Elucidating the causal relationship between 486 genetically predicted blood metabolites and the risk of gastric cancer: a comprehensive Mendelian randomization analysis.

Background: Previous epidemiological studies have yielded inconclusive results regarding the causality between blood metabolites and the risk of gastric cancer (GC). To address this shortcoming, we conducted a two-sample Mendelian randomization (MR) study, combined with metabolomics techniques, to elucidate the causality between 486 genetically predicted blood metabolites and GC.

Methods: MR analysis and metabolomics techniques such as ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) and gas chromatography/tandem mass spectrometry (GC-MS/MS) technologies were employed to assess the causality of 486 genetically predicted blood metabolites on the risk of GC.

Proton ARC based LATTICE radiation therapy: feasibility study, energy layer optimization and LET optimization.

LATTICE, a spatially fractionated radiation therapy (SFRT) modality, is a 3D generalization of GRID and delivers highly modulated peak-valley spatial dose distribution to tumor targets, characterized by peak-to-valley dose ratio (PVDR). Proton LATTICE is highly desirable, because of the potential synergy of the benefit from protons compared to photons, and the benefit from LATTICE compared to GRID. Proton LATTICE using standard proton RT via intensity modulated proton therapy (IMPT) (with a few beam angles) can be problematic with poor target dose coverage and high dose spill to organs-at-risk (OAR).

An epigenetically distinct HSC subset supports thymic reconstitution.

Hematopoietic stem cells (HSCs) with multilineage potential are critical for effective T cell reconstitution and restoration of the adaptive immune system after allogeneic Hematopoietic Cell Transplantation (allo-HCT). The Kit subset of HSCs is enriched for multipotential precursors, but their T-cell lineage potential has not been well-characterized. We therefore studied the thymic reconstituting and T-cell potential of Kit HSCs.

Waldenström macroglobulinemia presenting as bilateral bloody pleural effusion: A case report.

Rationale: Pleural effusion, especially bilateral bloody pleural effusion, is a rare complication of Waldenström macroglobulinemia (WM). Pleural effusion in patients with WM has many causes, such as infection, tumor invasion of the pleura, and rupture of the thoracic duct or its branches. Patients with WM presenting to the respiratory department with chest tightness and shortness of breath need more differential diagnosis by respiratory physicians, which is helpful for effective treatment.

Isolation and Culture of Primary Human Mammary Epithelial Cells.

The mammary gland is a fundamental structure of the breast and plays an essential role in reproduction. Human mammary epithelial cells (HMECs), which are the origin cells of breast cancer and other breast-related inflammatory diseases, have garnered considerable attention. However, isolating and culturing primary HMECs in vitro for research purposes has been challenging due to their highly differentiated, keratinized nature and their short lifespan.

Behavioral Studies of Zebrafish Reveal a New Perspective on the Reproductive Toxicity of Micro- and Nanoplastics.

The escalating prevalence of microplastics and nanoplastics in aquatic environments is a major challenge affecting the behavior and reproductive health of aquatic organisms while posing potential risks to human health and ecosystems. This review focuses on the neurobehavioral changes and reproductive toxicity of MNPs in zebrafish and their relationships. At the same time, the neurobehavioral changes caused by MNPs were studied, and the synergistic effects of the interaction of these pollutants with other environmental contaminants were explored.

Generation of G51D and 3D mice reveals decreased α-synuclein tetramer-monomer ratios promote Parkinson's disease phenotypes.

Mutations in the α-Synuclein (αS) gene promote αS monomer aggregation that causes neurodegeneration in familial Parkinson's disease (fPD). However, most mouse models expressing single-mutant αS transgenes develop neuronal aggregates very slowly, and few have dopaminergic cell loss, both key characteristics of PD. To accelerate neurotoxic aggregation, we previously generated fPD αS E46K mutant mice with rationally designed triple mutations based on the α-helical repeat motif structure of αS (fPD E46K→3 K).

Combined measurement of serum zinc with PSA ameliorates prostate cancer screening efficiency via support vector machine algorithms.

Background: Early screening of prostate cancer (PCa) is pivotal but challenging in the clinical scenario due to the phenomena of false positivity or false negativity of some serological evaluations, e.g. PSA testing.

Secretome Analyses Identify FKBP4 as a -Associated Protein in CSF and iPS Cells from Parkinson's Disease Patients with Mutations.

Mutations in the gene increase the risk of developing Parkinson's disease (PD). However, most carriers of mutations do not develop PD throughout their lives. The mechanisms of how mutations contribute to PD pathogenesis remain unclear.

Maternal deprivation causes CaMKII downregulation and modulates glutamate, norepinephrine and serotonin in limbic brain areas in a rat model of single prolonged stress.

Background: Early life stress is a major risk factor for later development of psychiatric disorders, including post-traumatic stress disorder (PTSD). An intricate relationship exists between various neurotransmitters (such as glutamate, norepinephrine or serotonin), calcium/calmodulin-dependent protein kinase II (CaMKII), as an important regulator of glutamatergic synaptic function, and PTSD. Here, we developed a double-hit model to investigate the interaction of maternal deprivation (MD) as an early life stress model and single prolonged stress (SPS) as a PTSD model at the behavioral and molecular levels.

A deep unrolled neural network for real-time MRI-guided brain intervention.

Accurate navigation and targeting are critical for neurological interventions including biopsy and deep brain stimulation. Real-time image guidance further improves surgical planning and MRI is ideally suited for both pre- and intra-operative imaging. However, balancing spatial and temporal resolution is a major challenge for real-time interventional MRI (i-MRI).

Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.

Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlate with PD-related motor impairments.

An orthogonal matching pursuit optimization method for solving minimum-monitor-unit problems: Applications to proton IMPT, ARC and FLASH.

Background: The intensities (i.e., number of protons in monitor unit [MU]) of deliverable proton spots need to be either zero or meet a minimum-MU (MMU) threshold, which is a nonconvex problem.

Identification and validation of a novel prognostic circadian rhythm-related gene signature for stomach adenocarcinoma.

Circadian rhythm genes were reported to be strongly associated with the development and prognosis of circadian rhythm disorders related to stomach adenocarcinoma (STAD), which is one of the most prevalent cancers. This study aimed to identify a circadian rhythm-related gene signature that could help predict STAD outcome. Using bioinformatics analysis approaches, 105 genes were examined in 350 patients with STAD.

On-Tissue Chemical Derivatization for Comprehensive Mapping of Brain Carboxyl and Aldehyde Metabolites by MALDI-MS Imaging.

The visualization of small metabolites by MALDI mass spectrometry imaging in brain tissue sections is challenging due to low detection sensitivity and high background interference. We present an on-tissue chemical derivatization MALDI mass spectrometry imaging approach for the comprehensive mapping of carboxyls and aldehydes in brain tissue sections. In this approach, the AMPP (1-(4-(aminomethyl)phenyl)pyridin-1-ium chloride) derivatization reagent is used for the covalent charge-tagging of molecules containing carboxylic acid (in the presence of peptide coupling reagents) and aldehydes.

Aberrant somatic calcium channel function in cNurr1 and LRRK2-G2019S mice.

In Parkinson's disease (PD), axons of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) degenerate before their cell bodies. Calcium influx during pacemaker firing might contribute to neuronal loss, but it is not known if dysfunctions of voltage-gated calcium channels (VGCCs) occur in DA neurons somata and axon terminals. We investigated T-type and L-type VGCCs in SNc-DA neurons of two mouse models of PD: mice with a deletion of the Nurr1 gene in DA neurons from an adult age (cNurr1 mice), and mice bearing the G2019S mutation in the gene coding for LRRK2 (G2019S mice).

SEA-Net: Structure-Enhanced Attention Network for Limited-Angle CBCT Reconstruction of Clinical Projection Data.

This work aims to improve limited-angle (LA) cone beam computed tomography (CBCT) by developing deep learning (DL) methods for real clinical CBCT projection data, which is the first feasibility study of clinical-projection-data-based LA-CBCT, to the best of our knowledge. In radiation therapy (RT), CBCT is routinely used as the on-board imaging modality for patient setup. Compared to diagnostic CT, CBCT has a long acquisition time, e.

Impaired Aversive Memory Formation in GPR37L1KO Mice.

GPR37L1 is an orphan G-protein-coupled receptor, which is implicated in neurological disorders, but its normal physiological role is poorly understood. Its close homologue, GPR37, is implicated in Parkinson's disease and affective disorders. In this study, we set out to characterize adult and middle-aged global GPR37L1 knock-out (KO) mice regarding emotional behaviors.

Decreased Prosaposin and Progranulin in the Cingulate Cortex Are Associated with Schizophrenia Pathophysiology.

Prosaposin (PSAP) and progranulin (PGRN) are two lysosomal proteins that interact and modulate the metabolism of lipids, particularly sphingolipids. Alterations in sphingolipid metabolism have been found in schizophrenia. Genetic associations of PSAP and PGRN with schizophrenia have been reported.