The UPRising connection between endoplasmic reticulum stress and the tumor microenvironment.

The tumor microenvironment (TME) represents a dynamic network of cancer cells, stromal cells, immune mediators, and extracellular matrix components, crucial for cancer progression. Stress conditions such as oncogene activation, nutrient deprivation, and hypoxia disrupt the endoplasmic reticulum (ER), activating the unfolded protein response (UPR), the main adaptive mechanism to restore ER function. The UPR regulates cancer progression by engaging cell-autonomous and cell-non-autonomous mechanisms, reprogramming the stroma and promoting immune evasion, angiogenesis, and invasion.

Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in COPD.

Unlabelled: Rationale/Objective: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively.

Methods: Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene.

Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N-of-1 trial.

Background And Purpose: Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD.

The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi.

The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex uses its rhomboid pseudo-protease subunit, Dsc2, to assess the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex likely interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation.

Screening of BindingDB database ligands against EGFR, HER2, Estrogen, Progesterone and NF-κB receptors based on machine learning and molecular docking.

Breast cancer, the second most prevalent cancer among women worldwide, necessitates the exploration of novel therapeutic approaches. To target the four subgroups of breast cancer "hormone receptor-positive and HER2-negative, hormone receptor-positive and HER2-positive, hormone receptor-negative and HER2-positive, and hormone receptor-negative and HER2-negative" it is crucial to inhibit specific targets such as EGFR, HER2, ER, NF-κB, and PR. In this study, we evaluated various methods for binary and multiclass classification.

Dopaminergic- and Serotonergic-Dependent Behaviors Are Altered by Lanthanide Series Metals in .

The lanthanide series elements are transition metals used as critical components of electronics, as well as rechargeable batteries, fertilizers, antimicrobials, contrast agents for medical imaging, and diesel fuel additives. With the surge in their utilization, lanthanide metals are being found more in our environment. However, little is known about the health effects associated with lanthanide exposure.

Potential of Marine Sponge Metabolites against Prions: Bromotyrosine Derivatives, a Family of Interest.

The screening of 166 extracts from tropical marine organisms (invertebrates, macroalgae) and 3 cyclolipopeptides from microorganisms against yeast prions highlighted the potential of Verongiida sponges to prevent the propagation of prions. We isolated the known compounds purealidin Q (), aplysamine-2 (), pseudoceratinine A (), aerophobin-2 (), aplysamine-1 (), and pseudoceratinine B () for the first time from the Wallisian sponge . We then tested compounds - and sixteen other bromotyrosine and bromophenol derivatives previously isolated from Verongiida sponges against yeast prions, demonstrating the potential of -, , , aplyzanzine C (), purealidin A (), psammaplysenes D () and F (), anomoian F (), and N,N-dimethyldibromotyramine ().

The Gene in the Unfolded Protein Response Pathway Is a Candidate Target for Host-Induced Gene Silencing.

Fungal HacA/Hac1 transcription factors play a crucial role in regulating the unfolded protein response (UPR). The UPR helps cells to maintain endoplasmic reticulum (ER) protein homeostasis, which is critical for growth, development, and virulence. The gene encodes a domain rich in basic and acidic amino acids (Bsc) and a basic leucine zipper (bZip) domain, and features a non-conventional intron (Nt20).

Association between Left Atrial Function and Survival in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multisystemic autoimmune disorder in which cardiac involvement is frequent and portends negative prognosis. Left ventricular (LV) diastolic dysfunction is one of the most common cardiac alterations in these patients, and left atrial (LA) reservoir strain (Ɛ) measurement using speckle tracking echocardiography has been proposed as a novel parameter for a better assessment of LV diastolic function. Therefore, the aim of this study was to test the prognostic value of Ɛ in a large multicenter cohort of SSc patients.

A comprehensive luminal breast cancer patient-derived xenografts (PDX) library to capture tumor heterogeneity and explore the mechanisms of resistance to CDK4/6 inhibitors.

Breast cancer (BC) is marked by significant genetic, morphological and clinical heterogeneity. To capture this heterogeneity and unravel the molecular mechanisms driving tumor progression and drug resistance, we established a comprehensive patient-derived xenograft (PDX) biobank, focusing particularly on luminal (estrogen receptor, ER+) and young premenopausal patients, for whom PDX models are currently scarce. Across all BC subtypes, our efforts resulted in an overall success rate of 17% (26 established PDX lines out of 151 total attempts), specifically 15% in luminal, 12% in human epidermal growth factor receptor 2 positive (HER2+) and 35% in triple negative BC.

The first example of polymeric lanthanide -trifluoroacetates in chemical solution deposition of up-converting NaGdF:Yb,Er,Nd thin films.

A series of lanthanide -trifluoroacetates {(detaH)[La(tfa)](CHCN)(HO)} and (detaH)[Ln(tfa)] (Ln = Pr-Eu), mixed-ligand complexes [La(tfa)(CHCN)(HO)], [Gd(tfa)(deta)](PrOH) and [Yb(tfa)(deta)](tfa), as well as detaH(tfa) were isolated and characterized. All lanthanide -trifluoroacetates contain two types of 1D anionic chains [Ln(tfa)] and cavities occupied by detaH cations and solvating HO and CHCN molecules. The thermal behavior of (detaH)[Ln(tfa)] in air is investigated by TGA, VT-PXRD and total X-ray scattering with PDF analysis, and the formation of metal fluorides occurs upon heating to 300 °C.

Subclassification of obesity for precision prediction of cardiometabolic diseases.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000).

Measurement reproducibility and storage impact on VOC/SVOC emission rate from decorative materials.

Building materials are the major sources of Volatile and Semi-Volatile Organic Compounds (VOCs and SVOCs) in indoor air. Measurements of emission rates of these compounds are likely to be influenced by variation in certain environmental factors resulting in intra-specimen variability. This study aims to (i) evaluate the reproducibility of measurements between specimens and (ii) evaluate the impact of storage on VOC and SVOC emissions from antifungal acrylic paint (applied on polyester-cellulose).

Clinical Approach to STRIDE-II in Real-Life Settings: Analysis and Practical Recommendations.

Background: We aimed to (1) analyze the applicability of the updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations in real-world clinical practice, (2) identify barriers to their implementation, and (3) propose practical measures to overcome these obstacles.

Methods: This qualitative study was based on a survey, a literature review, and expert opinions. Nine inflammatory bowel disease (IBD) experts identified 7 areas likely to be controversial or potential implementation barriers in daily clinical practice: endoscopy, histology, ultrasound, quality of life, biomarkers, symptom control, and patient-reported outcomes (PROs).

In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions.

Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear.

Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis.

Rab11 family interacting protein 4 (Rab11-FIP4) regulates endocytic trafficking. A possible role for Rab11-FIP4 in the regulation of lysosomal function has been proposed, but its precise function in the regulation of cellular homeostasis is unknown. By mRNA array and protein analysis, we found that Rab11-FIP4 is downregulated in the lysosomal storage disease cystinosis, which is caused by genetic defects in the lysosomal cystine transporter, cystinosin.

Glucose impacts onto the reciprocal reprogramming between mammary adipocytes and cancer cells.

An established hallmark of cancer cells is metabolic reprogramming, largely consisting in the exacerbated glucose uptake. Adipocytes in the tumor microenvironment contribute toward breast cancer (BC) progression and are highly responsive to metabolic fluctuations. Metabolic conditions characterizing obesity and/or diabetes associate with increased BC incidence and mortality.

Reaching and stepping respond differently to medication and cueing in Parkinson's disease.

The basal ganglia contribute to internal timekeeping, and dopaminergic medication has been observed to moderate timing deficits associated with Parkinson's Disease (PD) during single joint movements. However, it is unclear whether similar effects can be observed in multi-joint movements. Twenty-five people with PD and twelve healthy peers performed repetitive reaching and stepping-in-place tasks with and without auditory cues at their self-selected maximal cadence.

Identification of new therapeutic targets related to endoplasmic reticulum stress and mitochondrial dysfunction to reduce the risk of rupture in degenerative ascending aortic aneurysm.

Background: Ascending Thoracic Aortic Aneurysm (ATAA) is a progressive dilation of the aorta that can be complicated by its dissection leading to death in 80-90% of the patients. When associated with aging and atherosclerosis, the outcome is worse and reconstructive surgery is the only effective therapy. Our objective was to characterize differential expressed genes (DEG) involved in endoplasmic reticulum (ER) and mitochondria dysfunction in patients with degenerative ATAA.

Unlocking nature's brilliance: using Antarctic extremophile Shewanella baltica to biosynthesize lanthanide-containing nanoparticles with optical up-conversion.

Both lanthanide-containing and fluorine-containing nanomaterials present challenging targets for microbial biosynthesis because these elements are toxic to most bacteria. Here, we overcome these challenges by using an Antarctic Shewanella baltica strain that tolerates these elements and report the first biosynthesis of lanthanide-doped fluoride nanoparticles (NPs) from them. NaYF NPs doped with Er/Yb are prototypical lanthanide-based upconverting nanoparticles (UCNPs) with upconverted luminescence at visible wavelengths under infrared excitation.

DAB2IP loss in luminal a breast cancer leads to NF-κB-associated aggressive oncogenic phenotypes.

Despite proven therapy options for estrogen receptor-positive (ER+) breast tumors, a substantial number of patients with ER+ breast cancer exhibit relapse with associated metastasis. Loss of expression of RasGAPs leads to poor outcomes in several cancers, including breast cancer. Mining the The Cancer Genome Atlas (TCGA) breast cancer RNA-Seq dataset revealed that low expression of the RasGAP DAB2IP was associated with a significant decrease in relapse-free survival in patients with Luminal A breast cancer.

Synthesis of Amphiphilic Polyacrylates as Peelable Coatings for Optical Surface Cleaning.

Optical instruments require extremely high precision, and even minor surface contamination can severely impact their performance. Peelable coatings offer an effective and non-damaging method for removing contaminants from optical surfaces. In this study, an amphiphilic polyacrylate copolymer (PMLEA) was synthesized via solution radical copolymerization using the lipophilic monomer lauryl acrylate (LA) and hydrophilic monomers ER-10, methyl methacrylate (MMA), and butyl acrylate (BA).

Eligibility for Adjuvant Cyclin-Dependent Kinase 4/6 Inhibitors in Endocrine Receptor-Positive and HER2-Negative Early Breast Cancer by Age and Type of Surgery.

Despite early diagnosis, approximately 20% of patients with ER-positive and HER2-negative breast cancer (BC) will experience disease recurrence. Improved survival has been reported with adjuvant treatment combining cyclin-dependent kinase 4/6 inhibitors with endocrine therapy, in high-risk patients with ER-positive and HER2-negative BC, regardless of age. Older patients have higher rates of ER-positive/HER2-negative BC than younger patients.