Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be ...heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.
The impacts of the eastern-Pacific (EP) and central-Pacific (CP) El Niño-Southern Oscillation (ENSO) on the southern China wintertime rainfall (SCWR) have been investigated. Results show that ...wintertime rainfall over most stations in southern China is enhanced (suppressed) during the EP (CP) El Niño, which are attributed to different atmospheric responses in the western North Pacific (WNP) and South China Sea (SCS) during two types of ENSO. When EP El Niño occurs, an anomalous low-level anticyclone is present over WNP/the Philippines region, resulting in stronger-than-normal southwesterlies over SCS. Such a wind branch acts to suppress East Asian winter monsoon (EAWM) and enhance moisture supply, implying surplus SCWR. During CP El Niño, however, anomalous sinking and low-level anticyclonic flow are found to cover a broad region in SCS. These circulation features are associated with moisture divergence over the northern part of SCS and suppressed SCWR. General circulation model experiments have also been conducted to study influence of various tropical sea surface temperature (SST) patterns on the EAWM atmospheric circulation. For EP El Niño, formation of anomalous low-level WNP anticyclone is jointly attributed to positive/negative SST anomalies (SSTA) over the central-to-eastern/ western equatorial Pacific. However, both positive and negative CP Niño-related-SSTA, located respectively over the central Pacific and WNP/SCS, offset each other and contribute a weak but broad-scale anticyclone centered at SCS. These results suggest that, besides the vital role of SST warming, SST cooling over SCS/WNP during two types of El Niño should be considered carefully for understanding the El Niño-EAWM relationship.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and Aims
Trimethylation of Lys36 on histone 3 (H3K36me3) catalyzed by histone methyltransferase SET domain‐containing 2 (SETD2) is one of the most conserved epigenetic marks from yeast to ...mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor.
Approach and Results
Here, using a liver‐specific Setd2 depletion model, we found that Setd2 deficiency is sufficient to trigger spontaneous HCC. Meanwhile, Setd2 depletion significantly increased tumor and tumor size of a diethylnitrosamine‐induced HCC model. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also by regulating lipid metabolism in the liver. Setd2 deficiency down‐regulated H3K36me3 enrichment and expression of cholesterol efflux genes and caused lipid accumulation. High‐fat diet enhanced lipid accumulation and promoted the development of HCC in Setd2‐deficient mice. Chromatin immunoprecipitation sequencing analysis further revealed that Setd2 depletion induced c‐Jun/activator protein 1 (AP‐1) activation in the liver, which was trigged by accumulated lipid. c‐Jun acts as an oncogene in HCC and functions through inhibiting p53 in Setd2‐deficient cells.
Conclusions
We revealed the roles of Setd2 in HCC and the underlying mechanisms in regulating cholesterol homeostasis and c‐Jun/AP‐1 signaling.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Since the identification of the first RNA demethylase and the establishment of methylated RNA immunoprecipitation-sequencing methodology 6 to 7 years ago, RNA methylation has emerged as a ...widespread phenomenon and a critical regulator of transcript expression. This new layer of regulation is termed “epitranscriptomics.” The most prevalent RNA methylation, N6-methyladenosine (m6A), occurs in approximately 25% of transcripts at the genome-wide level and is enriched around stop codons, in 5′- and 3′-untranslated regions, and within long internal exons. RNA m6A modification regulates RNA splicing, translocation, stability, and translation into protein. m6A is catalyzed by the RNA methyltransferases METTL3, METTL14, and METTL16 (writers), is removed by the demethylases FTO and ALKBH5 (erasers), and interacts with m6A-binding proteins, such as YTHDF1 and IGF2BP1 (readers). RNA methyltransferases, demethylases, and m6A-binding proteins are frequently upregulated in human cancer tissues from a variety of organ origins, increasing onco-transcript and oncoprotein expression, cancer cell proliferation, survival, tumor initiation, progression, and metastasis. Although RNA methyltransferase inhibitors are not available yet, FTO inhibitors have shown promising anticancer effects in vitro and in animal models of cancer. Further screening for selective and potent RNA methyltransferase, demethylase, or m6A-binding protein inhibitors may lead to compounds suitable for future clinical trials in cancer patients.
► Five 3-D hydrate samples are formed to study CH4–CO2 replacement with liquid CO2. ► Liquid CO2 adapts to hydrate reservoirs with/without underlying gas or free water. ► CH4 replacement rate and ...amount increase with the increase of hydrate saturation. ► Saturations of water and hydrate have different effect on CH4 replacement percent. ► There exists a phase zone that replacement rate and percent of CH4 are higher.
The dynamics of CH4 replacement in natural gas hydrate with liquid CO2 was studied with a high pressure three-dimensional reactor. Five groups of hydrate samples were formed to investigate the effect of hydrate reservoir properties on CH4–CO2 replacement reaction. The results showed that CH4 in the hydrate gradually moves to the liquid CO2 phase while CO2 in the liquid phase penetrates into the hydrate under pressure–temperature conditions not only within the phase zone surrounded by (LCO2–VCO2), (water–HCO2–LCO2), and (water–HCH4–VCH4) curves but also that above (LCO2–VCO2) and (water–HCH4–VCH4) curves. The replacement rate and amount of CH4 increase with the increase of hydrate saturation in the sediments. Compared with injecting gaseous CO2 method, liquid CO2 injection is also benefit for the recovery of CH4 from hydrate reservoir with much free water or that without underlying gas room to the extent that the injection of liquid CO2 is kept by high gas saturation. The replacement percent of CH4 hydrate decreases with the increase of hydrate saturation, but increases with the increase of water saturation. A higher replacement percent is obtained in the zone surrounded by three phase curves of (LCO2–VCO2), (water–HCO2–LCO2) and (water–HCH4–VCH4).
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•The simulation, monitoring and control of laser cladding process are reviewed.•The defects of the cladding layer can be reduced by the assistance of external field.•Amorphous and high-entropy alloy ...in laser cladding material systems are summarized.•Self-lubricating coatings with a wide temperature range should be further studied.•Ultrasonic vibration assisted processing should be combined with laser cladding.
In industries such as aerospace, petrochemistry and automobile, many parts of different machines are under environment which shows high temperature and high pressure, and have their proneness to wear and corrosion. Therefore, the wear resistibility and stability under high temperature need to be further improved. Nowadays, Laser cladding (LC) is widely used in machine parts repairing and functional coating due to its advantages such as lower dilution rate, small heat-affected zone and good metallurgical bonding between coating and substrate. In this paper, LC is introduced in detail from aspects of process simulation, monitoring and parameter optimization. At the same time, the paper gives a comprehensive review over LC material system as high entropy alloys (HEAs), amorphous alloy and single crystal alloy have been gradually showing their advantages over traditional metal materials in LC. In addition, the applications of LC in functional coatings and in maintenance of machine parts are also outlined. Also, the existing problems and the development trend of LC is discussed then.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Colorectal cancer is one of the most common cancers in the world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, the epigenomic status in colorectal ...cancer patient tissues remains elusive. Here, together with genomic and transcriptomic analysis, we use ChIP-Seq to profile active enhancers at the genome wide level in colorectal cancer paired patient tissues (tumor and adjacent tissues from the same patients). In total, we sequence 73 pairs of colorectal cancer tissues and generate 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq samples. Our analysis identifies 5590 gain and 1100 lost variant enhancer loci in colorectal cancer, and 334 gain and 121 lost variant super enhancer loci. Multiple key transcription factors in colorectal cancer are predicted with motif analysis and core regulatory circuitry analysis. Further experiments verify the function of the super enhancers governing PHF19 and TBC1D16 in regulating colorectal cancer tumorigenesis, and KLF3 is identified as an oncogenic transcription factor in colorectal cancer. Taken together, our work provides an important epigenomic resource and functional factors for epigenetic studies in colorectal cancer.
The Newtonian gravitational constant, G, is one of the most fundamental constants of nature, but we still do not have an accurate value for it. Despite two centuries of experimental effort, the value ...of G remains the least precisely known of the fundamental constants. A discrepancy of up to 0.05 per cent in recent determinations of G suggests that there may be undiscovered systematic errors in the various existing methods. One way to resolve this issue is to measure G using a number of methods that are unlikely to involve the same systematic effects. Here we report two independent determinations of G using torsion pendulum experiments with the time-of-swing method and the angular-acceleration-feedback method. We obtain G values of 6.674184 × 10
and 6.674484 × 10
cubic metres per kilogram per second squared, with relative standard uncertainties of 11.64 and 11.61 parts per million, respectively. These values have the smallest uncertainties reported until now, and both agree with the latest recommended value within two standard deviations.
Full text
Available for:
KISLJ, NUK, SBMB, UL, UM, UPUK
To demonstrate the use of 3-dimensional (3D)-printed intracranial lesion models for complex neurosurgery to increase the success rate of clinical surgeries via practice in simulated surgeries.
We ...collected computed tomographic, magnetic resonance (MR), and computed tomographic images from patients with intracranial tumor or aneurysm, conducted multimodal image reconstruction, and then constructed a 3D-printed model with the skull base, cerebral arteries, and brain tumor or aneurysm. Forty-nine simulated surgeries were carried out on the model under a microscope, and actual surgery was carried out after validation and accumulation of experience.
The 3D-printed brain tumor models were used to design the surgical route, to simulate piecemeal resection of tumors through keyhole approach, and to verify the extent of tumor resection. A drill was used for bone flap removal and milling of bony structures such as the anterior clinoid process, tuberculum sellae, petrous apex, and internal acoustic meatus. The tumors were removed by laser knife and cavitron ultrasonic aspiration. The 3D-printed aneurysm models were used to assess the feasibility of different keyhole approaches and to select the aneurysm clip. Actual surgery was based on the results of the simulated surgery. Postoperative MR image review showed that 84% (21/25) of patients had total tumor resection and 16% (4/25) subtotal resection. Digital subtraction angiography confirmed complete clipping of all aneurysms (24 cases/39 aneurysms).
3D-printed craniocerebral models provide effective simulated surgery conditions for keyhole surgeries of complex brain tumors or aneurysms and aid in preoperative surgical design, accumulation of surgical experience, and validation of surgical outcomes.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
