E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.

The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific deletion mouse strain ( ) and found that is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux.

FragPT2: Multifragment Wave Function Embedding with Perturbative Interactions.

Embedding techniques allow the efficient description of correlations within localized fragments of large molecular systems while accounting for their environment at a lower level of theory. We introduce FragPT2: a novel embedding framework that addresses multiple interacting active fragments. Fragments are assigned separate active spaces, constructed by localizing canonical molecular orbitals.

Effect of Divalent Cations on Polarity and Hydration at the Lipid/Water Interface Probed by 4-Aminophthalimide-Based Dyes.

The ion binding to the lipid/water interface can substantially influence the structural, functional, and dynamic properties of the cell membrane. Despite extensive research on ion-lipid interactions, the specific effects of ion binding on the polarity and hydration at the lipid/water interface remain poorly understood. This study explores the influence of three biologically relevant divalent cations─Mg, Ca, and Zn─on the depth-dependent interfacial polarity and hydration of zwitterionic DPPC lipid in its gel phase at room temperature.

Benchmark computations of nearly degenerate singlet and triplet states of N-heterocyclic chromophores. II. Density-based methods.

In this paper, we demonstrate the performance of several density-based methods in predicting the inversion of S1 and T1 states of a few N-heterocyclic triangulene based fused ring molecules (popularly known as INVEST molecules) with an eye to identify a well performing but cost-effective preliminary screening method. Both conventional linear-response time-dependent density functional theory (LR-TDDFT) and ΔSCF methods (namely maximum overlap method, square-gradient minimization method, and restricted open-shell Kohn-Sham) are considered for excited state computations using exchange-correlation (XC) functionals from different rungs of Jacob's ladder. A well-justified systematism is observed in the performance of the functionals when compared against fully internally contracted multireference configuration interaction singles and doubles and/or equation of motion coupled-cluster singles and doubles (EOM-CCSD), with the most important feature being the capture of spin-polarization in the presence of correlation.

Comparative Analysis of Patient-Reported Outcome Measures in Manual Small-Incision Cataract Surgery Versus Phacoemulsification for Brown Cataracts.

Objective The objective of this study is to compare patient-reported outcome measures using the Catquest Questionnaire in patients undergoing phacoemulsification (Phaco) versus manual small-incision cataract surgery (MSICS). Materials and methods This descriptive cross-sectional study included patients aged 40 years and older with cataracts classified as nuclear sclerosis (NS) grade 3 or higher. Demographic details were recorded and a comprehensive ophthalmological exam was done.

Intraocular Inflammation (IOI) Associated with Faricimab Therapy: One-year Real World Outcomes.

Purpose: To report one-year real-world evidence on intraocular inflammation (IOI) adverse events (AEs) in patients undergoing faricimab therapy in a tertiary care hospital.

Methods: A retrospective review of electronic medical records was conducted for patients receiving faricimab treatment for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) at Moorfields Eye Hospital between September 1st, 2022, and August 31st, 2023. The primary outcome was the incidence of IOI (excluding endophthalmitis).

Designing highly tunable nanostructured peptide hydrogels using differential thermal histories to achieve variable cellular responses.

In this study, we demonstrate a unique and promising approach to access peptide-based diverse nanostructures in a single gelator regime that is capable of exhibiting different surface topographies and variable physical properties, which, in turn, can effectively mimic the extracellular matrix (ECM) and regulate variable cellular responses. These diverse nanostructures represent different energy states in the free energy landscape, which have been created through different self-assembling pathways by providing variable energy inputs by simply altering the gelation induction temperature from 40 °C to 90 °C. The highly entangled network structure with long fibers was created by higher energy inputs, , inducing the gelation at a higher temperature in the 70-90 °C range, whereas the less entangled nanoscale network with short fibers was obtained at a lower gelation induction temperature of 40-60 °C.

Herbal Medicine for the Management of Wounds: A Systematic Review of Clinical Studies.

Background: Cuts and wounds are unfortunate yet inevitable events. Traditional remedies have historically harnessed various plants for wound healing, undergoing clinical and pre-clinical scrutiny. Hence, this systematic review focuses on clinically researched herbal formulations for wound healing.

Upshot of Some Bioactive Compounds on Angiogenesis in Retinal Pigment Epithelial Cells.

Nowadays, the use of monoclonal antibodies to target angiogenic signalling pathways is common, but, unfortunately, the clinical activity of these agents is limited. Thus, the development of approaches targeting multiple pathways for anti-angiogenic effect will lead to increase the clinical benefit. For this purpose, oleuropein, hesperidin, piperine, proanthocyanidins and retinoic acid, which have previously been proven to be bioactive components, anti-angiogenic performances were experimentally tested in retinal pigment epithelial cells.

Maternal and infant predictors of human milk macronutrient and energy concentrations in rural Bangladesh: an observational cohort study.

Background: Human milk macronutrient (protein, fat, and carbohydrate) and energy concentrations vary based on maternal and infant factors and time postpartum.

Objective: To determine the change in milk macronutrient and energy concentrations from approximately 2 to 5 months postpartum and identify factors associated with this variation among a lactation cohort in Bangladesh.

Methods: In this prospective observational lactation cohort in rural Sylhet, Bangladesh, we collected hand-expressed mid-feed human milk samples and analyzed macronutrient concentrations using mid-infrared spectroscopy.

Emergence of an unconventional Enterobacter cloacae-derived Iturin A C-15 as a potential therapeutic agent against methicillin-resistant Staphylococcus aureus.

Antimicrobial resistance poses a significant global health threat by reducing the effectiveness of conventional antibiotics, particularly against pathogens like Methicillin-resistant Staphylococcus aureus (MRSA). This study investigates the antimicrobial potential of rhizospheric soil bacteria from Prosopis cineraria (Sangri) in the Thar Desert. Bacterial strains isolated from these samples were observed to produce secondary metabolites, notably, Iturin A C-15 cyclic lipopeptide (SS1-3-P) which was extracted from strain Enterobacter cloacae SS1-3 and was purified and characterized using reverse-phase HPLC, ESI-LC/MS, Nile-Red Assay, and FT-IR analysis.

On-the-spot spirometry & combined salbutamol & glycopyrronium reversibility testing in obstructive airway disease: A real-world appraisal.

Background & objectives Spirometric glycopyrronium responsiveness, a new advent, needs to be examined at in terms of degree and frequency in different obstructive-airway diseases diagnosed in real world practise. Methods Serial and willing symptomatic affected individuals of suspected airway disease underwent a pragmatic post-consultation spirometry-protocol on the same day with salbutamol followed by glycopyrronium bromide. The diagnosis of asthma (FEV1-reversibility ≥ 200 ml + 12%), chronic obstructive pulmonary disease (COPD) (FEV1/FVC<0.

Ultrastructural imaging biomarkers in diabetic macular edema: A major review.

Diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy and causes significant morbidity in patients. Anti-vascular endothelial growth factor (VEGF) agents are the mainstay of treatment for DME, with steroid implants being used for the treatment of anti-VEGF resistant eyes. Over the years, several classification systems have been devised to describe the patterns of DME using optical coherence tomography (OCT).

Cerebral collateral flow state in acute ischemic stroke correlates with clinical functional outcomes in non-thrombectomy patients.

Introduction: Hypoperfusion index ratio (HIR) measured by computerized tomography perfusion (CTP) has been shown to predict collateral flow state in acute ischemic stroke (AIS). Low HIR (<0.4) is indicative of good collateral flow state.

Constrictive pericarditis following epicardial pacemaker implant: a diagnostic dilemma.

Constrictive pericarditis is a rare complication after cardiac surgery. It is mostly seen in adults. We report a case of constrictive pericarditis in a 3-year-old child with right ventricular dysfunction after permanent pacemaker implantation during infancy for congenital complete heart block.

Single-Molecule Tracking dataset for histone H3 (hht1) from live and fixed cells of Schizosaccharomyces pombe.

Single-molecule tracking provides direct real-time measurements of protein dynamics in live cells with high spatiotemporal resolution. In the last decade, this method has been adopted by several labs to understand the dynamics of DNA replication, transcription, telomerase, chromatin remodeling, etc. in a variety of model systems (bacteria, yeast S.

Comparison of Biomarkers Playing a Role in Pterygium Development in Pterygium and Recurrent Pterygium Tissues.

Pterygium is a nonneoplastic elastotic degeneration characterized by subepithelial growth. It manifests as an ocular lesion originating from the bulbar conjunctiva, extending to the corneal surface, and reaching the visual axis in some cases. Although the exact cause is unknown, prolonged exposure to ultraviolet radiation is considered the most significant contributing factor.

Forced Degradation Study of an Anti-Diabetic Drug Imeglimin: Impurity Profiling and Structure Elucidation Using LC-Q-ToF-MS/MS and NMR.

Rationale: The present study aims to establish structures of the degradation products of an anti-diabetic drug, Imeglimin (IMG) approved for the treatment of type 2 diabetes mellitus in the year 2021. Degradation pathways are proposed along with in silico toxicity assessments of the observed degradation products (DPs) of the drug.

Methods: A reversed-phase high-performance liquid chromatography (RP-HPLC), equipped with a photodiode array detector, was used to separate the observed DPs with a Phenomenex Luna PFP (250 × 4.

Revisiting the Emerging Role of Light-Based Therapies in the Management of Spinal Cord Injuries.

The surge in spinal cord injuries (SCI) attracted many neurobiologists to explore the underlying complex pathophysiology and to offer better therapeutic outcomes. The multimodal approaches to therapy in SCI have proven to be effective but to a limited extent. The clinical basics involve invasive procedures and limited therapeutic interventions, and most preclinical studies and formulations are yet to be translated due to numerous factors.

Comparison of different nebulisation systems for capsaicin cough challenge testing.

https://bit.ly/45P1X8V.

Mechanistic Understanding of Superior Methylene Blue Adsorption Capacity in a Novel g-CN Modified Amorphous Na-Ca-Mg Silicate Adsorbent: Insights from Multinuclear Solid-State NMR Spectroscopy.

Silicate-based adsorbents offer significant advantages over traditional materials, particularly due to their superior thermal and chemical stability, enhanced regenerability, and the ability to endure more rigorous operating conditions. In this study, an amorphous Na-Ca-magnesium silicate adsorbent (SAAM) and its g-CN-modified counterpart (gCN-SAAM) were synthesized via alkali activation and a subsequent thermal process, respectively. The g-CN modification resulted in a novel hybrid adsorbent with a remarkable methylene blue (MB) adsorption capacity of 420 mg g, four times higher than the unmodified sample, setting a new benchmark.

Effect of Size-Controlled Nanofluid on Mechanical Properties, Microstructure, and Rheological Behavior of Cement Slurry for Oil Well Cementing.

The optimal design of cement slurry by balancing various cement additives and cement is critical for effective oil well cementation job. However, given adverse circumstances of application, existing additives may not be sufficient to perform suitably in challenging conditions, leading to premature cement hydration, formation of microcracks, and gas channeling pathways. Thus, this study explores the use of a single-step silica nanofluid (NP size: 5-10, 90-100, and 250-300 nm and concentration: 1, 3, and 5 wt %) as an additive and explores its effect on thickening time, fluid loss, and rheological behavior of class G cement slurry at high-pressure and high-temperature (HPHT) conditions (135 °C and 3625 psi).

The real-world association between digital markers of circadian disruption and mental health risks.

While circadian disruption is recognized as a potential driver of depression, its real-world impact is poorly understood. A critical step to addressing this is the noninvasive collection of physiological time-series data outside laboratory settings in large populations. Digital tools offer promise in this endeavor.