JC virus spread is potentiated by glial replication and demyelination-linked glial proliferation.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating infection of the immunosuppressed brain, mediated by the gliotropic polyomavirus JCV. JCV replicates in human glial progenitor cells and astrocytes, which undergo viral T antigen-triggered mitosis, enabling viral replication. We asked if JCV spread might therefore be accelerated by glial proliferation. Using both in vitro analysis and a human glial chimeric mouse model of JCV infection, we found that dividing human astrocytes supported JCV propagation to a substantially greater degree than did mitotically quiescent cells. Accordingly, bulk and single cell RNA-sequence analysis revealed that JCV-infected glia differentially manifested cell cycle-linked disruption of both DNA damage response and transcriptional regulatory pathways. In vivo, JCV infection of humanized glial chimeras was greatly accentuated by cuprizone-induced demyelination and its associated mobilization of GPCs. Importantly, in vivo infection triggered the death of uninfected as well as infected glia, reflecting significant bystander death. Together, these data suggest that JCV propagation in PML may be accelerated by glial cell division. As such, the accentuated glial proliferation attending disease-associated demyelination may provide an especially favorable environment for JCV propagation, thus potentiating oligodendrocytic bystander death and further accelerating demyelination in susceptible hosts.

Shared patterns of glial transcriptional dysregulation link Huntington's disease and schizophrenia.

Huntington's disease and juvenile-onset schizophrenia have long been regarded as distinct disorders. However, both manifest cell-intrinsic abnormalities in glial differentiation, with resultant astrocytic dysfunction and hypomyelination. To assess whether a common mechanism might underlie the similar glial pathology of these otherwise disparate conditions, we used comparative correlation network approaches to analyse RNA-sequencing data from human glial progenitor cells (hGPCs) produced from disease-derived pluripotent stem cells. We identified gene sets preserved between Huntington's disease and schizophrenia hGPCs yet distinct from normal controls that included 174 highly connected genes in the shared disease-associated network, focusing on genes involved in synaptic signalling. These synaptic genes were largely suppressed in both schizophrenia and Huntington's disease hGPCs, and gene regulatory network analysis identified a core set of upstream regulators of this network, of which OLIG2 and TCF7L2 were prominent. Among their downstream targets, ADGRL3, a modulator of glutamatergic synapses, was notably suppressed in both schizophrenia and Huntington's disease hGPCs. Chromatin immunoprecipitation sequencing confirmed that OLIG2 and TCF7L2 each bound to the regulatory region of ADGRL3, whose expression was then rescued by lentiviral overexpression of these transcription factors. These data suggest that the disease-associated suppression of OLIG2 and TCF7L2-dependent transcription of glutamate signalling regulators may impair glial receptivity to neuronal glutamate. The consequent loss of activity-dependent mobilization of hGPCs may yield deficient oligodendrocyte production, and hence the hypomyelination noted in these disorders, as well as the disrupted astrocytic differentiation and attendant synaptic dysfunction associated with each. Together, these data highlight the importance of convergent glial molecular pathology in both the pathogenesis and phenotypic similarities of two otherwise unrelated disorders, Huntington's disease and schizophrenia.

Effect of Light-Emitting Grid Panel on Indoor Aquaculture for Measuring Fish Growth.

This study is related to Smart Aqua Farm, which combines artificial intelligence (AI) and Internet of things (IoT) technology. This study aimed to monitor fish growth in indoor aquaculture while automatically measuring the average size and area in real time. Automatic fish size measurement technology is one of the essential elements for unmanned aquaculture. Under the condition of labor shortage, operators have much fatigue because they use a primitive method that samples the size and weight of fish just before fish shipment and measures them directly by humans. When this kind of process is automated, the operator's fatigue can be significantly reduced. Above all, after measuring the fish growth, predicting the final fish shipment date is possible by estimating how much feed and time are required until the fish becomes the desired size. In this study, a video camera and a developed light-emitting grid panel were installed in indoor aquaculture to acquire images of fish, and the size measurement of a mock-up fish was implemented using the proposed method.

Coscinoderines A-J: Trisubstituted Pyridinium-Containing Norterpenoids Isolated from Coscinoderma bakusi, a Tropical Marine Sponge.

Ten new norterpene alkaloids, coscinoderines A-J (1-10), were isolated from the marine sponge Coscinoderma bakusi. Each coscinoderine contains a 1,2,5-trisubstituted pyridinium moiety bearing a terpene unit at the C-2 position. Their structures were elucidated by analysis of NMR and HRMS data, and the absolute stereochemistry of 4 with a 2-methylbutyl group attached to the nitrogen was determined from a comparison of the calculated and measured ECD spectra. The isolation of coscinoderines expands the repertoire of pyridinium alkaloids isolated from marine sponges.

Traditional Vietnamese medicine Kovir capsule for non-severe COVID-19 patients: A phase III double-blind randomized controlled trial.

The number of COVID-19 infections is still increasing with the omicron variant. Although vaccination has shown its effectiveness, efficacious treatments are still required. Kovir, a Vietnamese herbal medicine, has shown potential effects for non-severe COVID-19 patients in terms of symptom resolution and prevention of disease progression in previous studies. This phase-3 trial evaluated the safety and efficacy of Kovir for non-severe COVID-19 adults. Participants were randomized to the Kovir (381 patients) or placebo (192 patients) groups. Outcomes were progression to severe/critical COVID-19, a daily symptom score based on 11 pre-defined symptoms, time to symptom resolution, a negative reverse transcription polymerase chain reaction, an EQ-5D-5L quality of life (QOL) score, and serious adverse events. Only one patient (in the placebo group) progressed to severe COVID-19, thus we could not conclude the effect of Kovir on the prevention of disease progression. Kovir significantly reduced time to symptom resolution (median: 7 vs. 11 days, hazard ratio [95% confidence interval]: 2.03 [1.66-2.48]) compared to placebo. Kovir also increased the QOL score on days 7 and 14. No safety concerns were observed. To conclude, Kovir is safe and facilitates symptom relief for non-severe COVID-19 patients. We advocate using Kovir in the early phase of COVID-19 for non-severe adult patients.

Scalarane Sesterterpenoids Isolated from the Marine Sponge Hyrtios erectus and their Cytotoxicity.

Eighteen scalarane sesterterpenoids (1-18), including eight new derivatives (1-8), were isolated from the sponge Hyrtios erectus (family Thorectidae), the extract of which showed cytotoxicity against the HeLa and MCF-7 cell lines. Of the new derivatives, six compounds (1-6) were found to contain a γ-hydroxybutenolide moiety capable of reversible stereoinversion at the hydroxylated carbon center. Under the influence of other adjacent functional groups, each derivative exhibited a different stereochemical behavior, which was fully deduced by ROESY experiments. All the isolated compounds were examined for their cytotoxicity by MTS assay using staurosporine as a positive control (IC50 0.18 and 0.13 µΜ against HeLa and MCF-7 cells, respectively), and they were found to show weak growth inhibitory activities against HeLa and MCF-7 cells, with a minimal IC50 value of 20.0 µΜ. The compounds containing a γ-hydroxybutenolide moiety (1-3, 10, 12) showed cytotoxicity, with IC50 values ranging from 24.3 to 29.9 µΜ, and the most potent derivative was heteronemin (16). Although the cytotoxicities of isolated compounds were insufficient to discuss the structure-activity relationship, this research could contribute to expanding the structural diversity of scalaranes and understanding the stereochemical behavior of γ-hydroxybutenolides.

Traditional Vietnamese medicine Kovir capsule in patients with mild COVID-19: A double-blind randomized controlled trial.

Kovir capsule, a polyherbal medicine developed from Ren Shen Bai Du San formulation, has been used in various diseases including respiratory infections. A randomized, placebo-controlled, double-blind study was conducted to evaluate the safety and efficacy of Kovir capsule (TD0069) in the treatment of mild COVID-19 patients. Patients aged from 18 to 65 years who were PCR-confirmed with SARS-CoV-2 and had the mild disease were recruited and randomized to either Kovir capsule (34 patients) or placebo (32 patients) for up to 14 days or until discharge. Efficacy outcomes were time to viral clearance, daily viral load, time to symptom resolution, daily symptom score based on 16 pre-defined symptoms, and progression to severe/critical COVID-19. Safety outcomes were adverse events. Viral load decreased over time similarly in the two groups. Viral clearance time was also similar in both groups (median: 8 days). Kovir group had a more rapid decrease of symptom score and significantly lower time to symptom resolution than placebo (median: 4 vs. 7 days). Two patients in the placebo group developed severe COVID-19. No patient experienced adverse events. Kovir capsule is safe and can improve symptom resolution in mild COVID-19 patients. A large-scale trial is required to confirm these findings.

Apply MIKE 11 model to study impacts of climate change on water resources and develop adaptation plan in the Mekong Delta, Vietnam: a case of Can Tho city.

Can Tho city in the Mekong Delta is in the top ten areas affected by climate change. Therefore, assessing climate change impacts, social and economic activities require proposed solutions to respond to climate change. This study aims to (i) apply the MIKE 11 model (Hydrodynamic module and Advection-Dispersion module) to simulate the impacts of climate change scenarios on water resources in Can Tho city; (ii) calculate water balance in Can Tho city; and (iii) suggest climate change adaptation plan for sustainable social-economic activities of the city. The results show that when the rainfall changes due to climate change, the flow rate tends to decrease at high tide and increase at low tide. When the sea level rises due to climate change, the flow rate tends to increase at high tide and decrease at low tide. For 2030, the flow will decrease up to 15.6% and 14.3% at the low tide period for RCP 2.6 and RCP 8.5 compared to the present, respectively. The flow will increase up to 63.5% and 58.9% at the high tide period for RCP 2.6 and RCP 8.5 compared to the present, respectively. The water demand evaluation shows that the water resource reserve in Can Tho city meets water demands in current and future scenarios under climate change. While rainwater and groundwater can provide enough water in the rainy season, the city has to use surface water during the dry season due to a lack of rainwater. Of these, agriculture contributes the most water demands (85%). Eight adaptation measures to climate change for Can Tho city are developed from 2021 to 2050.

Secondary Metabolites from the Marine Sponges of the Genus Petrosia: A Literature Review of 43 Years of Research.

Sponges are prolific sources of various natural products that have provided the chemical scaffolds for new drugs. The sponges of the genus Petrosia inhabit various regions and contain a variety of biologically active natural products such as polyacetylenes, sterols, meroterpenoids, and alkaloids. This review aims to provide a comprehensive summary of the chemical structures and biological activities of Petrosia metabolites covering a period of more than four decades (between 1978 and 2020). It is also described in this review that the major groups of metabolites from members of the genus Petrosia differed with latitude. The polyacetylenes were identified to be the most predominant metabolites in Petrosia sponges in temperate regions, while tropical Petrosia species were sources of a greater variety of metabolites, such as meroterpenoids, sterols, polyacetylenes, and alkaloids.

Development and clinical application of a preimplantation genetic testing for monogenic disease (PGT-M) for beta thalassemia in Vietnam.

PURPOSE: The purpose of this research is to study the clinical outcomes using a next-generation sequencing-based protocol allowing for simultaneous testing of mutations in the beta thalassemia (HBB) gene, including single nucleotide polymorphism (SNP) markers for PGT-M along with low-pass whole genome analysis of chromosome aneuploidies for PGT-A. METHODS: A combined PGT-M (thalassemia) plus PGT-A system was developed for patients undergoing IVF in Vietnam. Here we developed a system for testing numerous thalassemia mutations plus SNP-based testing for backup mutation analysis and contamination control using next-generation sequencing (NGS). Low -pass next-generation sequencing was used to assess aneuploidy in some of the clinical PGT cases. Patients underwent IVF followed by embryo biopsy at the blastocyst stage for combined PGT-A/M. RESULTS: Two cases have completed the entire process including transfer of embryos, while a further nine cases have completed the IVF and PGT-M/A analysis but have not completed embryo transfer. In the two cases with embryo transfer, both patients achieved pregnancy with an unaffected, euploid embryo confirmed through prenatal diagnosis. In the further nine cases, 39 embryos were biopsied and all passed QC for amplification. There were 8 unaffected embryos, 31 carrier embryos, and 11 affected embryos. A subset of 24 embryos also had PGT-A analysis with 22 euploid embryos and 2 aneuploid embryos. CONCLUSIONS: Here we report the development and clinical application of a combined PGT-M for HBB and PGT-A for gross chromosome aneuploidies from 11 patients with detailed laboratory findings along with 2 cases that have completed embryo transfer.

An immortalized human adipose-derived stem cell line with highly enhanced chondrogenic properties.

Human adipose-derived stem cells (ASCs) are a commonly used cell type for cartilage tissue engineering. However, donor-to-donor variability, cell heterogeneity, inconsistent chondrogenic potential, and limited expansion potential can hinder the use of these cells for modeling chondrogenesis, in vitro screening of drugs and treatments for joint diseases, or translational applications for tissue engineered cartilage repair. The goal of this study was to create an immortalized ASC line that showed enhanced and consistent chondrogenic potential for applications in cartilage tissue engineering as well as to provide a platform for investigation of biological and mechanobiological pathways involved in cartilage homeostasis and disease. Starting with the ASC52telo cell line, a hTERT-immortalized ASC line, we used lentivirus to overexpress SOX9, a master regulator of chondrogenesis, and screened several clonal populations of SOX9 overexpressing cells to form a new stable cell line with high chondrogenic potential. One clonal line, named ASC52telo-SOX9, displayed increased GAG and type II collagen synthesis and was found to be responsive to both mechanical and inflammatory stimuli in a manner similar to native chondrocytes. The development of a clonal line such as ASC52telo-SOX9 has the potential to be a powerful tool for studying cartilage homeostasis and disease mechanisms in vitro, and potentially as a platform for in vitro drug screening for diseases that affect articular cartilage. Our findings provide an approach for the development of other immortalized cell lines with improved chondrogenic capabilities in ASCs or other adult stem cells.

High-depth transcriptomic profiling reveals the temporal gene signature of human mesenchymal stem cells during chondrogenesis.

Mesenchymal stem/stromal cells (MSCs) provide an attractive cell source for cartilage repair and cell therapy; however, the underlying molecular pathways that drive chondrogenesis of these populations of adult stem cells remain poorly understood. We generated a rich data set of high-throughput RNA sequencing of human MSCs throughout chondrogenesis at 6 different time points. Our data consisted of 18 libraries with 3 individual donors as biologic replicates, with each library possessing a sequencing depth of 100 million reads. Computational analyses with differential gene expression, gene ontology, and weighted gene correlation network analysis identified dynamic changes in multiple biologic pathways and, most importantly, a chondrogenic gene subset, whose functional characterization promises to further harness the potential of MSCs for cartilage tissue engineering. Furthermore, we created a graphic user interface encyclopedia built with the goal of producing an open resource of transcriptomic regulation for additional data mining and pathway analysis of the process of MSC chondrogenesis.-Huynh, N. P. T., Zhang, B., Guilak, F. High-depth transcriptomic profiling reveals the temporal gene signature of human mesenchymal stem cells during chondrogenesis.

Development of a Solar-Powered IoT-Based Instrument for Automatic Measurement of Water Clarity.

Water clarity is the most common indicator of water quality. The purpose of the study was to develop an instrument which can automatically measure water clarity in place of manual measurement by Secchi disk. The instrument is suspended by buoys at the water surface and uses solar energy to measure the light intensity of LED bulbs after passing through a water column; the result is then converted to Secchi depth by using a regression function. Measurement data are stored in a cloud server so that mobile users can access via an Internet connection. Three experiments were conducted to examine the instrument performance: (i) to ensure light intensity of the LED bulbs is strong enough to pass through the water column; (ii) to determine the regression relationship between the measured light intensity of the instrument and Secchi depth; and (iii) to evaluate the coefficient of variation (CV) of the measured water clarity when using our instrument and a conventional Secchi disk. Experiment results show that the measured values of light intensity are stable with the average CV = 5.25%. Moreover, although there are slight differences between the Secchi depth measured by our instrument and those measured by Secchi disk, the measurements by our instrument can efficiently replace the measurements by conventional Secchi disk, which can be affected by weather conditions as well as by human subjectivity.

Accumulation rates of natural radionuclides (40K, 210Pb, 226Ra, 238U, and 232Th) in topsoils due to long-term cultivations of water spinach (Ipomoea Aquatica Forssk.) and rice (Oryza Sativa L.) based on model assessments: A case study in Dong Nai province, Vietnam.

In topsoils, the activity concentrations of natural radionuclides (hereafter NRs) increase due to the addition of NRs from fertilizers, irrigation water, and air dust pollution. On the other hand, various physical-chemical and environmental processes such as radioactive decay, volatilization, leaching, erosion, and plant uptake were responsible for the decrease of the activity concentrations of NRs in the topsoils. In this study, behaviours of 40K, 210Pb, 226Ra, 238U, and 232Th in topsoils were modelled by the CEMC soil model and the HYDRUS-1D model. An exponential equation was proposed for estimating the accumulation rates of these radionuclides in the topsoils. Long-term accumulation of radionuclides was assessed for water spinach (Ipomoea Aquatica Forssk.) soil (hereafter VES) and rice (Oryza sativa L.) soil (hereafter RIS). We found that the current agricultural practices caused the increase of 40K activity concentration in the water spinach soil, and 40K, 210Pb, 226Ra, and 232Th activity concentrations in the rice soil. The accumulation rates of radionuclides were in the order 238U < 232Th < 226Ra < 210Pb < 40K. 25 years of cultivation with water spinach can increase/decrease + (165 ± 6) Bq of 40K, - (8.2 ± 0.7) Bq of 210Pb, - (4.3 ± 0.2) Bq of 226Ra, - (7 0.3 ± 0.3) Bq of 238U, and - (1.8 ± 0.1) Bq of 232Th in 1 kg soil. For rice cultivation, these values are + (1004 ± 39), + (3.3 ± 0.2), + (3.0 ± 0.2), - (5.1 ± 0.3), (2.2 ± 0.1) Bq kg-1 for 40K, 210Pb, 226Ra, 238U, and 232Th, respectively.

Modelling the mitigation speeds of 137Cs, 90Sr and 131I in the topsoils and assessment of the radiological hazards.

Fate modelling of artificial radionuclides (ARs) in top soils are necessary to assess the radiological effects to population. Among ARs, 137Cs, 90Sr and 131I are very important since the large abundances in the environment. In this study, the fates of 137Cs, 90Sr and 131I in the surface soil layers were simulated by the soil model which was developed by the Canadian Centre for Environmental Modelling and Chemistry (CEMC). The scenario that 137Cs, 90Sr and 131I contaminated in topsoil in the exclusion of Fukushima Daiichi nuclear power plant (NPP) accident was evaluated. The results show the expected time for the minimum hazardous level of exposure. It is 115.5 days after the exposure, when the total effective dose is 1 mSv y-1 in which 0.46 mSv y-1 from ingestion and 0.54 mSv y-1 from gamma exposure. Hazard levels due to exposure progresses are varied in order gamma exposure (82.14%) > ingestion (17.47%) > inhalation (0.39%). The hazard levels from radionuclides are varied in order 137Cs (63.34%) > 131I (33.48%) > 90Sr (3.18%).

Emerging roles for long noncoding RNAs in skeletal biology and disease.

Normal skeletal development requires tight coordination of transcriptional networks, signaling pathways, and biomechanical cues, and many of these pathways are dysregulated in pathological conditions affecting cartilage and bone. Recently, a significant role has been identified for long noncoding RNAs (lncRNAs) in developing and maintaining cellular phenotypes, and improvements in sequencing technologies have led to the identification of thousands of lncRNAs across diverse cell types, including the cells within cartilage and bone. It is clear that lncRNAs play critical roles in regulating gene expression. For example, they can function as epigenetic regulators in the nucleus via chromatin modulation to control gene transcription, or in the cytoplasm, where they can function as scaffolds for protein-binding partners or modulate the activity of other coding and noncoding RNAs. In this review, we discuss the growing list of lncRNAs involved in normal development and/or homeostasis of the skeletal system, the potential mechanisms by which these lncRNAs might function, and recent improvements in the methodologies available to study lncRNA functions in vitro and in vivo. Finally, we address the likely utility of lncRNAs as biomarkers and therapeutic targets for diseases of the skeletal system, including osteoarthritis, osteoporosis, and in cancers of the skeletal system.

Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage.

The ability to develop tissue constructs with matrix composition and biomechanical properties that promote rapid tissue repair or regeneration remains an enduring challenge in musculoskeletal engineering. Current approaches require extensive cell manipulation ex vivo, using exogenous growth factors to drive tissue-specific differentiation, matrix accumulation, and mechanical properties, thus limiting their potential clinical utility. The ability to induce and maintain differentiation of stem cells in situ could bypass these steps and enhance the success of engineering approaches for tissue regeneration. The goal of this study was to generate a self-contained bioactive scaffold capable of mediating stem cell differentiation and formation of a cartilaginous extracellular matrix (ECM) using a lentivirus-based method. We first showed that poly-L-lysine could immobilize lentivirus to poly(ε-caprolactone) films and facilitate human mesenchymal stem cell (hMSC) transduction. We then demonstrated that scaffold-mediated gene delivery of transforming growth factor ß3 (TGF-ß3), using a 3D woven poly(ε-caprolactone) scaffold, induced robust cartilaginous ECM formation by hMSCs. Chondrogenesis induced by scaffold-mediated gene delivery was as effective as traditional differentiation protocols involving medium supplementation with TGF-ß3, as assessed by gene expression, biochemical, and biomechanical analyses. Using lentiviral vectors immobilized on a biomechanically functional scaffold, we have developed a system to achieve sustained transgene expression and ECM formation by hMSCs. This method opens new avenues in the development of bioactive implants that circumvent the need for ex vivo tissue generation by enabling the long-term goal of in situ tissue engineering.

Micro-finite element (µFE) modeling of the siamang (Symphalangus syndactylus) third proximal phalanx: the functional role of curvature and the flexor sheath ridge.

Phalangeal curvature is a commonly used morphological feature for the interpretation of extant and fossil primate locomotor behaviour. Here, we build on a recent biomechanical study (Richmond, 2007) in two ways: first, we use a 3D micro-FE model, which models the real internal microstructure (i.e., cortical thickness and trabecular bone structure) and, second, we model four siamang third proximal phalanges. We test identical 2D homogenized FE models and two 3D micro-FE phalanx models that are mathematically straightened to isolate the biomechanical significance of curvature. We further investigate how varying the loading configuration (e.g., boundary constraints) and modeling (e.g., 2D versus 3D) affects the biomechanical behaviour of the phalanx. Finally, we examine how intraspecific variation in external and internal bony morphology affects the biomechanical behaviour of the phalanx. Simulation results demonstrate that the general pattern of strain and displacement is similar between the 3D micro-FE and 2D homogenized FE models but the absolute values differ substantially. The biomechanical behaviour of the 3D FE models more closely match the relative strain patterns from the validation experiment than the 2D homogenized FE models, indicating the 3D microstructure model is preferable. Varying the loading configuration can have dramatic effects on the biomechanical behaviour of the phalanx depending on individual morphology, but overall a cantilevered beam model is an equally valid, if not better, configuration for modeling the phalanx as other previously-proposed models. Variation in flexor ridge morphology has a substantial effect on phalanx strain; the taller the ridge, the less strain incurred by other regions of the palmar shaft. Finally, phalangeal curvature reduces overall strain experienced by the phalanx, but does not necessarily reduce bending or increase the compression-to-tension ratio. These results confirm the adaptive role of phalangeal curvature during flexed-finger grasping postures and demonstrate that modeling variation in cortical thickness and flexor ridge morphology improves the behaviour of the FE model, which has important implications for the functional interpretation of phalanx form.