Bicyclic polyprenylated acylphloroglucinol-related meroterpenoids as potent DRAK2 inhibitors from Hypericum patulum.

As a both edible and medicinal plant, Hypericum patulum (Hypericaceae) is used as a natural herbal tea, scented tea, and folk medicine. In this study, eight undescribed bicyclic polyprenylated acylphloroglucinol-related meroterpenoids named hyperpatins A-H, along with eight known ones, were isolated from this plant. Their structures were elucidated on the basis of spectroscopic techniques, chemical method, X-ray crystallographic experiments, and electronic circular dichroism analyses.

[ Injection inhibits peritoneal dialysis fluid-induced endothelial-mesenchymal transition in HMrSV5 cells by regulating the TGF-β/Smad signaling pathway].

Objectives: To investigate the inhibitory effect of Danshen Injection on endothelial-mesenchymal transition (EndMT) induced by peritoneal dialysis fluid in HMrSV5 cells and the role of the TGF‑β/Smad signaling pathway in mediating this effect.

Methods: HMrSV5 cells cultured in 40% peritoneal dialysis solution for 72 h to induce EndMT were treated with 0.05%, 0.

Procalcitonin-guided use of antibiotic in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: a randomized clinical trial.

Objectives: The objectives of this study are to analyse the effect and safety of procalcitonin (PCT)-guided antibiotic therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods: We conducted a multicentre, open-label, randomized controlled trial amongst patients hospitalized for AECOPD in six hospitals in China. Enrolled patients were randomly assigned to either the PCT-guided group or the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy-guided group.

An oncoprotein CREPT functions as a co-factor in MYC-driven transformation and tumor growth.

Understanding the mechanisms behind MYC-driven oncogenic transformation could pave the way for identifying novel drug targets. This study explored the role of CREPT in MYC-induced malignancy by generating MYC-transformed mouse embryonic fibroblasts (MEFs) with conditional CREPT deletion. Our results demonstrated that the loss of CREPT significantly impaired MYC-induced colony formation and cell proliferation, indicating that CREPT is essential for the malignant transformation of MEFs.

Exploring the mechanism of carbamazepine decreasing testosterone levels based on cAMP/PKA/CREB pathway.

The aim of this study was to explore the molecular mechanisms underlying carbamazepine (CBZ)-induced testicular toxicity and testosterone reduction in rats. For this purpose, Sprague-Dawley (SD) rats were intervened with 200 mg/kg CBZ for 12 weeks, and R2C cells were exposed to CBZ at concentrations of 0.5, 1 and 1.

Research on the timing for subsequent water flooding in Alkali-Surfactant-Polymer flooding in Daqing Oilfield based on automated machine learning.

Determining the optimal timing for subsequent water flooding in Alkali-Surfactant-Polymer (ASP) flooding is essential to maximizing both the technical and economic outcomes of oilfield blocks. This study identified eight critical parameters that influence the benefits of ASP flooding and established parameter ranges based on data from completed blocks and actual field measurements. The optimal timing for subsequent water flooding was determined by evaluating cumulative net profit variations throughout the ASP flooding lifecycle.

Beyond mitochondrial transfer, cell fusion rescues metabolic dysfunction and boosts malignancy in adenoid cystic carcinoma.

Cancer cells with mitochondrial dysfunction can be rescued by cells in the tumor microenvironment. Using human adenoid cystic carcinoma cell lines and fibroblasts, we find that mitochondrial transfer occurs not only between human cells but also between human and mouse cells both in vitro and in vivo. Intriguingly, spontaneous cell fusion between cancer cells and fibroblasts could also emerge; specific chromosome loss might be essential for nucleus reorganization and the post-hybrid selection process.

Mechanistic insights into cadmium exacerbating 2-Ethylhexyl diphenyl phosphate-induced human keratinocyte toxicity: Oxidative damage, cell apoptosis, and tight junction disruption.

Organophosphate flame retardants 2-ethylhexyldiphenyl phosphate (EHDPP) and cadmium (Cd) are ubiquitous in environmental matrices, and dermal absorption is a major human exposure pathway. However, their detrimental effects on the human epidermis remain largely unknown. In this study, human keratinocytes (HaCaT cells) were employed to examine the toxicity and underlying mechanisms of co-exposure to EHDPP and Cd.

The Relationship between Different Delivery Timing and the Outcome of Premature Rupture of Membranes in Primiparous Women.

Objective: To investigate the relationship between different delivery timing and the outcome of premature rupture of membranes (PROM) in primiparous women.

Methods: Within the context of exploring optimal delivery strategies for managing PROM, we conducted a retrospective study at Shijiazhuang Fourth Hospital. From May 2019 to May 2022, a total of 400 single pregnant women with premature rupture of membranes (PROM) at different gestational weeks (28-36 weeks) were enrolled.

Transcutaneous auricular vagus nerve stimulation for epilepsy.

Background: Several studies have suggested that transcutaneous vagus nerve stimulation (tVNS) may be effective for the treatment of epilepsy. However, auricular acupoint therapy (including auricular acupuncture and auricular point-sticking therapy), a method of stimulating the vagus nerve, has been poorly reviewed. This systematic review is the first to categorize auricular acupoint therapy as transcutaneous auricular vagus nerve stimulation (taVNS), aiming to assess the efficacy of taVNS in patients with epilepsy (PWE), and to analyse the results of animal experiments on the antiepileptic effects of taVNS.

Spatial distribution characteristics and influencing factors of traditional villages based on geodetector: Jiarong Tibetan in Western Sichuan, China.

Jiarong Tibetan is a regional group with distinctive regional characteristics and possess precious traditional village resources. Studying the spatial distribution and influencing factors of traditional villages is of vital significance for the protection and renewal of villages and the revitalization of cultural heritage. Nevertheless, due to the fact that the Jiarong Tibetan inhabited area has not been clearly defined for a long time, there is a lack of holistic discussion on the distribution features and driving mechanisms of traditional villages in this region.

Discovery of Oral AMP-Activated Protein Kinase Activators for Treating Hyperlipidemia.

Activation of AMP-activated protein kinase (AMPK) is proposed to alleviate hyperlipidemia. With cordycepin and N6-(2-hydroxyethyl) adenosine (HEA) as lead compounds, a series of adenosine-based derivatives were designed, synthesized, and evaluated on activation of AMPK. Finally, compound V1 was identified as a potent AMPK activator with the lipid-lowering effect.

Tit for tat? A study on the relationship between work connectivity behavior after-hours and employees' time banditry behavior.

Based on Conservation of Resources Theory, this study tries to reveal the mechanism of action of work connectivity behavior after-hours triggering employees' time banditry behavior. By using Mplus7.4 software the analysis of 429 leader-employee paired data collected in three stages reveals that work connectivity behavior after-hours has a positive effect on work alienation and psychological distress.

Effect of Shenqi Jieyu formula on inflammatory response pathway in hippocampus of postpartum depression rats.

Aim: To investigate whether SJF functions in similar manner as the key substance in the inflammatory process, soluble epoxide hydrolase (sEH) inhibitor, to inhibit the arachidonic acid metabolic pathway and nuclear factor kappa-B(NF-κB) signal path in the hippocampi of postpartum depression rats.

Methods: The rats were subcutaneous injected estradiol benzoate and progesterone to build PPD rat model. SJF, paroxetine hydrochloride and sEH inhibitor (AUDA) were used to treat PPD rats for 3 weeks.

Antiphospholipid antibody-related hepatic vasculitis in a juvenile after non-severe COVID-19: a case report and literature review.

Antiphospholipid antibodies (aPL) are both laboratory evidence and causative factors for a broad spectrum of clinical manifestations of antiphospholipid syndrome (APS), with thrombotic and obstetric events being the most prevalent. Despite the aPL-triggered vasculopathy nature of APS, vasculitic-like manifestations rarely exist in APS and mainly appear associated with other concurrent connective tissue diseases like systemic lupus erythematous. Several studies have characterized pulmonary capillaritis related to pathogenic aPL, suggesting vasculitis as a potential associated non-thrombotic manifestation.

Organophosphorus Flame Retardant TPP-Induced Human Corneal Epithelial Cell Apoptosis through Caspase-Dependent Mitochondrial Pathway.

A widely used organophosphate flame retardant (OPFR), triphenyl phosphate (TPP), is frequently detected in various environmental media and humans. However, there is little known on the human corneal epithelium of health risk when exposed to TPP. In this study, human normal corneal epithelial cells (HCECs) were used to investigate the cell viability, morphology, apoptosis, and mitochondrial membrane potential after they were exposed to TPP, as well as their underlying molecular mechanisms.

Health risk assessment of heavy metal(loid)s in road dust via dermal exposure pathway from a low latitude plateau provincial capital city: The importance of toxicological verification.

The human health risk assessment through the dermal exposure of metal (loid)s in dust from low latitude and high geological background plateau cities was largely unknown. In this study, the road dust samples were harvested from a typical low-latitude plateau provincial capital city Kunming, Southwest China. The total concentration and dermal bioaccessibility of heavy metal (loid)s in road dust were determined, and their health risks as well as cytotoxicity on human skin keratinocytes were also assessed.

Recognizing Functional Groups of MES/APG Mixed Surfactants for Enhanced Solubilization toward Benzo[]pyrene.

Benzo[]pyrene is difficult to remove from soil due to its high octanol/water partition coefficient. The use of mixed surfactants can increase solubility but with the risk of secondary soil contamination, and the compounding mechanism is still unclear. This study introduced a new approach using environmentally friendly fatty acid methyl ester sulfonate (MES) and alkyl polyglucoside (APG) to solubilize benzo[]pyrene.

The establishment of diseased human whole organ model by normothermic machine perfusion technique: Principle of concept.

Background: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers.

Simultaneous determination of BGT-002 and its acyl glucuronide metabolite ZM326E-M2 in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

BGT-002, a new type of ATP-citrate lyase inhibitor, is a promising therapeutic for treatment of hypercholesterolemia. After an oral administration of BGT-002 to subjects, it underwent extensive metabolism and an acyl monoglucuronide (ZM326E-M2) on 1- carboxylic acid group was the major circulating metabolite. In this study, an LC-MS/MS method was developed and validated for the simultaneous determination of BGT-002 and ZM326E-M2 in plasma and the evaluation of their pharmacokinetic characteristics in humans.