5-Fluorouracil Loaded Prebiotic-Probiotic Liposomes Modulating Gut Microbiota for Improving Colorectal Cancer Chemotherapy.

The gut microbiota exerts inhibitory effects on the occurrence and progression of colorectal cancer (CRC) through various mechanisms. Compared to traditional microbiota regulation methods, prebiotics and probiotics demonstrate significant advantages in terms of safety and patient adaptability. Their synergy not only improves the intestinal environment but also enhances the host's anti-tumor immune response.

The novel β-hairpin antimicrobial peptide D-G(RF)3 demonstrates exceptional antibacterial efficacy.

The clinical application of most natural antimicrobial peptides (AMPs) is hindered by their lack of a synergistic combination of high antibacterial efficacy, low toxicity, and stability, necessitating frequent complex modifications that incur significant labor and economic costs. Therefore, it is imperative to optimize the antibacterial properties of AMPs using some simplified approach. In this study, we designed a library of β-hairpin AMPs with identical β-turn sequences (-D-Pro-Gly-) and varying repetition units (IR, FR, and WK).

Unlocking the neuroprotective potential of Ziziphora clinopodioides flavonoids in combating neurodegenerative diseases and other brain injuries.

Ziziphora clinopodioides Lam. (Z. clinopodioides) is a traditional Chinese and ethnic medicine in Xinjiang, China with various therapeutic effects.

Total Synthesis of Artapilosine A and Artapilosine B.

Artapilosines A and B, isolated from , demonstrated significant anti-HIV reverse transcriptase activity. In this work, we present the first asymmetric total synthesis of (-)-artapilosine A and of its enantiomer (+)-artapilosine A, achieved in 10 steps with overall yields of 0.9% and 0.

Targeting AhR suppresses hepatocyte ferroptosis in MASH by regulating the Pten/Akt/β catenin axis.

Aryl hydrocarbon Receptor (AhR), an essential host regulator, has been observed to be significantly upregulated in patients with Metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanism remains unclear. The specific AhR antagonist CH223191 and siRNAs were employed to investigated the role of AhR and its potential as a therapeutic target for MASH in mice and hepatocytes model.

Pentacyclic triterpenoids with cytotoxic activity from the stems of Syzygium jambos (L.) Alston.

Phytochemical investigation of the stems of Syzygium jambos (L.) Alston resulted in the isolation of five new pentacyclic triterpenoids, including three oleananes (1, 2, and 5) and two ursanes (3 and 4), along with 23 known compounds (6-28). Their structures were elucidated by comprehensive spectroscopic analysis and chemical methods.

Quantification of serum daratumumab in multiple myeloma patients by LC-MS/MS, comparison with ELISA.

Daratumumab is a fully human immunoglobulin G1 monoclonal antibody employed for treating relapsed/refractory multiple myeloma and light-chain amyloidosis. Quantifying monoclonal antibodies in serum presents challenges due to interference from biological matrices. This research aimed to develop and verify an liquid chromatography tandem-mass spectrometry (LC-MS/MS) approach for quantifying serum daratumumab, employing immunoglobulin G purification without alkylation, and to assess its applicability in patients with multiple myeloma receiving intravenous daratumumab.

Urolithin B inhibits LPS-induced macrophage M1 polarization via miR155-5p mediated MAPK/NF-кB pathway.

This study investigated inhibiting mechanisms of Urolithin B (Uro B) on macrophage M1 polarization. Uro B (50 μM) could inhibit the PGE2, COX-2, NO, iNOS, TNF-α, IL-1β and IL-6 levels compared with model group ( < 0.05) as well as the CD86 and F4/80 expression.

Spirocyclic iridoid alkaloids from .

Plumerianoids A-D (1-4) with a new intact spirocyclic iridoid alkaloid skeleton, along with a new degraded alkaloid 8--plumerianine (5), and a known one (6), were isolated and characterized from . The structure of 6 was revised as (8,13)-plumerianine. These alkaloids consist of three epimeric pairs (1/2, 3/4, and 5/6), exhibiting virtually identical NMR spectra within each pair.

Preclinical Evaluation and Pilot Clinical Study of CD137 PET Radiotracer for Noninvasive Monitoring Early Responses of Immunotherapy.

Given the variability in the effectiveness of immune checkpoint blocking therapy among patients and tumor types, development of noninvasive methods for longitudinal assessment of immune cell function and early tumor response is crucial for precision immunotherapy. CD137 (4-1BB), a marker of activated T cells, plays a significant role in immunotherapy. However, its potential as an imaging biomarker for activated T cells in the tumor microenvironment has not been explored.

"3D channel maze" to control drug release from multiple unit tablets.

Diffusion is defined as general mechanism for drug release from advanced delivery systems, yet dynamic structure of dosage form intrinsically plays an unknown role. The synchrotron radiation X-ray micro-computed tomography (SR-μCT) three-dimensional (3D) imaging and in-depth analysis of 3D structures were applied to readily differentiate materials and accurately capture internal structure changes of multiple unit pellet system (MUPS) and the constituent pellets, visualizing internal 3D structure of a MUPS of theophylline tablets for their 3 levels hierarchy structures: pellets with rapid drug release characteristics, a protective cushion layer and a matrix layer. Drug release pathways were extracted from SR-μCT images and a 3D maze network was constructed using pore network analysis to quantify the internal structural evolution during drug release.

Molecular basis of lipid and ligand regulation of prostaglandin receptor DP2.

Prostaglandin D2 receptor 2 (DP2) is an important anti-inflammatory and antiallergic drug target. While inactive DP2 structures are known, its activation mechanisms and biased signaling remain unclear. Here, we report cryo-EM structures of an apo DP2-Gi complex, a DP2-Gi complex bound to the endogenous ligand Prostaglandin D (PGD), and a DP2-Gi complex bound to indomethacin, an arrestin-biased ligand, at resolutions of 2.

Advancements and challenges in immunocytokines: A new arsenal against cancer.

Immunocytokines, employing targeted antibodies to concentrate cytokines at tumor sites, have shown potential advantages such as prolonged cytokine half-lives, mitigated adverse effects, and synergistic antitumor efficacy from both antibody and cytokine components. First, we present an in-depth analysis of the advancements of immunocytokines evaluated in preclinical and clinical applications. Notably, anti-PD-1-based immunocytokines can redirect cytokines to intratumoral CD8 T cells and reinvigorate them to elicit robust antitumor immune responses.

An overview of the functions and mechanisms of APOBEC3A in tumorigenesis.

The APOBEC3 (A3) family plays a pivotal role in the immune system by performing DNA/RNA single-strand deamination. Cancers mostly arise from the accumulation of chronic mutations in somatic cells, and recent research has highlighted the A3 family as a major contributor to tumor-associated mutations, with A3A being a key driver gene leading to cancer-related mutations. A3A helps to defend the host against virus-induced tumors by editing the genome of cancer-associated viruses that invade the host.

A peptide-centric local stability assay enables proteome-scale identification of the protein targets and binding regions of diverse ligands.

By using a limited-proteolysis strategy that employs a large amount of trypsin to generate peptides directly from native proteins, we found that ligand-induced protein local stability shifts can be sensitively detected on a proteome-wide scale. This enabled us to develop the peptide-centric local stability assay, a modification-free approach that achieves unprecedented sensitivity in proteome-wide target identification and binding-region determination. We demonstrate the broad applications of the peptide-centric local stability assay by investigating interactions across various biological contexts.

Rh(II)-Catalyzed Selective C(sp)-H/C(sp)-H Bonds Cascade Insertion to Construct [6-8-6] Benzo-Fused Scaffold.

The fused eight-membered carbocycles (EMCs) play vital roles in the medicinal and biological investigations of many natural products and marketed drugs. The traditional synthesis of [6-8-6] benzo-fused derivatives involves multistep reactions and low yields, making the development of a one-step synthesis method a more challenging work. Here, we present a novel strategy for one-step construction of [6-8-6] benzo-fused scaffold from propargyl diazoacetates substituted with benzyl-nitrogen heterocyclic ring via Rh(ll)-catalyzed carbene/alkyne metathesis (CAM) and selective C-H bond insertion.

Brain Resident Ly6C Monocytes Are Necessary for Maintaining Adult Hippocampal Neurogenesis.

Adult hippocampal neurogenesis (AHN) is crucial to various brain functions. Neurodegeneration, neuroinflammation and stress can impair AHN, contributing to the development of neurological and psychiatric disorders. Stress is known to extensively affect both the brain and peripheral immune system.

C(sp)-H Carbonylative Cyclization of Hydrazones with CO: Synthesis of Pyrazolone Derivatives.

A novel method is reported to synthesize various pyrazolones through transition-metal-free and redox-neutral 1°, 2°, or 3° C(sp)-H carbonylative cyclization using 1 atm of CO as a green carbonyl source, featuring good functional group tolerance, a broad substrate scope, facile scalability, and easy product transformation. The utility of this method could be demonstrated by the applications in preparing useful synthetic intermediates and bioactive compounds.

Application and research progress of synthetic lethality in the development of anticancer therapeutic drugs.

With the tremendous success of the PARP inhibitor olaparib in clinical practice, synthetic lethality has become an important field for the discovery and development of anticancer drugs. More and more synthetic lethality targets have been discovered with the rapid development of biotechnology in recent years. Currently, many drug candidates that were designed and developed on the basis of the concept of synthetic lethality have entered clinical trials.

[ (Blume) Miq] maintains uric acid homeostasis via regulating gut microbiota and restrains renal inflammation in hyperuricemic nephropathy.

Introduction: The kidney damage caused by the deposition of uric acid in the kidneys is of urgent need for new treatment drugs due to its complex pathogenesis. (Blume) Miq. Also known as , which has a significant therapeutic effect on hyperuricemia nephropathy (HN), however, the specific mechanism of its action is still unknown.

fMRI used to observe the acute craniocerebral response of esophageal cancer related depressive patients treated by rTMS: Initial experience.

To observe the immediate craniocerebral response, changes of spontaneous nerve activity and functional connection after repeated transcranial magnetic stimulation (rTMS) in esophageal cancer patients with depression (ECPD) by functional magnetic resonance imaging (fMRI), and to explore the therapeutic effect, neuroactivity response and mechanism. Eleven patients with ECPD were enrolled to treated with single rTMS. The patients were examined by fMRI before and after the treatment.