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Summary: The cytokine interleukin-23 (IL-23) is involved in the pathogenesis of inflammatory and autoimmune conditions including inflammatory bowel disease (IBD). IL23R is enriched in intestinal Tregs, yet whether IL-23 modulates intestinal Tregs remains unknown. Here, investigating IL-23R signaling in Tregs specifically, we show that colonic Tregs highly express Il23r compared with Tregs from other compartments and their frequency is reduced upon IL-23 administration and impairs Treg suppressive function. Similarly, colonic Treg frequency is increased in mice lacking Il23r specifically in Tregs and exhibits a competitive advantage over IL-23R-sufficient Tregs during inflammation. Finally, IL-23 antagonizes liver X receptor pathway, cellular cholesterol transporter Abca1, and increases Treg apoptosis. Our results show that IL-23R signaling regulates intestinal Tregs by increasing cell turnover, antagonizing suppression, and decreasing cholesterol efflux. These results suggest that IL-23 negatively regulates Tregs in the intestine with potential implications for promoting chronic inflammation in patients with IBD.

Although advances in genomics and experimental gene therapy have opened new possibilities for treating otherwise incurable diseases, the transduction of nucleic acids into the cells and delivery in vivo remain challenging. The high molecular weight and anionic nature of nucleic acids require their packing into nanoparticles for the delivery. The efficacy of nanoparticle drugs necessitates the high bioactivity of constituents, but their distribution in organisms is mostly governed by the physical properties of nanoparticles, and therefore, generation of stable particles with strictly defined characteristics is highly essential. Using previously designed efficient cell-penetrating peptide NF55, we searched for strategies enabling control over the nanoparticle formation and properties to further improve transfection efficacy. The size of the NF55/pDNA nanoparticles correlates with the concentration of its constituents at the beginning of assembly, but characteristics of nanoparticles measured by DLS do not reliably predict the applicability of particles in in vivo studies. We introduce a new formulation approach called cryo-concentration, where we acquired stable and homogeneous nanoparticles for administration in vivo. The cryo-concentrated NF55/pDNA nanoparticles exhibit several advantages over standard formulation: They have long shelf-life and do not aggregate after reconstitution, have excellent stability against enzymatic degradation, and show significantly higher bioactivity in vivo.

Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation. We conclude that the pH dependent change of the net charge of the CPP may very well be the key factor leading to the high delivery efficiency and the optimal binding strength between CPPs to siRNAs, while the hydrophobicity, secondary structure of the CPP, and the positions of the positive charges are responsible for the stability of the CPP/siRNA particles. Also, CPPs with distinct hydrophobic and hydrophilic regions may assemble into nanoparticles that could be described as core-shell formulations.

Summary: Stem cells balance cellular fates through asymmetric and symmetric divisions in order to self-renew or to generate downstream progenitors. Symmetric commitment divisions in stem cells are required for rapid regeneration during tissue damage and stress. The control of symmetric commitment remains poorly defined. Using single-cell RNA sequencing (scRNA-seq) in combination with transcriptomic profiling of HSPCs (hematopoietic stem and progenitor cells) from control and m6A methyltransferase Mettl3 conditional knockout mice, we found that m6A-deficient hematopoietic stem cells (HSCs) fail to symmetrically differentiate. Dividing HSCs are expanded and are blocked in an intermediate state that molecularly and functionally resembles multipotent progenitors. Mechanistically, RNA methylation controls Myc mRNA abundance in differentiating HSCs. We identified MYC as a marker for HSC asymmetric and symmetric commitment. Overall, our results indicate that RNA methylation controls symmetric commitment and cell identity of HSCs and may provide a general mechanism for how stem cells regulate differentiation fate choice. : Cheng et al. uncover RNA methylation as a guardian in hematopoietic stem cell (HSC) fate decisions. m6A maintains hematopoietic stem cell symmetric commitment and identity. This study may provide a general mechanism for how RNA methylation controls cellular fate. Keywords: m6A, RNA methylation, hematopoietic stem cell, cell identity, symmetric and asymmetric cell division, MYC

Epigenetic regulation of key transcriptional programs is a critical mechanism that controls hematopoietic development, and, thus, aberrant expression patterns or mutations in epigenetic regulators occur frequently in hematologic malignancies. We demonstrate that the Polycomb protein L3MBTL1, which is monoallelically deleted in 20q- myeloid malignancies, represses the ability of stem cells to drive hematopoietic-specific transcriptional programs by regulating the expression of SMAD5 and impairing its recruitment to target regulatory regions. Indeed, knockdown of L3MBTL1 promotes the development of hematopoiesis and impairs neural cell fate in human pluripotent stem cells. We also found a role for L3MBTL1 in regulating SMAD5 target gene expression in mature hematopoietic cell populations, thereby affecting erythroid differentiation. Taken together, we have identified epigenetic priming of hematopoietic-specific transcriptional networks, which may assist in the development of therapeutic approaches for patients with anemia.

Defining the role of epigenetic regulators in hematopoiesis has become critically important, because recurrent mutations or aberrant expression of these genes has been identified in both myeloid and lymphoid hematological malignancies. We found that PRMT4, a type I arginine methyltransferase whose function in normal and malignant hematopoiesis is unknown, is overexpressed in acute myelogenous leukemia patient samples. Overexpression of PRMT4 blocks the myeloid differentiation of human stem/progenitor cells (HSPCs), whereas its knockdown is sufficient to induce myeloid differentiation of HSPCs. We demonstrated that PRMT4 represses the expression of miR-223 in HSPCs via the methylation of RUNX1, which triggers the assembly of a multiprotein repressor complex that includes DPF2. As part of the feedback loop, PRMT4 expression is repressed posttranscriptionally by miR-223. Depletion of PRMT4 results in differentiation of myeloid leukemia cells in vitro and their decreased proliferation in vivo. Thus, targeting PRMT4 holds potential as a novel therapy for acute myelogenous leukemia.

Generalized lymphangiomatosis (GLA) is a very rare condition in adults, characterized by diffused proliferation of lymphatic vessels that requires differential diagnosis from other vascular disorders such as cavernous or capillary hemangioma. This is because of overlapping characteristics on histopathological examination. Therefore, imaging features such as CT and MRI are useful to evaluate morphological characteristics, location, and the extent of the spread as well as differential diagnosis with other pathologies. We report a case of a 22-year-old female patient with left hemothorax after thoracoscopic sympathectomy for the treatment of hand sweating. The patient underwent drainage and cleaning of the left pleura. Chest computed tomography and lumbar spine magnetic resonance imaging showed multiple fat infiltration foci of the lumbar spine and pelvis. A wing bone biopsy of the pelvis was initially performed for the diagnosis of chronic osteomyelitis. Afterwards, the patient continued to have pleural drainage and developed hemothorax and chylothorax, amounting to 3000 mL. The chest tube was blocked with a mixture of biological glue and lipiodol (2 mL of glue, ratio of glue to lipiodol: 1:4) and a 3 i-ED coil complex. After the intervention, the pleural fluid decreased; the left pleural fluid was still 15 mm thick, and the amount of fluid drained after 1 week was 100 mL. Aspiration of the chest wall lesion showed fluid rich in fat droplets. Combined with the results of lumbar spine magnetic resonance imaging and the old biopsy, this was consistent with generalized lymphangiomatosis.

Introduction: Effective vascular anastomosis is crucial for successful hand surgery, particularly in traumatic injuries where rapid restoration of blood flow is essential. The Synovis microvascular anastomotic coupler system presents a novel approach by potentially offering faster and more reliable outcomes than traditional suturing methods. This study was conducted to assess the effectiveness and safety of the Synovis coupler for microvascular anastomoses in the wrist, evaluating anastomosis time, patency rates, and complication rates. Methods: This retrospective study examined 25 microvascular anastomoses (22 arteries and 3 veins) in 24 patients at a major trauma center. The primary outcomes measured were anastomosis time and vascular patency, which were assessed immediately post-operation and at subsequent follow-ups. Results: The average time required for anastomosis using the coupler was 7.3 min. Immediate post-operative vascular patency was 100%, with a long-term patency rate of 88%. Complications included arterial narrowing at the coupler site in 3 arteries, and complete occlusion in 3 arteries, accounting for a 12% long-term complication rate. Conclusion: Although the Synovis coupler demonstrated a significant reduction in anastomosis time and high patency rates, our data suggest that its effectiveness is more pronounced in venous anastomoses. The higher complication rates in arterial anastomoses warrant cautious use in these cases. Further research, including prospective randomized controlled trials, is needed to validate these findings and optimize patient selection criteria for using couplers in microvascular surgery.

Summary: Computer-vision and machine-learning (ML) approaches are being developed to provide scalable, unbiased, and sensitive methods to assess mouse behavior. Here, we used the ML-based variational animal motion embedding (VAME) segmentation platform to assess spontaneous behavior in humanized App knockin and transgenic APP models of Alzheimer’s disease (AD) and to test the role of AD-related neuroinflammation in these behavioral manifestations. We found marked alterations in spontaneous behavior in AppNL-G-F and 5xFAD mice, including age-dependent changes in motif utilization, disorganized behavioral sequences, increased transitions, and randomness. Notably, blocking fibrinogen-microglia interactions in 5xFAD-Fggγ390–396A mice largely prevented spontaneous behavioral alterations, indicating a key role for neuroinflammation. Thus, AD-related spontaneous behavioral alterations are prominent in knockin and transgenic models and sensitive to therapeutic interventions. VAME outcomes had higher specificity and sensitivity than conventional behavioral outcomes. We conclude that spontaneous behavior effectively captures age- and sex-dependent disease manifestations and treatment efficacy in AD models.

Background: A core feature of body dysmorphic disorder (BDD) is body image disturbance. Many with BDD misperceive and are dissatisfied with the sizes and shapes of body parts, but detailed quantification and analysis of this has not yet been performed. To address this gap, we applied Somatomap 3D, a digital avatar tool, to quantify body image disturbances by assessing body size estimation (BSE) accuracy and body dissatisfaction. Methods: Sixty-one adults (31 with BDD, 30 healthy controls) created avatars to reflect their perceived current body and ideal body by altering 23 body part sizes and lengths using Somatomap 3D. Physical measurements of corresponding body parts were recorded for comparison. BSE accuracy (current minus actual) and body dissatisfaction (ideal minus current) were compared between groups and in relation to BDD symptom severity using generalized estimating equations. Results: Individuals with BDD significantly over- and under-estimated certain body parts compared to healthy controls. Individuals with BDD overall desired significantly thinner body parts compared to healthy controls. Moreover, those with worse BSE accuracy had greater body dissatisfaction and poorer insight. Conclusion: In sum, this digital avatar tool revealed disturbances in body image in individuals with BDD that may have perceptual and cognitive/affective components.

Caragobius urolepis has a wide range of distribution, from brackish to freshwater water, ranging from India to the Philippines and Fiji, including the Vietnamese Mekong Delta (VMD), where it lives mainly in the coastal regions and plays a vital role in food supply. Our preliminary observation showed that its population tended to decline, but little is known about this species. This study, therefore, was conducted to provide data on the ovarian structure, spawning pattern and season, length at first maturity, and batch fecundity of this fish. The study of 306 specimens caught with trawl nets from April 2022 to March 2023 in two coastal areas of VMD—Dong Hai, Bac Lieu (DHBL), and Dam Doi, Ca Mau (DDCM)—showed that this goby spawned more than once because the oocytes in stage IV ovary showed different stages of development. It could release eggs monthly during a 12-month study, with a peak in July–September since stage IV ovaries were found monthly during the study period and the GSI exhibited a high value in July–September. The fish length at first maturity and batch fecundity varied with the site, as they were 18.8 cm and 3,757–9,187 (6,142 ± 707 SE eggs/female) in DDCM and 20.5 cm and 3,760–11,118 (5,634 ± 750 SE eggs/female) in DHBL. The findings provide valuable foundations for exploiting their resources and serve as a basis for studying artificial reproduction. It is suggested to avoid catching these fish species during the breeding season to ensure sustainable exploitation in the future.

This study investigates the concentrations of atmospheric aerosol particles (PM, including PM2.5 and PM10), as well as the presence and distribution of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in ambient air in Bien Hoa City (Dong Nai province, Vietnam) during the dry and rainy seasons in 2023. The concentrations of 7 PCDDs and 10 PCDFs congeners in PM10 or PM2.5 were determined using gas chromatography-mass spectrometry (GC-MS). The results show that the concentration of PM10 and PM2.5 were 54.7 ± 9.4 µg/m3, 65.3 ± 7.6 µg/m3, and 39.6 ± 7.9 µg/m3, 58.9 ± 12.6 µg/m3, in the rainy season and dry season, respectively. This reveals that while only PM2.5 concentration levels in the dry seasonexceed national ambient air quality standards, but all of PM2.5 concentration levels consistently exceeded WHO guidelines. The study highlights the dominance of PM2.5 and its adverse health implications, as evidenced by the PM2.5/PM10 ratio (0.74 and 0.85 for the rainy and dry seasons, respectively) and its association with worse air quality. Analysis of PCDD/Fs concentrations in PM samples demonstrates their comparable levels in both seasons, with OCDD being the most abundant species. Furthermore, the study estimates the toxic equivalency (TEQ) of PCDD/Fs and assesses health risks, revealing a potentially high cancer risk from exposure to these pollutants, particularly PM2.5 under WHO2005-TEQ. Several PCDD/Fs- WHO2005-TEQ congeners exhibit higher concentration levels in PM2.5 compared to PM10, suggesting differential particulate matter dynamics and potential environmental implications. These findings underscore the urgent need for mitigation strategies to alleviate air pollution and reduce associated health risks in the dioxin hotspot of Vietnam.

Agonists of the secretin receptor have potential applications for diseases of the cardiovascular, gastrointestinal, and metabolic systems, yet no clinically-active non-peptidyl agonists of this receptor have yet been developed. In the current work, we have identified a new small molecule lead compound with this pharmacological profile. We have prepared and characterized a systematic structure-activity series around this thiadiazole scaffold to better understand the molecular determinants of its activity. We were able to enhance the in vitro activity and to maintain the specificity of the parent compound. We found the most active candidate to be quite stable in plasma, although it was metabolized by hepatic microsomes. This chemical probe should be useful for in vitro studies and needs to be tested for in vivo pharmacological activity. This could be an important lead toward the development of a first-in-class orally active agonist of the secretin receptor, which could be useful for multiple disease states.

The durability of LED bulbs ensures that the lights can operate for a long time without needing to be replaced or maintained too often. The brightness of high-power LED bulbs provides a strong and efficient light source, saves energy, and has a long lifespan. The traditional method of testing LED bulb life span has limitations such as long testing time, limited accuracy, high cost, inability to predict accurately, and failure to respond quickly. Therefore, the development of new and improved testing methods is necessary to effectively and accurately evaluate and ensure the durability of LED bulbs. This research paper proposes a hybrid Six Sigma method based on the recursive Kalman filter and Weibull distribution to estimate the lifespan of Bulb LEDs. The goal of the new method for evaluating LED bulb life is to provide accurate, reliable, and multi-dimensional information about the life of LED lamps, meeting the requirements of accuracy, diversity, time-saving, resources, credibility, and the ability to evaluate from a variety of perspectives. As a result of the research, the recursive Kalman filter method has strengths such as high accuracy, flexibility, saving computational resources, the ability to handle inaccurate data, and scalability. When applied to LED bulb life assessment, it provides an accurate and reliable estimate of LED lamp life. Research results on longevity testing were reduced from 1650 h to 710 h. The end-of-life test time is 710 h, and the aging time per life test cycle is 135 h. The cost of life testing is reduced from 2100.17 USD to 410.12 USD. This LED bulb lifespan testing method can be applied to similar types of LED products to improve the company's productivity and business efficiency.

Background: Early identification of children at high risk of obesity can provide clinicians with the information needed to provide targeted lifestyle counseling to high-risk children at a critical time to change the disease course. Objectives: This study aimed to develop predictive models of childhood obesity, applying advanced machine learning methods to a large unaugmented electronic health record (EHR) dataset. This work improves on other studies that have (i) relied on data not routinely available in EHRs (like prenatal data), (ii) focused on single-age predictions, or (iii) not been rigorously validated. Methods: A customized sequential deep-learning model to predict the development of obesity was built, using EHR data from 36,191 diverse children aged 0–10 years. The model was evaluated using extensive discrimination, calibration, and utility analysis; and was validated temporally, geographically, and across various subgroups. Results: Our results are mostly better or comparable to similar studies. Specifically, the model achieved an AUROC above 0.8 in all cases (with most cases around 0.9) for predicting obesity within the next 3 years for children 2–7 years of age. Validation results show the model's robustness and top predictors match important risk factors of obesity. Conclusions: Our model can predict the risk of obesity for young children at multiple time points using only routinely collected EHR data, greatly facilitating its integration into clinical care. Our model can be used as an objective screening tool to provide clinicians with insights into a patient's risk for developing obesity so that early lifestyle counseling can be provided to prevent future obesity in young children.

Summary: Background: Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. The OPTiMISE trial showed that this deprescribing can be achieved with no differences in blood pressure control at 3 months compared with usual care. We aimed to examine effects of deprescribing on longer-term hospitalisation and mortality. Methods: This randomised controlled trial enrolled participants from 69 general practices across central and southern England. Participants aged 80 years or older, with systolic blood pressure less than 150 mm Hg and who were receiving two or more antihypertensive medications, were randomly assigned (1:1) to antihypertensive medication reduction (removal of one antihypertensive) or usual care. General practitioners and participants were aware of the treatment allocation following randomisation but individuals responsible for analysing the data were masked to the treatment allocation throughout the study. Participants were followed up via their primary and secondary care electronic health records at least 3 years after randomisation. The primary outcome was time to all-cause hospitalisation or mortality. Intention-to-treat analyses were done using Cox regression modelling. A per-protocol analysis of the primary outcome was also done, excluding participants from the intervention group who did not reduce treatment or who had medication reinstated during the initial trial 12-week follow-up period. This study is registered with the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT2016-004236-38) and the ISRCTN Registry (ISRCTN97503221). Findings: Between March 20, 2017, and Sept 30, 2018, a total of 569 participants were randomly assigned. Of these, 564 (99%; intervention=280; control=284) were followed up for a median of 4·0 years (IQR 3·7–4·3). Participants had a mean age of 84·8 years (SD 3·4) at baseline and 273 (48%) were women. Medication reduction was sustained in 109 participants at follow-up (51% of the 213 participants alive in the intervention group). Participants in the intervention group had a larger reduction in antihypertensives than the control group (adjusted mean difference –0·35 drugs [95% CI –0·52 to –0·18]). Overall, 202 (72%) participants in the intervention group and 218 (77%) participants in the control group experienced hospitalisation or mortality during follow-up (adjusted hazard ratio [aHR] 0·93 [95% CI 0·76 to 1·12]). There was some evidence that the proportion of participants experiencing the primary outcome in the per-protocol population was lower in the intervention group (aHR 0·80 [0·64 to 1·00]). Interpretation: Half of participants sustained medication reduction with no evidence of an increase in all-cause hospitalisation or mortality. These findings suggest that an antihypertensive deprescribing intervention might be safe for people aged 80 years or older with controlled blood pressure taking two or more antihypertensives. Funding: British Heart Foundation and National Institute for Health and Care Research.

This study investigates the factors influencing the adoption of digital learning platforms among university students in Cambodia, integrating multiple theoretical frameworks: the Technology Acceptance Model (TAM), Unified Theory of Acceptance and Use of Technology (UTAUT), and Self-Determination Theory (SDT). Conducting a cross-sectional survey with 369 students from various institutions, this study employed partial least squares structural equation modelling (PLS-SEM) to analyze the data. The findings revealed significant connections among motivational factors, perceived ease of use, usefulness, and subsequent adoption behaviours. This study contributes significantly to the global discourse on digital education, particularly from the perspective of a developing country, at a pivotal point in its educational evolution in the digital age. This highlights the importance of enhancing intrinsic and extrinsic motivations among students to improve the adoption and effective use of digital learning resources, offering practical recommendations for educational stakeholders in Cambodia and similar contexts.

This dataset explores the perception of happiness and job satisfaction among Vietnamese general school teachers and administrators (principals and vice-principles) in implementing a new curriculum. This study uses SPSS Statistics 26.0 and Exel to analyze data on the opinions of 782 general school teachers and administrators (principles and vice-principles) about satisfaction and happiness at work and influencing factors such as gender, age, experience, income, and workplace, workplaces, difficulties, sources of support when implementing new programs. This dataset contributes to a better understanding of the factors influencing educators' well-being and job satisfaction in the context of curriculum change, providing insights into educational policy and practice in Vietnam and beyond.

Summary: Developmental causes of the most common arrhythmia, atrial fibrillation (AF), are poorly defined, with compensation potentially masking arrhythmic risk. Here, we delete 9 amino acids (Δ9) within a conserved domain of the giant protein titin’s A-band in zebrafish and human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs). We find that ttnaΔ9/Δ9 zebrafish embryos’ cardiac morphology is perturbed and accompanied by reduced functional output, but ventricular function recovers within days. Despite normal ventricular function, ttnaΔ9/Δ9 adults exhibit AF and atrial myopathy, which are recapitulated in TTNΔ9/Δ9-hiPSC-aCMs. Additionally, action potential is shortened and slow delayed rectifier potassium current (IKs) is increased due to aberrant atrial natriuretic peptide (ANP) levels. Strikingly, suppression of IKs in both models prevents AF and improves atrial contractility. Thus, a small internal deletion in titin causes developmental abnormalities that increase the risk of AF via ion channel remodeling, with implications for patients who harbor disease-causing variants in sarcomeric proteins.

Valproic acid and phenytoin are two prevalent antiepileptic medications known for their narrow indices and propensity for cardiovascular and respiratory system toxicity. Therefore, therapeutic drug monitoring (TDM) of valproic acid (VAL) and phenytoin (PHE) concentrations in patient plasma is extremely beneficial for improving clinical choices, avoiding adverse reactions, and optimizing treatment for individual patients. In this study, a rapid and sensitive ultra-performance liquid chromatographic tandem mass spectrometer (UPLC-MS/MS) method was developed and validated for the simultaneous quantitative determination of valproic acid (VAL) and phenytoin (PHE) in human plasma. Negative electron spray ionization (ESI-) mode with selective ion recording (SIR) was employed to determine the transitions of m/z 142.98 and m/z 250.93 for VAL and PHE, respectively. The internal standard (IS) betamethasone (BETA) was ionized using positive electron spray ionization (ESI+) and detected by multi-reaction monitoring (MRM) mode to obtain precursor ions and specific fragment ions for quantification, and the MRM transition was chosen to be m/z 393.17 → 355.16. The separation was performed using a Phenomenex Synergi Hydro-RP (4 μm, 250 × 4.6 mm, I.D.) with an isocratic mobile phase consisting of acetonitrile – water (75:25, v/v) at a flow rate of 0.8 mL/min. The column temperature was maintained at 25 °C. The lower limit of quantification of VAL and PHE was 3.6 μg/mL and 0.72 μg/mL, respectively, which resulted in a recovery of more than 85 % for most analytes. According to US-FDA bioanalytical technique validation, the specificity, intra- and inter-day precision and accuracy, matrix effect, carryover, dilution, and stability of all analytes were within acceptable ranges. This analytical method was successful in evaluating the levels of valproic acid and phenytoin in human plasma from epileptic patients.

Acetylcholinesterase (AChE) inhibition is a significant strategy for preventing Alzheimer's disease (AD) and neurodegenerative diseases. In this study, a dereplication system was utilized to rapidly identify and characterize acetylcholinesterase-interacting compounds by comparing UPLC-MS/MS profile screening approach and molecular docking analysis, derived from the extracts and fractions of the stem of Glycosmis parviflora (Sims) Little. Eleven potential AChE inhibitors were isolated and identified from the ethyl acetate extract of G. parviflora, including an undescribed alkaloid (9), namely glybomine D, eight known alkaloids (1−8), a flavonoid (10), and a phytosterol (11). The inhibitory potential of these compounds against AChE was assessed, with O-methylglycosolone (6), 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (1), skimmianine (4) and arborine (2), regarded as effective inhibitors, yielding IC50 values of 39.81 μM, 41.53 μM, 49.40 μM, and 59.92 μM, respectively. Notably, O-methylglycosolone exhibited the highest potency. Four of these potent AChE inhibitors exhibited mixed-type inhibition. However, O-methylglycosolone (6), 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (1), and arborine (2) were first reported modulating with acetylcholinesterase activity. Furthermore, molecular docking revealed O-methylglycosolone (6) superior binding affinity (–23.749 kcal/mol) compared to other compounds, mainly by interacting with the peripheral anionic site of AChE, which forms hydrogen bonds and hydrophobic forces may play an important role, interaction with amino acid residues such as Tyr341, Tyr72, Ser293, and Arg296 in the active cavity, which is crucial for effective and selective inhibition of AChE activity. ADMET predictions suggest that arborine (2), skimmianine (4), and O-methylglycosolone (6) demonstrate favorable permeability across the blood–brain barrier, while 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (1) exhibits comparatively reduced permeability. These findings highlight the potential of these compounds as natural AChE inhibitors for treating neurodegenerative diseases.

Introduction: Moringa oleifera, Vernonia amygdalina, and Centella asiatica are herbs used in traditional Chinese medicine and are commonly used in Southeast Asian countries to treat a variety of diseases. The experimental evidence showed that M. oleifera leaves, V. amygdalina leaves, and C. asiatica had the effect of supporting their treatment of diabetes. This study investigated the anti-hyperglycemic effect of a novel herbal formula from M. oleifera leaf, V. amygdalina leaf, and C. asiatica aerial part extracts. Methods: The extract was examined for anti-hyperglycemic capacity in oral glucose tolerance test in normal mice. To confirm their role in a higher model, the extract was studied in the streptozotocin (STZ)-induced hyperglycemic model. Plasma glucose concentration, body weight, organ weight, malondialdehyde, glutathione in liver and kidneys, and pancreatic histology were also evaluated. Besides, in vitro properties of the extract were tested including α-amylase and α-glucosidase inhibitory, and antioxidant activities. Results: After 7-day of treatment, the extract showed strong anti-hyperglycemic activity in the STZ-induced hyperglycemic mice, plasma glucose levels were reduced by 48.75 % and 54.13 % in the group administered with 200 mg/kg and 400 mg/kg of the extract, respectively, compared with the hyperglycemic control. The extract had the effect to protect the liver and kidneys against oxidation stress by enhancing glutathione levels in the liver and decreasing malondialdehyde levels in the liver and kidneys. The pancreatic β-cell protection was also observed by improving the size and number of pancreatic islets by the extract compared to the hyperglycemic control. The extract showed a significant α-amylase and α-glucosidase inhibitory activities, and antioxidant activity through DPPH and ABTS quenching and reducing power abilities. Discussion: These results demonstrated remarkable potential of the combined extract of M. oleifera leaves, V. amygdalina leaves, and aerial part of C. asiatica in the management of diabetes.

Background and Aims: Hepatocellular carcinoma (HCC) incidence is increasing and correlated with metabolic dysfunction-associated steatotic liver disease (MASLD; formerly nonalcoholic fatty liver disease), even in patients without advanced liver fibrosis who are more likely to be diagnosed with advanced disease stages and shorter survival time, and less likely to receive a liver transplant. Machine learning (ML) tools can characterize large datasets and help develop predictive models that can calculate individual HCC risk and guide selective screening and risk mitigation strategies. Methods: Tableau and KNIME Analytics were used for descriptive analytics and ML tasks. ML models were developed using standard laboratory and clinical parameters. Sci-kit learn algorithms were used for model development. Data from University of California (UC), Davis, were used to develop and train a pilot predictive model, which was subsequently validated in an independent dataset from UC San Francisco. MASLD and HCC patients were identified by International Classification of Diseases-9/10 codes. Results: Of the patients diagnosed with MASLD (n = 1561 training; n = 686 validation), HCC developed in 14% (n = 227) of the UC Davis training cohort and 25% (n = 176) of the UC San Francisco validation cohort. Liver fibrosis determined by the noninvasive Fibrosis-4 score was the strongest single predictor for HCC in the model. Using the validation cohort, the model predicted HCC development at 92.06% accuracy with an area under the curve of 0.97, F1-score of 0.84, 98.34% specificity, and 74.41% sensitivity. Conclusion: ML models can aid physicians in providing early HCC risk assessment in patients with MASLD. Further validation will translate to cost-effective, personalized care of at-risk patients.

Resumen: Introducción: La deglución es un proceso esencial para mantener la homeostasis corporal. Con el envejecimiento, se producen cambios tanto en las estructuras centrales como periféricas, dando lugar a la presbifagia, la cual implica alteraciones morfológicas y funcionales en el proceso deglutorio. Sin embargo, los reportes de prevalencia de dificultades deglutorias en adultos mayores son escasos en la actualidad. Objetivos: Determinar la prevalencia de dificultades deglutorias producto del envejecimiento, y cómo se relacionan las dificultades autorreportadas con parámetros de seguridad, eficiencia, competencia y confortabilidad. Método: Se realiza una investigación exploratoria-descriptiva considerando la valoración de autopercepción de 18 adultos mayores de la ciudad de Iquique, Chile. Resultados: Se reportó una prevalencia del 27,78% en cuanto a las dificultades deglutorias autopercibidas. Conclusiones: Los resultados orientan a la necesidad de una mayor utilización de instrumentos de pesquisa temprana, como lo son los cuestionarios de autorreporte. Abstract: Introduction: Swallowing is an essential process in maintaining body homeostasis. With aging, changes occur in both central and peripheral structures, giving rise to presbyphagia, which involves morphological and functional alterations in the swallowing process. However, reports on the prevalence of swallowing difficulties in older adults are currently scarce. Objectives: To determine the prevalence of swallowing difficulties due to aging, and how self-reported difficulties are related to safety, efficiency, competence, and comfort parameters. Method: To this end, exploratory-descriptive research was carried out considering the self-perception assessment of 18 older adults from the city of Iquique, Chile. Results: A prevalence of 27.78% was reported in terms of self-perceived swallowing difficulties. Conclusions: Results inform the need for greater use of early screening instruments, such as self-report questionnaires.

Duodenal adenocarcinoma is very rare. Its clinical picture is nonspecific and the diagnosis is often accidental. The factors that affect survival are difficult to determine because the number of patients is not high. The common site of duodenal tumors and surgical removal are also debatable. The treatment guidelines published so far have mostly been evaluated in retrospective studies conducted over a 20-year period with relatively small sample sizes. The author presents a case of duodenal adenocarcinoma in a 62-year-old male patient with a clinical manifestation of melena. Duodeno-cephalo-pancreatectomy was the surgical option.

Currently, renewable energy-based generators are considered worldwide to achieve net zero targets. However, the stochastic nature of renewable energy systems leads to regulation and control challenges for power system operators, especially in remote and regional grids with smaller footprints. A hybrid system (i.e., solar, wind, biomass, energy storage) could minimise this issue. Nevertheless, the hybrid system is not possible to develop in many islands due to the limited land area, geographical conditions, and others. Hydrogen as a carrier of clean energy can be used in locations where the installation of extensive or medium-scale renewable energy facilities is not permissible due to population density, geographical constraints, government policies, and regulatory issues. This paper presents a techno-economic assessment of designing a green hydrogen-based microgrid for a remote island in North-east Australia. This research work determines the optimal sizing of microgrid components using green hydrogen technology. Due to the abovementioned constraints, the green hydrogen production system and the microgrid proposed in this paper are located on two separate islands. The paper demonstrates three cost-effective scenarios for green hydrogen production, transportation, and electricity generation. This work has been done using Hybrid Optimisation Model for Multiple Energy Resources or HOMER Pro simulation platform. Simulation results show that the Levelized Cost of Energy using hydrogen technology can vary from AU$0.37/kWh to AU$1.08/kWh depending on the scenarios and the variation of key parameters. This offers the potential to provide lower-cost electricity to the remote community. Furthermore, the CO2 emission could be reduced by 17,607,77 kg/year if the renewable energy system meets 100% of the electricity demand. Additionally, the sensitivity analysis in this paper shows that the size of solar PV and wind used for green hydrogen production can further be reduced by 50%. The sensitivity analysis shows that the system could experience AU$0.03/kWh lower levelized cost if the undersea cable is used to transfer the generated electricity between islands instead of hydrogen transportation. However, it would require environmental approval and policy changes as the islands are located in the Great Barrier Reef.

Working in a stem cell laboratory necessitates a thorough understanding of complex cell culture protocols, the operation of sensitive scientific equipment, adherence to safety standards, and general laboratory etiquette. For novice student researchers, acquiring the necessary specialized knowledge before their initial laboratory experience can be a formidable task. Similarly, for experienced laboratory personnel, efficiently and uniformly training new trainees to a rigorous standard presents a significant challenge. In response to these issues, we have developed an educational and interactive virtual cell culture environment. This interactive virtual lab aims to equip students with foundational knowledge in maintaining cortical brain organoids and to instill an understanding of pertinent safety procedures and laboratory etiquette. The gamification of this training process seeks to provide laboratory supervisors in highly specialized fields with an effective tool to integrate students into their work environments more rapidly and safely.

Aims: Pulmonary hypertension (PH) is characterised by an increase in pulmonary arterial pressure, ultimately leading to right ventricular failure and death. We have previously shown that nerve growth factor (NGF) plays a critical role in PH. Our objectives here were to determine whether NGF controls Connexin-43 (Cx43) expression and function in the pulmonary arterial smooth muscle, and whether this mechanism contributes to NGF-induced pulmonary artery hyperreactivity. Methods and results: NGF activates its TrkA receptor to increase Cx43 expression, phosphorylation, and localization at the plasma membrane in human pulmonary arterial smooth muscle cells, thus leading to enhanced activity of Cx43-dependent GAP junctions as shown by Lucifer Yellow dye assay transfer and fluorescence recovery after photobleaching -FRAP- experiments. Using both in vitro pharmacological and in vivo SiRNA approaches, we demonstrate that NGF-dependent increase in Cx43 expression and activity in the rat pulmonary circulation causes pulmonary artery hyperreactivity. We also show that, in a rat model of PH induced by chronic hypoxia, in vivo blockade of NGF or of its TrkA receptor significantly reduces Cx43 increased pulmonary arterial expression induced by chronic hypoxia and displays preventive effects on pulmonary arterial pressure increase and right heart hypertrophy. Conclusions: Modulation of Cx43 by NGF in pulmonary arterial smooth muscle cells contributes to NGF-induced alterations of pulmonary artery reactivity. Since NGF and its TrkA receptor play a role in vivo in Cx43 increased expression in PH induced by chronic hypoxia, these NGF/Cx43-dependent mechanisms may therefore play a significant role in human PH pathophysiology.

Purpose: The murine oxygen-induced retinopathy (OIR) model is one of the most widely used animal models of ischemic retinopathy, mimicking hallmark pathophysiology of initial vaso-obliteration (VO) resulting in ischemia that drives neovascularization (NV). In addition to NV and VO, human ischemic retinopathies, including retinopathy of prematurity (ROP), are characterized by increased vascular tortuosity. Vascular tortuosity is an indicator of disease severity, need to treat, and treatment response in ROP. Current literature investigating novel therapeutics in the OIR model often report their effects on NV and VO, and measurements of vascular tortuosity are less commonly performed. No standardized quantification of vascular tortuosity exists to date despite this metric’s relevance to human disease. This proof-of-concept study aimed to apply a previously published semi-automated computer-based image analysis approach (iROP-Assist) to develop a new tool to quantify vascular tortuosity in mouse models. Design: Experimental study. Subjects: C57BL/6J mice subjected to the OIR model. Methods: In a pilot study, vasculature was manually segmented on flat-mount images of OIR and normoxic (NOX) mice retinas and segmentations were analyzed with iROP-Assist to quantify vascular tortuosity metrics. In a large cohort of age-matched (postnatal day 12 [P12], P17, P25) NOX and OIR mice retinas, NV, VO, and vascular tortuosity were quantified and compared. In a third experiment, vascular tortuosity in OIR mice retinas was quantified on P17 following intravitreal injection with anti-VEGF (aflibercept) or Immunoglobulin G isotype control on P12. Main Outcome Measures: Vascular tortuosity. Results: Cumulative tortuosity index was the best metric produced by iROP-Assist for discriminating between OIR mice and NOX controls. Increased vascular tortuosity correlated with disease activity in OIR. Treatment of OIR mice with aflibercept rescued vascular tortuosity. Conclusions: Vascular tortuosity is a quantifiable feature of the OIR model that correlates with disease severity and may be quickly and accurately quantified using the iROP-Assist algorithm. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Xanthine oxidase (XO) has been widely recognized as a pivotal enzyme in developing hyperuricemia, primarily contributing to the excessive production of uric acid during purine metabolism in the liver. One of the standard treatment approaches involves reducing uric acid levels by inhibiting XO activity. In this study, the leaf extract of Dolichandrone spathacea, traditionally used in folk medicine, was found to inhibit XO activity in the ethyl acetate and butanol fractions at a concentration of 100 µg/mL, their values were 78.57 ± 3.85 % (IC50 = 55.93 ± 5.73 µg/ml) and 69.43 ± 8.68 % (IC50 = 70.17 ± 7.98 µg/ml), respectively. The potential XO inhibitory components were isolated by bioactivity assays and the HR-ESI-MS and NMR spectra system. The main constituents of leaf extracts of Dolichandrone spathacea, six compounds, namely trans-4-methoxycinnamic acid (3), trans-3,4-dimethoxycinnamic acid (4), p-coumaric acid (5), martynoside (6), 6-O-(p-methoxy-E-cinnamoyl)-ajugol (7), and scolymoside (17), were identified as potent XO inhibitors with IC50 values ranging from 19.34 ± 1.63 μM to 64.50 ± 0.94 μM. The enzyme kinetics indicated that compounds 3–5, 7, and 17 displayed competitive inhibition like allopurinol, while compound 6 displayed a mixed-type inhibition. Computational studies corroborated these experimental results, highlighting the interactions between potential metabolites and XO enzyme. The hydrogen bonds played crucial roles in the binding interaction, especially, scolymoside (17) forms a hydrogen bond with Mos3004, exhibited the lowest binding energy (−18.3286 kcal/mol) corresponding to the lowest IC50 (19.34 ± 1.63 μM). Furthermore, nine compounds were isolated for the first time from this plant. In conclusion, Dolichandrone spathacea and its constituents possess the potential to modulate the xanthine oxidase enzyme involved in metabolism.

Application of sensors is becoming prevalent in research and production settings. With increasing battery power, improved case and component durability, and consistent data connectivity, precision technologies, such as accelerometers, can help identify changes in livestock behavior. The objective of this study is to identify the variation among individual animals and among different accelerometer devices. A repeated 4 × 4 Latin-square design was utilized to identify differences between accelerometer, animal, and week. Twelve ewes separated into three age groups were randomly assigned to 4 different accelerometers deployed as an ear tag weekly over the course of 4 weeks. Manual behavior observations were paired to calculated accelerometer metrics and were used for training and validation dataset to predict animal behavior using random forest machine learning. Movement variation had the greatest importance in predicting behaviors. Across the four week study, differences were found for animal and week through each of the calculated metrics. Differences in accelerometers were detected for 80 % of the calculated metrics. This study shows the importance to account for variation among individual animals and accelerometer devices in experimental designs.

2-Methyl-1-butanol (2MB) and 3-Methyl-1-butanol (3MB) are microbial volatile organic compounds (VOCs) and found in indoor air. Here, we applied rice as a bioindicator to investigate the effects of these indoor microbial volatile pollutants. A remarkable decrease in germination percentage, shoot and root elongation, as well as lateral root numbers were observed in 3MB. Furthermore, ROS production increased by 2MB and 3MB, suggesting that pentanol isomers could induce cytotoxicity in rice seedlings. The enhancement of peroxidase (POD) and catalase (CAT) activity provided evidence that pentanol isomers activated the enzymatic antioxidant scavenging systems, with a more significant effect observed in 3MB. Furthermore, 3MB induced higher activity levels of glutathione (GSH), oxidized glutathione (GSSG), and the GSH/GSSG ratio in rice compared to the levels induced by 2MB. Additionally, qRT-PCR analysis showed more up-regulation in the expression of glutaredoxins (GRXs), peroxiredoxins (PRXs), thioredoxins (TRXs), and glutathione S-transferases (GSTUs) genes in 3MB. Taking the impacts of pentanol isomers together, the present study suggests that 3MB exhibits more cytotoxic than 2MB, as such has critical effects on germination and the early seedling stage of rice. Our results provide molecular insights into how isomeric indoor microbial volatile pollutants affect plant growth through airborne signals.

Mesopores and silanol nests are known two technological keys that essentially control the catalytic performance of ZSM-5 zeolite. However, designing and controlling them without using chemicals so that the produced ZSM-5 can have strongly enhanced catalytic properties and more importantly can be applied at industrial scale have still been a big challenge up to now. The present study employed the 10 MeV electron beam (EB) generated from an industrial linear accelerator to introduce both the O-vacancy rich mesopores and stable triad-silanol nests in ZSM-5. The structural modification of irradiated ZSM-5 samples was explored by using SEM and FTIR combined with positron annihilation spectroscopy (PAS) including positron annihilation lifetime (PAL), Doppler broadening (DB) of electron–positron annihilation energy and electron momentum distribution (EMD). Obtained results indicated that EB irradiation could recover the defective-crystal structure as well as intensively modify the structures of ZSM-5. In particular, the mechanism for the solid-state crystallization and the formation of the O-vacancy rich mesopores (maximum size of ∼4.5 nm) in ZSM-5 under the combined EB irradiation (10−110 kGy) and calcination (600 °C) was, for the first time, proposed. The mechanism for the formation of stable triad-silanol nests in the channels of irradiated and calcined ZSM-5 zeolites was also explored. The present study, therefore, opens a new research path of applying both EB irradiation and calcination to produce ZSM-5 with novel features for industrial catalytic application at large-production scale.

Objective: This study investigated the safety of performing surgical repair for doubly committed ventricular septal defects by right vertical infra-axillary minithoracotomy (RVIAT). Methods: A retrospective comparative study was performed to evaluate the outcomes of patients who underwent doubly committed ventricular septal defects closure from January 2019 to May 2022. Seventy-four patients were enrolled in the study and treated with either the median sternotomy approach (MSA: n = 37) or the RVIAT approach (RVIAT: n = 37). Results: The median weight and age in the MSA group were significantly lower than those in the RVIAT group (MSA: 6.0 kg [interquartile range] (IQR), 5.2 to 8.7 kg] vs RVIAT: 7.5 kg [IQR, 5.6-14 kg]; P = .034 and MSA: 4.9 months [IQR, 3.6-9.4 month] vs 9.6 months [IQR, 5.0-60.4 months]; P = .0084). No patients died, and no patients in the RVIAT group required conversion to the MSA approach. The mean prebypass surgical time was longer in the RVIAT group (36.1 ± 8.2 minutes vs 31.8 ± 5.6 minutes; P = .03). There were no significant differences between the 2 groups in cardiopulmonary bypass time, aortic crossclamp time, or operation time. Significantly shorter ventilation times were observed in the RVIAT group (11.9 ± 8.2 hours vs 15.4 ± 6.3 hours; P = .006). Conclusions: Closure of doubly committed ventricular septal defects through the pulmonary trunk by the RVIAT approach is feasible and safe, and does not increase the risk of bypass-related complications.

Background: The information on prevalence of undiagnosed hyperglycemia, and hypertension among the adult in Vietnam is limited. The aim of this study was to identify the prevalence of undiagnosed intermediate hyperglycemia, hyperglycemia, and hypertension and some associated factors among adults aged ≥40 years living in Ba Vi district in Hanoi, Vietnam. Methods: A cross-sectional study was conducted among 1814 adults aged ≥40 years nine communes in Ba Vi district, a semi rural area, in Hanoi, Vietnam. Lists of the adults aged ≥40 years living in nine communes, who reported undiagnosed for hypertension, and diabetes, were made. From the lists, the participants were randomly selected based on the selection criteria. Participants were people who reported they are free of hypertension, diabetes, prediabetes at the day of data collection. Participants were collected information on sociodemographic characteristics, blood pressure measurement, and 3 ml fasting venous blood samples by certified phlebotomists. The main study outcomes variables were intermediate hyperglycemia, hyperglycemia, and hypertension. Results: Prevalence of undiagnosed intermediate hyperglycemia, hyperglycemia, and hypertension among the participants were 47.8 %, 8.2 %, and 40.0 %, respectively. Higher prevalence of undiagnosed intermediate hyperglycemia (53.3 % vs 46.2 %), hyperglycemia (13.5 % vs 7.9 %), and high blood pressure (52.8 % vs 33.9 %) were found among males compared with females. Conclusion: High prevalence of undiagnosed intermediate hyperglycemia, hyperglycemia, and hypertension were found in the middle-aged adults in Vietnam. Improving the individual's awareness and early screening for diabetes, and hypertension in adults for timely management are necessary.

This study employs a quantitative research approach to explore the impact of perceived ease of use and perceived usefulness on citizen engagement in Cambodian public governance using the Telegram platform. The study further investigates the mediating role of public value creation in this relationship. Utilizing Partial Least Squares Structural Equation Modeling (PLS-SEM), the study validates six hypotheses by surveying 290 Cambodian Telegram users engaged in public governance activities. The findings reveal that perceived ease of use and usefulness significantly and positively influence citizen engagement. Moreover, public value creation serves as a mediating factor in these relationships. The study offers empirical evidence supporting the Technology Acceptance Model (TAM) within the unique context of e-governance in a developing nation. The results provide crucial insights for policymakers and public administrators in Cambodia, emphasizing the need to prioritize user-friendly and valuable digital platforms for effective citizen engagement. Limitations and directions for future research are also discussed.

ABSTRACT: Objectives: In Eastern Europe, HIV-1 transmitted drug resistance (TDR) data, especially in the integrase (IN) region, are limited. In Estonia, INSTI (integrase strand transfer inhibitors) TDR has been studied only prior to the INSTI scale-up in late 2010s. The current study aimed to determine the levels of protease (PR), reverse transcriptase (RT) and IN surveillance drug resistance mutations (SDRMs) among newly diagnosed patients in Estonia in 2017. Methods: The study included 216 newly diagnosed HIV-1 individuals from 1 January until 31 December 2017 in Estonia. Demographic and clinical data were obtained from the Estonian Health Board, the Estonian HIV Cohort Study (E-HIV) and clinical laboratories’ databases. The PR-RT and IN regions were sequenced and analysed for SDRMs and subtype determination. Results: Seventy-one percent (151/213) of available HIV-positive samples were successfully sequenced. The overall level of TDR was 7.9% (12/151; 95% CI 4.4%–13.8%); no dual or triple class resistance was detected. No major INSTI mutations were found. The distribution of SDRMs for NNRTI, NRTI and PI was 5.9% (9/151), 1.3% (2/151) and 0.7% (1/151), respectively. The predominant NNRTI mutation was K103N. CRF06_cpx was the predominant variant (59%) in the Estonian HIV-1 population, followed by subtype A (9%) and subtype B (8%). Conclusion: Although no major INSTI mutations were found, close monitoring of INSTI SDRMs is needed considering the extensive use of the first- and second-generation INSTIs. PR-RT TDR is slowly rising in Estonia, indicating the need for continuous surveillance in the future. Low genetic barrier NNRTIs should be avoided in the treatment regimens.

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.

Fitz-Hugh-Curtis (FHCS) is characterized by an inflammation of the hepatic capsule concomitant or following pelvic infection due to Chlamydia trachomatis or Neisseria gonorrhea. It is a rare condition occurring most often in a woman of childbearing age and very rare in male patients. Splenic involvement is also a rare form of abdominal tuberculosis. The association of these two conditions is very uncommon. We report the exceptional case of a 58- year-old HIV-positive male patient, with whom abdominal ultrasound helped diagnose FHCS associated with abdominal tuberculosis invovlving the spleen.

Objective: To develop a generative adversarial network (GAN) to segment major blood vessels from retinal flat-mount images from oxygen-induced retinopathy (OIR) and demonstrate the utility of these GAN-generated vessel segmentations in quantifying vascular tortuosity. Design: Development and validation of GAN. Subjects: Three datasets containing 1084, 50, and 20 flat-mount mice retina images with various stains used and ages at sacrifice acquired from previously published manuscripts. Methods: Four graders manually segmented major blood vessels from flat-mount images of retinas from OIR mice. Pix2Pix, a high-resolution GAN, was trained on 984 pairs of raw flat-mount images and manual vessel segmentations and then tested on 100 and 50 image pairs from a held-out and external test set, respectively. GAN-generated and manual vessel segmentations were then used as an input into a previously published algorithm (iROP-Assist) to generate a vascular cumulative tortuosity index (CTI) for 20 image pairs containing mouse eyes treated with aflibercept versus control. Main Outcome Measures: Mean dice coefficients were used to compare segmentation accuracy between the GAN-generated and manually annotated segmentation maps. For the image pairs treated with aflibercept versus control, mean CTIs were also calculated for both GAN-generated and manual vessel maps. Statistical significance was evaluated using Wilcoxon signed-rank tests (P ≤ 0.05 threshold for significance). Results: The dice coefficient for the GAN-generated versus manual vessel segmentations was 0.75 ± 0.27 and 0.77 ± 0.17 for the held-out test set and external test set, respectively. The mean CTI generated from the GAN-generated and manual vessel segmentations was 1.12 ± 0.07 versus 1.03 ± 0.02 (P = 0.003) and 1.06 ± 0.04 versus 1.01 ± 0.01 (P < 0.001), respectively, for eyes treated with aflibercept versus control, demonstrating that vascular tortuosity was rescued by aflibercept when quantified by GAN-generated and manual vessel segmentations. Conclusions: GANs can be used to accurately generate vessel map segmentations from flat-mount images. These vessel maps may be used to evaluate novel metrics of vascular tortuosity in OIR, such as CTI, and have the potential to accelerate research in treatments for ischemic retinopathies. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Basalt Fiber Asphalt Concrete (BFAC) is an environmentally friendly and durable material with potential road, bridge, and infrastructure construction applications. This study investigates the application of Machine Learning (ML) models, specifically the classical Gradient Boosting (CGB) algorithm, in conjunction with metaheuristic algorithms, to predict the Marshall Stability (MS) and optimize the design of BFAC mixtures. The model is trained and tested on a comprehensive dataset of experimental samples, taking into account various input parameters, including basalt fiber (BF) properties, asphalt binder characteristics, and aggregate gradation. Hyperparameter tuning is employed to enhance the model's predictive performance using metaheuristic algorithms such as Particle Swarm Optimization (PSO), Hunger Games Search (HGS), and Bald Eagle Search (BES) and compared regarding the convergence and computational efficiency. The findings demonstrate that BES outperforms other algorithms, achieving the highest performance. The CGB-BES model is then applied to three optimization scenarios, focusing on maximizing the MS while minimizing BF and asphalt binder content. Post-processing and interpretation of the results reveal the importance of combining ML and materials engineering expertise. By highlighting the synergy between CGB-BES model and domain-specific knowledge, materials engineers can effectively optimize the mixtures and improve the design and performance of BFAC.

Sauropus androgynus is grown commonly in Vietnam, which has a high content of bioactive substances including chlorophyll, polyphenols, and antioxidant activity. Sauropus androgynus is used as food or a colorant for traditional Vietnamese cakes. Green pigments are employed in various industrial sectors, such as food, drinks, soap, and drug. Chlorophyll can be replaced synthetic green pigments that might be unhealthy. In this study, the effect of chlorophyll extraction efficiency and perceptional green color by extraction condition combinined with physical pretreatment methods was investigated using Sauropus androgynus leave as a model. Fresh raw materials were pre-treated by blanching, freezing and microwave treatment at 55w/g for 3 min and then extracted with 40% (v/v) ethanol solvent. The best chlorophyll recovery efficiency (CRE) from Sauropus androgynus by heat pretreatment methods with and without microwave assistance was 32.035% and 25.784% of chlorophyll content in material; or 1.081 mg/g d. w and 0.862 mg/g d. w of fresh leaves, respectively. The chlorophyll extract is then spray-dried to form a water-dispersible powder. Chlorophyll extracted with microwave-assisted pretreatment having high CRE that has potential applications in food production, but green color is not much more favorable than the non-microwave assisted sample.

Biofilms are found in many infections in the forms of surface-adhering aggregates on medical devices, small clumps in tissues, or even in synovial fluid. Although antibiotic resistance genes are studied and monitored in the clinic, the structural and phenotypic changes that take place in biofilms can also lead to significant changes in how bacteria respond to antibiotics. Therefore, it is important to better understand the relationship between biofilm phenotypes and resistance and develop approaches that are compatible with clinical testing. Current methods for studying antimicrobial susceptibility are mostly planktonic or planar biofilm reactors. In this work, we develop a new type of biofilm reactor—three-dimensional (3D) microreactors—to recreate biofilms in a microenvironment that better mimics those in vivo where bacteria tend to form surface-independent biofilms in living tissues. The microreactors are formed on microplates, treated with antibiotics of 1000 times of the corresponding minimal inhibitory concentrations (1000 × MIC), and monitored spectroscopically with a microplate reader in a high-throughput manner. The hydrogels are dissolvable on demand without the need for manual scraping, thus enabling measurements of phenotypic changes. Bacteria inside the biofilm microreactors are found to survive exposure to 1000 × MIC of antibiotics, and subsequent comparison with plating results reveals no antibiotic resistance-associated phenotypes. The presented microreactor offers an attractive platform to study the tolerance and antibiotic resistance of surface-independent biofilms such as those found in tissues.

A 45-year-old male with diabetes, hypertension and hyperlipidemia was referred to urology due to persistent symptoms of urinary frequency, urgency, nocturia, erectile dysfunction, and constant pain localized to the bladder, pelvis, and perineal area, 3–4 months after SARS-CoV-2 infection. A bladder biopsy showed urothelial mucosa and submucosa with hemorrhage and fibrin microthrombi in blood vessels. Hydrodistention of the bladder and pelvic floor physical therapy resolved symptoms, though bladder and pain symptoms returned upon reinfection with SARS-CoV-2. Urinalysis revealed elevated urinary interleukin-8, which may indicate localized bladder inflammation.

This paper introduces an innovative methodology for simulating fluid flow through doubly porous media. This technique combines finite element (FE) simulations and machine learning (ML) methods. The approach involves training ML models with a dataset of FE simulation outcomes, enabling predictions of macroscopic permeability under varied conditions. This strategy addresses the limitations of conventional simulation methods, which suffer from high computational demands and lack of systematic insight. The approach's precision and efficiency are confirmed through numerical experiments, achieving a coefficient of determination of 0.998. The outcomes underline the potential of the FEM-assisted ML strategy to considerably enhance fluid flow simulations in porous media. The technique can find applications across diverse domains within civil engineering. Furthermore, developing an intuitive graphical user interface (GUI) streamlines the application of the proposed approach.

Optimal dietary intake of omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFAs) is critical to human health across the lifespan. However, omega-3 index (O3I) determination is not routinely assessed due to complicated procedures for n3-LCPUFA analysis from the phospholipid (PL) fraction of erythrocytes. Herein, a high-throughput method for lipidomics based on multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry was applied to identify circulating PLs as surrogate biomarkers of O3I in two randomized placebo-controlled trials. An untargeted lipidomic data workflow using a subgroup analysis of serum extracts from sunflower oil versus high-dose fish oil (FO)-supplemented participants revealed that ingested n3-LCPUFAs were primarily distributed as their phosphatidylcholines (PCs) relative to other PL classes. In both high-dose FO (5.0 g/day) and EPA-only trials (3.0 g/day), PC (16:0_20:5) was the most responsive PL, whereas PC (16:0_22:6) was selective to DHA-only supplementation. We also demonstrated that the sum concentration of both these PCs in fasting serum or plasma samples was positively correlated to the O3I following FO (r = 0.708, P = 1.02 × 10−11, n = 69) and EPA- or DHA-only supplementation (r = 0.768, P = 1.01 × 10−33, n = 167). Overall, DHA was more effective in improving the O3I (ΔO3I = 4.90 ± 1.33%) compared to EPA (ΔO3I = 2.99 ± 1.19%) in young Canadian adults who had a poor nutritional status with an O3I (3.50 ± 0.68%) at baseline. Our method enables the rapid assessment of the O3I by directly measuring two circulating PC species in small volumes of blood, which may facilitate screening applications for population and precision health.

Estimation and correlation of the Hildebrand solubility parameter (δ) of polymers and small molecules is a common practice in membrane material science and is accomplished by experimental and numerical routes. In this paper, we revisit, update, and compare both routes to enhance the accuracy in the determination of δ. Best practices for the experimental determination of polymer solubility parameters are provided, and the viability of Dynamic Light Scattering (DLS) was demonstrated as an alternative to conventional time- and material-consuming techniques, such as Ubbelohde viscometry and swelling measurements. Glassy and rubbery polymers, including high fractional free volume (FFV) microporous polymers such as PIM-1 and poly(1-trimethylsilyl-1-propyne) (PTMSP), are among the samples included in this study with great relevance to membrane science. In an attempt to enhance the accuracy of numerical estimate of polymer solubility parameters via the group contribution method, we provide updated group contribution parameters, along with their uncertainty, according to the technique recently reported by Smith et al. These updated group contribution parameters result in a mean absolute relative error of 9.0% in predicting the solubility parameter on a test set of 40 polymers, which is on par with the average 10% error reported previously. We also show, using machine learning techniques, that augmenting the group contribution model with extra parameters or non-linear relationships does not improve its accuracy. Results of the updated group contribution technique and dynamic light scattering measurements were compared to experimental viscometry on four test polymers, and the difference between the three techniques is compared.