Identification and functional analysis of lactic acid metabolism-related differentially expressed genes in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality rate that seriously threatens human health. We aimed to investigate the expression, prognostic value, and immune cell infiltration of lactic acid metabolism-related genes (LAMRGs) in HCC using bioinformatics.Methods: The HCC database (The Cancer Genome Atlas–Liver Hepatocellular Carcinoma) was downloaded from the Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) between normal and tumor groups were identified. The LAMRGs were obtained from literature and GeneCards and MSigDB databases. Lactic acid metabolism-related differentially expressed genes (LAMRDEGs) in HCC were screened from the DEGs and LAMRGs. Functional enrichment analyses of the screened LAMRDEGs were further conducted using Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA). The genes were used in multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to construct a prognostic model. Then, a protein-protein interaction network was constructed using STRING and CTD databases. Furthermore, the CIBERSORTx online database was used to assess the relationship between immune cell infiltration and hub genes.Results: Twenty-eight lactic acid metabolism-related differentially expressed genes (LAMRDEGs) were identified. The GO and KEGG analyses showed that the LAMRDEGs were related to the prognosis of HCC. The GSEA indicated that the LAMRDEGs were significantly enriched in tumor related pathways. In the multivariate Cox regression analysis, 14 key genes (E2F1, SERPINE1, GYS2, SPP1, PCK1, CCNB1, CYP2C9, IGFBP3, KDM8, RCAN1, ALPL, FBP1, NQO1, and LCAT) were found to be independent prognostic factors of HCC. Finally, the LASSO and Cox regression analyses showed that six key genes (SERPINE1, SPP1, CCNB1, CYP2C9, NQO1, and LCAT) were associated with HCC prognosis. Moreover, the correlation analyses revealed that the expression of the six key genes were associated with immune infiltrates of HCC.Conclusion: The LAMRDEGs can predict the prognosis and may be associated with immune cells infiltration in patients with HCC. These genes might be the promising biomarkers for the prognosis and treatment of HCC

Tuberous Sclerosis complex protein 2-independent activation of mTORC1 by human cytomegalovirus pUL38

The mammalian target of rapamycin complex 1 (mTORC1) controls cell growth and anabolic metabolism and is a critical host factor activated by human cytomegalovirus (HCMV) for successful infection. The multifunctional HCMV protein pUL38 previously has been reported to activate mTORC1 by binding to and antagonizing tuberous sclerosis complex protein 2 (TSC2) (J. N. Moorman et al., Cell Host Microbe 3:253–262, 2008, http://dx.doi.org/10.1016/j.chom.2008.03.002). pUL38 also plays a role in blocking endoplasmic reticulum stress-induced cell death during HCMV infection. In this study, we showed that a mutant pUL38 lacking the N-terminal 24 amino acids (pHA-UL38(25–331)) was fully functional in suppressing cell death during infection. Interestingly, pHA-UL38(25–331) lost the ability to interact with TSC2 but retained the ability to activate mTORC1, although to a lesser extent than full-length pHA-UL38. Recombinant virus expressing pHA-UL38(25–331) replicated with ∼10-fold less efficiency than the wild-type virus at a low multiplicity of infection (MOI), but it grew similarly well at a high MOI, suggesting an MOI-dependent importance of pUL38-TSC2 interaction in supporting virus propagation. Site-directed mutational analysis identified a TQ motif at amino acid residues 23 and 24 as critical for pUL38 interaction with TSC2. Importantly, when expressed in isolation, the TQ/AA substitution mutant pHA-UL38 TQ/AA was capable of activating mTORC1 just like pHA-UL38(25–331). We also created TSC2-null U373-MG cell lines by CRISPR genome editing and showed that pUL38 was capable of further increasing mTORC1 activity in TSC2-null cells. Therefore, this study identified the residues important for pUL38-TSC2 interaction and demonstrated that pUL38 can activate mTORC1 in both TSC2-dependent and -independent manners. IMPORTANCE HCMV, like other viruses, depends exclusively on its host cell to propagate. Therefore, it has developed methods to protect against host stress responses and to usurp cellular processes to complete its life cycle. mTORC1 is believed to be important for virus replication, and HCMV maintains high mTORC1 activity despite the stressful cellular environment associated with infection. mTORC1 inhibitors suppressed HCMV replication in vitro and reduced the incidence of HCMV reactivation in transplant recipients. We demonstrated that mTORC1 was activated by HCMV protein pUL38 in both TSC2-dependent and TSC2-independent manners. The pUL38-independent mode of mTORC1 activation also has been reported. These novel findings suggest the evolution of sophisticated approaches whereby HCMV activates mTORC1, indicating its importance in the biology and pathogenesis of HCMV

Strong Photoluminescence Enhancement of MoS2 through Defect Engineering and Oxygen Bonding

We report on a strong photoluminescence (PL) enhancement of monolayer MoS2 through defect engineering and oxygen bonding. Micro- PL and Raman images clearly reveal that the PL enhancement occurs at cracks/defects formed during high temperature vacuum annealing. The PL enhancement at crack/defect sites could be as high as thousands of times after considering the laser spot size. The main reasons of such huge PL enhancement include: (1) the oxygen chemical adsorption induced heavy p doping and the conversion from trion to exciton; (2) the suppression of non-radiative recombination of excitons at defect sites as verified by low temperature PL measurements. First principle calculations reveal a strong binding energy of ~2.395 eV for oxygen molecule adsorbed on an S vacancy of MoS2. The chemical adsorbed oxygen also provides a much more effective charge transfer (0.997 electrons per O2) compared to physical adsorbed oxygen on ideal MoS2 surface. We also demonstrate that the defect engineering and oxygen bonding could be easily realized by oxygen plasma irradiation. X-ray photoelectron spectroscopy further confirms the formation of Mo-O bonding. Our results provide a new route for modulating the optical properties of two dimensional semiconductors. The strong and stable PL from defects sites of MoS2 may have promising applications in optoelectronic devices.Comment: 23 pages, 9 figures, to appear in ACS Nan

Discovery and Timing analysis of new pulsars in globular cluster NGC 5024: new observations from FAST

NGC 5024 (M53) is the most distant globular cluster (GC) with known pulsars. In this study, we report the discovery of a new binary millisecond pulsar PSR J1312+1810E (M53E) and present the new timing solutions for M53B to M53E, based on 22 observations from the Five-hundred-meter Aperture Spherical radio Telescope (FAST).These discoveries and timing work benefit from FAST's high sensitivity. We find that M53C is the only isolated millisecond pulsar known in this distant globular cluster, with a spin period of 12.53 ms and spin period derivative of $5.26 \times 10^{-20} \, \rm s \; s^{-1}$. Our results reveal the orbital periods of 47.7, 5.8, and 2.4 days for M53B, D, and E, respectively. The companions, with a mass of 0.25, 0.27, and 0.18 ${\rm M}_\odot$, respectively, are likely to be white dwarf stars; if they are extended objects, they don't eclipse the pulsars. We find no X-ray counterparts for these millisecond pulsars in archival $Chandra$ images in the band of 0.3-8 keV. The characteristics of this pulsar population are similar to the population of millisecond pulsars in the Galactic disk, as expected from the low stellar density of M53.Comment: 10 pages, 4 figures, accepted for publication in ApJ

Effects of yeast extract supplemented in diet on growth performance, digestibility, intestinal histology, and the antioxidant capacity of the juvenile turbot (Scophthalmus maximus)

An 8-week feeding experiment was conducted on the juvenile turbot (Scophthalmus maximus) to evaluate the influence of yeast extract (YE) supplementation in the diet on growth performance, feed utilization, body composition, nutrient digestibility, intestinal histology, and antioxidant capacity. Four experimental diets were formulated with graded levels of yeast extract 0 (YE0), 1% (YE1), 3% (YE3), and 5% (YE5) and fed to turbots (initial body weight: 4.2 ± 0.1 g) with three replicates per diet and 200 fish in each replicate, respectively. The results showed that turbots fed with diets YE1 and YE3 displayed a significantly higher specific growth rate and protein efficiency rate than those fed with diets YE0 and YE5, while the feed conversion ratios in YE1 and YE3 groups were lower than those in YE0 and YE5. Fish fed with diets YE3 and YE5 showed higher body crude protein contents than those in groups YE0 and YE1. The highest apparent digestibility coefficients for dry matter and crude protein, digestive enzyme activities (trypsin, lipase, and amylase), and the height of the intestinal fold were observed in the YE3 group. YE3 treatment displayed a significantly higher superoxide dismutase (SOD) activity than the YE0 group, while the malondialdehyde (MDA) content in YE1 was significantly lower than those in YE0 and YE5. No significant difference was observed in serum physiological and biochemical parameters among all treatments. Overall, appropriate dietary supplementation of the yeast extract could improve the growth performance, digestibility, and antioxidant capacity of the juvenile turbot, and the recommended yeast extract level in the feed is 2.47%

Induced ferroelectric phases in SrTiO3 by a nanocomposite approach

Inducing new phases in thick films via vertical lattice strain is one of the critical advantages of vertically aligned nanocomposites (VANs). In SrTiO3 (STO), the ground state is ferroelastic, and the ferroelectricity in STO is suppressed by the orthorhombic transition. Here, we explore whether vertical lattice strain in three-dimensional VANs can be used to induce new ferroelectric phases in SrTiO3:MgO (STO:MgO) VAN thin films. The STO:MgO system incorporates ordered, vertically aligned MgO nanopillars into a STO film matrix. Strong lattice coupling between STO and MgO imposes a large lattice strain in the STO film. We have investigated ferroelectricity in the STO phase, existing up to room temperature, using piezoresponse force microscopy, phase field simulation and second harmonic generation. We also serendipitously discovered the formation of metastable TiO nanocores in MgO nanopillars embedded in the STO film matrix. Our results emphasize the design of new phases via vertical epitaxial strain in VAN thin films

Effects of sludge pellet mulch on soil physicochemical properties and soil enzyme activities

The drinking-water treatment sludge (DWTS) possesses intricate characteristics, which restrict its broad applicability. To tackle this issue, we employed DWTS obtained from the Minhang District of Shanghai as the primary constituent, blending it with a low-alkaline curing material to produce pelletized mulch. This investigation primarily focuses on evaluating the environmental safety of sludge pellet mulch (SPM) and scrutinizing alterations in soil physicochemical properties at various mulch thicknesses. The outcomes affirm the durability of SPM and the compliance of eight heavy metals with prescribed standards concerning their concentration, pH, and EC values. After applying SPM, noteworthy enhancements were observed in soil moisture, organic matter content, available nutrients, and the activity of four enzymes. Furthermore, a reduction in soil temperature was observed. For urban landscape mulching, SPM within the range of 9.6–28.8 kg/m2 emerged as the preferred choice, yielding the most favorable overall soil quality improvements

Dielectric relaxation, resonance and scaling behaviors in Sr3Co2Fe24O41 hexaferrite

The dielectric properties of Z-type hexaferrite Sr(3)Co(2)Fe(24)O(41) (SCFO) have been investigated as a function of temperature from 153 to 503 K between 1 and 2 GHz. The dielectric responses of SCFO are found to be frequency dependent and thermally activated. The relaxation-type dielectric behavior is observed to be dominating in the low frequency region and resonance-type dielectric behavior is found to be dominating above 10(8) Hz. This frequency dependence of dielectric behavior is explained by the damped harmonic oscillator model with temperature dependent coefficients. The imaginary part of impedance (Z″) and modulus (M″) spectra show that there is a distribution of relaxation times. The scaling behaviors of Z″ and M″ spectra further suggest that the distribution of relaxation times is temperature independent at low frequencies. The dielectric loss spectra at different temperatures have not shown a scaling behavior above 10(8) Hz. A comparison between the Z″ and the M″ spectra indicates that the short-range charges motion dominates at low temperatures and the long-range charges motion dominates at high temperatures. The above results indicate that the dielectric dispersion mechanism in SCFO is temperature independent at low frequencies and temperature dependent at high frequencies due to the domination of resonance behavior