YTHDF2 upregulation and subcellular localization dictate CD8 T cell polyfunctionality in anti-tumor immunity.

RNA methylation is an important regulatory process to determine immune cell function but how it affects the anti-tumor activity of CD8 T cells is not fully understood. Here we show that the N-methyladenosine (mA) RNA reader YTHDF2 is highly expressed in early effector or effector-like CD8 T cells. We find that YTHDF2 facilitates nascent RNA synthesis, and mA recognition is fundamental for this distinctively nuclear function of the protein, which also reinforces its autoregulation at the RNA level.

Evaluation of treatment information quality on hypertension and diabetes on WeChat and TikTok: A cross-sectional content analysis.

This study aimed to assess the quality of the information in WeChat and TikTok videos related to hypertension and diabetes treatment. A sample of 120 Chinese videos was collected based on specific inclusion and exclusion criteria. The quality was evaluated using DISCERN, JAMA and the latest edition of Chinese guidelines for hypertension and diabetes prevention and treatment, and two observers independently scored each video using the three assessment tools.

The role of gut microbiota and the gut-lung axis in sepsis: A case study of a pregnant woman with severe rickettsial pneumonia and septic shock complicated by MODS.

Key Clinical Message: In this case report, we describe the successful management of severe scrub typhus with pneumonia, sepsis, and multiple organ dysfunction in a pregnant woman. Despite initial challenges, the patient responded favorably to fecal microbiota transplantation and oral fecal microbiota capsule therapy.

Abstract: Scrub typhus, caused by , can lead to severe multiorgan dysfunction and carries a mortality rate of up to 70% if not treated properly.

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.

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.

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.

Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer.

The clinical implications of extrachromosomal DNA (ecDNA) in cancer therapy remain largely elusive. Here, we present a comprehensive analysis of ecDNA amplification spectra and their association with clinical and molecular features in multiple cohorts comprising over 13,000 pan-cancer patients. Using our developed computational framework, GCAP, and validating it with multifaceted approaches, we reveal a consistent pan-cancer pattern of mutual exclusivity between ecDNA amplification and microsatellite instability (MSI).

Modulator of TMB-associated immune infiltration (MOTIF) predicts immunotherapy response and guides combination therapy.

Patients with high tumor mutational burden (TMB) levels do not consistently respond to immune checkpoint inhibitors (ICIs), possibly because a high TMB level does not necessarily result in adequate infiltration of CD8 T cells. Using bulk ribonucleic acid sequencing (RNA-seq) data from 9311 tumor samples across 30 cancer types, we developed a novel tool called the modulator of TMB-associated immune infiltration (MOTIF), which comprises genes that can determine the extent of CD8 T cell infiltration prompted by a certain TMB level. We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle.

Interferon Regulatory Factor 5 Regulates the Phagocytosis of Microglia and Alleviate Alzheimer's Pathology.

Microglia play a critical role in the pathophysiology of Alzheimer's disease. They are involved in Aβ-induced neuroinflammatory responses, regulating the production of inflammatory mediators. Interferon regulatory factor 5 (IRF5) plays a central role in inflammatory diseases in the periphery, the role of which in central nervous system remains elusive.

Early-onset familial essential tremor is associated with nucleotide expansions of spinocerebellar ataxia in China.

Background: Essential tremor (ET) is a neurological disease characterized by action tremor in upper arms. Although its high heritability and prevalence worldwide, its etiology and association with other diseases are still unknown.

Method: We investigated 10 common spinocerebellar ataxias (SCAs), including SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, SCA36, dentatorubral-pallidoluysian atrophy (DRPLA) in 92 early-onset familial ET pedigrees in China collected from 2016 to 2022.

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.

The liver microenvironment orchestrates FGL1-mediated immune escape and progression of metastatic colorectal cancer.

Colorectal cancer (CRC) patients with liver metastases usually obtain less benefit from immunotherapy, and the underlying mechanisms remain understudied. Here, we identify that fibrinogen-like protein 1 (FGL1), secreted from cancer cells and hepatocytes, facilitates the progression of CRC in an intraportal injection model by reducing the infiltration of T cells. Mechanistically, tumor-associated macrophages (TAMs) activate NF-ĸB by secreting TNFα/IL-1β in the liver microenvironment and transcriptionally upregulate OTU deubiquitinase 1 (OTUD1) expression, which enhances FGL1 stability via deubiquitination.

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.

TRIM50 Inhibits Gastric Cancer Progression by Regulating the Ubiquitination and Nuclear Translocation of JUP.

Unlabelled: Gastric cancer is one of the most frequent cancers in the world. Emerging clinical data show that ubiquitination system disruptions are likely involved in carcinoma genesis and progression. However, the precise role of ubiquitin (Ub)-mediated control of oncogene products or tumor suppressors in gastric cancer is unknown.

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.

PFKFB2 is a favorable prognostic biomarker for colorectal cancer by suppressing metastasis and tumor glycolysis.

Purpose: This study was to investigate the biological effect of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2) in colorectal cancer (CRC).

Methods: PFKFB2 was selected by metabolism polymerase chain reaction (PCR) array from CRC cells under alkaline culture medium (pH 7.4) and acidic culture medium (pH 6.

An immunogenic and oncogenic feature-based classification for chemotherapy plus PD-1 blockade in advanced esophageal squamous cell carcinoma.

Although chemotherapy plus PD-1 blockade (chemo+anti-PD-1) has become the standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), reliable biomarkers for this regimen are lacking. Here we perform whole-exome sequencing on tumor samples from 486 patients of the JUPITER-06 study and develop a copy number alteration-corrected tumor mutational burden that depicts immunogenicity more precisely and predicts chemo+anti-PD-1 efficacy. We identify several other favorable immunogenic features (e.