Helium (He) bubbles are typical radiation defects in structural materials in nuclear reactors after high dose energetic particle irradiation. In the past decades, extensive studies have been ...conducted to explore the dynamic evolution of He bubbles under various conditions and to investigate He-induced hardening and embrittlement. In this review, we summarize the current understanding of the behavior of He bubbles in metals; overview the mechanisms of He bubble nucleation, growth, and coarsening; introduce the latest methods of He control by using interfaces in nanocrystalline metals and metallic multilayers; analyze the effects of He bubbles on strength and ductility of metals; and point out some remaining questions related to He bubbles that are crucial for design of advanced radiation-tolerant materials.
Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of ...lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown.
We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot.
We found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes.
Our findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lysosome is a key subceilular organelle in the execution of the autophagic process and at present little is known whether lysosomal function is controlled in the process of autophagy. In this study, ...we first found that suppression of mammalian target of rapamycin （mTOR） activity by starvation or two mTOR catalytic inhibitors （PP242 and To- rinl）, but not by an allosteric inhibitor （rapamycin）, leads to activation of lysosomal function. Second, we provided evidence that activation of lysosomal function is associated with the suppression of mTOR complex 1 （mTORC1）, but not mTORC2, and the mTORC1 localization to lysosomes is not directly correlated to its regulatory role in lysosomal function. Third, we examined the involvement of transcription factor EB （TFEB） and demonstrated that TFEB acti- vation following mTORC1 suppression is necessary but not sufficient for lysosomal activation. Finally, Atg5 or Atg7 deletion or blockage of the autophagosome-lysosome fusion process effectively diminished lysosomal activation, sug- gesting that lysosomal activation occurring in the course of autophagy is dependent on autophagosome-lysosome fu- sion. Taken together, this study demonstrates that in the course of autophagy, lysosomal function is upregulated via a dual mechanism involving mTORC1 suppression and autophagosome-lysosome fusion.
Clayey silt reservoirs bearing natural gas hydrates (NGH) are considered to be the hydrate-bearing reservoirs that boast the highest reserves but tend to be the most difficult to exploit. They are ...proved to be exploitable by the first NGH production test conducted in the South China Sea in 2017. Based on the understanding of the first production test, the China Geological Survey determined the optimal target NGH reservoirs for production test and conducted a detailed assessment, numerical and experimental simulation, and onshore testing of the reservoirs. After that, it conducted the second offshore NGH production test in 1225 m deep Shenhu Area, South China Sea (also referred to as the second production test) from October 2019 to April 2020. During the second production test, a series of technical challenges of drilling horizontal wells in shallow soft strata in deep sea were met, including wellhead stability, directional drilling of a horizontal well, reservoir stimulation and sand control, and accurate depressurization. As a result, 30 days of continuous gas production was achieved, with a cumulative gas production of 86.14 ×104 m3. Thus, the average daily gas production is 2.87 ×104 m3, which is 5.57 times as much as that obtained in the first production test. Therefore, both the cumulative gas production and the daily gas production were highly improved compared to the first production test. As indicated by the monitoring results of the second production test, there was no anomaly in methane content in the seafloor, seawater, and atmosphere throughout the whole production test. This successful production test further indicates that safe and effective NGH exploitation is feasible in clayey silt NGH reservoirs. The industrialization of hydrates consists of five stages in general, namely theoretical research and simulation experiments, exploratory production test, experimental production test, productive production test, and commercial production. The second production test serves as an important step from the exploratory production test to experimental production test.
Vibronic coupling is a central issue in molecular spectroscopy. Here we investigate vibronic coupling within a single pentacene molecule in real space by imaging the spatial distribution of ...single-molecule electroluminescence via highly localized excitation of tunneling electrons in a controlled plasmonic junction. The observed two-spot orientation for certain vibronic-state imaging is found to be evidently different from the purely electronic 0-0 transition, rotated by 90°, which reflects the change in the transition dipole orientation from along the molecular short axis to the long axis. Such a change reveals the occurrence of strong vibronic coupling associated with a large Herzberg-Teller contribution, going beyond the conventional Franck-Condon picture. The emergence of large vibration-induced transition charges oscillating along the long axis is found to originate from the strong dynamic perturbation of the anti-symmetric vibration on those carbon atoms with large transition density populations during electronic transitions.
We aimed to test the sensitivity of naso-oropharyngeal saliva and self-administered nasal (SN) swab compared to nasopharyngeal (NP) swab for COVID-19 testing in a large cohort of migrant workers in ...Singapore. We also tested the utility of next-generation sequencing (NGS) for diagnosis of COVID-19. Saliva, NP and SN swabs were collected from subjects who presented with acute respiratory infection, their asymptomatic roommates, and prior confirmed cases who were undergoing isolation at a community care facility in June 2020. All samples were tested using RT-PCR. SARS-CoV-2 amplicon-based NGS with phylogenetic analysis was done for 30 samples. We recruited 200 subjects, of which 91 and 46 were tested twice and thrice respectively. In total, 62.0%, 44.5%, and 37.7% of saliva, NP and SN samples were positive. Cycle threshold (Ct) values were lower during the earlier period of infection across all sample types. The percentage of test-positive saliva was higher than NP and SN swabs. We found a strong correlation between viral genome coverage by NGS and Ct values for SARS-CoV-2. Phylogenetic analyses revealed Clade O and lineage B.6 known to be circulating in Singapore. We found saliva to be a sensitive and viable sample for COVID-19 diagnosis.
The catalytic subunit p110δ of phosphoinositide 3‐kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. ...Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small‐interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of β‐catenin and T‐cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3β (GSK‐3β) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD‐mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of β‐catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with β‐catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK‐3β/β‐catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.
PIK3CD is significantly overexpressed in colorectal cancer (CRC) and can induce CRC cell growth and invasion. PIK3CD exerts its functions through activating AKT/GSK‐3β/β‐catenin signaling. PIK3CD might be a novel independent prognostic biomarker and a potential therapeutic target for CRC.
Torreya grandis cv. Merrillii is an important economic tree widely cultivated in hilly subtropical areas in China and some parts of Japan and Korea. Crown and root rot was found on T. grandis in ...Zhejiang Province of China. Three isolates with similar morphology were isolated from diseased samples, and used for identification and pathogenicity tests. The pathogenicity of the isolates was confirmed by fulfilling Koch's postulates. The pathogen was identified as Fusarium commune based on morphological characteristics and phylogenetic tree constructed by combining ITS and TEF‐1α gene sequences. This is the first report of F. commune causing crown and root rot on T. grandis in China.
Artesunate (ART) is an anti-malaria drug that has been shown to exhibit anti-tumor activity, and functional lysosomes are reported to be required for ART-induced cancer cell death, whereas the ...underlying molecular mechanisms remain largely elusive. In this study, we aimed to elucidate the molecular mechanisms underlying ART-induced cell death. We first confirmed that ART induces apoptotic cell death in cancer cells. Interestingly, we found that ART preferably accumulates in the lysosomes and is able to activate lysosomal function via promotion of lysosomal V-ATPase assembly. Furthermore, we found that lysosomes function upstream of mitochondria in reactive oxygen species production. Importantly, we provided evidence showing that lysosomal iron is required for the lysosomal activation and mitochondrial reactive oxygen species production induced by ART. Finally, we showed that ART-induced cell death is mediated by the release of iron in the lysosomes, which results from the lysosomal degradation of ferritin, an iron storage protein. Meanwhile, overexpression of ferritin heavy chain significantly protected cells from ART-induced cell death. In addition, knockdown of nuclear receptor coactivator 4, the adaptor protein for ferritin degradation, was able to block ART-mediated ferritin degradation and rescue the ART-induced cell death. In summary, our study demonstrates that ART treatment activates lysosomal function and then promotes ferritin degradation, subsequently leading to the increase of lysosomal iron that is utilized by ART for its cytotoxic effect on cancer cells. Thus, our data reveal a new mechanistic action underlying ART-induced cell death in cancer cells.
Background: Artesunate is capable of inducing cell death in cancer cells.
Results: Artesunate accumulates in lysosomes and promotes lysosomal function and ferritin degradation, leading to mitochondrial reactive oxygen species production and eventually cell death.
Conclusion: Intracellular iron and ferritin degradation is essential for artesunate-induced lysosomal activation and cell death.
Significance: This work reveals a novel mechanism underlying artesunate-induced cell death.
The entorhinal cortex is of great importance in cognition and memory, its dysfunction causes a variety of neurological diseases, particularly Alzheimer's disease (AD). Yet so far, research on ...entorhinal cortex is still limited. Here, we provided the first single‐nucleus transcriptomic map of primate entorhinal cortex aging. Our result revealed that synapse signaling, neurogenesis, cellular homeostasis, and inflammation‐related genes and pathways changed in a cell‐type‐specific manner with age. Moreover, among the 7 identified cell types, we highlighted the neuronal lineage that was most affected by aging. By integrating multiple datasets, we found entorhinal cortex aging was closely related to multiple neurodegenerative diseases, particularly for AD. The expression levels of APP and MAPT, which generate β‐amyloid (Aβ) and neurofibrillary tangles, respectively, were increased in most aged entorhinal cortex cell types. In addition, we found that neuronal lineage in the aged entorhinal cortex is more prone to AD and identified a subpopulation of excitatory neurons that are most highly associated with AD. Altogether, this study provides a comprehensive cellular and molecular atlas of the primate entorhinal cortex at single‐cell resolution and provides new insights into potential therapeutic targets against age‐related neurodegenerative diseases.
We provided the first single‐nucleus transcriptomic map of primate entorhinal cortex aging. Our result revealed that synapse signaling, neurogenesis, cellular homeostasis, and inflammation‐related genes and pathways changed in a cell‐type‐specific manner with age. By integrating multiple datasets, we found entorhinal cortex aging was closely related to multiple neurodegenerative diseases, particularly for Alzheimer's disease.
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