Glycine-Histidine-Lysine (GHK) Alleviates Neuronal Apoptosis Due to Intracerebral Hemorrhage via the miR-339-5p/VEGFA Pathway

Glycine-histidine-lysine (GHK) is a human tripeptide that enhances wound healing, exerts neuroprotective effects against neurodegenerative disease, and improves tissue regeneration. This study examined whether GHK can alleviate injury due to intracerebral hemorrhage (ICH). Briefly, adult Wistar rats in GHK pretreatment groups were injected with GHK (1 or 10 mg/kg, i.p.) every 24 h for 3 days. Water content and intact neurons were detected in the rats 3 days after ICH, and the neurological deficit scores were examined in the rats at 4, 24, 72, and 168 h after ICH. Apoptosis was evaluated via caspase-3 immunohistochemistry, Nissl staining, and TUNEL assay. We also examined the effect of GHK on the expression of related proteins in SH-SY5Y cells via Western blotting. The expression of miR-339-5p was examined via real-time polymerase chain reaction analyses. GHK improved neurological deficits, reduced water content in the brain and inhibited neuronal apoptosis in ICH rats. It also prevented the apoptosis of SH-SY5Y cells with hemin treatment. Furthermore, GHK downregulated miR-339-5p expression, and overexpression of miR-339-5p partially reversed the anti-apoptotic effects of GHK in SH-SY5Y cells. Our findings suggest that the p38 MAPK pathway is involved in the GHK-induced downregulation of miR-339-5p, and that the miR-339-5p/VEGFA axis plays a role in preventing neuronal apoptosis following ICH injury. These findings indicate that GHK may represent a novel therapeutic strategy for ICH

LLaVAR: Enhanced Visual Instruction Tuning for Text-Rich Image Understanding

Instruction tuning unlocks the superior capability of Large Language Models (LLM) to interact with humans. Furthermore, recent instruction-following datasets include images as visual inputs, collecting responses for image-based instructions. However, visual instruction-tuned models cannot comprehend textual details within images well. This work enhances the current visual instruction tuning pipeline with text-rich images (e.g., movie posters, book covers, etc.). Specifically, we first use publicly available OCR tools to collect results on 422K text-rich images from the LAION dataset. Moreover, we prompt text-only GPT-4 with recognized texts and image captions to generate 16K conversations, each containing question-answer pairs for text-rich images. By combining our collected data with previous multi-modal instruction-following data, our model, LLaVAR, substantially improves the LLaVA model's capability on text-based VQA datasets (up to 20% accuracy improvement) while achieving an accuracy of 91.42% on ScienceQA. The GPT-4-based instruction-following evaluation also demonstrates the improvement of our model on both natural images and text-rich images. Through qualitative analysis, LLaVAR shows promising interaction (e.g., reasoning, writing, and elaboration) skills with humans based on the latest real-world online content that combines text and images. We make our code/data/models publicly available at https://llavar.github.io/.Comment: Preprint. Work in progres

Exploring the Applicability of Building Energy Performance Certification Systems in Underground Stations in China

To improve the energy efficiency of underground metro stations, and in view of the absence of a comprehensive energy performance evaluation system for underground stations, this study introduced building Energy Performance Certification (EPC) tools into underground stations and conducted a comparative analysis of their applicability. The findings indicated that due to the unique characteristics of underground stations, China’s current EPC system was inapplicable to them. Specifically, (1) for basic items, although evaluation methods were available, due to the limited energy use data for the statistical method, the self-reference method was preferred, but its calculation encountered issues with missing reference values; (2) for prescribed items, the emphasis should be placed on the energy efficiency requirements of energy use systems rather than those of the thermal performance of envelopes; (3) for alternative items, the energy recovery measures related to the heat dissipation of trains and the piston wind should be addressed. Furthermore, a case study was conducted for verification of the proposed energy evaluation method, and the EPC system was updated based on the results of the comparison. The authors hope that this study will help improve China’s energy evaluation methods for underground stations and serve as a reference for expanding the EPC system to include public transportation buildings

Probing the CP Structure of the Top Quark Yukawa at the Future Muon Collider

We study the top-Higgs coupling with a CP violating phase $\xi$ at a future multi-TeV muon collider. We focus on processes that are directly sensitive to the top quark Yukawa coupling: $t\bar{t}h$, $tbh\mu\nu$, and $t\bar{t}h\nu\bar{\nu}$ with $h\rightarrow b\bar{b}$ and semileptonic top decays. At different energies, different processes dominate the cross section, providing complementary information. At and above an energy of $\mathcal{O}(10)$ TeV, vector boson fusion processes dominate. As we show, in the Standard Model there is destructive interference in the vector boson fusion processes $t\bar{t}h\nu\bar{\nu}$ and $tbh\mu\nu$ between the top quark Yukawa and Higgs-gauge boson couplings. A CP violating phase changes this interference, and the cross section measurement is very sensitive to the size of the CP violating angle. Although we find that the cross sections are measured to $\mathcal{O}(50\%)$ statistical uncertainty at $1\sigma$, a 10 and 30 TeV muon collider can bound the CP violating angle $|\xi|\lesssim9.0^\circ$ and $|\xi|\lesssim5.4^\circ$, respectively. However, cross section measurements are insensitive to the sign of the CP violating angle. To determine that the coupling is truly CP violating, observables sensitive to CP violation must be measured. We find in the $t\bar{t}h$ process the azimuthal angle between the $t+\bar{t}$ plane and the initial state muon+Higgs plane shows good discrimination for $\xi=\pm0.1\pi$. For the $tbh\mu\nu$ and $t\bar{t}h\nu\bar{\nu}$ processes, the operator proportional to $\left(\vec{p}_\mu\times\vec{p}_h\right)\cdot \vec{p}_t$ is sensitive to the sign of CP phase $\xi$. From these observables, we construct asymmetry parameters that show good distinction between different values and signs of the CP violating angle.Comment: 32 pages, 11 figure

PK-PD integration of enrofloxacin and cefquinome alone and in combination against Klebsiella pneumoniae using an in vitro dynamic model

Introduction:Klebsiella pneumoniae is classified as a critical pathogen in both animals and humans and infections can be fatal in chickens resulting in substantial economic losses. However, the misuse of antibiotics can also lead to drug resistance and a potential transmission chain between animals and humans. Three K. pneumoniae strains with different susceptibility phenotypes were chosen to study the pharmacokinetic/pharmacodynamic (PK/PD) integration of enrofloxacin (ENR) and cefquinome (CEQ) alone and in combination.Results: Checkerboard assay results indicated that the combination treatment for type strain ATCC 700603 was synergistic effect with a fractional inhibitory concentration index (FICI) of ≤0.5. The other two clinical strains demonstrated an additive effect (FICI >0.5 to ≤1). Furthermore, static time-kill curves indicated that enrofloxacin and cefquinome added singly were effective in killing K. pneumoniae at concentrations of >2 MIC and ≥1 MIC, respectively. Additionally, the combination of enrofloxacin and cefquinome led to an enhanced antibacterial activity of cefquinome. The dynamic time-kill curves indicated that enrofloxacin and cefquinome had bactericidal and bacteriostatic activities, respectively at ≥1.5 mg/L (single-dose) and 4 mg/L (8 h split-dose) causing a decrease in bacterial counts of ≥4.45 and >2 log10 CFU/mL. Enrofloxacin possessed no bacteriostatic effects against K. pneumoniae at a constant concentration of 1× MIC. Cefquinome used in combination with 1× MIC enrofloxacin exhibited bactericidal activity at ≥4 mg/L (12 h split-dose) with reductions of ≥3.65 log10 CFU/mL. The PK/PD parameters were also analyzed to determine the concentration and duration of the drugs needed to reduce bacteria by 3 log10 CFU/mL. For enrofloxacin alone, the AUC24h/MIC was 23.29 h and the Cmax/MIC was 3.18. For cefquinome alone, the %T > MIC was 48.66 and when used in combination with enrofloxacin was 18.04. The combined use of cefquinome and enrofloxacin can increase the antibacterial activity of cefquinome against K. pneumoniae under a 12-h split-dose regimen regardless of individual drug susceptibility.Discussion: The static and dynamic time-kill curves indicated that enrofloxacin exhibited concentration-dependent activity, while cefquinome exhibited time-dependent activity. In the in vitro dynamic model, enrofloxacin alone exhibited better antimicrobial effects against K. pneumoniae compared to cefquinome alone. However, the antibacterial effect of cefquinome can be enhanced by combining it with enrofloxacin. These findings suggest a potentially effective approach for combating K. pneumoniae infections

Integrated WiFi/PDR/Smartphone using an unscented Kalman filter algorithm for 3D indoor localization

Because of the high calculation cost and poor performance of a traditional planar map when dealing with complicated indoor geographic information, a WiFi fingerprint indoor positioning system cannot be widely employed on a smartphone platform. By making full use of the hardware sensors embedded in the smartphone, this study proposes an integrated approach to a three-dimensional (3D) indoor positioning system. First, an improved K-means clustering method is adopted to reduce the fingerprint database retrieval time and enhance positioning efficiency. Next, with the mobile phone’s acceleration sensor, a new step counting method based on auto-correlation analysis is proposed to achieve cell phone inertial navigation positioning. Furthermore, the integration of WiFi positioning with Pedestrian Dead Reckoning (PDR) obtains higher positional accuracy with the help of the Unscented Kalman Filter algorithm. Finally, a hybrid 3D positioning system based on Unity 3D, which can carry out real-time positioning for targets in 3D scenes, is designed for the fluent operation of mobile terminals

The protective mechanism of Dehydromiltirone in diabetic kidney disease is revealed through network pharmacology and experimental validation

Background:Salvia miltiorrhiza (SM) is an effective traditional Chinese medicine for treating DKD, but the exact mechanism is elusive. In this study, we aimed to investigate and confirm the method underlying the action of the active components of SM in the treatment of DKD.Methods: Renal tissue transcriptomics and network pharmacology of DKD patients was performed to identify the active components of SM and the disease targets of DKD. Next, the point of convergence among these three groups was studied. Potential candidate genes were identified and analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The component-target networks were modelled and visualized with Cytoscape. In addition, docking studies were performed to validate our potential target predictions. Lastly, in vitro and in vivo experiments were performed to understand the role of Dehydromiltirone (DHT), the active component of SM, in the phenotypic switching of mesangial cells.Results: Transcriptomics of DKD patients’ renal tissues screened 4,864 differentially expressed genes. Eighty-nine active components of SM and 161 common targets were found. Functional enrichment analysis indicated that 161 genes were enriched in apoptosis, the PI3K-AKT signaling pathway, and the AGE-RAGE signaling pathway in diabetes complications. Molecular docking and molecular dynamic simulations show that DHT can bind to functional PIK3CA pockets, thereby becoming a possible inhibitor of PIK3CA. In vitro study demonstrated that DHT reduced the expression of phenotypic switching markers α-SMA, Col-I, and FN in HMCs by downregulating the over-activation of the PI3K-AKT signaling pathway through the inhibition of PIK3CA. Furthermore, the DKD mouse model confirmed that DHT could reduce proteinuria and improve glomerular hypertrophy in vivo.Conclusion: DHT was identified as the key active component of SM, and its therapeutic effect on DKD was achieved by inhibiting the phenotypic switching of mesangial cells via the PIK3CA signaling pathway

GJ 1252b: A Hot Terrestrial Super-Earth With No Atmosphere

The increasing numbers of rocky, terrestrial exoplanets known to orbit nearby stars (especially M dwarfs) has drawn increased attention to the possibility of studying these planets' surface properties, and atmospheric compositions & escape histories. Here we report the detection of the secondary eclipse of the terrestrial exoplanet GJ1252b using the Spitzer Space Telescope's IRAC2 4.5 micron channel. We measure an eclipse depth of 149(+25/-32) ppm, corresponding to a day-side brightness temperature of 1410(+91/-125) K and consistent with the prediction for no atmosphere. Comparing our measurement to atmospheric models indicates that GJ1252b has a surface pressure of <10 bar, substantially less than Venus. Assuming energy-limited escape, even a 100 bar atmosphere would be lost in <1 Myr, far shorter than estimated age of 3.9+/-0.4 Gyr. The expected mass loss could be overcome by mantle outgassing, but only if the mantle's carbon content were >7% by mass - over two orders of magnitude greater than that found in Earth. We therefore conclude that GJ1252b has no significant atmosphere. Model spectra with granitoid or feldspathic surface composition, but with no atmosphere, are disfavored at >2 sigma. The eclipse occurs just +1.4(+2.8/-1.0) min after orbital phase 0.5, indicating e cos omega=+0.0025(+0.0049/-0.0018), consistent with a circular orbit. Tidal heating is therefore likely to be negligible to GJ1252b's global energy budget. Finally, we also analyze additional, unpublished TESS transit photometry of GJ1252b which improves the precision of the transit ephemeris by a factor of ten, provides a more precise planetary radius of 1.180+/-0.078 R_E, and rules out any transit timing variations with amplitudes <1 min.Comment: ApJL in press. 16 pages, 12 figures, 10 eclipses, 1 bandpass. Models will be available at journal websit