Modulation of Abnormal Vasoconstriction Through 2-Hydroxyisobutyrylation of Tropomyosin 3 Lys141: Targeting Histone Deacetylase 3 as a Key Approach.

Background: TPM3 (tropomyosin 3) is an actin-binding protein in vascular smooth muscle cells, where posttranslational modifications critically regulate its actin affinity, influencing cardiovascular function. Emerging evidence suggests that Khib (2-hydroxyisobutyrylation) plays a significant role in the cardiovascular system. Histone deacetylase 3 (HDAC3) serves as an "eraser" of Khib marks.

colonic fermentation of fermented Radix Astragali by and anti-hyperuricemia mechanism based on network pharmacology and experiment verification.

Aim: This research aimed to probe the effects of fecal microbiota and on the metabolism of Radix Astragali (RA) and solid fermenting Radix Astragali (FRA). It further explores pharmacological effects of RA, , and FRA on HUA mouse model and the mechanisms in HUA treatment.

Methods: Fecal microbiota and were used to ferment FRA and RA in vitro to probe the impacts of microbiota on the metabolism of active compound.

Fabrication of Polydopamine-Coated High-Entropy MXene Nanosheets for Targeted Photothermal Anticancer Therapy.

Transition metal carbides, nitrides, and carbonitrides (MXenes) have emerged as a promising class of 2D materials that can be used for various applications. Recently, a new form of high-entropy MXenes has been reported, which contains an increased number of elemental species that can increase the configurational entropy and reduce the Gibbs free energy. The unique structure and composition lead to a range of intriguing and tunable characteristics.

The Application of Deuteration Strategy in Drug Design.

Deuterated drugs, which are derived by the subtle exchange of a protium atom with a deuterium atom in drugs, exhibits significant difference in the perspective of pharmaceutical characteristics compared with the parent drugs. With the advantages including improving pharmacokinetic properties, reducing toxicity, inhibiting the interconversion between chiral drugs and restricting the interaction between drugs, deuterated drugs have attracted widespread attention from medicinal chemists. This review highlights the application of deuteration strategy in drug design and summarizes the progress of all the deuterated drugs available in the market or deuterated agents under investigation, for the purpose of providing references for all researchers engaged in this direction of drug development.

Clerodane diterpenoids from the vine stems of Fibraurea recisa Pierre and their hepatic gluconeogenesis inhibitory activity.

Fibraurea recisa Pierre is a vine plant and its vine stems are used as a traditional Chinese medicine to treat heat toxin, constipation, diarrhea, sore throat, eye inflammation, carbuncles, and skin ulcers. The alkaloid chemical composition of this plant has been extensively studied; however, investigations into non-alkaloid components remain limited. In this study, phytochemical studies of the vine stems of F.

Discovery of SET domain-binding primary alkylamine-tethered degraders for the simultaneous degradation of NSD2-long and RE-IIBP isoforms.

Nuclear receptor binding SET domain protein 2 (NSD2) is involved in various pathologic processes and is considered as an important target for cancer therapy. Due to alternative splicing, NSD2 has 3 isoforms: long, short and RE-IIBP. Although previous studies reported the degradation of PWWP1 domain-containing NSD2-long and short isoforms through PWWP1-binding molecules, the degradation of RE-IIBP which does not contain PWWP1 has been neglected to date.

Carboxylations of (Hetero)Aromatic C-H Bonds Using an Alkyl Silyl Carbonate Reagent.

In this paper, we report that the use of an alkyl silyl carbonate reagent combined with CsF and 18-crown-6 facilitates efficient direct carboxylations of (hetero)aromatic C-H bonds. This system also enables benzylic carboxylation of a toluene derivative and double carboxylation of methyl heteroarene. The carbonate reagent is characterized by its ease of handling and storage.

[Comparison on pharmacokinetics of six active components of Tripterygium wilfordii Polyglycosides Tablets between normal rats and rat model of adjuvant arthritis].

This work aimed to investigate the pharmacokinetics of six major blood-entering components(triptolide, triptophenolide, wilforgine, wilforine, tripterine, and wilforlide A) in Tripterygium wilfordii Polyglycosides Tablets(TWPT) between normal rats and the rat model of adjuvant arthritis, which was established by injection of Freund's complete adjuvant. Liquid chromatography-mass spectrometry(LC-MS) was employed to determine the content of six main components in the serum samples of normal and arthritic rats after administration of TWPT, and the pharmacokinetics of the six components were compared between normal and model rats. The specificity, linearity, accuracy, precision, stability, extraction recovery and matrix effect of the established LC-MS method all met the requirements.

Diazonium-based derivatization for enhanced detection of phosphorylated metabolites by LC-MS in cells.

Phosphorylated small molecule metabolites play crucial roles in physiological processes such as glycogen metabolism and inflammation regulation. However, their high polarity, structural similarity, poor chromatographic separation, and weak mass spectrometric signals make their accurate quantification challenging, thereby hindering the study of related metabolic mechanisms and diseases. To address these challenges, we developed a novel derivatization reagent, DMQX (5-diazomethane quinoxaline), and combined it with liquid chromatography-mass spectrometry (LC-MS).

Visible-Light-Mediated Radical -Hydroboration of Alkynes with NHC Borane.

Although the radical hydroboration of alkenes with N-heterocyclic carbene (NHC) borane is well documented, the radical hydroboration of alkynes, especially terminal alkynes, remains challenging. Herein, a photoredox-catalyzed radical -hydroboration of alkynes with NHC borane has been developed, which provided various alkenyl boron compounds in moderate to good yields. This protocol exhibits a broad substrate scope, as both internal and terminal alkynes were compatible.

The generic version of China Health Related Outcomes Measures (CHROME-G): psychometric testing and comparative performance with the EQ-5D-5L and SF-6Dv2 among the Chinese general population.

Objectives: The CHROME-G is the first generic preference-based measure developed in China. This study aimed to validate and compare the psychometric properties of the CHROME-G with the EQ-5D-5L and SF-6Dv2 among the Chinese general population.

Methods: A representative sample of the Chinese general population in terms of age, gender, education, and urban/rural residence was recruited for an online survey.

Pulmonary toxicity assessment of tumor necrosis factor α inhibitors in the treatment of IBD: a real world study based on US food and drug administration adverse events reporting system (FAERS).

Background: Tumor necrosis factor α (TNF-α) inhibitors are widely used in the treatment of inflammatory bowel disease (IBD), but there is still a lack of systematic risk assessment for pulmonary toxicity.

Methods: We calculated the pulmonary-related risk signals for four TNF-α inhibitors using the disproportionality analysis and also compared them with the pulmonary-related signals of seven other therapies.

Results: There were 8736 reports of pulmonary-related adverse events (AEs) to TNF-α inhibitors as the 'primary suspect (PS)' therapies.

Photodegradation of Dacarbazine Catalyzed by Vitamin B and Flavin Adenine Dinucleotide Under Visible-Light Irradiation.

Purpose: Drug photodegradation is a matter of great concern because it can result in potency loss and adverse side effects. This study examines the light-induced degradation of dacarbazine catalyzed by vitamin B and flavin adenine dinucleotide (FAD) under light-emitting diode (LED) or fluorescent light irradiation.

Methods: Dacarbazine was irradiated with LED (405 nm) or fluorescent light in the presence of various equivalents of vitamin B or FAD.

Advances in nanomedicine for retinal drug delivery: overcoming barriers and enhancing therapeutic outcomes.

Nanomedicine offers a promising avenue for improving retinal drug delivery, effectively addressing challenges associated with ocular diseases like age-related macular degeneration and diabetic retinopathy. Nanoparticles, with their submicron size and customisable surface properties, enable enhanced permeability and retention within retinal tissues, supporting sustained drug release and minimising systemic side effects. Nanostructured scaffolds further provide a supportive environment for retinal cell growth and tissue regeneration, crucial for treating degenerative conditions.

Integrative study of lung cancer adeno-to-squamous transition in EGFR TKI resistance identifies RAPGEF3 as a therapeutic target.

Although adeno-to-squamous transition (AST) has been observed in association with resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in clinic, its causality, molecular mechanism and overcoming strategies remain largely unclear. We here demonstrate that squamous transition occurs concomitantly with TKI resistance in PC9-derived xenograft tumors. Perturbation of squamous transition via DNp63 overexpression or knockdown leads to significant changes in TKI responses, indicative of a direct causal link between squamous transition and TKI resistance.

Unraveling the Guardian: p53's Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies.

DNA damage can lead to mutations that can alter the function of oncogenes or tumor suppressor genes, thus promoting the development of cancer. p53 plays a multifaceted and complex role in the DNA damage response and cancer progression and is known as the 'guardian of the gene'. When DNA damage occurs, p53 is activated through a series of post-translational modifications, which stabilize the protein and enhance its function as a transcription factor.

Effects of Three Modification Methods on the In Vitro Gastrointestinal Digestion and Colonic Fermentation of Dietary Fiber from Lotus Leaves.

Shear emulsifying (SE), ball milling (BM), and autoclave treatment (AT) were utilized for the modification of lotus leaves, and the effects on in vitro gastrointestinal digestion and colonic fermentation of insoluble dietary fiber (IDF) from lotus leaves were compared. Compared with SEIDF and ATIDF, BMIDF released more polyphenols and exhibited better antioxidant capacity during in vitro gastrointestinal digestion. The IDF of lotus leaves changed the gut microbiota composition during in vitro colonic fermentation.

Bioequivalence of cefdinir dispersible tablets in healthy Chinese subjects under fasting and fed conditions: a single-centred, randomized, open, single-dose, two-preparation, two-cycle, two-sequence, double-crossover trial.

Cefdinir is a broad-spectrum antibiotic with good antibacterial activity against gram-positive and gram-negative bacteria and can be used for the treatment of various sensitive bacterial infections, such as community-acquired pneumonia, urinary tract infection and gonorrhoea. Herein, a single-centred, randomized, open, single-dose, two-preparation, two-cycle, two-sequence, double-crossover trial with a 7-day washout was conducted to investigate the pharmacokinetics, bioequivalence and safety of cefdinir dispersible tablets and the reference formulation of cefdinir capsules in healthy Chinese volunteers. Fifty-six healthy subjects were recruited and randomly assigned to the fasting and fed groups.

CISepsis: a causal inference framework for early sepsis detection.

Introduction: The early prediction of sepsis based on machine learning or deep learning has achieved good results.Most of the methods use structured data stored in electronic medical records, but the pathological characteristics of sepsis involve complex interactions between multiple physiological systems and signaling pathways, resulting in mixed structured data. Some researchers will introduce unstructured data when also introduce confounders.

Low-calorie and high-protein diet has diverse impacts on the muscle, bone, and bone marrow adipose tissues.

The present study was designed to evaluate the influence of a high-protein diet under conditions of calorie restriction (CR) in the muscle, adipose tissue, bone, and marrow adipose tissue (MAT). It included three groups of 20 female Wistar Hannover rats, fed with the following diets for 8 wk: control group (C) fed with an AIN93M diet, CR group (R) fed with an AIN-93M diet modified to 30% CR, and CR + high-protein group (H) fed with an AIN-93M diet modified to 30% CR with 40% protein. Body composition was determined by DXA.

Breaking barriers: advancing cellular therapies in autoimmune disease management.

Autoimmune diseases occur due to a dysregulation within the immune system, leading to an aberrant assault on the organism's own tissues. The pathogenesis of these conditions is multifactorial, encompassing intricate interplays among genetic predispositions, environmental determinants, and hormonal fluctuations. The spectrum of autoimmune diseases is broad, impacting a multitude of organ systems, with notable examples such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), psoriasis, and vitiligo.

The FLOWERING LOCUS T-like genes from patchouli (Pogostemon cablin) antagonistically regulate flowering time.

Flowering is crucial for the reproductive success of plants. Patchouli (Pogostemon cablin), a widely utilized medicinal and aromatic plant from the Lamiaceae family, exhibits rare flowering and fails to produce seeds, thereby posing a challenge for plant evolution and breeding improvement. However, the mechanism underlying flowering in patchouli has not been investigated.

Voagafries A-E, undescribed indole alkaloids with anti-glioma activity from Voacanga africana.

Voagafries A-E, five undescribed monoterpenoid indole alkaloids (MIAs), were isolated from the stem bark of Voacanga africana. Voagafrie A (1) has a unique 6/5/5/6/6 spiral ring skeleton with an indolone-fused 9-oxo-3-aza-tricyclo[6,3,1,0]-12-alkane-10-carbonyllactone. Voagafrie B (2) is a rare 5,6-seco diazine scaffold, whereas voagafrie C (3) possesses an octahydropyrrolo[2,3-b] pyrrole-fused 2,8-diazabicyclo[3.