Search

Objectives: This study aimed to determine the relationship between oxidative stress (OS) measured by the oxidation-reduction potential (ORP) and the results of semen analysis among men from infertile couples., Methods: This cross-sectional study included 166 men from infertile couples, determined according to the World Health Organization guidelines. The general characteristics, semen analysis, sperm chromatin dispersion assay, and ORP of all subjects were evaluated and analyzed statistically., Results: Among 166 men from infertile couples, individuals with OS had a significantly higher DNA fragmentation index (DFI) than men without OS (22.37% ± 11.67% vs. 17.98% ± 8.98%). The sperm concentration, total sperm count, motility rate, and normal morphology were negatively correlated, while and an abnormal head and neck-tail were positively correlated with ORP. There was also a positive association between the DFI and OS level. The optimal ORP threshold for determining sperm quality was 0.77 mV/10 6 sperm/mL (sensitivity, 50.4%; specificity, 93.5%; positive predictive value, 52.9%; negative predictive value, 32.3%)., Conclusions: Determining the ORP suggests that OS has an adverse effect on the total sperm count, sperm motility, sperm concentration, morphology, vitality, and DNA fragmentation index.

Extracellular vesicles (EVs) can be produced from red blood cells (RBCs) on a large scale and used to deliver therapeutic payloads efficiently. However, not much is known about the native biological properties of RBCEVs. Here, we demonstrate that RBCEVs are primarily taken up by macrophages and monocytes. This uptake is an active process, mediated mainly by endocytosis. Incubation of CD14+ monocytes with RBCEVs induces their differentiation into macrophages with an Mheme-like phenotype, characterized by upregulation of heme oxygenase-1 (HO-1) and the ATP-binding cassette transporter ABCG1. Moreover, macrophages that take up RBCEVs exhibit a reduction in surface CD86 and decreased secretion of TNF-α under inflammatory stimulation. The upregulation of HO-1 is attributed to heme derived from haemoglobin in RBCEVs. Heme is released from internalized RBCEVs in late endosomes and lysosomes via the heme transporter, HRG1. Consequently, RBCEVs exhibit the ability to attenuate foam cell formation from oxidized low-density lipoproteins (oxLDL)-treated macrophages in vitro and reduce atherosclerotic lesions in ApoE knockout mice on a high-fat diet. In summary, our study reveals the uptake mechanism of RBCEVs and their delivery of heme to macrophages, suggesting the potential application of RBCEVs in the treatment of atherosclerosis., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Objective: Globally, there are more than six million deaths due to cerebrovascular disease, which is the second leading cause of death. Although the imaging findings of magnetic resonance imaging (MRI) are more accurate than computed tomography for acute ischemic stroke (AIS), it is uncommon in recombinant tissue plasminogen activator (rTPA) treatment. Alteplase is not only strongly recommended treatment for acute ischemic stroke within 4.5 hours, but also decreases the disability and mortality rate. Besides, low-dose rTPA was associated with significant reductions in symptomatic intracerebral hemorrhage (sICH), compared with standard one. However, the benefits of low-dose rTPA for the treatment of AIS without large vessel occlusion (LVO) have not been fully demonstrated. We evaluated whether the low-dose rTPA in AIS without LVO could improve prognosis in patients three months post-treatment., Patients and Methods: This was a cross-sectional study on patients with AIS treated within 4.5 hours of symptom onset admitted to Can Tho S.I.S General Hospital between February 2019 and July 2021. The eligibility criteria were patients aged > 18 years treated with low-dose rTPA (0.6 mg/kg) and screened by 3T MRI. Patients with a pre-hospital modified Rankin score (mRS) ≥ 2 points, intracranial hemorrhage, LVO, or ≥ 3 microbleeds on brain MRI were excluded. The primary outcomes were the favorable outcome rate at three months and safety, which were evaluated by the rates of intracranial hemorrhage and mortality at three months., Results: This study enrolled 92 eligible patients between February 2019 and July 2021. Their National Institute of Health Stroke Scale (NIHSS) scores were 7.5 ± 3.7 at admission, 3.3 ± 3.5 at discharge or seven days after discharge, and 2.2 ± 2.8 at three months. Their mRS were 2.9 ± 0.8 at admission, 1.4 ± 1.3 at discharge or seven days after discharge, and 1.1 ± 1.1 at three months. Elevated cardiac enzymes, age ≥ 75 years, and body mass index ≥ 25 were associated with increased poor outcomes at three months. While AIS was more common in men than women, a similar number of men (33.3%) and women had poor mRS. Three patients had complications associated with low-dose rTPA treatment: one (1.1%) had intracranial hemorrhage, one (1.1%) had new infarcts, and one (1.1%) had gastrointestinal bleeding. No deaths occurred within three months., Conclusions: Our study indicates the efficacy and safety of low-dose rTPA treatment for AIS without LVO within 4.5 hours. Patient selection for rTPA by 3T MRI decreased complications and mortality.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has increased the workload of healthcare workers (HCWs), impacting their health. This study aimed to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and identify factors associated with poor sleep among HCWs in Vietnam during the COVID-19 pandemic., Methods: In this cross-sectional study, 1000 frontline HCWs were recruited from various healthcare facilities in Vietnam between October 2021 and November 2021. Data were collected using a 3-part self-administered questionnaire, which covered demographics, sleep quality, and factors related to poor sleep. Poor sleep quality was defined as a total PSQI score of 5 or higher., Results: Participants' mean age was 33.20±6.81 years (range, 20.0-61.0), and 63.0% were women. The median work experience was 8.54±6.30 years. Approximately 6.3% had chronic comorbidities, such as hypertension and diabetes mellitus. About 59.5% were directly responsible for patient care and treatment, while 7.1% worked in tracing and sampling. A total of 73.8% reported poor sleep quality. Multivariate logistic regression revealed significant associations between poor sleep quality and the presence of chronic comorbidities (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.17 to 5.24), being a frontline HCW directly involved in patient care and treatment (OR, 1.59; 95% CI, 1.16 to 2.16), increased working hours (OR, 1.84; 95% CI,1.37 to 2.48), and a higher frequency of encountering critically ill and dying patients (OR, 1.42; 95% CI, 1.03 to 1.95)., Conclusions: The high prevalence of poor sleep among HCWs in Vietnam during the COVID-19 pandemic was similar to that in other countries. Working conditions should be adjusted to improve sleep quality among this population.

Objective: This study aimed to compare the efficacy of physiological intracytoplasmic sperm injection (PICSI) and intracytoplasmic sperm injection (ICSI) in terms of the fertilization rate and embryo quality using sibling oocyte cycles., Methods: This prospective, cross-sectional study collected data from 76 couples who underwent their first cycle at the Hue Center for Reproductive Endocrinology and Infertility, Vietnam, between May 2019 and November 2021. The inclusion criteria were cycles with at least eight oocytes and a sperm concentration of 5×106/mL. Sperm parameters, sperm DNA fragmentation (SDF), fertilization, and the quality of cleavage-stage embryos on day 2 and blastocysts on day 5 were examined., Results: From 76 ICSI cycles, 1,196 metaphase II (MII) oocytes were retrieved, half of which were randomly allocated to either the PICSI (n=592) or ICSI (n=604) treatment group. The results showed no significant difference between the two groups in terms of fertilization (72.80% vs. 75.33%, p=0.32), day 2 cleavage rate (95.13% vs. 96.04%, p=0.51), blastulation rate (52.68% vs. 57.89%), and high-quality blastocyst rate (26.10% vs. 31.13%, p=0.13). However, in cases where SDF was low, 59 cycles consisting of 913 MII oocytes produced a considerably higher blastulation rate with PICSI than with ICSI (50.49% vs. 35.65%, p=0.00). There were no significant differences between the pregnancy outcomes of the PICSI and ICSI embryo groups following embryo transfer., Conclusion: Using variable sperm quality provided no benefit for PICSI versus ICSI in terms of embryo outcomes. When SDF is low, PICSI appears to be able to produce more blastocysts.

Despite the high lethality of colorectal cancers (CRCs), only a limited number of genetic risk factors are identified. The mammalian ssDNA-binding protein complex CTC1-STN1-TEN1 protects genome stability, yet its role in tumorigenesis is unknown. Here, we show that attenuated CTC1/STN1 expression is common in CRCs. We generated an inducible STN1 knockout mouse model and found that STN1 deficiency in young adult mice increased CRC incidence, tumor size, and tumor load. CRC tumors exhibited enhanced proliferation, reduced apoptosis, and elevated DNA damage and replication stress. We found that STN1 deficiency down-regulated multiple DNA glycosylases, resulting in defective base excision repair (BER) and accumulation of oxidative damage. Collectively, this study identifies STN1 deficiency as a risk factor for CRC and implicates the previously unknown STN1-BER axis in protecting colon tissues from oxidative damage, therefore providing insights into the CRC tumor-suppressing mechanism.

The wire Arc Additive Manufacturing (WAAM) technique has evolved into a cutting-edge 3D printing technique. This study surveys the influences of trajectory on the characteristics of low-carbon steel samples generated by the WAAM technique. The results show that the grains in the WAAM samples are isotropic, with grain size numbers ranging from 7 to 12. Strategy 3, with a spiral trajectory, has the smallest grain size, while strategy 2, with a lean zigzag trajectory, has the largest. The variations in grain size are caused by differences in heat input and output during the printing process. The WAAM samples achieve a significantly higher UTS value than the original wire, demonstrating the WAAM technique's benefit. Strategy 3, with a spiral trajectory, achieves the highest UTS value, 616.5 MPa, 24% higher than the original wire. The UTS values of strategy 1 (horizontal zigzag trajectory) and strategy 4 (curve zigzag trajectory) are comparable. WAAM samples have significantly higher elongation values than the original wire, with only 22% elongation. The sample with the highest elongation value, 47.2%, was produced by strategy 3. Strategy 2 has an elongation value of 37.9%. The value of elongation is proportional to the value of UTS. WAAM samples have average elastic modulus values of 95.8 GPa, 173.3 GPa, 92.2 GPa, and 83.9 GPa, corresponding to strategies 1, 2, 3, and 4. Only a strategy 2 sample has a similar elastic modulus value to the original wire. All samples have dimples on the fracture surface, indicating that the WAAM samples are ductile. These fracture surfaces' equiaxial shape corresponds to the original microstructure's equiaxial shape. The results provide the optimal trajectory for the WAAM products is the spiral trajectory, while the lean zigzag trajectory gains only modest characteristics.

The research goal was to estimate the level of risk to human health posed by polycyclic aromatic hydrocarbons (PAHs) in Vietnamese takeaway coffee. A variety of roasted coffee beans were collected and tested for the presence of PAHs in various takeaway locations throughout Vietnam. Furthermore, the effect of roasting conditions on PAH concentrations in Vietnamese Robusta coffee was also studied and demonstrated. Gas chromatography-mass spectrometry, a modern, accurate, and fast method, was used to determine the research results. Six PAHs, namely naphthalene, anthracene, pyrene, fluorene, phenanthrene, and benz[a]anthracene, were found in the 100 collected samples, with average concentrations (μg/kg dry weight) of 943.7 ± 40.3, 195.1 ± 4.9, 36.1 ± 1.1, 33.3 ± 2.2, 28.2 ± 1.7, and 2.0 ± 0.1, respectively. It was found that the tested samples were almost free of PAH4 contamination. The research showed that the total value of PAH quantifications in Robusta coffee increased with increasing roasting temperature and decreased with increasing roasting time. In addition, the calculated value of the total hazard quotient (THQ) was less than 1, and the obtained value of the incremental lifetime carcinogenic risk (ILCR) did not exceed 1·10 -5 , meaning that coffee consumers in Vietnam are safe from exposure to PAHs present in the investigated coffee beans.

Extracellular vesicles hold great promise as a drug delivery platform for RNA-based therapeutics. However, there is a lack of experimental evidence for the intracellular trafficking of nucleic acid cargos, specifically, whether they are capable of escaping from the endolysosomal confinement in the recipient cells to be released into the cytosol and hence, interact with their cytoplasmic targets. Here, we demonstrated how red blood cell-derived extracellular vesicles (RBCEVs) release their therapeutic RNA/DNA cargos at specific intracellular compartments characteristic of late endosomes and lysosomes. The released cargos were functional and capable of knocking down genes of interest in recipient cells, resulting in tumor suppression in vitro and in an acute myeloid leukemia murine model without causing significant toxicity. Notably, surface functionalization of RBCEVs with an anti-human CXCR4 antibody facilitated their specific uptake by CXCR4 + leukemic cells, leading to enhanced gene silencing efficiency. Our results provide insights into the cellular uptake mechanisms and endosomal escape routes of nucleic acid cargos delivered by RBCEVs which have important implications for further improvements of the RBCEV-based delivery system., Competing Interests: Declaration of Competing Interest Minh TN Le is a scientific co-founder, advisor and shareholder of Carmine Therapeutics, a company that develops extracellular-vesicle-based therapies. Other authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The IL-6/IL-6R or IL-6/GP130 protein-protein interactions play a significant role in controlling the development of chronic inflammatory diseases, such as rheumatoid arthritis, Castleman disease, psoriasis, and, most recently, COVID-19. Modulating or antagonizing protein-protein interactions of IL6 binding to its receptors by oral drugs promises similar efficacy to biological therapy in patients, namely monoclonal antibodies. In this study, we used a crystal structure of the Fab part of olokizumab in a complex with IL-6 (PDB ID: 4CNI) to uncover starting points for small molecule IL-6 antagonist discovery. Firstly, a structure‑based pharmacophore model of the protein active site cavity was generated to identify possible candidates, followed by virtual screening with a significant database Drugbank. After the docking protocol validation, a virtual screening by molecular docking was carried out and a total of 11 top hits were reported. Detailed analysis of the best scoring molecules was performed with ADME/T analysis and molecular dynamics simulation. Furthermore, the Molecular Mechanics-Generalized Born Surface Area (MM/GBSA) technique has been utilized to evaluate the free binding energy. Based on the finding, one newly obtained compound in this study, namely DB15187, may serve as a lead compound for the discovery of IL-6 inhibitors.Communicated by Ramaswamy H. Sarma.

Rationale : Metastasis is a complex process with a molecular underpinning that remains unclear. We hypothesize that cargo proteins conducted by extracellular vesicles (EVs) released from tumors may confer growth and metastasis potential on recipient cells. Here, we report that a cytokine-like secreted protein, FAM3C, contributes to late-stage lung tumor progression. Methods : EV protein profiling was conducted with an unbiased proteomic mass spectrometry analysis on non-small cell lung cancer (NSCLC) and normal lung fibroblast cell lines. Expression of FAM3C was confirmed in a panel of NSCLC cell lines, and correlated to the invasive and metastatic potentials. Functional phenotype of endogenous FAM3C and tumor-derived EVs (TDEs) were further investigated using various biological approaches in RNA and protein levels. Metastasis potential of TDEs secreted by FAM3C-overexpressing carcinoma cells was validated in mouse models. Results : Transcriptomic meta-analysis of pan-cancer datasets confirmed the overexpression of FAM3C - a gene encoding for interleukin-like EMT inducer (ILEI) - in NSCLC tumors, with strong association with poor patient prognosis and cancer metastasis. Aberrant expression of FAM3C in lung carcinoma cells enhances cellular transformation and promotes distant lung tumor colonization. In addition, higher FAM3C concentrations were detected in EVs extracted from plasma samples of NSCLC patients compared to those of healthy subjects. More importantly, we defined a hitherto-unknown mode of microenvironmental crosstalk involving FAM3C in EVs, whereby the delivery and uptake of FAM3C via TDEs enhances oncogenic signaling - in recipient cells that phenocopies the cell-endogenous overexpression of FAM3C. The oncogenicity transduced by FAM3C is executed via a novel interaction with the Ras-related protein RalA, triggering the downstream activation of the Src/Stat3 signaling cascade. Conclusions : Our study describes a novel mechanism for FAM3C-driven carcinogenesis and shed light on EV FAM3C as a driver for metastatic lung tumors that could be exploited for cancer therapeutics., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

AcrAB-TolC tripartite efflux pump, which belongs to the RND superfamily, is a main multi-drug efflux system of Escherichia coli ( E. coli ) because of the broad resistance on various antibiotics. With the discovering of efflux pump inhibitors (EPIs), a combination between these and antibiotics is one of the most promising therapies. Therefore, building a virtual screening model with prediction capacities for the efflux pump inhibitory activities of candidates from DrugBank and ZINC15 dataset, is one of the key goals of this project. Based on the database of 170 diverse chemical structures collected from 28 research journals, two 2D-QSAR models and a 3D-pharmacophore model have been performed. On the AcrB protein (PDB 4DX7), two binding sites have been discovered that match to the hydrophobic trap in the distal pocket and the switch loop in the proximal pocket. After virtual screening processes, twenty candidate AcrAB-TolC inhibitors have been subjected to molecular dynamics simulations, binding free energy calculations and ADMET predictions. The results indicate that three compounds namely DB09233, DB02581, and DB15224 are potential inhibitors with ΔG bind of -42.30 ± 4.58, -40.76 ± 7.30 and -31.06 ± 7.63 kcal.mol -1 , respectively.Communicated by Ramaswamy H. Sarma.

The role of interleukin-8 (IL-8) and its receptor CXCR2 in inflammatory responses and tumor development and progression has been well documented. Our study aims to discover novel compounds as CXCR2 antagonists to block the IL-8 signaling pathway using an in silico drug design. Herein, a structure-based pharmacophore model was developed based on the crystal structure of inactive CXCR2 in a complex with an allosteric inhibitor. This model was validated and refined, followed by virtual screening with the ZINC15 database. Subsequent molecular docking allows for predicting the best pose of a ligand inside a receptor binding site. We found that the 35 top-ranked hits exhibited docking scores from -30.81 to -25.28 kJ/mol and better interaction potential comparing the reference inhibitor. Analysis of ADME and toxicity properties revealed the efficacy and safety of the selected seven compounds. To validate the stability of the protein-ligand complex structure MD simulations approach has also been performed and confirmed via the critical parameters. The MD results explained that the CXCR2 receptor bound with two best-proposed molecules, including ZINC77105530 and ZINC93176465, was quite stable states as observed from low RMSD, RMSF, Rg, SASA values, and high occupancy of the interaction types. Finally, our data identified that these compounds play as potential inhibitors of IL-8 signaling pathways with the MM/GBSA binding free energies of -41.77 ± 6.45 kcal/mol and -38.84 ± 6.16 kcal/mol, respectively.Communicated by Ramaswamy H. Sarma.

Background: Residential proximity to greenspace is associated with various health outcomes., Objectives: We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors., Methods: Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100 m and 500 m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income., Results: After multivariable adjustment, for the 500 m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lip ± cleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100 m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81)., Discussion: Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Colorectal cancer (CRC) is the fifth most common cancer with rising prevalence in Vietnam. However, there is no data about the mutational landscape and actionable alterations in the Vietnamese patients. During post-operative surveillance, clinical tools are limited to stratify risk of recurrence and detect residual disease., Method: In this prospective multi-center study, 103 CRC patients eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissue and paired white blood cells were sequenced to profile all tumor-derived somatic mutations in 95 cancer-associated genes. Our bioinformatic algorithm identified top mutations unique for individual patient, which were then used to monitor the presence of circulating tumor DNA (ctDNA) in serial plasma samples., Results: The top mutated genes in our cohort were APC , TP53 and KRAS . 41.7% of the patients harbored KRAS and NRAS mutations predictive of resistance to Cetuximab and Panitumumab respectively; 41.7% had mutations targeted by either approved or experimental drugs. Using a personalized subset of top ranked mutations, we detected ctDNA in 90.5% of the pre-operative plasma samples, whereas carcinoembryonic antigen (CEA) was elevated in only 41.3% of them. Interim analysis after 16-month follow-up revealed post-operative detection of ctDNA in two patients that had recurrence, with the lead time of 4-10.5 months ahead of clinical diagnosis. CEA failed to predict recurrence in both cases., Conclusion: Our assay showed promising dual clinical utilities in residual cancer surveillance and actionable mutation profiling for targeted therapies in CRC patients. This could lay foundation to empower precision cancer medicine in Vietnam and other developing countries., Competing Interests: V-AH, T-AT, TH, DQN, Y-TL, H-NN, HG and LT are current employees of Gene Solutions, Vietnam. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nguyen, Nguyen, Nguyen Hoang, Tran, Le Trinh, Le, Nguyen Tran, Pham, Dinh, Nguyen, Nguyen The, Mai, Chu, Pham, Nguyen, Ngo Ha, Nguyen, Nguyen, Lu, Do Thi, Truong, Nguyen, Nguyen, Giang and Tu.)

Objective: Intravenous (IV) recombinant tissue plasminogen activator is the standard of care for patients with acute ischemic stroke (AIS) who present to the hospital within 4.5 hours of symptom onset. However, IV thrombolysis, even bridging thrombolysis (combining intravenous thrombolysis and mechanical thrombectomy) has limited efficacy among patients who had occlusive lesions associated with high-grade arterial stenosis requiring revascularization to improve neurological deficits. We evaluated whether rescue stenting results in good outcomes among patients after the failure of intravenous thrombolysis and bridging thrombolysis., Patients and Methods: We retrospectively analyzed patients with AIS who underwent rescue stenting for large vessel occlusion with severe atherosclerotic stenosis between May 2020 and August 2022 at Can Tho S.I.S General Hospital. Primary outcomes included the incidence of hemorrhagic transformation and the rate of good outcomes (modified Rankin Scale < 3) at 3-month follow-up., Results: We identified 13 patients who received rescue stenting after the failure of IV alteplase and bridging thrombolysis, but only 11 patients met the inclusion criteria. All patients experienced successful recanalization, and 1 (9.1%) patient experienced new infarcts. Of these 11 patients, 10 (90.9%) had good outcomes 3 months after rescue stenting. Additionally, a loading dose of dual antiplatelet therapy (DAPT) applied concurrently with IV alteplase improved the recanalization rate for large target arteries but had no significant effect on the incidence of symptomatic intracranial hemorrhage., Conclusions: Rescue stenting appears to represent an additional therapeutic option in cases that fail to resolve with IV alteplase, which may improve clinical outcomes.

Aims: Early detection of colorectal cancer (CRC) provides substantially better survival rates. This study aimed to develop a blood-based screening assay named SPOT-MAS ('screen for the presence of tumor by DNA methylation and size') for early CRC detection with high accuracy. Methods: Plasma cell-free DNA samples from 159 patients with nonmetastatic CRC and 158 healthy controls were simultaneously analyzed for fragment length and methylation profiles. We then employed a deep neural network with fragment length and methylation signatures to build a classification model. Results: The model achieved an area under the curve of 0.989 and a sensitivity of 96.8% at 97% specificity in detecting CRC. External validation of our model showed comparable performance, with an area under the curve of 0.96. Conclusion: SPOT-MAS based on integration of cancer-specific methylation and fragmentomic signatures could provide high accuracy for early-stage CRC detection.

The interleukin-1 receptor like ST2 has emerged as a potential drug discovery target since it was identified as the receptor of the novel cytokine IL-33, which is involved in many inflammatory and autoimmune diseases. For the treatment of such IL-33-related disorders, efforts have been made to discover molecules that can inhibit the protein-protein interactions (PPIs) between IL-33 and ST2, but to date no drug has been approved. Although several anti-ST2 antibodies have entered clinical trials, the exploration of small molecular inhibitors is highly sought-after because of its advantages in terms of oral bioavailability and manufacturing cost. The aim of this study was to discover ST2 receptor inhibitors based on its PPIs with IL-33 in crystal structure (PDB ID: 4KC3) using virtual screening tools with pharmacophore modeling and molecular docking. From an enormous chemical space ZINC, a potential series of compounds has been discovered with stronger binding affinities than the control compound from a previous study. Among them, four compounds strongly interacted with the key residues of the receptor and had a binding free energy <  - 20 kcal/mol. By intensive calculations using data from molecular dynamics simulations, ZINC59514725 was identified as the most potential candidate for ST2 receptor inhibitor in this study., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Since interleukin-8 (IL-8/CXCL8) and its receptor, CXCR1 and CXCR2, were known in the early 1990s, biological pathways related to these proteins were proven to have high clinical value in cancer and inflammatory/autoimmune conditions treatment. Recently, IL-8 has been identified as biomarker for severe COVID-19 patients and COVID-19 prognosis. Boyles et al. (mAbs 12 (2020), pp. 1831880) have published a high-resolution X-ray crystal structure of the LY3041658 Fab in a complex human CXCL8. They described the ability to bind to IL-8 and the blocking of IL-8/its receptors interaction by the LY3041658 monoclonal antibody. Therefore, the study has been designed to identify potential small molecules inhibiting interleukin-8 by targeting LY3041658/IL-8 complex structure using an in silico approach. A structure‑based pharmacophore and molecular docking models of the protein active site cavity were generated to identify possible candidates, followed by virtual screening with the ZINC database. ADME analysis of hit compounds was also conducted. Molecular dynamics simulations were then performed to survey the behaviour and stability of the ligand-protein complexes. Furthermore, the MM/PBSA technique has been utilized to evaluate the free binding energy. The final data confirmed that one newly obtained compound, ZINC21882765, may serve as the best potential inhibitor for IL-8.

Objective: In cases of acute ischemic stroke (AIS) caused by intracranial large vessel occlusion, rescue intracranial stenting (RIS) has recently emerged as a treatment option for achieving recanalization when mechanical thrombectomy (MT) fails. However, few studies to date have reported on the beneficial outcomes of RIS. Our goal was to analyze whether RIS use can improve prognosis in patients 3 months post-treatment., Patients and Methods: A retrospective analysis was performed on a prospective cohort of patients with AIS treated with RIS at Can Tho S.I.S General Hospital. The study inclusion criteria were evidence of intracranial large vessel occlusion, absence of intracranial hemorrhage (ICH), and severe stenosis or reocclusion after MT. Patients with tandem occlusions, failure to follow up after discharge, or severe or fatal illness concomitant with AIS were excluded from the study. The primary outcome was the "non-poor" prognosis status rate at 3 months after RIS and post-procedural symptomatic ICH (sICH)., Results: The post-treatment outcomes of 85 eligible patients who received RIS between August 2019 and May 2021 were assessed. Of the 85 included patients, 82 (96.5%) achieved successful recanalization, and 4 (4.7%) experienced sICH. At 3-months post-treatment, 47 (55.3%) patients had "non-poor" outcomes, whereas 35 (41.2%) had good outcomes. The use of dual antiplatelet therapy was associated with new infarcts (relative risk [RR]: 0.1; 95% confidence interval [CI]: 0.01-0.7) and sICH occurrence (RR: 0.1; 95% CI: 0.01-0.9)., Conclusions: Our study suggests that despite the occurrence of post-procedural sICH in a small proportion of cases, RIS could serve as a useful alternative or additional treatment in the event of MT failure.

The World Health Organization declared monkeypox a global public health emergency on 23 July 2022. This disease was caused by the monkeypox virus (MPXV), which was first identified in 1958 in Denmark. The MPXV is a member of the Poxviridae family, the Chordopoxvirinae subfamily, and the genus Orthopoxvirus, which share high similarities with the vaccinia virus (the virus used to produce the smallpox vaccine). For the initial stage of infection, the MPXV needs to attach to the human cell surface glycosaminoglycan (GAG) adhesion molecules using its E8 protein. However, up until now, neither a structure for the MPXV E8 protein nor a specific cure for the MPXV exists. This study aimed to search for small molecules that inhibit the MPXV E8 protein, using computational approaches. In this study, a high-quality three-dimensional structure of the MPXV E8 protein was retrieved by homology modeling using the AlphaFold deep learning server. Subsequent molecular docking and molecular dynamics simulations (MDs) for a cumulative duration of 2.1 microseconds revealed that ZINC003977803 (Diosmin) and ZINC008215434 (Flavin adenine dinucleotide-FAD) could be potential inhibitors against the E8 protein with the MM/GBSA binding free energies of -38.19 ± 9.69 and -35.59 ± 7.65 kcal·mol -1 , respectively.

Background: Point-of-care ultrasound (POCUS) is rapidly becoming ubiquitous across healthcare specialties. This is due to several factors including its portability, immediacy of results to guide clinical decision-making, and lack of radiation exposure to patients. The recent growth of handheld ultrasound devices has improved access to ultrasound for many clinicians. Few studies have directly compared different handheld ultrasound devices among themselves or to cart-based ultrasound machines. We conducted a prospective observational study comparing four common handheld ultrasound devices for ease of use, image quality, and overall satisfaction. Twenty-four POCUS experts utilized four handheld devices (Butterfly iQ+™ by Butterfly Network Inc., Kosmos™ by EchoNous, Vscan Air™ by General Electric, and Lumify™ by Philips Healthcare) to obtain three ultrasound views on the same standardized patients using high- and low-frequency probes., Results: Data were collected from 24 POCUS experts using all 4 handheld devices. No single ultrasound device was superior in all categories. For overall ease of use, the Vscan Air™ was rated highest, followed by the Lumify™. For overall image quality, Lumify™ was rated highest, followed by Kosmos™. The Lumify™ device was rated highest for overall satisfaction, while the Vscan Air™ was rated as the most likely to be purchased personally and carried in one's coat pocket. The top 5 characteristics of handheld ultrasound devices rated as being "very important" were image quality, ease of use, portability, total costs, and availability of different probes., Conclusions: In a comparison of four common handheld ultrasound devices in the United States, no single handheld ultrasound device was perceived to have all desired characteristics. POCUS experts rated the Lumify™ highest for image quality and Vscan Air™ highest for ease of use. Overall satisfaction was highest with the Lumify™ device, while the most likely to be purchased as a pocket device was the Vscan Air™. Image quality was felt to be the most important characteristic in evaluating handheld ultrasound devices., (© 2022. The Author(s).)

The importance of multi-omic-based approaches to better understand diverse pathological mechanisms including neurodegenerative diseases has emerged. Spatial information can be of great help in understanding how biomolecules interact pathologically and in elucidating target biomarkers for developing therapeutics. While various analytical methods have been attempted for imaging-based biomolecule analysis, a multi-omic approach to imaging remains challenging due to the different characteristics of biomolecules. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a powerful tool due to its sensitivity, chemical specificity, and high spatial resolution in visualizing chemical information in cells and tissues. In this paper, we suggest a new strategy to simultaneously obtain the spatial information of various kinds of biomolecules that includes both labeled and label-free approaches using ToF-SIMS. The enzyme-assisted labeling strategy for the targets of interest enables the sensitive and specific imaging of large molecules such as peptides, proteins, and mRNA, a task that has been, to date, difficult for any MS analysis. Together with the strength of the analytical performance of ToF-SIMS in the label-free tissue imaging of small biomolecules, the proposed strategy allows one to simultaneously obtain integrated information of spatial distribution of metabolites, lipids, peptides, proteins, and mRNA at a high resolution in a single measurement. As part of the suggested strategy, we present a sample preparation method suitable for MS imaging. Because a comprehensive method to examine the spatial distribution of multiple biomolecules in tissues has remained elusive, our strategy can be a useful tool to support the understanding of the interactions of biomolecules in tissues as well as pathological mechanisms.

Background: Point-of-care ultrasound (POCUS) training has been increasing among internal medicine (IM) residency programs, but few programs can provide longitudinal training due to barriers such as lack of trained faculty., Aim: Describe the development of a longitudinal POCUS track for IM residents using local and external resources, including a national POCUS certificate program., Setting: University-based IM residency program affiliated with a public and veterans affairs hospital., Participants: Twelve IM residents from 2018 to 2021., Program Description: Residents complete a national POCUS certificate program by attending live courses and completing online modules, an image portfolio, and final knowledge/skills assessments. Locally, residents participate in 1-month procedure and diagnostic POCUS rotations and provide peer-to-peer POCUS teaching of residents and medical students., Program Evaluation: The POCUS track increased residents' use and comfort with diagnostic and procedural applications. All residents rated being satisfied or very satisfied with the track and would recommend it to prospective applicants (100%). The most commonly reported barriers to utilizing POCUS per residents were time constraints (83%), lack of available ultrasound equipment (83%), and lack of trained faculty (58%)., Discussion: IM residency programs with limited faculty expertise in POCUS can leverage external resources to provide longitudinal POCUS training to its residents., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS). Thalassemia carriers were identified with prevalence of 13.13% (772), including 7.82% (460) carriers of α-thalassemia (α-thal), 5.31% (312) carriers of β-thalassemia (β-thal), and 0.63% (37) concurrent α-/β-thal carriers. Deletional mutations (368) accounted for 80.0% of α-thal carriers, of which, -- SEA (Southeast Asian) ( n  = 254; 55.0%) was most prevalent, followed by the -α 3.7 (rightward) ( n  = 66; 14.0%) and -α 4.2 (leftward) ( n  = 45; 9.8%) deletions. Hb Westmead ( HBA2 : c.369C>G) ( n  = 53) and Hb Constant Spring (Hb CS or HBA2 : c.427T>C) (in 28) are the two most common nondeletional α-globin variants, accounting for 11.5 and 6.0% of α-thal carriers. We detected 11 different β-thal genotypes. Hb E ( HBB : c.79G>A) (in 211) accounted for 67.6% of β-thal carriers. The most common β-thal genotypes were associated with mutations at codon 17 (A>T) ( HBB : c.52A>T), codons 41/42 (-TTCT) ( HBB : c.126&#95;129delCTTT), and codon 71/72 (+A) ( HBB : c.217&#95;218insA) (prevalence 0.70%, 0.68%, and 0.2%, respectively). Based on mutation frequencies calculated in this study, estimates of 5021 babies in Vietnam are affected with clinically severe thalassemia annually. Our data suggest a higher thalassemia carrier frequency in Vietnam than previously reported. We established that combining NGS with gap-PCR creates an effective large-scale thalassemia screening method that can detect a broad range of mutations.

As cancer poses a significant threat to the well-being of humans on a global scale, many researchers have embarked on the search for effective anticancer therapeutic agents. In recent years, many drugs have been shown to have extraordinary anticancer effects. However, in a lot of cases the treatment is accompanied by undesirable side effects due to some intrinsic properties linked to the therapeutic agents, such as poor targeting selectivity and short half-life in the circulation. In this regard, extracellular vesicles (EVs), a diverse family of natural cell-derived vesicles, steal the show as potential anticancer immunotherapy or delivery vectors of anticancer agents since they are an innate mechanism of intercellular communication. Here, we describe some of the most hotly-debated issues regarding the use of EVs as anticancer therapeutics. First, we review the biology of EVs providing the most up-to-date definition of EVs as well as highlighting their circulation kinetics and homing properties. Next, we share our views on popular methods reported for EV isolation, characterization, and functional analysis. Pioneering and innovative reports along with emerging challenges in the field of EV imaging and EV drug loading strategies are then discussed. Finally, we examine in detail the therapeutic application of EVs in cancer treatment, including their role in cancer immunotherapy and as natural delivery systems for anticancer agents including natural compounds such as paclitaxel and doxorubicin. We consider standardised protocols and proper analytical approaches to be crucial in improving the reproducibility and rigor in EV research and ensuring the successful translation of EVs as anticancer therapeutics., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: This study was performed to determine the effect of swim-up (SU) and density gradient centrifugation (DGC) on sperm survival and DNA fragmentation., Methods: Individual semen samples were analyzed before each was divided into two aliquots (half for SU and half for DGC) for calculation of sperm survival and the DNA fragmentation index (DFI). Sperm DNA fragmentation was determined using the sperm chromatin dispersion test., Results: The DFI of the 63 semen samples processed using both procedures was lower than that of the fresh semen samples. The DFI was significantly lower for samples processed using the SU than DGC method. In the sperm survival test, the SU technique was associated with increased sperm motility and vitality following preparation. After 24 hours, however, the concentration and percentage of surviving sperm were significantly lower in the SU than DGC group., Conclusions: Both semen preparation techniques help to minimize sperm DNA fragmentation; however, when the DFI is <30%, the SU technique is more appropriate than DGC. While DGC may be superior for intrauterine insemination, the SU method may be preferable for in vitro fertilization or maturation.

The advent of novel therapeutics in recent years has urged the need for a safe, non-immunogenic drug delivery vector capable of delivering therapeutic payloads specifically to diseased cells, thereby increasing therapeutic efficacy and reducing side effects. Extracellular vesicles (EVs) have garnered attention in recent years as a potentially ideal vector for drug delivery, taking into account their intrinsic ability to transfer bioactive cargo to recipient cells and their biocompatible nature. However, natural EVs are limited in their therapeutic potential and many challenges need to be overcome before engineered EVs satisfy the levels of efficiency, stability, safety and biocompatibility required for therapeutic use. Here, we demonstrate that an enzyme-mediated surface functionalization method in combination with streptavidin-mediated conjugation results in efficient surface functionalization of EVs. Surface functionalization using the above methods permits the stable and biocompatible conjugation of peptides, single domain antibodies and monoclonal antibodies at high copy number on the EV surface. Functionalized EVs demonstrated increased accumulation in target cells expressing common cancer associated markers such as CXCR4, EGFR and EpCAM both in vitro and in vivo . The functionality of this approach was further highlighted by the ability of targeting EVs to specifically deliver therapeutic antisense oligonucleotides to a metastatic breast tumor model, resulting in increased knockdown of a targeted oncogenic microRNA and improved metastasis suppression. The method was also used to equip EVs with a bifunctional peptide that targets EVs to leukemia cells and induces apoptosis, leading to leukemia suppression. Moreover, we conducted extensive testing to verify the biocompatibility, and safety of engineered EVs for therapeutic use, suggesting that surface modified EVs can be used for repeated dose treatment with no detectable adverse effects. This modular, biocompatible method of EV engineering offers a promising avenue for the targeted delivery of a range of therapeutics while addressing some of the safety concerns associated with EV-based drug delivery., Competing Interests: Competing Interests: M.T.N.L. and J.S. are scientific co-founders and advisors of Carmine Therapeutics, a company that develops extracellular-vesicle-based therapies. M.P and J.S. are an employee and scientific co-founder of the nanobody company Jotbody, respectively. Other authors declare no conflict of interest., (© The author(s).)

Interleukin 6 (IL-6) is a cytokine with various biological functions in immune regulation, hematopoiesis, and inflammation. Elevated IL-6 levels have been identified in several severe disorders such as sepsis, acute respiratory distress syndrome (ARDS), and most recently, COVID-19. The biological activity of IL-6 relies on interactions with its specific receptor, IL-6Rα, including the membrane-bound IL-6 receptor (mIL-6R) and the soluble IL-6 receptor (sIL-6R). Thus, inhibition of the interaction between these two proteins would be a potential treatment for IL-6 related diseases. To date, no orally available small-molecule drug has been approved. This study focuses on finding potential small molecules that can inhibit protein-protein interactions between IL-6 and its receptor IL-6Rα using its crystal structure (PDB ID: 5FUC). First, two pharmacophore models were constructed based on the interactions between key residues of IL-6 (Phe74, Phe78, Leu178, Arg179, Arg182) and IL-6Rα (Phe229, Tyr230, Glu277, Glu278, Phe279). A database of approximately 22 million compounds was screened using 3D-pharmacophore models, molecular docking models, and ADMET properties. By analyzing the interactive capability of successfully docked compounds with important amino acids, 12 potential ligands were selected for further analysis via molecular dynamics simulations. Based on the stability of the complexes, the high interactions rate of each ligand with the key residues of IL-6/IL-6Rα, and the low binding free energy calculation, two compounds ZINC83804241 and ZINC02997430, were identified as the most potential IL-6 inhibitor candidates. These results will pave the way for the design and optimization of more specific compounds to combat cytokine storm in severe coronavirus patients., Competing Interests: The authors have declared that no competing interests exist.

The RIG-I pathway can be activated by RNA containing 5' triphosphate, leading to type I interferon release and immune activation. Hence, RIG-I agonists have been used to induce immune responses against cancer as potential immunotherapy. However, delivery of 5' triphosphorylated RNA molecules as RIG-I agonists to tumour cells in vivo is challenging due to the susceptibility of these molecules to degradation. In this study, we demonstrate the use of extracellular vesicles (EVs) from red blood cells (RBCs), which are highly amenable for RNA loading and taken up robustly by cancer cells, for RIG-I agonist delivery. We evaluate the anti-cancer activity of two novel RIG-I agonists, the immunomodulatory RNA (immRNA) with a unique secondary structure for efficient RIG-I activation, and a 5' triphosphorylated antisense oligonucleotide with dual function of RIG-I activation and miR-125b inhibition (3p-125b-ASO). We find that RBCEV-delivered immRNA and 3p-125b-ASO trigger the RIG-I pathway, and induce cell death in both mouse and human breast cancer cells. Furthermore, we observe a significant suppression of tumour growth coupled with increased immune cell infiltration mediated by the activation of RIG-I cascade after multiple intratumoral injections of RBCEVs loaded with immRNA or 3p-125b-ASO. Targeted delivery of immRNA using RBCEVs with EGFR-binding nanobody administrated via intrapulmonary delivery facilitates the accumulation of RBCEVs in metastatic cancer cells, leading to potent tumour-specific CD8 + T cells immune response. This contributes to prominent suppression of breast cancer metastasis in the lung. Hence, this study provides a new strategy for efficient RIG-I agonist delivery using RBCEVs for immunotherapy against cancer and cancer metastasis., (© 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background: To evaluate 10-year long-term refractive visual stability and participants' satisfaction in the refractive treatment of myopic eyes undergoing topography-guided transepithelial surface ablation using a 1KHz excimer laser., Patients and Methods: This single-center prospective survey assessed participants' satisfaction 10 years after the treatment using a non-validated questionnaire with regards to visual outcome, dry eye, and visual disturbance symptoms. Pre- and postoperative visual and refractive data were evaluated., Results: Of 106 participants (54% females) with a mean patient age of 36 (± 8.6) years, 166 eyes were included. Mean preoperative spherical equivalent (SE) was - 4.23 (± 2.48) diopters (D). Uncorrected distant visual acuity (UCVA) after 10 years was ≥ 1.0 (Snellen) in 92% of the eyes. Manifest SE was within ± 1.0 D of the desired refraction in 86% of the eyes after 10 years. Mean quality of life (QOL) improvement was high (9.15 out of 10 points). Dry eye symptoms were reported by 35 out of 104 (34%) patients. Visual symptoms like halos or starbursts were reported by 24 out of 101 (24%) and 12 out of 100 (12%) patients, respectively., Conclusions: Topography-guided transepithelial surface ablation for myopia provided stable long-term results in terms of UCVA and SE. Participant satisfaction was high, with only low rates of dry eye or visual symptoms., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Identification of tumor-derived mutation (TDM) in liquid biopsies (LB), especially in early-stage patients, faces several challenges, including low variant-allele frequencies, interference by white blood cell (WBC)-derived mutations (WDM), benign somatic mutations and tumor heterogeneity. Here, we addressed the above-mentioned challenges in a cohort of 50 nonmetastatic colorectal cancer patients, via a workflow involving parallel sequencing of paired WBC- and tumor-gDNA. After excluding potential false positive mutations, we detected at least one TDM in LB of 56% (28/50) of patients, with the majority showing low-patient coverage, except for one TDM mapped to KMT2D that recurred in 30% (15/30) of patients.

The human P-glycoprotein (P-gp) and the NorA transporter are the major culprits of multidrug resistance observed in various bacterial strains and cancer cell lines, by extruding drug molecules out of the targeted cells, leading to treatment failures in clinical settings. Inhibiting the activity of these efflux pumps has been a well-known strategy of drug design studies in this regard. In this manuscript, our earlier published machine learning models and homology structures of P-gp and NorA were utilized to screen a chemolibrary of 95 in-house chalcone derivatives, identifying two hit compounds, namely, F88 and F90, as potential modulators of both transporters, whose activity on Staphylococcus aureus strains overexpressing NorA and resistant to ciprofloxacin was subsequently confirmed. The findings of this study are expected to guide future research towards developing novel potent chalconic inhibitors of P-gp and/or NorA., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Minh-Tri Le et al.)

Objective: As the associations of sperm DNA fragmentation with morphology have not been examined in detail, this study aimed to investigate the relationship between abnormalities of morphological details and DNA integrity in human sperm., Methods: In this cross-sectional study, men from infertile couples were enrolled at Hue Center for Reproductive Endocrinology and Infertility, Vietnam. Conventional semen parameters, including morphological details, were analyzed following the World Health Organization 2010 criteria. Sperm DNA fragmentation was evaluated using a sperm chromatin dispersion assay. The relationships and correlations between semen parameters, sperm morphology, and the type of halosperm and the DNA fragmentation index (DFI) were analyzed., Results: Among 130 men in infertile couples, statistically significant differences were not found in the sperm halo type between the normal and abnormal sperm morphology groups. The percentage of round-head spermatozoa was higher in the DFI >15% group (16.98%±12.50%) than in the DFI ≤15% group (13.13% ±8.82%), higher values for amorphous heads were found in the DFI >15% group, and lower values for tapered heads were observed in the DFI ≤15% group; however, these differences were not statistically significant. Small-halo sperm and the DFI were positively correlated with round-head sperm (r=0.243, p=0.005 and r=0.197, p=0.025, respectively)., Conclusion: The rate of general sperm morphological abnormalities in semen analysis was not related to sperm DNA integrity. However, round sperm heads were closely associated with sperm DNA fragmentation.

Interactions between interleukin (IL)-8 and its receptors, CXCR1, and CXCR2, serve crucial roles in inflammatory conditions and various types of cancers. Inhibition of this signaling pathway has been exploited as a promising strategy in treating these diseases. However, most studies only focused on the design of allosteric antagonists-bound receptors on the intracellular side of IL-8 receptors. Recently, the first cryo-EM structures of IL-8-CXCR2-Gi complexes have been solved, revealing the unique binding and activation modes of the endogenous chemokine IL-8. Hence, we set to identify small molecule inhibitors for IL-8 using critical protein-protein interaction between IL-8 and CXCR2 at the orthosteric binding site. The pharmacophore models and molecular docking screened compounds from DrugBank and NCI databases. The oral bioavailability of the top 23 ligands from the screening was then predicted by the SwissAMDE tool. Molecular dynamics simulation and free binding energy calculation were performed for the best compounds. The result indicated that DB14770, DB12121, and DB03916 could form strong interactions and stable protein-ligand complexes with IL-8. These three candidates are potential IL-8 inhibitors that can be further evaluated by in vitro experiments in the next stage., Competing Interests: The authors have declared that no competing interests exist.

We developed a high-resolution and comprehensive typing method for swine leukocyte antigen 3 (SLA-3), an MHC class I gene, employing locus-specific genomic PCR followed by subsequent direct sequencing. A total of 292 individuals from nine pure, one cross-breed and six cell lines were successfully typed. A total of 21 SLA-3 alleles were identified, of which four were found to be novel alleles. However, the allelic diversity of SLA-3 was lower than that of previously reported class I genes, SLA-1 and -2. More SLA-3 alleles were observed in the Landrace and Yorkshire breeds than the other breeds. SLA-3*04:01 was identified in seven out of nine breeds and was the most widely distributed allele across all breeds. Therefore, the typing method reported in this study completes our efforts to develop high-resolution typing methods for major SLA molecules, facilitating the combined analysis of major SLA genes from field samples, which is important to understand the relationship between the adaptive immune responses against pathogens and the immunogenetic makeup of an individual., (© 2021 Stichting International Foundation for Animal Genetics.)

The main protease 3CL pro is one of the potential targets against coronavirus. Inhibiting this enzyme leads to the interruption of viral replication. Chalcone and its derivatives were reported to possess the ability to bind to 3CL pro protease in the binding pocket. This study explored an in-house database of 269 chalcones as 3CL pro inhibitors using in silico screening models, including molecular docking, molecular dynamics simulation, binding free energy calculation, and ADME prediction.  C264  and  C235  stand out as the two most potential structures. The top hit compound  C264  was with the Jamda score of -2.8329 and the MM/GBSA binding energy mean value of -28.23 ± 3.53 kcal/mol, which was lower than the reference ligand. Despite the lower mean binding energy (-22.07 ± 3.39 kcal/mol), in-depth analysis of binding interaction suggested  C235  could be another potential candidate. Further, in vitro and in vivo experiments are required to confirm the inhibitory ability., Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02000-3., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Background: Detection or monitoring of brain damage is a clinically crucial issue. Nucleic acids in the whole blood can be used as biomarkers for brain injury. Polymerase chain reaction (PCR) which is one of the most commonly used molecular diagnostic assays requires isolated nucleic acids to initiate amplification. Currently used nucleic acid isolation procedures are complicated and require laboratory equipments., Objective: In this study, we tried to develop a simple and convenient method to isolate nucleic acids from the whole blood sample using a tiny battery-powered electric device. The quality of the isolated nucleic acids should be suitable for PCR assay without extra preparation., Methods: A plastic device with separation chamber was designed and printed with a 3D printer. Two platinum electrodes were placed on both sides and a battery was used to supply the electricity. To choose the optimal nucleic acid isolation condition, diverse lysis buffers and separation buffers were evaluated, and the duration and voltage of the electricity were tested. Western blot analysis and PCR assay were used to determine the quality of the separated nucleic acids., Results: 2ul of whole blood was applied to the cathode side of the separation chamber containing 78 ul of normal saline. When the electricity at 5 V was applied for 5 min, nucleic acids were separated from segment 1 to 3 of the separation chamber. The concentration of nucleic acids peaked around 7~8 mm from cathode side. PCR assay using the separation buffer as the template was performed successfully both in conventional and realtime PCR methods. The hemoglobin in the whole blood did not show the inhibitory effect in our separation system and it may be due to structural modification of hemoglobin during electric separation., Conclusion: Our simple electric device can separate nucleic acids from the whole blood sample by applying electricity at 5 V for 5 min. The separation buffer solution taken from the device can be used for PCR assay successfully., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Depression is a common mental disorder in people with epilepsy. Depression has a negative impact on medical and surgical treatment of epilepsy thus affecting the quality of life. Despite its high prevalence, depression has been under-recognized and treated improperly. It may also lead to missed work, increased healthcare system utilization, and higher direct medical costs., Objectives: This study aimed to evaluate the accuracy of the Vietnamese Patient Health Questionnaire (PHQ-9) as a screening tool for depression in people with epilepsy., Methods: This cross-sectional study was conducted prospectively at epilepsy clinic at Nguyen Tri Phuong hospital, Ho Chi Minh City, Viet Nam from December 2019 to March 2020. A total of 91 adult people with epilepsy were recruited. After completing the Vietnamese PHQ-9 questionnaires, each participant was interviewed in a structured clinical interview for DSM-5 (SCID-5) to establish a diagnosis of major depressive disorder. The diagnostic accuracy of the PHQ-9 was assessed using diagnostic efficiency statistics compared with the gold standard structured interview., Results: The prevalence of major depression in this sample was 25.3%. The areas under receiver operating characteristic (ROC) curve index of PHQ-9 had an estimated value of 0.91. The PHQ-9 at a cutoff point of 8 had the great overall balance of sensitivity (87.0%) and specificity (82.4%). At the cutoff point of 10, PHQ-9 had a higher specificity of 94.1%, but a lower sensitivity of 78.0%., Conclusions: The Vietnamese version PHQ-9 is an efficient and valid screening tool for depression in people with epilepsy in clinic settings., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Purdue Make It system is a unique automated platform capable of small-scale in situ synthesis, screening small-molecule reactions, and performing direct label-free bioassays. The platform is based on desorption electrospray ionization (DESI), an ambient ionization method that allows for minimal sample workup and is capable of accelerating reactions in secondary droplets, thus conferring unique advantages compared with other high-throughput screening technologies. By combining DESI with liquid handling robotics, the system achieves throughputs of more than 1 sample/s, handling up to 6144 samples in a single run. As little as 100 fmol/spot of analyte is required to perform both initial analysis by mass spectrometry (MS) and further MS n structural characterization. The data obtained are processed using custom software so that results are easily visualized as interactive heatmaps of reaction plates based on the peak intensities of m / z values of interest. In this paper, we review the system's capabilities as described in previous publications and demonstrate its utilization in two new high-throughput campaigns: (1) the screening of 188 unique combinatorial reactions (24 reaction types, 188 unique reaction mixtures) to determine reactivity trends and (2) label-free studies of the nicotinamide N -methyltransferase enzyme directly from the bioassay buffer. The system's versatility holds promise for several future directions, including the collection of secondary droplets containing the products from successful reaction screening measurements, the development of machine learning algorithms using data collected from compound library screening, and the adaption of a variety of relevant bioassays to high-throughput MS.

In this work toward a sustainable operation of a self-powered wireless sensor, we investigated a multiband Wi-Fi/3G/4G/5G energy harvester based on a novel wideband circularly polarized antenna, a quadplexer, and rectifiers at four corresponding bands. This proposed antenna consisted of four sequentially rotated dual-dipoles, fed by a hybrid feeding network with equal amplitude and an incremental 90° phase delay. The feeding network was composed of three Wilkinson power dividers and Schiffman phase shifters. Based on the sequential rotation method, the antenna obtained a -10 dB reflection coefficient bandwidth of 71.2% from 1.4 GHz to 2.95 GHz and a 3 dB axial ratio (AR) bandwidth of 63.6%, from 1.5 GHz to 2.9 GHz. In addition, this antenna gain was higher than 6 dBi in a wide bandwidth from 1.65 GHz to 2.8 GHz, whereas the peak gain was 9.9 dBi. The quad-band rectifier yielded the maximum AC-DC conversion efficiency of 1.8 GHz and was 60% at -1 dBm input power, 2.1 GHz was 55% at 0 dBm, 2.45 GHz was 55% at -1 dBm, and 2.6 GHz was 54% at 0.5 dBm, respectively. The maximum RF-DC conversion efficiency using the wideband circularly polarized antenna was 27%, 26%, 25.5%, and 27.5% at -6 dBm of input power, respectively.

Background: A direct association between metabolic syndrome (MetS) and sperm production/function has been proposed. In this cross-sectional study, we aimed to determine the impact of MetS on sperm survival. Men from infertile couples treated at Hue University Hospital, Vietnam, were enrolled in this study, which spanned the October 2018 to October 2020 period. The general characteristics of the patients, including body mass index (BMI), waist-to-hip ratio (WHR), the levels of different biochemicals, and semen parameters were determined, and sperm survival tests (SSTs) were performed. The modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III for the Asian population was used for MetS diagnosis., Results: Men with an abnormal waist circumference (≥ 90 cm) showed a higher rate of abnormal SST results (30.1% vs. 16.7%, p = 0.012). The frequency of abnormal SST results in patients with MetS (72.3%) was significantly higher than that in individuals without MetS (53.4%) (p = 0.02). Furthermore, the percentage of abnormal SST results in patients with MetS and with BMI ≥ 23 was significantly higher than those in individuals without MetS (77.1% vs. 55.2%, p = 0.03). Weak negative correlations were also observed between the patients' age and the SST results., Conclusion: Sperm viability was lower in men with MetS. We also observed that age and BMI were independent factors associated with abnormal SST., (© 2021. The Author(s).)

Objective: Somatic mutations in UBA1 cause a newly defined syndrome known as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome). More than 50% of patients currently identified as having VEXAS met diagnostic criteria for relapsing polychondritis (RP), but clinical features that characterize VEXAS within a cohort of patients with RP have not been defined. We undertook this study to define the prevalence of somatic mutations in UBA1 in patients with RP and to create an algorithm to identify patients with genetically confirmed VEXAS among those with RP., Methods: Exome and targeted sequencing of UBA1 was performed in a prospective observational cohort of patients with RP. Clinical and immunologic characteristics of patients with RP were compared based on the presence or absence of UBA1 mutations. The random forest method was used to derive a clinical algorithm to identify patients with UBA1 mutations., Results: Seven of 92 patients with RP (7.6%) had UBA1 mutations (referred to here as VEXAS-RP). Patients with VEXAS-RP were all male, were on average ≥45 years of age at disease onset, and commonly had fever, ear chondritis, skin involvement, deep vein thrombosis, and pulmonary infiltrates. No patient with VEXAS-RP had chondritis of the airways or costochondritis. Mortality was greater in VEXAS-RP than in RP (23% versus 4%; P = 0.029). Elevated acute-phase reactants and hematologic abnormalities (e.g., macrocytic anemia, thrombocytopenia, lymphopenia, multiple myeloma, myelodysplastic syndrome) were prevalent in VEXAS-RP. A decision tree algorithm based on male sex, a mean corpuscular volume >100 fl, and a platelet count <200 ×10 3 /μl differentiated VEXAS-RP from RP with 100% sensitivity and 96% specificity., Conclusion: Mutations in UBA1 were causal for disease in a subset of patients with RP. This subset of patients was defined by disease onset in the fifth decade of life or later, male sex, ear/nose chondritis, and hematologic abnormalities. Early identification is important in VEXAS given the associated high mortality rate., (Published 2021. This article is a U.S.Government work and is in the public domain in the USA.)

Competing Interests: Competing interests: None declared.

A series of MnO 2 -Co 3 O 4 -CeO 2 catalysts with different ceria loading (0.75, 1.26 and 1.88 Ce/Mn molar ratio) were synthesized by a co-precipitation technique and the catalytic activity was tested for selective catalytic reduction of NO x by C 3 H 6 or NH 3 . The catalysts were characterized by various physicochemical techniques to examine the effect of ceria loading on the properties of catalysts, such as crystallinity of metal species, surface area, porosity, and acidity using physical adsorption analysis, SEM-EDX, H 2 -TPR, XRD, NH 3 -TPD and in-situ FTIR spectroscopy. Ceria loading had a significant effect on the reduction of NO x , with the catalyst having low amount of ceria loading (Ce/Mn = 0.75) showing excellent performance at low-temperature conditions, but the activity declined at higher temperature. The high ceria loading (Ce/Mn = 1.88) catalyst showed poor activity compared to the counterparts owing to the lower number of acid sites and the resulting lower adsorption capacity., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Respiratory distress syndrome (RDS) is one of the leading causes of early neonatal morbidity and mortality in late preterm infants (LPIs) worldwide. This matched cohort study aimed to assess how the antenatal dexamethasone use affect the respiratory distress (RD) proportion in preterm newborns between 34 0/7 weeks and 36 6/7 weeks of gestation., Methods: This was a prospective cohort study on 78 women with singleton pregnancy who were in threatened preterm birth and had not received prior dexamethasone, who were admitted between 34 0/7 weeks and 36 6/7 weeks at Hue University of Medicine and Pharmacy Hospital from June 2018 to May 2020. The matched control group without dexamethasone use included 78 pregnant women diagnosed with threatened late preterm births who were at similar gestational ages and estimated fetal weights as the treatment group. The treatment group received 6 mg intramuscular dexamethasone every 12 h for a total of 4 doses or until delivery. Primary outcome was the rate of neonatal RD. Secondary neonatal outcomes included the need for respiratory support, neonatal intensive care unit (NICU) admission, hypoglycemia, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal death. Statistical analyses were performed by using SPSS software, version 26.0., Results: The proportion of RD in LPI was significantly lower in the treatment group than in the matched control group (10.3% vs. 23.1%, respectively), adjusted Odds Ratio [aOR] 0.29; 95% confidence interval [CI] 0.10 - 0.83 and p = 0.021. Neonatal hypoglycemia was more common in the dexamethasone group than in the matched group (25.6% vs. 12.8%, respectively; aOR, 2.59; 95% CI, 1.06 - 6.33; p = 0.037). There were no significant between-groups differences in the incidence of respiratory support, NICU admission or length of hospital stay., Conclusions: Administration of antenatal dexamethasone to women at risk for late preterm birth could help to lower the proportion of respiratory distress in late preterm infants., (© 2021. The Author(s).)

Using desorption electrospray ionization (DESI) as part of an automated high-throughput system, tandem mass spectra of the compounds in a pharmaceutical library were recorded in the positive mode under standardized conditions. Quality control filtering yielded an MS/MS library of 16 662 spectra. Fragmentation of subsets of the compounds in the library chosen to contain a single instance of a particular functional group (amide, piperazine, sulfonamide) was predicted by experts, and the results were compared with the experimental data. Expert performance was good to excellent for all the cases evaluated. Substituents on the functional groups were found to exert important secondary control over the fragmentation, with the main effect observed being product ion stabilization by aromatic substitution, which was consistent across the different groups evaluated. These substituent effects are generally explicable in terms of standard physical organic chemistry considerations of product ion stability as controlling fragmentation. A somewhat unexpected feature was the incidence of homolytic cleavages, driven by the stability of substituted amine radical cations. The findings of this study are intended to lay the groundwork for machine learning approaches to performing MS/MS spectrum → structure and structure → MS/MS spectrum operations on the same experimental data set. The effort involved and the success achieved in computer-aided interpretation, now underway, will be compared with the expert performance as described here.

In injection molding, the temperature control of the dynamic mold is an excellent method for improving the melt flow length, especially of thin-wall products. In this study, the heating efficiency of a novel heating strategy based on induction heating was estimated. With the use of this heating strategy, a molding cycle time similar to the traditional injection molding process could be maintained. In addition, this strategy makes it easier to carry out the heating step due to the separation of the heating position and the mold structure as well as allowing the ease of magnetic control. The results show that, with an initial mold temperature of 30 °C and a gap (G) between the heating surface and the inductor coil of 5 mm, the magnetic heating process can heat the plate to 290 °C within 5 s. However, with a gap of 15 mm, it took up to 8 s to reach 270 °C. According to the measurement results, when the mold heating time during the molding process increased from 0 to 5 s, the flow length increased significantly from 71.5 to 168.1 mm, and the filling percentage of the thin-wall product also increased from 10.2% to 100%. In general, the application of external induction heating (Ex-IH) during the molding cycle resulted in improved melt flow length with minimal increase in the total cycle time, which remained similar to that of the traditional case.

Objectives: This study aimed to evaluate the diagnostic performances of the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative prediction of ovarian cancer., Methods: In a prospective cohort study, data were collected from 475 patients with ovarian masses diagnosed by gynecologic examination / ultrasound who were hospitalized at the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital, Vietnam, between January 2018 and June 2020. ROMA and CPH-I were calculated based on measurements of serum carbohydrate antigen (CA-125) and human epididymis protein (HE4). The final diagnosis was based on clinical features, radiologic and histologic findings, and the International Federation of Gynecology and Obstetrics (FIGO) 2014 stages of ovarian cancer were recorded. Matching the values of ROMA and CPH-I to postoperative histopathology reports resulted in the preoperative prediction values., Results: Among the 475 women, 408 had benign tumors, 5 had borderline tumors and 62 had malignant tumors. The two indices showed similar discriminatory performances with no significant differences (p > 0.05). At an optimal cut-off, the sensitivities/specificities of ROMA and CPH-I for ovarian cancer diagnosis were 74.2% and 91.8%, 87.1% and 78.5%, respectively. The optimal cut-off for CPH-I was 1.89%. The areas under the ROC curves (AUCs) of ROMA and CPH-I were 0.882 (95% CI: 0.849-0.909) and 0.898 (95% CI: 0.867-0.924), respectively., Conclusions: The introduction of the Copenhagen Index to help stratify the malignancy risk of ovarian tumors, irrespective of menopausal status, might be applied as a simple alternative with a similar efficacy to ROMA in clinical practice., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)