Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.

Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.

Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.

CRISPR/Cas9-Based Protocol for Precise Genome Editing in Induced Pluripotent Stem Cells.

The advent of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based genome editing has marked a significant advancement in genetic engineering technology. However, the editing of induced pluripotent stem cells (iPSCs) with CRISPR presents notable challenges in ensuring cell survival and achieving high editing efficiency. These challenges become even more complex when considering the specific target site.

NHC-BH-CH: synthesis, characterization and electrochemical properties of the N-heterocyclic-carbene-stabilized fullerene-borane complex.

NHC-[60]fullereborane (NHC-BH-CH) has been synthesized, isolated in pure form, and characterized. The reaction of C with NHC-borane produced NHC-BH-CH as the first air-stable and separatable fullerene-borane compound. The formation of a N-heterocyclic carbene stabilized this borane complex of C, and the structure of the complex was unambiguously determined throughsingle-crystal X-ray analysis.

Uncovering seed vigor responsive miRNA in hybrid wheat and its parents by deep sequencing.

Background: Two-line hybrid wheat technology system is one way to harness wheat heterosis both domestically and internationally. Seed vigor is a crucial parameter for assessing seed quality, as enhanced seed vigor can lead to yield increments of over 20% to a certain extent. MicroRNAs (miRNAs) were known to participate in the development and vigor of seed in plants, but its impact on seed vigor in two-line hybrid wheat remains poorly elucidated.

Ten Reasons Why Neurologists Should Refer Patients With Alzheimer Dementia to Music Therapy.

Background: Alzheimer dementia (AD) constitutes a major societal problem with devastating neuropsychiatric involvement. Pharmaceutical interventions carry a heightened risk of side effects; thus, nonpharmacological interventions such as music-based interventions (MBIs), including music therapy, are recommended.

Recent Findings: The 2023 Neurology release of the Music Based Intervention Toolkit for Brain Disorders of Aging showcased music's emerging role as an intervention to manage symptoms of various brain disorders while defining the building blocks of MBIs to guide research in the exploration of music's therapeutic potential.

Andrographolide suppresses the malignancy of pancreatic cancer via alleviating DNMT3B-dependent repression of tumor suppressor gene ZNF382.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type that urgently requires effective therapeutic strategies. Andrographolide, a labdane diterpenoid compound abundant in Andrographis paniculata, has anticancer effects against various cancer types, but its anticancer activity and mechanism against PDAC remain largely uncharacterized.

Purpose: This study explores novel drug target(s) and underlying molecular mechanism of andrographolide against PDAC.

AGR2-mediated unconventional secretion of 14-3-3ε and α-actinin-4, responsive to ER stress and autophagy, drives chemotaxis in canine mammary tumor cells.

Background: Canine mammary tumors (CMTs) in intact female dogs provide a natural model for investigating metastatic human cancers. Our prior research identified elevated expression of Anterior Gradient 2 (AGR2), a protein disulfide isomerase (PDI) primarily found in the endoplasmic reticulum (ER), in CMT tissues, highly associated with CMT progression. We further demonstrated that increased AGR2 expression actively influences the extracellular microenvironment, promoting chemotaxis in CMT cells.

A high efficiency precision genome editing method with CRISPR in iPSCs.

The use of genetic engineering to generate point mutations in induced pluripotent stem cells (iPSCs) is essential for studying a specific genetic effect in an isogenic background. We demonstrate that a combination of p53 inhibition and pro-survival small molecules achieves a homologous recombination rate higher than 90% using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in human iPSCs. Our protocol reduces the effort and time required to create isogenic lines.

High-Selectivity Hydrogen Gas Sensors based on Mesoporous PbO-ZnO Nanocomposites.

Hydrogen heralded as a promising renewable and environmentally friendly energy carrier, carries inherent risks owing to its highly flammable nature. A mere 4 % concentration of hydrogen in the air can trigger an explosion. To counteract this peril, a composite material comprising PbO-ZnO (2 : 1) was synthesized, characterized, and subsequently employed to fabricate a hydrogen sensing device.

Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection: a randomized controlled trial.

Background: Saline nasal irrigation is an effective therapy for relieving common cold symptoms. This study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation (PSNI) on children with mild and asymptomatic infection with Omicron.

Methods: This randomized controlled trial was conducted in Shanghai, China, and 403 children with mild and asymptomatic infection with Omicron were included.

The landscape of abnormal pathway activation confers COVID-19 patients' molecular sequelae earlier than clinical phenotype.

The 2019 coronavirus disease (COVID-19) pandemic poses a significant threat to human health. After SARS-CoV-2 infection, major clinical concerns are organ damage and possible sequelae. In this study, we analyzed serum multi-omics data based on population-level, including healthy cohort, non-COVID-19 and COVID-19 covered different severity cohorts.

[Treatment and prognosis analysis of 488 patients with FIGO 2018 stage Ⅲc squamous cervical cancer].

To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy).

Active regression model for clinical grading of COVID-19.

Background: In the therapeutic process of COVID-19, the majority of indicators that physicians have for assisting treatment have come from clinical tests represented by proteins, metabolites, and immune levels in patients' blood. Therefore, this study constructs an individualized treatment model based on deep learning methods, aiming to realize timely intervention based on clinical test indicator data of COVID-19 patients and provide an important theoretical basis for optimizing medical resource allocation.

Methods: This study collected clinical data from a total of 1,799 individuals, including 560 controls for non-respiratory infectious diseases (Negative), 681 controls for other respiratory virus infections (Other), and 558 coronavirus infections (Positive) for COVID-19.

Evaluation of FeO-MnO@RGO magnetic nanocomposite as an effective persulfate activator and metal adsorbent in aqueous solution.

A reduced graphene oxide (RGO) supported FeO-MnO nanocomposite (FeO-MnO@RGO) was successfully prepared for catalytic degradation of oxytetracycline (20 mg/L) by potassium persulfate (PS) and adsorption removal of mixture of Pb, Cu, and Cd ions (each 0.2 mM) in the synchronous scenario. The removal efficiencies of oxytetracycline, Pb, Cu, and Cd ions were observed as high as 100%, 99.

Diagnostic AI Modeling and Pseudo Time Series Profiling of AD and PD Based on Individualized Serum Proteome Data.

Parkinson's disease (PD), Alzheimer's disease (AD) are common neurodegenerative disease, while mild cognitive impairment (MCI) may be happened in the early stage of AD or PD. Blood biomarkers are considered to be less invasive, less cost and more convenient, and there is tremendous potential for the diagnosis and prediction of neurodegenerative diseases. As a recently mentioned field, artificial intelligence (AI) is often applied in biology and shows excellent results.

CaSee: A lightning transfer-learning model directly used to discriminate cancer/normal cells from scRNA-seq.

Single-cell RNA sequencing (scRNA-seq) is one of the most efficient technologies for human tumor research. However, data analysis is still faced with technical challenges, especially the difficulty in efficiently and accurately discriminating cancer/normal cells in the scRNA-seq expression matrix. If we can address these challenges, we can have a deeper understanding of the intratumoral and intertumoral heterogeneity.

The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors.

Canine mammary tumor (CMT) is the most prevalent neoplasm in female dogs. Tumor recurrence and metastasis occur in malignant CMT (MMT) dogs after surgery. Identification of serum prognostic biomarkers holds the potential to facilitate prediction of disease outcomes.

Photochromic Dithienylethene Monolayer-Modified Gold Nanoparticles as a Tunable Floating Gate in the Fabrication of Nonvolatile Organic Memory.

Nonvolatile memory (NVM) devices were fabricated by implanting a self-assembled monolayer (SAM) of functional dithienylethene (DTE) derivative on the gold nanoparticle (Au-NP) surface in a pentacene-based organic transistor. The Au-NPs and DTE served as a charge-trapping medium and tunneling barrier layer, respectively. The transfer characteristic of the NVM device showed a narrow hysteresis window and wide memory window, indicating that the DTE-SAM served as a variable barrier layer to regulate the trapping and detrapping of external free charges at the Au-NPs.

Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease.

While amyloid-β (Aβ) plaques are considered a hallmark of Alzheimer's disease, clinical trials focused on targeting gamma secretase, an enzyme involved in aberrant Aβ peptide production, have not led to amelioration of AD symptoms or synaptic dysregulation. Screening strategies based on mechanistic, multi-omics approaches that go beyond pathological readouts can aid in the evaluation of therapeutics. Using early-onset Alzheimer's (EOFAD) disease patient lineage PSEN1 iPSC-derived neurons, we performed RNA-seq to characterize AD-associated endotypes, which are in turn used as a screening evaluation metric for two gamma secretase drugs, the inhibitor Semagacestat and the modulator BPN-15606.

Application of Artificial Intelligence Modeling Technology Based on Fluid Biopsy to Diagnose Alzheimer's Disease.

There are no obvious clinical signs and symptoms in the early stages of Alzheimer's disease (AD), and most patients usually have mild cognitive impairment (MCI) before diagnosis. Therefore, early diagnosis of AD is very critical. This paper mainly discusses the blood biomarkers of AD patients and uses machine learning methods to study the changes of blood transcriptome during the development of AD and to search for potential blood biomarkers for AD.

Serum Level of Tumor-Overexpressed AGR2 Is Significantly Associated with Unfavorable Prognosis of Canine Malignant Mammary Tumors.

Canine malignant mammary tumors (MMTs) are prevalent malignancy in intact female dogs with a high incidence of metastasis and recurrence. A current lack of easily accessible tumor biomarkers hinders a timely assessment of the disease outcome. We previously identified anterior gradient protein 2 (AGR2) with higher protein abundance in canine MMT tissues compared with normal counterparts.