•People with positive SARS-CoV-2 RNA from respiratory tract specimens are infectious sources of COVID-19.•SARS-CoV-2 RNA from respiratory tract specimens may be persistent or recurrently positive ...during the course of this disease.•Active surveillance of SARS-CoV-2 RNA should be performed for infectivity assessment.
The ongoing outbreak of COVID-19 that began in Wuhan, China, has constituted a Public Health Emergency of International Concern, with cases confirmed in multiple countries. Currently, patients are the primary source of infection. We report a confirmed case of COVID-19 whose oropharyngeal swab test of SARS-CoV-2 RNA turned positive in convalescence. This case highlights the importance of active surveillance of SARS-CoV-2 RNA for infectivity assessment.
Mitochondria, which play central roles in immunometabolic diseases, have their own genome. However, the functions of mitochondria-located noncoding RNAs are largely unknown due to the absence of a ...specific delivery system. By circular RNA (circRNA) expression profile analysis of liver fibroblasts from patients with nonalcoholic steatohepatitis (NASH), we observe that mitochondrial circRNAs account for a considerable fraction of downregulated circRNAs in NASH fibroblasts. By constructing mitochondria-targeting nanoparticles, we observe that Steatohepatitis-associated circRNA ATP5B Regulator (SCAR), which is located in mitochondria, inhibits mitochondrial ROS (mROS) output and fibroblast activation. circRNA SCAR, mediated by PGC-1α, binds to ATP5B and shuts down mPTP by blocking CypD-mPTP interaction. Lipid overload inhibits PGC-1α by endoplasmic reticulum (ER) stress-induced CHOP. In vivo, targeting circRNA SCAR alleviates high fat diet-induced cirrhosis and insulin resistance. Clinically, circRNA SCAR is associated with steatosis-to-NASH progression. Collectively, we identify a mitochondrial circRNA that drives metaflammation and serves as a therapeutic target for NASH.
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•Mitochondria-located circRNA SCAR inhibits mROS output and fibroblast activation•circRNA SCAR shuts down mPTP by binding to ATP5B•Lipid-induced ER stress impairs PGC-1α-mediated circRNA SCAR expression•Mitochondria-specific delivery of circRNA SCAR alleviates metaflammation in vivo
A mitochondrial circRNA that is dysregulated in NAFLD patients’ liver fibroblasts directly binds and regulates the mitochondrial permeability transition pore to modulate mitochondrial metabolism and inflammation, providing a potential therapeutic angle.
Avoiding and controlling dam crest cracking is one of the most difficult problems facing high core rockfill dams of more than 100 m. However, few studies have been conducted on the characteristics ...and causes of dam crest cracking based on long-term measurement data. In this study, a real case of a dam suffering cracking at the crest was studied. The dam has a maximum height of 186 m and has been in service for 10 years. The spatiotemporal characteristics of the dam crest cracking were determined based on monitoring data obtained using crack monitoring instruments, radar detection, seismic refraction tomography, and pit exploration. The causes of dam cracking were analyzed based on the deformation inclination and strain index. The factors controlling the cracking (such as the dam structure, geological structure, and materials' properties) were investigated. The results show the following. 1) The cracks mainly occurred at the interface between the core wall and the downstream dam shell. 2) The cracks mainly developed during the impoundment and operation periods with high water levels, and there was no convergence trend within the 10 years of operation. 3) Uneven settlement and uneven horizontal displacement were the main reasons for the crack formation. 4) The factors influencing the cracking include dam zoning, the geological structure, wetting, and the rheological properties of the rockfill materials, and the reservoir level. The results of this study provide an important engineering reference for the prevention and control of dam crest cracking in high rockfill dams.
•Spatiotemporal characteristics of the dam crest cracking were revealed.•The causes of dam cracking were analyzed through inclination and strain index.•It is shown that uneven deformation is the main reason for cracks.•The influences of structure, material and geology on cracks were discussed.
The computational fluid dynamics (CFD) method based on solving the Reynolds-averaged Navier-Stokes equations was used to simulate the flow field of the body-wave interaction. A dynamic mesh strategy, ...which combines the sliding interface technique and the dynamic layering technique, was adopted to handle the mesh update due to the body motion in the simulation. This mesh strategy was capable of treating the arbitrary translational and rotational motions of the body. To validate its performance, the mesh strategy was implemented with the CFD solver ANSYS-Fluent and was applied to solve the 2-D problem of a freely floating box-shaped structure subjected to the focused wave. The present numerical results were compared with the published experimental data and numerical results. For the case of wave generation, the present dynamic mesh strategy incurred 4% loss in accuracy and 6% loss in efficiency compared to the static mesh strategy. For the case of body-wave interaction, the accuracies of the present dynamic mesh strategy and the dynamic overset mesh technique were at the same level. In addition, an application of the present dynamic mesh strategy to the 3-D simulation of a damaged ship capsizing in regular beam wave was demonstrated.
Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, ...the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted.
In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection.
We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes.
These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.
The Dadu River travels in the mountainous areas of southwestern China, one of regions with the most hazards that has long suffered from frequent geohazards. The early identification of landslides in ...this region is urgently needed, especially after the recent Luding earthquake (MS 6.8). While conventional ground-based monitoring techniques are limited by the complex terrain conditions in these alpine valley regions, space interferometric synthetic aperture radar (InSAR) provides an incomparable advantage in obtaining surface deformation with high precision and over a wide area, which is very useful for long-term and slow geohazard monitoring. In this study, more than 500 Sentinel-1 SAR images with four frames acquired during 2017~2022 were collected to detect the hidden landslide regions from the Jinchuan to Ebian Section along the Dadu River, based on joint-scatterer InSAR (JS-InSAR) and small baseline subset (SBAS) techniques. The results showed that our method could be successfully applied for landslide monitoring in complex mountainous regions. Furthermore, 143 potential landslide regions spreading over an 800 km area along the Dadu River were extracted by integrating the deformation measurements and optical images. Our study can provide a reference for large-scale geological hazard surveys in mountainous areas, and the InSAR technique will be encouraged for the local government in future long-term monitoring applications in the Dadu River Basin.
Tuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate ...whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment.
Eighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV group) and 26 with TB mono-infection (TB group). Clinical data and demographic characteristics were reviewed. The severity of DILI and incidences of liver failure and death were compared. Risk factors of clinical outcomes were defined.
The patterns of DILI were similar in both groups. Compared with patients in the TB group, patients in the TB-HBV group who did not receive anti-HBV therapy before anti-TB treatment were more susceptible to Grade-4 severity of DILI (36.2% vs. 7.7%, P = 0.005), liver failure (67.2% vs. 38.5%, P = 0.013) and poor outcomes (37.9% vs. 7.7%, P = 0.005). Age > 50 years (48.1% vs. 22.6%, P = 0.049), cirrhosis (50.0% vs. 15.4%, P = 0.046) and total bilirubin > 20 mg/dl (51.6% vs. 14.8%, P = 0.005) were independent risk factors for the rate of death in the TB-HBV group, and HBV DNA > 20,000 IU/ml had borderline significance (44.1% vs. 20.8%, P = 0.081). In the TB-HBV group, nucleos(t)ide analogues as rescue therapy were not able to reduce short-term death (33.3% vs. 36.8%, P = 0.659) once liver failure had occurred.
Patients on anti-TB therapy with chronic HBV co-infection are more susceptible to developing liver failure and having poor outcomes during anti-TB treatment. Regular monitoring of liver function and HBV DNA level is mandatory. Anti-HBV treatment should be considered in those with high viral levels before anti-TB treatment.
Acute-on-chronic liver failure is a distinct clinical syndrome characterized by a dysregulated immune response and extensive hepatocyte death without satisfactory therapies. As a cytoplasmic ...degradative and quality-control process, autophagy was implicated in maintaining intracellular homeostasis, and decreased hepatic autophagy was found in many liver diseases and contributes to disease pathogenesis. Previously, we identified the therapeutic potential of mesenchymal stem cells (MSCs) in ACLF patients; however, the intrinsic mechanisms are incompletely understood. Herein, we showed that MSCs restored the impaired autophagic flux and alleviated liver injuries in ACLF mice, but these effects were abolished when autophago-lysosomal maturation was inhibited by leupeptin (leu), suggesting that MSCs exerted their hepatoprotective function in a pro-autophagic dependent manner. Moreover, we described a connection between transcription factor EB (TFEB) and autophagic activity in this context, as evidenced by increased nuclei translocation of TFEB elicited by MSCs were capable of promoting liver autophagy. Mechanistically, we confirmed that let-7a-5p enriched in MSCs derived exosomes (MSC-Exo) could activate autophagy by targeting MAP4K3 to reduce TFEB phosphorylation, and MAP4K3 knockdown partially attenuates the effect of anti-let-7a-5p oligonucleotide via decreasing the inflammatory response, in addition, inducing autophagy. Altogether, these findings revealed that the hepatoprotective effect of MSCs may partially profit from its exosomal let-7a-5p mediating autophagy repairment, which may provide new insights for the therapeutic target of ACLF treatment.
An integrated numerical method that couples a seakeeping solver based on the potential flow theory and a Navier–Stokes (NS) solver with the volume of fluid (VOF) model was developed to study the ...behaviour of a damaged ship in beam seas. The dynamics of water flooding and sloshing in the compartments were calculated by the NS solver, whereas the hydrodynamic forces induced by the sea waves on the external hull surface were calculated using the seakeeping solver. At each time step, the instantaneous ship motion was applied to the excitation of the internal water motion; the corresponding load inside the compartments was added to the resultant external force, which was used to update the ship’s motion. To assess its performance, the integrated method was used to simulate the roll decay of a damaged Ro–Ro ferry and the ferry’s motion in regular beam seas. Validation against experimental data showed that the proposed method can yield satisfactory results with acceptable computational costs.
► An integrated method was developed to study damaged ship flooding in beam seas. ► The sea wave loads on the hull surface were calculated by a seakeeping solver. ► The floodwater dynamics were calculated using a Navier–Stokes solver. ► The interactive dynamics between the ship, sea waves and floodwater were analysed.
Aims A field experiment was conducted to quantify annual nitrous oxide (N₂O) fluxes from control and fertilized plots under open-air and greenhouse vegetable cropping systems in southeast China. We ...compiled the reported global field annual N₂O flux measurements to estimate the emission factor of Í fertilizer for N₂O and its background emissions from vegetable fields. Methods Fluxes of N₂O were measured using static chamber-GC techniques over the 2010-2011 annual cycle with multiple cropping seasons. Results The mean annual N₂O fluxes from the controls were 46.1 ± 2.3 ìg N 2 ON m⁻² hr⁻¹ and 68.3 ± 4.1 µg N₂O-N m⁻² hr⁻¹ in the open-air and greenhouse vegetable systems, respectively. For the plots receiving 900 kgNha⁻¹, annual N₂O emissions averaged 90.6 ± 8.9 µg N₂O-N m⁻² hr⁻¹ and 106.4 ± 6.6 µg N₂O-N m⁻² hr⁻¹ in the open-air and greenhouse vegetable systems, respectively. By pooling published field N₂O flux measurements taken over or close to a full year, the N₂O emission factor for N fertilizer averaged 0.63 ± 0.09 %, with a background emission of 2.67 ± 0.80 kg N₂O-N ha⁻¹ in Chinese vegetable fields. Annual N₂O emissions from Chinese vegetable systems were estimated to be 84.7 Gg N₂O-N yr⁻¹ consisting of 72.5 Gg N₂O-N yr⁻¹ and 12.2 Gg N₂O-N yr⁻¹ in the open-air and greenhouse vegetable systems, respectively. Conclusions While N₂O emissions from the greenhouse vegetable cropping system tended to be slightly higher compared to the open-air system in our experiment, the synthesis of literature data suggests that N₂O emissions would be greater at low N-rates but smaller at high N-rates in greenhouse systems than in open-air vegetable cropping systems. The estimates of this study suggest that vegetable cropping systems covering 11.4 % in national total cropping area, contributed 21-25 % to the total N₂O emission from Chinese croplands.
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