Design, synthesis and biological evaluation of 3,3-dimethyl-2,3,4,9-tetrahydro-1H-carbazole derivatives as AcrB inhibitors with potent antibiofilm effect for reversing bacterial multidrug resistance.

A series of novel 3,3-dimethyl-2,3,4,9-tetrahydro-1H-carbazole derivatives were rationally designed, synthesized and evaluated for their biological activity as AcrB inhibitors. The compounds were assessed for their antibiotic potentiating effects, followed by evaluation of Nile Red efflux inhibition, and off-target effects including activity on the outer and inner bacterial membranes. Ten compounds potentiated antibiotic activity at sub-inhibitory concentrations, reducing the minimum inhibitory concentrations (MICs) of at least one of the tested antibiotics by at least 8-fold, with three derivatives (7c, 11g, and 11i) achieving 32-fold MIC reductions at 128 μg/mL.

Pulsed field ablation for idiopathic premature ventricular complexes: evaluation of acute and chronic lesion characteristics with cardiac magnetic resonance imaging.

Background: To date, data about pulsed field ablation (PFA) for ventricular arrhythmias are limited, and cardiac magnetic resonance (CMR) characteristics of acute and chronic PFA lesions in the ventricles have not been described. This study sought to examine feasibility and efficacy of premature ventricular complex (PVC) ablation using focal PFA, as well as assess acute and chronic lesion characteristics using CMR.

Methods: This was a prospective, single-arm study performed at two centers in China.

Application of Machine Learning in the Prediction of the Acute Aortic Dissection Risk Complicated by Mesenteric Malperfusion Based on Initial Laboratory Results.

Background: Mesenteric malperfusion (MMP) represents a severe complication of acute aortic dissection (AAD). Research on risk identification models for MMP is currently limited.

Methods: Based on a retrospective study of medical records from the Beijing Anzhen Hospital spanning from January 2016 to June 2022, we included 435 patients with AAD and allocated their data to training and testing sets at a ratio of 7:3.

Sr-MOF-based hydrogel promotes diabetic tissue regeneration through simultaneous antimicrobial and antiinflammatory properties.

Severe tissue dysfunction in diabetic patients has been a challenging clinical problem. Both bacterial infections and chronic inflammation contribute to diabetic microenvironmental disorders and poor tissue regeneration. In this paper, a composite hydrogel (Gelma@Sr-ZIF-8) was prepared by incorporating a strontium (Sr)-doped metal-organic framework (Sr-ZIF-8) into Gelatin methacryloyl (Gelma) hydrogel, which could reverse diabetic microenvironmental disorders and promote tissue regeneration in diabetic wounds.

A Deep Learning Model for Identifying the Risk of Mesenteric Malperfusion in Acute Aortic Dissection Using Initial Diagnostic Data: Algorithm Development and Validation.

Background: Mesenteric malperfusion (MMP) is an uncommon but devastating complication of acute aortic dissection (AAD) that combines 2 life-threatening conditions-aortic dissection and acute mesenteric ischemia. The complex pathophysiology of MMP poses substantial diagnostic and management challenges. Currently, delayed diagnosis remains a critical contributor to poor outcomes because of the absence of reliable individualized risk assessment tools.

Depletion of γ-glutamyl cyclotransferase suppresses the proliferation, migration and invasion of breast cancer cells accompanied by the activation of PI3K/AKT/mTOR pathway.

Breast cancer is a prevalent and deadly disease affecting women worldwide. Recent studies have shown that γ-glutamyl cyclotransferase (GGCT), an enzyme involved in glutathione metabolism, is consistently upregulated in various cancers. However, its specific role in breast cancer remains poorly understood.

CCN5-Derived Peptide Ameliorates Liver Fibrosis in Mice through Inhibiting the ERK1/2 and PI3K Signaling Pathways.

Liver fibrosis is a pathological process characterized by the activation of hepatic stellate cells (HSCs) and the excessive accumulation of extracellular matrix (ECM) proteins. Cellular communication network 5 (CCN5) has been recently recognized for its ability to counteract the profibrotic effects of CCN2 in fibrotic diseases. Herein, we report the discovery of a CCN5-derived peptide CDP199 that effectively suppresses HSC activation and reduces ECM protein deposition.

Terahertz Reconfigurable Planar Graphene Hybrid Yagi-Uda Antenna.

In this paper, we design a frequency reconfigurable antenna for terahertz communication. The antenna is based on a Yagi design, with the main radiating elements being a pair of dipole antennas printed on the top and bottom of a dielectric substrate, respectively. The director and reflector elements give the antenna end-fire characteristics.

Machine Learning Models With Prognostic Implications for Predicting Gastrointestinal Bleeding After Coronary Artery Bypass Grafting and Guiding Personalized Medicine: Multicenter Cohort Study.

Background: Gastrointestinal bleeding is a serious adverse event of coronary artery bypass grafting and lacks tailored risk assessment tools for personalized prevention.

Objective: This study aims to develop and validate predictive models to assess the risk of gastrointestinal bleeding after coronary artery bypass grafting (GIBCG) and to guide personalized prevention.

Methods: Participants were recruited from 4 medical centers, including a prospective cohort and the Medical Information Mart for Intensive Care IV (MIMIC-IV) database.

Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis metabolic regulation of histone H3K9 lactylation in epithelial cells.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored.

A Novel Signature Based on Angiogenesis-Related Genes Predicts the Prognosis and Immunotherapy Response in HER2-Positive Breast Cancer.

HER2-positive breast cancer is one of the most prevalent subtypes of breast cancer and represents a significant health concern for women worldwide due to its high morbidity and mortality rates. Recent studies have consistently underscored the pivotal role of angiogenesis in the development and progression of HER2-positive breast cancer. Here, we developed a prognostic signature based on angiogenesis-related genes (ARGs) to categorize HER2-positive breast cancer patients and provide insights into their survival outcomes.

Mussel-Derived and Bioclickable Peptide Mimic for Enhanced Interfacial Osseointegration via Synergistic Immunomodulation and Vascularized Bone Regeneration.

Inadequate osseointegration at the interface is a key factor in orthopedic implant failure. Mechanistically, traditional orthopedic implant interfaces fail to precisely match natural bone regeneration processes in vivo. In this study, a novel biomimetic coating on titanium substrates (DPA-Co/GFO) through a mussel adhesion-mediated ion coordination and molecular clicking strategy is engineered.

Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis.

The role of co-agonists of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) in chronic kidney disease (CKD) remains unclear. Herein we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease severity. Interestingly, GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic mice and non-diabetic mice undergoing unilateral ureteral obstruction (UUO).

Thrombospondin-1 promotes mechanical stress-mediated ligamentum flavum hypertrophy through the TGFβ1/Smad3 signaling pathway.

Lumbar spinal canal stenosis is primarily caused by ligamentum flavum hypertrophy (LFH), which is a significant pathological factor. Nevertheless, the precise molecular basis for the development of LFH remains uncertain. The current investigation observed a notable increase in thrombospondin-1 (THBS1) expression in LFH through proteomics analysis and single-cell RNA-sequencing analysis of clinical ligamentum flavum specimens.

A Novel Method for Filled/Unfilled Grain Classification Based on Structured Light Imaging and Improved PointNet+.

China is the largest producer and consumer of rice, and the classification of filled/unfilled rice grains is of great significance for rice breeding and genetic analysis. The traditional method for filled/unfilled rice grain identification was generally manual, which had the disadvantages of low efficiency, poor repeatability, and low precision. In this study, we have proposed a novel method for filled/unfilled grain classification based on structured light imaging and Improved PointNet++.

Discovery and Design of Novel Cyclic Peptides as Specific Inhibitors Targeting CCN2 and Disrupting CCN2/EGFR Interaction for Kidney Fibrosis Treatment.

Kidney fibrosis is a serious consequence of chronic kidney disease (CKD), and currently, there is no effective pharmacological treatment available. Cellular communication network-2 (CCN2/CTGF) is an extracellular matrix (ECM) protein that regulates the fibrotic process by activating the epidermal growth factor receptor (EGFR) signaling pathway. We herein present the discovery and structure-activity relationship study of novel peptides targeting CCN2 to develop potent and stable specific inhibitors of the CCN2/EGFR interaction.

Utilizing Metal-Thiocatecholate Functionalized UiO-66 Framework for Photocatalytic Hydrogen Evolution Reaction.

Exploiting clean energy is essential for sustainable development and sunlight-driven photocatalytic water splitting represents one of the most promising approaches toward this goal. Metal-organic frameworks (MOFs) are competent photocatalysts owing to their tailorable functionality, well-defined structure, and high porosity. Yet, the introduction of the unambiguous metal-centered active site into MOFs is still challenging since framework motifs capable of anchoring metal ions firmly are lacking.

Recent advances in responsive hydrogels for diabetic wound healing.

Poor wound healing after diabetes mellitus remains a challenging problem, and its pathophysiological mechanisms have not yet been fully elucidated. Persistent bleeding, disturbed regulation of inflammation, blocked cell proliferation, susceptible infection and impaired tissue remodeling are the main features of diabetic wound healing. Conventional wound dressings, including gauze, films and bandages, have a limited function.

Immunomodulatory biomaterials for implant-associated infections: from conventional to advanced therapeutic strategies.

Implant-associated infection (IAI) is increasingly emerging as a serious threat with the massive application of biomaterials. Bacteria attached to the surface of implants are often difficult to remove and exhibit high resistance to bactericides. In the quest for novel antimicrobial strategies, conventional antimicrobial materials often fail to exert their function because they tend to focus on direct bactericidal activity while neglecting the modulation of immune systems.

Revealing the novel autophagy-related genes for ligamentum flavum hypertrophy in patients and mice model.

Background: Fibrosis is a core pathological factor of ligamentum flavum hypertrophy (LFH) resulting in degenerative lumbar spinal stenosis. Autophagy plays a vital role in multi-organ fibrosis. However, autophagy has not been reported to be involved in the pathogenesis of LFH.

EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway.

The most common spinal disorder in elderly is lumbar spinal canal stenosis (LSCS). Previous studies showed that ligamentum flavum hypertrophy (LFH) with fibrosis as the main pathological change is one of the pathogenic factors leading to LSCS. Epidermal Growth Factor (EGF) is known to have an intimate relationship with fibrosis in various tissues.

Conversion of a Fused or Ankylosed Hip to Total Hip Arthroplasty: Is the Direct Anterior Approach in the Lateral Decubitus Position an Ideal Solution?

Background: Total hip arthroplasty (THA) using the direct anterior approach (DAA) is becoming increasingly popular due to its potential benefits over the posterolateral approach (PLA). However, few studies have compared the efficacies of these two surgical approaches in hip fusion treatment. This study compared early clinical direct anterior and posterolateral THA outcomes in hip fusion treatment.

Comparative physiological and transcriptomic analyses reveal key regulatory networks and potential hub genes controlling peanut chilling tolerance.

The unclear molecular mechanism by which peanuts adapt to chilling stress limits progress in molecular breeding for peanut chilling tolerance. Here, the physiological and transcriptional differences between two genotypes with contrasting tolerance under chilling stress were compared. The inhibition of photosynthesis mainly caused by stomatal factors was a common response of peanut seedlings to chilling stress.