Asymmetric Synthesis of Unprotected Tryptophan Derivatives Using Gramines via Ni(II) Complexes.

We herein report the synthesis of substituted tryptophans using Ni(II) complexes of glycine and gramines. This reaction proceeds under operationally convenient and mild conditions, using inexpensive, nontoxic, and easily accessible reagents. The reactions feature high yields and virtually complete thermodynamically controlled diastereoselectivity, providing a convenient method for the synthesis of tailor-made tryptophans.

Factors Influencing Background Parenchymal Enhancement in Breast Contrast-Enhanced Mammography: A Retrospective Study.

Objective: To evaluate the association between background parenchymal enhancement (BPE) level and extent on contrast-enhanced mammography (CEM) with age, menopausal status, breast density, and menstrual cycle phase in women. Additionally, to characterize the dynamic changes in BPE during CEM.

Methods: This retrospective study included 103 women who underwent CEM at a single institution between September 2019 and November 2021 for screening or diagnostic purposes.

Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial.

Background: GLP-1 receptor agonists have neurotrophic properties in in-vitro and in-vivo models of Parkinson's disease and results of epidemiological studies and small randomised trials have suggested possible benefits for risk and progression of Parkinson's disease. We aimed to establish whether the GLP-1 receptor agonist, exenatide, could slow the rate of progression of Parkinson's disease.

Methods: We did a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial at six research hospitals in the UK.

Deep learning-based Monte Carlo dose prediction for heavy-ion online adaptive radiotherapy and fast quality assurance: A feasibility study.

Background: Online adaptive radiotherapy (OART) and rapid quality assurance (QA) are essential for effective heavy ion therapy (HIT). However, there is a shortage of deep learning (DL) models and workflows for predicting Monte Carlo (MC) doses in such treatments.

Purpose: This study seeks to address this gap by developing a DL model for independent MC dose (MCDose) prediction, aiming to facilitate OART and rapid QA implementation for HIT.

Synthesis of Unprotected Racemic Tryptophan Derivatives Using Gramine via Nickel(II) Complex.

A chemical method for the preparation of nonprotected tryptophan via nickel(II) complexes under simple operating conditions was established. The carefully designed nickel(II) glycinates are inexpensive and can be quantitatively recovered releasing the target tryptophans in high yield. The method has a wide range of synthesis generality, allowing the preparation of various substituted tryptophans.

Late-Stage Stitching Enabled by Palladium-Catalyzed Tryptophan C4 Amination: Peptide Ligation and Cyclodimerization.

Here, we report on methods for late-stage peptide diversification through palladium-catalyzed site-selective C(sp)-H amination of tryptophan residues at the C4 position, utilizing tryptophan-amine cross-links. Our strategy enables practical access to C-N bonds, facilitating the construction of cyclopeptides via late-stage cyclodimerization of structurally complex peptides, which poses significant challenges for organic synthesis. The synthetic utility of this protocol is demonstrated through the synthesis of 30- to 38-membered macrocyclic peptides.

Development of multifunctional immobilized bacterial agents for multi-pesticides degradation and environment remediation.

The proliferation of weeds, pests, and plant diseases in crop cultivation has driven the increased application of herbicide lactofen, insecticide acetamiprid, and fungicide carbendazim, contributing to environmental pollution. Microorganisms are requently employed to remove pesticide residues from the environment. However, Liquid bacterial agents encounter difficulties in transportation and preservation during application and the current immobilized bacterial agents have a single degradation function.

Hypoxia-guided treatment planning for lung cancer with dose painting by numbers.

Tumor hypoxia significantly impacts the efficacy of radiotherapy. Recent developments in the technique of dose painting by numbers (DPBN) promise to improve the tumor control probability (TCP) in conventional radiotherapy for hypoxic cancer. The study initially combined the DPBN method with hypoxia-guided dose distribution optimization to overcome hypoxia for lung cancers and evaluated the effectiveness and appropriateness for clinical use of the DPBN plans.

A Chinese Girl With LIG4 Syndrome and Hematopoietic Stem Cell Transplantation: A Rare Case Report and Review of the Literature.

LIG4 syndrome is an exceptionally rare primary immune deficiency. It is an autosomal recessive genetic disease, falling within the spectrum of genetic disorders characterized by impaired DNA damage response mechanisms. Common clinical characteristics encompass microcephaly, growth retardation, developmental delays, facial deformities, variable immune deficiencies, pancytopenia, heightened susceptibility to malignant tumors, and significant clinical and cellular radiosensitivity.

Rh(II)-Catalyzed Selective C(sp)-H/C(sp)-H Bonds Cascade Insertion to Construct [6-8-6] Benzo-Fused Scaffold.

The fused eight-membered carbocycles (EMCs) play vital roles in the medicinal and biological investigations of many natural products and marketed drugs. The traditional synthesis of [6-8-6] benzo-fused derivatives involves multistep reactions and low yields, making the development of a one-step synthesis method a more challenging work. Here, we present a novel strategy for one-step construction of [6-8-6] benzo-fused scaffold from propargyl diazoacetates substituted with benzyl-nitrogen heterocyclic ring via Rh(ll)-catalyzed carbene/alkyne metathesis (CAM) and selective C-H bond insertion.

Partial unidirectional translocation from 5AL to 7BS leads to dense spike in an EMS-induced wheat mutant.

Background: As the inflorescence of wheat, spike architecture largely determines grain productivity. Dissecting the genetic basis for the spike morphology of wheat can contribute to the designation of ideal spike morphology to improve grain production.

Results: The present study characterizes a dense spike1 (ds1) mutant, derived from Nongda3753, induced by EMS treatment, which exhibits a dense spike and reduced plant height.

An endoplasmic reticulum localized acetyl-CoA transporter is required for efficient fatty acid synthesis in .

is an obligate intracellular parasite that can infect humans and diverse animals. Fatty acids are critical for the growth and proliferation of , which has at least two pathways to synthesize fatty acids, including the type II de novo synthesis pathway in the apicoplast and the elongation pathway in the endoplasmic reticulum (ER). Acetyl-CoA is the key substrate for both fatty acid synthesis pathways.

Concurrent control chart pattern recognition in manufacturing processes based on zero-shot learning.

In real industrial settings, collecting and labeling concurrent abnormal control chart pattern (CCP) samples are challenging, thereby hindering the effectiveness of current CCP recognition (CCPR) methods. This paper introduces zero-shot learning into quality control, proposing an intelligent model for recognizing zero-shot concurrent CCPs (C-CCPs). A multiscale ordinal pattern (OP) feature considering data sequential relationship is proposed.

Incretin-Based Multi-Agonist Peptides Are Neuroprotective and Anti-Inflammatory in Cellular Models of Neurodegeneration.

Glucagon-like peptide-1 (GLP-1)-based drugs have been approved by the United States Food and Drug Administration (FDA) and are widely used to treat type 2 diabetes mellitus (T2DM) and obesity. More recent developments of unimolecular peptides targeting multiple incretin-related receptors ("multi-agonists"), including the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and the glucagon (Gcg) receptor (GcgR), have emerged with the aim of enhancing drug benefits. In this study, we utilized human and mouse microglial cell lines, HMC3 and IMG, respectively, together with the human neuroblastoma SH-SY5Y cell line as cellular models of neurodegeneration.

Comparison of elastic stable intramedullary nailing versus Kirschner wires in treatment of pediatric radial neck fractures.

Purpose: The aim of the study was to compare the different internal fixations between elastic stable intramedullary nailing and Kirschner wires in treatment of angulated radial neck fractures.

Methods: We retrospectively reviewed the patients with radial neck fracture without associated injuries who underwent surgery approach in our department during April 2011-March 2020. There were 62 patients meeting all the criteria with complete clinical data, with median age of 7.

A machine learning-based approach to predict energy layer for each field in spot-scanning proton arc therapy for lung cancer: A feasibility study.

Background: Determining the optimal energy layer (EL) for each field, under considering both dose constraints and delivery efficiency, is crucial to promoting the development of proton arc therapy (PAT) technology.

Purpose: This study aimed to explore the feasibility and potential clinical benefits of utilizing machine learning (ML) technique to automatically select EL for each field in PAT plans of lung cancer.

Methods: Proton Bragg peak position (BPP) was employed to characterize EL.

Type 2 diabetes mellitus/obesity drugs: A neurodegenerative disorders savior or a bridge too far?

Glucagon-like peptide-1 (GLP-1) receptor agonist-based drugs (incretin mimetics) have meaningfully impacted current treatment of type 2 diabetes mellitus (T2DM), and their actions on satiety and weight loss have led to their use as an obesity medication. With multiple pleotropic actions beyond their insulinotropic and weight loss ones, including anti-inflammatory and anti-insulin-resistant effects selectively mediated by their receptors present within numerous organs, this drug class offers potential efficacy for an increasing number of systemic and neurological disorders whose current treatment is inadequate. Among these are a host of neurodegenerative disorders that are prevalent in the elderly, such as Parkinson's and Alzheimer's disease, which have bucked previous therapeutic approaches.

DPP-4 inhibitors sitagliptin and PF-00734,200 mitigate dopaminergic neurodegeneration, neuroinflammation and behavioral impairment in the rat 6-OHDA model of Parkinson's disease.

Epidemiological studies report an elevated risk of Parkinson's disease (PD) in patients with type 2 diabetes mellitus (T2DM) that is mitigated in those prescribed dipeptidyl peptidase 4 (DPP-4) inhibitors. With an objective to characterize clinically translatable doses of DPP-4 inhibitors (gliptins) in a well-characterized PD rodent model, sitagliptin, PF-00734,200 or vehicle were orally administered to rats initiated either 7-days before or 7-days after unilateral medial forebrain bundle 6-hydroxydopamine (6-OHDA) lesioning. Measures of dopaminergic cell viability, dopamine content, neuroinflammation and neurogenesis were evaluated thereafter in ipsi- and contralateral brain.

Sitagliptin elevates plasma and CSF incretin levels following oral administration to nonhuman primates: relevance for neurodegenerative disorders.

The endogenous incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) possess neurotrophic, neuroprotective, and anti-neuroinflammatory actions. The dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin reduces degradation of endogenous GLP-1 and GIP, and, thereby, extends the circulation of these protective peptides. The current nonhuman primate (NHP) study evaluates whether human translational sitagliptin doses can elevate systemic and central nervous system (CNS) levels of GLP-1/GIP in naive, non-lesioned NHPs, in line with our prior rodent studies that demonstrated sitagliptin efficacy in preclinical models of Parkinson's disease (PD).

Palladium(II)-Catalyzed Heck Coupling: Direct Stereoselective Synthesis of -Aryl Glycosides from Nonactivated Glycals and Thianthrenium Salts.

Here, we report an efficient Pd(II)-catalyzed Heck coupling reaction utilizing modular and readily available thianthrenium salts. The tunability and ease of thianthrenium salts facilitated the integration of glycals with drugs, natural products, and peptides. This method allows the incorporation of diverse glycals into structurally varied aglycon components without directing groups or prefunctionalization and provides a practical method for synthesizing -aryl glycosides, offering a new avenue for the production of complex glycosides with potential applications.

Engineering a Dual-Receptor Targeted Multivalent Probe for Enhanced Magnetic Resonance Imaging of Metastatic Cancer.

Noninvasive monitoring of cancer metastasis is essential to improving clinical outcomes. Molecular MRI (mMRI) is a special implementation of noninvasive molecular imaging that promises to offer a powerful means for early detection and analysis of pathological states of cancer by tracking molecular markers. However, this is often hindered by the challenging issue of obtaining transformable mMRI contrast agents with high sensitivity, specificity, and broad applicability, given the high tumor heterogeneity and complex metastatic features.