Multiple Binding Modes of Inhibitors to Human Carbonic Anhydrases: An Update on the Design of Isoform-Specific Modulators of Activity.

Human carbonic anhydrases (hCAs) are widespread zinc enzymes that catalyze the hydration of CO to bicarbonate and a proton. Currently, 15 isoforms have been identified, of which only 12 are catalytically active. Given their involvement in numerous physiological and pathological processes, hCAs are recognized therapeutic targets for the development of inhibitors with biomedical applications.

SMURF1 and SMURF2 directly target GLI1 for ubiquitination and proteasome-dependent degradation.

The transcription factor GLI1 is the main and final effector of the Hedgehog signaling pathway, which is involved in embryonic development, cell proliferation and stemness. Whether activated through canonical or non-canonical mechanisms, GLI1 aberrant activity is associated with Hedgehog-dependent cancers, including medulloblastoma, as well as other tumoral contexts. Notwithstanding a growing body of evidence, which have highlighted the potential role of post translational modifications of GLI1, the complex mechanisms modulating GLI1 stability and activity have not been fully elucidated.

Evaluation of the Bond Strengths Between Dental Ceramics and Co-Cr Frameworks Made with Digital and Conventional Techniques.

Purpose: Evaluate the influence of different Co-Cr framework manufacturing techniques on the bond strength between metal and two types of veneering ceramic with and without a metal primer.

Materials And Methods: 72 metal specimens were fabricated using the same Co-Cr alloy (Keramit NP; Nobil Metal) with three different techniques: ingots for casting (Keramit NP); disks for CAD/CAM milling (Synergy Drive Keramit NP); and powder for SLM (Keramit NP-S). Each of the 24-specimen groups, was divided into two subgroups, according to the application, or not, of Nobil Metal Bonding (NMB) (Nobil Metal).

The pace of life for forest trees.

Tree growth and longevity trade-offs fundamentally shape the terrestrial carbon balance. Yet, we lack a unified understanding of how such trade-offs vary across the world's forests. By mapping life history traits for a wide range of species across the Americas, we reveal considerable variation in life expectancies from 10 centimeters in diameter (ranging from 1.

The biogeography of the Amazonian tree flora.

We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions.

Oral Care in Head and Neck Radiotherapy: Proposal for an Oral Hygiene Protocol.

This review aims to provide a comprehensive overview of the literature on the oral side effects caused by radiotherapy for head and neck cancers. Various treatments are examined to mitigate these sequelae, and a protocol is proposed for dentists and dental hygienists to manage oncological patients. A literature search was conducted to select relevant articles addressing the effects of radiotherapy treatments on the oral cavity, with a particular focus on the development of mucositis, candidiasis, changes in salivary pH, trismus, fibrosis, and alterations in the oral biofilm.

Comparison of mechanical and surface properties of two 3D printed composite resins for definitive restoration.

Statement Of Problem: Additive manufacturing (AM) technology is emerging as an innovative approach in the dental field. In recent years, manufacturers have introduced 3-dimensionally printed composite resins (3D-CRs) that are specifically designed for the AM of definitive prostheses; however, the mechanical and surface properties of these materials require investigation.

Purpose: The purpose of this in vitro study was to assess and compare the mechanical and surface properties of 2 commercially available 3D-CRs for definitive restoration after artificial aging.

Relative dose intensity of first-line triplet chemotherapy in metastatic colorectal cancer.

Purpose: Relative dose intensity (RDI) is a measurement of chemotherapy (CT) dose defined as the actual dose received divided by the standard calculated dose during a set period. The study objective was to assess the impact of a RDI ≥ 80% on response and survival of patients treated in first line CT by FOLFOXIRI or FOLFIRINOX ± Bevacizumab (BV) for an unresectable metastatic colorectal cancer (mCRC).

Materials And Methods: It was a retrospective, non-interventional, multicenter study calculating RDI from the first cycles of CT to the first CT-scan evaluation (CT-scan1).

Perception of the oral health risks of passive smoking from traditional cigarettes, electronic cigarettes, and heated tobacco products: A cross-sectional study.

Introduction: Tobacco smoke is a major health risk factor for smokers but also for non-smokers due to passive smoking. These risks come from conventional cigarette smoke but also from aerosol produced by electronic cigarettes and heated tobacco products (HTPs). The aim of this study was to investigate population knowledge about the adverse effects of passive smoking from traditional cigarettes, electronic cigarettes, and HTPs.

Potential Benefits of Photon-Counting CT in Dental Imaging: A Narrative Review.

Advancements in oral imaging technology are continually shaping the landscape of dental diagnosis and treatment planning. Among these, photon-counting computed tomography (PCCT), introduced in 2021, has emerged as a promising, high-quality oral technology. Dental imaging typically requires a resolution beyond the standard CT systems achievable with the specialized cone-beam CT.

Different effects of whitening treatment on natural teeth and teeth treated with Icon resin: an experimental study in vitro.

Background: It is quite common for white spots to develop on a tooth, due sometimes to a defective formation of the enamel layer, and sometimes to patches of demineralisation as a result of poor oral hygiene during orthodontic treatment with fixed braces. ICON DMG is currently the only noninvasive treatment for white spots. After a preliminary etching, it infiltrates the enamel, filling the spaces between the prisms with a resinous material that has a refraction coefficient very similar to that of healthy tooth enamel.

Consistent patterns of common species across tropical tree communities.

Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge.

Mapping density, diversity and species-richness of the Amazon tree flora.

Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness.

More than 10,000 pre-Columbian earthworks are still hidden throughout Amazonia.

Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest.

Retrospective clinical study of 1472-unit monolithic zirconia restorations with feather-edge margins realized with digital workflow.

Objectives: To evaluate the clinical performance of monolithic zirconia restorations with feather-edge margins fabricated by digital impressions.

Materials And Methods: All participants that present monolithic zirconia restorations with feather-edge margins realized with digital workflow were evaluated during scheduled periodontal maintenance between February and September 2022 according to predetermined inclusion criteria. Clinical performance was assessed using the modified USPHS and periodontal parameters.

Discovery of a novel series of potent carbonic anhydrase inhibitors with selective affinity for μ Opioid receptor for Safer and long-lasting analgesia.

In this study, we investigated the development of dual-targeted ligands that bind to both μ-opioid receptor (MOR) and carbonic anhydrase (CA) enzymes, using fentanyl structure as a template. We synthesized and evaluated 21 novel compounds with dual-targeted affinity identifying the lead candidate compound 8, showing selective affinity for MOR and potent inhibition of several cytosolic CA isoforms. By means of repeated treatment of 3 daily administrations for 17 days, fentanyl (0.

KCTD1 is a new modulator of the KCASH family of Hedgehog suppressors.

The Sonic Hedgehog (Hh) signal transduction pathway plays a critical role in many developmental processes and, when deregulated, may contribute to several cancers, including basal cell carcinoma, medulloblastoma, colorectal, prostate, and pancreatic cancer. In recent years, several Hh inhibitors have been developed, mainly acting on the Smo receptor. However, drug resistance due to Smo mutations or non-canonical Hh pathway activation highlights the need to identify further mechanisms of Hh pathway modulation.

Assessment Methods for Marginal and Internal Fit of Partial Crown Restorations: A Systematic Review.

Background: Different methods are used for the analysis of marginal and internal fit of partial crowns, but not all of them are applicable for in vivo studies. The aim of this review is to search the available methods, described in the current literature, to assess marginal and internal fit in partial crowns.

Methods: an electronic search was performed on Pubmed and Web of Science databases to find studies published from 1 January 2017 up to 2 March 2023, following PRISMA guidelines and Cochrane handbook for systematic reviews.

Paternity data reveal high MHC diversity among sires in a polygynandrous, egalitarian primate.

Evidence from human and nonhuman primates suggests that females avoid breeding with close kin and may choose mates based on MHC diversity, which can improve offspring survival. In despotic societies, female mate choice may be hindered by male sexual coercion, but in egalitarian societies, females may be less constrained. Among northern muriquis-an egalitarian, polygynandrous primate with male philopatry-analyses of new data on paternity and variation at microsatellite and MHC loci, combined with behavioural and life-history data, revealed that sires showed higher MHC diversity than expected by chance and were never close kin of dams, consistent with predictions of female mate choice and close inbreeding avoidance.

Influence of Platform-Switched Restoration on Bone Resorption in Patients Treated with Wide-Diameter, External-Hex-Connection Dental Implants: A 10-Year Follow-up Study.

To investigate and assess the differences in crestal bone loss (CBL) between wide-diameter, external-hexagon-connection implants restored with platform-switching (PS) and platform-matching (PM) restorations with a follow-up of 10 years. This study retrospectively analyzed the updated and enlarged dataset of a 5-year prospective clinical study at 10-year follow-up. The data concerns 182 healthy adult subjects treated in a private dental practice who received a single wide-diameter implant with an external hexagon connection in the molar area, restored with either a PS restoration (test) or PM restoration (control).

Hedgehog-GLI and Notch Pathways Sustain Chemoresistance and Invasiveness in Colorectal Cancer and Their Inhibition Restores Chemotherapy Efficacy.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality and chemoresistance is a major medical issue. The epithelial-to-mesenchymal transition (EMT) is the primary step in the emergence of the invasive phenotype and the Hedgehog-GLI (HH-GLI) and NOTCH signaling pathways are associated with poor prognosis and EMT in CRC. CRC cell lines harboring KRAS or BRAF mutations, grown as monolayers and organoids, were treated with the chemotherapeutic agent 5-Fluorouracil (5-FU) alone or combined with HH-GLI and NOTCH pathway inhibitors GANT61 and DAPT, or arsenic trioxide (ATO) to inhibit both pathways.

Unraveling Amazon tree community assembly using Maximum Information Entropy: a quantitative analysis of tropical forest ecology.

In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies.

Dental calculus microbiome correlates with dietary intake.

Background: Dental calculus is the result of dental plaque mineralization, originating from the tooth-associated bacterial biofilm. Recent evidence revealed that the dental calculus microbiome has a more complex composition than previously considered, including an unstructured mix of both aerobes and anaerobes bacteria. Actually, we lack information about the influence of host lifestyle factors, such as diet and health on this highly biodiverse ecosystem.