Process optimizations for the synthesis of an intermediate of dydrogesterone.

Dydrogesterone (DG) is a potent progesterone drug that can be used to treat almost all progesterone-deficiency in women. However, there are few reports on DG process studies, and the by-products are unclear, which make the process optimization challenging. In this paper, we report the process optimization studies for the synthesis of 9α,10β-pregest-5,7-diene-3,20-diethylene glycol ketone (1), an intermediate of DG.

Targeting regulation of lipid metabolism with polysaccharide of traditional Chinese medicine for the treatment of non-alcoholic fatty liver disease: A review.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic diseases in the world, and the effective treatment of NAFLD has been listed as a key problem to be solved urgently in contemporary medicine. Polysaccharides in traditional Chinese medicine (TCM) have a wide range of pharmacological activities. A large number of preclinical studies have confirmed that TCM polysaccharides can interfere with the occurrence and development of NAFLD at multiple interrelated levels, such as improving lipid metabolism and insulin resistance, regulating oxidative stress, alleviating immune inflammatory response, and regulating intestinal microbiota, thus showing great potential as a new anti-NAFLD drug.

Effects of Tai Chi on Multiple Brain Networks Structure-Function Couplings in Individuals with Subthreshold Depression: A Randomized Controlled Trial.

Introduction: Subthreshold depression represents a prodromal stage of major depressive disorder and may be associated with abnormalities in brain structural and functional networks. While studies have shown that mind-body exercises such as Tai Chi can alleviate subthreshold depression, the underlying mechanisms remain unclear. Purpose: This study aimed to explore the potential mechanisms of Tai Chi for improving subthreshold depression from the perspective of structure-function coupling of brain networks.

Discovery of novel tranylcypromine-indazole-based derivatives as LSD1 inhibitors for acute myeloid leukemia treatment.

As an epigenetic enzyme, Lysine-specific demethylase (LSD1) has emerged as a promising target for cancer therapy. Based on the structure of tranylcypromine indazole, a series of LSD1 inhibitors have been designed and synthesized in this work. Most compounds have excellent inhibitory activity against LSD1.

EXPRESS: Facial attractiveness influenced cooperative behavior in the Stag Hunt game: evidence from neural electrophysiology.

Facial attractiveness plays a significant role in interpersonal interactions, influencing various aspects of life. This study is the first to explore, from a neurological perspective, the impact of facial attractiveness on individual cooperative behavior in the context of the Stag Hunt game. 26 participants took part in a two-person Stag Hunt experimental task while their electroencephalogram (EEG) data was recorded.

Dynamic metabolic profiling of sea cucumbers (Apostichopus japonicus) under predation stress.

The present study utilized non-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the metabolomic responses of sea cucumber (Apostichopus japonicus) juveniles under predation stress induced by sea stars (Asterina pectinifera) at various time points (3 h, 12 h, 72 h, and 96 h). The findings revealed significant temporal changes in the metabolic profiles of the sea cucumber juveniles under predation stress, with 25, 72, 55, and 53 metabolic products exhibiting significantly different expression levels at each time point (positive ion mode, P < 0.05), respectively.

A Novel Natural Penetration Enhancer for Transdermal Drug Delivery: In Vitro/In Vivo Evaluation and Penetration Enhancement Mechanism.

: This study aimed to identify and develop a novel, safe, and effective transdermal penetration enhancer derived from the leaves of (L.) Britt, and to explore the underlying mechanisms of its penetration enhancement effects. : To evaluate the safety profile of the penetration enhancer, both skin irritation tests and histopathological analyses were conducted.

The mutualistic relationship between M2c macrophages of TGFβ1 induction and gastric cancer cells: the correlation between protective mechanisms in the tumor microenvironment and polarization of subtypes of cells.

Gastric cancer (GC) is one of the most common malignant tumors worldwide, with fast metastasis and high mortality rate. GC cells and tumor immune microenvironment exhibit high heterogeneity. Multiple pieces of evidence suggest that TGFβ1 intervenes in the tumor microenvironment, immune cells and GC prognosis.

Combined heavy metals (As and Pb) affects antioxidant status and lipid metabolism in zebrafish (Danio rerio).

The potential risk of coexistence of mixed heavy metals in the aquatic environment has increased with the development of technology. Lead (Pb) and arsenic (As) are among the most widely applied heavy metals, whose single toxicity has been extensively investigated, but their combined toxicity has been reported relatively rarely. In this study, different concentrations of Pb (40 μg/L, 4 mg/L), As (32 μg/L, 3.

Targeting ferroptosis in the treatment of ulcerative colitis by traditional Chinese medicine: A novel therapeutic strategies.

Background: The incidence of ulcerative colitis (UC) has been rising rapidly in recent years, and there is currently no effective method to prevent its recurrence. Owing to its long treatment duration, difficulty in treatment, prolonged remission, and high costs, it has attracted global attention. Exploring safe, effective, and sustainable treatment regimens has become an urgent global issue.

WNT inhibitor SP5-mediated SERPING1 suppresses lung adenocarcinoma progression via TSC2/mTOR pathway.

The long-term outlook for patients grappling with lung cancer (LC) remains bleak, with lung adenocarcinoma (LUAD) emerging as the most predominant histological subtype. Our Mendelian randomization (MR) investigation spotlighted that heightened levels of the circulating protein serpin peptidase inhibitor family G1 (SERPING1) substantially mitigated LC risk. The fusion of multi-omics strategies unveiled that SERPING1 exhibited diminished expression in LUAD patients compared to healthy individuals both in tissues and serum, with LUAD individuals showcasing elevated SERPING1 expression demonstrating improved prognoses.

Thienopyrimidine: A promising scaffold in the development of kinase inhibitors with anticancer activities.

Protein kinases represent a highly promising drug target, with over 80 drugs that target about two dozen different protein kinases have been approved by the US FDA, particularly in cancer treatment. Over the past decades, the unique structural characteristics of the thienopyrimidine ring system provide an adaptive platform for designing potent anticancer agents, especially various kinase inhibitors, which has attracted widespread attention. Some of these thienopyrimidines as anticancer kinase inhibitors have already been marketed or are currently undergoing clinical/preclinical studies for the treatment of cancers, such as Olmutinib, Pictilisib, SNS-314, PF-03758309, and Fimepinostat, highlighting the substantial advantages of the thienopyrimidine scaffold in the discovery of anticancer agents.

Morphological development of the endosperm epidermal cells in waxy wheat cultivars.

Endosperm epidermal cells (EECs) accumulate large quantities of nutrients; they also play key roles in facilitating solute transport. Comprehensive knowledge about the dynamic development of EECs is needed to understand the relationship between their dual functions. In this study, the developmental characteristics of EECs in wheat grains of two near-isogenic lines (Shimai19-P and Shimai19-N) and in the parent wheat cultivar Shimai19 were compared using light and scanning electron microscopy.

Numerical investigation of production performance of challenging gas hydrates from deposits with artificial fractures and impermeable barriers.

In this research, a novel reservoir stimulation scheme combining impermeable artificial barriers and high-conductivity artificial fractures was introduced for gas hydrate extraction from clayey silt deposits, and the injection-production performance was numerically investigated using hydrates at the Shenhu SH2 site as the typical case scenario. The results indicated that impermeable barriers effectively addressed the challenges including boundary water intrusion, decomposition gas leakage, and injected hot fluid loss. Especially, artificial barriers and fractures exert a synergistic stimulation effect of "1 + 1 > 2".

Discharge transition experience and nursing needs of elderly patients with hip fracture: A qualitative systematic review.

Background: Unmet nursing needs during hospital discharge for elderly patients with hip fractures may lead to increased readmission rates and mortality.

Objective: To investigate the discharge transition experience and nursing needs of elderly patients with hip fracture.

Methods: Five electronic databases (PubMed, Web of science, Ovid, CINAHL, Embase) were searched from Jan.

Discovery of 2,4-diaminopyrimidine derivatives as potent inhibitors of FAK capable of activating the Hippo pathway for the treatment of esophageal squamous cell carcinoma.

In this work, we report the discovery of 2,4-diaminopyrimidine derivatives bearing a urea moiety as FAK inhibitors capable of activating the Hippo pathway in Esophageal Squamous Cell Carcinoma (ESCC). Extensive structure-activity relationship studies were conducted based on the lead FAK inhibitor TAE-226 to enhance the inhibitory potency, and the most potent compound 8b (MY-1576) as a FAK inhibitor ultimately was identified. Compound MY-1576 exhibited potent FAK inhibitory activity, in vitro anticancer activities, and acceptable PK properties.

Bionic Olfactory Neuron with In-Sensor Reservoir Computing for Intelligent Gas Recognition.

Gas sensing and recognition are closely related to the sustainable development of human society, current electronic noses (e-noses) typically focus on detecting specific gases, with only a few capable of recognizing complex odor mixtures. Further, these sensors often struggle to distinguish between isomers and homologs, as these compounds usually have similar physical and chemical properties, yielding nearly identical sensor responses. Even the mammalian olfactory systems consisting of a large variety of receptor cells and efficient neuron networks sometimes fail in this task.

Continuous Hyaluronic Acid Supply by a UHMWPE/PEEK Interlocking Scaffold for Metatarsophalangeal Joint Prosthesis Lubricating Applications.

Wear is one of the main causes of prothesis failure in hemiarthroplasty of small joints such as the metatarsophalangeal joint, to which lubrication improvement is a promising solution. Inspired by the natural joint structure and lubrication mechanisms, we developed a novel composite strategy for metatarsophalangeal joint hemiarthroplasty. An ultrahigh-molecular-weight polyethylene (UHMWPE) lubrication layer is interlocked within a 3D-printed poly(ether ether ketone) (PEEK) scaffold, and hyaluronic acid (HA) is introduced for hydrophilic modification of the UHMWPE matrix.

Gushan virus: a newly discovered virus found in mosquitoes of Shandong, China.

Arboviruses persist as a significant threat to global public and human health. The advent of macrogenomics technology has substantially expanded our understanding of mosquito-borne viruses by facilitating the direct identification and characterization of viruses from diverse environmental samples. In 2022, we conducted mosquito surveillance in the Shandong region of China and discovered a novel virus, tentatively named Gushan virus based on the site of discovery.

Early neuroimaging features of subthreshold depression: Abnormalities in frontoparietal white matter microstructure and functional activity.

Subthreshold depression (StD) is a prevalent mood disorder, and may be at higher risk of depression. Although previous neuroimaging studies have investigated brain abnormalities in StD, the changes of structure and functional activities in the frontoparietal network (FPN) remain far from be elucidated. In the present study, we aimed to investigate structural and functional activity changes in FPN among young individuals with StD, utilizing diffusion tensor imaging (DTI) and functional magnetic resonance imaging(fMRI).

Dynamic molecular responses of the sea urchin Strongylocentrotus intermedius to pathogen infection: Insights from a serial comparative transcriptome analysis.

To explore the dynamic molecular responses to pathogen infection in sea urchins, the sea urchin Strongylocentrotus intermedius were infected by a causative pathogen strain of sea urchin black peristomial membrane disease. Specimens were collected at 0, 6, 12, 24, 48, 72, and 96 h post-infection (hpi), and comparative transcriptome analysis were performed. The results showed that 1) a total of 771, 1437, 3477, 8417, 1566, and 2171 differentially expressed genes (DEGs) were identified at 6, 12, 24, 48, 72, and 96 hpi compared with the 0 hpi (as the control), respectively.

Educational assortative mating and couples' linked occupational trajectories in China.

Educational assortative mating profoundly influences couples' division of labor; however, we know little about how it shapes couples' paired occupational trajectories. We employed multi-channel sequence analysis to discern types of couples' linked occupational trajectories based on the couple-level data from China Labor-force Dynamics Survey (CLDS), and multinomial logistic models to examine how educational assortative mating is associated with couples' occupational trajectories. For most occupational types, husbands had more advantaged or at least similar occupational trajectories than their wives.

Strong and tough adhesive hydrogel based on polyacrylate/carboxylated cellulose nanofibers/Zr for high-sensitivity motion monitoring and controlled transdermal drug delivery.

Monitoring athletes' movement is crucial for health management and personalized care. Targeted, controlled drug delivery can also enhance treatment effectiveness for chronic pain from issues like muscle strain or joint inflammation. Therefore, multifunctional materials are needed to integrate monitoring, diagnosis, intervention, and treatment within a single system.

A novel EYA1 splicing mutation in a Chinese branchio-oto syndrome family with functional analysis and reproductive intervention.

Objectives: Branchio-oto syndrome (BOS) is a group of autosomal dominant genetic diseases, multisystem disorders excluding renal anomalies. There are clinical heterogeneity and ethnic diversity in BOS, which reported in more studies in European populations than in Asian populations, with a prevalence rate of approximately 1/40000. As the most common disease-causing gene, the mutation types of EYA1 range from missense to various frameshift, splicing and nonsense variants.

Language function improvement and cortical activity alteration using scalp acupuncture coupled with speech-language training in post-stroke aphasia: A randomised controlled study.

Background: Scalp acupuncture is commonly used as a complementary treatment to improve language function in patients with post-stroke aphasia. Our objectives were to evaluate the impact of scalp acupuncture on the cerebral cortex of post-stroke aphasia patients.

Methods: This assessor-blinded, parallel-arm design, single-center, randomized clinical trial recruited 64 patients with post-stroke aphasia.