Dredging and sediment discharge in a river with floodplain. Physicochemical and microbiological effects in Paraná river.

Alterations caused by human activities in the environment, such as dredging, modify the physicochemical conditions and affect the habitat. Maintenance dredging that allows large vessels access to inland ports is a recurring disruptive action. The study aimed to evaluate, during a maintenance dredging operation in a port area of the Paraná River, the modifications in the structure of the river, the presence of contaminants and bacterial organisms.

Facile green synthesis of silver doped NiO nanoparticles using aloe vera latex for efficient energy storage and photocatalytic applications.

Herein, we report the biosynthesis of pure NiO and NiO nanoparticles doped with Silver (Ag@NiO NPs) 2, 4, 6, and 8 mol% from aloe vera extract by solution combustion method at 400 °C and calcined at 500 °C for 3 h. By utilizing silver-doped NiO nanoparticles synthesized with Aloe Vera latex, which not only enhances the material's properties but also promotes environmentally friendly fabrication methods. The morphological, structural elemental compositions were analysed through SEM, HRTEM, SAED, XRD and EDAX.

Longitudinal Assessment of Structural and Functional Changes in Rod-cone Dystrophy: A 10-year Follow-up Study.

Purpose: Emerging clinical trials for inherited retinal disease (IRD) require an understanding of long-term progression. This longitudinal study investigated the genetic diagnosis and change in retinal structure and function over 10 years in rod-cone dystrophies (RCDs).

Design: Longitudinal observational follow-up study.

Iron management and exercise training in individuals with chronic kidney disease: lived experiences.

Background: Non-anaemic iron deficiency is highly prevalent in people living with chronic kidney disease (CKD) but is underdiagnosed and undertreated, especially in earlier stages of CKD. A multicentre trial assessing the effect of intravenous iron supplementation in iron-deficiency but not anaemic people with CKD included a qualitative sub-study that aimed to explore the patient experience and psychosocial impact of living with CKD and iron deficiency, and the experience of the therapeutic intervention (intravenous iron and exercise).

Methods: Semi-structured interviews were conducted with 23 trial participants blinded to treatment.

Foaming purees as a strategy to modify oral processing time.

Food structure modification by increasing viscosity or adding heterogeneity to the food product has shown to effectively change food oral processing. In this study, it was hypothesized that the addition of gas to purees could affect oral processing. This was achieved by creating different structures in purees using a gas syphon, vacuum and syphon + vacuum.

Mechanically robust surface-degradable implant from fiber silk composites demonstrates regenerative potential.

Through millions of years of evolution, bones have developed a complex and elegant hierarchical structure, utilizing tropocollagen and hydroxyapatite to attain an intricate balance between modulus, strength, and toughness. In this study, continuous fiber silk composites (CFSCs) of large size are prepared to mimic the hierarchical structure of natural bones, through the inheritance of the hierarchical structure of fiber silk and the integration with a polyester matrix. Due to the robust interface between the matrix and fiber silk, CFSCs show maintained stable long-term mechanical performance under wet conditions.

Artificial Intelligence-Driven Approaches to Managing Surgeon Fatigue and Improving Performance.

Surgeon fatigue significantly affects cognitive and motor functions, increasing the risk of errors and adverse patient outcomes. Traditional fatigue management methods, such as structured breaks and duty-hour limits, are insufficient for real-time fatigue detection in high-stakes surgeries. With advancements in artificial intelligence (AI), there is growing potential for AI-driven technologies to address this issue through continuous monitoring and adaptive interventions.

Identifying Predictors of Extended Intensive Care Unit Stay Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: An Analysis of 101 ACS NSQIP Pediatric Participating Centers.

Background: While prolonged operative time and increased levels fused have been shown to increase the risk of prolonged intensive care unit (ICU) length-of-stay (LOS), studies are limited in guiding decision-making regarding the need for intensive care postoperatively. This is especially the case among the cohort of adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF); associations between comorbidities and ICU LOS are not well-delineated.

Methods: AIS patients who underwent PSF from January 1st, 2016 to December 1st, 2016 at 101 participating centers were identified using the American College of Surgeons (ACS) National Surgical Quality Im-provement Project (NSQIP) Pediatric database.

Tarsal Tunnel Syndrome - A Comprehensive Review.

Tarsal tunnel syndrome (TTS) refers to compression of the posterior tibial nerve as it traverses the tarsal tunnel in the ankle. First described by Keck and Lam in 1962, TTS is an underdiagnosed cause of heel pain and foot dysfunction. The tarsal tunnel contains the tibial nerve, posterior tibial artery, and tendons of the tibialis posterior, flexor digitorum longus, and flexor hallucis longus muscles.

Patient experience with acute hepatic porphyria before and after long-term givosiran treatment in a qualitative interview study.

Background: Acute hepatic porphyria (AHP) is characterized by debilitating and potentially life-threatening neurovisceral attacks, possible chronic symptoms, and long-term complications. In a phase 1/2 open-label extension (OLE) study and the phase 3 ENVISION study, givosiran led to sustained improvement in annualized attack rate and quality of life (QOL) measures. To capture the patient experience of symptoms and impacts of AHP, and any changes experienced during treatment with givosiran, qualitative interviews were conducted with study participants.

Quantitative analysis of retinal vascular parameters changes in school-age children with refractive error using artificial intelligence.

Aim: To quantitatively analyze the relationship between spherical equivalent refraction (SER) and retinal vascular changes in school-age children with refractive error by applying fundus photography combined with artificial intelligence (AI) technology and explore the structural changes in retinal vasculature in these children.

Methods: We conducted a retrospective case-control study, collecting data on 113 cases involving 226 eyes of schoolchildren aged 6-12 years who attended outpatient clinics in our hospital between October 2021 and May 2022. Based on the refractive spherical equivalent refraction, we categorized the participants into four groups: 66 eyes in the low myopia group, 60 eyes in the intermediate myopia group, 50 eyes in the high myopia group, and 50 eyes in the control group.

Diagnosis and surgical treatment of obstructed hemivagina and ipsilateral renal anomaly in a dog: a case report.

Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA), also called Herlyn-Werner-Wunderlich syndrome, is an extremely rare Müllerian duct anomaly accompanied by Wolffian duct anomalies. A 10-year-old intact female Yorkshire Terrier weighing 3.35 kg was presented with anorexia, depression, vomiting, and abdominal pain.

Discovery of Rezatapopt (PC14586), a First-in-Class, Small-Molecule Reactivator of p53 Y220C Mutant in Development.

p53 is a potent transcription factor that is crucial in regulating cellular responses to stress. Mutations in the gene are found in >50% of human cancers, predominantly occurring in the DNA-binding domain (amino acids 94-292). The Y220C mutation accounts for 1.

Expanding the Chemical Space of Reverse Fosmidomycin Analogs.

Multidrug-resistant pathogens pose a major threat to human health, necessitating the identification of new drug targets and lead compounds that are not susceptible to cross-resistance. This study demonstrates that novel reverse thia analogs of the phosphonohydroxamic acid antibiotic fosmidomycin inhibit 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme for , , and that is absent in humans. Some novel analogs with large α-phenyl substituents exhibited strong inhibition across these three DXR orthologues, surpassing the inhibitory activity of fosmidomycin.

4T1 Cell Membrane Biomimetic Nanovehicle for Enhanced Breast Cancer Treatment.

In this study, hollow mesoporous silica nanoparticles (HMSN) coated with a 4T1 tumor cell membrane were used to construct biomimetic nanomaterials (DTX@CHMSN) for the treatment of breast cancer. The nanodrug can improve the water solubility of polyenetaxel (DTX) by taking advantage of the special structure, good biocompatibility, and adjustable surface chemical properties of HMSN. Hollow mesoporous silica nanoparticles are coated with 4T1 cell membranes derived from homologous tumors (CHMSN).

N-Arylsulfonylated C-Homoaporphines as a New Class of Antiplatelet and Antimicrobial Agents.

A series of novel N-arylsulfonylated C-homoaporphine alkaloids were synthesized under microwave irradiation and evaluated for their antiplatelet and antimicrobial activities. Among the series, compounds , , , , , , , , and demonstrated highly potent (∼3-fold) platelet aggregation inhibitory activity than acetylsalicylic acid (IC = 21.34 μg/mL).

Mining Druggable Sites in Influenza A Hemagglutinin: Binding of the Pinanamine-Based Inhibitor M090.

Assessing the binding mode of drug-like compounds is key in structure-based drug design. However, this may be challenged by factors such as the structural flexibility of the target protein. In this case, state-of-the-art computational methods can be valuable to explore the linkages between structural and pharmacological data.

Optimizing Linezolid: Transforming It into a Selective MAO-B Inhibitor via a Toxicity-to-Activity Optimization Approach.

Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor.

Discovery of Novel Pyrimidine Derivatives as Human Pin1 Covalent Inhibitors.

Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) is a unique peptidyl-prolyl isomerase (PPIase), and inactivation of Pin1 with a covalent inhibitor is a potential strategy for developing anticancer agents. Herein, a series of sulfolane amino-substituted 2-chloro-5-nitropyrimidine derivatives were disclosed as structurally distinct covalent inhibitors toward Pin1, which were validated for their covalent binding to Cys113 of Pin1 by X-ray cocrystal structures of compounds (IC = 11.55 μM) and (IC = 3.

Asymmetric Synthesis, Structure Determination, and Biologic Evaluation of Isomers of TLAM as PFK1 Inhibitors.

Inhibiting phosphofructokinase-1 (PFK1) is a promising approach for treating lactic acidosis and mitochondrial dysfunction by activating oxidative phosphorylation. Tryptolinamide (TLAM) has been shown as a PFK1 inhibitor, but its complex stereochemistry, with 16 possible isomers complicates further development. We conducted an asymmetric synthesis, determined the absolute configurations, and evaluated the PFK1 inhibitory activity of the TLAM isomers.

A Conjugate of an EGFR-Binding Peptide and Doxorubicin Shows Selective Toxicity to Triple-Negative Breast Cancer Cells.

Selective targeting of cancer cells via overexpressed cell-surface receptors is a promising strategy to enhance chemotherapy efficacy and minimize off-target side effects. In this study, we designed peptide 31 (YHWYGYTPERVI) to target the overexpressed epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) cells. Peptide 31 is internalized by TNBC cells through EGFR-mediated endocytosis and shares sequence and structural similarities with human EGF (hEGF), a natural EGFR ligand.

Structure-Based Design of Novel TLR7/8 Agonist Payloads Enabling an Immunomodulatory Conjugate Approach.

Dual activation of the TLR7 and TLR8 pathways leads to the production of type I interferon and proinflammatory cytokines, resulting in efficient antigen presentation by dendritic cells to promote T-cell priming and antitumor immunity. We developed a novel series of TLR7/8 dual agonists with varying ratios of TLR7 and TLR8 activity for use as payloads for an antibody-drug conjugate approach. The agonist-induced production of several cytokines in human whole blood confirmed their functional activity.

Development of a Buchwald-Hartwig Amination for an Accelerated Library Synthesis of Cereblon Binders.

In recent years, targeted protein degradation (TPD) has emerged as a powerful therapeutic modality utilizing both heterobifunctional ligand-directed degraders (LDDs) and molecular glues (e.g., CELMoDs) to recruit E3 ligases for inducing polyubiquitination and subsequent proteasomal degradation of target proteins.

Discovery of a Potent Triazole-Based Reversible Targeted Covalent Inhibitor of Cruzipain.

Cruzipain (CZP) is an essential cysteine protease of , the etiological agent of Chagas disease, and a promising druggable target. To date, no CZP inhibitors have reached clinical use, with research efforts mostly hampered by insufficient potency, limited target selectivity or lack of bioactivity translation from the isolated enzyme to the parasite in cellular environments. In this study, we report the design of , a 1,2,3-triazole-based targeted covalent inhibitor with nanomolar potency (IC = 28 nM) and null inhibition of human cathepsin L.

Advances in Psychoactive Alkaloid Delivery, Ergoline Analogues, and Serotonin Receptor Modulation for Enhanced Therapeutic Outcomes.

Recent advancements in pharmaceutical research have focused on developing novel psychoactive compounds and receptor modulators that enhance therapeutic outcomes while minimizing adverse effects. This Patent Highlight examines three innovative approaches: (1) transmucosal delivery of dephosphorylated psychoactive alkaloids, (2) nonhallucinogenic serotonin receptor modulators, and (3) ergoline analogues designed for treating neurological disorders. These innovations offer breakthroughs in drug delivery, receptor targeting, and structural modifications, aiming to address challenges in the treatment of mood disorders, neurological diseases, and chronic pain while improving bioavailability and reducing side effects and hallucinogenic properties.