Search

There is a growing demand for the consumption of medicinal mushrooms and their products. Ganoderma lucidum and Cordyceps militaris are two important medicinal mushrooms with significant pharmacological activities. In this study, we aim to develop a preparation of the extracts of these two mushrooms, and investigate its composition, antioxidant activities, and protective effects against oxidative damage. Liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (LC-QTOF MS) was employed to analyze the chemical profiles of the mixture. A total of 94 compounds were identified as belonging to phenolic acids, flavonoids, triterpenes, and nucleosides. In addition, HPLC-DAD was used to quantify major compounds. Ferulic and cinnamic acids were predominant in the phenolic acid groups, with corresponding concentrations of 0.41 and 0.29 mg/g. The concentration of ganoderic acid A was 0.08 mg/g, and the contents of adenosine and cordycepin were 0.53 and 0.14 mg/g, respectively. The mixture could scavenge free radicals and reduce ferric ions in vitro. The preparation also showed nontoxic but proliferative effects on human fibroblast cells. In addition, it could protect fibroblasts against oxidative stress, reducing 21–22% of cell death in the presence of H2O2. These findings provide more information on the applications of medicinal mushrooms in the functional food and pharmaceutical industries.

Endovenous laser ablation (EVLA) is a minimally invasive surgical procedure, often guided by ultrasound (US) imaging, for treating venous insufficiencies. US imaging limitations in accurately visualizing the catheter and the lack of a temperature monitoring system can lead to sub-optimal outcomes. An integrated photoacoustic (PA)-guided EVLA system has been previously developed and reported to overcome the shortcomings of US-guided procedure. In this study, we further characterized the system and tested the in vivo utility. In addition, PA thermometry was further explored by compensating the variation of PA signal with temperature with respect to the temperature-dependent absorption of blood and water. In vivo imaging results indicated that the PA-guided EVLA system can provide high contrast and accurate images of the ablation catheter tip overlaid on US images of the background tissue. Additionally, absorption-compensated PA signal amplitudes over a relevant range of temperature were measured and demonstrated.

Summary: Current single-cell RNA sequencing (scRNA-seq) protocols are limited by the number of cells that can be simultaneously sequenced, restricting the ability to resolve heterogeneity of rare cell types. We describe here a protocol for rapid isolation of myeloid cells from tumor-harboring mouse cerebellum without cell sorting to minimize cell damage for scRNA-seq. This protocol includes the procedures for further enrichment of myeloid cells using CD11b+ magnetic beads, followed by the generation of scRNA library and sequencing analysis.For complete details on the use and execution of this protocol, please refer to Dang et al. (2021).

Summary: Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation. Our analyses reveal significant TAM heterogeneity, identify markers of ontologically distinct TAM subsets, and show the impact of brain microenvironment on the differentiation of tumor-infiltrating monocytes. TAM composition undergoes dramatic changes with treatment and differs significantly between molecular-targeted and radiation therapy. We identify an immunosuppressive monocyte-derived TAM subset that emerges with radiation therapy and demonstrate its role in regulating T cell and neutrophil infiltration in MB.

Summary: Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this “balancing act” remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor κB (NF-κB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a “default” Spic-dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-κB and STATs attune inflammatory responses and iron metabolism in macrophages.

Aim: To describe prevalence of early initiation of breastfeeding and associated factors among Vietnamese mothers. Methods: A self-administered questionnaire was used to survey 1812 mothers whose infants were aged 0 to less than 30 months in multi-center Vietnam. Multivariate logistic regression was performed to identify factors associated independently with early initiation of breastfeeding. Results: Prevalence of early initiation of breastfeeding was 57.2 % and this prevalence was higher in female infants compared with male infants (p = 0.004). Factors associated with increased odds of early initiation of breastfeeding include female infants (aOR: 1.33; 95%CI: 1.06 to 1.68) living in urban areas (aOR: 1.34, 95%CI: 1.05 to 1.71), giving birth in private hospitals (aOR: 1.94, 95%CI: 1.25 to 3.03), vaginal birth (aOR: 1.70, 95%CI: 1.34 to 2.16). Factors associated with decreased odds of early initiation of breastfeeding include higher educational level, mother's weight gain during pregnancy, and infant complication at birth. Compared with mothers who had not experienced skin-to-skin contact with their babies, the prevalence of early initiation of breastfeeding was higher in mothers who experienced 90 min (aOR: 10.98, 95%CI: 6.79 to 17.75). Conclusion: Focusing on modifiable factors should be a key priority to help improve early initiation of breastfeeding practice.

Background: Low-dose oral food challenge (LD-OFC) is an approach to avoid complete elimination in high-risk patients with wheat allergy (WA). We examined the 3-year prognosis after LD-OFC among patients who passed and failed LD-OFC. Methods: Children with immediate-type WA aged ≤6 years with a history of reaction to ≤390 mg of wheat protein underwent their first LD-OFC with 52 mg (baseline LD-OFC). After passing the LD-OFC, children stepped up to 390, 1300, and 5200 mg step-by-step every 3–6 months. After failing LD-OFC, children repeated LD-OFC every 6–12 months. We assessed wheat tolerance defined as consuming 5200 mg without symptoms for 3 years after baseline LD-OFC. Results: The median age of 124 children was 2.4 years, and the wheat- and ω-5-gliadin-specific immunoglobulin E (IgE) levels (kUA/L) were 23.6 and 2.1, respectively. Upon baseline LD-OFC, 57% passed (LD-tolerant), whereas 43% failed (LD-reactive). Within 3 years, 38% of the LD-reactive group passed re-administered LD-OFC, and 70% of all participants avoided complete elimination. The percentage of the participants who became capable of consuming 390 mg (87% vs. 18%), 1300 mg (78% vs. 13%), and acquired tolerance (70% vs. 13%) was significantly higher in the LD-tolerant group than in the LD-reactive group (p

The graphene oxide-silver nanocomposites (AgNPs@GO) have attracted much attention due to their targeted effect and nontoxicity against normal cells. The toxic factors, including the chemical reagents during the synthesis of AgNPs@GO, must be considered and minimized for the cancer treatment application. This study aims to apply the response surface methodology (RSM) with central composite design (CCD) for investigating independent factors, including mass ratio Ag+/GO, temperature, and reaction time, to find the optimal conditions for graphene oxide-silver nanocomposite (AgNPs@GO) synthesis. The green tea leaves extract was used as an alternative reducing agent for the green synthesis of AgNPs@GO. The maximum absorption wavelength of AgNPs, highly dependent on silver nanoparticles' size and shape, was utilized as the target function. The results show optimal conditions for the green synthesis of AgNPs@GO with the mass ratio of Ag+/GO is 2:1 at 30 °C for 40 minutes. The average maximum absorption wavelength of the synthesized AgNPs@GO at the optimal condition of 416.78 nm, with silver nanoparticles on the GO sheet having an average size of 21.2 ± 5.61 nm, the round shape and distributed on the GO sheets uniformly, without aggregation. In addition, the synthesized AgNPs@GO was against HepG2, MDA231, and MDA453, with the IC₅₀ of 152.582, 152.428, and 199.844 μg/mL, respectively.

Although silver nanoparticles have long attracted scientists due to their remarkable antibacterial properties, the tendency of AgNPs to agglomerate results in diminished antibacterial activities and increased toxicity against normal cells. Among carbon-based nanomaterials, graphene oxide (GO), the oxidized form of graphene, can be utilized as a base for AgNPs to grow and disperse. Regarding the chemical approach, it is conventional to engage sodium borohydride (NaBH4) or hydrazine to reduce silver ions. However, using excessive amounts of these chemicals raises concerns about toxicity in biomedical applications and environmental issues. Here, this work report the synthesis of AgNPs@GO nanocomposites by reducing silver nitrate on GO using various green reducing agents, including ascorbic acid, Houttuynia cordata Thunb. leaf extract, Coffea robusta L. Linden (Robusta green coffee) bean extract, and Camellia sinensis (L.) Kuntze (green tea) leaf extract. The synthesized AgNPs@GO were characterized by X-ray diffraction spectrum, UV–Vis analysis, and dynamic light scattering, followed by an evaluation of the antibacterial activity using the diffusion agar method. The results demonstrate the high potential of green tea as a green-reducing agent in the synthesis procedure of AgNPs. The synthesized AgNPs@GO using green tea extract showed a similar UV–Vis spectral shape compared to the AgNPs@GO synthesized using NaBH4 with the maximum absorption wavelengths of AgNPs at 428 nm and GO at 203.5 nm. The AgNPs@GO synthesized also had the smallest average diameter (609.67 nm) and the highest magnitude of the zeta potential (29.83 mV) among all synthesized samples. Noteworthy is that AgNPs@GO synthesized with green tea extract demonstrated significant stability over 40 days. Furthermore, the results of the antibacterial experiments reveal that the diameter of the inhibitory zone was approximately 2 mm, half that of the control drug amoxicillin (1 mg/mL). In summary, green tea leaf extract emerged as the most effective reducing agent for the eco-friendly synthesis of stable and durable AgNPs@GO. This indicates a suitable and straightforward process for large-scale antibacterial production with potential applications in biological wastewater treatment.

Introduction: To date, newborn screening (NBS) for proximal urea cycle disorders, including Ornithine transcarbamylase deficiency (OTCD), was not recommended due to the lack of appropriate tests and insufficient evidence of the benefits. This study aimed to investigate the potential of tandem mass spectrometry (MS/MS) for OTCD screening and its value in guiding further investigation to obtain a final diagnosis in high-risk patients. Methods: The study included patients with OTCD referred to the National Children's Hospital between April 2020 and November 2023. A retrospective evaluation of amino acid concentrations measured by MS/MS and their ratios in patients with early-onset and late-onset OTCD was conducted. Results: While all ten early-onset cases had glutamine concentrations above the upper limit, only five of them had citrulline concentrations below the lower limit of the reference interval. Only two late-onset cases had elevated glutamine levels, while all had citrulline within reference intervals. The Cit/Phe ratio was decreased, and the Gln/Cit and Met/Cit ratios were increased in all early-onset OTCD cases, while they were abnormal in only one late-onset case. Conclusions: The preliminary results suggest that hyperglutaminemia, in combination with low or normal citrulline concentrations and specific ratios (Gln/Cit, Met/Cit, and Cit/Phe), can serve as reliable markers for screening early-onset OTCD in high-risk patients. However, these markers proved less sensitive for detecting the late-onset form, even in symptomatic patients.

The main objective of the present study is to synthesize iron oxide catalysts with engineered crystal defects and to clarify their crucial impact on the final catalytic activity in the CO2 hydrogenation process. The method used to engineer the desired crystal defects is based on changing the precipitation reaction conditions, such as the addition rate and the order of the precipitant during the primary phase of the synthesis of iron oxide catalysts. The catalyst synthesis process is based on the formation of iron oxalates in the first step, followed by thermal decomposition into iron oxides in the second step, which were subsequently tested as catalysts in CO2 hydrogenation. The reversed double-beam photoacoustic spectroscopy used for advanced characterization of the prepared catalysts demonstrated that the observed change in catalytic activity is related to the energy and density of electron traps connected with the defects in the crystal lattice of the catalysts. These defects occur during the precipitation of oxalates, and their formation is significantly affected by changes in the precipitation conditions, i.e., the course of nucleation and growth of iron oxalate crystals. The results of the presented study thus affirmed the cardinal importance of defect engineering in heterogeneous catalysis.

Objective: To compare the perioperative, oncological, and functional outcomes between single-port robot-assisted radical prostatectomy (SP-RARP) and multiport robot-assisted radical prostatectomy (MP-RARP) via a meta-analysis. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 15, 2022. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines. The risk ratio and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 368 retrieved abstracts, 41 underwent full-text review, and seven studies were included in the final analysis, comprising a total cohort of 1,934 cases of RARP (355 SP-RARP cases and 1,579 MP-RARP cases). Compared to MP-RARP, the SP-RARP group had less postoperative pain score (MD = –0.7, 95% CI –1 to –0.4, P

The detection of ampicillin plays a crucial role in managing and monitoring its usage and resistance. This study introduces a simple and effective biosensor for ampicillin detection, utilizing the unique absorbance features of Mn-doped ZnS capped by chitosan micromaterials in conjunction with β-lactamase activity. The biosensors can detect ampicillin concentrations from 13.1 to 72.2 μM, with a minimum detection limit of 2.93 μM for sensors based on 300 mg/L of the sensing material. In addition, these sensors show high specificity for ampicillin over other antibiotics such as penicillin, tetracycline, amoxicillin, cephalexin, and a non-antibiotic-glucose. This specificity is demonstrated by an enhancing effect when beta-lactamase is used, as opposed to a quenching effect observed at 340 nm in the absorbance spectrum when no beta-lactamase is present. This research highlights the potential of affordable chitosan-capped Mn-doped ZnS micromaterials for detecting ampicillin through simple absorbance measurements, which could improve the monitoring of antibiotics in both clinical and environmental settings.

Summary: If our visual system has a distinct computational process for motion trajectories, such a process may minimize redundancy and emphasize variation in object trajectories by adapting to the current statistics. Our experiments show that after adaptation to multiple objects traveling along trajectories with a common tilt, the trajectory of an object was perceived as tilting on the repulsive side. This trajectory aftereffect occurred irrespective of whether the tilt of the adapting stimulus was physical or an illusion from motion-induced position shifts and did not differ in size across the physical and illusory conditions. Moreover, when the perceived and physical tilts competed during adaptation, the trajectory aftereffect depended on the perceived tilt. The trajectory aftereffect transferred between hemifields and was not explained by motion-insensitive orientation adaptation or attention. These findings provide evidence for a trajectory-specific adaptable process that depends on higher-order representations after the integration of position and motion signals.

Background: In coronary artery disease (CAD), plaque progression and plaque composition are associated with cardiovascular risk. Whether compositional plaque progression in non-obstructive CAD differs between women and men is less studied. Methods: We included 31 patients (42% women) with chronic non-obstructive CAD from the Norwegian Registry of Invasive Cardiology, undergoing serial coronary computed tomography angiography (CCTA) on clinical indication (median inter-scan interval 1.8 [1.5–2.2] years). We performed quantitative and qualitative plaque analysis of all coronary artery segments. Results: Women were older compared to men (65 ± 8 years vs. 55 ± 12 years, p = 0.019), while there was no difference in the prevalence of hypertension, diabetes, smoking or statin treatment between groups. At baseline, women had a higher total plaque burden, more calcified plaques, and less fibro-fatty and necrotic core plaques compared to men (all p

Guidelines for the management of in-hospital cardiac arrest resuscitation are often drawn from evidence generated in out-of-hospital cardiac arrest populations and applied to the in-hospital setting. Approach to airway management during resuscitation is one example of this phenomenon, with the recommendation to place either a supraglottic airway or endotracheal tube when performing advanced airway management during in-hospital cardiac arrest based mainly in clinical trials conducted in the out-of-hospital setting. The Hospital Airway Resuscitation Trial (HART) is a pragmatic cluster-randomized superiority trial comparing a strategy of first choice supraglottic airway to a strategy of first choice endotracheal intubation during resuscitation from in-hospital cardiac arrest. The design includes a number of innovative elements such as a highly pragmatic design drawing from electronic health records and a novel primary outcome measure for cardiac arrest trials—alive-and-ventilator free days. Many of the topics explored in the design of HART have wide relevance to other trials in in-hospital cardiac arrest populations.

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.

Objective: Circulating tumor DNA (ctDNA) offers a minimally-invasive alternative to study genomic changes in recurrent malignancies. With a high recurrence rate, the overall survival in high-grade serous ovarian carcinoma (HGSC) has remained low. Our objectives were to determine whether ctDNA from plasma adequately represents HGSC, and to find mutational changes at relapse suggesting therapy options that could alter patient outcome. Methods: We collected 152 longitudinal plasma and 92 fresh tissue samples from 29 HGSC patients, sequencing and detecting mutations with a gene panel of more than 700 cancer-related genes. Tumor content was measured using TP53 VAF. We analyzed the concordance between the mutations in tissue and plasma samples and calculated correlations to patient outcomes. We also searched for novel mutations appearing at relapse. Results: The concordance rate between mutations in plasma compared to tumor tissue was 83 % at diagnosis and 90 % at relapse. CtDNA was released similarly from the tubo-ovarian tumors, intra-abdominal metastases and ascites. CtDNA release was high when CA-125 level was elevated. The TP53 VAF in ctDNA from plasma samples before the third cycle of primary chemotherapy showed a negative correlation to patient outcome. At relapse, 19 novel, pathogenic DNA mutations appeared, suggesting possible actionable alterations and biological mechanisms related to chemoresistance. Conclusion: Relapse ctDNA samples reflect tissue samples well and longitudinal sampling provides a timely source for mutational profiling. The emerging genetic mutations at recurrence propose that ctDNA accurately represents the widespread disease and provides possibilities for personalized therapy options.

Phthalates are widely used as plasticizer and associated with various health issues. Recently, non-phthalate plasticizers are replacing phthalates; however, the exposure to these substances and the risk in Japan is unclear. In this study, we assessed the concentrations of phthalates, non-phthalate plasticizers, and phthalate degradation products in house dust and determined their respective exposure risks via oral and dermal routes. Twelve phthalates, seven non-phthalate plasticizers, and two degradation products were determined in the house dust obtained from 100 Japanese homes. The median concentration of di(2-ethylhexyl) phthalate (DEHP), accounting for 85 % of the total concentration of phthalates and non-phthalate plasticizers detected in this study, was 2.1 × 103 μg/g of dust. Apart from DEHP, diisononyl phthalate (DINP) and di(2-ethylhexyl) terephthalate (DEHT) were the most abundant in the house dust, accounting for 6.2 % (median: 1.7 × 102 μg/g of dust) and 6.1 % (median: 1.7 × 102 μg/g of dust) of the total concentrations, respectively. DEHP and DEHT concentrations in house dust were higher in apartment and small houses (floor area: ≤30 m2 or 31–60 m2 for DEHP and 31–60 m2 for DEHT) than in detached and large houses (floor area: ≥121 m2). Conversely, di-n-butyl phthalate (DnBP) concentrations were significantly higher in detached and large houses (floor area: ≥121 m2) than in apartment and small houses (floor area: ≤30 m2). The total hazard quotient (HQ), using the maximum concentration in house dust, revealed that oral and dermal exposure to house dust was 1.3 × 10-6–0.11 for adults (all substances) and 1.6 × 10-5–2.2 × 10-2 for preschool children (except for DnBP and DEHP), suggesting no risk. The HQs for DnBP and DEHP exposure via house dust for preschool children using the maximum values were 0.46 and 1.2, and 6.0 × 10-3 and 0.18 using the median values, indicating that risk of DEHP exposure should be exhaustively determined by considering other exposure routes that were not evaluated in this study, such as diet.

Background: Epicardial adipose tissue (EAT) accumulation has been associated with inflammation, atherosclerosis and microvascular dysfunction. Whether increased EAT volume is associated with coronary plaque vulnerability and demand myocardial ischemia in patients with non-obstructive coronary artery disease (CAD) is less explored. Methods: In 125 patients (median age 63[58, 69] years and 58% women) with chest pain and non-obstructive CAD, EAT volume was quantified on non-contrast cardiac CT images. EAT volume in the highest tertile (>125 ml) was defined as high EAT volume. Total coronary plaque volume and plaque vulnerability were quantified by coronary CT angiography (CCTA). Demand myocardial ischemia was detected by contrast dobutamine stress echocardiography. Results: High EAT volume was more common in men and associated with higher BMI, hypertension, increased left ventricular mass index (LVMi), C-reactive protein (CRP) and positive remodelling (all p

Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for detecting and profiling longitudinal genomics changes in cancer. While copy-number alterations (CNAs) play a major role in cancers, treatment effect monitoring using copy-number profiles has received limited attention as compared to mutations. A major reason for this is the insensitivity of CNA analysis for the real-life tumor-fraction ctDNA samples. We performed copy-number analysis on 152 plasma samples obtained from 29 patients with high-grade serous ovarian cancer (HGSC) using a sequencing panel targeting over 500 genes. Twenty-one patients had temporally matched tissue and plasma sample pairs, which enabled assessing concordance with tissues sequenced with the same panel or whole-genome sequencing and to evaluate sensitivity. Our approach could detect concordant CNA profiles in most plasma samples with as low as 5% tumor content and highly amplified regions in samples with ∼1% of tumor content. Longitudinal profiles showed changes in the CNA profiles in seven out of 11 patients with high tumor-content plasma samples at relapse. These changes included focal acquired or lost copy-numbers, even though most of the genome remained stable. Two patients displayed major copy-number profile changes during therapy. Our analysis revealed ctDNA-detectable subclonal selection resulting from both surgical operations and chemotherapy. Overall, longitudinal ctDNA data showed acquired and diminished CNAs at relapse when compared to pre-treatment samples. These results highlight the importance of genomic profiling during treatment as well as underline the usability of ctDNA.

In this work, the effect of an ammonium nitrate ionic liquid on the corrosion susceptibility of an Al-Cu-Mg alloy was investigated. The effect of the nitrate anion and the ammonium cation on the anodic and cathodic kinetics were studied separately using potentiodynamic polarisation testing, electrochemical impedance spectroscopy and scanning electron microscopy. The results revealed a significant anodic inhibition, associated with a cation/anion synergy. The cathodic kinetics however increase with the presence of nitrates, associated with nitrate reduction reaction. Conversely, longer alkyl chain seemed to reduce the effect of nitrates. Such findings are promising in the context of developing ecofriendly chromate alternatives.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80%–85% of total cases and leading to millions of deaths worldwide. Drug resistance is the primary cause of treatment failure in NSCLC, which urges scientists to develop advanced approaches for NSCLC treatment. Among novel approaches, the miRNA-based method has emerged as a potential approach as it allows researchers to modulate target gene expression. Subsequently, cell behaviors are altered, which leads to the death and the depletion of cancer cells. It has been reported that miRNAs possess the capacity to regulate multiple genes that are involved in various signaling pathways, including the phosphoinositide 3-kinase, receptor tyrosine kinase/rat sarcoma virus/mitogen-activated protein kinase, wingless/integrated, retinoblastoma, p53, transforming growth factor β, and nuclear factor-kappa B pathways. Dysregulation of these signaling pathways in NSCLC results in abnormal cell proliferation, tissue invasion, and drug resistance while inhibiting apoptosis. Thus, understanding the roles of miRNAs in regulating these signaling pathways may enable the development of novel NSCLC treatment therapies. However, a comprehensive review of potential miRNAs in NSCLC treatment has been lacking. Therefore, this review aims to fill the gap by summarizing the up-to-date information on miRNAs regarding their targets, impact on cancer-associated pathways, and prospective outcomes in treating NSCLC. We also discuss current technologies for delivering miRNAs to the target cells, including virus-based, non-viral, and emerging extracellular vesicle-based delivery systems. This knowledge will support future studies to develop an innovative miRNA-based therapy and select a suitable carrier to treat NSCLC effectively.

Given that histone acetylation via histone acetyltransferases (HATs) and histone deacetylases (HDACs) is significant in memory formation, HDAC2 has been thoroughly investigated as a potential therapeutic target for the treatment of cognitive dysfunction. Although HDAC inhibitors have been discovered through in vitro enzyme assay, off-target effects on other HDACs are common due to their conserved catalytic domains. Each HDAC could be regulated by specific intracellular molecular mechanisms, raising the possibility that a cell-based assay could identify selective inhibitors targeting specific HDACs through their regulatory mechanisms. Here, we propose a versatile, cell-based reporter system for screening HDAC2 inhibitors. Through RNA-sequencing from human cultured neuronal cells, we determined that expression of a transcriptional repressor, inhibitor of DNA binding 1 (ID1), is increased by knockdown of HDAC2. We also established the knock-in neuronal cell lines of a bioluminescence reporter gene to ID1. The knock-in cell lines showed significant reporter activity by known HDAC inhibitors and by HDAC2-knockdown but not by HDAC1-knockdown. Thus, our neuronal cell-based reporter system is a promising method for screening the specific inhibitors of HDAC2 but not HDAC1, by potentially targeting not only HDAC2, but also the regulatory mechanisms of HDAC2 in neurons.

Objectives: We aimed to clarify the content of care provided by midwives working in hospitals and clinics in Japan and the unmet needs in midwifery care from mothers’ perspectives. Design: This study employed a qualitative approach through semi-structured interviews. Setting: Fifteen Japanese women, whose youngest singleton children were aged 12–18 months, were asked to recall their experiences with midwives, from pregnancy through the first postpartum year. Verbatim records were analyzed using thematic analysis. Results: Seven themes regarding the care provided by midwives were generated: confirmation of physical condition, maintenance and promotion of perinatal physiological process, support for better preparation for childbirth, assistance in labour and childbirth, support for a new life with a baby at home, support for the family, and care for comfort and confidence as a mother. Unmet needs were identified in all themes, except for ‘confirmation of physical condition’ and ‘support for the family’. Ten subthemes, under the five themes of unmet needs, were integrated into three categories: midwives’ responses to potential concerns, lack of continuity of care, and lack of personalised care. Key conclusions and implications for practice: Midwives in hospitals and clinics in Japan mainly provided care from pregnancy to one-month postpartum, in line with global core competencies. However, they could respond more effectively to the potential concerns of women, and provide continuous, personalised care more sufficiently. Improving working environments for midwives and collaborating with postpartum public health services are key to addressing these unmet needs of women, leading to women-centred care.

Dominant dynamin 2 (DNM2) mutations are responsible for the autosomal dominant centronuclear myopathy (AD-CNM), a rare progressive neuromuscular disorder ranging from severe neonatal to mild adult forms. We previously demonstrated that mutant-specific RNA interference is an efficient therapeutic strategy to rescue the muscle phenotype at the onset of the symptoms in the AD-CNM knockin-Dnm2R465W/+ mouse model. Our objective was to evaluate the long-term benefit of the treatment along with the disease time course. We demonstrate here that the complete rescue of the muscle phenotype is maintained for at least 1 year after a single injection of adeno-associated virus expressing the mutant-specific short hairpin RNA (shRNA). This was achieved by a maintained reduction of the mutant Dnm2 transcript. Moreover, this long-term study uncovers a pathological accumulation of DNM2 protein occurring with age in the mouse model and prevented by the treatment. Conversely, a physiological DNM2 protein decrease with age was observed in muscles from wild-type mice. Therefore, this study highlights a new potential pathophysiological mechanism linked to mutant protein accumulation and underlines the importance of DNM2 protein expression level for proper muscle function. Overall, these results strengthen the allele-specific silencing approach as a robust, safe, and efficient therapy for AD-CNM.

Uveal melanoma is the most common primary intraocular malignancy and can occur in the choroid, the ciliary body, or the iris. It is most often diagnosed based on clinical examination by an ophthalmologist. Nearly all patients present with visual symptoms. Characteristic findings on clinical examination include pigmented or pale choroidal masses with serous retinal detachments and acoustic hollowness seen with ocular ultrasonography. CT and MRI of the orbits are not traditionally utilized for the diagnosis of uveal melanoma. We present 3 cases in which uveal melanoma was an incidental finding on neuroimaging for unrelated conditions in asymptomatic patients. Radiologists should maintain a high suspicion for uveal melanoma when an intraocular mass of greater than 2 mm in thickness is seen on CT or MRI.

Background and Aims: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) progresses with a highly multicentric occurrence (MO) even after radical hepatectomy. Despite several efforts to clarify the pathogenesis of MO, the underlying molecular mechanism remains elusive. The aim of this study was to evaluate alterations in DNA methylation in noncancerous liver tissues in the MO of HCC. Methods: A total of 203 patients with HCV-related HCC who underwent radical hepatectomy at our hospital between January 2008 and January 2012 were recruited. We defined a group of nonearly recurrence of HCC (NR) for ≥3 years after radical hepatectomy and a group of early recurrence of HCC (ER) with MO within 2 years after radical hepatectomy. Results: Three patients each were selected in the NR and ER groups in the first set, and 13 patients in the NR group and 17 patients in the ER group were selected in the second set. Genome-wide DNA methylation profiles were obtained from noncancerous liver tissues using a Human Methylation 450 BeadChip, and the differences between the groups were analyzed for each set. After excluding single nucleotide polymorphism-associated methylation sites and low-call sites, 401,282 sites were assessed using a generalized linear model without any adjustments. Nine gene regions, APBB1P, CLSTN3, DLG5, IRX5, OAS1, SOX12, SNX19, TENM2, and TRIM54, exhibiting a significant difference (P < .001) in DNA methylation levels were identified in the common direction between the 2 analysis sets. Conclusion: Alterations in DNA methylation of 9 genes in noncancerous liver tissues appear to be involved in MO after radical hepatectomy for HCV-related HCC.

Groundwater in southern Hanoi, Vietnam has been recently detected to possess high concentration of ammonium ion (NH4+). Otherwise, one of the abundant sources of NH4+ comes from municipal solid waste landfills. Bentonite-clay mixtures (BCMs) widely utilized as landfill bottom barriers in various countries, but limited in Vietnam should perform well to isolate NH4+ from groundwater. This study is to evaluate combined effects of temperature and initial ammonium concentration on adsorption, diffusion, and permeability through mixtures of indigenous clay with 0 %, 5 %, 10 %, 15 % bentonite. The results indicated more effective NH4+ adsorption capacity for low initial concentration than high initial concentration in all temperatures (20, 35, and 50 °C). The temperature dependency showed an increase in adsorption coefficient from 20 °C to 35 °C and a decrease in the range of 35 °C and 50 °C. Whereas diffusion coefficient and hydraulic conductivity for all cases keep increasing gradually in both temperature ranges. The reasonable mass of bentonite content of 15 % should be added into local clay for landfill bottom liners in such conditions of elevated temperature at 50 °C and interaction of ammonium solution 1000 mg/L. The micro-structures via SEM images of these materials provided the proofs of both improvement of hydraulic barrier properties for indigenous clay owing to bentonite presence and NH4+ effects on their micro-structures.

DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.

Summary: Background: Normative values for different morphometric parameters of muscle fibres during paediatric development, i.e. from 0 to 18 years, are currently unavailable. They would be of major importance to accurately evaluate pathological changes and could be used as reference biomarkers for evaluating treatment response in clinical trials, or physiological adjustments in sports or ageing. Methods: Data were derived from 482 images with a total of 33 094 fibres from 10 μm cross-sections of snap-frozen muscle from 83 deltoid muscle biopsies from patients, 0–18 years, without neuromuscular pathology stained with ATPase 9.4. Data was acquired and analysed with patented image analysis algorithms from “CARPACCIO.cloud”. Several parameters were extracted or calculated, including cross-sectional area (CSA), fibre type, circularity, as well as the Minimum diameter of Feret (MinFeret). Findings: This study illustrates changes in quantitative parameters for muscle morphology over the course of paediatric development and the pivotal changes occurring around puberty. Only fibre size parameters (MinFeret, CSA) are dependent on gender, and only after puberty. All other parameters vary in a similar manner for females and males. The proportion of type 1 fibres is essentially constant from birth to age 10, decreasing to ≈40% by age 18. Circularity decreases with age, to plateau after age 10 for both fibre types. Interpretation: Normative values and reference charts for muscle fibre types in this age range have been generated to allow comparison of data from patients in pathology laboratories working on neuromuscular diseases. Funding: BPI FRANCE, PULSALYS, Association de l’Institut de Myologie, French National Research Agency (ANR), LABEX CORTEX of Université de Lyon.

Ischiopagus conjoined twinning is a rare congenital defect. The surgical separation of conjoined twins is difficult because of the complex anatomy and physiology. Careful preoperative assessment, planning, and effective surgical teams are critically important for achieving a good outcome. We describe the successful separation of ischiopagus tetrapus conjoined twins as a representative case demonstrating the growth of pediatric surgery in southern Vietnam.

Purpose: While schools worldwide have employed closed-circuit television (CCTV) to discourage school violence, the literature shows that stakeholder attitudes toward adopting this technology are inconsistent across cultures. Generally, they are concerned with effectiveness, necessity, privacy, and operational transparency. Based on the Technology Acceptance Model for Video Surveillance (TAM-VS) theory, this study examined the attitudes of educational stakeholders, namely educators and students, toward adopting CCTV in Vietnam. This study aims to investigate which criteria Vietnamese stakeholders use to evaluate the necessity of CCTV and whether the concerns of Vietnam, a developing country, are similar to those of developed countries. Methods: This study addressed these research questions by purposely sampling and interviewing 49 Vietnamese high school students, recent high school graduate students, teachers, and administrators. It employed semi-structured and in-depth interviews to gather content-rich data and applied thematic analysis to discover new insights from stakeholders under the modified TAM-VS framework. The study also followed the COREQ guidelines to improve the transparency and rigor of the data collection and analysis. Findings: On an exploratory basis, most Vietnamese stakeholders believed that while CCTV cannot comprehensively prevent school violence, its effectiveness overshadows privacy concerns. Regarding operational transparency concerns, participants suggested that better communication, consent collection, and the right to amend school policies related to CCTV are important. From the participants’ perspective, the three criteria for evaluating the necessity of CCTV were (1) its effectiveness in controlling school violence, (2) serving other purposes to enhance overall schooling performance, and (3) insufficient existing methods. Conclusions: This study provides context-rich insights into the perceptions of the necessity, effectiveness, privacy, and operational transparency concerns of CCTV across different stakeholders in the education and developing country context. On the practical contribution, the research identifies strategies that school administrators can employ to promote CCTV acceptance in Vietnamese high schools.

Background: Acylcarnitines are essential for mitochondrial fatty acid oxidation. Earlier studies suggest that impaired energy metabolism may be implicated in the pathogenesis of microvascular angina. We explored metabolites from the carnitine pathway as predictors of cardiovascular disease (CVD) - and all-cause mortality among patients with non-obstructive coronary artery disease (NOCAD). Methods: A total of 1046 patients with suspected stable coronary syndrome underwent coronary angiography during 2000–2004, with findings of NOCAD. Serum levels of 8 selected carnitine metabolites were analyzed through liquid chromatography tandem mass spectrometry. Associations with CVD- and all-cause mortality were assessed by multivariable Cox regression models. Results: Median age at inclusion was 57 years. 51.5% were men. During median (25th- 75th percentiles), 14.1 (13.2–15.4) years of follow-up, 5.7% of the participants died from CVD and the incidence of all-cause mortality was 17.3%. Serum acetyl, octanoyl- and palmitoylcarnitine predicted CVD mortality with multivariable HR and 95% CI (per SD increment log transformed) of 1.36 (1.01–1.83), 1.49 (1.15–1.93) and 2.07 (1.49–2.85), p ≤ 0.04, respectively. Higher serum acetyl- and palmitoylcarnitines were also associated with increased risk of all-cause mortality (HR (95% CI): 1.27 (1.01–1.50), and 1.51 (1.26–1.81), p ≤ 0.007. Baseline levels of the precursors trimethyllysine and ƴ-butyrobetaine, carnitine or the odd chained propionylcarnitine and (iso)valerylcarnitine were not associated with adverse outcomes. Conclusion: Elevated serum even-chained acylcarnitines predicted adverse long-term prognosis in NOCAD. The strongest risk estimates were observed for palmitoylcarnitine, which predicted both CVD- and all-cause mortality after extensive multivariable adjustments. Underlying pathomechanisms should be further elucidated.

Summary: Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12–71·55], 49·11 [41·26–58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2–152·3], 80·0 [50·8–125.9] and 95·1 [63·1–143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Titanium dioxide/graphene aerogel (TiO2/GA) was synthesized via a one-pot hydrothermal method and characterized by various spectroscopic techniques, including X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscope, transmission electron microscopy, Raman spectroscopy, and UV-Vis spectroscopy. The influences of pH and TiO2/GA dose on the photocatalytic performance were investigated against positive dye methylene blue (MB) under UV light control. The characterization of TiO2/GA revealed that the synthesized TiO2 nanosize of 12–22.5 nm was uniformly distributed onto the graphene layers. The bandgap of the as-prepared nanocomposite was 2.63 eV, lower than that of pure TiO2 (3.2 eV). The kinetic studies exhibited that the adsorption–desorption equilibrium was achieved after 60 min following the pseudo-second-order. Meanwhile, 99.9% of MB was eliminated after 120 min at pH 9 with a 20 mg catalyst. The degradation data were well fitted to the pseudo-first-order kinetic model. Accordingly, applying TiO2/GA as an efficient photocatalyst indicates a potential pathway for the degradation of organic contaminants in wastewater treatment.

In the ever fast-paced urbanization and globalization, the impact of climate change has manifested. There is an urgent need for new types of occupations that balance the built environment and nature (especially forests). For that reason, the concept of vernacular landscape has gotten attention in many disciplines but been regarded as a stand-alone tool or study subject. The paper aims to investigate the co-presence of vernacular and political landscapes (which termed by J. B. Jackson). The hypothesis of this study is that understanding interaction of the vernacular and political way of settling with forests throughout history can pull out problem statements for the future development. By analysis of archival documents combined with fieldwork and interpretive mapping in Thua Thien Hue Province through the key historical periods, the result reveals that the co-presence of the two landscapes has become increasingly profound over time. Simultaneously, there is a trend of decentralization in the territory. Problem statements drawn from the result set a basis for future studies of alternative environmental design and settling model linked with forests to adapt to climate change.

Inflammatory myofibroblastic tumor (IMT) is an uncommon neoplasm that rarely arises in the genitourinary system. IMTs in the vulva in infants are extremely rare in the literature. The tumor consists of myofibroblastic spindle cells accompanied by inflammatory cell infiltration. In this article, we aimed to describe the case of IMT in the vulva. A newborn girl presented with a mass in the vulva detected in the prenatal period. The patient was treated with surgery and chemotherapy. Follow-up 8 months after surgery showed no signs of recurrence. In conclusion, IMT has a variable clinical presentation, surgery is the optimal approach, but in cases without complete resection, chemotherapy is essential.

Among the various functionalities of hydrides, their use in hydrogen storage has been the most intensively studied because hydrides can store hydrogen compactly and safely. Thus, hydrides are key materials for the hydrogen economy. Here, the hydrogen storage material Al3FeH3.9 has been synthesized from cost-effective earth-abundant metals, Fe and Al. Hydrides consisting of Al and transition metals with low hydrogen affinities are rare because such alloys are unstable. However, it is expected that appropriate mixing of the chemical states of hydrogen atoms would allow synthesis of Al-Fe hydrides. The experimentally determined crystal structure of Al3FeD3.9 suggests realization of the mixing of the chemical state of hydrogen. Al3FeH3.9 is more thermodynamically stable than AlH3, and it is likely that the mixing of the chemical state of hydrogen atoms is the source of increased stability. The results of this study confirm that by controlling the chemical states of hydrogen, it is possible to tune the thermodynamic stability of hydrides and thus realize novel functional hydrides.

Background: Vietnam implemented various public health interventions such as contact tracing and testing, mandatory quarantine, and lockdowns in response to coronavirus disease 2019 (COVID-19). However, the effects of these measures on the epidemic remain unclear.Methods: This article describes the public health interventions in relation to COVID-19 incidence. Maximum likelihood estimations were used to assess containment delays (time between symptom onset and start of isolation) and multivariable regression was employed to identify associated factors between interventions and COVID-19 incidence. The effective reproductive numbers (Rt) were calculated based on transmission pairs.Results: Interventions were introduced periodically in response to the epidemic. Overall, 817 (55.4%) among 1474 COVID-19 cases were imported. Based on a serial interval of 8.72 ± 5.65 days, it was estimated that Rt decreased to below 1 (lowest at 0.02, 95% CI 0–0.12) during periods of strict border control and contact tracing, and increased ahead of new clusters. The main method to detect cases shifted over time from passive notification to active case-finding at immigration or in lockdown areas, with containment delays showing significant differences between modes of case detection.Conclusions: A combination of early, strict, and consistently implemented interventions is crucial to control COVID-19. Low-middle income countries with limited capacity can contain COVID-19 successfully using non-pharmaceutical interventions.

Pancreatic cysts in infants are rare. To the best of our knowledge, there are only 38 cases of pancreatic cysts detected among children under 2 years of age. To date, no pediatric case has been reported in Vietnam. Due to its limited incidence, the correct diagnosis and optimal management are still not clearly defined. Here, we present the successful excision of a true congenital pancreatic cyst in a newborn at our center. Literature on this topic was also reviewed.