Polyphenol metabolomics reveals the applications and prospects of polyphenol-rich plants in natural dyes.

Polyphenols, as one of the primary compounds produced by plant secondary metabolism, have garnered considerable attention because of their non-toxic, environmentally friendly, and biodegradable properties, as well as their notable medicinal value. This study presents a metabolomic analysis of polyphenols from 11 woody plants, including , , and , investigating a total of 40 polyphenolic metabolites. A differential metabolite dynamics map highlighted the five most differentiated substances among the 11 plants, including vitexin, dihydromyricetin, genistin, resveratrol, and isorhamnetin.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Molecular Insights into the Regulation of GNPTAB by TMEM251.

In vertebrates, newly synthesized lysosomal enzymes traffick to lysosomes through the mannose-6-phosphate (M6P) pathway. The Golgi membrane protein TMEM251 was recently discovered to regulate lysosome biogenesis by controlling the level of GlcNAc-1-phosphotransferase (GNPT). However, its precise function remained unclear.

Linking Iris Cis-Regulatory Variants to Primary Angle-Closure Glaucoma Via Clinical Imaging and Multiomics.

Purpose: To elucidate the genetic basis of primary angle-closure glaucoma (PACG) by identifying pathogenic tissue and critical tissue-specific variants.

Methods: The correlations among PACG susceptibility, axial length (AL), and anterior chamber depth (ACD) were evaluated using meta-analyses. Propensity score matching was utilized on 2161 participants from the Handan Eye Study to determine the risk factors independent of ACD and AL for PACG.

Understanding Typology of Preexposure Prophylaxis (PrEP) Persistence Trajectories Among Male PrEP Users in the United States.

Introduction: Understanding longitudinal patterns of preexposure prophylaxis (PrEP) use among men who have sex with men could offer insights for developing efficient and timely interventions to promote PrEP persistence.

Setting: We extracted 2 years of pharmacy fill records for 4000 males who initiated PrEP in 2017 at a national chain pharmacy in the United States.

Methods: Group-based trajectory models were used to develop PrEP trajectory clusters, with periods of use defined based on optimal PrEP seroprotection probabilities (ie, PrEP use frequency ≥4 doses/week).

A modular platform for bioluminescent RNA tracking.

A complete understanding of RNA biology requires methods for tracking transcripts in vivo. Common strategies rely on fluorogenic probes that are limited in sensitivity, dynamic range, and depth of interrogation, owing to their need for excitation light and tissue autofluorescence. To overcome these challenges, we report a bioluminescent platform for serial imaging of RNAs.

Acquired hemophilia A: a narrative review and management approach in the emicizumab era.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by inhibitory autoantibodies to factor (F)VIII. The goals of treatment are 2-fold, namely immunosuppressive therapy to eradicate the inhibitor and hemostatic management to control bleeding. Emicizumab, a bispecific antibody that acts as a FVIIIa-mimetic, has seen growing use in AHA following its approval for congenital hemophilia A.

Short-term Effects of Pulsed Electromagnetic Field Therapy for Achilles Tendinopathy: A Randomized Controlled Trial.

Background: Pulsed electromagnetic field (PEMF) therapy is a potential nonoperative treatment for Achilles tendinopathy, but the current published literature on its effects is sparse.

Purpose: To evaluate the therapeutic efficacy of PEMF therapy and eccentric exercise for Achilles tendinopathy.

Study Design: Randomized controlled trial; Level of evidence, 1.

Rac1 GTPase Regulates the βTrCP-Mediated Proteolysis of YAP Independently of the LATS1/2 Kinases.

Oncogenic mutations in the gene are detected in >90% of pancreatic cancers (PC). In genetically engineered mouse models of PC, oncogenic drives the formation of precursor lesions and their progression to invasive PC. The Yes-associated Protein (YAP) is a transcriptional coactivator required for transformation by the RAS oncogenes and the development of PC.

Gentle Rhodamines for Live-Cell Fluorescence Microscopy.

Rhodamines have been continuously optimized in brightness, biocompatibility, and color to fulfill the demands of modern bioimaging. However, the problem of phototoxicity caused by the excited fluorophore under long-term illumination has been largely neglected, hampering their use in time-lapse imaging. Here we introduce cyclooctatetraene (COT) conjugated rhodamines that span the visible spectrum and exhibit significantly reduced phototoxicity.

Hydraulic traits exert greater limitations on tree-level maximum sap flux density than photosynthetic ability: Global evidence.

Transpiration is a key process that couples the land-atmosphere exchange of water and carbon, and its maximum water transport ability affects plant productivity. Functional traits significantly influence the maximum transpiration rate; however, which factor plays the dominant role remains unknown. SAPFLUXNET dataset, which includes sap flux density of diverse species worldwide, provides fundamental data to test the importance of photosynthetic and hydraulic traits on maximum tree-level sap flux density (J).

3D Printing of Hierarchical Structures Made of Inorganic Silicon-Rich Glass Featuring Self-Forming Nanogratings.

Hierarchical structures are abundant in nature, such as in the superhydrophobic surfaces of lotus leaves and the structural coloration of butterfly wings. They consist of ordered features across multiple size scales, and their advantageous properties have attracted enormous interest in wide-ranging fields including energy storage, nanofluidics, and nanophotonics. Femtosecond lasers, which are capable of inducing various material modifications, have shown promise for manufacturing tailored hierarchical structures.

Impact of APOE ε4 and ε2 on plasma neurofilament light chain and cognition in autosomal dominant Alzheimer's disease.

Background: Apolipoprotein E (APOE) genotypes have been suggested to influence cognitive impairment and clinical onset in presenilin-1 (PSEN1) E280A carriers for autosomal dominant Alzheimer's disease (ADAD). Less is known about their impact on the trajectory of biomarker changes. Neurofilament light chain (NfL), a marker of neurodegeneration, begins to accumulate in plasma about 20 years prior to the clinical onset of ADAD.

Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

Background: Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals.

Methods: In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care.

Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial.

Background And Objectives: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI.

Methods: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted.