The long noncoding RNA TINCR shows aberrant expression in human squamous carcinomas. However, its expression and function in gastric cancer remain unclear. We report that TINCR is strongly ...upregulated in human gastric carcinoma (GC), where it was found to contribute to oncogenesis and cancer progression. We also revealed that TINCR overexpression is induced by nuclear transcription factor SP1. Silencing TINCR expression inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, whereas TINCR overexpression promoted cell growth, as documented in the SGC7901 and BGC823 cell lines. Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and apoptosis of GC cells. Together, our findings suggest that TINCR contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.
The intensity of Northeast Pacific marine heatwaves (MHWs) has been related to local stochastic atmospheric forcing with limited predictability, but their evolution and persistence may be controlled ...by large‐scale climate influences. A Linear Inverse Model containing both sea surface temperature and sea surface height (SSH) anomalies is used to identify the “optimal” conditions for observed Northeast Pacific MHW events that developed two‐to‐four seasons later. These optimal initial conditions include SSH anomalies that are responsible for most of the MHW growth, suggesting the relevance of subsurface ocean dynamics. Moreover, Northeast Pacific MHW growth occurs as part of a basin‐scale dynamical mode that links the North Pacific to central equatorial Pacific El Niño events, whose subsequent development may lengthen MHW duration.
Plain Language Summary
The Northeast Pacific Ocean has experienced episodes of intense and persistent abnormally warm conditions, also known as marine heatwaves (MHWs), with devastating ecological impacts. Being able to predict these extreme events a few seasons in advance is therefore very important, but has proven elusive. Understanding why marine heatwaves differ from one event to the next, especially in terms of their strength and how long they last, is limited due to our inability to predict aspects of daily weather that help drive these events. However, whether a new marine heatwave might occur, and if so how it might then evolve, may be partly understood by relating it to climate conditions extending throughout the Pacific. In this study, we use an empirical method to construct a model capturing how such climate conditions may change over time, and therefore whether a marine heatwave could be anticipated. Our model finds specific ocean surface conditions appearing to lead to the development of the Northeast Pacific marine heatwaves 6–12 months later. These conditions are related to a unique pattern of sea surface anomalies spanning the North Pacific and the central tropical Pacific, which also links extra‐tropical marine heatwaves with subsequent tropical central Pacific warming.
Key Points
A large‐scale precursor to Northeast Pacific marine heatwaves (MHWs) with anomalies in both the North and Tropical Pacific is identified
This optimal precursor includes initial sea surface height anomalies that are key to MHW growth
The initial condition leading to optimal development of Northeast Pacific MHWs can also lead to subsequent Central Pacific El Niño events
Axonal degeneration is central to clinical disability and disease progression in multiple sclerosis (MS). Myeloid cells such as brain-resident microglia and blood-borne monocytes are thought to be ...critically involved in this degenerative process. However, the exact underlying mechanisms have still not been clarified. We have previously demonstrated that human endogenous retrovirus type W (HERV-W) negatively affects oligodendroglial precursor cell (OPC) differentiation and remyelination via its envelope protein pathogenic HERV-W (pHERV-W) ENV (formerly MS-associated retrovirus MSRV-ENV). In this current study, we investigated whether pHERV-W ENV also plays a role in axonal injury in MS. We found that in MS lesions, pHERV-W ENV is present in myeloid cells associated with axons. Focusing on progressive disease stages, we could then demonstrate that pHERV-W ENV induces a degenerative phenotype in microglial cells, driving them toward a close spatial association with myelinated axons. Moreover, in pHERV-W ENV-stimulated myelinated cocultures, microglia were found to structurally damage myelinated axons. Taken together, our data suggest that pHERV-W ENV-mediated microglial polarization contributes to neurodegeneration in MS. Thus, this analysis provides a neurobiological rationale for a recently completed clinical study in MS patients showing that antibody-mediated neutralization of pHERV-W ENV exerts neuroprotective effects.
Lake Tai is China's third largest freshwater lake and an important water resource for agriculture, industrial sectors, and as drinking water for several large cities. In this study, the occurrence of ...five antibiotic resistance genes (sul1, blaTEM, blaNDM-1, blaCTX-M-32, mcr-1) was investigated in water and sediment samples collected from Lake Tai. Antibiotic resistances are currently increasing, posing a significant threat to public health. The sulfonamide resistance gene sul1 was highly abundant in all analyzed water and sediment samples. In addition, the two β-lactamase genes blaTEMand blaNDM-1 – encoding clinically relevant antibiotic resistances – were detected in 67.1 and 7.3% of the water samples and in 70.7 and 15.4% of the sediment samples. The third β-lactamase gene, blaCTX-M-32, was only detected in water samples (13.4%), while the colistin resistance gene mcr-1 was not detected in any of the samples. No significant variations between different sampling sites or time points could be observed. The investigation of drinking water treatment at Lake Tai, using lake water as influent, showed a significant reduction of the antibiotic resistance genes through the treatment process. Microbial source tracking showed only low fecal contamination by humans, ruminants, and pigs, indicating the relevance of other sources such as fish farms. Overall, our results provide important insights into the occurrence and abundance of antibiotic resistance genes in the Lake Tai water system and their elimination via drinking water treatment.
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•Five clinically relevant antibiotic resistance genes were investigated in the Tai Lake, China.•The genes sul1, blaTEM, blaNDM-1, and blaCTX-M-32 were prevalent in the Tai Lake.•The colistin resistance gene mcr-1 could not be detected.•No significant variations between sampling sites and time points could be observed.•Antibiotic resistance gene load is on an equal or even lower level compared to other surface water bodies.
Since December 2019, the novel coronavirus disease 2019 (COVID-19) that emerged in Wuhan city has spread rapidly around the world. The risk for poor outcome dramatically increases once a patient ...progresses to the severe or critical stage. The present study aims to investigate the risk factors for disease progression in individuals with mild to moderate COVID-19.
We conducted a cohort study that included 1007 individuals with mild to moderate COVID-19 from three hospitals in Wuhan. Clinical characteristics and baseline laboratory findings were collected. Patients were followed up for 28 days for observation of disease progression. The end point was the progression to a more severe disease stage.
During a follow up of 28 days, 720 patients (71.50%) had recovered or were symptomatically stable, 222 patients (22.05%) had progressed to severe disease, 22 patients (2.18%) had progressed to the critically ill stage and 43 patients (4.27%) had died. Multivariate Cox proportional hazards models identified that increased age (hazard ratio (HR) 2.56, 95% CI 1.97–3.33), male sex (HR 1.79, 95% CI 1.41–2.28), presence of hypertension (HR 1.44, 95% CI 1.11–1.88), diabetes (HR 1.82, 95% CI 1.35–2.44), chronic obstructive pulmonary disease (HR 2.01, 95% CI 1.38–2.93) and coronary artery disease (HR 1.83, 95% CI 1.26–2.66) were risk factors for disease progression. History of smoking was protective against disease progression (HR 0.56, 95% CI 0.34–0.91). Elevated procalcitonin (HR 1.72, 95% CI 1.02–2.90), urea nitrogen (HR 1.72, 95% CI 1.21–2.43), α-hydroxybutyrate dehydrogenase (HR 3.02, 95% CI 1.26–7.21) and D-dimer (HR 2.01, 95% CI 1.12–3.58) at baseline were also associated with risk for disease progression.
This study identified a panel of risk factors for disease progression in individuals with mild to moderate COVID-19.
Abstract Cation chloride co-transporters are important determinants for the efficacy of inhibitory neurotransmission in the spinal cord and alterations in their expression levels contribute to ...allodynia and hyperalgesia associated with neuropathy. However, it remains unknown whether these co-transporters contribute to chronic inflammatory pain. We investigated the expression of potassium-chloride co-transporter 2 (KCC2) and sodium-potassium-chloride co-transporter 1 (NKCC1) in the rat spinal cord after peripheral inflammation induced by complete Freund’s adjuvant (CFA) injection. Our results suggest that the expression of KCC2, but not that of NKCC1, was significantly reduced in CFA-injected rats. We also found that blockade of endogenous brain-derived neurotrophic factor-tyrosine receptor kinase B pathway inhibited the inflammation-induced KCC2 downregulation. Moreover, intrathecal injection of KCC2 antisense oligodeoxynucleotides into naïve rats reduced KCC2 expression in the spinal cord, leading to behavioral hypersensitivity similar to the hyperalgesia induced by peripheral inflammation. Taken together, these results indicate that peripheral inflammation induces downregulation of KCC2 in the dorsal horn of the spinal cord, which may in turn facilitate the development and/or maintenance of chronic inflammatory pain. The data also support the notion that disinhibition in the spinal cord is a general feature of inflammatory and neuropathic pain conditions, and suggest new therapeutic intervention.
Recent evidence highlights long noncoding RNAs (lncRNAs) as crucial regulators of cancer biology that contribute to tumorigenesis. LncRNA TUG1 was initially detected in a genomic screen for genes ...upregulated in response to taurine treatment in developing mouse retinal cells. Our previous study showed that TUG1 could affect cell proliferation through epigenetically regulating HOXB7 in human non-small cell lung cancer. However, the clinical significance and potential role of TUG1 in GC remains unclear. In this study, we found that TUG1 is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that knockdown of TUG1 repressed GC proliferation both in vitro and in vivo. Mechanistic investigations showed that TUG1 has a key role in G0/G1 arrest. We further demonstrated that TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15, p16, p21, p27 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Together, our results suggest that TUG1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for new therapies in human GC.
Mineral sequestration of waste materials provides a promising method for CO2 sequestration, due to its potential as a finishing step in industries which produce CO2 and alkaline solid by-products. ...However, a number of challenges in mineral carbonation that remain to be resolved, including overcoming the slow kinetics of mineral–fluid reactions, dealing with the large volume of source material required, and reducing the energy needed to hasten the carbonation process. In order to overcome the slow reaction kinetics, experiments on accelerated carbonation are being conducted worldwide. As a result, studies of the operational parameters of the carbonation reaction are progressing. The present study examined the effect of two operational parameters on the mineralization of Australian coal fly ashes for CO2 sequestration at laboratory scale. In this study, carbonation tests were carried out for three Australian coal fly ash samples (S1, S2, S3) inside a continuously stirred reaction chamber. Different water-to-solid ratios (from 0.1 to 1) and reaction temperatures (20–80 °C) were tested under a moderate initial CO2 gas pressure of 3 MPa, and the pressure drop due to carbonation with time was recorded until a constant pressure was achieved at the end of each test. The quantity of CO2 stored in each test was estimated by applying ideal gas law to the test conditions. The formation of carbonates during testing was confirmed by performing micro-structural analysis using scanning electron microscopy. According to the results, a 0.2–0.3 water-to-solid mix ratio recorded the highest sequestration potential for all three fly ashes, and was identified as the optimum for mineralization. The increase of reaction temperature resulted in a faster rate of initial CO2 transfer into the fly ash material but did not have a significant impact on the overall sequestration. Of the three tested ashes, S3 ash sample showed the highest sequestration potential of 27.05 kg of CO2 per ton of fly ash under test conditions. The results confirm the possibility of manipulating the water-to-solid mix ratio and the reaction temperature to enhance the carbonation reaction for mineral CO2 sequestration.
•Coal fly ash can be used in mineral sequestration of CO2 through accelerated carbonation.•The sequestration rate and efficiency can be optimized by manipulating process parameters.•Water and ash mixing ratio affects the overall sequestration and 0.2–0.3 ratio was found.•The increase of reaction temperature results faster rate of initial CO2 transfer.•Australian fly ashes can sequester up to 27.05 kg of CO2 per ton of fly ash.
Abstract On the 17th of October 2021 a grandstand of the Goffert stadium partially collapsed while a crowd was jumping on it. It was concluded that the main reason of the collapse was that the load ...of a jumping crowd exceeded the design load of 4 kN/m2, as specified in the NEN 6702. The load also exceeds the current design load of 5 kN/m2 NEN-EN 1991-1-1. A geometrically and physically non-linear finite element (FEM) model was used to obtain the backbone curve of the response of the grandstand. The push-down analysis was force-controlled to allow the grandstand to rotate and deform freely, so that the failure mechanism could develop freely. The jumping load was modelled with a Fourier series based on the contact ratio, the coordination, and the weight of the crowd. These three parameters were estimated with video footage of the collapse. The mass of the people was roughly 3.5 kN/m2. An equivalent SDOF system was set up based on analytical formulae and the backbone curve. With this model the non-linear dynamic behaviour of the grandstand was assessed. Failure was found with the estimated jumping load after roughly the same number of jumps as was seen on video.
Abstract This paper presents the application of reverse engineering in assessing the dynamic loading on an industry steel structure. The studied steel structure is subjected to a frequently occurring ...plug load from the pipeline of a conveying system. This dynamic load leads to significant vibrations of the structure, and it is likely to govern the fatigue analysis. To assess the magnitude of the dynamic load, vibration measurements have been performed. Velocities in the transverse, longitudinal and vertical directions are measured at five points throughout the structure for a continuous period of seven days. A parametric finite element (FE) model of the structure is properly set up such that its eigenfrequencies match the dominant vibration frequencies found in the measurement data. Furthermore, a linear time history (LTH) analysis with impulse loading is carried out, to interpret and reproduce the measured vibrations. Two selected measurements transients, one representative excitation and one randomly selected excitation, are used to validate and fine-tune the FE model to match the vibration responses of the structure. The magnitude and duration of the impulse load is determined such that the response of the analysis model corresponds best to the measurement data in terms of the first and the second peak velocities, as well as the dominant frequencies. Lastly, a statistical analysis is performed to determine the distribution of vibration velocities over the entire measurement period. With the combination of vibration measurements, FEM analysis and statistical analysis, a good estimation of the occurred dynamic load and the amount of stress cycles in 50 years is made for the fatigue analysis of the steel structure.
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