Ginsenoside Rg1 Attenuates Oligomeric Aβ1-42-Induced Mitochondrial Dysfunction

Mitochondrial dysfunction is one of the major pathological changes seen in Alzheimer's disease (AD). Amyloid beta-peptide (Aβ), a neurotoxic peptide, accumulates in the brain of AD subjects and mediates mitochondrial and neuronal stress. Therefore, protecting mitochondrion from Aβ-induced toxicity holds potential benefits for halting and treating and perhaps preventing AD. Here, we report that administration of ginsenoside Rg1, a known neuroprotective drug, to primary cultured cortical neurons, rescues Aβ-mediated mitochondrial dysfunction as shown by increases in mitochondrial membrane potential, ATP levels, activity of cytochrome c oxidase (a key enzyme associated with mitochondrial respiratory function), and decreases in cytochrome c release. The protective effects of Rg1 on mitochondrial dysfunction correlate to neuronal injury in the presence of Aβ. This finding suggests that ginsenoside Rg1 may attenuate Aβ-induced neuronal death through the suppression of intracellular mitochondrial oxidative stress and may rescue neurons in AD

Towards precise classification of cancers based on robust gene functional expression profiles

BACKGROUND: Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level. RESULTS: Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles. CONCLUSION: This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level

A B7-CD28 Family-Based Signature Demonstrates Significantly Different Prognosis and Immunological Characteristics in Diffuse Gliomas

The B7-CD28 gene family plays a crucial role in modulating immune functions and has served as potential targets for immunotherapeutic strategies. Therefore, we systematically analyzed B7-CD28 family gene expression profiles and constructed a B7-CD28 family-based prognostic signature to predict survival and immune host status in diffuse gliomas. The TCGA dataset was used as a training cohort, and three CGGA datasets (mRNAseq_325, mRNAseq_693 and mRNA-array) were employed as validation cohorts to intensify the findings that we have revealed in TCGA dataset. Ultimately, we developed a B7-CD28 family-based signature that consisted of CD276, CD274, PDCD1LG2 and CD80 using LASSO Cox analysis. This gene signature was validated to have significant prognostic value, and could be used as a biomarker to distinguish pathological grade and IDH mutation status in diffuse glioma. Additionally, we found that the gene signature was significantly related to intensity of immune response and immune cell population, as well as several other important immune checkpoint genes, holding a great potential to be a predictive immune marker for immunotherapy and tumor microenvironment. Finally, a B7-CD28 family-based nomogram was established to predict patient life expectancy contributing to facilitate personalizing therapy for tumor sufferers. In summary, this is the first mathematical model based on this gene family with the aim of providing novel insights into immunotherapy for diffuse glioma

An Hα\alpha Imaging Survey of the Low-surface-brightness Galaxies Selected from the Fall Sky Region of the 40%\% ALFALFA \ion{H}{1} Survey

We present the observed H$\alpha$ flux and derived star formation rates (SFRs) for a fall sample of low$-$surface$-$brightness galaxies (LSBGs). The sample is selected from the fall sky region of the 40$\%$ ALFALFA {\ion{H}{1}} survey $-$ SDSS DR7 photometric data, and all the $H\alpha$ images were obtained using the 2.16 m telescope, operated by the National Astronomy Observatories, Chinese Academy of Sciences. A total of 111 LSBGs were observed and $H\alpha$ flux was measured in 92 of them. Though almost all the LSBGs in our sample are {\ion{H}{1}}$-$rich, their SFRs derived from the extinction and filter$-$transmission$-$corrected $H\alpha$ flux, are less than 1M_{\sun}$yr^{-1}$. LSBGs and star forming galaxies have similar {\ion{H}{1}} surface densities, but LSBGs have much lower SFRs and SFR surface densities than star$-$forming galaxies. Our results show that LSBGs deviate from the Kennicutt-Schmidt law significantly, which indicate that they have low star formation efficiency. The SFRs of LSBGs are close to average SFRs in Hubble time and support the previous arguments that most of the LSBGs are stable systems and they tend to seldom contain strong interactions or major mergers during their star formation histories

An Hα\alpha Imaging Survey of the Low-surface-brightness Galaxies Selected from the Fall Sky Region of the 40%\% ALFALFA \ion{H}{1} Survey

We present the observed H$\alpha$ flux and derived star formation rates (SFRs) for a fall sample of low$-$surface$-$brightness galaxies (LSBGs). The sample is selected from the fall sky region of the 40$\%$ ALFALFA {\ion{H}{1}} survey $-$ SDSS DR7 photometric data, and all the $H\alpha$ images were obtained using the 2.16 m telescope, operated by the National Astronomy Observatories, Chinese Academy of Sciences. A total of 111 LSBGs were observed and $H\alpha$ flux was measured in 92 of them. Though almost all the LSBGs in our sample are {\ion{H}{1}}$-$rich, their SFRs derived from the extinction and filter$-$transmission$-$corrected $H\alpha$ flux, are less than 1M_{\sun}$yr^{-1}$. LSBGs and star forming galaxies have similar {\ion{H}{1}} surface densities, but LSBGs have much lower SFRs and SFR surface densities than star$-$forming galaxies. Our results show that LSBGs deviate from the Kennicutt-Schmidt law significantly, which indicate that they have low star formation efficiency. The SFRs of LSBGs are close to average SFRs in Hubble time and support the previous arguments that most of the LSBGs are stable systems and they tend to seldom contain strong interactions or major mergers during their star formation histories

SkyMath: Technical Report

Large language models (LLMs) have shown great potential to solve varieties of natural language processing (NLP) tasks, including mathematical reasoning. In this work, we present SkyMath, a large language model for mathematics with 13 billion parameters. By applying self-compare fine-tuning, we have enhanced mathematical reasoning abilities of Skywork-13B-Base remarkably. On GSM8K, SkyMath outperforms all known open-source models of similar size and has established a new SOTA performance

CD8(+) T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPR(dn) , hIAPP and PNPLA3(I148M) . Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8(+) T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs' liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.Peer reviewe

The atomic gas of star-forming galaxies at z∼\sim0.05 as revealed by the Five-hundred-meter Aperture Spherical Radio Telescope

We report new HI observations of four z$\sim$0.05 star-forming galaxies undertaken during the commissioning phase of the Five-hundred-meter Aperture Spherical Radio Telescope (FAST). FAST is the largest single-dish telescope with a 500 meter aperture and a 19-Beam receiver. Exploiting the unprecedented sensitivity provided by FAST, we aim to study the atomic gas, via the HI 21cm emission line, in low-$z$ star-forming galaxies taken from the Valpara\'iso ALMA/APEX Line Emission Survey (VALES) project. Together with previous ALMA CO($J=1-0$) observations, the HI data provides crucial information to measure the gas mass and dynamics. As a pilot HI survey, we targeted four local star-forming galaxies at $z\sim0.05$. In particular, one of them has already been detected in HI by the Arecibo Legacy Fast ALFA survey (ALFALFA), allowing a careful comparison. We use an ON-OFF observing approach that allowed us to reach an rms of 0.7mJy/beam at a 1.7km/s velocity resolution within only 20 minutes ON-target integration time. We demonstrate the great capabilities of the FAST 19-beam receiver for pushing the detectability of the HI emission line of extra-galactic sources. The HI emission line detected by FAST shows good consistency with the previous ALFALFA results. Our observations are put in context with previous multi-wavelength data to reveal the physical properties of these low-$z$ galaxies. We find that the CO($J=1-0$) and HI emission line profiles are similar. The dynamical mass estimated from the HI data is an order of magnitude higher than the baryon mass and the dynamical mass derived from the CO observations, implying that the mass probed by dynamics of HI is dominated by the dark matter halo. In one case, a target shows an excess of CO($J=1-0$) in the line centre, which can be explained by an enhanced CO($J=1-0$) emission induced by a nuclear starburst showing high velocity dispersion.Comment: 5 pages, 3 figures, 2 appendix, A&A Letter accepte

ALMA [N \i\i ] 205 \mu m Imaging Spectroscopy of the Lensed Submillimeter galaxy ID 141 at redshift 4.24

We present the Atacama Large Millimeter/submillimeter Array (ALMA) observation of the Sub-millimeter galaxy (SMG) ID 141 at z=4.24 in the [N II] 205 $\mu$m line (hereafter [N II]) and the underlying continuum at (rest-frame) 197.6 $\mu$m. Benefiting from lensing magnification by a galaxy pair at z=0.595, ID 141 is one of the brightest z$>4$ SMGs. At the angular resolutions of $\sim1.2''$ to $1.5''$ ($1'' \sim6.9$ kpc), our observation clearly separates, and moderately resolves the two lensed images in both continuum and line emission at $\rm S/N>5$ . Our continuum-based lensing model implies an averaged amplification factor of $\sim5.8$ and reveals that the de-lensed continuum image has the S\'ersic index $\simeq 0.95$ and the S\'ersic radius of $\sim0.18'' (\sim 1.24$ kpc). Furthermore, the reconstructed [N II] velocity field in the source plane is dominated by a rotation component with a maximum velocity of $\sim 300$ km/s at large radii, indicating a dark matter halo mass of $\sim 10^{12}M_{\odot}$. This, together with the reconstructed velocity dispersion field being smooth and modest in value ($<100$ km/s) over much of the outer parts of the galaxy, favours the interpretation of ID 141 being a disk galaxy dynamically supported by rotation. The observed [N II]/CO (7-6) and [N II]/[C II] 158 $\mu$m line luminosity ratios, which are consistent with the corresponding line ratio vs. far-infrared color correlation from local luminous infrared galaxies, imply a de-lensed star formation rate of ($1.8\pm 0.6)\times10^3M_\odot$/yr and provide an independent estimate on the size of the star-forming region $0.7^{+0.3}_{-0.3}$ kpc in radius.Comment: 13 pages, 6 figures, 2 tables, accepted by ApJ, lensing model code can be found here https://gitlab.com/cxylzlx/tiny_len