Melanophilin-induced primary cilia promote pancreatic cancer metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors because of its high metastatic ability. The glutamine (Gln)-deficient microenvironment contributes to PDAC metastasis; however, the underlying molecular mechanisms remain unclear. Here, we demonstrated that melanophilin (MLPH) promotes PDAC metastasis by inducing the regrowth of primary cilia.

Recombinant Thrombomodulin Domain 1 Modulates Macrophage Polarization and Enhances Healing in Corneal Alkali Burns.

Purpose: Corneal alkali burns are severe ocular injuries characterized by intense inflammation, tissue damage, and vision impairment, with current treatments often insufficient in restoring corneal function and clarity. This study aimed to evaluate the therapeutic effects of recombinant thrombomodulin domain 1 (rTMD1) in the treatment of corneal alkali burns, focusing on its impact on inflammation, tissue repair, fibrosis, and neovascularization.

Methods: A murine model of corneal alkali burn was utilized to investigate the therapeutic potential of rTMD1.

Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase.

Gene-directed enzyme prodrug therapy (GDEPT) has been developed over several decades as a targeted cancer treatment aimed at minimizing toxicity to healthy cells. This approach involves three key components: a non-toxic prodrug, a gene encoding an enzyme that converts the prodrug into an active chemotherapy drug, and a gene carrier to target cancer cells. In this study, the prodrug doxifluridine was enzymatically converted into the chemotherapy drug 5-fluorouracil via thymidine phosphorylase, using human mesenchymal stem cells (hMSCs) as delivery vehicles.

Mental and Physical Wellbeing of Carer-Employees in Canada.

Today, an increasing number of Canadian adults are providing unpaid care to their family members and friends while working full or part-time. We conducted a national survey of unpaid caregiving for older people in 2022 to learn who these people are, why they care, and to identify the social, economic, and health impacts of unpaid caregiving. Our findings show that many of these caregivers are also employees.

Wearable and implantable biosensors: mechanisms and applications in closed-loop therapeutic systems.

This review article examines the current state of wearable and implantable biosensors, offering an overview of their biosensing mechanisms and applications. We also delve into integrating these biosensors with therapeutic systems, discussing their operational principles and incorporation into closed-loop devices. Biosensing strategies are broadly categorized into chemical sensing for biomarker detection, physical sensing for monitoring physiological conditions such as pressure and temperature, and electrophysiological sensing for capturing bioelectrical activities.

Extracellular vesicles isolated from Arabidopsis thaliana leaves reveal characteristics of mammalian exosomes.

Plant-derived extracellular vesicles (EVs), containing a myriad of bioactive proteins, microRNAs, lipids, and secondary metabolites, have recently become the focus of rising interest due to their important roles in various applications. The widely accepted method for isolating plant EVs is differential ultracentrifugation plus density gradient centrifugation. However, the combination of differential ultracentrifugation and density gradient centrifugation for the isolation of plant EVs is time-consuming and labor-intensive.

The Pros and Cons of Hystero-preservation on Pelvic Reconstructive Surgery.

In the "boat at the dock" theory, pelvic organ prolapse (POP) may happen when the ropes (uterine supportive ligaments) break and/or the water level drops (pelvic floor muscles). Thus, it causes the boat (uterus and other pelvic organs) to slip from normal position and protrude out of the vagina. Surgical intervention with or without hysterectomy (hystero-preservation) is the most effective treatment for POP.

Inactivation of SARS-CoV-2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Gold Nanorods under Near-Infrared Laser Irradiation.

Since the angiotensin-converting enzyme 2 (ACE2) protein is abundant on the surface of respiratory cells in the lungs, it has been confirmed to be the entry-point receptor for the spike glycoprotein of SARS-CoV-2. As such, gold nanorods (AuNRs) functionalized with ACE2 ectodomain (ACE2ED) act not only as decoys for these viruses to keep them from binding with the ACE2-expressing cells but also as agents to ablate infectious virions through heat generated from AuNRs under near-infrared (NIR) laser irradiation. Using plasmid containing the SARS-CoV-2 spike protein gene (with a D614G mutation), spike protein pseudotyped viral particles with a lentiviral core and green fluorescent protein reporter were constructed and used for transfecting ACE2-expressing HEK293T cells.

Inhibition of SARS-CoV-2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Micro/Nanoparticles.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral infection is reliant upon the binding between angiotensin-converting enzyme 2 receptor (ACE2) and spike protein (S). Therefore, ACE2 is a key receptor for SARS-CoV-2 to infect the host.

Modularity and diversity of target selectors in Tn7 transposons.

To spread, transposons must integrate into target sites without disruption of essential genes while avoiding host defense systems. Tn7-like transposons employ multiple mechanisms for target-site selection, including protein-guided targeting and, in CRISPR-associated transposons (CASTs), RNA-guided targeting. Combining phylogenomic and structural analyses, we conducted a broad survey of target selectors, revealing diverse mechanisms used by Tn7 to recognize target sites, including previously uncharacterized target-selector proteins found in newly discovered transposable elements (TEs).

Optogenetically engineered Ca2+ oscillation-mediated DRP1 activation promotes mitochondrial fission and cell death.

Mitochondrial dynamics regulate the quality and morphology of mitochondria. Calcium (Ca2+) plays an important role in regulating mitochondrial function. Here, we investigated the effects of optogenetically engineered Ca2+ signaling on mitochondrial dynamics.

Engineering of Cyano Functionalized Benzo[]imidazol-2-ylidene Ir(III) Phosphors for Blue Organic Light-Emitting Diodes.

In this study, we designed and synthesized three series of blue emitting homoleptic iridium(III) phosphors bearing 4-cyano-3-methyl-1-phenyl-6-(trifluoromethyl)-benzo[]imidazol-2-ylidene (mfcp), 5-cyano-1-methyl-3-phenyl-6-(trifluoromethyl)-benzo[]imidazol-2-ylidene (ofcp), and 1-(3-(-butyl)phenyl)-6-cyano-3-methyl-4-(trifluoromethyl)-benzo[]imidazol-2-ylidene (5-mfcp) cyclometalates, respectively. These iridium complexes exhibit intense phosphorescence in the high energy region of 435-513 nm in the solution state at RT, to which the relatively large T → S transition dipole moment is beneficial for serving as a pure emitter and an energy donor to the multiresonance thermally activated delayed fluorescence (MR-TADF) terminal emitters via Förster resonance energy transfer (FRET). The resulting OLEDs achieved true blue, narrow bandwidth EL with a max EQE of 16-19% and great suppression of efficiency roll-off with ν-DABNA and -DABNA.

ATM- and ATR-induced primary ciliogenesis promotes cisplatin resistance in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of its late diagnosis and chemoresistance. Primary cilia, the cellular antennae, are observed in most human cells to maintain development and differentiation. Primary cilia are gradually lost during the progression of pancreatic cancer and are eventually absent in PDAC.

Profiling the Genome-Wide Landscape of Short Tandem Repeats by Long-Read Sequencing.

Short tandem repeats (STRs) are highly variable elements that play a pivotal role in multiple genetic diseases and the regulation of gene expression. Long-read sequencing (LRS) offers a potential solution to genome-wide STR analysis. However, characterizing STRs in human genomes using LRS on a large population scale has not been reported.

Detection of Structural Variations and Fusion Genes in Breast Cancer Samples Using Third-Generation Sequencing.

Structural variations (SVs) are common genetic alterations in the human genome that could cause different phenotypes and diseases, including cancer. However, the detection of structural variations using the second-generation sequencing was limited by its short read length, which restrained our understanding of structural variations. In this study, we developed a 28-gene panel for long-read sequencing and employed it to Oxford Nanopore Technologies and Pacific Biosciences platforms.

Recombinant thrombomodulin domain 1 rescues pathological angiogenesis by inhibition of HIF-1α-VEGF pathway.

Pathological angiogenesis (PA) contributes to various ocular diseases, including age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, which are major causes of blindness over the world. Current treatments focus on anti-vascular endothelial growth factor (VEGF) therapy, but persistent avascular retina, recurrent intravitreal neovascularization, and general adverse effects are reported. We have previously found that recombinant thrombomodulin domain 1 (rTMD1) can suppress vascular inflammation.

SREBP1-Induced Glutamine Synthetase Triggers a Feedforward Loop to Upregulate SREBP1 through Sp1 O-GlcNAcylation and Augments Lipid Droplet Formation in Cancer Cells.

Glutamine and lipids are two important components of proliferating cancer cells. Studies have demonstrated that glutamine synthetase (GS) boosts glutamine-dependent anabolic processes for nucleotide and protein synthesis, but the role of GS in regulating lipogenesis remains unclear. This study identified that insulin and glutamine deprivation activated the lipogenic transcription factor sterol regulatory element-binding protein 1 (SREBP1) that bound to the GS promoter and increased its transcription.

Screening of sleep assisting drug candidates with a Drosophila model.

Lately, Drosophila has been favored as a model in sleep and circadian rhythm research due to its conserved mechanism and easily manageable operation. These studies have revealed the sophisticated parameters in whole-day sleep profiles of Drosophila, drawing connections between Drosophila sleep and human sleep. In this study, we tested several sleep deprivation protocols (mechanical shakes and light interruptions) on Drosophila and delineated their influences on Drosophila sleep.

Pathophysiological implications of hypoxia in human diseases.

Oxygen is essentially required by most eukaryotic organisms as a scavenger to remove harmful electron and hydrogen ions or as a critical substrate to ensure the proper execution of enzymatic reactions. All nucleated cells can sense oxygen concentration and respond to reduced oxygen availability (hypoxia). When oxygen delivery is disrupted or reduced, the organisms will develop numerous adaptive mechanisms to facilitate cells survived in the hypoxic condition.

Safety of intrastromal injection of polyhexamethylene biguanide and propamidine isethionate in a rabbit model.

keratitis (AK) is difficult to treat, especially when the corneal deep stroma is involved. Intrastromal injection of antimicrobial agents is an effective adjuvant therapy for deep recalcitrant microbial keratitis; however, it has not been used to treat AK due to suspected drug toxicity. The purpose of this study was to evaluate the toxicity of corneal intrastromal injection of polyhexamethylene biguanide (PHMB) and propamidine isethionate (Brolene®, Sanofi) in New Zealand white rabbits.

Dysregulation of antimicrobial peptide expression distinguishes Alzheimer's disease from normal aging.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with unknown mechanism that is characterized by the aggregation of abnormal proteins and dysfunction of immune responses. In this study, an integrative approach employing analysis and wet-lab experiment was conducted to estimate the degrees of innate immune system relevant gene expression, neurotoxic Aβ generation and neuronal apoptosis in normal and a transgenic model of AD. Results demonstrated mRNA levels of antimicrobial peptide (AMP) genes gradually increased with age in wild-type flies, while which exhibited a trend for an initial decrease followed by subsequent increase during aging in the AD group.

A model to predict NAPLEX outcomes and identify students needing additional preparation.

Introduction: Studies have been conducted to identify factors that may predict North American Pharmacist Licensure Examination (NAPLEX) outcomes, but there is no proposed single or combination of predictors that can be implemented reliably in academia. We aimed to develop a NAPLEX outcomes predictive model that could be practical, measurable, and reliable.

Methods: The study cohort consisted of students who graduated from 2012 to 2016 who had taken NAPLEX and whose first-attempt examination scores were available to the school of pharmacy.

IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis.

IL-17 has been implicated in the pathogenesis of multiple sclerosis (MS). Here, we show that blockade of IL-17A, but not IL-17F, attenuated experimental autoimmune encephalomyelitis (EAE). We further show that IL-17A levels were elevated in the CSF of relapsing-remitting MS (RRMS) patients and that they correlated with the CSF/serum albumin quotient (Qalb), a measure of blood-brain barrier (BBB) dysfunction.