Synthesis of Sulfonated Peptides Using a Trifluoromethyltoluene-Protected Amino Acid.

A scalable, seven step synthesis is reported for a trifluoromethyl toluene protected sulfonated phenylalanine building block whose utility was demonstrated in the synthesis of four CXCR4-derived sulfonopeptides. When compared to a conventional trichloroethyl protected building block, overall yield was improved by up to 4-fold. We believe this building block will prove to be of significant value for the synthesis of a variety of peptide targets containing phenylalanine sulfonate, a bioisostere of tyrosine sulfate, enabling orthogonal protection strategies and improving synthetic efficiency and yield.

Developing an evaluation model for urban tourism competitiveness: combining community construction and community service to foster sustainable development of cities.

Introduction: This study aims to develop a comprehensive evaluation model for urban tourism competitiveness in China. Given China's transition into a mature tourist destination, there is a pressing need for a framework that can assess the effectiveness of its urban tourism strategies. The model presented in this study is designed to provide a holistic understanding of the factors influencing urban tourism competitiveness in the Chinese context.

Total Synthesis of a PSGL-1 Glycopeptide Analogue for Targeted Inhibition of P-Selectin.

The high affinity interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin is mediated by a multimotif glycosulfopeptide (GSP) recognition domain consisting of clustered tyrosine sulfates and a Core 2 -glycan terminated with sialyl Lewis (C2--sLe). These distinct GSP motifs are much more common than previously appreciated within a wide variety of functionally important domains involved in protein-protein interactions. However, despite the potential of GSPs to serve as tools for fundamental studies and prospects for drug discovery, their utility has been limited by the absence of chemical schemes for synthesis on scale.

Cerebrospinal fluid amyloid-β and cerebral microbleed are associated with distinct neuropsychiatric sub-syndromes in cognitively impaired patients.

Background: Neuropsychiatric symptoms (NPS) are prevalent in cognitively impaired individuals including Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI). Whereas several studies have reported the associations between NPS with AD pathologic biomarkers and cerebral small vessel disease (SVD), but it remains unknown whether AD pathology and SVD contribute to different sub-syndromes independently or aggravate same symptoms synergistically.

Method: We included 445 cognitively impaired individuals (including 316 MCI and 129 AD) with neuropsychiatric, cerebrospinal fluid (CSF) biomarkers (Aβ42, p-tau, and t-tau) and multi-model MRI data.

Small vessel disease and cognitive reserve oppositely modulate global network redundancy and cognitive function: A study in middle-to-old aged community participants.

Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment.

Association Between Small Vessel Disease and Financial Capacity: A Study Based on Cognitively Normal Older Adults.

Background: Financial capacity is vital for the elderly, who possess a substantial share of global wealth but are vulnerable to financial fraud.

Objective: We explored the link between small vessel disease (SVD) and financial capacity in cognitively unimpaired (CU) older adults via both cross-sectional and longitudinal analyses.

Methods: 414 CU participants underwent MRI and completed the Financial Capacity Instrument-Short Form (FCI-SF).

Alteration of functional connectivity network in population of objectively-defined subtle cognitive decline.

The objectively-defined subtle cognitive decline individuals had higher progression rates of cognitive decline and pathological deposition than healthy elderly, indicating a higher risk of progressing to Alzheimer's disease. However, little is known about the brain functional alterations during this stage. Thus, we aimed to investigate the functional network patterns in objectively-defined subtle cognitive decline cohort.

Effect of cerebral small vessel disease on the integrity of cholinergic system in mild cognitive impairment patients: a longitudinal study.

We aimed to investigate the effect of cerebral small vessel disease (SVD) on cholinergic system integrity in mild cognitive impairment (MCI) patients. Nucleus basalis of Meynert (NBM) volume and cholinergic pathways integrity was evaluated at baseline, 1-, 2-, and 4-year follow-ups in 40 cognitively unimpaired (CU) participants, 29 MCI patients without SVD, and 23 MCI patients with SVD. We compared cholinergic markers among three groups and examined their associations with SVD burden in MCI patients.

The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer's disease continuum participants.

Background: Glymphatic dysfunction is a crucial pathway for dementia. Alzheimer's disease (AD) pathologies co-existing with cerebral small vessel disease (CSVD) is the most common pathogenesis for dementia. We hypothesize that AD pathologies and CSVD could be associated with glymphatic dysfunction, contributing to cognitive impairment.

An Investigation of Cerebral Vascular Functional Properties in Middle-to-Old Age Community People With High Vascular Risk Profiles.

Background: Vascular degeneration is an important cause of brain damage in aging. Assessing the functional properties of the cerebral vascular system may aid early diagnosis and prevention.

Purpose: To investigate the relationships between potential vascular functional markers and vascular risks, brain parenchymal damage, and cognition.

Higher intracranial arterial pulsatility is associated with presumed imaging markers of the glymphatic system: An explorative study.

Background: Arterial pulsation has been suggested as a key driver of paravascular cerebrospinal fluid flow, which is the foundation of glymphatic clearance. However, whether intracranial arterial pulsatility is associated with glymphatic markers in humans has not yet been studied.

Methods: Seventy-three community participants were enrolled in the study.

Identifying psychosis subtypes use individualized covariance structural differential networks and multi-site clustering.

Background: Similarities among schizophrenia (SZ), schizoaffective disorder (SAD) and bipolar disorder (BP) including clinical phenotypes, brain alterations and risk genes, make it challenging to perform reliable separation among them. However, previous subtype identification that transcend traditional diagnostic boundaries were based on group-level neuroimaging features, ignoring individual-level inferences.

Methods: 455 psychoses (178 SZs, 134 SADs and 143 BPs), their first-degree relatives (N = 453) and healthy controls (HCs, N = 220) were collected from Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP I) consortium.

Identification of FXYD6 as the novel biomarker for glioma based on differential expression and DNA methylation.

Objective: As a single-transmembrane protein of the FXYD family, FXYD6 plays different roles under physiological and pathological status, especially in the nervous system. This study aims to identify FXYD6 as a biomarker for glioma, by analyzing its expression and methylation patterns.

Methods: Using TCGA and GTEx datasets, we analyzed FXYD6 expression in various tissues, confirming its levels in normal brain and different glioma grades via immunoblotting and immunostaining.

Gray matter structural covariance networks patterns associated with autopsy-confirmed LATE-NC compared to Alzheimer's disease pathology.

Background: Cases with the limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC), Alzheimer's disease (AD), and mixed AD+TDP-43 pathology (AD+LATE-NC) share similar symptoms, which makes it a challenge for accurate diagnosis. Exploring the patterns of gray matter structural covariance networks (SCNs) in these three types may help to clarify the underlying mechanism and provide a basis for clinical interventions.

Methods: We included ante-mortem MRI data of 10 LATE-NC, 39  AD, and 25  AD+LATE-NC from the ADNI autopsy sample.

Degeneration of cholinergic white matter pathways and nucleus basalis of Meynert in individuals with objective subtle cognitive impairment.

We evaluated alterations in the nucleus basalis of Meynert (NBM) volume and integrity of cholinergic white matter pathways in objective subtle cognitive impairment (Obj-SCI) individuals. NBM segmentation and cholinergic pathways tracking were conducted at baseline, 12-, 24-, and 48-month follow-ups in 41 Obj-SCI individuals and 61 healthy controls (HC). The baseline and 4-year rate of change in NBM volume and cholinergic pathways mean diffusivity were compared.

Associations of Alzheimer's Disease Pathology and Small Vessel Disease With Cerebral White Matter Degeneration: A Tract-Based MR Diffusion Imaging Study.

Background: White matter (WM) degeneration is a key feature of Alzheimer's disease (AD). However, the underlying mechanism remains unclear.

Purpose: To investigate how amyloid-β (Aβ), tau, and small vascular disease (SVD) jointly affect WM degeneration in subjects along AD continuum.

Decoupling of Regional Cerebral Blood Flow and Brain Function Along the Alzheimer's Disease Continuum.

Background: Alzheimer's disease (AD) is accompanied with impaired neurovascular coupling. However, its early alteration remains elusive along the AD continuum.

Objective: This study aimed to investigate the early disruption of neurovascular coupling in cognitively normal (CN) and mild cognitive impairment (MCI) elderly and its association with cognition and AD pathologies.

Distinct cerebral small vessel disease impairment in early- and late-onset Alzheimer's disease.

Objective: This study investigated cerebral small vessel disease (CSVD) damage patterns in early-onset and late-onset Alzheimer's disease (EOAD and LOAD) and their effects on cognitive function.

Methods: This study included 93 participants, 45 AD patients (14 EOAD and 31 LOAD), and 48 normal controls (13 YNC and 35 ONC) from the ADNI database. All participants had diffusion tensor imaging data; some had amyloid PET and plasma p-tau data.

Distinct resting-state functional connectivity patterns of Anterior Insula affected by smoking in mild cognitive impairment.

Smoking is a modifiable risk factor for Alzheimer's disease (AD). The insula plays a vital role in both smoking and cognition. However, the smoking effects on insula-related networks in cognitively normal controls (CN) and mild cognitive impairment (MCI) patients remain unknown.

Inferior Frontal Sulcal Hyperintensity on FLAIR is Associated with Small Vessel Disease but not Alzheimer's Pathology.

Background: The inferior frontal sulci are essential sites on the route of cerebrospinal fluid outflow. A recent study suggests that inferior frontal sulcal hyperintensities (IFSH) on FLAIR images might be related to glymphatic dysfunction.

Objective: To investigate whether IFSH is associated with Alzheimer's disease (AD) pathology and cerebral small vessel disease (SVD) burden.

Modeling disrupted synapse formation in wolfram syndrome using hESCs-derived neural cells and cerebral organoids identifies Riluzole as a therapeutic molecule.

Dysregulated neurite outgrowth and synapse formation underlie many psychiatric disorders, which are also manifested by wolfram syndrome (WS). Whether and how the causative gene WFS1 deficiency affects synapse formation remain elusive. By mirroring human brain development with cerebral organoids, WFS1-deficient cerebral organoids not only recapitulate the neuronal loss in WS patients, but also exhibit significantly impaired synapse formation and function associated with reduced astrocytes.

Effects of APOE ε2 allele on basal forebrain functional connectivity in mild cognitive impairment.

Background: Basal forebrain cholinergic system (BFCS) dysfunction is associated with cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Apolipoprotein E (APOE) ε2 is a protective genetic factor in AD and MCI, and cholinergic sprouting depends on APOE.

Objective: We investigated the effect of the APOE ε2 allele on BFCS functional connectivity (FC) in cognitively normal (CN) subjects and MCI patients.