metal oxide semiconductors has been an active area of research and development, attracting significant scientific interest. These SERS substrates are known as plasmon-free SERS substrates because they are not based on noble metal nanoparticles but mainly on the defects, structure, and surface morphology of semiconductors to enhance the Raman signal. In this study, we fabricated a SERS substrate based on molybdenum oxide, using reactive DC magnetron sputtering and then used different simple and effective strategies to enhance the Raman signal. The results show that nanorod structure, oxygen deficiency engineering, phase engineering, and optical properties can be easily controlled by varying sputtering time and annealing time of MoO x SERS substrates. The analysis methods XRD, PL, and Raman show that with the optimal fabricated conditions. The presence of oxygen defects and a mixed MoO 3 , Mo 9 O 26 phase structure in as well as the nanorod structure of MoO x SERS substrates could likely enhance Raman signals via a chemical mechanism (CM) and electromagnetic mechanism (EM). The MoO x SERS substrates were also used to detect R6G at low concentrations, with an EF of 1.14 × 10 6 (at 0.01 ppm), LOD of 0.01 ppm, and good temporal stability and reproducibility.

Chordomas are rare, generally slow-growing spinal tumors that nonetheless exhibit progressive characteristics over time, leading to malignant phenotypes and high recurrence rates, despite maximal therapeutic interventions. The tumors are notoriously resistant to therapies and are often located in regions that complicate achieving gross total resections. Cell lines from these tumors are rare as well. We cultured a new chordoma cell line (ARF-8) derived from an extensive clival chordoma that extended back to the cervical spine. We characterized the ARF-8 cellular and extracellular vesicle (EV) proteomes, as well as the impacts of ARF-8 EVs on the proteomes and secretomes of recipient cells (both ARF-8 and human osteoblasts) in autocrine and paracrine settings. Our proteomic analyses suggested roles for transforming growth factor beta (TGFB/TGFβ), cell-matrix interactions involving the epithelial-to-mesenchymal transition (EMT), and cell-extracellular matrix interactions in cell migration, consistent with a migratory/metastatic tumor phenotype. We demonstrated that ARF-8 tumor cell migration was dependent on general (arginine-glycine-aspartic acid [RGD]-based) integrin activity and that ARF-8 EVs could promote such migration. ARF-8 EVs also prompted proteomic/secretomic changes in human osteoblast cells, again with indications that cell-cell and cell-extracellular matrix interactions would be activated. All the characteristics typically associated with chordomas as cancers-migration and invasion, therapeutic resistance, metastatic potential-can be driven by tumor EVs. Overall, ARF-8 EVs promoted predicted tumorigenic phenotypes in recipient cells and suggested novel therapeutic targets for chordomas.

Brain age is a powerful marker of general brain health. Furthermore, brain age models are trained on large datasets, thus giving them a potential advantage in predicting specific outcomes - much like the success of finetuning large language models for specific applications. However, it is also well-accepted in machine learning that models trained to directly predict specific outcomes (i.e., direct models) often perform better than those trained on surrogate outcomes. Therefore, despite their much larger training data, it is unclear whether brain age models outperform direct models in predicting specific brain health outcomes. Here, we compare large-scale brain age models and direct models for predicting specific health outcomes in the context of Alzheimer's Disease (AD) dementia. Using anatomical T1 scans from three continents (N = 1,848), we find that direct models outperform brain age models without finetuning. Finetuned brain age models yielded similar performance as direct models, but importantly, did not outperform direct models although the brain age models were pretrained on 1000 times more data than the direct models: N = 53,542 vs N = 50. Overall, our results do not discount brain age as a useful marker of general brain health. However, in this era of large-scale brain age models, our results suggest that small-scale, targeted approaches for extracting specific brain health markers still hold significant value.

Accurate Alzheimer's Disease (AD) progression prediction is essential for early intervention. The TADPOLE challenge, involving 92 algorithms, used multimodal biomarkers to predict future clinical diagnosis, cognition, and ventricular volume. The winning algorithm, FROG, utilized a Longitudinal-to-Cross-sectional (L2C) transformation to convert variable longitudinal histories into fixed-length feature vectors, which contrasted with most existing approaches that fitted models to entire longitudinal histories, e.g., AD Course Map (AD-Map) and minimal recurrent neural networks (MinimalRNN). The TADPOLE challenge only utilized the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. To evaluate FROG's generalizability, we trained it on the ADNI dataset and tested it on three external datasets covering 2,312 participants and 13,200 timepoints. We also introduced two FROG variants. One variant, L2C feedforward neural network (L2C-FNN), unified all XGBoost models used by the original FROG with an FNN. Across external datasets, L2C-FNN and AD-Map were the best for predicting cognition and ventricular volume. For clinical diagnosis prediction, L2C-FNN was the best, while AD-Map was the worst. L2C-FNN compared favorably with other approaches regardless of the number of observed timepoints, and when predicting from 0 to 6 years into the future, underscoring its potential for long-term dementia progression prediction. Pretrained ADNI models are publicly available: GITHUB&#95;LINK.

Background and Objectives : Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH; OMIM 238970) is one of the rare urea cycle disorders. Ornithine carrier 1 deficiency causes HHH syndrome, characterized by failure of mitochondrial ornithine uptake, hyperammonemia, and accumulation of ornithine and lysine in the cytoplasm. The initial presentation and time of diagnosis in HHH highly varies. Genetic analysis is critical for diagnosis. Materials and Methods : This study encompassed retrospective and prospective analyses of four unrelated Vietnamese children diagnosed with HHH syndrome. Results : The age of diagnosis ranged from 10 days to 46 months. All four cases demonstrated hyperornithinemia and prolonged prothrombin time. Three out of four cases presented with hyperammonemia, elevated transaminases, and uraciluria. No homocitrulline was detected in the urine. Only one case depicted oroticaciduria. Genetic analyses revealed three pathogenic variants in the SLC25A15 gene, with the c.535C>T (p.Arg179*) variant common in Vietnamese patients. The c.562&#95;564del (p.Phe188del) and c.408del (p.Met137Cysfs*10) variants were detected in one case. The latter variant has yet to be reported in the literature on HHH patients. After intervention with a protein-restricted diet, ammonia-reducing therapy, and L-carnitine supplementation, hyperammonemia was not observed, and liver enzyme levels returned to normal. Conclusions : Our results highlighted the clinical and biochemical heterogeneity of HHH syndrome and posed that HHH syndrome should be considered when individuals have hyperammonemia, elevated transaminase, and decreased prothrombin time.

Objective: To determine whether translocation carriers have a reduced number of usable blastocysts compared with infertile controls., Design: Retrospective cohort study., Setting: Single infertility practice., Patient(s): All cycles of balanced translocation carriers undergoing in vitro fertilization with preimplantation genetic testing for structural rearrangements at a single infertility center compared with an age-matched control cycles of infertile patients undergoing preimplantation genetic testing for aneuploidy from January 2012 to August 2022., Intervention(s): Balanced translocation carriers., Main Outcome Measure(s): The primary outcome measures were blastulation rate, usable blastulation rates, and live birth rate (LBR). The secondary outcome measures were sustained implantation rate, fertilization rate, number of oocytes retrieved, number of metaphase II oocytes, total blastulation failure, number of 2-pronuclear embryos, and number of euploid embryos. Outcome measures were compared between male translocation carriers and controls, female translocation carriers and controls, and Robertsonian and reciprocal translocation carriers., Result(s): A total of 1,291 retrieval cycles from 993 patients were included, of whom 255 patients were translocation carriers, whereas 738 were controls. Of those with translocations, 30 (11.5%) were Robertsonian carriers, and 231 (88.5%) were reciprocal carriers. There was a statistically significant difference in the blastulation rate between carriers and controls (59.5% vs. 62.1%). However, usable blastulation rates (47.2% vs. 50.0%) were equivalent between groups. There were no differences in the number of oocytes retrieved (18.5 vs. 18.3), number of 2-pronuclear embryos (13.4 vs. 12.5), sustained implantation rate (71.9% vs. 75.1%), or LBR (63.3% vs. 66.1%) between translocation carriers and controls. In both male and female translocation carriers vs. controls, there were no differences in usable blastulation rates or LBRs. When comparing Robertsonian with reciprocal translocation carriers, the rates of blastulation, usable blastulation, sustained implantation, and live birth were equivalent., Conclusion(s): Despite fewer euploid embryos, there were no differences in the rates of usable blastulation or live birth in balanced translocation carriers, regardless of sex of affected partner or type of rearrangement, compared with controls. Routine karyotyping for blastulation failure may not be necessary on the basis of these findings., Competing Interests: Declaration of Interests K.N.L. has nothing to disclose. M.M. has nothing to disclose. N.G.P. has nothing to disclose. L.L. has nothing to disclose. A.S.-M. has nothing to disclose. J.F. reports travel support from Ferring Pharmaceuticals for the ASPRIe Annual Meeting. E.O. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The silver nanoparticles-sodium alginate-chitosan (AgNPs-Alg-Chi) nanocomposite film is a compelling material with demonstrated antibacterial efficacy against various pure bacterial strains. However, its potential cytotoxicity at elevated Ag doses warrants investigation. There is a notable dearth of studies assessing its antibacterial effectiveness against clinically relevant bacterial strains, notably Cutibacterium acnes . This study aims to assess the antibacterial efficacy of the low-dose AgNPs-Alg-Chi nanocomposite films on both pure bacterial strains and strains isolated from clinical samples obtained from 65 acne patients. The films were synthesized using green methods, incorporating kumquat ( Citrus japonica ) extract as a silver ion-reducing agent. The material characterization methods include UV-Vis and FTIR spectroscopies, SEM-EDS, XPS, cell culture, and MTT assay. We successfully fabricated the AgNPs-Alg-Chi nanocomposite films with a low-loading dose of Ag NPs (≤11 μg mL -1 , and 37.8 ± 11.5 nm in size). The AgNPs-Alg-Chi nanocomposite film demonstrated comparable antibacterial efficacy to the AgNPs-Chi solution, with MIC values ranging from 3.67 to 5.50 μg mL -1 ( p > 0.05) across all strains. Importantly, the AgNPs-Alg-Chi films demonstrated excellent biocompatibility with human keratinocytes (HaCaT cells), maintaining cell viability above 70%. The present AgNPs-Alg-Chi nanocomposite films synthesized by a green approach demonstrated potent antibacterial activity, making them promising for further development into suitable products for human use., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Coatings with antibiofilm properties are desirable for biomedical applications. Titanium dioxide (TiO 2 ) has been explored as an antimicrobial agent in materials development primarily due to it being an excellent photocatalyst. Candida glabrata ( C. glabrata ) is an emerging human fungal pathogen with known high resistance to oxidative stress. Here, we fabricated a polydimethylsiloxane/titanium dioxide (PDMS/TiO 2 ) nanocomposite coating and tested its antibiofilm activities against C. glabrata . The resulting nanocomposite exhibited >50% reduction in C. glabrata biofilm formation with 2.5 wt % TiO 2 loading, even in the dark. Through ROS detection and surface characterization, the antibiofilm activity was attributed to the synergistic interaction of TiO 2 nanoparticles with the PDMS matrix, which resulted in the impediment of hydrophobic recovery. This work provides a design strategy to develop antibiofilm coatings against C. glabrata ., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF), namely known as dioxins, are persistent organic compounds with high toxicity. The presence of dioxins in soil is a major environmental issue worldwide, as it negatively impacts both ecosystems and human health. Thus, several advanced techniques have been applied to overcome this issue, offering promising treatment efficiency and cost-effectiveness. This review employs a meta-analysis strategy to provide an up-to-date assessment of the global situation of dioxin-contaminated soil. Dioxin concentrations are commonly higher in industrial and urban areas than in rural areas, primarily due to anthropogenic activities such as chemical manufacturing and waste incineration. Furthermore, several advanced bioremediation technologies for dioxin treatment, including biosurfactants, composting, and phytoremediation were highlighted and thoroughly discussed. Aerobic composting has proven to be robust in removing dioxins, achieving treatment efficiencies ranging from 65% to 85%. Whereas, phytoremediation, particularly when involving agricultural crops like zucchini, cucumber, and wheat, shows great promise in dioxin removal through various mechanisms, including root uptake and transpiration. Notably, biosurfactants such as rhamnolipids and sophorolipids have been effectively used to remediate dioxin-contaminated soil due to their significantly enhanced bioavailability of dioxins and their interaction with microbes. This review provides a comprehensive understanding of advanced biotechnologies for remediating dioxin-contaminated soil. It also addresses the technical and economic aspects of dioxin treatment and identifies future directions and research perspectives to fill knowledge gaps in this field., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To explore the significance of socioeconomic factors such as race and ethnicity as predictors of mortality in submassive and massive acute pulmonary embolism (PE)., Materials and Methods: Hospitalizations of patients aged >18 years with acute, nonseptic PE from 2016 to 2019 were identified from the National Inpatient Sample and divided into interventional radiology (IR) (catheter-directed thrombolysis and thrombectomy) and non-IR (tissue plasminogen activator) treatments. Statistical analyses calculated significant odds ratios (ORs) via 95% confidence intervals (CIs). The primary outcome of interest was mortality rate. Comorbidities affecting mortality were examined secondarily., Results: Non-Hispanic (NH) Black, Hispanic, and Asian/Pacific Islander patients were significantly less likely to undergo an IR procedure for acute, nonseptic PE compared with White patients (NH Black, OR, 0.83 [95% CI, 0.76-0.90], P < .05; Hispanic, 0.78 [0.68-0.89], P = .06; Asian/Pacific Islander, 0.71 [0.51-0.98], P = .72); however, these differences were eliminated when propensity score matching was performed for age, biological sex, and primary insurance type or for primary insurance type alone. NH Black patients were significantly more likely to die than White patients, regardless of undergoing non-IR or IR treatment. Overall risk of death was 41% higher for NH Black patients than for White patients (relative risk, 1.41 [95% CI, 1.24-1.60]; P < .001)., Conclusions: NH Black patients have a higher risk of mortality from acute, nonseptic PE than White patients. Independent of race, undergoing IR management for acute, nonseptic PEs was associated with a lower mortality rate. Matching for primary insurance type eliminates differences in mortality between races, suggesting that socioeconomic status may determine outcomes in acute PE., (Copyright © 2024. Published by Elsevier Inc.)

ABSTRACTS Bone cysts of the talar body are a benign, rare condition. Remove bone cysts, autologous bone grafting is a treatment method many authors recognize. Approaching the calcaneal bone cysts of the talar body encounters difficulties due to the narrow surgical field, poor blood supply, and the entire surface of the talar body being covered with cartilage. Endoscopic talar joint surgery to remove cysts bone, autologous bone grafting in the treatment of calcaneal bone cysts of the talar body is a progressive step, with many advantages, overcoming the mentioned difficulties, albeit being a challenging technique. We report a case of bone cysts of the talar body treated with endoscopic ankle joint surgery to remove cysts bone and autologous bone grafting at Viet Duc University Hospital, with good postoperative results, and no recurrence after 8 months of follow-up.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial contact site and cristae organizing system (MICOS) complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae-shaping factors, has not been fully determined. Here, we examine the MICOS complex in Schizosaccharomyces pombe, a minimal model whose genome only encodes for four core subunits. Using an unbiased proteomics approach, we identify a poorly characterized inner mitochondrial membrane protein that interacts with MICOS and is required to maintain cristae morphology, which we name Mmc1. We demonstrate that Mmc1 works in concert with MICOS to promote normal mitochondrial morphology and respiratory function. Mmc1 is a distant relative of the dynamin superfamily of proteins (DSPs), GTPases, which are well established to shape and remodel membranes. Similar to DSPs, Mmc1 self-associates and forms high-molecular-weight assemblies. Interestingly, however, Mmc1 is a pseudoenzyme that lacks key residues required for GTP binding and hydrolysis, suggesting that it does not dynamically remodel membranes. These data are consistent with the model that Mmc1 stabilizes cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane. Our study reveals a new class of proteins that evolved early in fungal phylogeny and is required for the maintenance of cristae architecture. This highlights the possibility that functionally analogous proteins work with MICOS to establish cristae morphology in metazoans., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Using data from Vietnamese-origin older immigrants/refugees in the Houston, Texas area, we assessed their overall health, chronic conditions, disability, depressive symptoms, and cognitive impairment, and examined the association between their chronic conditions and disability by comorbidity clusters. The mean age of the sample was 76 years old. The majority were married in fair/poor health with several chronic conditions and disabilities and lived with families in low-income households. Hypertension and arthritis were the most common health conditions, but cognitive impairment had the most significant impact on their disability. They experienced similar health conditions to other older Americans but had higher rates of depressive symptoms and cognitive impairment possibly due to cultural factors that may have delayed mental health treatment. Culturally and linguistically tailored services created by policymakers, healthcare professionals, and local social service agencies are recommended for the well-being of immigrants/refugees who migrated to the U.S. for a better life., (© 2023. W. Montague Cobb-NMA Health Institute.)

Background: Consumers' preferences for food crops are guided by quality attributes. This study aimed at deciphering the genetic basis of quality traits, especially tuber flesh color (FC) and oxidative browning (OB) in Dioscorea alata, based on the genome-wide association studies (GWAS) approach. The D. alata panel was planted at two locations in Guadeloupe. At harvest, the FC was scored visually as white, cream, or purple on longitudinally sliced mature tubers. The OB was scored visually as the presence or absence of browning after 15 min of exposure of the sliced samples to ambient air., Results: Phenotypic characterization for FC and OB of a diverse panel of D. alata genotypes highlighted significant variation within the panel and across two locations. The genotypes within the panel displayed a weak structure and could be classified into three subpopulations. GWAS identified 14 and 4 significant associations for tuber FC and OB, respectively, with phenotypic variance, explained values ranging from 7.18% to 18.04%. Allele segregation analysis at the significantly associated loci highlighted the favorable alleles for the desired traits, i.e., white FC and no OB. A total of 24 putative candidate genes were identified around the significant signals. A comparative analysis with previously reported quantitative trait loci indicated that numerous genomic regions control these traits in D. alata., Conclusion: Our study provides important insights into the genetic control of tuber FC and OB in D. alata. The major and stable loci can be further utilized to improve selection in breeding programs for developing new cultivars with enhanced tuber quality. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Background: Intranasal administration has been adopted in traditional medicine to facilitate access to the bloodstream and central nervous system (CNS). In modern medicine, nasal drug delivery systems are valuable for disease treatment because of their noninvasiveness, good absorption, and fast-acting effects., Objective: This study aimed to systematically organize preclinical and clinical studies on intranasal herbal medicines to highlight their potential in drug development., Methods: A comprehensive search for literature until February 2023 was conducted on PubMed and the Web of Science. From the selected publications, we extracted key information, including the types of herbal materials, target diseases, intranasal conditions, methods of toxicity evaluation, main outcomes, and mechanisms of action, and performed quality assessments for each study., Results: Of the 45 studies, 13 were clinical and 32 were preclinical; 28 studies used herbal extracts, 9 used prescriptions, and 8 used natural compounds. The target diseases were rhinosinusitis, influenza, fever, stroke, migraine, insomnia, depression, memory disorders, and lung cancer. The common intranasal volumes were 8-50 µl in mice, 20-100 µl in rats, and 100-500 µl in rabbits. Peppermint oil, Ribes nigrum folium, Melia azedarach L., Elaeocarpus sylvestris, Radix Bupleuri, Da Chuan Xiong Fang, Xingnaojing microemulsion, and Ginsenoside Rb1 emerged as potential candidates for rapid intranasal therapy. The in vivo toxicity assessments were based on mortality, body weight, behavioral changes, mucociliary activity, histopathology, and blood tests. Most intranasal treatments were safe, except for Cyclamen europaeum, Jasminum sambac, Punica granatum L., and violet oil, which caused mild adverse effects. At lower doses, intranasal herbal treatments often show greater effects than oral administration. The actions of intranasal herbal medicine mainly involve regulating inflammation and neurotransmission, with the olfactory bulb and anterior cingulate cortex to be relevant brain regions., Conclusion: Intranasal delivery of herbal materials holds promise for enhancing drug delivery efficacy and reducing treatment duration, offering a potential future perspective for developing intranasal therapies for various diseases., 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 GmbH. All rights reserved.)

Ethnopharmacological Relevance: Perillae Folium, the leaves and twigs of Perilla frutescens (L.) Britton, has been included in many traditional Chinese medicine herbal formulas to treat depression. However, the precise antidepressant mechanism of the essential oil from Perillae Folium (PFEO) has not been fully investigated., Aim of the Study: To assess the effects and potential mechanisms of PFEO on depression using animal models and network pharmacology analysis., Materials and Methods: PFEO was intranasally administered to a mouse model of social defeat stress (SDS). The antidepressant effects of PFEO on SDS-induced mice were evaluated using behavioral tests. Enzyme-linked immunosorbent assay (ELISA) and western blot were performed to measure the levels of depression-related biomarkers in the hippocampus and serum of the mice. The chemical compounds of PFEO were determined using gas chromatography-mass spectrometry (GC-MS). Network pharmacology and molecular docking analyses were conducted to investigate the potential bioactive components of PFEO and the mechanisms underlying the antidepressant effects. To validate the mechanisms of the bioactive compounds, in vitro models using PC12 and BV2 cells were established and the blood-brain barrier (BBB) permeability was evaluated., Results: The intranasal administration of PFEO suppressed SDS-induced depression in mice by increasing the time spent in the social zone and the social interactions in the social interaction test and by decreasing the immobility time in the tail suspension and forced swimming tests. Moreover, the PFEO treatment reduced the SDS-induced anxiety-like behavior, as inferred from the increased activity in the central zone observed in the open field test and in the open arms observed in the elevated plus maze test. PFEO administration recovered the SDS-induced decrease in the levels of 5-HT, NE, gamma-aminobutyric acid (GABA), and p-ERK in the hippocampus of mice. Furthermore, the increased serum corticosterone level was also attenuated by the PFEO treatment. A total of 21 volatile compounds were detected in PFEO using GC-MS, among which elemicin (15.52%), apiol (15.16%), and perillaldehyde (12.79%) were the most abundant ones. The PFEO compounds targeted 32 depression-associated genes, which were mainly related to neural cells and neurotransmission pathways. Molecular docking indicated good binding affinities between the bioactive components of PFEO (apiol, β-caryophyllene, elemicin, and myristicin) and the key targets, including ACHE, IL1B, IL6, MAOB, SLC6A2, SLC6A3, SLC6A4, and tumor necrosis factor. Among the four compounds, β-caryophyllene, elemicin, and myristicin were more effective in reducing neurotoxicity and neuroinflammation. Elemicin showed the highest BBB permeability rate., Conclusions: This study shows the antidepressant activities of PFEO in an SDS-induced mouse model and suggests its potential mechanisms of action: regulation of the corticosterone levels, hippocampal neurotransmitters, and ERK signaling. Apiol, β-caryophyllene, elemicin, and myristicin may be the main contributors to the observed effects induced by PFEO. Further studies are needed to fully elucidate the underlying mechanisms and the main PFEO bioactive components., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Isolated cerebral mucormycosis is rare in immunocompetent adults and is only sparsely reported to be associated with obstructive hydrocephalus., Observations: Here, the authors report a case of obstructive hydrocephalus secondary to central nervous system mucormycosis without other systems or rhino-orbital involvement and its technical surgical management. A 23-year-old, incarcerated, immunocompetent patient with history of intravenous (IV) drug use presented with syncope. Although clinical and radiographic findings failed to elucidate an infectious pathology, endoscopy revealed an obstructive mass lesion at the level of the third ventricle, which, on microbiological testing, was confirmed to be Rhizopus fungal ventriculitis. Perioperative cerebrospinal fluid diversion, endoscopic third ventriculostomy, endoscopic biopsy technique, patient outcomes, and the literature are reviewed here. The patient received intrathecal and IV amphotericin B followed by a course of oral antifungal treatment and currently remains in remission., Lessons: The patient's unique presentation and diagnosis of isolated cerebral mucormycosis reveal this pathogen as a cause of ventriculitis and obstructive hydrocephalus in immunocompetent adult patients, even in the absence of infectious sequelae on neuroimaging.

Background: Citrus reticulata Blanco essential oil (CBEO) has attracted increasing attention as a potential treatment for depression and anxiety in recent years. However, there is limited evidence regarding the active compounds responsible for its therapeutic effects. In addition, substantial amounts of CBEO and prolonged therapy are often required. This study aims to investigate the rapid acting antidepressant and anxiolytic effects of CBEO, identify the underlying composition as well as optimize its dosage and duration., Methods: CBEO composition was determined using gas chromatography-mass spectrometry (GC-MS), and the corresponding targets were obtained from the SwissTargetPrediction database. Depression-related targets were collected from DisGeNET, GeneCards, Therapeutic Target Database, and Online Mendelian Inheritance in Man. Subsequently, the overlap between CBEO and depression targets was utilized to build a network diagram depicting the relationship between the active ingredients and targets using Cytoscape software. The STRING database facilitated the construction of a protein-protein interaction network, and the Ma'ayan Laboratory Enrichment tool was employed for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Wiki pathway analyses. Molecular docking was conducted using AutoDock Vina and Discovery Studio Visualizer. Topological analysis predicted the main antidepressant active ingredients in CBEO. A mixture of these compounds was prepared based on their relative GC-MS ratios. Tail suspension test, elevated plus maze, corticosterone-induced PC12 cells, and lipopolysaccharide (LPS)-induced BV2 cells were used to validate the antidepressant and anxiolytic potential of CBEO and CBEO's main bioactive constituents., Results: CBEO contains 18 components that target 121 proteins. We identified 595 targets associated with depression; among them, 29 targets were located between essential oils and depression. Topological results revealed that linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol were the major active compounds of CBEO in the management of depression. GO analysis identified G protein-coupled opioid receptor activity, phospholipase C-activating G protein-coupled receptor, and neuron projections that were mostly related to molecular functions, cellular components, and biological processes. Neuroactive ligand-receptor interactions, chemical carcinogenesis, and calcium signaling pathways were the major pathways identified in KEGG analysis. Molecular docking showed that the main bioactive ingredients of CBEO had favorable binding affinities for Protein-Protein Interaction's hub proteins, including OPRM1, PTGS2, ESR1, SLC6A4, DRD2, and NR3C1. These five compounds were then mixed at 0.8:5:0.6:2:1 (w/w) ratio to form a CBEO antidepressant active compound mixture. An acute intranasal treatment of CBEO (25 mg/kg) only demonstrated an antidepressant effect, whereas the main bioactive compounds combination (12.5 mg/kg) illustrated both antidepressant and anxiolytic effects in mice. Linalool, p-cymene, and terpinene-4-ol exhibited neuroprotective and anti-neuroinflammation in the in vitro study, while these effects were not observed for α-terpinene and α-terpineol., Conclusion: Linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol cymene might be mainly contributing to CBEO's antidepressant effect by regulating neuroactive ligand-receptor interaction, neuron projection, and receptor signaling pathway. A mixture of these compounds showed rapid antidepressant potential via intranasal administration, which was comparable to that of CBEO. The mixture also exhibited an anxiolytic effect while not seen in CBEO., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khanh Nguyen, Kwon, Kim, Tran, Huong Nguyen and Yang.)

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namely RP11-856F16 . 2 (rs74606067) and SLC41A3 (rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identified TAAR6 as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.

The Burkholderia glumae bacterium causes bacterial grain rot in rice, posing significant threats to the crop's yield, particularly thriving during the rice flowering and grain filling stages. This disease is especially evident in rice grains before harvest, presenting challenges in the detection and classification of rice panicles. Firstly, diseased grains may mix with healthy ones, complicating their separation. Secondly, the size of grains on a panicle varies from small to large, which can be problematic when detected using object detection methods. Thirdly, disease classification can be conducted by evaluating the extent of infection on rice panicles to assess its impact on yield. Finally, the challenges in detection, classification, and preprocessing for disease identification and management necessitate the adoption of diverse approaches in machine learning and deep learning to develop optimal methods and support smart agriculture., (© 2024 The Author(s).)

Background: Pterocarpus santalinus L. essential oil (PSEO) is traditionally employed for treating fever and mental aberrations. We aim to explore the antidepressant potential of intranasal PSEO in social defeat stress (SDS)-expose mice and identify its mechanisms and components., Methods: PSEO components were analyzed using gas chromatography-mass spectrometry (GC-MS). C57BL/6 mice underwent a 10-day SDS with intranasal PSEO (10, 20 mg/kg) for 21 days. Efficacy was evaluated through changes in behaviors and serum corticosterone (CORT), hippocampal neurotransmitter, and inflammatory cytokine levels. In vitro effects were examined using primary hippocampal neurons, PC12 and BV2 cells., Results: GC-MS identified 22 volatile compounds in PSEO, and (+)-ledene (16.7%), cedrol (13.5%), and isoaromadendrene epoxide (7.0%) as major components. PSEO (20 mg/kg) significantly reversed SDS-induced social withdrawal, increased open-area explorations in the open field test (OFT) and elevated plus maze (EPM) test, and reduced immobility time in the tail suspension test (TST) and forced swimming test (FST). PSEO downregulated serum CORT and hippocampal interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels, while increasing hippocampal gamma-aminobutyric acid (GABA), norepinephrine (NE), and serotonin (5-HT) levels. PSEO (0.1, 1, 10 µg/mL) reduced neurotoxicity and neuroinflammation in PC12 and BV2 cells, respectively. PSEO (10 µg/mL) enhanced glutamic acid decarboxylase 6 (GAD6)- and GABA B receptor 1 (GABABR1)-positive puncta in the hippocampal neurons and FM1-43 fluorescence intensity., Conclusion: Intranasal PSEO exhibited antidepressant-like effects on SDS-exposed mice, potentially through modulating stress hormone, neurotransmission, and neuroinflammation. Further investigation into the pharmacokinetics, bioavailability, and mechanisms of (+)-ledene, cedrol, and isoaromadendrene epoxide is needed., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

SARS-CoV-2 (SC2) has been intensely studied since its emergence. However, the mechanisms of host immune dysregulation triggered by SC2 remain poorly understood. That said, it is well established that many prominent viral families encode microRNAs (miRNAs) or related small viral RNAs (svRNAs) capable of regulating human genes involved in immune function. Importantly, recent reports have shown that SC2 encodes its own svRNAs. In this study, we have identified 12 svRNAs expressed during SC2 infection and show that one of these svRNAs can regulate target gene expression via complementary binding to mRNA 3' untranslated regions (3'UTRs) much like human microRNAs., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Data from the Vietnamese Aging and Care Survey (VACS) showed the high prevalence of disability, depressive symptoms, and cognitive impairment in older Vietnamese immigrants and refugees. We proposed a Community-Engaged Dementia Education Program to examine the Houston Vietnamese American community's literacy on dementia and develop a one-pager educational material. This is a cross-sectional, qualitative study (interviews and focus groups) using the Cultural Exchange Model as a conceptual framework. We interviewed fourteen Vietnamese key informants and assessed the community's knowledge of dementia based on Edwards' 9-stage Community Readiness Model. The community's low literacy on dementia (Stages 2-3: Denial/resistance to vague awareness) was revealed. Approaches to introducing dementia conversations to the community and what to include in the one-pager were discussed. Based on the key informants' insight, we developed a dementia one-pager tailored to the community by using lay language with a representative image of the target population, indicating warning signs of dementia, and encouraging them to see their doctors for cognitive check-ups. The plan for the next steps includes utilizing the local ethnic media, collaborating with the existing pillars of the Cultural Exchange model, leveraging the university students' learning opportunities, and disseminating the culturally and linguistically tailored one-pager., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Although blood remains a gold standard diagnostic fluid for most health exams, it involves an unpleasant and relatively invasive sampling procedure (finger pricking or venous draw). Saliva contains many relevant and useful biomarkers for diagnostic purposes, and its collection, in contrast, is noninvasive and can be obtained with minimal effort. Current saliva analyses are, however, achieved using chromatography or lateral flow assays, which, despite their high accuracy and sensitivity, can demand expensive laboratory-based instruments operated by trained personnel or offer only semiquantitative results. In response, we investigated electrochemical aptamer-based (E-AB) biosensors, a reagentless sensing platform, to allow for continuous and real-time measurements directly in undiluted, unstimulated human whole saliva. As a proof-of-concept study, we developed E-AB biosensors capable of detecting low-molecular-weight analytes (glucose and adenosine monophosphate (AMP)). To our knowledge, we report the first E-AB sensor for glucose, an approach that is inherently independent of its chemical reactivity in contrast to home glucometers. For these three sensors, we evaluated their figures of merits, stability, and reusability over short- and long-term exposure directly in saliva. In doing so, we found that E-AB sensors allow rapid and convenient molecular measurements in whole saliva with unprecedented sensitivities in the pico- to nanomolar regime and could be regenerated and reused up to 7 days when washed and stored in phosphate-buffered saline at room temperature. We envision that salivary molecular measurements using E-AB sensors are a promising alternative to invasive techniques and can be used for improved point-of-care clinical diagnosis and at-home measurements.

The ability of amphipathic peptides to arrange themselves in aqueous solutions, known as self-assembly, has been found to reduce the effectiveness of these peptides in interacting with cell membranes. Therefore, minimizing their tendency to self-assemble could be a potential strategy for enhancing the pharmacological properties of antimicrobial peptides (AMPs). To explore this idea, this study prepared a series of natural peptides mastoparan C ( MPC ) with increased net charge and hydrophilicity via alanine-to-lysine substitution and investigated the impact on the biological activity. The preliminary data suggested the influence of both the overall positive charge and the position of a lysine residue on the self-assembly of MPC and its derivatives. Besides, the analogue MPC-A5K,A8K displayed higher anticancer activity and comparable antimicrobial activity with significantly lower hemolysis than MPC . Hence, reducing self-assembly by expanding the cationic area could be a promising approach for developing potent and selective AMPs., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation., Competing Interests: Declaration of interests K.G.A. has received consulting fees on SARS-CoV-2 and the COVID-19 pandemic., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Micro- and nano-plastics (MNPs) have received considerable attention over the past 10 years due to their environmental prevalence and potential toxic effects. With the increase in global plastic production and disposal, MNP pollution has become a topic of emerging concern. In this review, we describe MNPs in the atmospheric environment, and potential toxicological effects of exposure to MNPs. Studies have reported the occurrence of MNPs in outdoor and indoor air at concentrations ranging from 0.0065 items m -3 to 1583 items m -3 . Findings have identified plastic fragments, fibers, and films in sizes predominantly <1000 μm with polyamide (PA), polyester (PES), polyethylene terephthalate (PET), polypropylene (PP), rayon, polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), polyacrylonitrile (PAN), and ethyl vinyl acetate (EVA) as the major compounds. Exposure through indoor air and dust is an important pathway for humans. Airborne MNPs pose health risks to plants, animals, and humans. Atmospheric MNPs can enter organism bodies via inhalation and subsequent deposition in the lungs, which triggers inflammation and other adverse health effects. MNPs could be eliminated through source reduction, policy/regulation, environmental awareness and education, biodegradable materials, bioremediation, and efficient air-filtration systems. To achieve a sustainable society, it is crucial to implement effective strategies for reducing the usage of single-use plastics (SUPs). Further, governments play a pivotal role in addressing the pressing issue of MNPs pollution and must establish viable solutions to tackle this significant challenge., 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.)

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA., (© 2023. The Author(s).)

Background: My Dispense is a virtual pharmacy simulation developed for students to train and practice dispensing skills in a safe environment that causes no harm to patients. This study was aimed to investigate learners' perspectives on the effectiveness of MyDispense and its suitability to integrate into the clinical pharmacy module in Viet Nam., Methods: A mixed method approach was undertaken. Fourth- and fifth-year pharmacy students at University of Medicine and Pharmacy at Ho Chi Minh city and community pharmacists were invited to complete a survey questionnaire and to participate in semi-structured interviews., Results: A total of 92/99 participants agreed to take part, of which 75% of participants were students and 65.2% were female. About three-quarters of the participants agreed or strongly agreed that MyDispense improved their dispensing skills, such as patient counselling (70.6%) and collecting patient infomation (85.9%). The majority of the participants (84.8%) considered that MyDispense was suitable to integrate into the clinical pharmacy module. Qualitative analysis from the interviews highlighted the advantages of MyDispense, comprising high interactivity with users, safe environment for practicing medication dispensing, and diversity of common marketed medications. In addition, certain barriers of this programme were also reported, including the complicated process, inconsistent quality of product images, and mixed English-Vietnamese languages., Conclusions: From learner's perspectives, MyDispense was an effective tool to enhance dispensing skills and was suitable to integrated into the clinical pharmacy module in Viet Nam., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Hemophilia A (HEMA) is an X-linked bleeding disorder caused by reduced/absent coagulation factor VIII expression, as a result of pathogenic variants in the F8 gene. Preimplantation prevention of HEMA should ideally include direct pathogenic F8 variant detection, complemented by linkage analysis of flanking markers to identify the high-risk F8 allele. Linkage analysis is particularly indispensable when the pathogenic variant cannot be detected directly or identified. This study evaluated the suitability of a panel of F8 intragenic and extragenic short tandem repeat markers for standalone linkage-based preimplantation genetic testing for monogenic disorder (PGT-M) of the Inv22 pathogenic variant, an almost 600 kb paracentric inversion responsible for almost half of all severe HEMA globally, for which direct detection is challenging., Methods: Thirteen markers spanning 1 Mb and encompassing both F8 and the Inv22 inversion interval were genotyped in 153 unrelated females of Viet Kinh ethnicity., Results: All individuals were heterozygous for ≥ 1 marker, ~ 90% were heterozygous for ≥ 1 of the five F8 intragenic markers, and almost 98% were heterozygous for ≥ 1 upstream (telomeric) and ≥ 1 downstream (centromeric) markers. A prospective PGT-M couple at risk of transmitting F8 Inv22 were fully informative at four marker loci (2 intra-inversion, 1 centromeric, 1 telomeric) and partially informative at another five (2 intra-inversion, 3 centromeric), allowing robust phasing of low- and high-risk haplotypes. In vitro fertilization produced three embryos, all of which clearly inherited the low-risk maternal allele, enabling reliable unaffected diagnoses. A single embryo transfer produced a clinical pregnancy, which was confirmed as unaffected by amniocentesis and long-range PCR, and a healthy baby girl was delivered at term., Conclusion: Robust and reliable PGT-M of HEMA, including the common F8 Inv22 pathogenic variant, can be achieved with sufficient informative intragenic and flanking markers., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial inner membrane-localized MICOS complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae shaping factors, has not been fully determined. Here, we examine the MICOS complex in Schizosaccharomyces pombe , a minimal model whose genome only encodes for four core subunits. Using an unbiased proteomics approach, we identify a poorly characterized inner mitochondrial membrane protein that interacts with MICOS and is required to maintain cristae morphology, which we name Mmc1. We demonstrate that Mmc1 works in concert with MICOS complexes to promote normal mitochondrial morphology and respiratory function. Bioinformatic analyses reveal that Mmc1 is a distant relative of the Dynamin-Related Protein (DRP) family of GTPases, which are well established to shape and remodel membranes. We find that, like DRPs, Mmc1 self-associates and forms high molecular weight assemblies. Interestingly, however, Mmc1 is a pseudoenzyme that lacks key residues required for GTP binding and hydrolysis, suggesting it does not dynamically remodel membranes. These data are consistent with a model in which Mmc1 stabilizes cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane. Our study reveals a new class of proteins that evolved early in fungal phylogeny and is required for the maintenance of cristae architecture. This highlights the possibility that functionally analogous proteins work with MICOS to establish cristae morphology in metazoans.

This study explored the potential for predicting the quantities of microplastics (MPs) from easily measurable parameters in peatland sediment samples. We first applied correlation and Bayesian network analysis to examine the associations between physicochemical variables and the number of MPs measured from three districts of the Long An province in Vietnam. Further, we trained and tested three machine learning models, namely Least-Square Support Vector Machines (LS-SVM), Random Forest (RF), and Long Short-Term Memory (LSTM) to predict the composite quantities of MPs using physicochemical parameters and sediment characteristics as predictors. The results indicate that the quantity of MPs and characteristics such as color and shape in the samples were mostly influenced by pH, TOC, and salinity. All three predictive models demonstrated considerable accuracies when applied to the testing dataset. This study lays the groundwork for using basic physicochemical variables to predict MP pollution in peatland sediments and potentially locations and environments., 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.)

SARS-CoV-2 infection can result in a range of outcomes from asymptomatic/mild disease to severe COVID-19/fatality. In this study, we investigated the differential expression of small noncoding RNAs (sncRNAs) between patient cohorts defined by disease severity. We collected plasma samples, stratified these based on clinical outcomes, and sequenced their circulating sncRNAs. Excitingly, we found YRNA HY4 displays significant differential expression (p=0.025) between patients experiencing mild and severe disease. In agreement with recent reports identifying plasma YRNAs as indicators of influenza infection severity, our results strongly suggest that circulating HY4 levels represent a powerful prognostic indicator of likely SARS-CoV-2 patient infection outcome., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

Background: Blood urea nitrogen to albumin ratio (BAR) is increasingly recognized as an early predictor for short-term outcomes in critically ill patients, but the association of BAR with long-term outcomes in critically ill surgical patients remains underexplored., Methods: We enrolled consecutive patients who were admitted to surgical intensive care units (ICUs) at Taichung Veterans General Hospital between 2015 and 2020, and the dates of death were retrieved from Taiwan's National Health Insurance Research Database. In addition to Cox regression, we also used propensity score matching to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year post-hospital mortality of the variables., Results: A total of 8,073 eligible subjects were included for analyses. We found that age, male gender, high Charlson Comorbidity Index, high Acute Physiology and Chronic Health Evaluation II score, positive microbial culture, and leukocytosis were predictors for mortality, whereas high body mass index, scheduled surgery, and high platelet counts were protective factors against long-term mortality. The high BAR was independently associated with increased post-hospital mortality after adjustment for the aforementioned covariates (adjHR 1.258, 95% CI, 1.127-1.405). Notably, the association tended to be stronger in females and patients with fewer comorbidities and lower disease severity of critical illness. The propensity score matching, dividing subjects by BAR higher or lower than 6, showed a consistent association between week-one BAR and post-hospital mortality (adjHR 1.503, 95% CI 1.247-1.811)., Conclusions: BAR is a newly identified predictor of short-term outcome, and we identified long-term outcome-relevant factors, including BAR, and the identified factors may be useful for risk stratification of long-term outcomes in patients discharged from surgical ICUs., (© 2023. The Author(s).)