Functionalized Periosteum-Derived Microsphere-Hydrogel with Sequential Release of E7 Short Peptide/miR217 for Large Bone Defect Repairing.

Large bone defects are still a persistent challenge in orthopedics. The availability limitations and associated complications of autologous and allogeneic bone have prompted an increasing reliance on tissue engineering and regenerative medicine. In this study, we developed an injectable scaffold combining an acellular extracellular periosteal matrix hydrogel with poly(d,l-lactate--glycol-acetate) microspheres loaded with the E7 peptide and miR217 (miR217/E7@MP-GEL).

A Preclinical Immunogenicity Study of the Recombinant Human Papillomavirus Nine-Valent Virus-like Particle Vaccine.

Background: Cervical cancer is associated with persistent infection of high-risk human papillomaviruses (HPVs). Prophylactic HPV vaccines have been recommended and have significant efficacy in preventing cervical cancer. Multivalent HPV vaccines have a better preventative effect on HPV-related diseases.

Systematic review and meta-analysis of the impact of the refreezing and rebiopsy embryos on reproductive outcomes in patients undergoing freeze-thaw embryo transfer.

Objective: To explore whether refreezing and rebiopsy affect reproductive outcomes.

Design: Systematic review and meta-analysis.

Setting: Not applicable.

Unraveling the Growth Mechanism of Chiral Inorganic Nanocrystals via High-Resolution Electron Microscopy.

Chiral inorganic nanomaterials have attracted broad interest due to their intriguing chirality-dependent performances. However, there is a lack of experimental studies and atomic-level evidence on their growth mechanism. Herein, high-crystalline chiral tellurium nanowires were synthesized in an alkali solution by using tellurium oxide as an inorganic source and hydrazine hydrate as a reductant.

DCBLD1 Modulates Angiogenesis by Regulation of the VEGFR-2 Endocytosis in Endothelial Cells.

Background: Unwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (discoidin, CUB, and LCCL domain-containing protein 1) is a coreceptor of VEGFR-2 (vascular endothelial growth factor receptor-2) and modulates angiogenesis in endothelial cells.

Methods: A carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or endothelial cell-specific conditional knockout mice in vivo.

Virtual MR Elastography and Multi-b-value DWI Models for Predicting Microvascular Invasion in Solitary BCLC Stage A Hepatocellular Carcinoma.

Rationale And Objectives: To evaluate the performance of virtual MR elastography (vMRE) for predicting microvascular invasion (MVI) in Barcelona Clinic Liver Cancer (BCLC) stage A (≤ 5.0 cm) hepatocellular carcinoma (HCC) and to construct a combined nomogram based on vMRE, multi-b-value DWI models, and clinical-radiological (CR) features.

Methods: Consecutive patients with suspected HCC who underwent multi-b-value DWI examinations were prospectively collected.

Kaempferol alleviates rheumatoid arthritis through pyroptosis based on bioinformatics analysis and experimental validation.

Kaempferol has an anti-inflammatory effect on rheumatoid arthritis (RA), but the mechanism by which inflammatory reactions are relieved via pyroptosis is still unclear. In the present study, The bioinformatics technology was used to analyze the relationship between pyroptosis the hub genes and the downstream cytokines in RA from three the Gene Expression Omnibus (GSE12021, GSE1919 and GSE29746). Molecular docking analysis of kaempferol and caspase1 (CASP1) was executed with Autodock tools.

Baseline body composition and 3D-extracellular volume fraction for predicting pancreatic fistula after distal pancreatectomy in pancreatic body and/or tail adenocarcinoma.

Rationale And Objectives: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a threatening complication in body and/or tail pancreatic ductal adenocarcinoma (PDAC) receiving distal pancreatectomy (DP) and is difficult to predict preoperatively. We aimed to identify the role of baseline CT-based body composition analysis and extracellular volume (ECV) map in predicting the risk of CR-POPF preoperatively.

Materials And Methods: A total of 329 resectable PDAC patients were enrolled and underwent multiphasic contrast-enhanced CT.

Multifunctional chiral metal hydrogen-bonded organic frameworks constructed from lanthanide ions with a trigonal prismatic coordination environment.

Two pairs of chiral enantiomers D/L-Dy(PMP)·2HO (D-1/L-1) and D/L-Yb(PMP)·2HO (D-2/L-2) were synthesized by the introduction of enantiomerically pure D/L-PMP (PMP = (phosphonomethyl)proline) ligands into lanthanide coordination chemistry. The chiral characteristics of these products were confirmed by single crystal X-ray diffraction, second harmonic generation (SHG) measurements and circular dichroism (CD) spectroscopy. These complexes are composed of 1D chains constructed from lanthanide ions with a trigonal prismatic coordination geometry and PMP ligands.

Rational design and discovery of novel hydrazide derivatives as potent succinate dehydrogenase inhibitors inspired by natural d/l-camphor.

Background: Succinate dehydrogenase inhibitors (SDHIs) have rapidly become one of the fastest-growing categories of fungicides used against plant pathogenic fungi. Recent research advancements have emphasized that structural modifications of SDHIs using naturally sourced scaffolds represent an innovative strategy for developing new, highly effective, broad-spectrum fungicides. A novel series of d/l-camphorhydrazide derivatives potentially targeting fungal succinate dehydrogenase (SDH) were designed, synthesized and evaluated for their antifungal effects against Rhizoctonia solani, Fusarium graminearum, Valsa mali and Botrytis cinerea.

Pathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases.

Neurodegenerative diseases are the leading cause of human disability and immensely reduce patients' life span and quality. The diseases are characterized by the functional loss of neuronal cells and share several common pathogenic mechanisms involving the malfunction, structural distortion, or aggregation of multiple key regulatory proteins. Cellular phase separation is the formation of biomolecular condensates that regulate numerous biological processes, including neuronal development and synaptic signaling transduction.

Visualizing Immune Checkpoint Inhibitors Derived Inflammation in Atherosclerosis.

Background: Immune checkpoint inhibitor (ICI) usage has resulted in immune-related adverse events in patients with cancer, such as accelerated atherosclerosis. Of immune cells involved in atherosclerosis, the role of CCR2+ (CC motif chemokine receptor 2-positive) proinflammatory macrophages is well documented. However, there is no noninvasive approach to determine the changes of these cells in vivo following ICI treatment and explore the underlying mechanisms of immune-related adverse events.

Functional Characterization of Reduced Folate Carrier and Protein-Coupled Folate Transporter for Antifolates Accumulation in Non-Small Cell Lung Cancer Cells.

Antifolates are important for chemotherapy in non-small cell lung cancer (NSCLC). They mainly rely on reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) to enter cells. PCFT is supposed to be the dominant transporter of the two in tumors, as it operates optimally at acidic pH and has limited transport activity at physiological pH, whereas RFC operates optimally at neutral pH.

Asundexian versus Apixaban in Patients with Atrial Fibrillation.

Background: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding.

Methods: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban.

A Light-Driven In Vitro Enzymatic Biosystem for the Synthesis of α-Farnesene from Methanol.

Terpenoids of substantial industrial interest are mainly obtained through direct extraction from plant sources. Recently, microbial cell factories or in vitro enzymatic biosystems have emerged as promising alternatives for terpenoid production. Here, we report a route for the synthesis of α-farnesene based on an in vitro enzyme cascade reaction using methanol as an inexpensive and renewable C1 substrate.

Template-assisted covalent modification underlies activity of covalent molecular glues.

Molecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed 'template-assisted covalent modification'.

High-Sensitivity Troponin T, NT-proBNP, and Cognitive Outcomes in SPRINT.

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.

Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.

Profiling lipid mediators in serum from children with H1N1 influenza.

Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory responses that aim to contain and eliminate microbial invaders. Various lipid mediators (LMs) are biosynthesized and play a critical role in fighting viruses during inflammation; thus, by profiling the LMs in patients, researchers can obtain mechanistic insights into diseases, such as the pathways disrupted.

No Differences in 2-Year Reoperation Rates for Meniscus Allograft Transplant With Concomitant Cartilage Restoration or Osteotomy: A National Database Study.

Purpose: To investigate reoperation rates after meniscus allograft transplant (MAT), comparing rates with and without concomitant articular cartilage and osteotomy procedures using a national insurance claims database.

Methods: We performed a retrospective cohort study of patients who underwent MAT from 2010 to 2021 with a minimum 2-year follow-up using the PearlDiver database. Using Current Procedural Terminology and International Classification of Diseases codes, we identified patients who underwent concomitant procedures including chondroplasty or microfracture, cartilage restoration defined as osteochondral graft or autologous chondrocyte implantation (ACI), or osteotomy.