Computational prediction of protein interactions in single cells by proximity sequencing.

Proximity sequencing (Prox-seq) simultaneously measures gene expression, protein expression and protein complexes on single cells. Using information from dual-antibody binding events, Prox-seq infers surface protein dimers at the single-cell level. Prox-seq provides multi-dimensional phenotyping of single cells in high throughput, and was recently used to track the formation of receptor complexes during cell signaling and discovered a novel interaction between CD9 and CD8 in naïve T cells. The distribution of protein abundance can affect identification of protein complexes in a complicated manner in dual-binding assays like Prox-seq. These effects are difficult to explore with experiments, yet important for accurate quantification of protein complexes. Here, we introduce a physical model of Prox-seq and computationally evaluate several different methods for reducing background noise when quantifying protein complexes. Furthermore, we developed an improved method for analysis of Prox-seq data, which resulted in more accurate and robust quantification of protein complexes. Finally, our Prox-seq model offers a simple way to investigate the behavior of Prox-seq data under various biological conditions and guide users toward selecting the best analysis method for their data.

Shared sequence characteristics identified in non-canonical rearrangements of HSV-1 genomes.

IMPORTANCE: Mutations and genetic rearrangements are the primary driving forces of evolution. Viruses provide valuable model systems for investigating these mechanisms due to their rapid evolutionary rates and vast genetic variability. To investigate genetic rearrangements in the double-stranded DNA genome of herpes simplex virus type 1, the viral population was serially passaged in various cell types. The serial passaging led to formation of defective genomes, resulted from cell-specific non-canonical rearrangements (NCRs). Interestingly, we discovered shared sequence characteristics underlying the formation of these NCRs across all cell types. Moreover, most NCRs identified in clinical samples shared these characteristics. Based on our findings, we propose a model elucidating the formation of NCRs during viral replication within the nucleus of eukaryotic cells.

Phase-locked and phase-unlocked multicolor solitons in a fiber laser.

Multicolor solitons are nonlinear pulses composed of two or more solitons centered at different frequencies, propagating with the same group velocity. In the time domain, multicolor solitons consist of an envelope multiplying a more rapidly varying fringe pattern that results from the interference of these frequency components. Here, we report the observation in a fiber laser of a novel, to the best of our knowledge, type of dynamics in which different frequency components still have the same group velocity but have different propagation constants. This causes the relative phases between the constituent spectral components to change upon propagation, corresponding to the fringes moving under the envelope. This leads to small periodic energy variations that we directly measure. Our experimental results are in good agreement with realistic numerical simulations based on an iterative cavity map.

Design, synthesis and biological evaluation of novel quinazoline derivatives as immune checkpoint inhibitors.

In this work, we report 14 novel quinazoline derivatives as immune checkpoint inhibitors, IDO1 and PD-L1. The antitumor screening of synthesized compounds on ovarian cancer cells indicated that compound V-d and V-l showed the most activity with IC50 values of about 5 µM. Intriguingly, compound V-d emerges as a stand out, triggering cell death through caspase-dependent and caspase-independent manners. More importantly, V-d presents its ability to hinder tumor sphere formation and re-sensitized cisplatin-resistant A2780 cells to cisplatin treatment. These findings suggest that compound V-d emerges as a promising lead candidate for the future development of immuno anticancer agents.

Drug-induced hepatotoxicity and association with slow acetylation variants NAT2*5 and NAT2*6 in Cameroonian patients with tuberculosis and HIV co-infection.

BACKGROUND: Human immunodeficiency virus (HIV) and tuberculosis (TB) are major contributors to morbidity and mortality in sub-Saharan Africa including Cameroon. Pharmacogenetic variants could serve as predictors of drug-induced hepatotoxicity (DIH), in patients with TB co-infected with HIV. We evaluated the occurrence of DIH and pharmacogenetic variants in Cameroonian patients. METHODS: Treatment-naïve patients with HIV, TB or TB/HIV co-infection were recruited at three hospitals in Cameroon, between September 2018 and November 2019. Appropriate treatment was initiated, and patients followed up for 12 weeks to assess DIH. Pharmacogenetic variants were assessed by allele discrimination TaqMan SNP assays. RESULTS: Of the 141 treatment naïve patients, the overall incidence of DIH was 38% (53/141). The highest incidence of DIH, 52% (32/61), was observed among HIV patients. Of 32 pharmacogenetic variants, the slow acetylation variants NAT2*5 was associated with a decreased risk of DIH (OR: 0.4; 95%CI: 0.17-0.96; p = 0.038), while NAT2*6 was found to be associated with an increased risk of DIH (OR: 4.2; 95%CI: 1.1-15.2; p = 0.017) among patients treated for TB. Up to 15 SNPs differed in ≥ 5% of allele frequencies among African populations, while 25 SNPs differed in ≥ 5% of the allele frequencies among non-African populations, respectively. CONCLUSIONS: DIH is an important clinical problem in African patients with TB and HIV. The NAT2*5 and NAT2*6 variants were found to be associated with DIH in the Cameroonian population. Prior screening for the slow acetylation variants NAT2*5 and NAT2*6 may prevent DIH in TB and HIV-coinfected patients.

A Review of Classification, Diagnosis, and Management of Hydrocele.

This article summarizes and updates a number of issues related to hydrocele including anatomy, embryology, classification, etiology, clinical manifestations, imaging findings, and management. Hydrocele is an abnormal collection of serous fluid between the parietal and visceral layers arising from the mesothelial lining of the tunica vaginalis that surrounds the testis and spermatic cord directly. Hydroceles result from an imbalance of secretion and reabsorption of fluid from the tunica vaginalis. Hydroceles can be divided into two types as primary and secondary. The diagnosis should be based on medical history, clinical manifestations, and imaging studies. Understanding the causes and types of hydroceles is useful for accurately diagnosing and treatment strategy. Hydroceles can be managed by conservative treatment, fluid aspiration, or hydrocelectomy.

Inhibitory Activity of Compounds Isolated from Ligustrum robustum (Roxb.) against HepG2 Liver Cancer Cells: Isocubein and 4-(2-Acetoxyethyl)phenol as Potential Candidates.

Many herbal species in the genus Ligustrum have been shown to contain compounds with anti-cancer biological activity. This study aimed to isolate some compounds from the leaves of Ligustrum robustum (Roxb.) Blume (L. robustum) and evaluate their effects against liver cancer cells. As a result, seven previously reported compounds (1-7) were isolated, including four lignans (1-4) and three phenolic derivatives (5-7). The structures of these compounds were determined using spectroscopic methods and comparison with reported data. All isolates were assessed for their inhibitory effects on HepG2 liver cancer cells. Screening results revealed that two compounds, isocubein (3) and 4-(2-acetoxyethyl)phenol (7), exhibited strong inhibitory activity against cell proliferation, with IC50 values of 3.1±0.9 and 4.5±14 µM, respectively. Further analyses demonstrated that both compounds could suppress the formation and development of 3D tumorspheres in terms of quantity and size. Additionally, isocubein (3) and 4-(2-acetoxyethyl)phenol (7) exhibited the ability to inhibit the migration of HepG2 cells. This study represents the first report on the inhibitory activity against HepG2 liver cancer cells of extracts and isolated compounds from L. robustum, providing valuable information for future research aiming to develop products for liver cancer treatment.

Unveiling the role of heterophase nanostructure in MnO2-based colorimetric sensors for ascorbic acid detection.

Nanozymes based on manganese oxide (MnO2) are demonstrated to be promising probes in colorimetric sensing applications. In this study, the r-MnO2/ß-MnO2 heterophase nanostructure was simply prepared by a calcination process with controllable temperature. The characterization of the nanostructured material was confirmed by SEM, UV-vis spectroscopy, Raman, TGA-DSC, and XRD analysis. The r-MnO2/ß-MnO2 exhibits a remarkably good catalytic activity in the oxidation process of 3,3',5,5'-tetramethylbenzidine (TMB) compared with the r-MnO2 or Mn2O3 nanostructure owing to its heterophase junctions. The enhanced performance of the colorimetric sensor for ascorbic acid (AA) detection was investigated using the r-MnO2/ß-MnO2 heterophase nanostructure as probe. The r-MnO2/ß-MnO2 material enhanced the monitoring of AA in the wide linear range from 1 µM to 50 µM with a limit of detection of 0.84 µM. This work presents a promising and straightforward approach for the construction of MnO2-based colorimetric sensor and their practical application in plant growth monitoring.

Non-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High-Fat, High-Fructose, High-Cholesterol Diet Mouse Model.

Chronic inflammation is a key player in metabolic dysfunction-associated fatty liver disease (MAFLD) progression. Necroptosis, an inflammatory cell death pathway, is elevated in MAFLD patients and mouse models, yet its role is unclear due to the diverse mouse models and inhibition strategies. In our study, we inhibited necroptosis by targeting mixed lineage kinase domain-like pseudokinase (MLKL), the terminal effector of necroptosis, in a high-fat, high-fructose, high-cholesterol (HFHFrHC) mouse model of diet-induced MAFLD. Despite the HFHFrHC diet upregulating MLKL (2.5-fold), WT mice livers showed no increase in necroptosis markers or associated proinflammatory cytokines. Surprisingly, Mlkl-/- mice experienced exacerbated liver inflammation without protection from diet-induced liver damage, steatosis, or fibrosis. In contrast, Mlkl+/- mice showed a significant reduction in these parameters that was associated with elevated Pparα and Pparγ levels. Both Mlkl-/- and Mlkl+/- mice on the HFHFrHC diet resisted diet-induced obesity, attributed to the increased beiging, enhanced oxygen consumption, and energy expenditure due to adipose tissue, and exhibited improved insulin sensitivity. These findings highlight the tissue-specific effects of MLKL on the liver and adipose tissue, and they suggest a dose-dependent effect of MLKL on liver pathology.

High Prevalence of Colistin-Resistant Encoding Genes Carriage among Patients and Healthy Residents in Vietnam.

Background and Objectives: We aimed to investigate the carriage of colistin-resistant genes among both patients with a history of antibiotic exposure and apparently healthy adults with no recent healthcare contact. Materials and Methods: Stool swabs were collected from healthy people, and specimens were collected at the infection foci from the patients. Eleven primer/probe sets were used to perform the Multiplex Real-Time PCR assay with the QuantiNova Multiplex Probe PCR kit for screening the carriage of colistin-resistant genes (mcr-1 to mcr-10) and 16S rRNA gene as internal control. Results: In total, 86 patients and 96 healthy residents were included. Twenty two patients (25.9%) were positive with at least one colistin-resistance encoding gene. The mcr-1 gene was the most frequent (16.5%), followed by mcr-9, mcr-6, and mcr-4 genes, where the prevalence was 11.8%, 10.6%, and 9.4%, respectively. No patient was positive with mcr-3, mcr-7, and mcr-8 genes. Eight patients (9.4%) were positive with multiple colistin-encoding genes. Twenty-three healthy people (24.0%) were positive with at least one colistin-resistance encoding gene, and the mcr-10 gene was the most frequent (27.0%), followed by the mcr-1, mcr-8, and mcr-9 genes, where the prevalence was 24.3%, 21.6%, and 13.5%, respectively. No person was positive with the mcr-2 and mcr-5 genes. Conclusions: Our findings underscore the urgent need for enhanced surveillance, infection control measures, and stewardship interventions to mitigate the spread of colistin resistance in Vietnam.

Anti-cancer activity of green synthesized silver nanoparticles using Ardisia gigantifolia leaf extract against gastric cancer cells.

Using extracts from herbs for silver nanoparticle synthesis is attracting attention for its anticancer activity. Ardisia gigantifolia is a herb used in traditional Chinese medicine for treating stomach ailments, and some compounds isolated from this plant exhibit the inhibitory activity against different cancer cells. However, the synthesis of silver nanoparticle using extract of Ardisia gigantiflia leaves and their anti-cancer activity was not reported. In this report, the green synthesized silver nanoparticles using Ardisia gigantiflia extract (Arg-AgNPs) has average diameter of 6 nm with functional groups including O-H, C-H, and CO founded on the surface of these nanoparticles. The viability assays results revealed Arg-AgNPs reduced gastric cancer cell proliferation in a dose-dependent manner, with IC50 values of 1.37 and 0.65 µg/mL for AGS cells and 1.03 and 0.96 µg/mL for MKN45 cells. Arg-AgNPs caused cell cycle arrest at the G0/G1 phase and suppressed cell migration. Additionally, Arg-AgNPs significantly increased the percentage of senescent cells and promoted overproduction of reactive oxygen species (ROS) compared to the control. Thus, this study indicates that Arg-AgNPs can be considered as a promising candidate against human gastric cancer cells.

Effects of Autoionizing Resonances on Wave-Packet Dynamics Studied by Time-Resolved Photoelectron Spectroscopy.

We report a combined experimental and theoretical study on the effect of autoionizing resonances in time-resolved photoelectron spectroscopy. The coherent excitation of N_{2} by ∼14.15 eV extreme-ultraviolet photons prepares a superposition of three dominant adjacent vibrational levels (v^{'}=14-16) in the valence b^{'} ^{1}Σ_{u}^{+} state, which are probed by the absorption of two or three near-infrared photons (800 nm). The superposition manifests itself as coherent oscillations in the measured photoelectron spectra. A quantum-mechanical simulation confirms that two autoionizing Rydberg states converging to the excited A ^{2}Π_{u} and B ^{2}Σ_{u}^{+} N_{2}^{+} cores are accessed by the resonant absorption of near-infrared photons. We show that these resonances apply different filters to the observation of the vibrational wave packet, which results in different phases and amplitudes of the oscillating photoelectron signal depending on the nature of the autoionizing resonance. This work clarifies the importance of resonances in time-resolved photoelectron spectroscopy and particularly reveals the phase of vibrational quantum beats as a powerful observable for characterizing the properties of such resonances.

Bone Marrow-Derived Mononuclear Cells in the Treatment of Neurological Diseases: Knowns and Unknowns.

Bone marrow-derived mononuclear cells (BMMNCs) have been used for decades in preclinical and clinical studies to treat various neurological diseases. However, there is still a knowledge gap in the understanding of the underlying mechanisms of BMMNCs in the treatment of neurological diseases. In addition, prerequisite factors for the efficacy of BMMNC administration, such as the optimal route, dose, and number of administrations, remain unclear. In this review, we discuss known and unknown aspects of BMMNCs, including the cell harvesting, administration route and dose; mechanisms of action; and their applications in neurological diseases, including stroke, cerebral palsy, spinal cord injury, traumatic brain injury, amyotrophic lateral sclerosis, autism spectrum disorder, and epilepsy. Furthermore, recommendations on indications for BMMNC administration and the advantages and limitations of BMMNC applications for neurological diseases are discussed. BMMNCs in the treatment of neurological diseases. BMMNCs have been applied in several neurological diseases. Proposed mechanisms for the action of BMMNCs include homing, differentiation and paracrine effects (angiogenesis, neuroprotection, and anti-inflammation). Further studies should be performed to determine the optimal cell dose and administration route, the roles of BMMNC subtypes, and the indications for the use of BMMNCs in neurological conditions with and without genetic abnormalities.

Syntheses and antitumor activities of neorautenol and shinpterocarpin analogs.

The natural products neorautenol and shinpterocarpin and their structural analogs were investigated as novel anticancer agents. Twenty-four analogs, including analogs containing a polar chain and simplified analogs, were synthesized efficiently by a modified method from previous reports. The antitumor screening of synthesized compounds toward six cancer cell lines indicated that compounds 37, 42 and 43 with a dialkylaminoethyl-type side chain exhibited more promising activity than neorautenol and shinpterocarpin against lung and colon cancer lines with a range of 4-9 µM. They showed selective toxicity in normal cells.

Design, synthesis and evaluation the bioactivities of novel 1,3-dimethyl-6-amino-1H-indazole derivatives as anticancer agents.

Indoleamine 2,3-dioxygenase (IDO1) is a heme-containing enzyme mainly responsible for the metabolism of tryptophan to kynurenine. To date, the IDO1 inhibitors have been developed intensively for the re-activation of the anticancer immune response. In this report, we designed, and synthesized novel 1,3-dimethyl-6-amino indazole derivatives as IDO1 inhibitors based on the structure of IDO1 active site. We further examined their anticancer activity on hypopharyngeal carcinoma cells (FaDu), squamous cell carcinoma of the oral tongue (YD-15), breast cancer cells (MCF7), and human dental pulp stem cells (HDPSC). Of them, compound N-(4-bromobenzyl)-1,3-dimethyl-1H-indazol-6-amine (7) remarkably suppressed IDO1 expression in a concentration - dependent manner. In addition, 7 was the most potential anticancer compound with inducing apoptosis activity as well as selectively activated extracellular signal-regulated kinases (ERK) in mitogen-activated protein kinase (MAPK) pathways on FaDu cells. Finally, compound 7 suppressed cell mobility in wound healing assay with the reduced expression of matrix metalloproteinase MMP9. Taken together, we believe that 7 is the most promising compound, which may be applied to treatment of hypopharyngeal carcinoma.

Comorbidities of diabetes and hypertension in Vietnam: current burden, trends over time, and correlated factors.

BACKGROUND: Vietnam conducted the national Noncommunicable Disease Risk-Factor Surveillance (STEPs) surveys in the years 2010, 2015, and 2021. This study aims to use STEPs data to assess the burden of comorbidity between diabetes and hypertension, analyze trends over time, and identify factors associated with this comorbidity. METHODS: The study extracted data for the population aged 25-64 years old from three STEPs surveys. Survey weight was used for all estimations of prevalence and 95% CI. Correlated factors with comorbidity were examined by a multivariate logistics model. RESULTS: The prevalence of comorbidity in 2021 was about 3.92% among Vietnamese people aged 25-64. In the last 10 years, this prevalence has increased more than 8 times (from 0.44% to 3.92%). Sub-populations demonstrating the most significant changes included the male population, people living in urban areas, and older people. Significant factors correlated with comorbidity included demographic factors, body mass index (BMI), and clustering of 4 noncommunicable diseases (NCDs) behavioral risk factors (OR = 3.48, p < 0.05). CONCLUSION: The high comorbidity between hypertension and diabetes underscores the imperative for integrated treatment and management approaches in Vietnam. Coordinated care is essential for addressing the complex interplay between these two prevalent conditions.

Individual-, social- and policy- factors associated with smoking cessation among adult male cigarette smokers in Hanoi, Vietnam: a longitudinal study.

BACKGROUND: Nearly one-in-two Vietnamese men smoke cigarettes placing them among the highest tobacco consumers in the world. Despite the need for smoking cessation to curb the burden of tobacco-related diseases in Vietnam, this rate remains at less than 30%. Therefore, this study examines individual-, social- and policy factors associated with smoking cessation among adult male smokers in Vietnam. METHODS: We established a longitudinal International Tobacco Control study of male smokers in Hanoi, Vietnam, in September 2018. This paper analyses 1525 men who participated in baseline and one-year follow-up. We applied a weighted multivariable logistic regression to examine the association between smoking cessation and individual-, social- and policy predictors. RESULTS: At follow-up, 14.8% of participants had quit smoking for at least 30 consecutive days during the last year. Among the persistent smokers, 56.6% expressed intention to quit smoking. Factors associated with smoking cessation included a lower number of cigarettes smoked per day (aOR = 0.96, 95% CI: 0.94, 0.99) and having several attempts to quit smoking (aOR = 2.16, 95% CI 1.13, 4.12). Intention to quit smoking was associated with multiple quit attempts, a chronic condition diagnosis, more tobacco-related knowledge, greater self-efficacy, and more worries about their future health. The perceived impact of smoke-free policy and health warning labels were positively associated with intention to quit at any stage. CONCLUSIONS: Interventions aimed at increasing smoking cessation should focus on all aspects of individual, social, and policy factors. Persistent smokers are more motivated to quit if they have made multiple quit attempts, more self-efficacy of quitting and worried about their future health, indicating that increasing smokers' beliefs and knowledge may be important for behavioural change. Health warning labels and tobacco taxation policies should be maintained and promoted as they are perceived to be particularly useful for persistent smokers' intention to quit.

Clinical and Laboratory Characteristics of Kawasaki Disease and COVID-19-Related Multisystem Inflammatory Syndrome in Children.

Geographical and racial factors constitute important distinctions between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C), but no study has been conducted in Vietnam. Forty-one children with KD from January 2018 to July 2020 and 42 with KD/MIS-C from August 2020 to December 2022 were included in this study. Of the patients, 52.3% were aged between 12 and 35 months. Only two were aged over 5 years, and both were belong to the KD/MIS-C group. A 59.5% of the patients were male. Apart from fever, all symptoms tended to be more frequent in patients with KD/MIS-C. The prevalence of diffuse skin rash, hand and foot edema or erythema and gastrointestinal signs was significantly higher in patients hospitalized with KD/MIS-C. There was no significant difference in laboratory findings between the two groups. Coronary artery dilation was more frequently observed in patients with KD/MIS-C compared to those with KD (40.5% vs. 14.6%, P = 0.009).

Assessing the robustness of COVID-19 vaccine efficacy trials: systematic review and meta-analysis, January 2023.

BackgroundVaccines play a crucial role in the response to COVID-19 and their efficacy is thus of great importance.AimTo assess the robustness of COVID-19 vaccine efficacy (VE) trial results using the fragility index (FI) and fragility quotient (FQ) methodology.MethodsWe conducted a Cochrane and PRISMA-compliant systematic review and meta-analysis of COVID-19 VE trials published worldwide until 22 January 2023. We calculated the FI and FQ for all included studies and assessed their associations with selected trial characteristics using Wilcoxon rank sum tests and Kruskal-Wallis H tests. Spearman correlation coefficients and scatter plots were used to quantify the strength of correlation of FIs and FQs with trial characteristics.ResultsOf 6,032 screened records, we included 40 trials with 54 primary outcomes, comprising 909,404 participants with a median sample size per outcome of 13,993 (interquartile range (IQR): 8,534-25,519). The median FI and FQ was 62 (IQR: 22-123) and 0.50% (IQR: 0.24-0.92), respectively. FIs were positively associated with sample size (p < 0.001), and FQs were positively associated with type of blinding (p = 0.023). The Spearman correlation coefficient for FI with sample size was moderately strong (0.607), and weakly positive for FI and FQ with VE (0.138 and 0.161, respectively).ConclusionsThis was the largest study on trial robustness to date. Robustness of COVID-19 VE trials increased with sample size and varied considerably across several other important trial characteristics. The FI and FQ are valuable complementary parameters for the interpretation of trial results and should be reported alongside established trial outcome measures.

Battery-Free and Real-Time Wireless Sensor System on Marine Propulsion Shaft Using a Wireless Power Transfer Module.

In this paper, we present a wireless sensor system (WSS) that integrated an inductive wireless power transfer (I-WPT) module for battery-free real-time monitoring of the status of rotating shaft in ships. Firstly, an optimized I-WPT module for seamless power supply was implemented using multiple Tx and Rx coils, and its power capability of 1.75 W with an efficiency of 75% was achieved. Secondly, as a result of the high-power transfer performance of the implemented I-WPT module, an entire WSS that integrated four sensors was designed on the rotary shaft. Finally, the designed WSS was installed on a small-scale test bench system with a shaft diameter of 200 mm; it was demonstrated that the status of a propulsion shaft could be monitored in real time without a battery.