Novel antimalarial 3-substituted quinolones isosteres with improved pharmacokinetic properties.

Aryl quinolone derivatives can target the cytochrome bc complex of Plasmodium falciparum, exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives.

Factors Predicting Fetal Growth Restriction and Fetal Cardiac Remodeling.

Objective: This study aimed to investigate factors influencing fetal growth restriction (FGR) occurrence and assess the clinical significance of fetal cardiac parameters in FGR prediction.

Methods: Pregnant women with clinically suspected FGR (n=179) and uncomplicated pregnancies (n=53) were included. All had undergone routine obstetric ultrasonography and fetal echocardiography.

Incorporating Mixed-Ligand Zeolitic Imidazolate Framework into Polydimethyldiethoxysilane (PDMDES) Membrane for Enhancing Alcohol Pervaporation Recovery.

In the present study, a zeolitic imidazolate framework with mixed ligands, ZIF-8-90, was synthesized and embedded into an ultrathin polydimethyldiethoxysilane (PDMDES) matrix to prepare a ZIF-8-90/PDMDES mixed matrix membrane (MMM) for the enhanced recovery of alcohols from dilute aqueous solutions via pervaporation, using a facile solution coating method. The synthesized ZIF-8-90 particles demonstrated superior hydrophobicity and thermal stability compared to those of both ZIF-8 and ZIF-90 particles. Furthermore, the hydrophobicity, thermal stability, and sorption ability for alcohols of the ZIF-8-90/PDMDES MMM were significantly improved, attributed to the incorporation of mixed-ligand ZIF-8-90.

Screening and affinity optimization of single domain antibody targeting the SARS-CoV-2 nucleocapsid protein.

The coronavirus disease 2019 (COVID-19) pandemic, which caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to a crisis with devastating disasters to global public economy and health. Several studies suggest that the SARS-CoV-2 nucleocapsid protein (N protein) is one of uppermost structural constituents of SARS-CoV-2 and is relatively conserved which could become a specific diagnostic marker. In this study, eight single domain antibodies recognized the N protein specifically which were named pN01-pN08 were screened using human phage display library.

Combining non-invasive liquid biopsy and a methylation analysis to assess surgical risk for early esophageal cancer.

Background: While the widespread use of endoscopic submucosal dissection (ESD) has significantly reduced the incidence of early esophageal cancer (ESCA), the limited ability of ESD to strip deep infiltrating esophageal lesions results in a considerable risk of intraoperative perforation. Circulating-free DNA (cfDNA) is widely used in modern tumor screening due to its non-invasive detection capabilities. A methylation analysis offers vital insights into the condition and advancement of malignancies due to its unique positioning, such as a marker of cancer.

Abnormal function of /p.R957P mutant in congenital cataract.

Aim: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.

Methods: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.

Novel mechanistic study of HDAC6 regulation of rheumatoid arthritis via CMA: exploring potential therapeutic targets.

Objective: Rheumatoid arthritis (RA) is a systemic autoimmune disease. Its pathogenesis has not yet been clarified, so it is urgent to explore therapeutic targets. Here, we clarified the role of HDAC6 in the mechanism of action of RA through mediating chaperone-mediated autophagy (CMA) to provide a clinical treatment of RA.

Fabrication of caffeoylquinic acid-loaded burdock polysaccharide nanoparticles and their antioxidant activity in hydrogen peroxide-damaged HepaRG cells.

Herein, burdock polysaccharide (BP) and modified burdock polysaccharide (MBP) were prepared, followed by the fabrication of chlorogenic acid (CA)-BP, CA-MBP, isochlorogenic acid A (ICA)-BP, and ICA-MBP nanoparticles. Afterward, the structural characteristics, physical stability, digestive characteristics, and antioxidant activity of hydrogen peroxide (HO)-damaged HepaRG cells were evaluated. The result indicated that the loading capacities of CA in BP-CA and MBP-CA were 0.

Mutation analysis of in patients with non-syndromic retinitis pigmentosa.

Purpose: To identify RHO mutations in patients with non-syndromic retinitis pigmentosa (NS-RP).

Methods: A total of 143 probands (46 family history and 97 sporadic cases) with NS-RP were recruited from Southeast China. The coding exons and adjacent intronic regions of RHO were PCR-amplified and sequenced by Sanger sequencing.

An Integrated Autonomous Dynamic Navigation Approach toward a Composite Air-Ground Risk Construction Scenario.

Unmanned transportation in construction scenarios presents a significant challenge due to the presence of complex dynamic on-ground obstacles and potential airborne falling objects. Consequently, the typical methodology for composite air-ground risk avoidance in construction scenarios holds enormous importance. In this paper, an integrated potential-field-based risk assessment approach is proposed to evaluate the threat severity of the environmental obstacles.

A novel single domain bispecific antibody targeting VEGF and TNF-α ameliorates rheumatoid arthritis.

Anti-TNF-α therapy fails in 30% of patients, where TNF-α may not be the key causative factor in these patients. We developed a bispecific single-domain antibody block TNF-α and VEGF (V5-3).The experiments showed that V5-3 effectively activated proliferation and migration of RA-FLS and HUVEC, tube-forming role of HUVEC, and expression of inflammatory factors in vitro.

Numerical and experimental analysis of pollen inhalation exposure in nasal airways following various middle turbinectomy.

Background: Middle turbinectomy (MT) has always been controversial. MT significantly alters the anatomy and redistributes the inhaled air. The current study is designed to quantify the effect of MT with varying resection volumes on airflow and associated pollen inhalation exposure characteristics in the nasal airways.

Direct cytoplasmic delivery of RNAi therapeutics through a non-lysosomal pathway for enhanced gene therapy.

The first approved RNAi therapeutics, ONPATTRO, in 2017 moves the concept of RNA interference (RNAi) therapy from research to clinical reality, raising the hopes for the treatment of currently incurable diseases. However, RNAi therapeutics are still facing two main challenges-susceptibility to enzymatic degradation and low ability to escape from endo/lysosome into the cytoplasm. Therefore, we developed disulfide-based nanospheres (DBNPs) as universal vehicles to achieve efficient RNA delivery to address these problems.

Change of Composition, Source Contribution, and Oxidative Effects of Environmental PM in the Respiratory Tract.

Fine particulate matter is a leading air pollutant, and its composition profile relates to sources and health effects. The human respiratory tract hosts a warmer and more humid microenvironment in contrast with peripheral environments. However, how the human respiratory tract impacts the transformation of the composition of environmental PM once they are inhaled and consequently changes of source contribution and health effects are unknown.

Targeted delivery of inhalable drug particles in the tracheobronchial tree model of a pediatric patient with bronchopneumonia: A numerical study.

Pneumonia is a common cause of hospitalization and death in children worldwide. Inhalation therapy is one of the methods treating pneumonia However, there are limited studies that distinguish between the physiology of children and adults, especially with respect to targeted drug delivery. A tracheobronchial (TB) tree model of an 11-year-old child with bronchopneumonia is selected as a testbed for in silico trials of targeted drug delivery.

Prediction of transport, deposition, and resultant immune response of nasal spray vaccine droplets using a CFPD-HCD model in a 6-year-old upper airway geometry to potentially prevent COVID-19.

This study focuses on the transport, deposition, and triggered immune response of intranasal vaccine droplets to the angiotensin-converting-enzyme-2-rich region, i.e., the olfactory region (OR), in the nasal cavity of a 6-year-old female to possibly prevent corona virus disease 19 (COVID-19).

Study of the Repellent Activity of 60 Essential Oils and Their Main Constituents against , and Nano-Formulation Development.

Mosquitoes are one of the most important disease vectors from a medical viewpoint in that they transmit several diseases such as malaria, filariasis, yellow and Dengue fever. Mosquito vector control and personal protection from mosquito bites are currently the most efficient ways to prevent these diseases. Several synthetic repellents such as DEET, ethyl butylacetylaminopropionate (IR3535) and 1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine) (Picaridin), have been widely used to prevent humans from receiving mosquito bites.

Prediction of Transport, Deposition, and Resultant Immune Response of Nasal Spray Vaccine Droplets using a CFPD-HCD Model in a 6-Year-Old Upper Airway Geometry to Potentially Prevent COVID-19.

This study focuses on the transport, deposition, and triggered immune response of intranasal vaccine droplets to the Angiotensin-converting enzyme 2-rich region (i.e., the olfactory region (OR)) in the nasal cavity of a 6-year-old female to possibly prevent COVID-19.

FOC winding defect detection based on improved texture features and low-rank representation model.

The defect detection of fiber-optic coils (FOCs) plays an important role in the quality control of the FOC production. In order to overcome the problems of poor performance and low reliability of existing methods, this paper provides a solution for winding defect detection of FOCs based on low-rank representation (LRR) technology. First, we design a feature matrix, which represents the image.

Septoplasty Effect on the Enhancement of Airflow Distribution and Particle Deposition in Nasal Cavity: A Numerical Study.

The surgery outcomes after fixing nasal airway obstruction (NAO) are sometimes not satisfactory in improving ventilations of airflow. A case study is presented in this paper with computational fluid dynamics applied to determine the key factors for successful septoplasty plans for a patient with a deviated nasal septum. Specifically, airflow, as well as particle transport and deposition were predicted in a pre-surgery nasal cavity model reconstructed from patient-specific Computer Tomography (CT) images and two post-surgery nasal cavity models (i.

Structural Characterization and Hypoglycemic Activity of a Novel Pumpkin Peel Polysaccharide-Chromium(III) Complex.

The aim of our study was to synthesize a pumpkin peel polysaccharide (PPP)-Cr(III) complex and investigate its hypoglycemic activity. Firstly, a novel PPP-Cr(III) complex with a Cr content of 23.77 mg/g was synthesized and characterized.

Targeted delivery of inhalable drug particles in a patient-specific tracheobronchial tree with moderate COVID-19: A numerical study.

The coronavirus disease 2019 (COVID-19) pandemic has led to severe social and economic disruption worldwide. Although currently no consent has been reached on a specific therapy that can treat COVID-19 effectively, several inhalation therapy strategies have been proposed to inhibit SARS-CoV-2 infection. These strategies include inhalations of antiviral drugs, anti-inflammatory drugs, and vaccines.

Long Non-Coding RNA NR-133666 Promotes the Proliferation and Migration of Fibroblast-Like Synoviocytes Through Regulating the miR-133c/MAPK1 Axis.

Long non-coding RNA (lncRNA) is involved in the regulation of rheumatoid arthritis (RA) and many other diseases. In this study, a new lncRNA, NR-133666, was identified to be highly expressed in the adjuvant-induced arthritis rat model using the Agilent lncRNA microarray assay. qRT-PCR verified that NR-133666 was upregulated in fibroblast-like synoviocyte of a collagen-induced arthritis (CIA) rat model.