Structural and functional insights into UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from Brucella ovis.

The peptidoglycan biosynthetic pathway involves a series of enzymatic reactions in which UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) plays a crucial role in catalyzing the conversion of UDP-N-acetylglucosamine-enolpyruvate (UNAGEP) to UDP-N-acetylmuramic acid. This reaction relies on NADPH and FAD and, since MurB is not found in eukaryotes, it is an attractive target for the development of antimicrobials. MurB from Brucella ovis, the causative agent of brucellosis in sheep, is characterized here.

Synthesis and antifungal activity of novel amide derivatives from quinic acid against the sweet potato pathogen Ceratocystis fimbriata.

Background: Ceratocystis fimbriata is a fungal pathogen that infects sweet potato roots, producing enormous economic losses. Cyclic polyhydroxy compound quinic acid is a common metabolite synthesized in plant tissues, including sweet potato tubers, showing weak antifungal properties. Although several O-acylated quinic acid derivatives have been synthesized and found in nature and their antifungal properties have been explored, derivatives based on modification of the carboxylic acid have never been evaluated.

Efficacy of estimations of Hartmann-Shack sensors in small pupil sizes.

Purpose: The purpose of this study was to evaluate the efficacy of the estimations of wavefront analyzers using Hartmann-Shack technology to measure optical aberrations when the pupil size is smaller than the evaluated pupil area.

Methods: Patients implanted with the monofocal ZCB00 intraocular lens (Johnson and Johnson) were examined with the KR-1W Wavefront Analyzer (Topcon) without pharmacological mydriasis and with it afterward. Optical aberrations were analyzed considering a 4-mm pupil and a 6-mm pupil for both examinations.

Unveiling the Potential of Haloalkenes as Electron Density Acceptors.

We report herein, by means of structural and computational analyses, a comprehensive study of the capability of differently substituted haloalkenes to behave as electron density acceptors in noncovalent interactions. The nature of these interactions between haloalkenes and Lewis bases highly depends on the number and nature of the halogen atoms bound to the carbon-carbon double bond. When hydrogen bonds, which generally dominate for mono- and dihaloalkenes, cannot be formed, we observe the establishment of attractive interactions in which an sp carbon atom, belonging to an acyclic C=C double bond, plays the role of the Lewis acid via its π* antibonding orbital.

A 4-Year Retrospective Study: Clinical Outcomes of XEN45 in Patients with Glaucoma.

Introduction: The main purpose of the current study was to evaluate the long-term effectiveness and safety of XEN45 implant, either alone or in combination with cataract surgery, in patients with glaucoma.

Methods: Retrospective and single center study conducted on consecutive patients who underwent a XEN45 implant, either alone or in combination with cataract surgery, between November 2016 and October 2021. The primary endpoint was the mean intraocular pressure (IOP) lowering from preoperative values.

Osimertinib in Patients With Treatment-Naive EGFR-Mutant Non-small Cell Lung Cancer: Overall Survival, Post-progression Management and Budget Impact Analysis in Real-World.

Introduction: The observational multicenter prospective FLOWER study (NCT04965701) confirmed effectiveness and safety of osimertinib in the real-world (RW) management of untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) patients.

Methods: Herein, we report updated survival data, post-progression management, cost/effectiveness and budget impact (BI) of osimertinib compared with a RW population receiving gefitinib or erlotinib.

Results: Overall, 189 Caucasian patients receiving first-line osimertinib were included.

The role of family functioning, attachment style, and care setting on pre-loss grief symptoms and burden in caregivers of terminally cancer patients.

Objectives: The aim of the present cross-sectional study was to investigate the associations between caregivers' attachment styles, family functioning, the care setting and pre-loss grief symptoms, the burden, and the caregivers' belief of patients' awareness of the terminal cancer diagnosis.

Methods: A total of 101 caregivers of patients with terminal cancer in residential hospice care and home care were interviewed and completed self-report questionnaires.

Results: Insecure attachment style and home care setting were associated with worse psychological effects in caregivers of patients with terminal cancer.

Stabilizing σ-hole Dimethyl Interactions.

Methyl groups bound to electronegative atoms, such as N or O, are recognized to participate in tetrel bonding as Lewis acids. On the other hand, the capability of methyl groups bound to electropositive atoms, such as B or Al, to act as Lewis bases has been recently reported. Herein, we analyze the combination of these two behaviors to establish attractive methyl···methyl interactions.

The effect of climate change on avian offspring production: A global meta-analysis.

Climate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decades, but considerable differences were found among species and populations.

Riboflavin kinase and pyridoxine 5'-phosphate oxidase complex formation envisages transient interactions for FMN cofactor delivery.

Enzymes catalysing sequential reactions have developed different mechanisms to control the transport and flux of reactants and intermediates along metabolic pathways, which usually involve direct transfer of metabolites from an enzyme to the next one in a cascade reaction. Despite the fact that metabolite or substrate channelling has been widely studied for reactant molecules, such information is seldom available for cofactors in general, and for flavins in particular. Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) act as cofactors in flavoproteins and flavoenzymes involved in a wide range of physiologically relevant processes in all type of organisms.

Exploring the Potential Energy Surface of Pt Sub-Nano Clusters Deposited over Graphene.

Catalytic systems based on sub-nanoclusters deposited over different supports are promising for very relevant chemical transformations such as many electrocatalytic processes as the ORR. These systems have been demonstrated to be very fluxional, as they are able to change shape and interconvert between each other either alone or in the presence of adsorbates. In addition, an accurate representation of their catalytic activity requires the consideration of ensemble effects and not a single structure alone.

Mechanism Insights into the Iridium(III)- and B(CF)-Catalyzed Reduction of CO to the Formaldehyde Level with Tertiary Silanes.

The catalytic system [Ir(CFCO)(κ-NSi)] [; NSi = (4-methylpyridin-2-yloxy)dimethylsilyl]/B(CF) promotes the selective reduction of CO with tertiary silanes to the corresponding bis(silyl)acetal. Stoichiometric and catalytic studies evidenced that species [Ir(CFCOO-B(CF))(κ-NSi)] (), [Ir(κ-NSi)][HB(CF)] (), and [Ir(HCOO-B(CF))(κ-NSi)] () are intermediates of the catalytic process. The structure of has been determined by X-ray diffraction methods.

Observational real-life study on regorafenib in recurrent glioblastoma: does dose reduction reduce toxicity while maintaining the efficacy?

Purpose: In the phase 2 REGOMA trial, regorafenib improved overall survival, as compared with lomustine, in glioblastoma (GBM) patients at first progression after chemoradiation. Recently, some real-life trials showed similar impact on survival but a higher rate of adverse events than in REGOMA, thus raising concerns over tolerability. The aim of this study was to assess the efficacy and tolerability of a lower intensity regorafenib regimen.

Phenotypic and functional analysis of γδ T cells in the pathogenesis of human T-cell lymphotropic virus type 1 infection.

The human T-cell leukemia virus type 1 (HTLV-1) is the cause of serious malignant and inflammatory diseases, including adult T-cell leukemia and lymphoma and tropical spastic paraparesis. The potential protective role of γδ T cells in HTLV-1 infection remains unclear. Here, demonstrate that there is a decrease in the amount of Vγ9Vδ2 T cells in patients with HTLV-1, especially in those with HTLV-1 associated pathologies.

First-Line Osimertinib in Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer: Outcome and Safety in the Real World: FLOWER Study.

Background: Osimertinib became the standard treatment for patients with untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) following results reported in the phase III randomized FLAURA trial. Because of strict exclusion criteria, patient populations included in pivotal trials are only partially representative of real-world patients.

Methods: We designed an observational, prospective, multicenter study enrolling patients with EGFR-mutant aNSCLC receiving first-line osimertinib to evaluate effectiveness, safety, and progression patterns in the real-world.

Peel Diffusion and Antifungal Efficacy of Different Fungicides in Pear Fruit: Structure-Diffusion-Activity Relationships.

Fungal pathogens can invade not only the fruit peel but also the outer part of the fruit mesocarp, limiting the efficacy of fungicides. In this study, the relationships between fungicide structure, diffusion capacity and in vivo efficacy were evaluated for the first time. The diffusion capacity from pear peel to mesocarp of 11 antifungal compounds, including -aminobenzoic acid, carbendazim, difenoconazole, dipicolinic acid, flusilazole, gentamicin, kojic acid, prochloraz, quinolinic acid, thiophanate methyl and thiram was screened.

Nucleophilic Reactivity at a ═CH Arm of a Lutidine-Based CNC/Rh System: Unusual Alkyne and CO Activation.

Reaction of an amido pincer complex [(CNC)*Rh(CO)] () (CNC* is the deprotonated form of CNC) with carbon dioxide gave a neutral complex [(CNC-CO)*Rh(CO)] (), which is the result of a C-C bond-forming reaction between the deprotonated arm of the CNC* ligand and CO. The molecular structure of showed a zwitterionic complex, where the CO moiety is covalently connected to the former ═CH arm of the CNC* pincer ligand. The unusual structure of allowed us to explore the reactivity of the CO moiety with selected primary amines RNH (benzylamine and ammonia), which afforded cationic complexes [(CNC)Rh(CO)][HRNC()O] (R = Bz (), H ()).

Optical aberrations in three different intraocular lens designs of a same platform.

Purpose: To compare internal optical aberrations between three different intraocular lenses (IOL) of the same Tecnis platform: monofocal ZCB00, multifocal ZMB00, and enlarged depth-of-focus (EDoF) Symfony ZXR00.

Methods: We included in this study 236 eyes of 118 patients who had been bilaterally implanted either with the monofocal, the multifocal, or the EDoF IOL. They were examined with the K1-RW wavefront analyzer (Topcon Medical Systems) 2 months after surgery.

Rhodium-NHC-Catalyzed gem-Specific O-Selective Hydropyridonation of Terminal Alkynes.

The dinuclear complex [Rh(μ-Cl)(η -coe)(IPr)] is an efficient catalyst for the O-selective Markovnikov-type addition of 2-pyridones to terminal alkynes. DFT calculations support a hydride-free pathway entailing intramolecular oxidative protonation of a π-alkyne by a κ N-hydroxypyridine ligand. Subsequent O-nucleophilic attack on a metallacyclopropene species affords an O-alkenyl-2-oxypyridine chelate rhodium intermediate as the catalyst resting state.

Dehydrogenation of formic acid using iridium-NSi species as catalyst precursors.

Using a low loading of the iridium(III) complexes [Ir(CFSO)(κ-NSi)] (1) (NSi = (4-methylpyridin-2-yloxy)diisopropylsilyl) and [{Ir(κ-NSi)}(μ-CFSO)] (2) (NSi = (4-methylpyridin-2-yloxy)dimethylsilyl) in the presence of EtN, it has been possible to achieve the solventless selective dehydrogenation of formic acid. The best catalytic performance (TOF ≈ 2900 h) has been achieved with 2 (0.1 mol%) and EtN (40 mol% to FA) at 373 K.

Meibomian Gland Changes in Open-angle Glaucoma Users Treated with Topical Medication.

Significance: Glaucoma patients treated with topical hypotensive eye drops often experience changes in the ocular surface, including the lid margin and the meibomian glands. In this study, the clinical parameters of the ocular surface have been analyzed to detect the presence of meibomian gland dysfunction-related dry eye disease.

Purpose: This study aimed to evaluate the meibomian gland dysfunction in glaucoma patients secondary to topical antiglaucomatous treatment.

Challenges in Chronic Myeloid Leukemia Management in South America.

Purpose Of Review: Chronic myeloid leukemia (CML) management in developing countries has improved in the last years, but the availability of therapeutic resources, monitoring, reimbursement, and financial issues may be a challenge and interfere with the best practices and results of CML treatment. This review points out the main challenges in CML management in South America.

Recent Findings: In this review, we describe the access to tyrosine kinase inhibitors and monitoring in different countries of South America.

Influence of Sex on Neuroretinal Degeneration: Six-Month Follow-Up in Rats With Chronic Glaucoma.

Purpose: To evaluate differences by sex in the neuroretina of rats with chronic glaucoma over 24 weeks of follow-up, and to assess by sex the influence on neurodegeneration of different methods of inducing ocular hypertension.

Methods: Forty-six Long-Evans rats-18 males and 28 females-with induced chronic glaucoma were analyzed. Glaucoma was achieved via 2 models: repeatedly sclerosing the episcleral veins (9 male/14 female) or by injecting poly(lactic-co-glycolic acid) microspheres measuring 20 to 10 µm (Ms20/10) into the anterior chamber (9 male/14 female).