Publications by authors named "Shi Leilei"

Emerging infectious diseases (EIDs) pose a significant threat to public health. Effective surveillance and early warning systems that monitor EIDs in a timely manner are crucial for their control. Given that more than half of EIDs are zoonotic, traditional integrated surveillance systems remain inadequate.

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Ghrelin is a class of brain and intestinal peptides. It regulates food intake and body glucose levels and maintains cellular homeostasis. In recent years, research has revealed that ghrelin may positively impact learning and memory.

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Sigma-1 receptor (Sig-1R) agonists has therapeutic effects in neurological disorders and possesses properties that can reverse cognitive dysfunction. This study investigated the therapeutic efficacy of Sig-1R activation on cognitive dysfunction in streptozotocin (STZ) combined with high fat and high sugar diet (HFD)-induced type 2 diabetic rats. By employing morris water maze (MWM) testing and computed tomography (CT) imaging, we observed that activation of Sig-1R effectively mitigated brain atrophy and cognitive impairment in diabetes-induced cognitive impairment (DCI) rats.

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Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and is characterized by spontaneous pain and neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as a target for analgesic development. It is an important receptor with anti-inflammatory properties and has been found to regulate DNP.

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This study aimed to clarify the protective effect of Glycyrrhizic acid (GL) against Diosbulbin B (DB) - induced liver injury in mice and investigate its mechanisms of action. A liver injury DB was established in mice through the oral administration of DB for 15 days. At the same time, GL was administered to the mice for treatment.

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Introduction: Soil nutrient supply drives the ecological functions of soil micro-food webs through bottom-up and top-down mechanisms in degraded agroecosystems. Nutrient limitation responds sensitively to variations in degraded agroecosystems through restoration practices, such as legume intercropping.

Objectives: This study examined the effects of legume intercropping on trophic cascade dynamics through resource supply in degraded purple soil ecosystems.

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Ethnopharmacological Relevance: Dioscorea bulbifera L. (DBL) was a traditional Chinese medicine commonly used to treat goitre and cancer. Nevertheless, its clinical application may lead to liver injury.

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Antifungal drug resistance is a critical concern, demanding innovative therapeutic solutions. The dual-targeting mechanism of action (MoA), as an effective strategy to reduce drug resistance, has been validated in the design of antibacterial agents. However, the structural similarities between mammalian and fungal cells complicate the development of such a strategy for antifungal agents as the selectivity can be compromised.

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  • Terahertz (THz) coherent phonons are being explored as effective low-energy, high-speed information carriers in advanced on-chip devices made of atomically thin materials.
  • This study focused on generating THz coherent phonons in exfoliated van der Waals (vdW) flakes of FeGeTe and FePS, discovering that the vdW flakes on a gold substrate produced significantly stronger THz phonons than those on a silicon substrate.
  • The findings were supported by frequency-domain Raman mapping and numerical simulations, which revealed that the increased surface field on the gold substrate enhances THz coherent phonon generation, suggesting a universal strategy applicable across different vdW materials.
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  • Scientists wanted to find out how Puerarin (PU) can protect the liver from damage caused by a plant called Dioscorea bulbifera (DB).
  • They conducted tests on mice to see how PU affected their liver health and checked for certain enzymes and proteins that show liver damage or inflammation.
  • Results showed that PU helped the mice gain weight, improved their liver condition, and changed the levels of important proteins, making it clear that PU can help fight liver injury caused by DB.
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  • Deep learning has been effectively utilized to enhance hit screening and molecular optimization, particularly for Wee1 inhibitors in this study.
  • Using various deep learning techniques, researchers optimized a specific Wee1 inhibitor, starting from GLX0198 with an initial IC of 157.9 nM, resulting in three significantly improved compounds with ICs of 13.5 nM, 33.7 nM, and 47.1 nM.
  • The best-performing compound demonstrated strong inhibitory effects on multiple cancer cell lines, with IC values below 100 nM, highlighting deep learning's potential in streamlining molecular optimization decisions.
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Several empirical and theoretical studies suggest the presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual gene expression variability. However, for the vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored.

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In the present work, we pioneered a coordinated self-assembly approach aimed at fabricating carrier-free hybrid nanoparticles to address the inherent challenges of the anaerobic microenvironment and the oxidative resistance induced by reductive glutathione (GSH) in photodynamic therapy (PDT). In these nanoparticles, protoporphyrin IX (PP), HIF-1α inhibitor of '-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe present hydrogen bond and coordination interaction. The nanoparticles exhibited efficient cellular uptake by CAL-27 cells, facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect.

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  • Hyperactivated PRMT5 is linked to cancer and its inhibitors could enhance immune responses, but broad inhibition negatively affects immune cells, necessitating targeted strategies for tumor treatments, especially in cancers lacking MMAP.
  • Researchers designed isogenic tumor lines using CRISPR to test the effects of PRMT5 inhibitors GSK3326595 and MRTX1719, focusing on their impact on tumor and T cell behavior.
  • The study found that MRTX1719 effectively inhibits PRMT5 specifically in MTAP-loss tumors, reduces immune resistance, and enhances T cell activity, making it promising when combined with immune checkpoint therapies like anti-PD-1 for cancer treatment.
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The branched architecture of neuronal dendrites is a key factor in how neurons form ordered networks and discoveries continue to be made identifying proteins and protein-protein interactions that direct or execute the branching and extension of dendrites. Our prior work showed that the molecular scaffold Pdlim5 and delta-catenin, in conjunction, are two proteins that help regulate the branching and elongation of dendrites in cultured hippocampal neurons and do so through a phosphorylation-dependent mechanism triggered by upstream glutamate signaling. In this report we have focused on Pdlim5's multiple scaffolding domains and how each contributes to dendrite branching.

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  • A study was conducted to evaluate the effects of palmar ginseng on cognitive impairment caused by type 2 diabetes in a rat model, focusing on its neuroprotective properties and mechanisms.
  • The research involved feeding rats a high-fat, high-sugar diet and administering palmar ginseng, followed by tests to assess changes in cognitive function, inflammation markers, and hippocampal tissue health.
  • Results showed that palmar ginseng lowered blood glucose levels, improved learning and memory, reduced neuronal damage, and influenced certain protein pathways linked to inflammation and neuroprotection.
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Glycine- and arginine-rich (GAR) motifs, commonly found in RNA-binding and -processing proteins, can be symmetrically (SDMA) or asymmetrically (ADMA) dimethylated at the arginine residue by protein arginine methyltransferases. Arginine-methylated protein motifs are usually read by Tudor domain-containing proteins. Here, using a GFP-Trap, we identify a non-Tudor domain protein, squamous cell carcinoma antigen recognized by T cells 3 (SART3), as a reader for SDMA-marked GAR motifs.

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Melasma is an acquired hypermelanotic condition characterized by the presence of irregular light-to-dark brown macules that primarily manifest on the sun-exposed areas of the skin, particularly the face. The management of melasma poses significant challenges, as it is often recalcitrant to treatment and tends to recur despite successful treatment. In this study, we explored a safe, easy, and effective melasma treatment strategy.

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  • Mitochondria are like tiny power plants in our cells that create energy, and they rely on special proteins to do this job.
  • A key enzyme called SUCLG1 helps control these proteins by managing a substance called succinyl-CoA, which affects the way another important protein, POLRMT, works with mitochondrial DNA.
  • In leukemia, certain mutations can boost SUCLG1 levels, improving mitochondrial production and helping cancer cells grow, but reducing SUCLG1 or POLRMT can slow down the disease.
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Persistent inflammation and disrupted immunoregulation are critical factors in impeding diabetic wound healing. While immunoregulatory hydrogel dressings hold significant promise for clinical applications in diabetic wound healing, the current application often demands intricate interventions and high-cost treatments involving cytokines and cell therapies. The development of single component immunoregulatory hydrogels remains a complex challenge.

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Several empirical and theoretical studies suggest presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual variability in gene expression. However, for vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored.

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While significant advances have been made in predicting static protein structures, the inherent dynamics of proteins, modulated by ligands, are crucial for understanding protein function and facilitating drug discovery. Traditional docking methods, frequently used in studying protein-ligand interactions, typically treat proteins as rigid. While molecular dynamics simulations can propose appropriate protein conformations, they're computationally demanding due to rare transitions between biologically relevant equilibrium states.

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Here we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.

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Photosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions.

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Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle.

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