Structure-Activity Relationship Studies of DNA Methyltransferase 1 Monovalent Degraders.

DNA methyltransferase 1 (DNMT1), which catalyzes maintenance methylation of hemimethylated DNA during DNA replication, is overexpressed in cancer. Recently, the first-in-class DNMT1-selective noncovalent small-molecule inhibitors, GSK3484862 and GSK3685032, were discovered. These inhibitors were also reported to degrade DNMT1.

L-shaped association between ankle-brachial index and coronary heart disease in Chinese adults with hypertension.

Background: Prior research has established that an ankle-brachial index (ABI) ≤ 0.9 is positively correlated with cardiovascular events, including coronary heart disease (CHD). The present study aimed to elucidate the dose-response relationship between ABI and CHD within a hypertensive population.

Induces Disturbance of Kynurenine Metabolism Through the Gut-Brain Axis: Implications for Alzheimer's Disease.

is one of the major pathogens of chronic periodontitis. can cause systemic inflammation, amyloid β protein deposition, and hyperphosphorylation of tau protein, leading to Alzheimer's disease (AD)-like lesions. oral infection causes gut microbiota alteration, gut barrier dysfunction, and intestinal immune response and inflammation.

Comparative efficacy of cetuximab combined with FOLFOX or CAPEOX in first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer: a multicenter case-control study.

FOLFOX combined with cetuximab is a recommended first-line treatment regimen for RAS/BRAF wild-type metastatic colorectal cancer (mCRC). CAPEOX combined with cetuximab differs from the FOLFOX regimen by using oral capecitabine instead of continuous infusion of fluorouracil, offering greater convenience and cost-effectiveness with higher patient acceptance. However, the comparative efficacy of these two regimens remains debatable, necessitating further evidence to explore any differences in their efficacy.

Cynaroside ameliorates TNBS-induced colitis by inhibiting intestinal epithelial cell apoptosis via the PI3K/AKT signalling pathway.

Background And Aims: Patients with Crohn's disease (CD) exhibit excessive apoptosis of intestinal epithelial cells (IECs), which contributes to damage to the intestinal barrier structure and function, thereby playing a role in the progression of colitis. Preventing IEC apoptosis and protecting the intestinal barrier are critical to alleviating colitis. Natural plant monomers have been reported to possess multiple pharmacological properties, particularly with the potential to treat CD.

Sources of polycyclic aromatic hydrocarbons exposure and their effects on glycolipid metabolism in pregnant women and their newborn in Haikou City, China.

Background: Polycyclic aromatic hydrocarbons (PAHs) are a class of large organic compounds that persist in the environment and are classified as an important subset of persistent organic pollutants (POPs). This study aimed to assess PAH exposure in pregnant women and newborns in Haikou City, China, and evaluate their impact on glycolipid metabolism.

Methods: A total of 300 pregnant women and their newborns were selected for the study between May 2022 and December 2023.

Hypoxia-Mimicking Microenvironment Scaffold for Enhanced Tendon Regeneration.

Tendon, a connective tissue structure, serves the crucial role of transmitting force between muscles and bones. However, tendon injury repair continues to pose a significant challenge in clinical settings. In this study, we utilized single-cell RNA sequencing to delve into the cell populations and signaling pathways that are integral to tendon healing.

Compensatory synaptotagmin-11 expression conceals parkinson's disease-like phenotypes in parkin knockout mice.

Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson's disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive.

Adrenocorticotropic Hormone versus Prednisolone for Infantile Epileptic Spasms Syndrome: A Systematic Review and Economic Evaluation.

Background:  Infantile epileptic spasms syndrome (IESS) is the most common epileptic encephalopathy in infancy and early childhood. At present, adrenocorticotropic hormone (ACTH) and prednisolone are commonly used as drug treatment regimens for IESS. However, evidence of efficacy and economics remains controversial.

CircMETTL6 Suppresses Ovarian Cancer Cell Growth and Metastasis Through Inhibition of GDF15 Transcription by Disrupting the NONO-POLR2A Complex.

Circular RNAs (circRNAs) are a distinctive class of non-coding RNAs with covalent closed-loop structure, lacking 5' caps and 3' poly(A) tails. These molecules are prevalent in eukaryotes and play key roles in cancer. Here, the function of a new circRNA, circMETTL6, in ovarian cancer is identified and investigated.

A comprehensive view of the molecular features within the serum and serum EV of Alzheimer's disease.

Conventional Alzheimer's disease research mainly focuses on cerebrospinal fluid, which requires an invasive sampling procedure. This method carries inherent risks for patients and could potentially lower patient compliance. EVs (Extracellular Vesicles) and blood are two emerging noninvasive mediators reflecting the pathological changes of Alzheimer's disease.

Asymmetric Relay Catalysis Enables Unreactive Allylic Alcohols to Participate in 1,3-Dipolar Cycloaddition of Azomethine Ylides.

Current synthetic transformations occur readily with starting materials that possess both innate reactivity and steric accessibility or functional-group-oriented reactivity. However, achieving reactions with inactive feedstock substrates remains significantly challenging and normally requires cumbersome prior functional group manipulations. Herein, we report an unprecedented example of catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with nonactivated alkenes enabled by copper/ruthenium relay catalysis.

Preoperative Oral Carbohydrate for Lower Extremity Arthroplasty: A Systematic Review and Meta-Analysis.

Background: The purpose of this study was to evaluate the effects of preoperative oral carbohydrate (CHO) loading on postoperative insulin resistance, hospital stay, and pain in patients undergoing elective arthroplasty.

Methods: Clinical randomized controlled trials on the effects of preoperative oral CHO loading in patients undergoing elective hip and knee arthroplasty were searched on PubMed, Web of Science, Cochrane Library, Embase, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure (CNKI) from inception to February 2024. The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the enrolled randomized controlled trials.

Structural and catalytic insights into MhpB: A dioxygenase enzyme for degrading catecholic pollutants.

The increasing environmental pollution from persistent aromatic compounds requires effective biodegradation strategies. In this study, we focused on MhpB, an extradiol dioxygenase (EDO) from Escherichia coli. It is known for its role in the degradation of catechols, key intermediates in the degradation of aromatic compounds.

Neoadjuvant immunotherapy with or without chemotherapy in locally advanced oral squamous cell carcinoma: Randomized, two-arm, phase 2 trial.

Patients with locally advanced oral squamous cell carcinoma (OSCC) have poor outcomes with standard care. Neoadjuvant therapy is shown to be effective for these patients. In the randomized, two-arm, phase 2, non-comparative trial, we investigate the efficacy and safety of the neoadjuvant programmed cell death 1 (PD-1) inhibitor camrelizumab with or without docetaxel-cisplatin-5-fluorouracil (TPF) chemotherapy in patients with resectable locally advanced OSCC.

Sleep deprivation accelerates Parkinson's disease via modulating gut microbiota associated microglial activation and oxidative stress.

The interplay between Parkinson's disease (PD) and sleep disturbances suggests that sleep problems constitute a risk factor for PD progression, but the underlying mechanisms remain unclear. Microglial activation and oxidative stress are considered to play an important role in the pathogenesis of aging and neurodegenerative diseases. We hypothesized that sleep deprivation (SD) could exacerbate PD progression via modulating microglial activation and oxidative stress.

Inverse design and fabrication of high-efficiency perfectly vertical LNOI grating couplers.

A perfectly vertical grating coupler (GC) on X-cut lithium niobate on insulator (LNOI) platform is designed and demonstrated. The optimized random grating structure of GC is designed by an inverse design method and exhibits a simulated coupling efficiency of approximately -2.52 dB and measured coupling efficiency of approximately -3.

Atomically Dispersed Metal Atoms: Minimizing Interfacial Charge Transport Barrier for Efficient Carbon-Based Perovskite Solar Cells.

Carbon-based perovskite solar cells (C-PSCs) exhibit notable stability and durability. However, the power conversion efficiency (PCE) is significantly hindered by energy level mismatches, which result in interfacial charge transport barriers at the electrode-related interfaces. Herein, we report a back electrode that utilizes atomically dispersed metallic cobalt (Co) in carbon nanosheets (Co/CN) to adjust the interfacial energy levels.

Unveiling the conserved nature of chloroplast genomes: insights from the assembly and analysis of four complete chloroplast genomes.

Introduction: , a genus within the Zingiberales order, is renowned for its diverse morphology, suggesting a rich genetic reservoir. However, genetic research on plants within the family has primarily focused on taxonomy and phylogenetics, with limited exploration into other genetic aspects, particularly the chloroplast genome. Given the significance of chloroplast genomes in evolutionary studies, a deeper understanding of their structure and diversity within Heliconia is essential.

Cholic acid inhibits ovarian steroid hormone synthesis and follicular development through farnesoid X receptor signaling in mice.

This study investigated the effects of cholic acid (CA) on steroid hormone synthesis and follicular development in mouse ovaries and the regulatory mechanism of CA on the expression of steroidogenesis-related genes in granulosa cells. The mice were divided into control and CA groups, and serum and ovarian samples were collected after 1, 2, and 4 months of treatment, respectively. The results showed that CA treatment for 1, 2, and 4 months reduced ovarian weights, disrupted the estrous cycle, decreased the numbers of antral follicles and corpora lutea, and lowered the serum levels of progesterone and estradiol.

Relationship between the density of in soil at harvest evaluated using real-time PCR and sweetpotato disease incidence.

Sweetpotato Stem Rot Nematode () causes the most devastating disease affecting sweetpotato production in China. The objectives of this study were: i) establish a quantification method using real-time PCR for of sweetpotato; ii) analyze the effect of density at harvest on the percentage of disease incidence in sweetpotatoes; and iii) evaluate the effect of soil physical properties on disease incidence. Populations of isolated from 28 different production areas in Henan Province exhibited identical sequences, and then real-time PCR specific primers (PRNf and PRNr) were designed.

Parishin B blocking TRIB3-AKT1 interaction inhibits breast cancer lung metastasis.

Background: TRIB3 has been reported to mediate breast cancer (BC) proliferation and metastasis by interacting with AKT1, and blocking the interaction between TRIB3 and AKT1 can inhibit the progression of BC. Besides, inhibiting TRIB3 to turn "cold tumor" hot has also been proved to be an effective therapeutic strategy for BC. Thus, this study aim to find drugs that can bind to TRIB3 to inhibit BC progression, and further elucidate its mechanism.

Effect of long-term transcutaneous auricular vagus nerve stimulation in multiple system atrophy-cerebellar subtype: a case report.

Background: Multiple system atrophy-cerebellar subtype (MSA-C) is a predominance of cerebellar ataxia and autonomic failure. MSA-C has a rapid progression, with average 9 years from symptom onset to death. Despite its prevalence, there is still a lack of effective treatments.

Fabricating an antioxidant and bacteriostatic soy protein isolate film double-crosslinked via dialdehyde cellulose nanofibers and Tara tannins for beef tallow and cooked pork preservation.

Although Tara tannins (TT) have given soy protein isolate (SPI) film antioxidant properties, the mechanical and barrier properties were not significantly improved. In this work, dialdehyde cellulose nanofibers (DACNF) were obtained through oxidation using sodium periodate and incorporated into SPI film with TT to obtain antioxidant and bacteriostatic properties. With increased DACNF content, the anti-swelling, mechanical and barrier properties of SPI film were enhanced due to a double-crosslinked structure based on the covalent and hydrogen bonds formed between DACNF, TT and SPI.