Transformable self-delivered supramolecular nanomaterials combined with anti-PD-1 antibodies alleviate tumor immunosuppression to treat breast cancer with bone metastasis.

Breast cancer is the most common malignant tumor that threatens women's life and health, and metastasis often occurs in the advanced stage of breast cancer, leading to pathological bone destruction and seriously reducing patient quality of life. In this study, we coupled chlorin e6 (Ce6) with mono-(6-amino-6-deoxy)-beta-cyclodextrin (β-CD) to form Ce6-CD, and combined ferrocene with the FFVLGC peptide and PEG chains to form the triblock molecule Fc-pep-PEG. In addition, the IDO-1 inhibitor NLG919 was loaded with Ce6-CD and Fc-pep-PEG to construct the supramolecular nanoparticle NLG919@Ce6-CD/Fc-pep-PEG (NLG919@CF).

QBT improved cognitive dysfunction in rats with vascular dementia by regulating the Nrf2/xCT/GPX4 and NLRP3/Caspase-1/GSDMD pathways to inhibit ferroptosis and pyroptosis of neurons.

Background: The novel phthalein component QBT, extracted from Ligusticum chuanxiong, shows promising biological activity against cerebrovascular diseases. This study focused on ferroptosis and pyroptosis to explore the effects of QBT on nerve injury, cognitive dysfunction, and related mechanisms in a rat model of vascular dementia (VaD).

Methods: We established a rat model of VaD and administered QBT as a treatment.

Physiologically based pharmacokinetic model of brivaracetam to predict the exposure and dose exploration in hepatic impairment and elderly populations.

Brivaracetam (BRV) is a new third-generation antiseizure medication for the treatment of focal epileptic seizures. Its use has been increasing among epileptic populations in recent years, but pharmacokinetic (PK) behavior may change in hepatic impairment and the elderly populations. Due to ethical constraints, clinical trials are difficult to conduct and data are limited.

Engineering a porphyrin COFs encapsulated by hyaluronic acid tumor-targeted nanoplatform for sequential chemo-photodynamic multimodal tumor therapy.

Numerous barriers hinder the entry of drugs into cells, limiting the effectiveness of tumor pharmacotherapy. Effective penetration into tumor tissue and facilitated cellular uptake are crucial for the efficacy of nanotherapeutics. Photodynamic therapy (PDT) is a promising approach for tumor suppression.

Renal-Targeted Drug Delivery by Chitosan Oligosaccharide Micelles with HSA-Enriched Protein Corona for the Treatment of Ischemia/Reperfusion-Induced Acute Kidney Injury.

Renal-specific nanoparticulate drug delivery systems have shown great potential in reducing systemic side effects and improving the safety and efficacy of treatments for renal diseases. Here, stearic acid-grafted chitosan oligosaccharide (COS-SA) was synthesized as a renal-targeted carrier due to the high affinity of the 2-glucosamine moiety on COS to the megalin receptor expressed on renal proximal tubular epithelial cells. Specifically, COS-SA/CLT micelles were prepared by encapsulating celastrol (CLT) with COS-SA, and different proportions of human serum albumin (HSA) were then adsorbed onto its surface to explore the interaction between the protein corona and cationic polymeric micelles.

Organic Photoredox-Catalyzed Site-Selective Alkylation of Glycine Derivatives and Peptides via Infrequent 1,2-Hydrogen Atom Transfer of Amidyl Radicals.

Herein, we disclose a visible-light-driven photoredox-catalyzed protocol for site-selective alkylation of glycine derivatives via 1,2-hydrogen atom transfer, which is distinguished by metal free and mild conditions, high chemoselectivity, and good functional group compatibility. This protocol provides a unique approach for synthesizing valuable α,β-diamino acid derivatives. Furthermore, the potential synthetic merit of this transformation is proven by a scale-up reaction and late-stage functionalization of peptides.

Mitochondrial dysfunction in sepsis: mechanisms and therapeutic perspectives.

Sepsis is a severe medical condition characterized by a systemic inflammatory response, often culminating in multiple organ dysfunction and high mortality rates. In recent years, there has been a growing recognition of the pivotal role played by mitochondrial damage in driving the progression of sepsis. Various factors contribute to mitochondrial impairment during sepsis, encompassing mechanisms such as reactive nitrogen/oxygen species generation, mitophagy inhibition, mitochondrial dynamics change, and mitochondrial membrane permeabilization.

Structural Optimization and Structure-Activity Relationship of 1-Pyrazole-4-carboxylic Acid Derivatives as DNA 6mA Demethylase ALKBH1 Inhibitors and Their Antigastric Cancer Activity.

DNA -methyladenine (6mA) demethylase ALKBH1 plays an important role in various cellular processes. Dysregulation of ALKBH1 is associated with the development of some cancer types, including gastric cancer, implicating a potential therapeutic target. However, there is still a lack of potent ALKBH1 inhibitors.

The Construction of Novel Spirocyclic Frameworks with Cyclobutane through Rh(III)-Catalyzed [3 + 2]-Annulation between Quinoxalines and Alkynylcyclobutanols.

An effective synthesis strategy for the preparation of 1'-spiro[indene-1,2'-quinoxaline] has been developed. This involves a Rh(III)-catalyzed [3 + 2]-annulation of quinoxalines with alkynylcyclobutanols. The developed protocol offers a straightforward method for the preparation of versatile heterocyclic compounds with a four-membered ring and is compatible with a wide range of functional groups.

Patient-reported outcome measures for medication treatment satisfaction: a systematic review of measure development and measurement properties.

Background: Medication Treatment Satisfaction (M-TS) from the patients' perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps.

Integrating computational and experimental approaches in discovery and validation of MmpL3 pore domain inhibitors for specific labelling of Mycobacterium tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to pose a significant global health threat. Identifying new druggable targets is crucial for the advancement of drug development. Equally critical is the development of precise methods for monitoring Mtb to effectively combat this disease.

B(CF)·HO-Catalyzed N-H and C-H Functionalization of Aromatic Amines with Sulfoxonium Ylides under Metal-Free Conditions.

Hydrogen-bonded aggregates of B(CF) and water are proven as strong Brønsted acid catalysts, which have the advantages of low toxicity and broad compatibility. Sulfoxonium ylides are stable surrogates of diazo compounds, which participate in various reactions due to their versatile reactivity. Based on these characteristics, a strategy for C-N bond or C-C bond construction of aromatic amines with sulfoxonium ylides under metal-free catalytic conditions was established.

CYP8B1 Catalyzes 12alpha-Hydroxylation of C Bile Acid: In Vitro Conversion of Dihydroxycoprostanic Acid into Trihydroxycoprostanic Acid.

Sterol 12α-hydroxylase (CYP8B1) is the unique P450 enzyme with sterol 12-oxidation activity, playing an exclusive role in 12-hydroxylating intermediates along the bile acid (BA) synthesis pathway. Despite the long history of BA metabolism studies, it is unclear whether CYP8B1 catalyzes 12-hydroxylation of C BAs, the key intermediates shuttling between mitochondria and peroxisomes. This work provides robust in vitro evidence that both microsomal and recombinant CYP8B1 enzymes catalyze the 12-hydroxylation of dihydroxycoprostanic acid (DHCA) into trihydroxycoprostanic acid (THCA).

Efficacy and safety of rectal chloral hydrate for pediatric procedural sedation: A systematic review and meta-analysis.

Background: To evaluate the efficacy and safety of rectal chloral hydrate (CH) in pediatric procedural sedation.

Methods: Seven electronic databases and 3 clinical trials registry platforms were searched, and the deadline was August 2022. Randomized controlled trials evaluating the efficacy and safety of rectal CH in pediatric procedural sedation were included by 2 reviewers.

Metabolomic profiling integrated with molecular exploring delineates the action of Ligusticum chuanxiong hort. on migraine.

Introduction: Ligusticum chuanxiong hort. (Chuanxiong, CX) is a well-known traditional edible-medicinal herb, especially in brain diseases. However, there is a lack of studies focusing on the action of CX in metabolites of migraine.

Glucosylated Nanovaccines for Dendritic Cell-Targeted Antigen Delivery and Amplified Cancer Immunotherapy.

Engineering nanovaccines capable of targeting dendritic cells (DCs) is desperately required to maximize antigen cross-presentation to effector immune cells, elicit strong immune responses, and avoid adverse reactions. Here, we showed that glucose transporter 1 (Glut-1) on DCs is a reliable target for delivering antigens to DCs, and thus, a versatile antigen delivery strategy using glucosylated nanovaccines was developed for DC-targeted antigen delivery and tumor immunotherapy. The developed glucosylated ovalbumin-loaded nanovaccines highly accumulated in lymph nodes and efficiently engaged with Glut-1 on DCs to accelerate intracellular antigen delivery and promote DC maturation and antigen presentation, which elicited potent antitumor immunity to prevent and inhibit ovalbumin-expressing melanoma.

Iron-Catalyzed Primary Amination of C(sp)-H Bonds.

Primary amines are privileged molecules in drug development. Yet, there is a noticeable scarcity of methods for directly introducing a primary amine group into the ubiquitous C(sp)-H bonds within organic compounds. Here, we report an iron-based catalytic system that enables direct primary amination of C(sp)-H bonds under aqueous conditions and air.

Reference guides for the safe use of drugs during pregnancy: a systematic review and comparative analysis.

Purpose: To comprehensively evaluate and compare all the available reference guides for the safe use of drugs during pregnancy, with the goal of determining the scientificity and reliability of these reference guides.

Methods: We searched PubMed, EMbase, CNKI, Wanfang Database, and VIP database to comprehensively identify the available reference guides. Moreover, we selected 103 drugs based on relevant literatures, and compared the recommendations of each drug from different reference guides.

Copper-promoted -directed C-H amination of 2-arylpyridines with NH-heterocycles.

Copper-mediated C-N coupling of azaheterocycles with aryl C-H bonds has been realized for the synthesis of N-(hetero)arylated heteroarenes. This method is characterized by high regioselectivity, atom economy and a wide substrate scope of 2-arylazines and azaheterocycles. The corresponding C-N coupling products were shown to undergo further transformation to synthesize more complex molecules.

A new long-acting analgesic formulation for postoperative pain management.

Local anesthetics (LA), as part of multimodal analgesia, have garnered significant interest for their role in delaying the initiation of opioid therapy, reducing postoperative opioid usage, and mitigating both hospitalization duration and related expenses. Despite numerous endeavors to extend the duration of local anesthetic effects, achieving truly satisfactory long-acting analgesia remains elusive. Drawing upon prior investigations, vesicular phospholipid gels (VPGs) emerge as promising candidates for extended-release modalities in small-molecule drug delivery systems.

Metal π-Lewis base activation in palladium(0)-catalyzed -alkylative cyclization of alkynals.

The Pd(0)-mediated umpolung reaction of an alkyne to achieve -difunctionalization is a potential synthetic methodology, but its insightful activation mechanism of Pd(0)-alkyne interaction has yet to be established. Here, a Pd(0)-π-Lewis base activation mode is proposed and investigated by combining theoretical and experimental studies. In this activation mode, the Pd(0) coordinates to the alkyne group and enhances its nucleophilicity through π-back-donation, facilitating the nucleophilic attack on the aldehyde to generate a -Pd(ii)-vinyl complex.

Phosphodiesterase-5 inhibitors and hearing impairment: a disproportionality analysis using the US food and drug administration adverse event reporting system.

Background: This study aimed to investigate the association between phosphodiesterase-5 inhibitors (PDE-5i) and hearing impairment adverse events (HIAEs) while providing an overview of the characteristics of drug-related HIAEs.

Research Design And Methods: We conducted a detailed pharmacovigilance analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, covering 2004 to 2022. By calculating the reporting odds ratio (ROR) and the information component (IC), we identified signals that indicate the association between PDE-5i use and HIAEs.

Discovering New Metallo-Deubiquitinase CSN5 Inhibitors by a Non-Catalytic Activity Assay Platform.

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, , that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5.