Ether bond-modified lipid nanoparticles for enhancing the treatment effect of hepatic fibrosis.

Lipid nanoparticle (LNP)-mediated RNA delivery holds significant potential for the treatment of various liver diseases. Ionizable lipids play a crucial role in the formulation of LNPs and directly influence their delivery efficiency. In this study, we introduced an innovative concept by incorporating an ether bond into the hydrophobic tail of ionizable lipids for the first time.

Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer.

The efficacy of cancer immunotherapy relies on a sufficient amount of functional immune cells. Triple-negative breast cancer lacks enough immune cell infiltration, and adjuvant therapy is necessary to prime anti-tumor immunity. However, the improvement in efficacy is unsatisfactory with concern about inducing systemic immunotoxicity.

Dual ferroptosis induction in N2-TANs and TNBC cells via FTH1 targeting: A therapeutic strategy for triple-negative breast cancer.

Tumor-associated neutrophils (TANs) play a critical role in the progression and prognosis of triple-negative breast cancer (TNBC), with N2-type TANs known for their pro-tumor characteristics. This study introduces CT-1, a derivative of cryptotanshinone that effectively suppresses TNBC growth while selectively reducing the proportion of N2-type TANs within tumor tissue. Notably, CT-1 induces simultaneous ferroptosis in both N2-type TANs and TNBC cells, a dual mechanism that enhances its therapeutic efficacy.

Bupivacaine multivesicular liposomes/meloxicam nanocrystals in a thermosensitive gel adapted to the "microenvironment" for long-term analgesia.

Current analgesics on the market exhibit a short duration of action and induce the production of inflammatory factors in tissues damaged by surgical procedures. Inflammatory factor production can create acidic environments, limiting drug delivery. In this study, we developed a novel injectable formulation comprising bupivacaine multivesicular liposomes of high osmotic pressure (H-MVL) and meloxicam nanocrystals (MLX) in a thermosensitive gel (H-MVL/MLX@GEL) adapted to the microenvironment for long-term postoperative analgesia.

DMR040, a potential antifungal compound.

Based on DMR022 [(AEEA-Gly)-AEEA-amphotericin B methyl ester, AEEA is the abbreviation of 8-amino-3,6-dioxaoctanoic acid] and DMR031 [(AEEA)-amphotericin B methyl ester], DMR040 [(AEEA)-amphotericin B methyl ester] was further designed and synthesised. Firstly, DMR040 was assessed for its antifungal activity and haemolytic toxicity with the broth dilution method and sterile defibrinated sheep blood, respectively. The minimal inhibitory concentration (MIC) of DMR040 (2 μg/mL) against Candida albicans ATCC 10231 and ATCC 90028 was reduced by 2 times compared to that of amphotericin B (1 μg/mL).

Polysaccharides from Yupingfeng granules ameliorated cyclophosphamide-induced immune injury by protecting intestinal barrier.

Immune injury is the main side effect caused by cyclophosphamide and the disruption of the intestinal barrier may be an important cause. Yupingfeng granules have been reported to have immunomodulatory effects and polysaccharides are important components of them. This study aimed to investigate the ameliorative effect of polysaccharides from Yupingfeng granules (YPFP) on cyclophosphamide induced immune injury and reveal their potential mechanisms based on its protective effect on the intestine.

Pseudogene KRT17P3 Promotes NSCLC Progression Through Mir-338-3p/USP7/C-Myc.

Background/aim: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, yet its underlying molecular mechanisms remain poorly understood. Previous research has identified the pseudogene KRT17P3 as a key player in NSCLC chemoresistance, but its functional role in tumor development has not been thoroughly investigated.

Materials And Methods: In this study, we utilized in vitro assays to evaluate the impact of KRT17P3 on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).

Interleukin 15-Presenting Nanovesicles with Doxorubicin-Loaded Ferritin Cores for Cancer Immunochemotherapy.

Interleukin 15 (IL15) is crucial for fostering the survival and proliferation of nature killer (NK) cells and cytotoxic T lymphocytes (CTLs), playing a pivotal role in tumor control. However, IL15 supplementary therapy encounters challenges such as systemic inflammation and non-specific stimulation of cancer cells. Herein, a nanovesicle termed DoxFILN, comprising a membrane presenting IL15/IL15 receptor α complexes (IL15c) and a core of doxorubicin-loaded ferritin (Dox-Fn) are reported.

Bifunctional nanomaterial enabled high-specific isolation of urinary exosomes for cervical cancer metabolomics analysis and biomarker discovery.

Cervical cancer (CC) remains a critical public health issue, highlighting the importance of early detection. However, current methods such as cytological and HPV testing face challenges of invasiveness and low patient compliance. Exosomes, emerging as crucial in cancer diagnosis, offer promise due to their noninvasive, highly specificity, and abundant biomarkers.

Niche-specific evolution and gene exchange of Salmonella in retail pork and chicken.

Salmonella exhibits extensive genetic diversity, facilitated by horizontal gene transfer occurring within and between species, playing a pivotal role in this diversification. Nevertheless, most studies focus on clinical and farm animal isolates, and research on the pangenome dynamics of Salmonella isolates from retail stage of the animal food supply chain is limited. Here, we investigated the genomes of 950 Salmonella isolates recovered from retail chicken and pork meats in seven provinces and one municipality of China in 2018.

Alisol A inhibits and stabilizes atherosclerotic plaques by protecting vascular endothelial cells.

Background And Aims: Dysfunction of endothelial cells represents a crucial aspect in the pathogenesis of atherosclerosis. The aim of this study was to explore the protective effects of alisol A on vascular endothelial cells and its possible mechanisms.

Methods: An atherosclerosis model was established by feeding ApoE-/- mice with high-fat chow.

Design, synthesis, and biological evaluation of 2,4-dimorpholinopyrimidine-5-carbonitrile derivatives as orally bioavailable PI3K inhibitors.

Introduction: Phosphoinositide-3-kinase (PI3K) is overexpressed in many tumors and is, thus, an ideal target for cancer treatments. Accordingly, there is an urgent need for the development of PI3K inhibitors with high potency and low toxicity.

Methods: In this study, we designed and synthesized a series of 2,4-dimorpholinopyrimidine-5-carbonitrile derivatives, which were evaluated for their PI3K inhibitory potency.

A tumor-conditional IL-15 safely synergizes with immunotherapy to enhance antitumor immune responses.

It is a challenge to invigorate tumor-infiltrating lymphocytes without causing immune-related adverse events, which also stands as a primary factor contributing to resistance against cancer immunotherapies. Interleukin (IL)-15 can potently promote expansion and activation of T cells, but its clinical use has been limited by dose-limiting toxicities. In this study, we develop a tumor-conditional IL-15 (pro-IL-15), which masks IL-15 with steric hindrance caused by Fc fragment and IL-15Rα-sushi domain.

Glycyrrhizic acid and patchouli alcohol in Huoxiang Zhengqi attenuate intestinal inflammation and barrier injury via regulating endogenous corticosterone metabolism mediated by 11β-HSD1.

Ethnopharmacological Relevance: Ulcerative colitis (UC), a chronic inflammatory bowel disease, has become a significant public health challenge due to the limited effectiveness of available therapies. Huoxiang Zhengqi (HXZQ), a well-established traditional Chinese formula, shows potential in managing UC, as suggested by clinical and pharmacological studies. However, the active components and mechanisms responsible for its effects remain unclear.

Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer.

Advanced colorectal cancer (CRC) responds poorly to current adjuvant therapies, partially due to its immunosuppressive intestinal microenvironment. We found that myeloid-derived suppressor cells (MDSCs) were enriched in orthotopic tumors due to treatment-induced succinate release, which activated tuft cells and upregulated interleukin 25 (IL-25) and interleukin 13 (IL-13). We engineered a cabozantinib (Cabo)-encapsulated and maytansine (DM1)-conjugated synthetic high-density lipoprotein (CD-sHDL) to modulate the tumor microenvironment.

Direct asymmetric synthesis of β-branched aromatic α-amino acids using engineered phenylalanine ammonia lyases.

β-Branched aromatic α-amino acids are valuable building blocks in natural products and pharmaceutically active compounds. However, their chemical or enzymatic synthesis is challenging due to the presence of two stereocenters. We design phenylalanine ammonia lyases (PAL) variants for the direct asymmetric synthesis of β-branched aromatic α-amino acids.

Novel RGD-decorated micelles loaded with doxorubicin for targeted breast cancer chemotherapy.

Nanotechnology has emerged as a promising innovative avenue for therapeutic intervention in cancer research. However, achieving satisfactory accumulation of nanoparticles in the tumor and fabricating optimized nanoparticles remain challenging. In this work, we developed a novel polymeric micelle system to actively target integrin receptors, which are usually overexpressed in breast cancer.

Superresolution imaging of antibiotic-induced structural disruption of bacteria enabled by photochromic glycomicelles.

Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic-induced structural disruption of bacteria.

Neo-5,10-seco-clerodane diterpenoids from Schnabelia terniflora.

Three new neo-5,10-seco-clerodane diterpenoids (1-3), four previously undescribed ethoxy/methoxy acetal analogues (4-7), one new etherified labdane diterpenoid (8), and seven known diterpenoids (9-15) were isolated from the whole plant of Schnabelia terniflora. Their structures were established on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction data, calculated electronic circular dichroism (ECD), and Mo(OAc)-induced circular dichroism. Compounds 2 and 3 represent the first examples of neo-5,10-seco-clerodane diterpenoids containing a 1H-pyrrole-2,5-dione and a pyrrolidine-2,5-dione moiety, respectively.

Design, synthesis and biological evaluation of novel cyano-cinnamate derivatives as mitochondrial pyruvate carrier inhibitors.

Mitochondrial pyruvate carrier (MPC) inhibitors promote the development of hair follicle stem cells without affecting normal cells, which is promising for the treatment of hair loss. Herein, a series of cyano-cinnamate derivatives of UK-5099 were designed and synthesized. All these new compounds have been tested for their ability to promote cellular lactate production in vitro.

Microfluidic-Enabled Assembly of Multicomponent Artificial Organelle for Synergistic Tumor Starvation Therapy.

Artificial organelles (AOs) encapsulating enzymes are engineered to facilitate biocatalytic reactions for exerting therapeutic effects in various diseases. Exploiting the confinement effect, these catalytic properties exhibit significant enhancements without being influenced by the surrounding medium, enabling more efficient cascade reactions. In this study, we present a novel approach for synergistic tumor starvation therapy by developing multicomponent artificial organelles that combine enzymatic oncotherapy with chemotherapy.