A Polyrotaxane-based pH-labile Drug Delivery System

A novel polyrotaxane (PR)-based triblock copolymer was exploited as polymeric carrier for doxorubicin (DOX). A sample holding a feed molar ratio of Pluronic F127 to β-CD to poly(ethylene glycol) methyl ether methacrylate (PEGMA) equal to 1:30:20 was synthesized via the in situ atom transfer radical polymerization (ATRP) and then conjugated with DOX using pH sensitive hydrazone linker. The resulting PR-DOX conjugates enabled to self-assemble into nano-particles of about 70 nm in diameter in aqueous solution as evidenced by TEM. The release of DOX was varied from 10 % to 37 % over 72 h at physiological and acidic pH, respectively. The PR-based triblock copolymer without DOX conjugation showed almost non toxicity, while these nano-particles with DOX conjugation presented increased toxicity

Activation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to the immunosuppression of mice infected with Angiostrongylus cantonensis

PCR primers used in this study. (DOC 41 kb

Therapeutic effects of Jiaotai pill on rat insomnia via regulation of GABA signal pathway

Purpose: To investigate the therapeutic effects of Jiaotai pill (JTP) on rats with insomnia induced by pchlorophenylalanine (PCPA).Methods: Rats with PCPA-induced insomnia were divided into 5 groups (n = 10), made up of control group, positive treatment group (estazolam 0.1 mg/kg), and 3 JTP treatment groups (0.6, 1.2 and 2.4 g/kg). Another group of 10 rats were treated as normal group. Rats in normal and control groups were treated with normal saline (10 mL/kg). After 14 days of drug treatment, the rats were injected intraperitoneally with sodium pentobarbital (45 mg/kg) and thereafter, latent period and sleeping time were recorded, while contents of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in hypothalamus were determined by high performance liquid chromatography (HPLC). Furthermore, the expressions of glutamate decarboxylase 65 (GAD-65), glutamate decarboxylase 67 (GAD-67), GABAaminotransferase (GABA)-T, anti-GABA transporter 1 (GAT)-1, anti-GABA transporter (GAT)-3, and GABA receptors (GABA-A and GABA-B) in the hypothalamus were analyzed by western blotting assay.Results: The results showed that JTP (0.6, 1.2 and 2.4 g/kg) significantly shortened latent period and prolonged sleeping time (p < 0.01). JTP also increased GABA level (p < 0.01), but decreased Glu contents of the rat hypothalamus (p < 0.01). Western blotting data indicate that JTP significantly upregulated the levels of GAD-65 (p < 0.01), GAD-67 (p < 0.05), GAT-1 (p < 0.01), GAT-3 (p < 0.01), GABA-A (p < 0.01) and GABA-B (p < 0.01), while the level of GABA-T was down-regulated.Conclusion: The results demonstrate that JTP possesses significant sedative effects on insomnia in rats, most probably through a mechanism involving GABA signal pathway.Keywords: Jiaotai pill, Insomnia, GABA, Glutamate, Estazolam, GABA signal pathwa

Clinical values of multiple Epstein-Barr virus (EBV) serological biomarkers detected by xMAP technology

<p>Abstract</p> <p>Background</p> <p>Serological examination of Epstein-Barr virus (EBV) antibodies has been performed for screening nasopharyngeal carcinoma (NPC) and other EBV-associated diseases.</p> <p>Methods</p> <p>By using xMAP technology, we examined immunoglobulin (Ig) A antibodies against Epstein-Barr virus (EBV) VCA-gp125, p18 and IgA/IgG against EA-D, EBNA1 and gp78 in populations with distinct diseases, or with different genetic or geographic background. Sera from Cantonese NPC patients (n = 547) and healthy controls (n = 542), 90 members of high-risk NPC families and 52 non-endemic healthy individuals were tested. Thirty-five of NPC patients were recruited to observe the kinetics of EBV antibody levels during and after treatment. Patients with other EBV-associated diseases were collected, including 16 with infectious mononucleosis, 28 with nasal NK/T cell lymphoma and 14 with Hodgkin's disease.</p> <p>Results</p> <p>Both the sensitivity and specificity of each marker for NPC diagnosis ranged 61–84%, but if combined, they could reach to 84.5% and 92.4%, respectively. Almost half of NPC patients displayed decreased EBV immunoactivities shortly after therapy and tumor recurrence was accompanied with high EBV antibody reactivates. Neither the unaffected members from high-risk NPC families nor non-endemic healthy population showed statistically different EBV antibody levels compared with endemic controls. Moreover, elevated levels of specific antibodies were observed in other EBV-associated diseases, but all were lower than those in NPC.</p> <p>Conclusion</p> <p>Combined EBV serological biomarkers could improve the diagnostic values for NPC. Diverse EBV serological spectrums presented in populations with different EBV-associated diseases, but NPC patients have the highest EBV activity.</p

High Reversibility of Lattice Oxygen Redox in Na-ion and Li-ion Batteries Quantified by Direct Bulk Probes of both Anionic and Cationic Redox Reactions

The reversibility and cyclability of anionic redox in battery electrodes hold the key to its practical employments. Here, through mapping of resonant inelastic X-ray scattering (mRIXS), we have independently quantified the evolving redox states of both cations and anions in Na2/3Mg1/3Mn2/3O2. The bulk-Mn redox emerges from initial discharge and is quantified by inverse-partial fluorescence yield (iPFY) from Mn-L mRIXS. Bulk and surface Mn activities likely lead to the voltage fade. O-K super-partial fluorescence yield (sPFY) analysis of mRIXS shows 79% lattice oxygen-redox reversibility during initial cycle, with 87% capacity sustained after 100 cycles. In Li1.17Ni0.21Co0.08Mn0.54O2, lattice-oxygen redox is 76% initial-cycle reversible but with only 44% capacity retention after 500 cycles. These results unambiguously show the high reversibility of lattice-oxygen redox in both Li-ion and Na-ion systems. The contrast between Na2/3Mg1/3Mn2/3O2 and Li1.17Ni0.21Co0.08Mn0.54O2 systems suggests the importance of distinguishing lattice-oxygen redox from other oxygen activities for clarifying its intrinsic properties.Comment: 33 pages, 8 Figures. Plus 14 pages of Supplementary Materials with 12 Figure

GABNet: global attention block for retinal OCT disease classification

IntroductionThe retina represents a critical ocular structure. Of the various ophthalmic afflictions, retinal pathologies have garnered considerable scientific interest, owing to their elevated prevalence and propensity to induce blindness. Among clinical evaluation techniques employed in ophthalmology, optical coherence tomography (OCT) is the most commonly utilized, as it permits non-invasive, rapid acquisition of high-resolution, cross-sectional images of the retina. Timely detection and intervention can significantly abate the risk of blindness and effectively mitigate the national incidence rate of visual impairments.MethodsThis study introduces a novel, efficient global attention block (GAB) for feed forward convolutional neural networks (CNNs). The GAB generates an attention map along three dimensions (height, width, and channel) for any intermediate feature map, which it then uses to compute adaptive feature weights by multiplying it with the input feature map. This GAB is a versatile module that can seamlessly integrate with any CNN, significantly improving its classification performance. Based on the GAB, we propose a lightweight classification network model, GABNet, which we develop on a UCSD general retinal OCT dataset comprising 108,312 OCT images from 4686 patients, including choroidal neovascularization (CNV), diabetic macular edema (DME), drusen, and normal cases.ResultsNotably, our approach improves the classification accuracy by 3.7% over the EfficientNetV2B3 network model. We further employ gradient-weighted class activation mapping (Grad-CAM) to highlight regions of interest on retinal OCT images for each class, enabling doctors to easily interpret model predictions and improve their efficiency in evaluating relevant models.DiscussionWith the increasing use and application of OCT technology in the clinical diagnosis of retinal images, our approach offers an additional diagnostic tool to enhance the diagnostic efficiency of clinical OCT retinal images

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

Baichuan 2: Open Large-scale Language Models

Large language models (LLMs) have demonstrated remarkable performance on a variety of natural language tasks based on just a few examples of natural language instructions, reducing the need for extensive feature engineering. However, most powerful LLMs are closed-source or limited in their capability for languages other than English. In this technical report, we present Baichuan 2, a series of large-scale multilingual language models containing 7 billion and 13 billion parameters, trained from scratch, on 2.6 trillion tokens. Baichuan 2 matches or outperforms other open-source models of similar size on public benchmarks like MMLU, CMMLU, GSM8K, and HumanEval. Furthermore, Baichuan 2 excels in vertical domains such as medicine and law. We will release all pre-training model checkpoints to benefit the research community in better understanding the training dynamics of Baichuan 2.Comment: Baichuan 2 technical report. Github: https://github.com/baichuan-inc/Baichuan