Breath and Beyond: Advances in Nanomedicine for Oral and Intranasal Aerosol Drug Delivery.

Designing and standardizing drug formulations are crucial for ensuring the safety and efficacy of medications. Nanomedicine utilizes nano drug delivery systems and advanced nanodevices to address numerous critical medical challenges. Currently, oral and intranasal aerosol drug delivery (OIADD) is the primary method for treating respiratory diseases worldwide.

The Significant Therapeutic Effects of Chinese Scorpion: Modern Scientific Exploration of Ion Channels.

Chinese scorpion (CS), a traditional animal-based medicine used for over a millennium, has been documented since AD 935-960. It is derived from the scorpion Karsch and is used to treat various ailments such as stroke, epilepsy, rheumatism, and more. Modern research has identified the pharmacological mechanisms behind its traditional uses, with active components like venom and proteins showing analgesic, antitumor, antiepileptic, and antithrombotic effects.

Bis-Iridoid Glycosides and Triterpenoids from and Their Potential as Inhibitors of ACC1 and ACL.

A comprehensive phytochemical investigation of the twigs/leaves and flower buds of , a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (- and -), 20 triterpenoids (, , and -), and 8 phenylpropanoids (-). Among these, amabiliosides A () and B () represent previously undescribed bis-iridoid glycosides, while amabiliosides C () and D () feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro--carboline-5-carboxylic acid moiety.

Vitamin C and MEK Inhibitor PD0325901 Synergistically Promote Oligodendrocytes Generation by Promoting DNA Demethylation.

DNA methylation and demethylation are key epigenetic events that regulate gene expression and cell fate. DNA demethylation via oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is typically mediated by TET (ten-eleven translocation) enzymes. The 5hmC modification is considered an intermediate state of DNA demethylation; it is particularly prevalent in the brain and is believed to play a role in the development of many cell types in the brain.

Utilizing Lactic Acid Bacteria to Improve Hyperlipidemia: A Comprehensive Analysis from Gut Microbiota to Metabolic Pathways.

Hyperlipidemia poses significant risks for cardiovascular diseases, with emerging evidence underscoring the critical role of gut microbiota in metabolic regulation. This study explores CAAS36, a probiotic strain with promising cholesterol-lowering capabilities, assessing its impact on hyperlipidemic hamsters. Utilizing 1H NMR-based metabolomics and 16S rRNA gene sequencing, we observed that CAAS36 treatment not only altered metabolic pathways but also reshaped gut microbiota composition.

Structure Elucidation and Immunostimulatory Activity Evaluation of a Galactoglucan from Hance.

Hance has a medicinal history of thousands of years in treating cough, diabetes, and gastrointestinal system diseases, and it is also a medicine food homology (MFH) plant in China. To evaluate the pharmacological activities of polysaccharides from the rhizomes of , polysaccharides were initially obtained by hot-water extraction and the ethanol precipitation method. A homogenous polysaccharide designated as AOP-w was isolated by a DE-52 column.

Identification of Chemical Constituents from Leaves and Stems of : Potential Antioxidant and Tyrosinase Inhibitory Properties.

Miq. is an important undergrowth species in southern China. The fruits of are recognized as one of "the four famous south medicines" and are also used in the production of preserved fruit.

Biofluid-Derived Exosomal LncRNAs: Their Potential in Obesity and Related Comorbidities.

Obesity has escalated into a critical global health crisis, tripling in prevalence since the mid-1970s. This increase mirrors the rise in metabolic-associated diseases such as type 2 diabetes (T2D) and its complications, certain cancers, and cardiovascular conditions. While substantial research efforts have enriched our understanding and led to the development of innovative management strategies for these diseases, the suboptimal response rates of existing therapies remain a major obstacle to effectively managing obesity and its associated conditions.

Dissolving microneedle synergistic rocaglamide-loaded liposome to regulate abnormal neutrophils for anti-psoriasis.

Psoriasis seriously affects the physical and mental health of patients. Rocaglamide (RocA), derived from Aglaia odorata, exhibits potent pharmacological activities. Although its efficacy in psoriasis is unclear, RocA could be a promising therapeutic drug.

Structure-Guided Development of ClpP Agonists with Potent Therapeutic Activities against Infection.

Peritonitis caused by poses a severe threat to patients with end-stage renal failure. Treating multidrug-resistant infections requires the use of antibiotics with diverse mechanisms of action. Caseinolytic protease P (ClpP) is a promising antibacterial target; however, selective activation of (ClpP) over human ClpP (ClpP) remains challenging.

Energy Transfer (EnT)-Mediated Stereoselective Aryl-Heterofunctionalization of Unactivated Alkynes via Radical Rearrangement.

In this study, we present a novel catalyst-free energy transfer mediated radical rearrangement strategy for the aryl-heterofunctionalization of unactivated alkynes, leading to the synthesis of polyfunctional olefins with exceptional stereoselectivity. This innovative approach, driven by visible light, exemplifies green chemistry principles by eliminating the reliance on transition metals, external oxidants, and photocatalysts. The broad applicability of our method is demonstrated through the successful synthesis of a diverse array of compounds, including vinyl sulfones, vinyl selenides, and vinyl sulfides.

Harnessing acylhydrazone-oxime exchange reaction to achieve diverse synthesis of glycosite-specific antibody-drug conjugates.

Glycosite-specific antibody-drug conjugates (gsADCs), which carry cytotoxic payloads at the conserved -glycosylation site, N297, of an IgG, have emerged as a promising ADC format with better therapeutic index. Conjugating the payloads aldehyde-based chemistry is more friendly to IgGs, and has been widely investigated. However, the efficiency of introducing an aldehyde tag at the N297 site is poor due to the complicated procedures required, such as the multiple-enzyme-catalyzed IgG glycoengineering process and the successive oxidation step, which always results in heterogeneous products and poor stability.

Mass Spectrometry-Based Protein Footprinting for Protein Structure Characterization.

ConspectusProtein higher-order structure (HOS) is key to biological function because the mechanisms of protein machinery are encoded in protein three-dimensional structures. Mass spectrometry (MS)-based protein footprinting is advancing protein structure characterization by mapping solvent-accessible regions of proteins and changes in H-bonding, thereby providing higher order structural information. Footprinting provides insights into protein dynamics, conformational changes, and interactions, and when conducted in a differential way, can readily reveal those regions that undergo conformational change in response to perturbations such as ligand binding, mutation, thermal stress, or aggregation.

Auto-RapTAC: A Versatile and Sustainable Platform for the Automated Rapid Synthesis and Evaluation of PROTAC.

The tedious synthesis and limited throughput biological evaluation remain a great challenge for discovering new proteolysis targeting chimera (PROTAC). To rapidly identify potential PROTAC lead compounds, we report a platform named Auto-RapTAC. Based on the modular characteristic of the PROTAC molecule, a streamlined workflow that integrates lab automation with "click chemistry" joint building-block libraries was constructed.

Structural insights into the LGR4-RSPO2-ZNRF3 complexes regulating WNT/β-catenin signaling.

WNT/β-catenin signaling plays key roles in development and cancer. ZNRF3/RNF43 modulates Frizzleds through ubiquitination, dampening WNT/β-catenin signaling. Conversely, RSPO1-4 binding to LGR4-6 and ZNRF3/RNF43 enhances WNT/β-catenin signaling.

Enalomics: A Mass Spectrometry-Based Approach for Profiling, Identifying, and Semiquantifying Enals in Biological Samples.

Human cells generate a bulk of aldehydes during lipid peroxidation (LPO), influencing critical cellular processes, such as oxidative stress, protein modification, and DNA damage. Enals, highly reactive α,β-unsaturated aldehydic metabolites, are implicated in various human pathologies, especially neurodegenerative disorders, cancer, and cardiovascular diseases. Despite their importance, endogenous enals remain poorly characterized, primarily due to their instability and low abundance.

E3 ligase FBXW7 suppresses brown fat expansion and browning of white fat.

Thermogenic fat, including brown and beige fat, dissipates heat via thermogenesis and enhances energy expenditure. Thus, its activation represents a therapeutic strategy to combat obesity. Here, we demonstrate that levels of F-box and WD repeat domain-containing 7 (FBXW7), an E3 ubiquitin protein ligase, negatively correlate with thermogenic fat functionality.

Preparation of sodium alginate and chitosan modified curcumin liposomes and study on the formation of protein corona.

Curcumin (CUR) is a polyphenolic compound extracted from plants with a wide range of pharmacological activities. However, the low stability and bioavailability limits its practical application. This work utilized the chitosan (CH) and sodium alginate (SA) to modify the surface of the liposome to improve the stability of curcumin.

Manganese is a potent inducer of lysosomal activity that inhibits de novo HBV infection.

Sodium taurocholate co-transporting polypeptide (NTCP) has been identified as an entry receptor for hepatitis B virus (HBV), but the molecular events of the viral post-endocytosis steps remain obscure. In this study, we discovered that manganese (Mn) could strongly inhibit HBV infection in NTCP-reconstituted HepG2 cells without affecting viral replication. We therefore profiled the antiviral effects of Mn2+ in an attempt to elucidate the regulatory mechanisms involved in early HBV infection.

Targeting QPCTL: An Emerging Therapeutic Opportunity.

Glutaminyl cyclases, including glutaminyl-peptide cyclotransferase (QPCT) and glutaminyl-peptide cyclotransferase-like protein (QPCTL), primarily catalyze the cyclization of N-terminal glutamine or glutamate to pyroglutamate (pGlu). QPCTL, in particular, modifies the N-terminus of CD47, thereby regulating its interaction with signal-regulatory protein alpha (SIRPα) and modulating phagocytosis of tumor cells by immune cells. Additionally, QPCTL cyclizes the N-termini of CCL2, CCL7, and CX3CL1, influencing the tumor microenvironment and inflammatory responses in cancer and other disorders.

Glycan Sequencing Based on Glycosidase-Assisted Nanopore Sensing.

Nanopores are promising sensors for glycan analysis with the accurate identification of complex glycans laying the foundation for nanopore-based sequencing. However, their applicability toward continuous glycan sequencing has not yet been demonstrated. Here, we present a proof-of-concept of glycan sequencing by combining nanopore technology with glycosidase-hydrolyzing reactions.

6-Indolo-[2,3-]-quinoxaline derivatives as promising bifunctional SHP1 inhibitors.

Dysfunction in the SHP1 enzyme can cause cancers and many diseases, so it is of great significance to develop novel small molecule SHP1 inhibitors. Through continuous monitoring of metabolic and targeted processes of SHP1 inhibitors in real-time, we can evaluate the effectiveness and toxicity of the inhibitors, further optimize drug design, and explore SHP1 biology. Indoloquinoxaline is an important class of N-containing heterocycle, which has been studied and applied in the pharmacological field and in optoelectronic materials.