Comparative proteomic analysis of human vitreous in rhegmatogenous retinal detachment and diabetic retinopathy reveals a common pathway and potential therapeutic target.

Background: The vitreous humor serves as a window into the physiological and pathological processes of the eye, particularly the retina. Diabetic retinopathy (DR), a leading cause of blindness, involves hyperglycemia-induced damage to retinal cells, leading to ischemia and elevated nitric oxide levels, culminating in vascular proliferation. Rhegmatogenous retinal detachment (RD) results from a break in the neuroretina, triggering ischemia, photoreceptor death, and cellular proliferation.

CD81-guided heterologous EVs present heterogeneous interactions with breast cancer cells.

Background: Extracellular vesicles (EVs) are cell-secreted particles conceived as natural vehicles for intercellular communication. The capacity to entrap heterogeneous molecular cargoes and target specific cell populations through EV functionalization promises advancements in biomedical applications. However, the efficiency of the obtained EVs, the contribution of cell-exposed receptors to EV interactions, and the predictability of functional cargo release with potential sharing of high molecular weight recombinant mRNAs are crucial for advancing heterologous EVs in targeted therapy applications.

Fatigue strength of bilayer yttria-stabilized zirconia after low-temperature degradation.

This study examined the impact of interfacial interactions on bilayer yttria-stabilized zirconia (YSZ) used in dental restorations. In-house bilayer structures of 3YSZ and 5YSZ composition underwent hydrothermal degradation to compare the properties of control and low-temperature degradation (LTD) treated groups. Biaxial flexural strength via piston-on-three-balls, staircase fatigue strength over 10 cycles at 15 Hz, phase characterization and quantification through XRD and Rietveld refinement, and fractography were conducted.

Synthesis of Gelatin Methacryloyl Analogs and Their Use in the Fabrication of pH-Responsive Microspheres.

pH-responsive hydrogels have numerous applications in tissue engineering, drug delivery systems, and diagnostics. Gelatin methacryloyl (GelMA) is a biocompatible, semi-synthetic polymer prepared from gelatin. When combined with aqueous solvents, GelMA forms hydrogels that have extensive applications in biomedical engineering.

Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer.

Purpose: This phase 1b/2 trial evaluated the efficacy and safety of capmatinib plus nazartinib in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC).

Methods: In phase 1b, patients with progression on first-/second-generation EGFR-TKIs received escalating doses of capmatinib 200-400 mg bid plus nazartinib 50-150 mg qd. Once the MTD/RP2D was declared, phase 2 commenced with patient enrollment into groups according to mutation status and prior lines of treatment: group 1 (fasted; EGFR-TKI resistant; 1-3 prior lines; EGFR; any T790M/MET); group 2 (fasted; EGFR-TKI naïve; 0-2 prior lines; de novo T790M+; any MET); group 3 (fasted; treatment-naïve; EGFR; T790M-; any MET); group 4 (with food; 0-2 prior lines; EGFR; any T790M/MET).

MicroRNA and renal fibrosis in autosomal dominant polycystic kidney disease: a longitudinal study.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder that may progress to kidney failure, accounting for 5-10% of all patients with end-stage kidney disease (ESKD). Clinical data, as well as molecular genetics and advanced imaging techniques have provided surrogate prognostic biomarkers to predict rapid decline in kidney function, nonetheless enhanced tools for assessing prognosis for ADPKD are still needed. The aim of this study was to analyze specific microRNAs involved in the pathogenesis of ADPKD and in the development of renal fibrosis, evaluating their potential role as predictors of renal function loss.

Nickel binding enables isolation and reactivity of previously inaccessible 7-aza-2,3-indolynes.

N-Heteroaromatics are key elements of pharmaceuticals, agrochemicals, and materials. N-Heteroarynes provide a scaffold to build these essential molecules but are underused because five-membered N-heteroarynes have been largely inaccessible on account of the strain of a triple bond in that small of a ring. On the basis of principles of metal-ligand interactions that are foundational to organometallic chemistry, in this work we report the stabilization of five-membered N-heteroarynes in the nickel coordination sphere.

Glass science behind lithium silicate glass-ceramics.

Objectives: Lithium silicate-based glass ceramics have evolved as a paramount restorative material in restorative and prosthetic dentistry, exhibiting outstanding esthetic and mechanical performance. Along with subtractive machining techniques, this material class has conquered the market and satisfied the patients' needs for a long-lasting, excellent, and metal-free alternative for single tooth replacements and even smaller bridgework. Despite the popularity, not much is known about the material chemistry, microstructure and terminal behaviour.

Role of HIV-1 Tat Protein Interactions with Host Receptors in HIV Infection and Pathogenesis.

Each time the virus starts a new round of expression/replication, even under effective antiretroviral therapy (ART), the transactivator of viral transcription Tat is one of the first HIV-1 protein to be produced, as it is strictly required for HIV replication and spreading. At this stage, most of the Tat protein exits infected cells, accumulates in the extracellular matrix and exerts profound effects on both the virus and neighbor cells, mostly of the innate and adaptive immune systems. Through these effects, extracellular Tat contributes to the acquisition of infection, spreading and progression to AIDS in untreated patients, or to non-AIDS co-morbidities in ART-treated individuals, who experience inflammation and immune activation despite virus suppression.

Exploring Electrophilic Hydrophosphination via Metal Phosphenium Intermediates.

Two Mo(0) phosphenium complexes containing ancillary secondary phosphine ligands have been investigated with respect to their ability to participate in electrophilic addition at unsaturated substrates and subsequent P-H hydride transfer to "quench" the resulting carbocations. These studies provide stoichiometric "proof of concept" for a proposed new metal-catalyzed electrophilic hydrophosphination mechanism. The more strongly Lewis acidic phosphenium complex, [Mo(CO)(PRH)(PR)] (R=Ph, Tol), cleanly hydrophosphinates 1,1-diphenylethylene, benzophenone, and ethylene, while other substrates react rapidly to give products resulting from competing electrophilic processes.

NOC1 is a direct MYC target, and its protein interactome dissects its activity in controlling nucleolar function.

The nucleolus is a subnuclear compartment critical in ribosome biogenesis and cellular stress responses. These mechanisms are governed by a complex interplay of proteins, including NOC1, a member of the NOC family of nucleolar proteins responsible for controlling rRNA processing and ribosomal maturation. This study reveals a novel relationship between NOC1 and MYC transcription factor, known for its crucial role in controlling ribosomal biogenesis, cell growth, and proliferation.

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer.

Background: Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia.

Small non-coding RNA profiling in patients with gastrointestinal cancer.

Background: Small non-coding (snc)RNAs, including microRNAs and P-element induced wimpy testis (PIWI)-interacting-RNAs (piRNAs), crucially regulate gene expression in both physiological and pathological conditions. In particular, some muscle-specific microRNAs (myomiRs) have been involved in the pathogenesis of cancer-induced muscle wasting. The aims of the present study were (i) to profile sncRNAs in both skeletal muscle and plasma of gastrointestinal cancer patients and (ii) to investigate the association among differentially expressed sncRNAs and the level of muscularity at body composition analysis.

Epidemiological and molecular characterization of HBV and HCV infections in HIV-1-infected inmate population in Italy: a 2017-2019 multicenter cross-sectional study.

HBV/HCV co-infection is common in HIV-1-infected prisoners. To investigate the characteristics of HIV co-infections, and to evaluate the molecular heterogeneity of HIV, HBV and HCV in prisoners, we carried-out a multicenter cross-sectional study, including 65 HIV-1-infected inmates enrolled in 5 Italian detention centers during the period 2017-2019. HIV-1 subtyping showed that 77.

Fatigue Threshold R-Curves for Dental Lithium Disilicate Glass-Ceramics.

Chemical and mechanical fatigue degradation in ceramic materials is generally inconspicuous yet ubiquitous, to the effect that clinical fractures still consist of the main cause of failure in all-ceramic restorations. Implications of this span wide, from a reduced survival prognosis for the affected teeth, including more frequent and increasingly invasive procedural interventions, to the financial burden borne by individuals and health care systems. To suffice as an effective corrective, restoration lifetimes need only to be extended so to outlive the patient.

Development of Y-TZP/MWCNT-SiO nanocomposite for dental protheses.

Y-TZP/MWCNT-SiO nanocomposite was synthesized by co-precipitation and hydrothermal treatment methods. After the characterization of the MWCNT-SiO powder, specimens were obtained from the synthesized material Y-TZP/MWCNT-SiO by uniaxial pressing for a second characterization and later comparison of its optical and mechanical properties with the conventional Y-TZP. The MWCNT-SiO was presented in bundles of carbon nanotubes coated by silica (mean length: 5.

Edge chipping damage in lithium silicate glass-ceramics induced by conventional and ultrasonic vibration-assisted diamond machining.

Objectives: Diamond machining of lithium silicate glass-ceramics (LS) induces extensive edge chipping damage, detrimentally affecting LS restoration functionality and long-term performance. This study approached novel ultrasonic vibration-assisted machining of pre-crystallized and crystallized LS materials to investigate induced edge chipping damage in comparison with conventional machining.

Methods: The vibration-assisted diamond machining was conducted using a five-axis ultrasonic high-speed grinding/machining machine at different vibration amplitudes while conventional machining was performed using the same machine without vibration assistance.

Speed-sintering and the mechanical properties of 3-5 mol% YO-stabilized zirconias.

Ever faster workflows for the fabrication of all-ceramic restorations are of high economic interest. For that purpose, sintering protocols have been optimized for use in modern sintering furnaces, the so-called speed-sintering. However, conventional furnaces are still the most widely used equipment to sinter zirconia restorations.

A step toward bio-inspired dental composites.

This feasibility study aimed to develop a new composite material of aligned glass flakes in a polymer resin matrix inspired by the biological composite nacre. The experimental composite was processed by an adapted method of pressing a glass flake and resin monomer system. By pressing and allowing the excess monomer to flow out, the long axis of the flakes was aligned.

Determination of Water Content in Direct Resin Composites Using Coulometric Karl Fischer Titration.

This study evaluated the water content and sorption of direct composites over 60 days using coulometric Karl Fischer titration (KFT). Plate-shaped specimens (10 × 10 × 1 mm of thickness) were built up using the composites Clearfil Majesty Posterior (CM), Grandio SO (GS), and Filtek Supreme XT (FS). Water contents were determined in non-stored specimens (control) or after storage in distilled water for up to 60 days ( = 5).

Streptogramin A derivatives as mitochondrial translation inhibitors to suppress glioblastoma stem cell growth.

New therapeutic strategies for glioblastoma treatment, especially tackling the tumour's glioblastoma stem cell (GSC) component, are an urgent medical need. Recently, mitochondrial translation inhibition has been shown to affect GSC growth, clonogenicity, and self-renewal capability, therefore becoming an attractive therapeutic target. The combination of streptogramins B and A antibiotics quinupristin/dalfopristin (Q/D), which inhibits mitochondrial ribosome function, affects GSCs more effectively in vitro than the standard of care temozolomide.

Changes of gene expression in peripheral blood mononuclear cells of lung cancer patients with or without anorexia.

Background & Aims: Anorexia is a disabling symptom in cancer and we aimed at investigating the role of changes in gene expression in lung cancer patients presenting with anorexia.

Methods: Genome-wide transcriptomic profiling was assessed in PBMCs RNA from newly diagnosed lung cancer patients and in a control group. RT-qPCR was used for selected genes.

Radical-Polar Crossover Catalysis with a d Metal Enabled by a Redox-Active Ligand.

Radical-polar crossover mechanisms are invoked in numerous late transition metal and photocatalyzed reactions. To the best of our knowledge, reductive radical-polar crossover mechanisms are not invoked for group 3 early transition metals due to their propensity to exist in high oxidation states. Through use of a redox-active (tris)amido ligand we have accessed this mechanism for use with early transition metals.

Small-Molecule Ebselen Binds to YTHDF Proteins Interfering with the Recognition of -Methyladenosine-Modified RNAs.

YTHDF proteins bind the -methyladenosine (m6A)-modified mRNAs, influencing their processing, stability, and translation. Therefore, the members of this protein family play crucial roles in gene regulation and several physiological and pathophysiological conditions. YTHDF proteins contain a hydrophobic pocket that accommodates the m6A embedded in the RRACH consensus sequence on mRNAs.

On the assignment of quartz-like LiAlSiO - SiO solid solutions in dental lithium silicate glass-ceramics: Virgilite, high quartz, low quartz or stuffed quartz derivatives?

Objectives: Here we aim to provide a background on X-Ray Diffraction analysis of quartz-like crystal structures with varying amounts of Al and Li substitution, existing confusions on their nomenclature and its implications for novel lithium silicate glass-ceramics.

Methods: We reviewed the literature dealing with modifications of the quartz crystal structure and their stuffed LiAlSiO derivates, LiAlSiO - SiO solid solutions, the terminology of such phases and criteria used to define the structure known as virgilite. Based on this information, we attempted to allocate the quartz-like phases found in CEREC Tessera, Initial LiSi Block and Amber® Mill in the range of LiAlO - SiO solid solutions.