A novel amino-pyrimidine inhibitor suppresses tumor growth via microtubule destabilization and Bmi-1 down-regulation.

Colorectal cancer (CRC), one of the diseases posing a threat to global health, according to the latest data, is the third most common cancer globally and the second leading cause of cancer-related deaths. The development and refinement of novel structures of small molecular compounds play a crucial role in tumor treatment and overcoming drug resistance. In this study, our objective was to screen and characterize novel compounds for overcoming drug resistance via the B Lymphoma Mo-MLV insertion region 1 (Bmi-1) reporter screen assay.

Screening and Preparation of Nanobodies for SIGLEC-15 Detection.

As an important member of the Siglec family, SIGLEC-15 plays an important role in osteoclast differentiation, bone remodeling, and tumor immune evasion. In the tumor microenvironment, SIGLEC-15 functions independently of the B7-H1/PD-1 pathway. In this study, the SIGLEC-15 fusion protein (SIGLEC-15-Fc) was successfully expressed and purified using a eukaryotic expression system.

Single-organelle visualization tracking natural glycosaminoglycans within mitochondria-lysosome crosstalk for inflammatory homeostasis.

Glycosaminoglycans (GAGs), as natural products with diverse biological activities, play a significant role in regulating inflammatory homeostasis. Nevertheless, the mechanism underlying their intracellular anti-inflammatory properties remains unclear. Herein, we propose a single-organelle visualization tracking framework, leveraging an advanced fluorescent imaging technology combined with labeling methods to dynamically trace the subcellular regulatory mechanisms of GAGs in eliminating inflammatory markers, such as reactive oxygen species (ROS).

Prospects and applications of efficient physical field processing technologies for polysaccharide extraction and quality improvement in edible mushrooms: A systematic review.

Edible mushroom-derived polysaccharides (EMPs) have been widely used in foods, medicine, and cosmetics due to theirs' diverse and versatile biological activities. Currently, many conventional extraction methods for extracting EMPs are struggling to meet the growing demand, and the produced EMPs with poor quality and low bioactivity. Novel physical field (e.

Polysaccharide from steamed Polygonatum sibiricum ameliorates ulcerative colitis by protecting the intestinal mucosal barrier and regulating gut microbiota.

Steamed Polygonatum sibiricum is widely applied in clinical practice for its tonic effect on gastrointestinal tract. A novel polysaccharide named PSSP-EF was extracted from the steamed roots of Polygonatum sibiricum using hot water extraction, ethanol precipitation, and chromatographic purification. PSSP-EF, with a molecular weight of 2.

Development and testing the psychometric properties of 20 bolt-on items for the EQ-5D-5L across 31 rare diseases.

Objective: Our objective was to develop and assess the psychometric properties of relevant bolt-on items for the EQ-5D-5L in patients with rare diseases (RDs).

Methods: Nineteen new EQ-5D-5L bolt-ons were developed based on literature review, expert input and qualitative interviews and focus groups with patients, caregivers and representatives of patient associations. A nationwide, cross-sectional, web-based survey in China included patients or caregivers of patients with 31 RDs in China (n=9,190).

Lobopaucinoids A-Q, bioactive terpenoids from the soft coral Lobophytum pauciflorum collected in the South China Sea.

Two undescribed rearranged diterpenoids, lobopaucinoids A and B (1 and 2), along with thirteen undescribed lobane-type diterpenoids lobopaucinoids C-O (3-15) including a C (11) and two C (12 and 13) undescribed norditerpenoids, were isolated from the soft coral Lobophytum pauciflorum Ehrenberg (Sarcophytidae family) collected from Xisha Islands of the South China Sea. Additionally, two undescribed prenyleudesmane-type diterpenoids, lobopaucinoids P and Q (16 and 17), as well as two known lobane diterpenoids (18 and 19), were also obtained. Their structures were elucidated based on comprehensive spectroscopic data, Mosher's method, Mo(OAc) or Rh(OCOCF)-induced circular dichroism experiment, quantum chemical calculations, and single-crystal X-ray diffraction and literature comparison.

Phase-separated condensates in autophagosome formation and autophagy regulation.

Biomacromolecules partition into numerous types of biological condensates or membrane-less organelles via liquid-liquid phase separation (LLPS). Newly formed liquid-like condensates may further undergo phase transition to convert into other material states, such as gel or solid states. Different biological condensates possess distinct material properties to fulfil their physiological functions in diverse cellular pathways and processes.

Iontophoresis-driven transdermal drug delivery system based on porous microneedles for hyperuricemia treatment.

An iontophoresis-driven porous microneedles (IPMNs) system has been developed for hyperuricemia management, which can be effectively prolong the anti-hyperuricemia effect. Porous microneedles (PMNs) with good biocompatibility, high porous volume, and excellent substance exchange capacity were firstly prepared for drug transdermal delivery and active iontophoresis.In vitro experiments showed that the transdermal delivery efficiency of anti-hyperuricemia drug (Allopurinol, AP) could be controlled using the iontophoresis current of IPMNs system.

SLC26A9 promotes the initiation and progression of breast cancer by activating the PI3K/AKT signaling pathway.

SLC26A9 is a member of the Slc26a family of multifunctional anion transporters that function as Cl channels in the stomach. We reported for the first time that SLC26A9 is involved in gastric tumorigenesis. However, the role of SLC26A9 in breast cancer has not yet been investigated.

Development of Chimeric Nanobody-Granzyme B Functionalized Ferritin Nanoparticles for Precise Tumor Therapy.

T-cell lymphomas (TCLs) are heterogeneous malignancies with limited treatment options and poor outcomes. The efficacy of traditional T-cell therapies, including chimeric antigen receptor (CAR) T cells, is often constrained by immunosuppressive factors and the tumor microenvironment. On the other hand, although direct Granzyme B (GrB) administration can effectively induce tumor cell apoptosis, it lacks universal tumor targeting and efficient cellular entry mechanisms.

Tongxinluo capsules for secondary prevention after ST-segment elevation myocardial infarction: A systematic review and meta-analysis.

Ethnopharmacological Relevance: Tongxinluo (TXL), a Chinese patent medicine, is commonly used for secondary prevention of cardiovascular events.

Aim Of The Study: To evaluate the efficacy and safety of TXL for secondary prevention after ST-segment elevation myocardial infarction (STEMI).

Materials And Methods: A search for relevant randomized controlled trials (RCTs) was conducted across seven electronic databases from inception to May 10, 2024.

Ginkgo Diterpene Lactone Meglumine for Functional Recovery in Patients with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Ethnopharmacological Relevance: The clinical efficacy of ginkgo diterpene lactone meglumine (GDLM), a Chinese patent medicine, in acute ischemic stroke (AIS) has garnered attention. However, the impact of GDLM on functional recovery in AIS patients has not been systematically reviewed or meta-analyzed.

Aim Of The Study: To evaluate the functional outcomes of GDLM in AIS patients.

Bioactive hydrogel formulations for regeneration of pathological bone defects.

Bone defects caused by osteoporosis, infection, diabetes, post-tumor resection, and nonunion often cause severe pain and markedly increase morbidity and mortality, which remains a significant challenge for orthopedic surgeons. The precise local treatments to these pathological complications is essential to avoid poor or failed bone repair. Hydrogel formulations serve as injectable innovative platforms that overcome microenvironmental obstacles and as delivery systems for controlled release of various bioactive substances to bone defects in a targeted manner.

Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals.

Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature. In this study, we targeted these defects at their source-embryos from same-sex parents-aiming to establish a stable, maintainable imprinting pattern de novo in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate.

Assessing the impact of non-pharmaceutical interventions against COVID-19 on 64 notifiable infectious diseases in Australia: A Bayesian Structural Time Series model.

Background: Several studies have examined the effect of non-pharmaceutical interventions (NPIs) on COVID-19 and other infectious diseases in Australia and globally. However, to our knowledge none have sufficiently explored their impact on other infectious diseases with robust time series model. In this study, we aimed to use Bayesian Structural Time Series model (BSTS) to systematically assess the impact of NPIs on 64 National Notifiable Infectious Diseases (NNIDs) by conducting a comprehensive and comparative analysis across eight disease categories within each Australian state and territory, as well as nationally.

Research note: Detection of IGF2BP2 gene polymorphism associated with growth and reproduction traits of pigeon.

The Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) gene is closely associated with the diseases, fat deposition, and growth and reproduction traits in animals. Investigations into the relationship between the IGF2BP2 gene polymorphism and growth and reproduction traits provide valuable breeding information for enhancing productivity and economic gains in pigeon. In this study, the single nucleotide polymorphisms (SNPs) in 13 exons and the 3' untranslated region (3'UTR) of the IGF2BP2 gene in 292 female pigeons Tianxiang 1 strain were detected through Sanger sequencing, and their association with pigeons' growth and reproduction traits were explored.

Antheraea pernyi silk nanofibrils with inherent RGD motifs accelerate diabetic wound healing: A novel drug-free strategy to promote hemostasis, regulate immunity and improve re-epithelization.

The chronic inflammation and matrix metalloprotease (MMP)-induced tissue degradation significantly disrupt re-epithelization and delay the healing process of diabetic wounds. To address these issues, we produced nanofibrils from Antheraea pernyi (Ap) silk fibers via a facile and green treatment of swelling and shearing. The integrin receptors on the cytomembrane could specifically bind to the Ap nanofibrils (ApNFs) due to their inherent Arg-Gly-Asp (RGD) motifs, which activated platelets to accelerate coagulation and promoted fibroblast migration, adhesion and spreading.

A mitochondria-targeted nanozyme with enhanced antioxidant activity to prevent acute liver injury by remodeling mitochondria respiratory chain.

Developing nanomedicines with enhanced activity to scavenge reactive oxygen species (ROS) has emerged as a promising strategy for addressing ROS-associated diseases, such as drug-induced liver injury. However, designing nanozymes that not only remove ROS but also accelerate the repair of damaged liver cells remains challenging. Here, a two-pronged black phosphorus/Ceria nanozyme with mitochondria-targeting ability (TBP@CeO) is designed.

Synthesis and biological evaluation of new dual APN/NEP inhibitors as potent analgesics.

An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.

Ligand guided in vivo crosslinking and affinity purification mass spectrometry for identifying membrane receptors of Tau.

Misfolded neurotoxic proteins, such as Tau protein, spread within the brain in many neurodegenerative diseases. Receptors play an important role in the recognition of spreading proteins for endocytosis. Blocking the receptors is essential to inhibit neurotoxic proteins spreading in the brain.

Targeting membrane integrity and imidazoleglycerol-phosphate dehydratase: Sanguinarine multifaceted approach against Staphylococcus aureus biofilms.

Background: Staphylococcus aureus is an opportunistic pathogen capable of readily forming biofilms, which can result in life-threatening infections involving different organs. Sanguinarine are benzo[c]phenanthridine alkaloids extracted from the Sanguinaria canadensis L. (Papaveraceae), which have a wide range of biological activities.

Baicalein-loaded porous silk fibroin microspheres modulate the senescence of nucleus pulposus cells through the NF-κB signaling pathway.

Intervertebral disc degeneration (IVDD), an age-associated degenerative condition, significantly contributes to low back pain, thereby adversely affecting individual health and quality of life, while also imposing a substantial societal burden. Baicalein, a natural flavonoid derived from Scutellaria baicalensis Georgi, demonstrates a range of pharmacological activities, including antioxidant, anti-inflammatory, anti-tumor, and antibacterial properties. This positions it as a promising candidate for the treatment of IVDD through intradiscal drug delivery.

Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer's disease spectrum.

Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment.

Evaluating the Evolution of ChatGPT as an Information Resource in Shoulder and Elbow Surgery.

Background: The purpose of this study was to evaluate the performance and evolution of Chat Generative Pre-Trained Transformer (ChatGPT; OpenAI) as a resource for shoulder and elbow surgery information by assessing its accuracy on the American Academy of Orthopaedic Surgeons shoulder-elbow self-assessment questions. We hypothesized that both ChatGPT models would demonstrate proficiency and that there would be significant improvement with progressive iterations.

Materials And Methods: A total of 200 questions were selected from the 2019 and 2021 American Academy of Orthopaedic Surgeons shoulder-elbow self-assessment questions.