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Abstract Malignant transformation (MT) is commonly seen in IDH-mutant gliomas. There has been a growing research interest in revealing its underlying mechanisms and intervening prior to MT at the early stages of the transforming process. Here we established a unique pair of matched 3D cell models: 403L, derived from a low-grade glioma (LGG), and 403H, derived from a high-grade glioma (HGG), by utilizing IDH-mutant astrocytoma samples from the same patient when the tumor was diagnosed as WHO grade 2 (tumor mutational burden (TMB) of 3.96/Mb) and later as grade 4 (TMB of 70.07/Mb), respectively. Both cell models were authenticated to a patient’s sample retaining endogenous expression of IDH1 R132H. DNA methylation profiles of the parental tumors referred to LGG and HGG IDH-mutant glioma clusters. The immunopositivity of SOX2, NESTIN, GFAP, OLIG2, and beta 3-Tubulin suggested the multilineage potential of both models. 403H was more prompt to cell invasion and developed infiltrative HGG in vivo. The differentially expressed genes (DEGs) from the RNA sequencing analysis revealed the tumor invasion and aggressiveness related genes exclusively upregulated in the 403H model. Pathway analysis showcased an enrichment of genes associated with epithelial-mesenchymal transition (EMT) and Notch signaling pathways in 403H and 403L, respectively. Mass spectrometry-based targeted metabolomics and hyperpolarized (HP) 1-13C pyruvate in-cell NMR analyses demonstrated significant alterations in the TCA cycle and fatty acid metabolism. Citrate, glutamine, and 2-HG levels were significantly higher in 403H. To our knowledge, this is the first report describing the development of a matched pair of 3D patient-derived cell models representative of MT and temozolomide (TMZ)-induced hypermutator phenotype (HMP) in IDH-mutant glioma, providing insights into genetic and metabolic changes during MT/HMP. This novel in vitro model allows further investigation of the mechanisms of MT at the cellular level. Graphic Abstract

Abstract Background Diphtheria is a re-emerging infectious disease and public health concern worldwide and in Vietnam with increasing cases in recent years. This study aimed to assess the anti-diphtheria toxoid antibodies status in Khanh Hoa Province and identify factors contributing to the vaccination policy in the south-central coast of Vietnam. Methods This was a cross-sectional study to evaluate the seroprevalence of anti-diphtheria toxoid antibodies among 1,195 participants, aged 5 – 40 years in Khanh Hoa Province, Vietnam. Immunoglobulin G antibody levels against diphtheria were detected using a commercial anti-diphtheria toxoid enzyme-linked immunosorbent assay (SERION ELISA classic Diphtheria Immunoglobulin G) and were categorized following the World Health Organization guidelines. Results The mean anti-diphtheria toxoid antibody levels were 0.07 IU/ml (95% Confidence Interval: 0.07–0.08). Anti-diphtheria toxoid antibody levels were found to be associated with age and history of diphtheria vaccination. The 5–15 years age group had the highest levels (0.09 IU/ml), while the older age group had the lowest antibody level (p

Antibiotic-resistant bacteria are becoming more common due to the overuse of antibiotics in aquaculture. Alternative antibiotic solutions are fascinating and under the consideration in many countries. This study's objective was to isolate and identify certain actinomycete isolates with inhibitory action against the hemorrhagic disease-causing Aeromonas hydrophila in intensively cultivated catfish. This investigation isolated ten actinomycete isolates from sediment and water samples of catfish ponds in Vinh Long province. Using the diffusion well method, the study identified all isolates with antogonisttic activity against A. hydrophila. In particular, two isolates, BCA1.2 and BCA1.5, presented the highest inhibitory activity with inhibitory diameter zones of 11±1.0 mm and 10±1.0 mm, respectively. Two actinomycete isolates, BCA1.2 and BCA1.5, had their growth affected by pH, temperature, and NaCl. The findings revealed that two of these isolates showed optimum growth in a pH range of 7.0–8.0 and at 37°C. Two isolates, BCA1.2 and BCA1.5, survived well on medium containing a high salt concentration of NaCl ranging from 3% to 7% and were able to utilize different sources of carbon. They produced a wide range of hydrolytic extracellular enzymes, such as cellulase, amylase, protease, lipase, and chitinase. Isolates BCA1.2 and BCA1.5 were identified as Streptomyces based on morphological, cultural, physiological, and biochemical characteristics and 16S rRNA gene sequencing.

Abstract Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process.

Abstract The present study explored the comparability in performance scores between the computer-delivered and face-to-face modes for the two speaking tests in the Vietnamese Standardized Test of English Proficiency (VSTEP) (the VSTEP.2 and VSTEP.3–5 Speaking tests) according to Vietnam’s Six-Level Foreign Language Proficiency Framework (VNFLPF) and test takers’ experiences. Data were collected from 75 and 82 VSTEP.2 and VSTEP.3–5 university English-majored test takers respectively in both computer-delivered and face-to-face conditions. A counterbalanced research design was adopted to minimise mode order effects. After test completion, 30 of the test takers, 15 from each proficiency test, were interviewed in the focus group format of 3–4 members per group. The results indicated mixed, selective effects of the testing mode. Overall, test scores were comparable in the VSTEP.2 Speaking test but significantly higher in favour of the face-to-face mode for the VSTEP.3–5 Speaking test. However, the statistically significant difference was observed in only one measure of the many analytical criteria (content development in the former test, and pronunciation in the latter test) with mixed mode advantages. The interview data has provided rich refreshing insights into how test takers viewed each testing mode against real-life communication. Their experiences further revealed a wide range of affective preferences involved in the inherent affordances or constraints of each testing mode and their communication and performance/outcome orientation. The findings offer important implications for extrapolation, test preparation and administration, and test taker/rater training in the particular context of the two English speaking proficiency tests in Vietnam and perhaps beyond.

Abstract The spread of misinformation poses a threat to the social media ecosystem. Effective countermeasures to mitigate this threat require that social media platforms be able to accurately detect low-credibility accounts even before the content they share can be classified as misinformation. Here we present methods to infer account credibility from information diffusion patterns, in particular leveraging two networks: the reshare network, capturing an account’s trust in other accounts, and the bipartite account-source network, capturing an account’s trust in media sources. We extend network centrality measures and graph embedding techniques, systematically comparing these algorithms on data from diverse contexts and social media platforms. We demonstrate that both kinds of trust networks provide useful signals for estimating account credibility. Some of the proposed methods yield high accuracy, providing promising solutions to promote the dissemination of reliable information in online communities. Two kinds of homophily emerge from our results: accounts tend to have similar credibility if they reshare each other’s content or share content from similar sources. Our methodology invites further investigation into the relationship between accounts and news sources to better characterize misinformation spreaders.

Abstract Background Epithelial ovarian cancer (EOC) is a global health burden, with the poorest five-year survival rate of the gynecological malignancies due to diagnosis at advanced stage and high recurrence rate. Recurrence in EOC is driven by the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that are supported by a complex extracellular matrix and immunosuppressive microenvironment. To target TICs to prevent recurrence, we identified genes critical for TIC viability from a whole genome siRNA screen. A top hit was the cancer-associated, proteoglycan subunit synthesis enzyme UDP-glucose dehydrogenase (UGDH). Methods Immunohistochemistry was used to characterize UGDH expression in histological and molecular subtypes of EOC. EOC cell lines were subtyped according to the molecular subtypes and the functional effects of modulating UGDH expression in vitro and in vivo in C1/Mesenchymal and C4/Differentiated subtype cell lines was examined. Results High UGDH expression was observed in high-grade serous ovarian cancers and a distinctive survival prognostic for UGDH expression was revealed when serous cancers were stratified by molecular subtype. High UGDH was associated with a poor prognosis in the C1/Mesenchymal subtype and low UGDH was associated with poor prognosis in the C4/Differentiated subtype. Knockdown of UGDH in the C1/mesenchymal molecular subtype reduced spheroid formation and viability and reduced the CD133 + /ALDH high TIC population. Conversely, overexpression of UGDH in the C4/Differentiated subtype reduced the TIC population. In co-culture models, UGDH expression in spheroids affected the gene expression of mesothelial cells causing changes to matrix remodeling proteins, and fibroblast collagen production. Inflammatory cytokine expression of spheroids was altered by UGDH expression. The effect of UGDH knockdown or overexpression in the C1/ Mesenchymal and C4/Differentiated subtypes respectively was tested on mouse intrabursal xenografts and showed dynamic changes to the tumor stroma. Knockdown of UGDH improved survival and reduced tumor burden in C1/Mesenchymal compared to controls. Conclusions These data show that modulation of UGDH expression in ovarian cancer reveals distinct roles for UGDH in the C1/Mesenchymal and C4/Differentiated molecular subtypes of EOC, influencing the tumor microenvironmental composition. UGDH is a strong potential therapeutic target in TICs, for the treatment of EOC, particularly in patients with the mesenchymal molecular subtype.

Background: Escalating evidence shows that ginseng possesses an antiaging potential with cognitive enhancing activity. As mountain cultivated ginseng (MCG) is cultivated without agricultural chemicals, MCG has emerged as a popular herb medicine. However, little is known about the MCG-mediated pharmacological mechanism on brain aging. Methods: As we demonstrated that glutathione peroxidase (GPx) is important for enhancing memory function in the animal model of aging, we investigated the role of MCG as a GPx inducer using GPx-1 (a major type of GPx) knockout (KO) mice. We assessed whether MCG modulates redox and cholinergic parameters, and memory function in aged GPx-1 knockout KOmice. Results: Redox burden of aged GPx-1 KO mice was more evident than that of aged wild-type (WT) mice. Alteration of Nrf2 DNA binding activity appeared to be more evident than that of NFκB DNA binding activity in aged GPx-1 KO mice. Alteration in choline acetyltransferase (ChAT) activity was more evident than that in acetylcholine esterase activity. MCG significantly attenuated reductions in Nrf2 system and ChAT level. MCG significantly enhanced the co-localization of Nrf2-immunoreactivity and ChAT-immunoreactivity in the same cell population. Nrf2 inhibitor brusatol significantly counteracted MCG-mediated up-regulation in ChAT level and ChAT inhibition (by k252a) significantly reduced ERK phosphorylation by MCG, suggesting that MCG might require signal cascade of Nrf2/ChAT/ERK to enhance cognition. Conclusion: GPx-1 depletion might be a prerequisite for cognitive impairment in aged animals. MCG-mediated cognition enhancement might be associated with the activations of Nrf2, ChAT, and ERK signaling cascade.

The public is increasingly concerned about the safety of fruit, so the production and preservation of high-quality fresh fruit is becoming more and more important. This work evaluated the use of a 405 nm light emitting diode (LED) for postharvest preservation of fresh green grapes under tropical temperatures of 29 ± 1 °C. LED exposure to green grapes was done for various lengths of time (0, 24, and 48 hours), corresponding to different dosages of 0, 0.7, and 1.4 kJ/cm2. After 7 days of testing, the results found that 95%, 75%, and 5% of the grapes had been invaded by microorganisms, which matched the pretreatment with LED light at 0 h, 24h, and 48 h. According to the first-order kinetic model, the constant rate of weight loss (k) was 0.039 ± 0.005 (control, LED-0h), 0.037 ± 0.009 (LED-24h), 0.062 ± 0.005 (day−1) (LED-48h), with all p-value < 0.001. Compared to the control condition, weight loss was mostly unaffected by LED-24h. No appreciable color changes were seen for LED-24h and 48h, indicating that the fruit has retained its original color as well as its freshness. In control samples, however, one-third of L* and a* values were reduced from baseline. The control samples are susceptible to fungus infection like Guignardia bidwellii, however, color development and morphology showed that LED-48h with an irradiation dose of 1.4 kJ/cm2 had outstanding anti-fungal effectiveness. These LEDs are a possible replacement for fluorescent lights in fruit market showcase and storage rooms, serving as both a source of illumination and protection against microbial contamination.

Summary: Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.

Summary: Background: The abdominal obesity trends and prevalence are important contributing factors to significant rise of many noncommunicable diseases in Vietnam but have not been well-documented in the literature. This study aimed to describe the prevalence and trends of obesity and abdominal obesity in Vietnam from 2009 to 2015 and evaluate how different definitions of obesity and abdominal obesity are associated with metabolic-related conditions. Methods: We conducted a secondary analysis based on the Vietnam STEPS (STEPwise approach to Surveillance) cross-sectional Survey 2009 and 2015. Obesity and abdominal obesity were defined using the body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) cut-offs from the World Health Organization (WHO) and International Diabetes Federation (IDF). Findings: Depending on the specific cut-offs, from 2009 to 2015, obesity prevalence increased from 0.8%–10% to 1.7%–16.4% in women and from 0.8%–10.3% to 1.7%–15% in men; abdominal obesity prevalence increased from 3%–31.3% to 8%–41.7% in women and from 0.3%–19.3% to 0.4%–25% in men. Abdominal obesity using WC-IDF and WHR-WHO definitions had noticeably higher sensitivity and lower specificity for metabolic-related conditions compared to the other four criteria. All anthropometric measurements were statistically correlated with biomarkers/blood pressure in 2009 and 2015 except for fasting glucose. Only WC-IDF and WHR-WHO definitions showed consistent association with all reported metabolic-related conditions regardless of sex and survey years. Interpretation: The prevalence of obesity and abdominal obesity in Vietnam is increasing rapidly, especially abdominal obesity in women regardless of the criteria used. More studies are needed to investigate how using different diagnostic criteria for obesity and abdominal obesity could better identify metabolic-related conditions. Funding: Authors received no funding for this study.

Abstract LIM domain-binding 3 (LDB3) is a member of the Enigma family of PDZ–LIM proteins. LDB3 has been reported as a striated muscle-specific Z-band alternatively spliced protein that plays an important role in mechanosensory actin cytoskeleton remodeling. This study shows that LDB3 is broadly expressed in the central and peripheral nervous system of human and mouse. LDB3 is predominantly expressed in the adult stages compared to early development and at a significantly higher level in the spinal cord than in the brain. As in skeletal muscle and heart, LDB3 is extensively alternatively spliced in the neurons. Three novel splice isoforms were identified suggesting splicing-dependent regulation of LDB3 expression in the nervous system. Expression of LDB3 in the motor cortex, cerebellum, spinal motor neuron, peripheral nerve, and neuromuscular junction in addition to skeletal muscle indicates important roles for this PDZ–LIM family protein in motor planning and execution. Moreover, expression in the hippocampal neurons suggests roles for LDB3 in learning and memory. LDB3 interactors filamin C and myotilin are also expressed in the spinal motor neuron, nerve, and neuromuscular junction, thereby providing the basis for neurogenic manifestations in myopathies associated with mutations in these so-called muscle proteins.

Abstract Background The cancer genome is commonly altered with thousands of structural rearrangements including insertions, deletions, translocation, inversions, duplications, and copy number variations. Thus, structural variant (SV) characterization plays a paramount role in cancer target identification, oncology diagnostics, and personalized medicine. As part of the SEQC2 Consortium effort, the present study established and evaluated a consensus SV call set using a breast cancer reference cell line and matched normal control derived from the same donor, which were used in our companion benchmarking studies as reference samples. Results We systematically investigated somatic SVs in the reference cancer cell line by comparing to a matched normal cell line using multiple NGS platforms including Illumina short-read, 10X Genomics linked reads, PacBio long reads, Oxford Nanopore long reads, and high-throughput chromosome conformation capture (Hi-C). We established a consensus SV call set of a total of 1788 SVs including 717 deletions, 230 duplications, 551 insertions, 133 inversions, 146 translocations, and 11 breakends for the reference cancer cell line. To independently evaluate and cross-validate the accuracy of our consensus SV call set, we used orthogonal methods including PCR-based validation, Affymetrix arrays, Bionano optical mapping, and identification of fusion genes detected from RNA-seq. We evaluated the strengths and weaknesses of each NGS technology for SV determination, and our findings provide an actionable guide to improve cancer genome SV detection sensitivity and accuracy. Conclusions A high-confidence consensus SV call set was established for the reference cancer cell line. A large subset of the variants identified was validated by multiple orthogonal methods.

The Ede are a Malayo-Polynesian language-speaking ethnic group residing primarily in Dak Lak, Dak Nong, Phu Yen, and Khanh Hoa provinces. They have a rich and unique tangible and intangible culture. From 2017 to 2020, the authors carried out many field trips to Kmrong Prŏng A and Kmrong Prŏng B villages (Ea Tu Commune, Buon Ma Thuot) to research, collect, and inventory the material and spiritual cultural heritage of the Ede for conservation and exhibition at the Dak Lak provincial museum. In this article, we introduce some traditional dishes of the Ede in Krmong Prŏng village, research and evaluate traditional aspects of their cuisine, and propose some recommendations and solutions to preserve and promote the unique Ede cuisine in the current period of development and integration.

The Atacama Large Millimeter/Submillimeter Array has revolutionized the field of dust polarization in protoplanetary disks across multiple wavelengths. Previous observations and empirical modeling have suggested multiple mechanisms of dust polarization toward HL Tau, including grain alignment and dust scattering. However, a detailed modeling of dust polarization based on grain alignment physics is not yet available. Here, using an updated POLARIS code, we perform numerical modeling of dust polarization arising from both grain alignment by the magnetically enhanced radiative torque mechanism and self-scattering to reproduce the HL Tau polarization observed at three wavelengths of 0.87, 1.3, and 3.1 mm. Our modeling results show that the observed multiwavelength polarization could be reproduced only when large grains contain embedded iron inclusions and those with slow internal relaxation must have wrong internal alignment (i.e., the grain’s major axis parallel to its angular momentum). The abundance of iron embedded inside grains in the form of clusters is constrained to be ≳16%, and the number of iron atoms per cluster is N _cl ∼ 9 × 10 ^2 . Maximum grain sizes probed at wavelengths of λ = 0.87, 1.3, and 3.1 mm are constrained at ∼60, 80, and 90 μ m, respectively.

Employing Chemical Vapor Deposition (CVD), we created and then investigated properties of a novel carbon-nanotube porous-copper composite (porous Cu-CNT composite). Field-Emission Scanning Electron Microscopy (FESEM) and Energy-Dispersive x-ray Spectroscopy (EDX) clearly revealed successful coating of CNTs, with its density increasing proportionally with the deposition time. In addition, Raman spectroscopy confirmed the constitution of the composite, which included oxygen, copper, and a high level of carbon. We also found out that the higher density of CNTs led to a significant improvement in light absorption in the visible spectrum, compared with the uncoated porous copper. This special property, combined with the porosity of the copper sample, as well as the exceptional thermal and optical properties of CNTs, makes the composite a highly promising candidate for photothermal applications.

Magnetic fields are ubiquitous in the Universe and are thought to play an important role in various astrophysical processes. Polarization of thermal emission from dust grains aligned with the magnetic field is widely used to measure the 2D magnetic field projected onto the plane of the sky, but its component along the line of sight is not yet constrained. Here, we introduce a new method to infer 3D magnetic fields using thermal dust polarization and grain alignment physics. We first develop a physical model of thermal dust polarization using the modern grain alignment theory based on the magnetically enhanced radiative torque alignment theory. We then test this model with synthetic observations of magnetohydrodynamic simulations of a filamentary cloud with our updated POLARIS code. Combining the tested physical polarization model with synthetic polarization, we show that the B-field inclination angles can be accurately constrained by the polarization degree from synthetic observations. Compared to the true 3D magnetic fields, our method based on grain alignment physics is more accurate than the previous methods that assume uniform grain alignment. This new technique paves the way for tracing 3D B-fields using thermal dust polarization and grain alignment theory and for constraining dust properties and grain alignment physics.

Rpn13 is a substrate receptor of the 26S proteasome and an anti-cancer drug target. Here, the authors identify and characterize XL5, a lead compound that binds to the N-terminal Pru domain of human Rpn13 (hRpn13), solve the NMR structure of XL5-ligated hRpn13 Pru and develop XL5-PROTACs that preferentially target an identified hRpn13 Pru fragment present in multiple myeloma cells.

Measurement(s) Somatic Mutation Analysis Technology Type(s) whole genome sequencing • Whole Exome Sequencing Factor Type(s) sequencing platform • sample prepration • library preparation • bioinformatics method Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16713655

This research presented a method to synthesize magnetic nanocrystalline cellulose-based nanocomposites using in-situ co-precipitation technique to produce ferromagnetic oxide particles (Fe3O4) that were grafted on the surface of cellulose nanocrystals (CNCs). The synthesized material was used to remove lead ions from aqueous solutions. Different physicochemical analyst techniques such as XRD, FTIR, SEM, and TEM were used to characterize the structure of the material upon the different ratios of cellulose nanocrystals/ Fe3O4. The XRD analysis showed that CNC/Fe3O4 nanocomposite has characteristic diffraction peaks corresponding to Fe3O4 and cellulose nanocrystals. The FTIR spectrum indicated the specific functional groups of Fe3O4 and CNC in the nanocomposite materials. The size of nanoparticles produced in this work were less than 15 nm with Fe3O4 and roughly 25 nm with CNC via image SEM and TEM. According to these studies, with the same Pb2+ concentration in water of 200 ppm, the best condition for homogenous materials was the 1:1 ratio (cellulose nanocrystals: Fe3O4) and the absorption capacity at time balance (qe) was 0.1132 mg/g. The lead adsorption of material was evaluated by the ICP-OES measurement method. The equilibrium data fitted the Freundlich isotherm model better than the Langmuir isotherm model. The new adsorbent can help removing 60 % of Pb2+ from the solution and can be magnetically separated from the continuous phase.

In this study, we proposed and tested a green method for producing microcrystalline cellulose (MCC) with high quality from waste banana pseudo-stem (BPS) after fruit harvesting. The MCC was synthesized by treating BPS with sulfuric acid, sodium hydroxide, and H2O2solution.The produced MCC material was then characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis to explore its properties. The removal of methylene blue (MB) in aqueous solution was conducted by batch adsorption method to evaluate the applicability of MCC for wastewater treatment. The results showed that the adsorption using MCC reached equilibrium after 15 min. The highest MB adsorption capacity of MCC reached 16.6mg/g at pH 6. The adsorption kinetics data were best described by the pseudo second order rate equation. Equilibrium isotherm data of adsorption were well fitted to the linear Langmuir isotherm model. Affecting factors such as adsorbent dosage, initial concentration of MB, and temperature were also investigated. These results suggest a great potential use of MCC for advanced wastewater treatment.

Measurement(s) single-cell gene expression analysis Technology Type(s) RNA sequencing Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment cell line Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13403753

Stroke is one of the leading causes of death and disability worldwide, with a disproportionate burden represented by low- and middle-income countries (LMICs). To improve post-stroke outcomes in LMICs, researchers have sought to leverage emerging technologies that overcome traditional barriers associated with stroke management. One such technology, inertial measurement units (IMUs), exhibit great potential as a low-cost, portable means to evaluate and monitor patient progress during decentralized rehabilitation protocols. As such, the aim of the present study was to determine the ability of a low-cost single IMU sensor-based wearable system (named the T’ena sensor) to reliably and accurately assess movement quality and efficiency in physically and neurologically healthy adults. Upper limb movement kinematics measured by the T’ena sensor were compared to the gold standard reference system during three functional tasks, and root mean square errors, Pearson’s correlation coefficients, intraclass correlation coefficients, and the Bland Altman method were used to compare kinematic variables of interest between the two systems for absolute accuracy and equivalency. The T’ena sensor and the gold standard reference system were significantly correlated for all tasks and measures (r range = 0.648—0.947), although less so for the Finger to Nose task (r range = 0.648—0.894). Results demonstrate that single IMU systems are a valid, reliable, and objective method by which to measure movement kinematics during functional tasks. Context-appropriate enabling technologies specifically designed to address barriers to quality health services in LMICs can accelerate progress towards the United Nations Sustainable Development Goal 3.

ATAC-seq (assay for transposase-accessible chromatin with high-throughput sequencing) is a powerful method to evaluate chromatin accessibility and nucleosome positioning at a genome-wide scale. This assay uses a hyperactive Tn5 transposase, to simultaneously cut open chromatin and insert adapter sequences. After sequencing, the reads generated through this technique are generally indicative of transcriptional regulatory elements that are located in accessible chromatin. This method was originally developed by Buenrostro et al. (2013), and since then it has been improved by the same authors several times, until their last update called OMNI ATAC-seq (Corces et al., 2017). Here, we describe an ATAC-seq protocol based on the OMNI-ATAC method, with a special focus on the initial steps of thawing cryopreserved cells, and the final steps of library purification using magnetic beads. This protocol can be of interest for laboratories working in a fast-paced environment.Graphic abstract: Flowchart of the protocol

Rapidly spinning magnetic grains can acquire large magnetic dipole moments due to the Barnett effect. Here we study the new effect of Barnett magnetic dipole–dipole interaction on grain–grain collisions and grain growth, assuming that grains are spun up by radiative torques. For the ideal situation in which grains have parallel Barnett dipole moments aligned with the ambient magnetic field, we find that the collision rate between grains having embedded iron inclusions can be significantly enhanced due to Barnett magnetic dipole–dipole interaction when grains rotate suprathermally by radiative torques. We discuss the implications of enhanced collision rate for grain growth and destruction in the circumstellar envelope of evolved stars, photodissociation regions, and protostellar environments. Our results first reveal the potential importance of the dust magnetic properties, magnetic fields, and the local radiation field for grain growth and destruction. Detailed numerical simulations of grain dynamics that take into account the variation of Barnett dipoles and grain alignment are required to quantify the exact role of Barnett dipole–dipole interaction in grain evolution.

We report the first measurement of polarized thermal dust emission toward the entire infrared dark cloud G11.11−0.12 taken by the polarimeter SOFIA/HAWC+ at 214 μ m. The obtained magnetic fields ( B -fields) from the polarized emission of the early-stage and massive filament tend to be perpendicular to its spine. We produce a map of B -field strengths for the center region of the filament. The strengths vary in the range of 100–600 μ G and are strongest along the filament's spine. The central region is sub-Alfvénic and mostly subcritical, meaning that B -fields dominate over turbulence and are strong enough to resist gravitational collapse. The alignment and properties of dust grains in the filament are studied using radiative torque (RAT) theory. We find the decrease of polarization degree P with emission intensity I , i.e., depolarization effect, of the form P ∝ I ^− ^α with α ∼ 0.8–0.9, implying a significant loss of grain alignment in the filament's spine. The depolarization can be explained by the decrease in RAT alignment efficiency toward the denser regions with weaker radiation field, which cannot be explained by B -field tangling. We study the effect of the enhanced magnetic relaxation by embedded iron inclusions on RAT alignment and find that the high polarization fraction P ∼ 20%–30% in the outer layer of the filament is potential evidence for the magnetically enhanced RAT alignment mechanism. This is the first time this effect is evaluated in a filament. Based on the polarization fraction and RAT alignment theory, we also find evidence for grain growth in the filament.

Corneal wound, associated with pain, impaired vision, and even blindness, is the most common ocular injury. In this study, we investigated the effect of a novel ferroptosis inhibitor, UAMC-3203 (10 nM–50 µM), in corneal epithelial wound healing in vitro in human corneal epithelial (HCE) cells and ex vivo using alkali-induced corneal wounded mice eye model. We evaluated in vivo acute tolerability of the compound by visual inspection, optical coherence tomography (OCT), and stereomicroscope imaging in rats after its application (100 µM drug solution in phosphate buffer pH 7.4) twice a day for 5 days. In addition, we studied the partitioning of UAMC-3203 in corneal epithelium and corneal stroma using excised porcine cornea. Our study demonstrated that UAMC-3203 had a positive corneal epithelial wound healing effect at the optimal concentration of 10 nM (IC50 value for ferroptosis) in vitro and at 10 µM in the ex vivo study. UAMC-3203 solution (100 µM) was well tolerated after topical administration with no signs of toxicity and inflammation in rats. Ex-vivo distribution study revealed significantly higher concentration (~12–38-fold) and partition coefficient (Kp) (~52 times) in corneal epithelium than corneal stroma. The UAMC-3203 solution (100 µM) was stable for up to 30 days at 4 °C, 37 °C, and room temperature. Overall, UAMC-3203 provides a new prospect for safe and effective therapy for corneal wounds.

Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA+/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.

Sustainable agriculture relies on practices and technologies that combine effectiveness with a minimal environmental footprint. RNA interference (RNAi), a eukaryotic process in which transcript expression is reduced in a sequence-specific manner, can be co-opted for the control of plant pests and pathogens in a topical application system. Double-stranded RNA (dsRNA), the key trigger molecule of RNAi, has been shown to provide protection without the need for integration of dsRNA-expressing constructs as transgenes. Consequently, development of RNA-based biopesticides is gaining momentum as a narrow-spectrum alternative to chemical-based control measures, with pests and pathogens targeted with accuracy and specificity. Limitations for a commercially viable product to overcome include stable delivery of the topically applied dsRNA and extension of the duration of protection. In addition to the research focus on delivery of dsRNA, development of regulatory frameworks, risk identification, and establishing avoidance and mitigation strategies is key to widespread deployment of topical RNAi technologies. Once in place, these measures will provide the crop protection industry with the certainty necessary to expend resources on the development of innovative dsRNA-based products. Readily evident risks to human health appear minimal, with multiple barriers to uptake and a long history of consumption of dsRNA from plant material. Unintended impacts to the environment are expected to be most apparent in species closely related to the target. Holistic design practices, which incorporate bioinformatics-based dsRNA selection along with experimental testing, represent important techniques for elimination of adverse impacts.

Herpes simplex virus type 2 (HSV-2) is a common causative agent of genital tract infections. Moreover, HSV-2 and HIV infection can mutually increase the risk of acquiring another virus infection. Due to the high GC content and highly repetitive regions in HSV-2 genomes, only the genomes of four strains have been completely sequenced (HG52, 333, SD90e, and MS). Strain G is commonly used for HSV-2 research, but only a partial genome sequence has been assembled with Illumina sequencing reads. In the current study, we de novo assembled and annotated the complete genome of strain G using PacBio long sequencing reads, which can span the repetitive regions, analyzed the ‘α’ sequence, which plays key roles in HSV-2 genome circulation, replication, cleavage, and packaging of progeny viral DNA, identified the packaging signals homologous to HSV-1 within the ‘α’ sequence, and determined both termini of the linear genome and cleavage site for the process of concatemeric HSV-2 DNA produced via rolling-circle replication. In addition, using Oxford Nanopore Technology sequencing reads, we visualized four HSV-2 genome isomers at the nucleotide level for the first time. Furthermore, the coding sequences of HSV-2 strain G have been compared with those of HG52, 333, and MS. Moreover, phylogenetic analysis of strain G and other diverse HSV-2 strains has been conducted to determine their evolutionary relationship. The results will aid clinical research and treatment development of HSV-2.

Summary: Most current tumor immunotherapy strategies leverage cytotoxic CD8+ T cells. Despite evidence for clinical potential of CD4+ tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the response of tumor-specific CD4+ TILs and draining lymph node (dLN) T cells. Computational approaches to characterize subpopulations identify TIL transcriptomic patterns strikingly distinct from acute and chronic anti-viral responses and dominated by diversity among T-bet-expressing T helper type 1 (Th1)-like cells. In contrast, the dLN response includes T follicular helper (Tfh) cells but lacks Th1 cells. We identify a type I interferon-driven signature in Th1-like TILs and show that it is found in human cancers, in which it is negatively associated with response to checkpoint therapy. Our study provides a proof-of-concept methodology to characterize tumor-specific CD4+ T cell effector programs. Targeting these programs should help improve immunotherapy strategies. : CD4+ T cells contribute to immune responses to tumors, but their functional diversity has hampered their utilization in clinical settings. Magen et al. use single-cell RNA sequencing to dissect the heterogeneity of CD4+ T cell responses to tumor antigens and reveal molecular divergences between anti-tumor and anti-viral responses. Keywords: CD4(+) T cells, Tumor-infiltrating lymphocytes, single-cell RNA-seq, cancer immunotherapy

ABSTRACT In filamentous fungi, an important kinase responsible for adaptation to changes in available nutrients is cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]). This kinase has been well characterized at a molecular level, but its systemic action and direct/indirect targets are generally not well understood in filamentous fungi. In this work, we used a pkaA deletion strain (ΔpkaA) to identify Aspergillus nidulans proteins for which phosphorylation is dependent (either directly or indirectly) on PKA. A combination of phosphoproteomic and transcriptomic analyses revealed both direct and indirect targets of PKA and provided a global perspective on its function. One of these targets was the transcription factor CreA, the main repressor responsible for carbon catabolite repression (CCR). In the ΔpkaA strain, we identified a previously unreported phosphosite in CreA, S319, which (based on motif analysis) appears to be a direct target of Stk22 kinase (AN5728). Upon replacement of CreA S319 with an alanine (i.e., phosphonull mutant), the dynamics of CreA import to the nucleus are affected. Collectively, this work provides a global overview of PKA function while also providing novel insight regarding significance of a specific PKA-mediated phosphorylation event. IMPORTANCE The cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling pathway is well conserved across eukaryotes, and previous work has shown that it plays an important role in regulating development, growth, and virulence in a number of fungi. PKA is activated in response to extracellular nutrients and acts to regulate metabolism and growth. While a number of components in the PKA pathway have been defined in filamentous fungi, current understanding does not provide a global perspective on PKA function. Thus, this work is significant in that it comprehensively identifies proteins and functional pathways regulated by PKA in a model filamentous fungus. This information enhances our understanding of PKA action and may provide information on how to manipulate it for specific purposes.

Formalin-fixed paraffin-embedded (FFPE) tissues are among the most widely available clinical specimens. Their potential utility as a source of RNA for transcriptome studies would greatly enhance population-based cancer studies. Although preliminary studies suggest FFPE tissue may be used for RNA sequencing, the effect of storage time on these specimens needs to be determined. We conducted this study to determine whether RNA in archived FFPE high-grade ovarian serous adenocarcinomas from Surveillance, Epidemiology and End Results (SEER) registries was present in sufficient quantity and quality for RNA-Seq analysis. FFPE tissues, stored from 7 to 32 years, were obtained from three SEER sites. RNA was extracted, quantified, quality assessed, and subjected to RNA-Seq (a whole transcriptome sequencing technology). FFPE specimens stored for longer periods of time had poorer RNA sample quality as indicated by negative correlations between specimen storage time and fragment distribution values (DV). In addition, sample contamination was a common issue among the RNA, with 41 of 67 samples having 5% to 48% bacterial contamination. However, regardless of specimen storage time and bacterial contamination, 60% of the samples yielded data that enabled gene expression quantification, identifying more than 10,000 genes, with the correlations among most biological replicates above 0.7. This study demonstrates that FFPE high-grade ovarian serous adenocarcinomas specimens stored in repositories for up to 32 years and under varying storage conditions are a promising source of RNA for RNA-Seq. We also describe certain caveats to be considered when designing RNA-Seq studies using archived FFPE tissues.

The recent outbreak of the COVID-19 pandemic in 2020 reasserted the necessity of artificial lung membrane technology to treat patients with acute lung failure. In addition, the aging world population inevitably leads to higher demand for better artificial organ (AO) devices. Membrane technology is the central component in many of the AO devices including lung, kidney, liver and pancreas. Although AO technology has improved significantly in the past few decades, the quality of life of organ failure patients is still poor and the technology must be improved further. Most of the current AO literature focuses on the treatment and the clinical use of AO, while the research on the membrane development aspect of AO is relatively scarce. One of the speculated reasons is the wide interdisciplinary spectrum of AO technology, ranging from biotechnology to polymer chemistry and process engineering. In this review, in order to facilitate the membrane aspects of the AO research, the roles of membrane technology in the AO devices, along with the current challenges, are summarized. This review shows that there is a clear need for better membranes in terms of biocompatibility, permselectivity, module design, and process configuration.

Background: Limited data are available on HIV viral suppression rates among men and women on antiretroviral therapy (ART) and factors associated with HIV RNA viral load (VL) suppression in Vietnam. Methods: We conducted a cross-sectional survey of 1255 adult patients on ART for at least 1 year across four provinces in Vietnam. Data collection included a standardised questionnaire, routine laboratory testing, and an HIV VL assay. Bivariate and logistic multivariate analyses were conducted to assess viral suppression rates and factors associated with unsuppressed HIV VL. Results: The median age was 34.5 years and the median time on ART was 46 months. Gender was 66% male (n=828) and 34% female (n=427). HIV viral suppression below 1000 copies/mL was 93%. Viral suppression among woman was not significantly different than among men (93.7% vs92.9%; P=0.59). On multivariate analysis, unsuppressed HIV VL was independently associated with lower CD4 cell count, social isolation, high stigma, not receiving a single-tablet daily regimen, multiple late appointments in past year, and immunological failure. Conclusion: On-treatment viral load suppression rates in Vietnam are high and already exceed the UNAIDS 90% target for viral suppression on ART. Gender does not impact viral suppression rates of patients on ART in Vietnam. Access to routine viral load testing should be improved, adherence monitoring and counselling streamlined, and ART regimens simplified to maintain viral suppression rates, as more people start ART. Psychological and social factors are also associated with unsuppressed HIV VL, necessitating treatment support interventions to address social isolation and stigma among people living with HIV in Vietnam.

Pneumocystis jirovecii is a fungus that can cause life-threatening pneumonia in immunocompromised patients. Here, the authors sequence the genomes of P. jirovecii and two other Pneumocystisspecies, and show the unexpected absence of chitin (a near universal fungal cell wall component).

Organic solvent nanofiltration (OSN) has been considered as one of the key technologies to improve the sustainability of separation processes. Recently, apart from enhancing the membrane performance, greener fabricate on of OSN membranes has been set as a strategic objective. Considerable efforts have been made aiming to improve the sustainability in membrane fabrication, such as replacing membrane materials with biodegradable alternatives, substituting toxic solvents with greener solvents, and minimizing waste generation with material recycling. In addition, new promising fabrication and post-modification methods of solvent-stable membranes have been developed exploiting the concept of interpenetrating polymer networks, spray coating, and facile interfacial polymerization. This review compiles the recent progress and advances for sustainable fabrication in the field of polymeric OSN membranes.

This research focuses on the development of a new 3-DOF (Degree of Freedom) force feedback system featuring a spherical arm mechanism and three magnetorheological (MR) brakes, namely two rotary MR brakes and one linear MR brake. The first rotary MR brake is integrated in the waist joint to reflect the horizontal tangent force, the other rotary MR brake is integrated in the shoulder joint to reflect the elevation tangent force, while the linear MR brake is integrated in the sliding joint of the arm to reflect the radial force (approach force). The proposed configuration can reflect a desired force to the operator at the end-effectors of the arm independently in 3 DOFs by controlling the current applied to the coils of the MR brakes. After the introduction, the configuration of the proposed force feedback system is presented. Afterward, the design and conducted simulation of the MR brakes for the systems are provided. The prototype of the force feedback system, which was manufactured for the experiment, is then presented as well as some of the obtained experimental results. Finally, the proposed control system is presented and its implementation to provide a desired feedback force to the operator is provided.

A macromolecular complex of the enzymes involved in human de novo purine biosynthesis, the purinosome, has been shown to consist of a core assembly to regulate the metabolic activity of the pathway. However, it remains elusive whether the core assembly itself can be selectively controlled in the cytoplasm without promoting the purinosome. Here, we reveal that pharmacological inhibition of the cytoplasmic activity of 3-phosphoinositide-dependent protein kinase 1 (PDK1) selectively promotes the formation of the core assembly, but not the purinosome, in cancer cells. However, alternative signaling cascades that are associated with the plasma membrane-bound PDK1 activity, including Akt-mediated cascades, regulate neither the core assembly nor the purinosome in our conditions. Along with immunofluorescence microscopy and a knock-down study against PDK1 using small interfering RNAs, we reveal that cytoplasmic PDK1-associated signaling pathways regulate subcellular colocalization of three enzymes that form the core assembly of the purinosome in an Akt-independent manner. Collectively, this study reveals a new mode of compartmentalization of purine biosynthetic enzymes controlled by spatially resolved signaling pathways.

Summary: Many tumors are hierarchically organized with a minority cell population that has stem-like properties and enhanced ability to initiate tumorigenesis and drive therapeutic relapse. These cancer stem cells (CSCs) are typically identified by complex combinations of cell-surface markers that differ among tumor types. Here, we developed a flexible lentiviral-based reporter system that allows direct visualization of CSCs based on functional properties. The reporter responds to the core stem cell transcription factors OCT4 and SOX2, with further selectivity and kinetic resolution coming from use of a proteasome-targeting degron. Cancer cells marked by this reporter have the expected properties of self-renewal, generation of heterogeneous offspring, high tumor- and metastasis-initiating activity, and resistance to chemotherapeutics. With this approach, the spatial distribution of CSCs can be assessed in settings that retain microenvironmental and structural cues, and CSC plasticity and response to therapeutics can be monitored in real time. : In this article, Wakefield and colleagues show that a subpopulation of cancer cells with characteristics of cancer stem cells can be identified and visualized in vitro and in vivo using a lentiviral-based fluorescent reporter that responds to the presence of the stemness master transcription factors SOX2 and OCT4.

Energy security is a topic of high importance to many countries throughout the world. Countries with access to vast energy supplies enjoy all of the economic and political benefits that come with controlling a highly sought after commodity. Given the desire to diversify away from fossil fuels due to rising environmental and economic concerns, there are limited technology options available for baseload electricity generation. Further complicating this issue is the desire for energy sources to be sustainable and globally scalable in addition to being economic and environmentally benign. Nuclear energy in its current form meets many but not all of these attributes. In order to address these limitations, TerraPower, LLC has developed the Traveling Wave Reactor (TWR) which is a near-term deployable and truly sustainable energy solution that is globally scalable for the indefinite future. The fast neutron spectrum allows up to a ∼30-fold gain in fuel utilization efficiency when compared to conventional light water reactors utilizing enriched fuel. When compared to other fast reactors, TWRs represent the lowest cost alternative to enjoy the energy security benefits of an advanced nuclear fuel cycle without the associated proliferation concerns of chemical reprocessing. On a country level, this represents a significant savings in the energy generation infrastructure for several reasons 1) no reprocessing plants need to be built, 2) a reduced number of enrichment plants need to be built, 3) reduced waste production results in a lower repository capacity requirement and reduced waste transportation costs and 4) less uranium ore needs to be mined or purchased since natural or depleted uranium can be used directly as fuel. With advanced technological development and added cost, TWRs are also capable of reusing both their own used fuel and used fuel from LWRs, thereby eliminating the need for enrichment in the longer term and reducing the overall societal waste burden. This paper describes the origins and current status of the TWR development program at TerraPower, LLC. Some of the areas covered include the key TWR design challenges and brief descriptions of TWR-Prototype (TWR-P) reactor. Selected information on the TWR-P core designs are also provided in the areas of neutronic, thermal hydraulic and fuel performance. The TWR-P plant design is also described in such areas as; system design descriptions, mechanical design, and safety performance.

In recent film boiling heat transfer studies with nanofluids, it was reported that deposition of nanoparticles on a surface significantly increases the nominal minimum heat flux (MHF) or Leidenfrost Point (LFP) temperature, considerably accelerating the transient cooling of overheated objects. It was suggested that the thin nanoparticle deposition layer and the resulting changes in the physico-chemical characteristics of the hot surface, such as surface roughness height, wettability and porosity, could greatly affect quenching phenomena. In this study, a set of water-droplet LFP tests are conducted using custom-fabricated surfaces which systemically separate the effects of surface roughness height (0-15 um), wettability (0-83°) and nanoporosity (∼23 nm). In addition, high-speed imaging of the evaporating droplets is used to explore the influence of these surface characteristics on the intermittent solid-liquid contacts in film boiling. The obtained results reveal that nanoporosity (not solely high surface wettability) is the crucial feature in efficiently increasing the LFP temperature by initiating heterogeneous nucleation of bubbles during short-lived solid-liquid contacts, which results in disruption of the vapor film, and that micro-posts on the surface intensify such effects by promoting intermittent liquid-surface contacts.

Oxidative RNA damage is linked to cell dysfunction and diseases. The present work focuses on the in vitro oxidation of 5-methylaminomethyl uridine (mnm5U), which belongs to the numerous post-transcriptional modifications that are found in tRNA. The reaction of oxone with mnm5U in water at pH 7.5 leads to two aldonitrone derivatives. They form by two oxidation steps and one dehydration step. Therefore, the potential oxidation products of mnm5U in vivo may not be only aldonitrones, but also hydroxylamine and imine derivatives (which may be chemically more reactive). Irradiation of aldonitrone leads to unstable oxaziridine derivatives that are susceptible to isomerization to amide or to hydrolysis to aldehyde derivative.

Childhood tuberculosis causes significant morbidity and mortality in Southeast Asia, yet little is known about the epidemiology and clinical characteristics of this disease in Viet Nam.To determine the demographics, clinical presentations, radiographic and microbiologic findings, treatment regimens, and outcomes of children admitted with tuberculosis (TB) to a national referral hospital in Viet Nam.We conducted a retrospective case series study of children ≤ 15 years old with bacteriologically confirmed or clinically diagnosed TB admitted to a national referral hospital in Ha Noi, Viet Nam from January through December 2007.One hundred three children were identified: median age 5 years (IQR 2-10), 44% female, 99% Kinh ethnicity, 27% residing in Ha Noi, 88% with BCG vaccination, 27% with known TB contact, and 38% malnourished. Intrathoracic TB was present in 62%, extrathoracic in 52%, both intra and extrathoracic in 19%, and undetermined site in 5%. The most common extrathoracic manifestation was peripheral lymphadenitis, and children under 5 were more likely to have miliary TB or both intra and extrathoracic TB. Fever and failure to thrive were common presenting symptoms among all participants (65% and 56%, respectively), 66% of those with intrathoracic TB presented with cough, and 92% of those with TB meningitis presented with severe neurologic impairment. Acid-fast bacilli smears and mycobacterial cultures were positive in 18% and 21% of children tested, and histopathology was positive in 88% of those biopsied. There were no adverse drug reactions necessitating change in therapy, and no inpatient mortality.Extrathoracic TB was common, treatment well tolerated and clinical outcomes excellent. Culture confirmation rates were low and emphasize the need for improved diagnostics.

The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.7 million sequencing reads (6.3 billion bp). Though a few major microbial clades dominate the planktonic marine niche, the dataset contains great diversity with 85% of the assembled sequence and 57% of the unassembled data being unique at a 98% sequence identity cutoff. Using the metadata associated with each sample and sequencing library, we developed new comparative genomic and assembly methods. One comparative genomic method, termed "fragment recruitment," addressed questions of genome structure, evolution, and taxonomic or phylogenetic diversity, as well as the biochemical diversity of genes and gene families. A second method, termed "extreme assembly," made possible the assembly and reconstruction of large segments of abundant but clearly nonclonal organisms. Within all abundant populations analyzed, we found extensive intra-ribotype diversity in several forms: (1) extensive sequence variation within orthologous regions throughout a given genome; despite coverage of individual ribotypes approaching 500-fold, most individual sequencing reads are unique; (2) numerous changes in gene content some with direct adaptive implications; and (3) hypervariable genomic islands that are too variable to assemble. The intra-ribotype diversity is organized into genetically isolated populations that have overlapping but independent distributions, implying distinct environmental preference. We present novel methods for measuring the genomic similarity between metagenomic samples and show how they may be grouped into several community types. Specific functional adaptations can be identified both within individual ribotypes and across the entire community, including proteorhodopsin spectral tuning and the presence or absence of the phosphate-binding gene PstS.

We report here that wild-type Escherichia coli grows on N-acetylmuramic acid (MurNAc) as the sole source of carbon and energy. Analysis of mutants defective in N-acetylglucosamine (GlcNAc) catabolism revealed that the catabolic pathway for MurNAc merges into the GlcNAc pathway on the level of GlcNAc 6-phosphate. Furthermore, analysis of mutants defective in components of the phosphotransferase system (PTS) revealed that a PTS is essential for growth on MurNAc. However, neither the glucose-, mannose/glucosamine-, nor GlcNAc-specific PTS (PtsG, ManXYZ, and NagE, respectively) was found to be necessary. Instead, we identified a gene at 55 min on the E. coli chromosome that is responsible for MurNAc uptake and growth. It encodes a single polypeptide consisting of the EIIB and C domains of a so-far-uncharacterized PTS that was named murP. MurP lacks an EIIA domain and was found to require the activity of the crr-encoded enzyme IIA-glucose (EIIAGlc), a component of the major glucose transport system for growth on MurNAc. murP deletion mutants were unable to grow on MurNAc as the sole source of carbon; however, growth was rescued by providing murP in trans expressed from an isopropylthiogalactopyranoside-inducible plasmid. A functional His6 fusion of MurP was constructed, isolated from membranes, and identified as a polypeptide with an apparent molecular mass of 37 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. Close homologs of MurP were identified in the genome of several bacteria, and we believe that these organisms might also be able to utilize MurNAc. [ABSTRACT FROM AUTHOR]

Wolfiporia cocos is commonly used as a traditional Chinese medicine for its diuretic, tonifying, and invigorating effects on the spleen. However, the epidermis of W. cocos is discarded as scrap during harvesting because of its low price, resulting in a great waste of resources and environmental pollution. In this work, the epidermis of W. cocos was studied and three new lanostane triterpenoids were isolated. The structures were determined using NMR and HRESIMS, with absolute configurations established by comparison of the calculated and experimental ECD spectra. The three new compounds were evaluated for their antimicrobial activities in vitro against Staphylococcus aureus , Escherichia coli , and Saccharomyces cerevisiae . None of the tested compounds showed inhibition against these three strains of indicator microbes at a concentration of 128 μg/ml. This study provides a reference for further medicinal development and the utilization of the epidermis of W. cocos .

A new biflavone (philonotisflavone-3'''-methyl ether), three diterpenes (lupulin G, lupulin H, lupulin I), a new ecdysteroid (ajugasterone E), and four known compounds were isolated from the whole plant of Ajuga lupulina Maxim. Their structures were determined by spectroscopic analysis, including MS, NMR and ECD spectral data. Compounds 1 - 3 has DPPH radical scavenging ability, and compound 1 has stronger activity than vitamin C. Compounds 2 , 3 , 7 and 8 have potential cytotoxic activity against Hela, with IC 50 values less than 20.0 μM. Abietane diterpenes 2 , 3 , 7 and 8 are also found to have NO inhibitory effects with IC 50 values less than 40.0 μM.

Ethnopharmacological Relevance: Darutigenol (DL) is a natural active product derived from the Chinese herbal medicine Sigesbeckia glabrescens (Makino) Makino. It is administered as a traditional Chinese medicine (TCM) to dispel rheumatism, benefit the joints, and detoxify. However, its potential mechanism in the treatment of rheumatoid arthritis (RA) remains unknown., Aims of the Study: The objectives of this research were to determine the effects and elucidate the modes of action of DL on RA-related joint inflammation., Materials and Methods: Network pharmacology and molecular docking were used to screen and validate candidate DL targets for RA treatment, respectively. A DBA/1 mouse rheumatoid arthritis model was induced with bovine type II collagen. Intragastric DL administration was followed by the calculation of the clinical arthritis index. A section of the ankle joint was excised and stained and the pathological changes in it were observed. Enzyme-linked immunosorbent assays (ELISA) and western blotting (WB) were used to clarify the mechanisms of DL in RA treatment., Results: DL effectively attenuated the inflammation, mitigated the articular cartilage degradation, and bone erosion, and alleviated the inflammatory joints associated with RA. Network pharmacology screened six key targets of DL while molecular docking revealed that it docked well with its protein targets. The DL treatment group presented with significantly less ankle joint redness and swelling, a lower arthritis index scores and serum and bone marrow supernatant IL-6 levels, more complete ankle joint surfaces, and less synovial inflammation, cartilage degradation, and bone erosion than the collagen-induced arthritis (CIA) group. The DL treatment also substantially downregulated the Janus kinase (JAK)1, JAK3, matrix metalloproteinase (MMP)2, MMP9, and phospho-signal transducer and activator of transcription (p-STAT)3 proteins in the joints., Conclusions: To the best of our knowledge, the present work was the first to demonstrate that DL has significant anti-inflammatory efficacy and reduces cartilage degradation and bone erosion. It also demonstrated that the anti-RA effect of DL may be explained by its ability to inhibit joint inflammation and reduce articular cartilage degradation through the interleukin (IL)-6/JAK1,3/STAT3 axis and downregulate MMP2 and MMP9. Hence, DL might play a therapeutic role in a mouse RA model., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)