Self-Assembly Nanomedicine Initiating Cancer-Immunity Cycle with Cascade Reactions for Boosted Immunotherapy.

Immune checkpoint blockade (ICB) therapy has been extensively integrated into cancer clinical management. However, its overall response rate is limited due to the stagnating cancer-immunity cycle (CIC) caused by the immunosuppressive tumor microenvironment (TME). Here, a multi-pronged nanomedicine, defined as LCCS, was constructed by the self-assembly of lactate oxidase, catalase, chlorin e6, and sorafenib.

Self-assembled palmitic acid-modified thymopentin functions as a delivery system of nanovaccine for cancer immunotherapy.

In clinical practice, thymopentin (TP-5) is a commonly utilized immunomodulatory peptide drug. The relatively short half-life of TP-5, however, significantly limits its applicability in immunotherapy. Inspired by the structure of the TLR2 ligand lipopeptide Pam3CSK4, fatty acid-modified TP-5 peptides were designed and synthesized in this study.

Bioresponsive nanoreactor initiates cascade reactions for tumor vascular normalization and lactate depletion to augment immunotherapy.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment. However, abnormal tumor vasculature and excess lactate contribute to tumor immunosuppression and confer resistance to ICB therapy, seriously limiting its clinical application. Here, we have developed a bioresponsive nanoreactor, ALMn, which consists of hollow manganese dioxide nanoparticles with encapsulation of lactate oxidase and L-Arginine, to overcome immunosuppression and sensitize ICB therapy.

BRD4-targeted photodegradation nanoplatform for light activatable melanoma therapy.

The targeted protein degradation (TPD) strategy modulates tumor growth pathways by degrading proteins of interest (POIs) and has reshaped anti-tumor drug research and development. Recently, the emergence of photodegradation-targeting chimeras (PDTACs) and laser irradiation at specific sites enables precise spatiotemporal controllability of TPD. Capitalizing on the advances of PDTACs, herein, we report a nanoplatform for efficiently delivering PDTAC molecule for photodegradation of bromodomain-containing protein 4 (BRD4) proteins, the key activators of oncogenic transcription.

BMP4 regulates differentiation of nestin-positive stem cells into melanocytes.

Hair follicle (HF) development and pigmentation are complex processes governed by various signaling pathways, such as TGF-β and FGF signaling pathways. Nestin + (neural crest like) stem cells are also expressed in HF stem cells, particularly in the bulge and dermal papilla region. However, the specific role and differentiation potential of these Nestin-positive cells within the HF remain unclear, especially regarding their contribution to melanocyte formation and hair pigmentation.

Engineered hypoxia-responsive albumin nanoparticles mediating mitophagy regulation for cancer therapy.

Hypoxic tumors present a significant challenge in cancer therapy due to their ability to adaptation in low-oxygen environments, which supports tumor survival and resistance to treatment. Enhanced mitophagy, the selective degradation of mitochondria by autophagy, is a crucial mechanism that helps sustain cellular homeostasis in hypoxic tumors. In this study, we develop an azocalix[4]arene-modified supramolecular albumin nanoparticle, that co-delivers hydroxychloroquine and a mitochondria-targeting photosensitizer, designed to induce cascaded oxidative stress by regulating mitophagy for the treatment of hypoxic tumors.

Direct reprogramming of human fibroblasts into hair-inducing dermal papilla cell-like cells by a single small molecule.

Dermal papilla cells (DPCs) are a crucial subset of mesenchymal cells in the skin responsible for regulating hair follicle development and growth, making them invaluable for cell-based therapies targeting hair loss. However, obtaining sufficient DPCs with potent hair-inducing abilities remains a persistent challenge. In this study, the Food and Drug Administration (FDA)-approved drug library was utilized to screen small molecules capable of reprogramming readily accessible human skin fibroblasts into functional DPCs.

Sucralose uses reward pathways to promote acute caloric intake.

Non-nutritive sweeteners (NNSs) are used to reduce caloric intake by replacing sugar with compounds that are sweet but contain little or no calories. In this study, we investigate how non-nutritive sweetener sucralose to promote acute food intake in the fruit fly Drosophila melanogaster. Our results showed that acute exposure to NNSs sweetness induces a robust hyperphagic response in flies.

Cell-Active, Arginine-Targeting Irreversible Covalent Inhibitors for Non-Kinases and Kinases.

Targeted covalent inhibitors (TCIs) play an essential role in the fields of kinase research and drug discovery. TCI strategies to target more common amino acid side-chains have yet to be demonstrated. Targeting other amino acids would also expand the pharmaceutical industry's toolbox for targeting other tough-to-drug proteins.

A rapid and reproducible method for generating germ-free .

Microbial communities exert a profound influence on various facets of animal behavior and physiology, making the comprehension of their interactions with hosts or the environment essential. , a widely recognized model organism, has been pivotal in elucidating host-microbe interactions. Despite the existence of several protocols for generating germ-free (GF) , their reproducibility has been constrained by the technical difficulty of maintaining airtight conditions in centrifuge tubes.

Magnesium peroxide-based biomimetic nanoigniter degrades extracellular matrix to awake T cell-mediated cancer immunotherapy.

As the elite force of our immune system, T cells play a determining role in the effectiveness of cancer immunotherapy. However, the clever tumor cells construct a strong immunosuppressive tumor microenvironment (TME) fortress to resist the attack of T cells. Herein, a magnesium peroxide (MP)-based biomimetic nanoigniter loaded with doxorubicin (DOX) and metformin (MET) is rationally designed (D/M-MP@LM) to awake T cell-mediated cancer immunotherapy via comprehensively destroying the strong TME fortress.

A postbiotic exopolysaccharide synergizes with Lactobacillus acidophilus to reduce intestinal inflammation in a mouse model of colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease marked by gut inflammation and microbial dysbiosis. Exopolysaccharides (EPS) from probiotic bacteria have been shown to regulate microbial composition and metabolism, but their role in promoting probiotic growth and alleviating inflammation in UC remains unclear. Here, we investigate BLEPS-1, a novel EPS derived from Bifidobacterium longum subsp.

Choline metabolism modulates cyclic-di-GMP signaling and virulence of Pseudomonas aeruginosa in a macrophage infection model.

Background: Bacterial pathogens frequently encounter host-derived metabolites during their colonization and invasion processes, which can serve as nutrients, antimicrobial agents, or signaling molecules for the pathogens. The essential nutrient choline (Cho) is widely known to be utilized by a diverse range of bacteria and may undergo conversion into the disease-associated metabolite trimethylamine (TMA). However, the impact of choline metabolism on bacterial physiology and virulence remains largely unexplored.

Continuous Flow Synthesis and Applications of Metal-Organic Frameworks: Advances and Innovations.

Metal-Organic Frameworks (MOFs) are an emerging class of solid-state materials comprising inorganic elements and organic molecules. These hybrid materials are widely recognized for their diverse properties, rendering them indispensable in the field of organic synthesis, material science and the pharmaceutical industry. Although the traditional batch methods for MOFs synthesis are well-developed, they often struggle with reproducibility, scalability and environmental issues.

A Self-Assembled Nano-Molecular Glue (Nano-mGlu) Enables GSH/HO-Triggered Targeted Protein Degradation in Cancer Therapy.

Molecular glues are promising protein-degrading agents that hold great therapeutic potential but face significant challenges in rational design, effective synthesis, and precise targeting of tumor sites. In this study, we first overcame some of these limitations by introducing a fumarate-based molecular glue handle onto specific ligands of therapeutic kinases (TBK1, FGFR, and Bcr-Abl), resulting in the effective degradation of these important cancer targets. Despite the broad applicability of the strategy, we unexpectedly discovered potent and widespread cytotoxicity across various cell lines, including noncancerous ones, rendering it less effective in cancer therapy.

A self-attention-driven deep learning framework for inference of transcriptional gene regulatory networks.

The interactions between transcription factors (TFs) and the target genes could provide a basis for constructing gene regulatory networks (GRNs) for mechanistic understanding of various biological complex processes. From gene expression data, particularly single-cell transcriptomic data containing rich cell-to-cell variations, it is highly desirable to infer TF-gene interactions (TGIs) using deep learning technologies. Numerous models or software including deep learning-based algorithms have been designed to identify transcriptional regulatory relationships between TFs and the downstream genes.

Mutagenesis studies suggest a mechanism for influenza polymerase stalling during polyadenylation.

Influenza polymerase (FluPol) carries out both viral transcription and replication using the same viral genome segment as a template to yield distinct end products. However, it remains largely unclear how FluPol synthesizes transcripts containing poly (A) tails during transcription termination, while producing fully complementary products during replication termination. In this study, through structural analysis combined with cell-based and biochemical assays, we identified that the PB1 Leu675/Asn676 and PB2 Arg38 residues of FluPol are critical for transcription termination and polyadenylation.

KAHA ligation as a platform for the rapid discovery of Protein Tyrosine phosphatase 1B (PTP1B) inhibitors.

We have successfully designed and assembled a 66-member library of protein tyrosine phosphatases (PTP) inhibitor candidates using α-ketoacid-hydroxylamine (KAHA) ligation. Subsequent in situ enzymatic screening revealed a potent hit (IC = 1.67 μM) against PTP1B, which displayed 6.

A FRET Autophagy Imaging Platform by Macrocyclic Amphiphile.

Autophagy is a ubiquitous process of organelle interaction in eukaryotic cells, in which various organelles or proteins are recycled and operated through the autophagy pathway to ensure nutrient and energy homeostasis. Although numerous fluorescent probes have been developed to image autophagy, these environment-responsive probes suffer from inherent deficiencies such as inaccuracy and limited versatility. Here, we present a modular macrocyclic amphiphile Förster Resonance Energy Transfer (FRET) platform (SC6A12C/NCM, SN), constructed through the amphiphilic assembly of sulfonatocalix[6]arene (SC6A12C) with N-cetylmorpholine (NCM) for lysosome targeting.

A new terpestacin-type sesterterpenoid with tricyclic 3/15/5 scaffold from an endophytic fungus sp. J019.

ABSTACTChemical investigation of an endophytic fungus, sp. J019, isolated from the plant species R. Br.

Application of Advanced High-Resolution Mass Spectrometric Techniques for the Analysis of Losartan Potassium Drug Substance Degradation Products: From Nontargeted to Targeted Screening.

Advances in techniques for quality analysis allow for a more detailed examination of drug impurities. High-resolution mass spectrometry (HRMS) contributes to detecting both known and unknown impurities. In this study, a combination of a nontargeted and targeted screening approach was established and applied to the detailed degradation profile of the losartan potassium (LP) drug substance.

TPepPro: a deep learning model for predicting peptide-protein interactions.

Motivation: Peptides and their derivatives hold potential as therapeutic agents. The rising interest in developing peptide drugs is evidenced by increasing approval rates by the FDA of USA. To identify the most potential peptides, study on peptide-protein interactions (PepPIs) presents a very important approach but poses considerable technical challenges.

A single-center clinical trial evaluating topical propranolol for preventing stress-induced hair loss.

There is currently a lack of pathological research on the hair loss caused by stress, and there is no effective treatment available. It has been previously reported that stress can cause sympathetic nerve activation and release of norepinephrine, which binds to beta-2 adrenergic receptors and causes a series of chemical reactions. Propranolol, as a beta-2 adrenergic receptors blocker, competitively antagonizes the effects of norepinephrine.