Transcriptome Signatures for Cognitive Resilience Among Individuals with Pathologically Confirmed Alzheimer Disease.

Introduction: Limited success to date in development of drugs that target hallmark Alzheimer disease (AD) proteins as a means to slow AD-related cognitive decline has sparked interest in approaches focused on cognitive resilience. We sought to identify transcriptome signatures among brain donors with neuropathologically confirmed AD that distinguish those with cognitive impairment from those that were cognitively intact.

Methods: We compared gene expression patterns in brain tissue from donors in four cohorts who were cognitively and pathologically normal (controls), met clinical and pathological criteria for AD (SymAD), or were cognitively normal prior to death despite pathological evidence of AD (cognitively resilient or AsymAD).

Synergistic immunochemotherapy targeted SAMD4B-APOA2-PD-L1 axis potentiates antitumor immunity in hepatocellular carcinoma.

Targeted and immunotherapy combined with interventional therapy can improve the prognosis of advanced cancer patients, and it has become a hot spot to find the new therapeutic schemes, but most of which are not satisfactory. Single-cell RNA sequencing was performed in PDX mouse models with or without TCC therapy. 2-'O-Methylation modification and multiplex immunofluorescence staining were used to explore the function and mechanism of SAMD4B in the immune context of HCC.

Study on the ability of indoor plants to absorb and purify benzene pollution.

The ability of indoor plants to purify benzene pollution is the basic basis for the selection of plants for ecological remediation of indoor benzene pollution. In this study, the purification rate and the purification amount per unit leaf area of 13 test plants at three benzene concentrations were determined by indoor fumigation experiments, and the benzene absorption and purification abilityability of indoor plants were comprehensively evaluated. The results showed that (1) there was a significant correlation between benzene concentration and purification rate and purification amount per unit leaf area.

GOLGA7 is essential for NRAS trafficking from the Golgi to the plasma membrane but not for its palmitoylation.

NRAS mutations are most frequently observed in hematological malignancies and are also common in some solid tumors such as melanoma and colon cancer. Despite its pivotal role in oncogenesis, no effective therapies targeting NRAS has been developed. Targeting NRAS localization to the plasma membrane (PM) is a promising strategy for cancer therapy, as its signaling requires PM localization.

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

Introduction: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.

Methods: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites.

Synergism of FAK and ROS1 inhibitors in the treatment of -deficient cancers mediated by FAK-YAP signaling.

deficiency is common in diffuse gastric cancer and triple negative breast cancer patients, both of which still lack effective therapeutics. ROS1 inhibition results in synthetic lethality in -deficient cancers, but often leads to adaptive resistance. Here, we demonstrate that upregulation of the FAK activity accompanies the emergence of resistance to ROS1 inhibitor therapy in gastric and breast -deficient cancers.

Novel loci for Alzheimer's disease identified by a genome-wide association study in Ashkenazi Jews.

Introduction: Most Alzheimer's disease (AD) loci have been discovered in individuals with European ancestry (EA).

Methods: We applied principal component analysis using Gaussian mixture models and an Ashkenazi Jewish (AJ) reference genome-wide association study (GWAS) data set to identify Ashkenazi Jews ascertained in GWAS (n = 42,682), whole genome sequencing (WGS, n = 16,815), and whole exome sequencing (WES, n = 20,504) data sets. The association of AD was tested genome wide (GW) in the GWAS and WGS data sets and exome wide (EW) in all three data sets (EW).

How Outstanding Universal Value Attractiveness and Tourism Crowding Affect Visitors' Satisfaction?

A World Heritage Site is a masterpiece of mankind and/or nature that possesses outstanding universal value (OUV). In this regard, the 5Cs strategic objectives (credibility, communication, capacity-building, conservation, and community) set by the World Heritage Committee have become a main issue for WHS sustainable development. As one of the key stakeholders of WHS, tourist's perceived OUV attractiveness, congestion, and attitudinal behavior have significant implications for heritage protection and tourism's sustainable development.

Stimulus-Organism-Response Framework: Is the Perceived Outstanding Universal Value Attractiveness of Tourists Beneficial to World Heritage Site Conservation?

Tourists have been attracted to world heritage sites (WHSs) by their Outstanding Universal Value (OUV). In view of the Stimulus-Organism-Response (S-O-R) framework and the theory of attitude and behavior, by employing 563 tourist samples from Mount Sanqingshan National Park, and using structural equation modeling, we examine tourist behavioral intention for heritage conservation, and the following conclusions were drawn: (1) the S-O-R theory revealed the behavioral intentions of tourists to protect WHSs; (2) as a stimulus, tourists' value perception and destination attachment were positively affected by the OUV attractiveness, and their perceived value had a positive influence on heritage conservation, although the hypothesis of destination attachment to heritage conservation was not supported; (3) heritage-conservation education and knowledge positively influenced tourists' behavioral intentions towards heritage protection, and tourists' heritage protection attitude had a positive influence on their behavioral intention; and (4) a framework of the influence mechanism for tourists' heritage conservation based on the S-O-R theory was proposed, while tourists' cognitive and affective attitudes impacted on heritage protection intention which, in turn, further enhanced the tourists' perception of the OUV. Conclusively, the measures and implications were proposed for improving conservation and management of WHSs, in particular to achieve the sustainable development of the tourist industry and world heritage sites.

Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal melanoma.

More than 85% of patients with uveal melanoma (UM) carry a GNAQ or GNA11 mutation at a hotspot codon (Q209) that encodes G protein α subunit q/11 polypeptides (Gα). GNAQ/11 relies on palmitoylation for membrane association and signal transduction. Despite the palmitoylation of GNAQ/11 was discovered long before, its implication in UM remains unclear.

Heritability Analyses Uncover Shared Genetic Effects of Lung Function and Change over Time.

Genetic influence on lung functions has been identified in previous studies; however, the relative longitudinal effects of genetic factors and their interactions with smoking on lung function remain unclear. Here, we identified the longitudinal effects of genetic variants on lung function by determining single nucleotide polymorphism (SNP) heritability and genetic correlations, and by analyzing interactions with smoking. Subject-specific means and annual change rates were calculated for eight spirometric measures obtained from 6622 Korean adults aged 40−69 years every two years for 14 years, and their heritabilities were estimated separately.

TMPRSS2 Serves as a Prognostic Biomarker and Correlated With Immune Infiltrates in Breast Invasive Cancer and Lung Adenocarcinoma.

TMPRSS2 is a transmembrane serine protease and plays a pivotal role in coronavirus disease 2019 (COVID-19). However, the correlation of TMPRSS2 with prognosis and immune infiltration in tumors has not yet been explored. Here, we analyzed the expression of TMPRSS2 in Oncomine and TIMER databases, the correlation between TMPRSS2 and overall survival in the PrognoScan, Kaplan-Meier plotter, and GEPIA databases.

Multistep Multiagent Reinforcement Learning for Optimal Energy Schedule Strategy of Charging Stations in Smart Grid.

An efficient energy scheduling strategy of a charging station is crucial for stabilizing the electricity market and accommodating the charging demand of electric vehicles (EVs). Most of the existing studies on energy scheduling strategies fail to coordinate the process of energy purchasing and distribution and, thus, cannot balance the energy supply and demand. Besides, the existence of multiple charging stations in a complex scenario makes it difficult to develop a unified schedule strategy for different charging stations.

Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis.

Background: Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M. pneumoniae infection in children, but macrolide-refractory M.

IRF8 Impacts Self-Renewal of Hematopoietic Stem Cells by Regulating TLR9 Signaling Pathway of Innate Immune Cells.

IRF8 is a key regulator of innate immunity receptor signaling and plays diverse functions in the development of hematopoietic cells. The effects of IRF8 on hematopoietic stem cells (HSCs) are still unknown. Here, it is demonstrated that IRF8 deficiency results in a decreased number of long-term HSCs (LT-HSCs) in mice.

A dual inhibitor overcomes drug-resistant FLT3-ITD acute myeloid leukemia.

FLT3 mutations are the most frequently identified genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Multiple FLT3 inhibitors are in various stages of clinical evaluation. However, resistance to FLT3 inhibitors resulting from acquired point mutations in tyrosine kinase domain (TKD) have limited the sustained efficacy of treatments, and a "gatekeeper" mutation (F691L) is resistant to most available FLT3 inhibitors.

DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis.

Cullin-RING E3 ubiquitin ligase (CRL)-4 is a member of the large CRL family in eukaryotes. It plays important roles in a wide range of cellular processes, organismal development, and physiological and pathological conditions. DDB1- and CUL4-associated factor 8 (DCAF8) is a WD40 repeat-containing protein, which serves as a substrate receptor for CRL4.

GNA13 regulates BCL2 expression and the sensitivity of GCB-DLBCL cells to BCL2 inhibitors in a palmitoylation-dependent manner.

GNA13, encoding one of the G protein alpha subunits of heterotrimeric G proteins that transduce signals of G protein-coupled receptors (GPCR), is frequently mutated in germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) with poor prognostic outcomes. Due to the "undruggable" nature of GNA13, targeted therapy for these patients is not available. In this study, we found that palmitoylation of GNA13 not only regulates its plasma membrane localization, but also regulates GNA13's stability.

PTPN2 regulates the activation of KRAS and plays a critical role in proliferation and survival of KRAS-driven cancer cells.

genes are the most commonly mutated in human cancers and play critical roles in tumor initiation, progression, and drug resistance. Identification of targets that block RAS signaling is pivotal to develop therapies for -related cancer. As RAS translocation to the plasma membrane (PM) is essential for its effective signal transduction, we devised a high-content screening assay to search for genes regulating KRAS membrane association.

Combination therapy of BCR-ABL-positive B cell acute lymphoblastic leukemia by tyrosine kinase inhibitor dasatinib and c-JUN N-terminal kinase inhibition.

Background: The Philadelphia chromosome (Ph), which leads to the creation and expression of the fusion gene product BCR-ABL, underlines the pathogenesis of chronic myelogenous leukemia (CML) and a fraction of adult and pediatric acute B-lymphoblastic leukemia (B-ALL). The BCR-ABL tyrosine kinase inhibitors (TKIs) have shown a remarkable clinical activity in patients with CML, but their efficacy in treating Ph B-ALL is limited. Identifying additional therapeutic targets is important for the effective treatment of Ph B-ALL.