Recent Advances in Radical Coupling Reactions Directly Involving Bicyclo[1.1.1]pentane (BCP).

BCP (bicyclo[1.1.1]pentane) is an ideal saturated carbon bioisostere, instead of the traditional benzene group, which has been extensively developed.

Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance.

Drug resistance is a common challenge in clinical tumor treatment. A reduction in drug sensitivity of tumor cells is often accompanied by an increase in autophagy levels, leading to autophagy-related resistance. The effectiveness of combining chemotherapy drugs with autophagy inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear.

Impact of psychotropic pro re nata prescription-monitoring programme on prescriptions for inpatients with psychiatric disorders: a retrospective observational study.

Background: Pro re nata (PRN) medication is used "as needed" for symptoms such as agitation and insomnia, in addition to regular daily pharmacotherapy of mental disorders. However, there is no high-quality evidence on the effectiveness of psychotropic PRN medications and concerns have been raised about their potential to contribute to polypharmacy. This study introduced a psychotropic PRN prescription-monitoring programme for psychiatric inpatients with the aim of examining the change before and after the implementation of the programme.

Untargeted metabolomics and functional analyses reveal that the secondary metabolite quinic acid associates with Angelica sinensis flowering.

Flowering is a critical step in the plant life cycle. Angelica sinensis (Oliv.) Diels is a medicinal crop whose root is a well-known herbal medicine used in Asia.

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit.

Delayed tooth extraction socket (TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils (ANs), and neutrophil extracellular traps (NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium (CM) collected from berberine-treated human bone marrow mesenchymal stem cells (BBR-HB-CM) accelerated TES healing.

Protocatechuic aldehyde sensitizes BRAF-mutant melanoma cells to temozolomide through inducing FANCD2 degradation.

Temozolomide (TMZ)-based chemotherapy is a primary regimen for melanoma patients who have failed targeted therapy or immunotherapy. However, the low response rate of TMZ-based chemotherapy challenges the patients' prognosis. BRAF mutation is the most frequently mutated site in melanoma.

SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis.

Metabolic requirements of dividing hepatocytes are prerequisite for liver regeneration after injury. In contrast to transcriptional dynamics during liver repair, its metabolic dependencies remain poorly defined. Here, we screened metabolic genes differentially regulated during liver regeneration, and report that SLC13A2, a transporter for TCA cycle intermediates, is decreased in rapid response to partial hepatectomy in mice and recovered along restoration of liver mass and function.

Personalized Medicine Through Semisolid-Extrusion Based 3D Printing: Dual-Drug Loaded Gummies for Enhanced Patient Compliance.

Purpose: The purpose of this research was to develop and characterize dual-drug Isoniazid-Pyridoxine gummies using Semisolid Extrusion (SSE) 3D printing technology, aimed at personalized dosing for a broad patient demographic, from pediatric to geriatric. This study leverages SSE 3D printing, an innovative approach in personalized medicine, to enable precise dose customization and improve patient adherence. By formulating dual drug-loaded gummies, the research addresses the challenges of pill burden and poor palatability associated with traditional tuberculosis regimens, ultimately enhancing the therapeutic experience and effectiveness for patients across various age groups.

Pharmacogenomic curriculum in Australian medical schools: a content analysis study.

Aims: To ascertain and describe pharmacogenomic concepts included in the intended curriculum of accredited Australian medical schools.

Methods: Content analysis of curriculum learning objectives of Australian medical schools was conducted, focusing on keywords and phrases pertaining to pharmacogenomic education. Learning objectives related to pharmacogenomics were categorized using (1) undergraduate medical genomic competencies per the Association of Professors in Human and Medical Genetics (2) Bloom's Taxonomy for cognitive and knowledge dimensions and (3) knowledge translation (enabling science, translation science and clinical implementation).

Advances in CRISPR-Cas systems for kidney diseases.

Recent advances in CRISPR-Cas systems have revolutionised the study and treatment of kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), lupus nephritis (LN), and polycystic kidney disease (PKD). CRISPR-Cas technology offers precise and versatile tools for genetic modification in monogenic kidney disorders such as PKD and Alport syndrome. Recent advances in CRISPR technology have also shown promise in addressing other kidney diseases like AKI, CKD, and DKD.

Discovery of Selenium-Containing Derivatives as Potent and Orally Bioavailable GLP-1R Agonists.

Glucagon-like peptide-1 receptor (GLP-1R) is a well-established target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. The development of orally bioavailable and long-acting small-molecule GLP-1R agonists is a pursuit in both academia and industry. Herein, new selenium (Se)-containing compounds were designed using a Se-oxygen bioisostere strategy on the danuglipron scaffold.

New alkaloids from Melodinus fusiformis and their cytotoxic activities.

Four new alkaloids, meloformisine A (1), meloformine B (2), meloformine F (3), meloformine G (4), along with five known alkaloids (5-9) were isolated from the leaves and twigs of Melodinus fusiformis. Their structures were elucidated on the basis of detailed spectroscopic evidence, including 1D and 2D NMR, MS, and single-crystal X-ray diffraction analysis. The structure of 1 was a novel indole alkaloid with an unprecedented 6/5/5/5/5 pentacyclic skeleton.

The effect of different wall materials on the physicochemical properties and antioxidant activity of pomegranate peel polyphenols (PPP) microcapsules.

Pomegranate peel polyphenols (PPP) are natural compounds known for their various biological activities; however, they are easily degraded by environmental conditions, leading to a reduction in their biological activity and health benefits. Therefore, improving the stability of PPP is a critical question that needs to be addressed. This study aimed to evaluate the efficacy of five common microcapsule wall materials-carboxymethyl cellulose sodium (CMCNa), sodium alginate (SA), gum Arabic (GA), beta-cyclodextrin (β-CD), and hydroxypropyl starch (HPS)-in encapsulating PPP to enhance its stability and antioxidant activity.

Application prospect of polysaccharide in the development of vaccine adjuvants.

Vaccination is an effective strategy for preventing infectious diseases. Subunit vaccines offer more precise targeting and safer protection compared with traditional inactivated virus vaccines. However, due to their poor immunogenicity, subunit vaccines necessitate the use of adjuvants to stimulate the immune system.

A nanobody-enzyme fusion protein targeting PD-L1 and sialic acid exerts anti-tumor effects by C-type lectin pathway-mediated tumor associated macrophages repolarizing.

Aberrant sialylated glycosylation in the tumor microenvironment is a novel immune suppression pathway, which has garnered significant attention as a targetable glycoimmune checkpoint for cancer immunotherapy to address the dilemma of existing therapies. However, rational drug design and in-depth mechanistic studies are urgently required for tumor sialic acid to become valuable glycoimmune targets. In this study, we explored the positive correlation of PD-L1 and sialyltransferase expression in clinical colorectal cancer tissues and identified their mutual regulation effects in macrophages.

Crepidamycins A-E, pyranonaphthoquinones from endophytic Streptomyces sp. MG-F-1 of Dendrobium crepidatum by the co-culture strategy.

On the basis of the co-culture strategy, five previously undescribed S-bridged pyranonaphthoquinones, crepidamycins A-E (1-5) and five known analogues (6-10) were isolated from a medicinal plant endophytic Streptomyces sp. MG-F-1 in Dendrobium crepidatum with Bacillus cereus MG-1. The structures and absolute configurations of 1-5 were elucidated by the interpretation of data from detailed spectroscopic analysis and electronic circular dichroism spectra, together with consideration of the biogenetic origins.

Vanillin and IGF1-loaded dual-layer multifunctional wound dressing with micro-nanofibrous structure for full-thickness wound healing acceleration.

Multifunctional dual-layer wound dressings hold significant promise for comprehensive full-thickness wound management by closely mimicking the native skin structure and features. Herein, we employed an innovative approach utilizing electrospinning techniques to develop a dual-layer dressing comprising a microfibrous Ecoflex®-Vanillin (Ex-Vnil) top layer (TL) and a nanofibrous Soluplus®-Insulin-like growth factor-1 (Sol-IGF1) bottom layer (BL). The tensile properties of dual-layer wound dressings were within the standard range for use in skin tissue regeneration.

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.

Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.

We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1 ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays.

Synergistic suppression of cell growth: Phenmiazine derivatives targeting p53 and MDM2 unveiled through hybrid computational method.

Lung cancer is the leading cause of mortality in both men and women due to genetic and epigenetic modifications. Our study focuses on fabricating phenmiazine ring leads by a functional group-based drug design to inhibit p53 -7A1W and MDM2-7AU9 proteins responsible for cancer cell growth. One hundred molecules are designed and allowed to bind inside the active site of 7A1W and 7AU9 protein using a glide dock platform and subjected to find MMGBSA.

Rapid determination of etomidate and its structural analogues in e-liquid by probe electrospray ionization quadrupole time-of-flight mass spectrometry.

Etomidate and its structural analogues, which have anesthetic effects, are classified as controlled psychotropic drugs. Electronic cigarettes (e-cigarettes) have become more and more popular. With the increase of adding etomidate and its analogues to electronic liquids (e-liquids), there is a trend of abuse, which is a tough problem urgently need to be solved.

Insights into tumor-derived exosome inhibition in cancer therapy.

Exosomes are critical mediators of cell-to-cell communication in physiological and pathological processes, due to their ability to deliver a variety of bioactive molecules. Tumor-derived exosomes (TDEs), in particular, carry carcinogenic molecules that contribute to tumor progression, metastasis, immune escape, and drug resistance. Thus, TDE inhibition has emerged as a promising strategy to combat cancer.